5$

!
MED%

Medicine$Notes$

Book$1$
Cardiology$Dermatology$Endocrine$Geriatrics$GI$Hematology$Infectious$Diseases$

CUHK%2014%
Cardiology!
Ischemic0Heart0Disease0(IHD) ............................................................................................................. 3!
STEMI.............................................................................................................................................................................................................. 6!
NSTEMI........................................................................................................................................................................................................ 14!
Unstable!angina ....................................................................................................................................................................................... 15!
Stable!angina............................................................................................................................................................................................. 16!

Pericardial0effusion0/0Cardiac0tamponade0心包填塞 ....................................................................... 18!

Hypertension0(HT)............................................................................................................................ 19!
Resistant!hypertension ........................................................................................................................................................................ 23!
Hypertensive!crisis................................................................................................................................................................................. 24!
Hypokalemic!hypertension ................................................................................................................................................................ 25!
Obstructive0sleep0apnea0(OSA)......................................................................................................... 25!
Infective0endocarditis0(IE) ................................................................................................................ 27!
Acute0rheumatic0fever0(ARF) ............................................................................................................ 28!
Chronic0rheumatic0heart0disease0(CRHD).......................................................................................... 29!
Mitral0regurgitation0(MR)................................................................................................................. 29!
Mitral0valve0prolapse0(MVP) ............................................................................................................ 32!
Mitral0stenosis0(MS)......................................................................................................................... 32!
Tricuspid0regurgitation0(TR).............................................................................................................. 35!
Aortic0regurgitation0(AR).................................................................................................................. 36!
Aortic0stenosis0(AS) .......................................................................................................................... 38!
Pulmonary0regurgitation0(PR)........................................................................................................... 41!
Pulmonary0stenosis0(PS)................................................................................................................... 41!
Astrial0Septal0Defect0(ASD)............................................................................................................... 41!
Ventricular0Septal0Defect0(VSD)........................................................................................................ 43!
Heart0failure0(HF) ............................................................................................................................. 43!
Diastolic0dysfunction........................................................................................................................ 47!
Acute0pulmonary0oedema0(APO)0 ................................................................................. 47!
Cardiogenic!pulmonary!edema......................................................................................................................................................... 48!
Pericarditis....................................................................................................................................... 50!
Palpitation ....................................................................................................................................... 52!
Sudden0cardiac0death ...................................................................................................................... 52!
Arrhythmia ...................................................................................................................................... 52!
Tachycardia ............................................................................................................................................................................................... 53!
Sinus!tachycardia.................................................................................................................................................................................... 53!
Supraventricular!tachycardia!(SVT)............................................................................................................................................... 54!
Atrioventricular!nodal!reentrant!tachycardia!(AVNRT)........................................................................................................ 55!
Atrial!flutter............................................................................................................................................................................................... 56!
Atrial!fibrillation!(AF) ........................................................................................................................................................................... 57!
Multi+focal!atrial!tachycardia!(MAT).............................................................................................................................................. 62!
Ventricular!ectopic!beats..................................................................................................................................................................... 63!
!

Cardiology!+!1!
Ventricular!tachycardia!(VT) ............................................................................................................................................................. 63!
Ventricular!fibrillation!(VF) ............................................................................................................................................................... 65!
Bigeminy..................................................................................................................................................................................................... 66!
Bradycardia ............................................................................................................................................................................................... 66!
Sinus!bradycardia ................................................................................................................................................................................... 67!
Sinus!block!/!pause!/!arrest ............................................................................................................................................................... 67!
Junctional!bradycardia ......................................................................................................................................................................... 67!
Sick!sinus!syndrome!/!Brady+tachy!syndrome.......................................................................................................................... 67!
Heart0block ...................................................................................................................................... 68!
Wenckebach!(second!degree,!Mobitz!type!I).............................................................................................................................. 68!
Complete!heart!block ............................................................................................................................................................................ 69!
WolffTParkinsonTWhite0(WPW)0Syndrome ....................................................................................... 69!
Long0QT0syndrome ........................................................................................................................... 70!
Brugada0syndrome........................................................................................................................... 71!
Dilated0cardiomyopathy .................................................................................................................. 72!
Hypertrophic0cardiomyopathy0(HCM) .............................................................................................. 73!
Restrictive0cardiomyopathy ............................................................................................................. 74!
Arrhythmogenic0Right0Ventricular0Cardiomyopathy0(dysplasia) ....................................................... 74!
Tetralogy0of0Fallot0(TOF) .................................................................................................................. 74!
Ebstein’s0anomaly............................................................................................................................ 74!
Dyslipidemia .................................................................................................................................... 75!
Cardiac0arrest .................................................................................................................................. 75!
Pulseless0electrical0activity0(PEA)0(Electromechanical0dissociation) .................................................. 76!
Treadmill0(Exercise0ECG) .................................................................................................................. 77!
CT0angiogram................................................................................................................................... 79!
Cardiac0catheterization .................................................................................................................... 79!
Coronary!angiogram.............................................................................................................................................................................. 79!
Percutaneous!Coronary!Intervention!(PCI) ................................................................................................................................ 79!
Coronary0Artery0Bypass0Surgery0/0Graft0(CABG) ............................................................................... 82!
Prosthetic0valve0replacement........................................................................................................... 83!
External0Defibrillation0/0Synchronized0DC0cardioversion................................................................... 84!
Pacemaker....................................................................................................................................... 84!
Temporary!pacemakers....................................................................................................................................................................... 84!
Permenant!pacemakers ....................................................................................................................................................................... 85!
Implantable0cardioverter0defibrillator0(ICD) ..................................................................................... 86!
Physical0examination0(Cardiovascular0exam).................................................................................... 87!
ECG0(electrocardiography) ............................................................................................................... 92!
Electrical!alternan .................................................................................................................................................................................. 95!
Ventricular!tachycardia........................................................................................................................................................................ 95!
Hyperkalemia ........................................................................................................................................................................................... 95!
Hypokalemia ............................................................................................................................................................................................. 96!
Hyper/hypoMg ........................................................................................................................................................................................ 96!
Hypercalcemia.......................................................................................................................................................................................... 96!
!

Cardiology!+!2!
Hypocalcemia ........................................................................................................................................................................................... 96!
Digoxin......................................................................................................................................................................................................... 96!
Class!IA!anti+arrhythmic!(e.g.!quinidine,!procainamide,!disopyramide)........................................................................ 96!
Class!III!anti+arrhythmic!(e.g.!amiodarone,!sotalol) ................................................................................................................ 96!
Pulmonary!embolism!(PE).................................................................................................................................................................. 96!
AF ................................................................................................................................................................................................................... 96!
Hypothermia ............................................................................................................................................................................................. 96!
Echocardiogram ............................................................................................................................... 97!
Transthoracic!Echocardiogram!(TTE)........................................................................................................................................... 97!
Drugs ............................................................................................................................................... 99!
Amiodarone............................................................................................................................................................................................... 99!
Digoxin.......................................................................................................................................................................................................100!
Nitroprusside..........................................................................................................................................................................................100!
ACEI ............................................................................................................................................................................................................100!
Labetalol ...................................................................................................................................................................................................101!
Calcium!channel!blocker!(CCB) ......................................................................................................................................................101!
Lasix!(Furosemide) ..............................................................................................................................................................................101!
Spironolactone!(Aldactone) .............................................................................................................................................................101!
Heparin......................................................................................................................................................................................................102!
Warfarin....................................................................................................................................................................................................103!
Direct!thrombin!inhibitors ...............................................................................................................................................................106!
Dabigatran ...............................................................................................................................................................................................106!
Factor!Xa!inhibitor!(+xaban).............................................................................................................................................................107!
Aspirin .......................................................................................................................................................................................................107!
Clopidogrel ..............................................................................................................................................................................................107!
Statin ..........................................................................................................................................................................................................108!
Fibrate........................................................................................................................................................................................................109!
!

Ischemic0Heart0Disease0(IHD)0
Definition!
+ Stable!angina!=!reproducible!chest!discomfort!on!exertion/stress,!relieved!within!5+10min!by!
rest!or!TNG!
+ Unstable!angina!=!symptoms!of!angina!with!1!of!the!following!features!
o Rest!angina,!≥20mins!in!duration!
o Severe!and!new!onset,!markedly!limits!physical!activity!
o Cresendo!pattern:!increasing!angina!that!is!more!frequent,!longer!in!duration!or!occur!
with!less!exertions!then!before!
+ NSTEMI!=!features!of!unstable!angina!+!myocardial!necrosis!(enzymes)!
+ STEMI!=!ischemic!chest!pain!+!ST+elevation!in!ECG!±!myocardial!necrosis!
!
Acute!coronary!syndrome!(ACS)!
+ ST!segment!elevation!myocardial!infarction!(STEMI):!acute!complete!occlusion!
o Previously!use!Q!wave!as!classification!(Q!wave!or!non+Q!wave),!but!autosy!found!that!
Q!wave!not!correlate!with!transmural!or!not,!so!use!ST!elevation!as!classification!(as!it!
guide!diff!Rx)!
+ Non+ST!segment!elevation!ACS!(NSTE+ACS):!partial!/subtotal!occlusion!
o NSTEMI!
o Unstable!angina!
o *!Differentiated!by!cardiac!enzyme!x!2!sets!with!4+6hr!apart!
!
STEMI!Vs!NSTEMI!
+ STEMI:!relatively!normal!vessel!!!sudden!blocked!by!thrombus!
o !!Transmural!infarct!
!

Cardiology!+!3!
+ Arrhythmia22
o *!Risk!is!low!after!successful!revascularization!
" Usually!occur!after!few!months!when!myocardium!become!scar!tissue!
" If!occur!early,!indicate!not!successful!revascularization!(re+MI)!
o Sinus!bradycardia!
" Atropine,!electrical!pacing!
o Sinus!tachycardia!
" Look!for!underlying!cause!e.g.!infection,!anemia,!HF!!!Rx!accordingly!
" Betablocker!
o Supraventricular!tachycardia!
" Adenosine,!verapamil!
o Atrial!flutter/!Atrial!fibrillation!
" In!heart!failure!!!digoxin!
" Not!in!heart!failure!!!betablocker,!diltiazem!
o Ventricular2ectopic!(extrasystole)!!
" The!commonest!post+MI!arrhythmia!
" Risk!of!VF!if!‘R!on!T!pattern’!is!seen!
" Cause:!ischemia!in!myocardium!!!affect!repolarization,!↑!risk!of!automacity,!re+
entry!circuit!!
• Risk!can!be!↓!by!PCI!(↓!ischemia)!
" No!therapy!needed!as!it!is!very!common,!but!if!too!frequent!(>10/min)!!!
consider!IV!amiodarone!
o Ventricular!tachycardia!/!VF!
" Amiodarone,!lignocaine,!procainamide!
" May!cause!sudden!cardiac!death!(SCD)!!
o **!Emergent!cardioversion!in!any!case!of!hemodynamic!instability!
+ Heart!block!
o 1st!&!mobitz!type!I!2nd!!!conservative!
o Mobitz!type!II!and!3rd!!!pacing!
" Conservative!if!inferior!MI!with!narrow!QRS!escape!rhythm!&!adequate!HR!
• Usually!transient!!
o May!be!transient!ischemia!as!RCA!supply!SAN!&!AVN!!
o Transient!from!increased!vagal!tone,!or!release!of!adenosine!!
" Need!permanent!pacing!in!anterior!MI!!
• Indicate!extensive!infarct!extending!to!AV!node!!
• Permenant!damage!from!ischemic!destruction!of!conduction!pathway!!
o Trifascicular!block!!!pacing!
+ Cardiac!wall!rupture!!
o Ventricular!free!wall!rupture!(VFWR)!!!cardiac!tamponade!
o Ventricular!septal!rupture!(VSR)!!!VSD!
+ Left!ventricular!aneurysm!
o Persistent!ST!elevation!
o Cx:!intractable!LV!failure!±!angina,!ventricular!arrhythmia,!thromboembolism!
+ MR!
o Rupture!of!subvalvular!chordae!tendineae!!
o Rupture!of!papillary!muscle!!
+ Post+MI!syndrome!(Dressler!syndrome)!/!Pericarditis!
o Inflammation!of!pericardial!tissue!overlying!infarcted!myocardium!
o Autoimmune:!myocardial!injury!stimulate!autoAb!against!heart!muscle!
o Fever,!severe!pleuritic!chest!pain,!pericardial!friction!rub!2+10!weeks!after!AMI!
" Must!be!differentiated!with!chest!pain!from!re+infarction:!radiating!to!trapezius!
muscles!
!

Cardiology!+!12!
 o ECG:!diffuse!ST+elevation!in!all!leads!
o Rx:!r/o!cardiac!tamponade,!rest,!650mg!aspirin!QID,!NSAID!±!steroids!
" **!Avoid!anticoagulant:!risk!of!cardiac!tamponade!
+ Left!ventricular!mural!thrombus!(LVMT)!
o Common!in!anterior!infarct!of!LV!wall!
o Due!to!!
" LV!regional+wall!akinesia!/!dyskinesia!with!blood!stasis!
" Injury!to!&!inflammation!of!endocardial!tissue!!!provides!a!thrombogenic!
surface!
" Hypercoagulable!state!
!
Subsequent!management!
+ Exercise2tolerance2test!
o Two!types!
" Submaximal!exercise!stress!test,!before!discharge!
" Maximal!exercise!stress!test,!4+6!weeks!after!infarction!
o For!risk!stratification,!high!risk!if!
" Angina!induced!by!low!workloads!
" Excercise!provoked!symptomatic!ventricular!arrhythmia!
" Depressed!ejection!fraction/!large!reversible!defect!on!perfusion!imaging!
" !!Go!for!CC!±!PCI!
+ Non+pharmacological!
o Discourage!smoking!including!family!members!
o Diet!control!!
o Exercising:!30min/d,!minimum!5d/wk!
o Control!DM!(HbA1c!<7%)!/lipid/hypertension!(<140/90!or!130/80!if!CKD!/!DM)!
o Educate!early!presentation!if!any!symptoms!of!angina!/!infarction!
o Cardiac!rehab!
+ Drugs!
o Aspirin!75+150mg!daily!±!clopidogrel!indefinitely!!
o ACEI2indicated!in!all!patients!(except!C/I,!e.g.!hyperK):!have!survival!benefit!
" Lisinopril:!start!with!2.5mg!daily,!then!titrate!up!according!to!clinical!response!
• Aware!of!1st!dose!hypotension,!monitor!renal!function!
" Consider!combined!ACEI/ARB!in!persistant!symptomatic!HF!&!LVEF!<40%!
despite!therapy!
o BB2(or!diltiazem,2verapamil):!for!all!unless!C/I!
" Metoprolol,!start!with!25mg!BD2!
o High2dose2statins2!
" Simvastatin!10+80mg!
" Given!to!all:!i.e.!independent!of!lipid!level,!for!plaque!stabilization!
" Target!best!at!1.8mmol/L,!at!least!2.6mmol/L!!!
• If!goal!not!achieved,!can!adjunct!with!ezetamide!!
" Initiate!early:!within!1+4!days!
o Nitrate!PRN!
" S/E:!headache,!dizziness!due!to!vasodilator!
" Only!symptomatic!improve,!not!improve!survival!
o Risk!factor!modification:!hyperlipidemia!!!lifestyle!modification!+!pharmacological!
" Drug!choice:!bile!acid!sequestrants!(LDL),!ezetimibe!(LDL),!fibrate!(TG),!nicotinic!
acid!(TG)!
" If!high!dose!statin!but!still!sub+optimum!lipid!!!!
• Ask!for!drug!compliance!&!lifestyle!
!

Cardiology!+!13!
 o CABG!
" Significant!(≥50%)!left!main!stem!disease!!
" Significant!(≥70%)!stenosis!of!proximal!LAD!&!proximal!L!circumflex!artery!
" Triple!vessels!disease!with!LVEF!<50%!
Pericardial0effusion0/0Cardiac0tamponade0心包填塞
+ ~50ml!of!pericardial!fluid!is!normally!present!in!the!pericardial!cavity!
+ Cardiac!Tamponade!(CTD):!large!amount!of!pericardial!fluid!compressing!the!heart!&!prevent!
it!from!relaxing!&!filling!in!blood!
o Depend!on!rate!of!fluid!accumulation:!percardium!is!not!very!compliant!(not!elastic),!so!
if!fluid!accumulate!over!short!period!of!time!!!no!time!to!stretch!!!build!up!pressure!
rapidly!&!cause!compression!on!the!RV!
o So!if!see!very!large!amount!of!fluid!accumulated!!!not!acute!condition!
!
Common!causes!
+ Cancer:!tumor!invade!into!pericardium!causing!effusion!
+ TB!pericarditis,!other!infective/!non+infective!pericarditis!
+ CRF!(uremia)!
+ Cardiac!trauma!/!related!to!cardiac!procedure!e.g.!PCI!
!
Presentation!of!cardiac!tamponade!
+ Tachypnea,!tachycardia,!hypotension!
+ The!Beck’s2triad:!hypotension,!elevated!JVP!&!muffled!heart!sound!
+ Pulsus!paradoxus:!exaggerated!↓!in!SBP!(>10)!&!pulse!wave!amplitude!during!inspiration!
+ Kussmaul’s!sign:!paradoxical!↑!in!JVP!on!inspiration!
+ Pulseless!electrical!activity!(PEA)!/!electromechanical!dissociation!
o ECG!activity!present!but!no!pulse!
+ ECG:!tachycardia,!low!voltage!(<5mm!in!limb!leads,!<10mm!in!chest!
leads),!electrical!alternans!
+ CXR:!large!globular!heart!but!relatively!clear!lung!field!
+ Echo:!RA,!RV,!LA!collapse,!distended!IVC,!↑!tricuspid!flow,!↓!mitral!
flow!during!inspiration!
!
Treatment!
+ Expand!intravascular!volume!with!D5!/!NS,!full!rate!if!in!shock!
+ Pericardiocentesis!if!in!shock!
o Before!procedure:!do!Echo!(esp!in!subcostal!window,!as!needle!enter!from!subcostal)!
o Must!have!>2.5cm!of!fluid,!otherwise!↑!risk!of!RV!puncture!
o Puncturing!the!pericardium!percutaneously!using!a!large!bore!needle!
" 2!approaches!
• Subxiphoid!/subcostal!approach:!safer!(if!puncture!heart!!!puncture!RV),!
but!more!difficult!to!do!as!need!to!cross!diaphragm!
• Apical:!more!dangerous!(if!puncture!heart!!!puncture!LV)!
o Confirm!the!site!of!needle!by!injecting!agitated!saline!(shake!the!syringe!for!few!times)!
inside!the!cavity,!then!do!Echo,!if!see!bubble!in!pericardium!!!right!site!
o Insert!the!guidewire!then!track!the!soft!tip!catheter!through!the!guidewire!&!connect!it!
to!a!drain!
o Risk:!damaging!epicardial!coronary!artery,!cardiac!perforation!
!
Prevention!
+ For!cancer!patient!who!have!expected!survival!of!>3m!
+ Pericardium!window!through!subxiphoid!incision!
!

Cardiology!+!18!
 " Centrally!acting!agent!(clonidine,!methyldopa)!
" Direct!vasodilator!(hydralazine,!minoxidil)!
+ Refer!to!hypertension!specialists!

Hypertensive0crisis0
Definition!
+ Malignant!hypertension!!
o BP!≥220/120!+!with!bilateral!grade!3/4!fundal!changes!(retinal!hemorrhage!&!exudate!
±!papilloedema)!
+ Hypertensive!emergency! !
o Malignant!/!severe!HT!+!acute!target!organ!damage!
+ Hypertensive!urgency!
o Malignant!HT!without!acute!target!organ!damage!
!
Presentation!
+ Headache,!nausea,!visual!disturbance!
+ End!organ!damage!
o Acute!renal!failure!!
o Heart!failure!!
o Acute!pulmonary!edema!(APO)!
o Acute!MI!
o Aortic!dissection!!
o Hypertensive!encephalopathy:!confusion,!seizure!
o Eclampsia!
o Intracranial!hemorrhage!(ICH)!
!
Management!
+ Complete!bed!rest,!NPO,!recheck!BP!
+ Assess!!
o Fundi:!Grade!III/IV!changes!!
o CVS:!Heart!failure,!radio+femoral!delay!!
o Renal:!Urine!output!(Foley!to!BSB)!
o CNS:!focal!signs,!GCS!
+ Blood!x!CBC,!RFT,!LFT,!cardiac!enzymes,!ABG!
+ Urine!dipstix,!albumin/Cr!ratio!
+ ECG,!CXR!
+ Lower!the!BP!!
o Avoid!sudden!drops!in!BP!as!poor!cerebral!autoregulation!
o But!in!grade!IV!fundal!changes!!!need!to!↓!>20+25%!of!baseline!ASAP!to!avoid!
hypertensive!encephalopathy!
o IV2labetalol/Na2nitroprusside/hydralazine!(in!elampsia)/phentolamine!(in!pheo!
crisis)!
" Make!sure!no!LV!dysfunction!/!reactive!airway!diseases!
" No!more!sublingual!nifedipine:!too!drastic!BP!drop!!!stroke!!
o Target!BP:!
" Chronic!HT,!elderly,!acute!CVA:!170+180/100!
" Previously!normotensive,!post+vascular/cardiac!surgery!(risk!of!bleeding):!
~140/80!
" Acute!aortic!dissection:!SBP!100+120!
+ BP/P!Q1H!or!BP!monitoring,!IA!line!may!be!needed!!
+ Find!the!cause!!
!

Cardiology!+!24!
Hypokalemic0hypertension0
Do!PRA/PAC!(Plasma!Renin!Activity!/!Plasma!Aldosterone!Concentration)!
+ Both!high!!
o Renovascular2hypertension2!
o Diuretics!
o Renin+secreting!tumor!!
o ?!Malignant!HT!!
+ Low!renin!high!aldosterone!!
o Primary2aldosteronism2
+ Both!low!
o Exogenous!minerulocorticoids!!
o Congenital!adrenal!hyperplasia!(CAH)!
o DOC+producing!tumor!!
o Cushing's2syndrome2!
o Syndrome!of!apparent!mineralocorticoid!excess!
" AR,!inactivation!11b+HSD!in!kidney!!!↑!local!conc!of!cortisol!!
" Also!caused!by!liquorice:!transient!block!11b+HSD!
o Liddle!syndrome!(pseudoaldosteronism)!
" Autosomal!dominant;!defect!in!epithelial!Na!channel!in!kidney,!↑!Na!absorption!
&!K!loss!
!
Management!!
+ Ask!about!diuretics!use,!check!volume!status!(mild!dehydrated)!!
+ If!no!symptoms!!!Paired!aldosterone+renin!!
o Both!high!!!RAS!!
o High!aldosterone,!low!renin!!!Conn's!!
o If!Cushingoid!!!Overnight!dexamethasone!suppression!test!!
!
Obstructive0sleep0apnea0(OSA)0
History!taking!
+ Loud!snoring!
+ Poor!sleep!quality,!restless!sleep,!nocturnal!choking!episodes!
+ Nocturia!
+ Daytime!sleepiness!
o Epworth!sleepiness!scale!(ESS):!scale!measuring!daytime!sleepiness!
+ Morning!headache!
+ Decreased!libido!
+ Cognitive!performance!↓!
!
Physical!exam!
+ BMI,!BP!
+ Possible!causes!for!upper!airway!obstruction!
o Nasal!septal!deviation!or!nasal!polyps!
o Craniofacial!abnormalities!
o Visculization!of!the!oropharynx!for!macroglossia,!redundant!tissue!around!soft!palate,!
elongated!uvula,!enlarged!tonsils!or!adenoids!
" Oropharyngeal!grading!
!
Diagnosis!
+ Simple!studies,!e.g.!pulse!oximetry,!video!recordings!
+ Embletta:!portable!polysomnography,!allow!ambulatory!sleep!studies!
!

Cardiology!+!25!
 o Same!as!inpatient!PSG!except!no!ECG!
+ Polysomnography!
o Monitor!O2!saturation,!airflow!at!nose!&!mouth,!ECG,!EMG!chest!&!abdominal!wall!
movement!
o Chest!movement!+ve!but!no!air!flow!(obstruction),!then!O2!saturation!decrease!
o Desaturation!during!REM!sleep!because!of!muscle!paralysis!during!that!time!
+ Apnea+hypopnea!index!(AHI)!
o <!5/hr!!!normal,!5+15!!!mild;!15+30!!!moderate;!>30!!!severe!
o Apnea!=!complete!cessation!of!airflow!for!≥10!sec!
o Hypopnea!=!airflow!↓!by!50%!for!10!sec!OR!↓!by!30%!+!↓!in!O2!saturation!/!arousal!
from!sleep!!
!
Complications!
+ Type!II!respiratory!failure,!pulmonary!HT!(hypoxia!!!vasoconstriction),!cor!pulmonale!
+ HT:!dose+dependent!
+ AF:!HT,!intermittent!hypoxia,!↑!sympathetic!tone!
+ Atherosclerosis:!intima+media!thickness!is!proportional!to!severity!of!OSA!
+ Stroke:!every!one+unit!increase!in!AHI!!!↑!risk!of!stroke!by!6%!
o HT,!atherosclerosis,!endothelial!dysfunction!
o Higher!BP!variability!(15mmHg!↓)!!!have!a!critical!effect!on!ischemic!penumbra!
surrounding!the!infracted!brian!
o Increased!cardiac!output!
o High!intra+cranial!pressure,!low!cerebral!blood!flow!(correlate!with!severity)!
o High!fibrinogen!concentration,!decreased!fibrinolysis,!increased!platetle!aggregation!
o Carciac!arrhythmia!
o Patent!foramen!ovale:!R!to!L!shunt!due!to!long!OSA!leading!to!pulmonary!HT!
+ Cognitive!decline:!loss!of!grey!matter!(temporal!lobe)!
!
Management!
+ Weight!reduction!
+ Positional!therapy:!don’t!sleep!in!supine!position!
+ Avoid!smoking,!alcohol!&!sedatives!
+ Avoid!sleep!deprivation!
+ CPAP! via!nasal!mask:!for!moderate!to!severe!disease!($5000+8000)!
o Can!↓!stroke!risk!
o Poor!compliance:!discomfort,!dry!mouth!
o If!still!unable!to!maintain!SaO2!>90%!with!CPAP!!!may!have!obesity!hypoventilation!
syndrome!(OHS)!!!need!BiPAP! ($25000)!which!has!backup!mode!
" Risk!of!REM!rebound!in!OHS!patients!once!treated!the!OSA!component!
• With!OSA,!REM!sleep!duration!shortened!due!to!frequent!partial!arousal,!
once!OSA!treated!!!REM!duration!↑!!!desat!during!REM!
+ Oral!appliances:!mandibular!advancement!device!
+ Surgical!treatment!
o Tracheostomy!
o Nasal!surgery!and!adeno+tonsillectomy!
o Uvulopalatophayryngoplasty!
o Radiofrequency!ablation!of!softpalate!
o Maxilloficial!surgery!

Cardiology!+!26!
Infective0endocarditis0(IE)0
Epidemiology!
+ 50%!in!normal!valves!!!acute!onset!(acute!heart!failure!±!emboli)!
+ 50%!in!abnormal!valves!!!subacute!onset!
o Prosthetic!valve,!aortic!/!mitral!valve!disease,!coarctation,!PDA,!VSD!
+ IV!drug!addicts!!!tricuspid!valve!
!
Infective!agents!
+ Streptococcus!viridans!(more!common!in!abnormal!valves)!
+ Enterococci!
+ Straphylococcus!aureus,!epidermidis!(more!common!in!normal!valves)!
+ Diphtheroid!!
+ Gram!–ve!bacteria:!HACEK!group!(Hemophilus,!Actinobacilis,!Cardiobacterium,!Eikenella,!
Kingella)!!
+ Fungi!(Candida,!Aspergillus,!Histoplasma)!
!
Other!causes!of!endocarditis!
+ SLE!(libman!sack!endocarditis)!
+ Malignancy!!
!
Clinical!features!
+ Cardiac!lesion!
o New!regurgitant!lesion!
o Prolong!PR!interval!!
+ Immune!complexes!
o Clubbing,!Osler’s!node!(painful,!red,!raised!lesions!on!fingers),!Roth's!spot!!
o Microscopic!hematuria!(GN)!
o Splenomegaly!
+ Emboli!phenomenon!
o Janeway!lesions!(non+tender,!macular!/!nodular!lesion!on!palm):!microabscesses!
o Splinter!hemorrhage!
!
Investigations!of!suspected!IE!
+ CBC,!R/LFT,!ESR,!CRP!
o May!have!microangiopathic!hemolytic!anemia,!thrombocytopenia!(?)!
+ Blood!culture!x!3!(different!time!&!different!site)!
+ Urine!x!WCC,!dysmorphic!RBC!(GN!caused!by!IE)!
+ Echo!
+ (CXR):!if!have!lung!abscess!!!think!of!tricuspid!valve!involvement!(IVDU)!
!
Diagnosis:!Modified!Duke’s!criteria! 3!markers:!
+ Definite:!2M!/!1M+3m!/!5m! + Microbiological!
+ Possible:!1M+1m!/!3m! + Echocardiological!!
+ Major!criteria! + Immunological!
o +ve!blood!culture!
" Typical!organism!in!2!separate!cultures!
" Persistently!+ve!blood!culture!>3!at!12h!apart!
o Endocaridium!involved!
" Positive!echocardiogram:!vegetation,!abscess,!dehiscence!of!prosthetic!valves!
" New!valvular!regurgitation!(change!in!murmur!not!sufficient)!
+ Minor!criteria!
!
o Predisposing!factor:!cardiac!lesion,!IV!drug!injection!
Cardiology!+!27!
 o Fever!>38°C!
o Vascular!
" Major!arterial!emboli,!septic!pulmonary!infarcts,!mycotic!aneurysm,!intracranial!
hemorrhage,!conjunctival!hemorrhage,!Janeway!lesions!
o Immunological!phenomena:!deposition!of!immune!complex!
" Glomerulonephritis,!Osler's!nodes,!Roth!spots,!rheumatoid!factor!
o Atypical!positive!blood!culture!!
o Atypical!echocardiogram!finding!(Removed!from!the!modified!Duke!criteria)!
!
Empirical!treatment!!
+ Subacute!IE:!CRHD,!degenerative!/!congenital!valvular!diseases!
o I.V.!ampicillin!2g!Q4H!+!gentamicin!1mg/kg!G8H!x!6!weeks!
+ Acute!IE:!IVDU!
o I.V.!cloxacillin!2g!Q4H!+!gentamicin!1mg/kg!Q8H!for!the!first!5!days!
o Alternative:!I.V.!cefazolin!2g!Q8H!
!
Most!updated!guideline!on!antibiotic!prophylaxis!
+ Which!patients?!
o Prosthetic!heart!valves:!if!infected!!!very!difficult!to!be!treated!by!A/B!alone!&!may!
damage!the!prosthetic!valve!which!may!need!repeat!surgery!
o Previous!infective!endocarditis!
o Congenital!heart!disease!with!!
" Unrepaired!cyanotic!CHD!
" Repaired!CHD!with!prosthetic!material/device!during!6!months!after!procedure!
• Endothelialization!of!prosthetic!material!occurs!within!6m!
" Repaired!CHD!with!residue!defect!at!site/adjacent!to!site!of!prosthetic!material!/!
device!
• This!inhibits!endothelialization!
o Cardiac!transplant!patient!who!developed!cardiac!valvopathy!
+ At!which!procedures?!
o All!dental!procedures!
o Procedures!involving!GI/GU!tract:!no!longer!indicated!
o Procedure!on!respiratory!tract!involving!incision!/!biopsy!(?)!
" Also!include!removal!of!tonsils!/!adenoids!
" Include!TBBX!but!not!bronchoscopy!alone!
+ How!to!prescribe?!
o Ampicillin!2g!IM/IV!+!gentamicin!1.5mg/kg!(max!80mg)!within!30mins!before!
o Then!ampicillin!1g!IM/IV!/!amoxicillin!1g!PO!6hr!later!
o For!penicillin!allergy:!
" Vancomycin!1g!IV!over!1!hour!+!gentamicin!1.5mg/kg!(max!80mg)!IV/IM!within!
30min!before!
Acute0rheumatic0fever0(ARF)0
Introduction!!
+ An!acute!immunologically!mediated!mulitsystem!inflammatory!disease!after2Group2A2β<
hemolytic2streptococcal2pharygitis2(Strept!pyogenes),!with!the!immune!reactions!targetted!
to!tissue!connective!tissues!and!basement!membrane!(collagen!type!IV)!!
o Molecular!mimicry!
!
Diagnosis:!Revised2Jones2Criteria!
+ 2M!/!1M+2m,!in!addition!to!evidence!of!recent!streptococcal!infection!
+ Major2Criteria!
!
o Carditis!
Cardiology!+!28!
 " Affect!all!layers:!pericardium,!epicardium,!myocardium!&!endocardium!!
" Presented!as!new!/!changing!murmur,!MR!>!AR!>!others!
o Polyarthritis!
" Migrating!arthritis!of!knees,!ankles,!elbows!&!wrists!
" Very!painful!but!very!responsive!to!anti+inflammatory!agents!
o Sydenham´s!chorea!(St.!Vitus’!dance)!
" Abrupt,!purposeless!movements!
" May!also!include!emotional!disturbances!&!inappropriate!behavior!
o Erythema!marginatum!
" Non+pruritic!rash!over!trunk!&!proximal!extremities!(spare!face),!migrate!from!
central!areas!to!periphery,!has!well+defined!borders!
o Subcutaneous!nodules!
" Usually!located!over!bones!/!tendons,!painless!&!firm!
+ Minor2Criteria!
o Fever!
o Arthralgia!
o Previous!rheumatic!fever!/!rheumatic!heart!disease!
o Acute!phase!reactants:!leukocytosis,!↑!ESR,!CRP!
o Prolonged!PR!interval!on!ECG!
+ Evidence2of2preceding2streptococcal2infection!
o ↑!ASOT!/!other!streptococcal!antibodies!
o Positive!throat!culture!for!Group!A!beta+hemolytic!streptococci!
o Positive!rapid!direct!Group!A!strep!carbohydrate!antigen!test!
o Recent!scarlet!fever!
!
Management!
+ Bed!rest!until!CRP!normalized!
+ Benzylpenicillin!/!penicillin!V!x!10!days!
+ Analgesic!for!carditis!/!arthritis!
+ Immobilize!joints!in!severe!arthritis!
+ Haloperidol!/!diazepam!for!chorea!
!
Secondary!prophylaxis!
+ If!carditis!+!valve!lesions!!!penicillin!until!40!y.o.!
+ If!carditis!but!no!valve!lesions!!!penicillin!x!10!years!
+ If!no!carditis!!!penicillin!x!5!years!or!until!21!y.o.!
Chronic0rheumatic0heart0disease0(CRHD)0
+ Develop!from!rheumatic!fever!(group!A!β+hemolytic!streptococcal!(Strept!pyogenes)!infection!
in!childhood!!!molecular!mimicry)!
+ Decreasing!incidence!as!nowadays,!use!antibiotics!(penicillin)!even!only!mild!sore!throat!/!
URTI!(now!these!patients!are!usually!immigrants)!
+ Affect!Mitral!(MS>MR)!>!Aortic!>!Tricuspid!>!Pulmonary!valve!
o Isolated!T!pathology!is!uncommon,!usually!with!MS!/!MR!
+ P/E:!Dental!surveillance:!possible!bacteremia!(strept!viridans:!month!flora)!!!infective!
endocarditis!
Mitral0regurgitation0(MR)0
+ The!most!common!valvular!disease!
!
Causes!
+ Chronic!
o Mitral2valve2prolapse!(MVP)!–!commonest!cause!
!

Cardiology!+!29!
 o Left2ventricular2dilatation!!
" Secondary!to!HF!!!remodeling!!!LV!dilatation!!!annular!dilatation!
" Dilated!cardiomyopathy!
o Rheumatic!heart!disease!!
" Affect!M!>!A!>!T!>>!P!valve!
" If!isolated!MR!!!very!unlikely!to!be!CRHD!as!it!should!affect!both!AV!&!MV!(?)!
o Cardiomyopathy:!HOCM!
o Connective!tissue!disorders:!Marfan’s!
o Annular!calcification:!elderly!
o Congenital!!
+ Acute!!
o Post<MI2
" Ruptured!chordae!tendinae!
" Papillary!muscle!dysfunction!/!rupture!
" !!Differentiated!by!Echo!
o Infective!endocarditis!
Another!classification!
+ Primary!Valvular!disease:!Mitral!Valve!Prolapse,!Rheumatic!Valvular!Disease,!CAD,!IE!
+ Secondary!to!a!Dilated!Annulus!/!Left!Ventricle:!Dilated!Cardiomyopathy!
+ Disturbed!Valvular!architecture:!ruptured!chordae!tendineae!/!papillary!muscle,!Infective!Endocarditis!
!
Another!classification!
+ Organic!MR:!need!to!treat!the!structure,!usually!need!surgery!
o !Rheumatic,!congenital,!IE,!post+MI…!
+ Functional!MR:!cardiomyopathy,!myocarditis,!LV!dysfunction!
o Treat!the!functional!problem!
!
Symptoms:!usually!progressive,!getting!more!severe!
+ Dyspnea!
o Exertional!dyspnea!!!paroxysmal!noctural!dyspnea!(PND)!!!heart!failure!
(hospitalization)!
+ Fatigue!
+ Palpitation!
+ Ankle!edema:!fluid!retention!due!to!heart!failure!!
+ May!develop!AF!(may!lead!to!acute!decompensation,!i.e.!acute!HF)!
o Due!to!enlarged!LA,!signify!severity!
+ Respiratory!symptoms!
o E.g.!airway!hypersensitivity,!e.g.!bronchitis,!↑!bronchial!secretions…!
o Due!to!chronic!venous!congestion!which!result!from!mitral!valve!problem!(not!only!
MR)!
+ Enlarged!L!atrium!may!compress!esophagus!
!
Physical!exam!
+ Pulse:!AF!common!
o May!be!jerky!due!to!↓!systolic!ejection!time!from!regurgitant!flow!!
+ JVP:!usually!normal!
o Uncommon!to!have!elevated!JVP!unless!have!heart!failure!
o If!no!other!signs!of!HF!!!more!likely!to!have!concomitant!TR!(TR!may!not!have!
murmur)!!!do!echo!
+ Palpation!
o Hypervolemic!apex!
o Parasternal!heave!and!palpable!P2!(pulmonary!HT)!!
+ Auscultation!
!

Cardiology!+!30!
 o Soft!S1!
o Pansystolic!murmur!best!heard!at!apex!radiating!to!axilla!
" Radiation!
• May!also!be!heard!over!the!back!(murmur!heard!over!the!back!must!be!
MR!not!others)!
• If!the!flow!is!towards!interatrial!wall!(eccentric!MR,!e.g.!MVP)!!!may!not!
radiate!to!axilla!but!LLSB!instead!
" Seagull!murmur:!special!type!of!MR!murmur!
• High!pitch,!similar!to!AS!(differentiated!by!best!heard!site)!
• Due!to!high!back!flow,!e.g.!MVP,!rupture!chordae!
" Other!causes!of!short!systolic!murmur!at!apex:!(from!250)!
• Mitral!valve!prolapse!
• Gallavardin!phenomenon!in!AS!(Try!listen!to!murmur!after!a!pause!+!
either!a!premature!beat!or!in!atrial!fibrillation:!AS!murmur!becomes!
louder!while!MR!murmur!remains!the!same)!
o Loud!P2!(pulmonary!HT)!
o (S3!may!be!present,!due!to!rapid!ventricular!filling!in!early!diastole)!!
+ **!Findings!in!acute!MR!
o Signs!of!HF:!sitting!upright,!rales!
o Murmur!may!be!very!subtle!&!short+lived!even!very!severe!MR!
!
Assess!severity!
+ Shift!of!apex!beat!
+ 3rd!heart!sound!heard!in!moderate!/!severe!cases!
+ Pulmonary!HT!!!loud!P2!&!RVH!
+ HF!
+ Presence!of!thrill!!!more!severe!
+ *Intensity!of!murmur!not!correlate!with!severity!
!
Investigation!
+ ECG:!P!mitrale,!AF,!LVH!
+ CXR:!pul!HT,!LVH!
+ Echo:!confirm!Dx!&!assess!severity!
!
Complications!
+ AF!
+ Systemic!embolization!
+ IE!
!
Management!of!acute!MR!
+ Vasodilators:!IV!TNG,!nitroprusside!
+ IABP!(intra+aortic!balloon!pump)!
+ Urgent!surgery!
!
Indications!for!surgical!repair!!
+ Acute!MR!
+ Symptomatic:!HF,!AF,!pul!HT2
+ EF!<60%!
+ Significant!LV!dilatation:!end+systolic!LV!diameter!>40mm!
+ IE!that!failed!medical!treatment,!e.g.!big!abscess,!bid!emboli!not!respond!to!drugs!
+ *!EURO!score:!predict!the!operative!mortality!risk!of!surgery!
o Depend!on!age,!sex,!pul!disease,!LV!dysfunction,!recent!MI,!pul!HT…!
!

Cardiology!+!31!
!
Choices!of!surgery!
+ Valvular2repair2
o Retain!geometry!of!ventricle,!longer!durability!&!better!outcome!
o If!patient!have!sinus!rhythm!after!OT,!may!not!need!life+long!anticoagulant!
+ Mechanical!valve!replacement!
o Much!poorer!durability,!valve!only!survive!for!20+30!years,!then!need!re+operation!
(carry!much!higher!risk!due!to!adhesion,!scar!etc)!
o Need!to!remove!the!whole!valve!!!will!destroy!the!heart!architecture!during!the!
surgery,!∴!if!initial!heart!Fx!already!very!poor!!!heart!Fx!may!further!deterioate!
" ∴!Should!not!do!valvular!replacement!if!EF!<30%,!should!continue!medical!
treatment!if!repair!not!possible!
o Need!life+long!anti+coagulant!
+ Percutaneous!MV!replacement!
o Transseptal!approach,!valve!sparing!(like!repair)!
o Immediately!function,!repositionable!
!
Timing!for!surgery!
+ For!moderate!to!severe!MVP:!better!to!do!earlier!
o Can!do!valvular!repair!if!do!surgery!earlier,!if!too!late!stage,!can!only!do!valvular!
replacement!
+ For!other!causes!!!better!to!wait!until!necessary!(e.g.!symptomatic)!
On general examination, this 60 years old lady is lying on bed not in distress. Cardiovascular examination reveals key
features of:
a irregularly irregular pulse of 100bpm
a diffused and displaced apex beat at 6th intercostal space at mid-clavicular line (parasternal heave is present)
auscultation reveals a soft S1 (and loud P2)
with a grade 3/6 pansystolic murmur radiating to axilla best heard over apex
Finally patient's JVP is normal, and there is no ankle edema nor basal crepitations.
In summary this clinical picture is compatible with a patient with mitral regurgitation and atrial fibrillation She also has
signs of pulmonary hypertension, but not in heart failure.
(There is no signs of overwarfarinization or any neurological deficit)
This patient has mitral regurgitation and atrial fibrillation, as evidented by an irregularly irregular pulse, a diffuse and
displaced apex beat, soft S1 on auscultation, and a grade 3/6 pansystolic murmur radiating to axilla best heard over
apex.
Patient also has signs of pulmonary hypertension as shown by a parasternal heave and a loud P2.
She is not in heart failure as demostrated by her normal JVP, and the absence of ankle edema and basal crepitations.

Mitral0valve0prolapse0(MVP)0
Causes!!
+ Myxedematous!degeneration!of!the!mitral!valve!tissue!
o Common!in!women,!worse!as!one!ages!!
+ Associated!with!ASD!
+ Associated!with!HCM!
+ Associated!with!Marfan's!syndrome!
!
Physical!exam!
+ Mid!systolic!click!followed!by!a!late!systolic!murmur!(NOT!pansystolic!!)!
o Aggravated!by!valsalva!maneuver!
!
Mitral0stenosis0(MS)00
DDx!
+ AF!with!dyspnea!of!pregnancy!
+ Asthma!!
+ Atrial!myxoma!
!
Causes!
!

Cardiology!+!32!
+ Rheumatic!heart!diseases!(most!common)!–!mitral!apparatus!calcification!
+ Congenital!stenosis!!
o Symptomatic:!6m+1yr!
+ Endocarditis!
+ Mitral!annular!calcification:!in!elderly!>!70!years!
+ Connective!tissue!disease!
!
Symptoms!
+ Left!heart!failure:!dyspnea,!orthopnea,!PND!
+ Palpitation!(AF:!90+95%!of!MS!have!AF)!
+ Hoarseness!of!voice!(enlarged!left!atrium)!
+ Hemoptysis!(ruptured!bronchial!veins!from!pulmonary!congestion)!
!
Valve!area!(sq!cm)! Mean!MV!gradient! !
<2.5! ! None!
1.5+2.5! <5mmHg! Exertional!dyspnea!
1.0+1.5! 5+12mmHg! Exertional!dyspnea,!pulmonary!
edema!(class!III!symptoms)!
<1.0!(critical)!! ≤12mmHg! Dyspnea!with!minimal!exertion!
/!at!rest!(Class!IV!symptoms)!
Pulmonary!HT! ! Fatigue,!RV!failure!
!
Natural!history!
+ Rheumatic!fever!!
+ After!10!years!!!abnormal!examination!
+ After!10!years!!!symptoms!!
o Ortner's!syndrome:!enlarged!LA!!!L.!recurrent!n.!compression!!!hoarseness!of!voice!
+ After!10!years!!!AF!!!disability!
+ **!May!have!develop!MR!when!MV!is!so!sclerosed!/!calcified!that!it!can’t!close!completely!
!
Physical!exam!
+ General!
o Pulse:!atrial2fibrillation!common!
o Malar!flush!(mitral!facies):!not!cross!nose!bridge!
" Due!to!back!pressure!and!build!up!of!CO2!in!severe!MS!
o JVP:!giant!a!wave!if!pulmonary!hypertension!present!
o Ascites!&!peripheral!edema:!if!pulmonary!hypertension!present!
+ Palpation!
o Tapping,!undisplaced!apex!beat!(only!in!pliable!MV,!no!in!densely!fibrotic!valve)!
o Parasternal!heave!(RV)!and!palpable!S1!&!P2!(pulmonary!HT)!!
+ Auscultation!
o Loud2S1:!as!valve!cusps!are!widely!apart!at!onset!of!systole!!
" But!if!very!severe!MS,!MV!may!not!be!very!mobile!!!not!load!S1!but!muffle!
indistinct!1st!HS!
o Loud!P2:!pulmonary!HT!
" Normally!S2!is!same!loudness!in!A!&!P!area,!now!louder!in!P!
o Opening!snap:!sudden!opening!of!mitral!valve,!followed!by!diastolic!murmur!
" High!LA!pressure!force!the!valves!cusps!apart,!but!valve!cone!is!halted!abruptly!
" Use!diaphragm!(high!pitch)!@!left!lower!sternal!border!
" Right!after!S2,!sound!like!splitting!
" If!presence!=!pliable!valve!
• Not!if!MV!is!not!pliable!(densely!fibrotic!valve)!
!

Cardiology!+!33!
 o Rumbling2low2pitch2mid<diastolic2murmur!best!heart!at!apex!with!bell!in!left!lateral!
position!!
" Presystolic!accentuation!(Presystolic!murmur)!!
" The!more!severe,!the!longer!the!diastolic!murmur!
" If!not!hear!clearly!!!can!move!bell!around!the!apex!a!little!bit,!&!remember!not!
press!hard!
o *!No!S3!in!significant!MS!
!
Assessing!severity!
+ Long!murmur!
+ Opening!snap!more!closer!to!S2!(open!in!higher!atrial!pressure)!
+ AF!
+ Pulmonary!HT!
!
Investigations!
+ CXR!
o LA!enlargement!
" Double!convexity!(double!silhouette!sign)!along!R!heart!border!!
" Convexity!of!left!heart!border!(enlarged!atrial!appendage)!
• Only!in!rheumatic!heart!disease!
" Elevation!of!left!mainstem!bronchus!(especially!if!90°!to!trachea)!
o RA!enlargement!in!secondary!TR!
o Pulmonary!arterial!HT!
" Enlargement!of!main!pulmonary!artery!&!central!pulmonary!vessels!
" Pruning!of!the!peripheral!vessels!
o Pulmonary!venous!HT!!!pulmonary!congestion!
" Upper!lobe!diversion,!Kerley!B!lines,!pleural!effusion!
o Calcification!!
" Calcification!in!the!mitral!valve!cusps!!
" Mitral!annular!calcification!(MAC)!!
+ ECG!
o Prolonged!P!wave,!with!a!double+saddleback!contour!(p!mitrale)!in!lead!II!
" RA!P!wave!followed!by!delayed!LA!P!wave!(due!to!enlarged!LA)!
o AF!
o RVH!due!to!pulmonary!arterial!hypertension!
+ Echo!
+ Exercise!test!for!functional!capacity!
!
Complications!
+ Left!atrial!enlargement!and!atrial!fibrillation!
+ Systemic!embolization!
+ Pulmonary!HT!
+ TR!
+ Right!heart!failure!!
+ Infective!endocarditis!
!
Management!
+ AF!!!!
o Digoxin!with!CCB,!BB!for!rate!control!(esp!important!during!pregnancy)!
o Anticoagulation!
o Cardioversion!if!fast!AF!
+ HF!(NYHA!class!III/IV)!!!
!

Cardiology!+!34!
 o Diuretics,!Na!restriction!
o Consider!surgery!
+ Moderate!to!severe!symptoms!/!pul!HT!!!
o Surgical!therapy,!balloon!valvuloplasty!/!valvotomy!!
!
Surgery!!
+ Percutaneous!transvenous!mitral!commissurotomy!(PTMC)!
+ Percutaneous!mitral!balloon!valvuloplasty!(PMBV)!
o Indications!
" Symptomatic!if!MVA!>1.5!&!resting!PASP!>50!(normal!25+28)!or!exercise!PASP!
>60!!
" Asymptomatic!if!MVA!≤!1.5!&!resting!PASP!>50!or!exercise!PASP!>60!
o Contraindication!!
" Mod+severe!MR!!!should!refer!to!CTS!surgeon!
" LA/LA!appendage!thrombus!!!should!treat!with!heparin!&!warfarin!
" Inability!to!perform!trans+septal!puncture!
o Need!to!do!Echo!before!OT!
" To!rule+out!concomitant!severe!MR!
• Balloon!valvuloplasty!may!lead!to!sudden!worsening!of!MR!!!e.g.!APO!
which!need!urgent!repair!
" To!see!the!valve!commissure,!to!assess!if!the!balloon!can!open!or!not!
• A!commissure!is!the!area!where!two!valve!leaflets!have!abnormally!come!
together!
• Chronic!rheumatic!heart!disease!!!fusion!of!commissure!
• If!there’s!dense!calcification!on!the!valves!!!balloon!valvuloplasty!may!
not!be!suitable!
o Inoue!Balloon!Catheter,!from!IVC,!cross!atrial!septum!through!foramen!ovale!/!create!a!
hole!to!LA!
+ Ballone!valvotomy!
o C/I:!calcified!valve!/!non!paliable!valve!(absence!of!opening!snap)!
+ Mechanical!valve!replacement!
o Indications!
" Recurrent!thromboemolism!despite!therapeutic!anti+coagulation!!
" Pulmonary!hypertension!/!haemoptysis,!even!asymptomatic!
" Heart!failure!
On general examination, this 70 years old lady is lying comfortably on bed not in distress.
Cardiovascular examination reveals key features of:
a irregularly irregular pulse of 100bpm suggestive of atrial fibrillation, with no signs of overwarfarinization
(a malar flush)
a tapping apex localised at 5th intercostal space 1cm lateral to mid clavicular line
parasternal heave is present (with a palpable P2)
auscutation reveals loud S1 and S2
and a grade 2/6 low pitch rumbling mid-diastolic murmur (with presystolic accentuation) best heard over the apex with a
bell when patient is in left lateral position
(an opening snap is as well present)
Her JVP is not elevated, there is no ankle edema or basal crepitations.
In summary, this clinical picture is compatible with a patient with mitral stenosis in atrial fibrillation, with signs of
pulmonary hypertension but not in heart failure.
This patient has mitral stensis with atrial fibrillation. Evidented by a irregularly irregular pulse, (a malar flush), a tapping
apex beat, loud S1, with a grade 2/6 low pitch rumbling mid-diastolic murmur (with presystolic accentuation) best heard
over the apex with a bell when patient is in left lateral position.
Patient also has signs of pulmonary hypertension evidented by a parasternal heave and a loud P2.
Patient is not in heart failure as there is no ankle edema, basal creptiation and a normal JVP.

Tricuspid0regurgitation0(TR)0
Cause!
+ Pulmonary!disease!/!LV!disease!!!pulmonary!HT:!more!common!cause!

Cardiology!+!35!
 o MR,!MS!!!congested!LA!!!pul!HT!!!RV!dilated!!!annulus!stretched!!!can’t!close!
completely!!!TR!
+ Infective!endocarditis!
+ Carcinoid!syndrome!
o 50%!of!patients!have!cardiac!abnormalities:!classically!caused!by!serotonin+induced!
fibrosis!of!valvular!endocardium!(cardiac!fibrosis),!esp!TV!&!PV!leading!to!TR!&!PS!!
+ Multiple!valves!defect,!e.g.!MR!
+ Late!complication!of!pacemaker!insertion!
o Damage!of!valvular!leaflet!/!chordae!/!trabeculae!when!inserting!the!lead!

Signs!!
+ ↑!JVP!with!prominent!c+v!wave!
+ Enlarged!pulsatile!liver,!jaundice!
+ Ankle!edema!&!hyperpigmentation!
+ Cardiac!cirrhosis!in!severe!cases!
+ Usually!no!murmur!due!to!relatively!low!pressures!in!right!heart,!but!if!audible!!!pansystolic!
murmur!(low!frequency)!
o Best!heard!on!lower!left!sternal!border!
o Increase!with!inspiration,!decrease!with!expiration!&!Valsalva!maneuver!
o Usually!very!soft,!loud!pansystolic!murmur!makes!lone!TR!unlikely!
o Very!severe!TR!in!pul!HT!!!no!loud!murmur!
" Because!RVH!!!TV!can’t!close!completely!
o ∴!Murmur!is!less!important!than!elevated!JVP!
+ Third!heart!sound!may!be!present:!best!heard!with!inspiration!at!left!lower!sternal!border!
+ Parasternal!heave:!left!lower!sternal!border!
+ Atrial!fibrillation!may!be!present!
+ **!Look!for!MR!/!other!murmurs!&!signs!of!pul!HT!(because!isolated!TR!is!very!rare!unless!IE!
in!IVDU,!usually!caused!by!severe!MR!or!pul!HT)!
Aortic0regurgitation0(AR)0
Causes!
+ Aortic!valve!insufficiency!
o Degenerative:!commonest!cause!in!elderly!
o Rheumatic!heart!disease!!
o Infective!endocarditis!!
o Ankylosing!spondylitis!!
o Bicuspid!valves:!esp!in!middle+aged!patient!with!AR!
o Large!VSD!(?)!
+ Aortic!root!dilatation!
o Marfan's!syndrome!
o Aortic!root!dissection/aneurysm!!
o Syphilitic!aortitis!!
o Ankylosing!spondylitis,!Rheumatoid!arthritis!
o HT,!trauma!
!
DDx!of!multiple!valvular!regurgitation!
+ Dilated!cardiomyopathy!
+ Infective!endocarditis!!!ask!for!the!temperature!chart!
!
Symptoms!
+ Asymptomatic!
+ Fatigue!and!dyspnea!(angina!less!a!feature!than!in!AS)!
!

Cardiology!+!36!
!
Physical!examination!
+ Pulse!!
o Regular!pulse:!AF!relatively!uncommon!in!pure!AR!
o Collapsing!pulse!(bisferiens!if!with!AS!)!&!Corrigan's!sign!
" Rapid!one!off!sign!
" Also!seen!in!elderly!with!severe!atherosclerosis!!!stiff!vessels,!non+compliance!
(not!elastic)!!!high!SBP!&!low!DBP!
o Nailbed!pulsation!(Quincke)!
+ Cubital!fossa:!locomotor!brachii!(prominent!pulsation!of!brachial!artery)!
+ Apex:!hypervolemic,!displaced!
o If!apex!not!displace!!!not!severe!AR,!unless!in!acute!severe!AR!(then!will!have!severe!
pul!edema)!
+ Auscultation!!
o Soft!A2!!
o Decresendo!early!diastolic!murmur!best!heard!at!left!lower!sternal!border!
" Strengthened!by!sit!up!and!lean2forward!with!full2expiration!
" Pulmonary!regurgitation!also!radiate!to!L!sternal!border,!but!!
• AR!is!louder!
• AR!murmur!is!louder!on!expiration!Vs!PR:!inspiration!
• Collapsing!pulse!in!AR!Vs!N/↓!volume!pulse!in!PR!due!to!↓!CO!
o *Usually!with!an!ejection!systolic!flow!murmur!!
" Due!to!the!torrential!blood!flow!/!due!to!coexisting!AS!
" Vs!AS:!loudest!at!LLSB!&!absence!of!AS!peripheral!signs!
o *Often!with!an!Austin!flint!murmur!!
" From!backflow!of!regurgitated!blood!and!hit!onto!the!closed!mitral!valves!
" Low!pitch!rumbling!mid+diastolic!and!presystolic!murmur!audible!at!apex!
" Vs!MS:!absence!of!loud!S1+openning!snap+tapping!apex!
+ End!by!
o Take!the!BP!of!this!patient!for!wide!pulse!pressure!
o Check!the!pupils!for!Argyll!Robertson!pupil!
o Look!for!stigmata!of!Marfan!syndrome!!
o Check!the!joints!for!ankylosing!spondylitis!and!rheumatoid!arthritis!
!
Assess!severity!
+ Wide!pulse!pressure!collapsing!pulse!
+ Soft!S2!
+ Long!diastolic!murmur!
+ Austin!flint!murmur!
+ Signs!of!left!ventricular!failure!!
!
Investigation!
+ ECG:!LVH!and!strain!
+ CXR:!widen!mediastinum,!heart!failure!
+ Echocardiogram:!confirm!the!diagnosis!and!for!the!severity!
o If!diameter!of!jet!>!2/3!of!diameter!of!LVOT!!!severe!
o If!diameter!of!jet!<!1/3!of!diameter!of!LVOT!!!mild!
+ Exercise!testing!for!functional!capacity!
+ Cardiac!catheterization!
+ CT!thorax!for!aortic!root!size!
!
!
!

Cardiology!+!37!
Treatment!
+ Medical!treatment!
o Diuretics!!
o Vasodilator!(nitrate!/!prazosin)!
o ACEI!(improving!HF,!maintain!systolic!function!&!prevent!LV!remodeling)!
+ Surgery!!
o Indications!for!surgery!
" Acute!AR,!e.g.!SBE!!!need!urgent!surgery!
" Symptomatic!severe!AR!(class!III!symptoms)!
" LV!function!<50%!
" Left!ventricular!dilatation!(end!diastolic!diameter!>75mm,!end!systolic!diameter!
>55mm)!!
" Frequent!ventricular!ectopic!beats!
" Need!for!concomitant!heart!surgery!
On general examination, this 80 years old lady is lying on bed without distress.
Cardiovascular examination reveals key features of:
a regular pulse of 80bpm, with the presence of collapsing pulse
corrigan's sign of visible carotid pulse is present, and its of bounding in nature
apex beat is diffused and displaced, at 6th intercostal space, 3cm lateral to midclavicular line
on ausculation, heart sound is dual with a soft S2, there is a grade 2/6 high pitch early distolic murmur best heard over
the left lower sternal border when patient leans forward with full expiration. (Another grade 5/6 ejection systolic murmur
with palpable thrill at aortic area is also present, which does/does not radiate to neck)
Finally, JVP is not elevated, and there is no ankle edema or basal crepitations.
In summary, this clinical picture is compatible with a patient with aortic regurgitation who is not in heart failure. For
etiology, marfanoid features or signs of infective endocarditis are absent. I would like to further examine this patient's
spine for ankylosing spondylits, peripheral joints for rheumatoid arthritis, and eyes for Argyll Robertson pupils.

0
Aortic0stenosis0(AS)0
Pathophysiology!!
+ Ventricular!pressure!normally!same!as!aortic!pressure!during!systole!
+ In!AS,!ventricles!need!to!build!up!high!pressure!but!aorta!still!may!have!low!pressure!
o In!low!systolic!BP!yet!still!have!pressure!overload!!!think!of!AS!
!
Etiology!
+ Supravalvular!
o William!syndrome!(rare)!
+ Valvular!!
o Congenital!AV!disease!
" E.g.!calcified!bicuspid!aortic!valve!(fusion!of!aortic!cusps!which!become!
thickened!with!varying!degree!of!calcification)!
o Degenerative!calcification!(senile)!
" Present!around!70+80!years!old!
" Can!be!controlled!by!controlling!smoking,!DM,!obesity,!emotion…!
o Post+inflammatory!disease!
" Rheumatic!valvular!disease!
" Non+rheumatic!inflammatory!process!
+ Infravalvular!
o HOCM!
!
Presentation!
+ Asymptomatic!
o *!Need!to!ask!really!asymptomatic!Vs!Patient!adapted!the!lifestyle!in!order!to!reduce!
symptoms!
o Latent!period:!increasing!obstruction,!myocardial!overload!
o Survival!no!change!much!even!if!change!valve!in!this!period!
!

Cardiology!+!38!
+ Angina,!myocardial!ischemia!
o LV!O2!demand!exceeds!supply!(LV!need!to!pump!harder!to!overcome!the!stenosis,!yet!
supply!↓)!
+ Dyspnea,!exertional!dyspnea!
+ Paroxysmal!nocturnal!dyspnea!
+ Congestive!HF!
+ Syncope!!
o DDx:!HOCM,!arrhythmia!
+ Uncommonly!cause!sudden!death!
+ Progress:!asymptomatic!!!angina!!!syncope!!!HF!
o Once!onset!of!severe!symptoms!!!survival!curve!drop!rapidly!
" Lifespan!2!years!after!onset!of!symptoms!
o Prognosis!of!having!HF!is!worse!than!syncope!than!angina!
" Once!patient!have!dilated!LV!AS,!patient!may!not!be!benefit!from!valve!
replacement!as!the!CO!may!be!too!low!for!surgery!
" So!important!to!pick!up!patient!in!earlier!stage!before!developing!HF!
!
Physical!examination!
+ Pulse:!slow!rising,!small!volume!(bisferiens!if!concomitant!AR!)!
+ Apex:!hyperdynamic!/pressure!overload!(may!be!slightly!displaced)!
o Although!apex!not!displaced,!still!have!LVH!(wall!thicker!but!not!dilated)!due!to!↑!
pressure!
+ Systolic!thrill!at!A+site!
+ Auscultation!!
o Soft!A2!!
o Harsh!ejection!systolic!murmur!@!aortic!area!radiates!to!neck!(bilateral)!
" Not!uncommon!to!be!heard!widely!over!the!precordium,!even!radiates!down!to!
apex!as!a!PSM!mimicking!MR!(Gallavardin!phenomenon)!
" Neck!radiation!Vs!carotid!bruit:!AS!murmur!is!bilateral!&!murmur!is!as!loud!as!
that!heard!at!A!area,!carotid!bruit!is!more!localized,!not!along!whole!course!of!
vessel!
" *!Hard!to!differentiate!from!infundibular!PS!
o Reversed!splitting!of!S2!(P2!occurs!before!A2)!
" Expiration:!A2!is!delayed!!!occurs!after!P2!
" Inspiration:!P2!is!delayed!!!split!is!diminished!
o **!Listen!hard!for!early!diastolic!murmur!at!LLSB!for!concomitant!AR!!!
+ Narrow!pulse!pressure!
+ Associated!AR!is!common!!!
o If!so,!think:!is!it!AR+AS,!or!AR+flow!murmur?!
o AS!vs!AR!dominance!
" Slow!rising!or!collapsing!pulse!!
" Narrow!or!wide!pulse!pressure!!
" Hyperdynamic!or!hypervolemic!apex!
Investigations!
+ ECG!!
o LVH!with!strain!pattern!of!increased!R!wave!on!V4+V6!
+ CXR!!
o Pulmonary!congestion,!increased!heart!size!(boot+shape:!LVH)!
+ Echocardiogram!!
o Confirm!diagnosis!and!for!the!severity!
o Size!of!valve,!transvalvular!pressure!gradient!(if!>40mmHg!!!severe),!maximum!aortic!
velocity,!EF!
!

Cardiology!+!39!
+ Exercise!testing!!
o Functional!capacity!
+ Cardiac!catheterization!
!
Grading!the!severity!of!AS!
+ Clinical!Signs!
o Narrow!pulse!pressure!
o Soft!2nd!heart!sound!
o Narrow!/!reverse!split!2nd!heart!sound!
o Systolic!thrill!/!heaving!apex!beat!
o Long!length!of!murmur,!late!peak!of!murmur!
" **!Intensity!of!murmur!NOT!related!with!severity!
o 4th!heart!sound!
o Cardiac!failure!
+ Investigations!
o Aortic!valve!area!<1cm2!!
o Systolic!gradient!across!the!aortic!leaflet!
!
DDx!
+ Aortic!sclerosis!(common!in!elderly,!also!have!ejection!systolic!murmur,!but!less!complications!
than!AS)!
o Absence!of!pressure!gradient!across!aortic!valve:!
o Normal!volume!
o Undisplaced!apex!beat!
o Localized!murmur!
o No!widened!pulse!pressure!
o Normal!/!loud!2nd!HS!!
" Vs!AS:!single!soft!blurred!2nd!HS!(A2!is!close!to!P2!due!to!AS!!!no!splitting)!
+ HOCM!!
o Jerky!pulse!
o Sustained!(double!/!triple)!apex!beat!
!
Complications!
+ Left!ventricular!failure!
+ Sudden!death!
+ Arrhythmia!&!conduction!abnormalities!(ventricular!arrhythmia,!heart!block)!
+ Systemic!embolization!
+ Infective!endocarditis!!
!
Follow+up!
+ Need!more!frequent!FU!for!moderate!to!severe!AS!or!bicuspid!valve!
o Do!ECG!and!blood!pressure!
o Not!do!exercise!test!if!there’s!severe!symptoms,!as!there’s!risk!of!sudden!death!during!
exercise!test!
!
Management!!
+ General:!avoid!strenuous!exercise!
+ Pharmacological!
o Diuretics,!nitrate!and!vasodilator!for!relieve!of!symptoms!of!HF!
+ Surgical!replacement!/!valve!debridement!
o Indications!
" Symptoms!(e.g.!chest!pain,!syncope)!
!

Cardiology!+!40!
 Heart!failure!(LV!function!<50%)!
"
Extremely!severe!AS!
"
• Valve!area!<0.6cm2,!mean!gradient!>60mmHg,!aortic!jet!velocity!>5m/s!
" Need!for!concomitant!cardiac!surgery,!e.g.!CABG!
o Need!to!do!cardiac!catheterization!to!rule!out!IHD!before!surgery!
" AS!commonly!a/w!atherosclerosis,!if!there’s!concomitant!IHD!!!do!CABG!at!the!
same!time!
• Because!if!CABG!is!needed!few!years!after!valve!replacement!!!mortality!
rate!↑!
+ Balloon!valvuloplasty!+/+!TAVI!(esp!in!high!risk!elderly)!
o Can!only!give!transient!benefit:!6+9!months!!!bridging!treatment!only!
o Risk!of!rupture!if!balloon!is!too!large!
o Transcatheter!aortic!valve!implantation!(TAVI)!
On General examination, this 80 years old lady is not in distress and lying on bed. Cardiovascular examination reveals
key features of:
a regular pulse of 80 bpm
a slow rising, low volume carotid pulse
hyperdynamic apex beat located at 5th intercostal space, 1cm lateral to midclavicular line parasternal heave is absent,
but systolic thrill is palpable on the aortic area
Auscultation reveals dual heart sounds with a soft S2
there is a grade 5/6 mid-systolic murmur, best heard over aortic area, radiating to the neck otherwise the diastolic
component is clear
JVP is normal, no ankle edema, and bilateral lung bases are clear.
In summary, this clinical picture is compatible with a patient with aortic stenosis, who is not in heart failure. The etiology
is unknown, but is usually due to degenerative, rheumatic heart disease, or congenital bicuspid valve.
This patient has aortic stenosis, evidented by a slow rising, low volume carotid pulse, hyperdynamnic non-displaced apex,
a dual heart sound with soft S2, and a grade 5/6 ejection systolic murmur best heard over aortic area radiating to the
neck.
She is not in heart failure, as shown by her normal JVP, absent of ankle edema, as well as the clear lung bases. Etiology
of her aortic stenosis is unknown, but is usually due to degerative, rheumatic heart disease, or congential bicuspid valve.
Although aortic sclerosis can also give rise to a similar mumur, the presence of slow rising carotid pulse and a
hyperdynamic apex make it more a aortic stenosis.

Pulmonary0regurgitation0(PR)0
Signs!!
+ Diastolic!murmur!
o Radiate!to!L!lower!sternal!border!
+ Loud!2nd!HS!due!to!pulmonary!HT!
Pulmonary0stenosis0(PS)0
+ Only!congenital!problem,!not!acquired!
+ May!cause!fatigue,!syncope!&!RV!failure!
+ A!harsh!murmur!on!P!area!radiating!to!left!neck!(&!back?),!accompanied!by!palpable!thrill!
+ Widely!split!S2!
Astrial0Septal0Defect0(ASD)0
Types!
+ Secundum!(75%)!
o Fossa!ovalis!defect:!can!be!corrected!by!catheter+based!Rx!
+ Primum!(15%)!
o Endocardial!cushion!defect!associate!with!mitral!valve!regurgitation!and!inlet!
ventricular!septal!defect!
+ Sinus!Venosus!(5+10%)!
o Located!near!to!the!junction!where!vena!cava!join!the!right!atrium,!associated!with!
partial!anomalous!pulmonary!venous!drainage!
+ Coronary!Sinus!defect!
o Very!rare,!communication!between!coronary!sinus!and!left!atrium!
!
Clinical!presentation!
+ Exercise!intolerance,!arial!arrhythmia!(may!present!late)!
!

Cardiology!+!41!
+ Pulmonary!HT!/!Eisenmenger!syndrome!
!
Physical!examinations!
+ Prominent!RV!heave,!loud!P2!
+ Systolic!murmur!pulmonary!area!(flow!murmur)!
+ Diastolic!rumbling!murmur!LLSB:!due!to!functional!TS!due!to!increased!flow!
+ Pansystolic!murmur!at!T!area:!if!have!dilated!tricuspid!valve!annulus!
+ Wide!fixed!splitting!2nd!HS:!not!always!present!!
o During!expiration,!R+to+L!shunt!increase!!!counteract!the!normal!respiratory!variation!
(increase!in!venous!return!in!inspiration)!!
!
Investigations!
+ CXR:!cardiomegaly!
+ ECG:!RBBB,!axis!deviation!(R!=!secundum,!L!=!primum),!abnormal!p+wave!inferior!leads!(sinus!
venosus)!
+ TTE:!mostly!diagnostic!
+ TEE:!to!assess!rim!adequacy!for!percutaneous!closure!(need!≥5mm!to!hold!the!device)!
o Also!look!for!anomalous!pulmonary!venous!drainage!
!
Treatment!
+ Benefit!of!ASD!closure!
o Improve!survival!(closure!performed!<25!years!old)!!
o AF!prevention!(closure!performed!<40!years!old)!!
o Prevent!pulmonary!HT!and!heart!failure!!
o Secondary!prevention!of!paradoxical!embolization!!
o Improved!exercise!tolerance!!
+ Catheter+based!Rx!!
o Indication!
" Secundum!ASD!<40mm!with!haemodynamically!significant!shunting!
(Qp/Qs>1.5)!!
" Smaller!shunts!if!paradoxical!embolisation!
o Peri+operative!issues!
" Local!anesthesia!(when!intracardiac!echo!used!for!guidance)!
" Right!femoral!vein!access!
" IV!Heparin!
" Double!anti+platelets!(aspirin/plavix)!3+6!months!until!endothelialization!
completed!
" IE!prophylaxis!for!6!months!
" FU!echo!!!life!long!IE!prophylaxis!if!residual!leak!(inhibit!endothelialization)!!
" MRI!should!be!safe!after!3!month!post+implant!
o Complications!
" Inherent!to!catheter!interventions!
" Anti+platelets:!allergy,!bleeding!
" Risk!of!infective!endocarditis!
" Potential!risk!of!erosion!to!nearly!cardiac!structures,!e.g.!RA!/!LA!leading!to!free!
wall!rupture!
" Mortality!rate!<1%!
+ Surgery!
o Indication!
" Too!Big!ASD!>40mm!
" Inadequate!rims!to!hold!the!device!
" Associated!partial!anomalous!pulmonary!venous!drainage!
!

Cardiology!+!42!
Ventricular0Septal0Defect0(VSD)0
Physical!examination!
+ Pan+systolic!murmur!over!precordium!
o Best!heard!at!LLSB,!no!radiation!
o Harsh!&!lower!pitch!(Vs!MR:!relatively!high!pitch)!
o Younger!patients!
+ Otherwise!normal:!normal!pulse,!normal!impulse…!
o Because!the!VSD!you!can!hear!in!an!adult!is!mostly!non+significant!(otherwise!already!
operated)!
Heart0failure0(HF)0
Causes!!!
+ Systolic!heart!failure!!!
o Contraction!defect!!!
" Ischemic!heart!disease!!!
" Arrhythmias!!!
" Cardiomayopathies!!!
" Infiltrations:!amyloid,!fibrosis,!hemochromatosis,!glycogen!storage!diseases!!!
" Myocarditis!!
o Volume!and!pressure!overloads!!!
" Hypertension!!!
" Valvular!heart!diseases!!!
+ Diastolic!heart!failure!!!
o Aging!and!IHD!with!fibrosis!!!
o Left!ventricular!hypertrophy!(from!hypertension)!!!
o Contrictive!pericariditis!!!
o Increased!intrathoracic!pressure!!
+ **!If!biventricular!diseases!!!
o IHD!less!likely!!!
o Chronic!triple!vessels!diseases:!slow!progression!!!
o Cardiomyopathy:!slow!progression!!!
o Myocarditis:!acute!onset!!
!!!!
Pathogenesis!!!
+ Reduced!cardiac!output!inadequate!to!meet!the!metabolic!demand!!!
+ Neurohormonal!compensation!!!
o Renin<angiotensin<aldosterone2system!
" Increased!afterload!by!peripheral!vasoconstriction!
" Increased!preload!by!fluid!retention,!worsening!congestion!
" Activate!sympathetic!system!
o Sympathetic2system!
" Increased!circulating!catecholamines!!!increased2mortality!
" Induce!myocytes!damage!and!necrosis!
" Induce!myocytes!hypertrophy!(increase!O2!demand)!
" Increase!heart!rate!(reduce!time!available!for!ventricular!filling)!!
" Peripheral!vasoconstriction!(alpha1R,!increase!afterload)!
" Reduced!beta+1R!density!
o Vasopressin2activation2!
" Increased!water!retention!
o Cytokine2production!!!
" Vasocontricters:!endothelin1,!big!endothelin!!!
" Proinflammatory:!TNFalpha,!IL+1,!IL+6!!!
!

Cardiology!+!43!
 " Fibrogenic:!TGFbeta!!!
+ Skeletal!muscle!deconditioning!!!
o Biochemical!!!
" Defective!oxidative!metabolism!!!
" Alteration!of!enzymatic!actions!!!
• Reduced!respiratory!enzymes!!!
• Increased!glycolysis!
• Phosphocreatine!depletion!!!
• Excessive!acidification!!!
o Histological!!!
" Muscle!fiber!atrophy!!!
" Increased!fast!twitch!type!II!fibers!!!
" Increased!lipid!content!!!
+ Peripheral!blood!flow!abnormalities!!!
o Reduced!cardiac!output!!!
o Neurohormonal!peripheral!vasoconstriction!!!
o High!limb!vascular!resistance!!!
o Reduced!vasodilatory!ability!of!muscles!!!
!
Diagnosis!
+ Diagnosis!is!clinical!!Base!on!sings!&!symptoms,!not!base!on!EF!
o E.g.!PND,!basal!crep,!JVP,!S3!gallop,!ankle!edema,!CXR…!
!
Presentation!!
+ Orthopnea!
o If!suddenly!no!orthopnea!without!treatment!!!not!a!good!sign!!!need!to!look!for!
biventricular!failure!!!↓!lung!congestion!
+ PND!
+ HypoNa!
o Effective!circulation!↓!!!activity!of!RAS!↑!!!fluid!retention!!!dilutional!hyponatremia!
" Degree!of!hyponatremia!indicate!severity!of!HF!
" Hyponatremia!can!also!caused!by!diuretics!
!
New!York!Heart!Association!Classification!of!heart!failure!
Class!I! ! Patients!with!no!limitation!of!activities!
! They!suffer!no2symptoms2from2ordinary2activities!
Class!II! ! Patients!with!slight,!mild!limitation!of!activity!
! They!are!comfortable!with!rest!or!with!mild!exertion!
Class!III! ! Patients!with!marked!limitation!of!activity!
! They!are!comfortable2only2at2rest.!
Class!IV! ! Patients!who!should!be!at!complete!rest,!confined!to!bed!or!chair!
! Any!physical!activity!brings!on!discomfort!and!symptoms2occur2at2rest!
Limitations!
! Discordance!with!cardiac!function!
! Non+cardiac!factors!contribute!to!symptoms!
! Tends!to!fluctuate!with!time!
!
Mortality!risk!of!AMI!by!Killip!class!
Class!I! ! No!clinical!signs!of!heart!failure!
Class!II! ! Rales!/!crackles!in!lungs,!an!S3!gallop!&!↑!JVP!
Class!III! ! Frank!acute!pulmonary!edema!(APO)!
!

Cardiology!+!44!
 Class!IV! ! Cardiogenic!shock!/!hypotension!(SBP!<!90mmHg)!&!evidence!of!
peripheral!vasoconstriction!(oliguria,!cyanosis,!or!sweating)!
!
Investigation!
+ CBC,!LRFT,!TFT!
+ Cardiac!enzymes:!Troponin!I!&!Troponin!T!
o Increase!in!MI,!ischemia,!HF,!renal!failure,!sepsis!!
+ BNP!!
o One!of!the!4!natriuretic!peptide!(ANP,!BNP,!CNP,!DNP)!
o Released!from!ventricles!during!P!or!V!overload!(LV!>!RV)!
o Lead!to!dilation!of!arteries!&!veins,!diuresis,!natriuresis!
o <100:!can!r/o!HF!(N!level)!
o >400:!can!be!due!to!HF,!pulmonary!embolism,!pulmonary!hypertension,!renal!failure!
o 100+400:!GREY!AREA!
+ ABG!
+ CXR:!signs!of!HF!(ABCDE)!
+ ECG:!ischemia,!ventricular!hypertrophies,!arrhythmia,!post!MI!
+ Echo!!
o Look!for!valvular!lesions!
o EF!to!differentiate!systolic!vs!diastolic!HF!
o If!patient!had!valve!replacement!
" Look!at!LV!systolic!function!&!valve!status!
" Look!for!prosthetic!valve!failure,!e.g.!paravalvular!leak!
!
Poor!prognostic!factor!!!assess!need!for!transplant!
+ Sinus!tachycardia!
+ Poor!EF!by!Echo!
+ Renin!/!adrenaline!↑!
+ Low!Na!
+ Poor!renal!function!
+ Exercise!test!max!O2!consumption!(VO2!max)!<!13.5ml/kg/min!
!
Acute!treatment!!!see!APO!
!
Long+term!management!
+ Patient!education!to!reinforce!importance!of!drug!compliance!
+ Cardiac!rehab:!exercise,!breath!exercise,!physio…!
+ Lifestyle!modification!
o Prop+up!&!bed!rest!if!severe!
o Fluid!&!salt!restriction!(<2g/!day)!
+ Treat!the!underlying!cause!
o ICD!for!arrhythmias!!!
o Control!hypertenison!!!
o Valvular!replacement!if!defected!!!
o Remove!any!reversible!causes!for!heart!disease!
!
Pharmacological!treatment!
+ ACEI!(e.g.!lisinopril):!have!survival!benefit!
o Recommended!for!ALL!heart!failure!patients!
o Symptomatic!improvement!&!improve!exercise!tolerance!
o Prevent!disease!progression!&!death!
o Effect!may!not!be!apparent!for!1+2!months!!
!

Cardiology!+!45!
 o S/E:!dry!cough!(due!to!acuumulation!of!bradykinin);!angioedema!
+ ARB!(e.g.!candesartan):!less!evidence!on!survival!benefit!compared!with!ACEI!
o Used!if!patient!cannot!tolerate!S/E!of!ACEI!(coughing)!
+ β<blocker:!have!survival!benefit!
o Metoprolol!(controlled!release),!carvedilol,!bisoprolol!
o C/I!in!acute!setting,!e.g.!APO!due!to!anti+inotropic!effect!
o Used!in!long!term!control!of!HF!&!AF,!start!with!low!dose!after!acute!phase!
" Usually!start!with!ACEI!1st,!then!slowly!titrate!BB!up!
o Mechanism!
" ↓!effect!of!excessive!circulating!catecholamine!
" ↓!contractility,!HR!&!BP!!!↓!oxygen!demand!
" ↓!HR!!!prolong!diastolic!filling!period!!!increase!subendocardial!myocardium!
blood!flow!
" ↓!remodeling!of!heart!&!↓!risk!of!arrhythmia!
+ Spironolactone!25mg!daily:!have!survival!benefit!
o Add!this!if!still!class!3/4!HF!despite!optimal!dosage!of!BB!/!ACEI!!
o Spironolactone!block!aldosterone!effect!!!↓!RAS!effect!
o S/E:!painful!gynaecomastia,!hyperK!
o NEJM/2011/Jan:/Eplerenone/used/in/Class/II/heart/failure/patients/improves/all/the/primary/
outcomes/including/mortality/rate,/but/hyperkalemia/is/a/possible/adverse/event,/need/to/
monitor/closely.!
+ Nitrites!+!hydralazine:!have!survival!benefit!
o For!those!who!cannot!tolerate!ACEI/ARB!
o Arteriole!&!vein!dilators!!!afterload!&!preload!
+ Digoxin:!may!improve!symptoms!&!↓!hospitalization!but!not!improve!survival! !
o Used!in!NYHA!III/IV!&!have!persistent!tachycardia!
o Can!be!used!in!sinus!rhythm,!but!particularly!in!concurrent!AF!pts!
o Mechanism!
" Blocks!Na/K!ATPase!!↓Ca!efflux!in!myocytes!!!mild!+ve!inotropic!!
" Central!effect!on!vagal!system!!!↑!AV!nodal!delay!&!control!AF!
o Narrow!therapeutic!index:!itself!proarrthymic!(VT)!when!overdose,!esp.!in!hypoK!!
o Getting!out!of!favor!due!to!S/E;!BB!can!be!used!to!control!AF!as!well!
+ Diuretics:!improve!symptoms!not!survival!
o Never!used!alone!to!treat!HF!
o Monitor!body!weight!for!dose!adjustment!
o S/E:!electrolyte!disturbance!
!
Surgical!treatment!
+ CRT!(cardiac!resynchronisation!therapy)!
o For!patient!with!poor!EF,!e.g.!NYHA!IV!!!20%!benefit!
" Should!assess!the!clinical!status!at!least!3!months!after!optimization!of!
medications!before!considering!device!therapy!
" Class!1!indication:!SR,!LVEF!≤!35%,!QRS!≥!120!msec,!NYHA!Class!III!/!ambulatory!
class!IV,!with!optimal!medical!therapy!!
o Best!for!patient!with!LBBB!with!wide!QRS!(i.e.!problem!in!conduction!system)!
" In!most!of!the!time!the!post!wall!of!LV!is!most!far!away!from!AV!node!!!late!
contraction!of!post!wall!!!blood!cannot!be!pumped!out!effectively!
" In!CRT,!a!lead!is!put!into!the!post!wall!!!synchronize!contraction!of!post!wall!
with!septal!wall!(&!the!rest!of!LV)!!!improve!EF!
" In!patient!with!LBBB!with!wide!QRS!!!no!need!to!do!Echo,!otherwise!do!pre<op2
Echo!to!locate!the!site!of!slowest!conduction!
!

Cardiology!+!46!
 o CRT!is!not!useful!in!IHD!which!have!lots!of!fibrosis!
" No!matter!where!to!put!the!lead!!!still!cannot!synchronize!the!whole!ventricle!
o Takes!a!few!months!to!work!!!no!role!in!acute!setting!
+ CRT+D:!CRT!defibrillator!
+ ICD!(Implantable!cardiovertor!defibrillator)!
o Most!patients!in!NYHA!I+III!die!of!arrhythmia!!!can!consider!ICD!
o Most!patients!in!NYHA!IV!die!of!pump!failure,!so!only!for!those!who!are!stable!(e.g.!no!
ankle!edema,!otherwise,!they!are!more!likely!die!of!HF!and!thus!won’t!benefit!from!ICD)!
+ CCM!(cardiac!contractility!modulation!therapy)!
o Put!2!leads!in!RV!without!entering!LV!
o Improve!contractility!of!heart!by!delivery!signal!at!refractory!state!!!↑!Ca!release!
o Limitations!!
" Not!for!very!very!poor!heart!function!
" Need!frequent!battery!changing!
o Advantages!
" Independent!of!underlying!heart!disease,!e.g.!scars!
" Not!↑!lethal!arrhythmia!
+ LV!assisted!device!!
o Artificial!pump!to!take!over!LV!function!(bridging!Rx!before!cardiac!transplantation)!
o May!lead!to!infection!if!placed!chronically!since!it!is!a!foreign!device!
+ Cardiac!transplantation!
Diastolic0dysfunction0
+ Heart!failure!with!normal!ejection!fraction!
+ Heart!become!more!stiff!!!↓!compliance!!!loss!/!↓!+ve!pressure!to!suck!blood!into!ventricle!
!!↓CO! !
o Risk!factor:!female,!HT!!!degenerative!!!stiffer!chambers!
+ Diastolic!dysfunction!!!ventricular!filling!more!depend!on!atrial!contraction!
o When!AF!!!symptoms!aggravated,!more!SOB…!
+ Typical!to!cause!↓!exercise!tolerance:!↓!diastolic!filling!time!when!HR!↑!
!
Management!
! Treatment!has!not!been!well!studied,!no!evidence+based!therapies!
! Direct!vasodilators!not!indicated!
! ARB:!candesartan!
! Diuretics!used!cautiously:!the!stiff!heart!is!dependent!on!adequate!preload!
o Use!in!acute!HF!with!fluid!overload!
o But!not!give!excessive!dose!after!acute!exacerbation!of!HF!(may!not!need!maintenance!
dose,!or!use!low!dose,!weak!diuretics)!
! Control!of!BP,!HR!in!AF,!and!other!risk!factors!
! As!these!patients!have!CAD,!HT!and/or!DM,!thus!ACEI!&!BB!may!already!be!indicated!
Acute0pulmonary0oedema0(APO)0
Precipitating!factors!for!cardiogenic!pulmonary!edema!
+ Acute!decompensation!of!pre+existing!chronic!HF!
o Infection!(most!common),!e.g.!chest!infection,!URTI!(flu),!UTI!
o Poor!compliance!to!medication!
o Poor!compliance!to!fluid!/!salt!restriction!
o Poor!BP!control!
o Renal!dysfunction!
o Surgery!!
+ Arrhythmia,!e.g.!new!onset!AF!
+ AMI!causing!acute!valve!failure!
!

Cardiology!+!47!
+ IE!cauing!acute!AR!
+ Aortic!dissection!
+ Myopathies,!e.g.!acute!myocarditis!!
+ Drugs!
o Nephrotoxic!drugs!!!acute!renal!failure!
o NSAIDs!!!fluid!retention,!ARF,!PU!(!!GIB!!!anemia)!
o +ve!inotropes!
+ High!out+put!state!
o Anemia,!pregnancy,!hyperthyroid!
+ Toxins:!alcohol,!street!drugs!
+ Unrelated!illness:!renal,!pulmonary,!hypothyroid,!GI!
!
DDx!of!non+cardiogenic!causes!of!API!
+ Thyrotoxic!
+ Renal!failure!
+ ARDS!(mimic!APO)!
!
! Cardiogenic!! Non+cardiogenic!!
History2! + AMI/!CHF!! + Other!insults!!
P/E2! + Low!cardiac!output!(cold!sweaty!palm)!! + Signs!of!trauma,!
+ Raised!JVP,!peripheral!edema! infection,!pacreatitis,!
+ Gallop!rhythm!! DIC!
Ix22 + BNP2>500pg/ml! + BNP2<100pg/ml!!
+ Cardiac!enyzme!raised!
+ ECG!show!ischemic!changes!
CXR2! + Large!heart! + Peripheral!infiltrates!
+ Central!infiltrates! + Vascular!pedicle!width!
+ Kerley!B!lines! <70mm!!
+ Vascular!pedicle!width!>70mm!!
Transthoracic2Echo! + Large!dilated!heart! !
+ Reduced!ejection!fraction!!
Pulmonary2artery2 + Pulmonary!artery!occulusion!pressure! + Pul!artery!occulusion!
catheterization2! >18mmHg!! pressure!<18mmHg!!

Cardiogenic0pulmonary0edema0
Presentation!
+ Sudden!onset!of!dyspnea!&!tachypnea!±!cough!with!frothy!pinkish!sputum!
o Classically!occurs!over!few!mins!but!may!be!over!hours!
o Worse!when!lying!down!
+ ±!Chest!pain,!palpitation!
!
P/E!
+ Patient!look!very!ill!&!dyspnic,!need!high!O2!supplement!
o Vs!chronic!L!HF!!!also!have!basal!creps,!but!look!much!more!stable!
+ Tachypnea!&!tachycardia!
+ Use!of!accessory!respiratory!muscles!
+ Bilateral!basal!fine!crepitus!
+ Increase!in!vocal!resonance!
+ Marked!HT!with!peripheral!vasoconstriction,!but!hypotension!may!occur!
!
!
!

Cardiology!+!48!
Investigations!
+ ECG,!cardiac!enzyme,!TnT:!r/o!ACS/MI!
+ CXR:!confirm!diagnsis!
o Bilateral!lower!zone!haziness:!bat!wing!appearance!
o Cardiomegaly!!
o Kerley!B!lines!
o Enlarged!hilum!
o Peri+bronchial!cuffing!
o Upper!lobe!pulmonary!venous!diversion!
o May!have!pleural!effusion!
+ ABG:!pH!&!respiratory!status!
+ RLFT,!CBC,!cloting,!glucose:!baseline!
+ Echo:!cardiac!function!status!
!
Management!!
+ Complete!bed!rest,!pop!up!
+ Low!salt!diet,!fluid!restriction!(NPO!if!very!ill),!restricted!IVF!<1L!
+ High!flow!O2/!Ventilation:!may!need!100%!O2!
o Correct!hypoxia!&!break!the!vicious!cycle!
" Impaired!LV!Fx!!!pul!edema!!!hypoxia!!!further!impair!LV!Fx!
o Consider!ventilatory!support!in!case!of!desaturation,!patient!exhaustion!or!cardiogenic!
shock!!
" Non+invasive!ventilation!1st:!CPAP!Vs!BiPAP!
• CPAP!open!up!the!collapsed!alveoli,!∴use!1st,!if!failed!!!BiPAP!
• BiPAP!is!better!in!type!2!resp!failure,!make!the!impending!failure!resp!ms!
to!fatigue!later,!but!may!↑!CV!mortality!
+ Close!monitoring!of!BP/P,!I/O,!RR,!SaO2,!Q30+60min!(initially)!
+ Treatment2principle:2Pre<load2reduction2&2after<load2reduction2
+ If!BP!stable!(>90mmHg)!
o BP!reduction!(usually!HT!in!APO)!except!in!cases!of!cardiogenic!shock!!
o IV2fluoximide!80mg!(double!the!usual!dose,!at!least!40mg)!
" ↓!fluid!retention!!!↓!pre+load!
" Don’t!give!oral!because!lots!of!gut!edema!in!acute!phases,!can!change!back!to!
oral!when!ankle!edema!improve!(signify!gut!edema!also!improve)!
" Can!give!all!80mg!at!once!in!the!morning!so!patient!no!need!to!get!up!to!pee!
o Vasodilator!
" Decrease!venous!return!to!heart!!!↓!pre+load!
" May!lead!to!hypotension!
" Titrate!dose!against!BP:!can!change!dose!rapidly!due!to!short!t½!!
" Choice!
• IV2nitroglycerin2(TNG)!infusion!
• IV2nitroprusside!(risk!of!cyanide!toxicity)!
• IV2nesiritide!!
• IV!morphine!(low!dose):!if!pt!is!anxious!/!agitated!/!need!intubation!
o Venodilation!(!↓!pre+load,!though!the!vasodilation!effect!is!much!
weaker!than!nitrate),!↓!anxiety!&!SOB!(↓!symp)!
o But!never!give!high!dose!morphine:!cause!respiratory!depression!
which!can!kill!the!patient!!!
o Add!digoxin!if!
" AF!
" Sinus!rhythm!&!remain!symptomatic!despite!using!diuretic,!ACEI!&!BB!
!
o *!Can!keep!BB!if!on!BB!originally!
Cardiology!+!49!
+ If!BP!unstable!(cardiogenic!shock)!
o Inotropes!infusion!(dobutamine/dopamine):!improve!contractility!!
" Dobutamine:!no!α+adrenergic!property,!stimulate!β1+adrenoceptor!!!↑!HR!&!
contractility,!vasodilation!(!may!further!↓!DBP!&!coronary!flow,!∴usu!used!with!
noradrenaline)!
" Dopamine!cause!tachycardia!!!not!preferred!
" If!BP!too!low!!!may!need!adrenaline,!but!risk!of!vasoconstriction!!!organ!
damage!
o Vasoactive!agent!(noradrenaline)!
" Vasoconstriction!(↑!DBP)!!!↑!coronary!perfusion!pressure!&!flow!
o If!BP!still!not!stabilized!/!refractory!to!Rx!!!very!poor!prognosis!
o Can!still!consider!
" IABP!!
" PCI!for!ischemia!/!MI!
" Intervention!for!severe!valvular!lesion,!e.g.!PTMC!for!MS!
" Cardioversion!if!associated!with!new+onset!AF!!
• But!risk!of!stroke!due!to!dislodgement!of!clot!in!atrium!
• Vs!chronic!AF!!!no!need!to!stop!AF,!use!other!methods!
+ Find!out!&!treat!underlying!cause!
o ECG:!arrhythmia,!ACS!
o CBC:!anemia,!infection!
o R/LFT:!renal!failure!can!mimic!HF,!HF!can!lead!to!hypoperfusion!of!kidney!
o Blood!gas:!metabolic!acidosis!in!hypoperfusion;!respiratory!acidosis!in!respiratory!
failure!(late!stage)!
o Cardiac!enzyme:!ACS!
o Coronary!angiogram:!ACS!
!
Monitor!treatment!response!
+ Orthopnea,!PND!
+ Sacral!/!ankle!edema,!skin!wrinkle!(sign!of!↓!in!edema)!
+ JVP,!basal!creps!
+ Body!weight!daily!
o BW!should!↓!for!few!kg!when!give!adequate!lasix!
o Can!give!information!for!next!admission:!whether!SOB!is!due!to!HF!or!not,!e.g.!SOB!
again!few!weeks!later!&!BW!is!few!few!kg!heavier!than!last!discharge!!!likely!HF!!
+ I/O!
Pericarditis0
Causes!
+ Infective!
o Viral!!
" Children:!coxsackie!virus!!
" Adults:!CMV,!herpes!virus,!HIV!
o Bacterial:!Pneumococcus,!TB!
o Fungal:!histoplasmosis,!IC!!!Aspergillus,!Candida,!Coccidioides!
+ Metabolic:!hypothyroidism,!uremia!
+ Autoimmune:!SLE,!rheumatic!fever!
+ Dressler’s!syndrome,!postpericardiotomy!syndrome!(after!CABG)!
+ Trauma!
+ Aortic!dissection!
+ Malignancy:!paraneoplastic!syndrome!
+ Drug+induced:!isoniazid,!cyclosporine,!hydralazine,!warfarin,!heparin!
!

Cardiology!+!50!
+ Radiation+induced!
+ Idiopathic!!
!
Presentation!
+ Pleuritic!chest!pain!
o Radiate!to!trapezius!ridge,!neck,!left!shoulder!or!arm!
o Worse!during!inspiration,!when!lying!flat,!or!during!swallowing!and!with!body!motion!
o Relieved!by!leaning!forward!while!seated!
+ Low+grade!intermittent!fever!
+ SOB,!cough!and!dysphagia!
!
Physical!exam!
+ Pericardial!friction!rub:!atrial!systolic,!ventricular!systolic!&!early!diastolic!rub!
+ Tachypnea!!
+ Ewart!sign:!percussion!dullness!&!bronchial!breathing!between!tip!of!left!scapula!&!vertebral!
column!
o Due!to!large!pericaridial!effusion!which!compress!the!left!lower!lobe!of!lung,!causing!
consolidation!/!atelectasis!
+ Fever:!usually!low!grade!!
+ Cyanosis,!hepatomegaly!&!ascites!
+ Tachycardia!&!cardiac!arrhythmias,!e.g.!premature!atrial!&!ventricular!contractions!
+ Signs!of!cardiac!tamponade!
!
Investigation!
+ ECG!
o Diffuse!concave!upward!ST!elevation,!except!in!leads!aVR!&!V1!
" ST!segment!elevation!more!in!lead!II!than!III!!!pericarditis!
• Vs!STEMI:!ST!elevate!more!in!lead!III!than!II!
o ST!depression!only!@!aVR!±!V1!
o Upright!T!waves!in!leads!with!ST!elevation!
o PR!depression!in!multiple!leads!(only!in!viral,!early!transient!in!hours)!
" PR!segment!deviates!opposite!to!P+wave!polarity!!
o PR!elevation!only!@!aVR!±!V1!
o **!If!can’t!differentiate!from!MI!!!can!do!ECG!15+30mins!again,!if!static!(no!evolution)!
!!less!likely!to!be!MI!
o **!Also!look!for!low!voltage!/!electrical!alternans!suggesting!effusion!!!
+ CBC!d/c,!RFT!(urea,!Cr)!
+ CRP,!ESR,!cardiac!enzyme!
+ Viral!serology!
+ CXR!
o Flask+shaped,!enlarged!cardiac!silhouette!in!large!pericardial!effusion!/!cardiac!
tamponade!!
" Normal!cardiac!silhouette!seen!in!patients!with!rapid!accumulation!&!
tamponade!
o R/O!aortic!dissection,!which!also!gived!statin!
+ Echo:!r/o!complications,!e.g.!pericardial!effusion!
+ Pericardiocentesis!with!pericardial!fluid!analysis!
!
Treatment!
+ NSAID!
+ Pericardiocentesis!if!pericardial!effusion!/!temponade!
!

Cardiology!+!51!
Palpitation0
History!!
+ Continuous!or!intermittent!!
+ Regular!or!irregular!!
+ Associated!symptoms:!chest!pain,!dizziness,!polyuria!!
+ Precipitating!factors!!
+ History!of!heart!diseases!!
!
Causes!!
+ Irregular!beats!!
o Ectopic!beats!(triggered!by!alcohol,!stress!or!debility,!strong!cheese,!chocs)!!
o Atrial!fibrillation!(usually!>120bpm)!!
+ Regular!beats!!
o Sinus!tachycardia!(anxiety,!hyperdynamic!circulation!like!anemia,!preg,!thyroid)!!
o SVT!(asso!with!post!episodic!polyuria)!!
o VT!(asso!with!syncope)!!
Sudden0cardiac0death0
DDx!
+ Hypertrophic!cardiomyopathy!(HCM)!
o Due!to!patchy!fibrosis!of!myocardium!affecting!conduction!pathway!
+ Long!QT!syndrome!
+ Brugada!syndrome!
!
SCD!survivor!due!to!malignant!arrhythmia!without!reversible!cause!!!!
+ Need!ICD!insertion!!
+ Also!need!to!test!for!Brugada!syndrome!
o Need!family!counseling!&!screening!
Arrhythmia0
Abnormal!impulse!formation!
+ Abnormal!automaticity!
+ Afterdepolarization!
o Abnormal!depolarization!occuring!in!phase!2,3!or!4!in!cardiac!cycle!
o Resulted!in!abnormally!premature!depolarization!of!cardiac!muscle!
o Early2afterdepolarization!
o Occurs!in!phase!2!or!3!
" Phase!2!due!to!augmented!opening!of!sodium!channels!
" Phase!3!due!to!opening!of!calcium!channels!
o Delayed2afterdepolarization!
" Occurs!in!phase!4!
" From!eg!digoxin!toxicity!
" Increased!cytosolic!hence!sarcoplasmic!reticulum!Ca!content!
" Efflux!hence!depolarizatioin!
!
Abnormal!impulse!conduction!
+ Conductioin!block!
+ Reentry!system!

Cardiology!+!52!
Tachycardia0
! Regular! Irregular!
Wide! Ventricular!tachycardia! Pre+excited!AF!(WPW)!
! ! Very!fast!rhythm!(RR!>0.2)!
SVT!with!aberrant!conduction! !
! AVRT! Polymorphic!VT:!Torsades!de!pointes!
! WPW! ! May!self!terminate!&!regain!
consciousness!
!
VF!
+ Non+perfusing!!!must!be!LOC!
+ Never!able!to!self!terminate!
Narrow! Sinus!tachycardia! Atrial!flutter!with!variable!conduction!
(supra+ ! P!wave!present! !

ventricular! ! Usually!>150/min! Multifocal!atrial!tachycardia!

origin)! ! Carotid!sinus!massage!(CSM):! ! A/w!COPD!!
appearance!of!P!wave,! ! Variable!P!morphology!&!varying!PR!
gradually!slow!down! interval!
!
!
PSVT! Atrial!fibrillation!
! No!P!wave,!regular! ! No!P!wave!
! CSM:!abrupt!cessation!of! ! Fibrillating!baseline!
tachycardia! ! Irregular!RR!interval!
! ! CSM:!no!improvement,!irregular!
Atrial!flutter!with!fixed!conduction! rhythm!
! P!Wave:!replaced!with!multiple!
F!(flutter)!waves,!usually!at!a!
ratio!of!2:1,!but!sometimes!3:1!!
! Flutter!baseline/!“saw+tooth”!
appearance!
! Fractional!block!
! CSM:!flutter!waves,!with!less!
fractional!block!

Cardiology!+!53!
Sinus0tachycardia0
Causes!
! Dehydration!
! Sepsis,!fever!
! PE/DVT!
! Hyperthyroidism!
! Exercise,!pain,!anxiety!
! Drug+induced,!e.g.!beta+agonsit!
! Underlying!heart!problem,!e.g.!sick+sinus!syndrome!(by!exclusion)!
!
Management!
! History!taking!
! Look!for!focus!of!infection,!measure!body!temp!
! Look!at!hydration!status!
! Palpate!calf!!!r/o!DVT!
! Examine!joints!!!r/o!gouty!attack!causing!pain!(common!in!elderly!)!

Supraventricular0tachycardia0(SVT)0
! Common!in!young,!female,!usually!triggered!by!premature!atrial!ectopics!
! Rarely!cause!syncope!
!
ECG!
+ Narrow!complex!tachycardia:!usually!HR!150+180/min!
+ P!waves!
o AVRT:!P!wave!in!ST!segment!
" Retrograde!atrial!acivation!!!inverted!P!waves!in!leads!II,!III,!aVF!
o AVNRT:!P!wave!fused!to!/!immediately!after!QRS!complex!
o Atrial!tachy:!P!wave!>!QRS!complex!
o **!In!all!Narrow!complex!tachycardia!!!all!give!ATP!for!diagnostic!purpose!!!!!!
" Unless!asthma:!give!diltiazem!(also!an!AV!node!blocking!agent)!slow!down!HR!to!
see!more!clearly!!!
" AVNRT!/!AVRT:!back!to!sinus!rhythm!with!absent!p!wave,!no!ectopic!p!wave!
" Atrial!tachycardia:!bizarre!p!wave,!sometimes!can!go!back!to!sinus!rhythm!
" Atrial!flutter:!flutter!waves!(ATP!cannot!terminate!flutter)!
o *!If!don’t!know!whether!there’s!any!P!waves!(e.g.!after!QRS!in!V1)!!!compare!with!ECG!
in!sinus!rhythm!!!look!for!similar!P!wave!!!if!present,!really!p+wave!
+ ST!&!T!wave!abnormalities!suggestive!of!myocardial!ischemia!are!common!during!rapid!
tachycardia!
!
Types!
+ Atrial!tachycardia!
+ AVNRT:!AV!nodal!re+entrant!tachycardia!
o A!circuit!inside!AV!node!!!some!signal!go!down!to!ventricle!and!some!go!backward!to!
atrium!
+ AVRT:!Atrioventricular!reciprocating!tachycardia!
o Vs!WPW:!AVRT!is!referring!to!the!tachycardia!episode!
" WPW!is!a!syndrome:!have!widen!QRS!even!not!in!tachy!
!
Management!of!regular!narrow!complex!tachycardia!
+ Hemodynamically!unstable:!unconscious!(cerebral!hypoperfusion),!↓!BP!
o Resuscitation,!synchronized!DC!cardioversion!(start!with!50J,!↑!by!50+100J!increments)!
+ Hemodynamically!stable!
!

Cardiology!+!54!
 o Vagal!maneuver:!activation!of!parasymp!
" Carotid!sinus!massage!
• Before!!!have!to!listen!for!carotid!bruit!to!rule!out!any!plaque!in!carotid!
artery!(risks!of!stroke)!!
• Firmly!pressing!the!bulb!at!the!top!carotid!artery!(superior!border!of!
thyroid!cartilage)!
• NOT!press!both!sides!at!the!same!time!(risk!of!stroke)!
" Ice!pack!to!face!/!ice!water!immersion!
• C/I!in!patient!with!IHD!
" Eyeball!pressure!!
• **!Risk!of!retinal!detachment!
" Valsalva!maneuver:!forced!expiration!against!a!closed!glottis!!
• In!practice:!blow!into!bladder!syringe!!!difficult!to!blow!!!like!against!
closed!glottis!
• ↑!intra+thoracic!pressure!!!affect!baro+receptors!within!arch!of!aorta!
o Usually!no!use!!!then!use!drug:!!
" IV!bolus!ATP2/2adenosine!(not!in!PWH!ward!)!(5+10mg!1st,!if!fail!!!double!
dosage!to!10+20mg!after!1+2mins)!
• Rule2out2asthma21st!!!(ATP!is!bronchoconstrictor)!
• By!fast!bolus:!otherwise!metabolized!before!arriving!heart!(t½!=!6+10s)!
• Give!under!cardiac!monitor!
• Also!need!to!warn!patient!for!transient!flushing!&!feeling!of!sudden!
cardiac!arrest!(ATP!is!nodal!blocker,!work!by!terminating!loop)!
• In!WPW,!have!risk!of!transforming!into!VF!!!make!sure!emergency!
trolley!in!nearby!!
• If!can!abort!SVT!!!likely!pSVT,!AVRT!/!AVNRT!
• If!transiently!slow!vertricular!rates!but!still!see!many!P!waves!!!atrial!
tachy!(abnormal!looking!P!waves)/!atrial!flutter!(flutter!wave)!!!likely!to!
recur!tachy!after!ATP!effect!gone!!!need!to!use!BB!
o IV!low!dose!verapamil!(Isoptin):!2.5+5mg!
" Make!sure!BP!not!too!low!
• Risk!of!↓!BP!as!it’s!a!–ve!inotropic!(esp.!if!already!on!other!anti+HT)!
" If!failed!!!repeat!with!5+10mg!after!15+30!mins!
o If!still!no!use!!!!
" Diltiazem:!more!vasoactive,!less!effective!than!verapamil!
" Admiodarone!(class!3!anti+arrhythmic!drugs:!prolongs!phase!3!of!cardiac!AP)!
• Long!term!side!effect:!pulmonary!fibrosis,!drug+induced!pleural!effusion!!
" Digoxin!
• Very!slow!onset!!
" Beta+blocker:!less!likely!used!
+ Long!term!management!in!patient!with!frequent!attacks!
o Ablation!of!accessory!pathway!by!radiofrequency!/!cryocatheter!
" 97%!cure!
" Risk!
• Damage!of!AV!node!!!need!pacemaker!(1%)!
• Tamponade!due!to!puncture!of!atrium!
o Beta+blocker,!verapamil,!class!I!&!III!agents!

Atrioventricular0nodal0reentrant0tachycardia0(AVNRT)0
Pathogenesis!!!
+ Common!AVNRT!!!

Cardiology!+!55!
 o Utilizes!the!slow!AV!nodal!pathway!as!the!anterograde!limb!of!the!circuit!and!the!AV!
nodal!pathway!as!the!retrograde!limb!!!
o Atria!contacts!simutaneously!as!that!in!ventricles!as!there!is!no!delay!effect!by!AV!node!
via!the!fast!anterograde!impulse!!!
o Inverted!P!waves!may!not!be!seen!on!the!ECG!since!they!are!buried!with!the!QRS!
complexes!!
+ Uncommon!AVNRT!!!
o Reverse!of!common!AVNRT!!!
o Inverted!p+wave!seen!after!QRS!complex!!!
!
Presentation!
+ Palpitation,!dizziness,!breathlessness!
+ *!Polyuria!(release!of!ANP!from!dilated!atrium)!
!!!!
Management!!!
+ Acute!treatment:!as!mentioned!above!
+ Chronic!phase!with!BB,2CCB!!!
+ Radiofrequency2ablation2after!electrophysiological2studies!
+ KM!Chow:!If!the!patient!had!infrequent!attack!of!PSVT:!Pill!in!the!pocket!(Flecainide:!class!Ic)!

Atrial0flutter0
Pathology!
+ Macroreentry!circuit!in!right!atrium!(throught!the!cavotricuspid2isthmus)!
+ With!atrial!depolarization!rate!~300/min!
+ AV!node!variable!blockade!in!fraction!!!2!to!1!(150/min),!3!to!1!(100/min)!
!!
Clinical!significance!+!atrial/flutter/rarely/seen/in/patients/with/normal/hearts!
+ Presented!with!palpitation,!chest!discomfort,!heart!failure!
+ Associated!with!
o Cardiomyopathy!
o Valvular!heart!disease!
o Ischemic!heart!disease!(IHD)!
o PE!
o Alcoholism!
o Thyrotoxicosis!
o Pericarditis!
!
ECG!
+ Sawtooth!atrial!activity!at!~300bpm!in!inferior!leads!
+ Counterclockwise!pattern,!where!flutter!waves!are!inverted!in!II,!III,!aVF!
+ Clockwise!pattern,!flutter!waves!are!upright!in!all!leads!
!!
Complications!
+ Thromboembolism!
+ Degenerates!into!atrial!fibrillation!
!!
Management!
+ Inital!ventricular!rate!control!(Betablockers,!CCB)!if!fast!
+ Cardioversion!
o More!sensitive!to!electrical!DC!shock,!low!energy!needed!
o More!resistant!to!chemical!cardioversion!
o RF2ablation!of!cardiac!tissue!that!initiate!/!maintain!the!flutter:!prevent!recurrence!
!

Cardiology!+!56!
+ Anticoagulation!
o 4!weeks!before!cardioversion!+!4!weeks!after!cardioversion!
o Lifelong!for!rate!control/!recurrent!atrial!flutter!

Atrial0fibrillation0(AF)0
+ Most!common!sustained!arrhythmia!
+ Incidence!increases!with!age!(10%!of!population!>80!yo)!
!
Types!(similar!stroke!risk)!
+ Paroxysmal!AF:!self+terminating;!<7!days!(usually!<48!hours)!
+ Persistent!AF:!>7days!OR!cardioversion!needed!
+ Long+standing:!>1!year!
+ Permanent:!patient!remain!in!arrhythmia!where!cadrioversion!is!not!successful!/!
inappropriate!
+ Recurrent!AF:!>2!episodes!
+ *!1st!AF!!!‘acute!AF’!!!need!further!Ix,!if!2nd!time!occur!!!paroxysmal!/!persistent!/!
permanent!
!
Pathophysiology!
+ Initiation!
o Multiple!foci!(mainly!at!L.!atrium!around!pulmonary!vein)!
" SA!node!not!working!well!!!replaced!by!multiple!atrial!focus!
o Re+entry!
o *!Heart!rate!may!be!fast!(most!of!the!time)!/!slow!(AV!nodal!block)!
! Maintenance!
o AF!!!atrial!dilation!!!↑!in!fibrous!&!fatty!deposition!in!atria!(remodeling)!!!↓!
electrophysiological!homoheneity!in!conduction!velocity!!!further!promote!AF!
o ∴!The!longer!the!patient!is!in!AF,!the!more!difficult!it!is!to!convert!back!to!sinus!rhythm!
! Consequences!
o Symptoms!
" ↓!cardiac!output!(loss!of!atrial!contraction!&!fast!ventricular!rate):!fatigue,!
syncope,!may!precipitate/worsen!heart!failure!
" Palpitation!
o Thromboembolism!!
" Fibrillatory!conduction!of!atria!promotes!blood!stasis!!
!
Complication!
! Thromboembolism!!!stroke:!originated!from!atrial!appendage!
o Rate!of!stroke:!5+9.6%!per!year!among!patients!at!high!risk!who!are!taking!aspirin!(not!
warfarin)!
o Responsible!for!23%!of!ischemic!stroke!
o Blood!clot!block!cerebral!artery!suddenly!!!severe!brain!damage!(Vs!atherosclerotic!
stroke:!gradual!occlusion!!!less!severe)!
! In!patient!with!WPW!syndrome:!rapid!conduction!down!accessory!pathway!(“loop+like!
conduction”)!!!hemodynamic!collapse!
! Chronic!elevated!HR!of!≥130/min!may!lead!to!secondary2cardiomyopathy!(L.!ventricular!
dysfunction)!
!
Causes!
+ Valvular!
o Mitral!valve!disease!(MR!/!MS)!
!

Cardiology!+!57!
 " Mitral!&!tricuspid!valves!are!related!to!atrium,!but!right!atrium!pressure!low!!!
less!effect!∴mitral!problem!most!common!
" MR/MS!!!↑!atrial!pressure!!!atrial!dilation!!!progressive!fibrosis!of!atrium!!!
ectopic!signals!
+ Non+valvular!
o HT,!IHD,!HF,!cardiomyopathy,!atrial!enlargement!/!↑!atrial!pressure!
o Thyrotoxicosis!
o Eletrolyte!disturbance,!esp!hypoK,!hypoMg!
o Pulmonary!disorders,!e.g.!PE,!COPD!
o Stress:!e.g.!sepsis!!!↑!sympathetic!tone!
o Drugs:!sympathomimmetics!/!amphetamine!
o Stimulants:!e.g.!caffeine!
o Advanced!age!>60!
" Commonly!coexist!with!sick!sinus!syndrome!(both!are!degenerative!disease)!
o Post!cardiac!surgery:!most!commonly!on!2nd+3rd!post+op!day!
o Myocarditis,!pericarditis:!affect!conduction!system!
o Tumors:!pheochromocytoma,!carcinoid!(rarely!cause!pAF)!
o Other:!excess!alcohol!intake,!obstructive!sleep!apnea!
o Idiopathic!(lone!AF)!
" Usually!in!young!patients,!have!lower!stroke!risk!
!
Investigations!
+ CBC,!LRFT,!bone!profile,!TFT!
+ ECG!(shaky!baseline)!
+ CXR!
+ Echocardiogram!!
o Assess!valve!Fx,!chamber!size,!peak!R!ventricular!pressure,!LVH,!pericarditis,!
pericardial!effusion!
o TEE:!transesophageal!echocardiography!
" Screen!for!thrombus!in!left!atrium!&!guide!cardioversion!
" More!sensitive!than!transthoracic!USG!as!air!in!lung!affect!USG!conduction,!&!
esophagus!is!just!next!to!L!atrium!
o Transthoracic!echocardiography!
+ Event!recorder!x!2!weeks!/!Holter!(24hr!ambulatory!ECG)!!
o Slow!AF!may!signify!sick!sinus!syndrome!
!
Management!principle!
+ Address!the!underlying!etiology!
+ Symptom!control:!rate!vs!rhythm!control!
+ Thromboembolism:!need!for!anticoagulation!
!
Acute!management!
! Hemodynamically!unstable!!
o Electrical!cardioversion!(biphasic!cardioversion!100J)!
! Hemodynamically!stable!
o Ventricular2rate2control2(diltiazem/verapamil,!betablockers,!digoxin)!!
" BB!(esmolol,!metoprolol,!propranolol)!
• Sympatholytic,!effective!for!prophylaxis!&!Rx,!slower!onset!then!CCB!!
" CCB+nondihydropyridine!(diltiazem!(can!given!as!continuous!IV!infusion),!
verapamil)!
• Slow!AV!nodal!conduction!
• C/I!in!HF!(+ve!inotropic!)!
!

Cardiology!+!58!
 " Digoxin:!for!AF!with!HF!&!hypotension,!take!several!hours!!
o Consider!anticoagulation2to!open!the!choice!for!cardioversion!
o Cardioversion2if!decided!for!rhythm!control!!
" If!AF!presents!<48h!!!cardioversion!!
• No!need!to!do!TEE!as!blood!clot!not!yet!formed!
" If!AF!presents!>48h!!!!
• Start!anticoagulant!for!3!weeks!before!cardioversion!+!4!weeks!warfarin!
afterwards!(prevent!thrombus!formation!due!to!atrial!stunning)!OR!
• TEE!with!heparin!coverate!then!cardioversion!+!4!weeks!warfarin!
afterwards!
" DRUGS:!class!I!or!III!antiarrhythmics!!
• Procainamide!(Class!Ia)!
• Flecainide/2propafenone!(Class!Ic):!no!structural!heart!disease!or!LV!
dysfunction!(due!to!pro+arrhythm)!
• Ibutilide,2dofetilide,2sotalol2(class!III):2CAD!/!LV!dysfunction!!
• Amiodarone!(Class!III):!severe!LV!dysfunction;!have!least!myocardial!
depressant!effect,!but!potential!extracardiac!S/E,!D+D!interactions!
" ELECTRICAL:!(better!if!AF!duration!>7!days)!!
• DC!cardioversion!
o Treat!reversible!cause!
!
Chronic!management!

! !
! Rate!control!Vs!rhythm!control!(AFFRIM!&!RACE)!
o No!difference!in!mortality,!bleeding,!thromboembolic!events!!!both!OK!if!
asymptomatic!
o Improved!excercise!capacity/QOL!in!rhythm!control!!!rhythm!control!preferred!if!
symptomatic!
o Only!~50%!remains!in!sinus!rhythm!after!5!years!of!rhythm!control,!crossover!rate!
high!!
o Potential!survival!benefit!from!rhythm!control,!offset!by!the!own!risk!!
o Importance!of!anticoagulation!!
! Rate!control!
o Uses!
" Reduce!symptoms!
!

Cardiology!+!59!
 " Improve!hemodynamics:!allow!time!for!ventricular!filling!!
" Prevention!of!tachycardiomyopathy!
o Indicated!in!!
" Elderly!
" Asymptomatic!
" When!rhythm!control!likely!to!fail!!
• Structural!heart!diseases!(e.g.!valular!lesion),!large!LA!>5.5,!longlasting!
AF!>12!months,!failed!repeated!cardioversion!!
o Target!heart!rate!
" Usually!controlled!at!(220+age)!x!60%!/!60+80bpm!at!rest!&!90+115bpm!during!
exercise!
" Considerations!(whether!rate!is!too!fast/slow?)!
• Asymptomatic!
• Palpitations:!drop!/!fast!/!irregular!
• Dyspnea!
• Dizziness!
• Malaise!/!fatigue!
• Chest!pain!
• Syncope!(presyncope)!
o Drugs:!AV!nodal!blocker!

" !
" BB!(Class!II):!esmolol,!metoprolol,!pronpanolol!
• Effective!in!adrenergically+mediated!&!pAF!!
• Relative!contraindicated!in!DM!
" Non+dihydropyridine!(AVN!blocker):!diltiazem,!verapamil!
" Digoxin:!for!AF!with!HF!&!hypotension!,!no!use!for!paroxysmal!AF!(?)!
• C/I!in!renal!impairment!
• C/I!in!AF!which!is!caused!by!or!a/w!hypoK!(hypoK!!!digoxin!toxicity)!
o Surgical!
" Block!&!pace:!AV!node!blockade!by!drugs!+!pacemaker!
" Ablate!&!pace:!AV!node!RFA!+!pacemaker!
! Rhythm!control:!convert!back!to!sinus!rhythm!
o Uses!
!
" Relief!Sx!
Cardiology!+!60!
 " Prevent!thromboembolism!
" *!May!reduce!rather!than!eliminate!recurrence!of!AF!
o Prefer!to!use!in!
" Young!patients!
" Those!with!arrhythmic!cardiomyopathy!
" Symptomatic!patients!
o Drug+induced!proarrhythmia!/!extra+cardiac!side!effects!are!frequent!
" Safety!rather!than!efficacy!considerations!
o Drugs:!class!I!or!III!antiarrhythmics!!

" !
" Class!IC!(flecainide/!propafenone):!reserved!for!pt!without!structural!cardiac!
abnormality/!LV!dysfunction!(due!to!pro+arrhythm)!
" Class!III!!
• Ibutilide,!dofetilide,!sotalol!!
o Avoided!in!pt!with!QT!prolongation!/!LVH!due!to!risk!of!
ventricular!arrhythmia!(Torsades!de!pointes,!i.e.!VT)!
• Amiodarone:!low!risk!of!proarrhythmia!but!cause!substantial!non+cardiac!
toxic!effects!!!reserved!for!severe!cardiomyopathy!!
• Dronedarone:!alternative!to!amiodarone!(less!S/E)!
o C/I!in!moderate/severe!HF!!(↑!HF!death)!
o Electrical:!(better!if!AF!duration!>7!days)!!
" DC!cardioversion!
o Surgical!
" MAZE!surgery!
" Pulmonary!vein!isolation!(proposed!as!the!origin!of!AF!foci)!
• Focal+vein!ablation!(@!pul!vein):!success!rate!not!very!high!(60+70%),!
risk:!pul.!vein!stenosis!!!only!done!in!selected!patients!
" Multi!site!atrial!pacing!
" Atrial!defibrillation!
! Watchman!device!(LAA!occlusion)!
o Placed!in!LA!appendage!to!prevent!LAA!thrombus!from!coming!out!
o 90%!atrial!thrombi!in!patient!with!non+valvular!AF!originated!from!LAA!
!

Cardiology!+!61!
 o But!NOT!proven!to!be!useful!to!prevent!stroke!
! Anti+coagulant!/!anti+platelet!
o Valvular!AF!!!MUST!give!warfarin!
" Dabigatran!not!proven!safe!yet!in!valvular!AF!
" MS!!!higher!thrombotic!risk!as!MS!itself!is!thrombogenic!!!need!higher!target,!
INR!2.5+3.5!(Vs!MR:!2+3)!
o Non+valvular!AF!!!calculate!the!risk!!
" Thromboembolic!events:!4%!in!non+valvular!AF!
o CHADS2!score!/!CHA2DS2VASc!(newer)!–!for!non+valvular!AF!
" C:!congestive!heart!failure!(systolic!HF)!
" H:!hypertension!
• BP!consistently!>!140/90!mmHg!/!treated!HT!on!medication!
" A:!age!>75!(1/2!marks)!
" D:!DM!
" S:!stroke!/!TIA!(2!marks)!
" V:!vascular!disease!(CAD,!PVD,!aortic!plaque)!
" A:!age!65+75!
" Sc:!sex!category:!female!
" 0!mark!!!use!Aspirin!
" 1!mark!!!aspirin!/!warfarin!/!dabigatran!
" ≥2!marks!!!warfarin!/!dabigatran!
" **!Warfarin!is!the!ONLY!choice!for!valvular!AF!(not!newer!drugs)!
• Target!INR:!2.0+3.0!(vs!in!double!mechanical!valve!!!target!2.5+3.5)!
" **!Aspirin!protect!the!heart!but!not!ischemic!stroke!!
o **!Need!to!balance!risk!&!benefit:!e.g.!if!high!fall!risk!in!fragile!elderly!(risk!of!ICH)!!!may!
give!aspirin!rather!than!anti+coagulant!(except!in!prosthetic!valve:!must!give!anti+
coagulant)!
o Bleeding!risk!when!using!warfarin:!HAS!BLED!score!
" H:!hypertension!
" A:!abnormal!L/RFT!(1!point!each)!
" S:!stroke!
" B:!bleeding!risk!(petechiae!/!ecchymosis!/!bruises)!
" L:!labile!INR!(INR!fluctuate!easily)!
" E:!ethanol!
" D:!drug!
" 3!or!more!!!higher!risk!of!bleeding!complication!!!need!careful!monitoring!(e.g.!
aim!lower!end!of!INR,!not!stopping!the!warfarin!)!

MultiTfocal0atrial0tachycardia0(MAT)0
Diagnosis!
! ≥3!morphologically!distinct!non+sinus!P!waves!
! Atrial!arates!of!100+130!bpm!
! Variable!AV!block!
!
Causes!
! Associatation:!respiratory!disease,!CHF,!hypoxemia!
! Trigger:!digoxin!/!theophyllin!toxicity,!hypoK,!hypoMg,!hypoNa!
!
Treatment!
! Treat!precipitants!
! Specific!treatment!usually!NOT!required!
! Metoprolol!/!verapamil!/!amiodarone:!can!be!used!for!rate!control!&!sometimes!restore!SR!
!

Cardiology!+!62!
! NOT!respond!to!DC!cardioversion!

Ventricular0ectopic0beats0
Introduction!!
! Unifocal!or!multifocal!
! Couplet!(2),!triplet!(3):!consecutive!ectopic!beats!
o *If/more/than/3,/it/becomes/ventricular/tachycardia!!
! Bigeminy!(2:1),!Trigeminy!(3:1):!alternate!sinus!and!ectopic!beats!
!!
Presentations!
! Asymptomatic!
! Missed!beat,!strong!beat!
!!
Clinical!significance!
! In/otherwise/health/subjects!
o Normal,!prevalence!increases!with!age!
o Usually!more!at!rest,!disappear!with!exercise!(ventricle! fire)!
o Rx:!Betablockers!only!if!highly!symptomatic!
! In/association/with/heart/diseases!
o >10!ectopics!per!hour!in!post+MI!=!poor!outcome!
o Ectopics!in!heart!failure!=!poor!outcome!
o Digoxin!toxicity,!Escape+ectopic!in!bradycardia!
o Rx:!Betablockers,!control!the!underlying!pathology!

Ventricular0tachycardia0(VT)0
Definition!
! More!than!3!consecuative!premature!ectopic!ventricular!beats!
!
Causes!!!!
+ Heart!valve!problem!
+ Heart!muscle!problem!!
o Cardiomyopathy!
o Myocarditis:!influenza,!coxsackie,!mumps!
+ Coronary!artery!disease!
o Chronic!CAD!
o Acute!MI!
+ Congenital!heart!disease!
o Long!QT!syndrome!
o Catecholamine+mediated!VT:!can!be!monomorphic!/!polymorphic!
" Exercise!stress!test,!isoproterenol!testing!
+ Drugs:!e.g.2illicit!drug!use!(esp.!cocaine!!!coronary!spasm!!!VT/VF)!
!
Types!
! Polymorphic!VT!
o Long!QT!in!baseline!!!Torsade!de!pointes!
o Acute!ischemia,!myocarditis!(normal!QTc)!
o Rapidly!degenerate!to!VF!!
! Monomorphic!VT!
o Tend!to!be!reproducible!and!recurrent!
o Almost!exclusively!in!patients!with!underlying!structural!heart!disease,!coronary!artery!
disease!or!dilated!cardiomyopathy!!
! Pulseless!(arrest)!
!

Cardiology!+!63!
! Non+sustained:!<30s!and!asymptomatic!
! Sustained!
o >30s!or!symptomatic!
o Hemodynamically!unstable!VT!that!requireds!termination!before!30s!
o VT!terminated!by!therapy!from!an!ICD!
!!
ECG!
+ Identify!VT:!wide!complex!regular!tachycardia!
o *!DDx:!SVT!with!pre+existing!BBB!/!aberrant!conduction,!antidromic!WPW!
" If!in!doubt!!!manage!as!VT!!(Stable!!!amiodarone,!unstable!!!shock)!
o Very!broad!QRS!>140ms!
o Extreme!left!axis!deviation!
o AV!dissociation!with!independent!P!wave!
o Capture!beat:!capture!the!beat!from!atrium!(normal!atrial!beat!in!the!middle!of!many!
ventricular!beats)!
o Fusion!beat!
" Concurrent!activation!of!same!chambers!by!2!stimuli:!ventricular!beat!coincides!
with!sinus!beat!/!ventricular!ectopic!beat!/!junctional!beat!
" E.g.!sinus!+!V!beat!
o Taller!left!rabbit!ear!in!lead!V1!
o QRS!deflections!concordance!in!the!precordial!leads!(all!+ve!/!+ve)!
o **!Other!clues!differentiating!VT!vs!SVT!
" History!of!myocardial!infarction/!cardiomyopathy!
" No!response!to!carotid!massage!or!adenosine!
" Intracardiac2or2esophageal2ECG!may!help!
+ Find!the!onset!&!offset!of!VT!
o Find!out!the!triggering!mechanism:!PVC!!!R!on!T!
o Usually!offset!is!return!of!sinus!rhythm!after!defibrillation/cardioversion!
+ If!there’s!sinus!beats!!
o Look!at!the!QT!interval:!any!prolonged!
o Any!LVH:!HOCM!!!normotensive!with!LVH!
!
Management!
+ Admit!the!patient!to!CCU!for!close!monitoring!!
o Defibrillator!machine!readily!available!
o Central!cardiac!monitoring!
o High!nurse!to!patient!ratio!
+ Assess!the!vitals!
+ If!the!patient!is!clinically!unstable,!e.g.!chest!pain,!SOB,!↓!conscious!state,!low!BP,!shock,!
pulmonary!congestion,!CHF,!AMI!
o !!DC!Synchronized!cardioversion:!synchronize!to!avoid!R!on!T!(if!polymorphic!VT!!!
can’t!synchronize!!!use!defibrillator)!
+ If!the!patient!is!clinically!stable!
o If!monomorphic!VT!
" !!Give!amiodarone!/!procainamide!/!lignocaine!
• More!preferred!than!lignocaine:!amiodarone!is!useful!for!all!kinds!of!
arrhythmia!including!SVT,!as!sometimes!VT!maybe!difficult!to!be!
differentiate!from!SVT!with!BBB!
" !!Correct!hypoK,!hypoMg,!acidosis,!hypoxia,!remove!all!pro+arrhythmogenic!
agents!
!

Cardiology!+!64!
 o If!polymorphic!VT!(Torsades!de!pointes)!!
" Correct!electrolytes,!maintain!K!>4.0!
" IV!MgSO4!5+10mmol!over!15min!irrespective!of!serum!level!
• HypoMg!can!cause!TdP!
" Isoproterenol/!isoprenaline!(non+selective!β+agonist)!infusion!/!rapid!
ventricular!pacing!/!overdrive!atrial!pacing2!
• Make!use!of!the!rate+dependent!property!of!QT+interval:!rising!heart!rate!
!!shorten!the!QT!(QTc!=!QT!/!square!root!of!RR)!
" Don’t!give!anti+arrhythmic!in!LQTS!as!most!anti+arrhythmic!prolong!QT!segment!
o If!sustainedd!VT!(>30s!/!symptomatic)!!!cardioversion!!
" Even!if!BP!is!OK,!need!cardioversion!because!it!may!deteriorate!rapidly!
+ Establish!the!cause!of!VT!
o History!taking!
" Review!history!for!drugs,!esp.!illicit!drug!use!
" Family!history!of!unexplained!sudden!cardiac!death!
o Blood!for!CBC,!LRFT,!Troponin!T!
" Electrolyte!disturbance!causing!VT:!hypoK,!hypoMg,!hypoCa!
o Urine!toxicology!if!any!clinical!suspicion!
o Echocardiogram!!
" Septal!thickness!(HOCM)!
" Vulvular!lesion!(especially!acute!vulvular!problem!e.g.!MR)!
" Hypokinesia!(cardiomyopathy)!
" Ischemic!changes!!
" RV!dysplasia!(arrhythmogenic!RV!dysplasia)!
o CT2angiogram!to!look!for!evidence!of!coronary!artery!disease!
o Cardiac!MRI:!myocarditis,!fatty!infiltrate!
+ Implant!ICD!for!sustained!monomorphic!VT!/!patients!with!high!risk!of!arrhythmic!death!(e.g.!
structural!heart!disease,!previous!MI)!
+ Catheter2ablative2therapy!for!VT!patients!with!identifiable!focus!(usually!without!structural!
heart!disease)!
+ For!recurrent!polymorphic!CT!suspected!to!be!related!ti!ischemia!without!repolarization!
abnormality!(esp!prolonged!QT)!!!IV!beta!blocker!/!amiodarone!(C/I!for!class!I!drugs)!

Ventricular0fibrillation0(VF)0
Treatment!

+ !
!

Cardiology!+!65!
+ Anti+arrhythmic!
o If!no!structural!defect!!!lignocaine!
o If!have!underlying!CHF!!!amiodarone!
+ After!successful!shock!!!return!to!narrow!complex!beat,!but!may!be!very!messy,!e.g.!AF!

Bigeminy0
+ Abnormal!heart!beats!occur!every!other!concurrent!beat!
+ Typical!example:!bigeminal!premature!ventricular!contractions!(PVC)!
+ Other!numbering!aberrant!rhythms!
o Trigeminal:!every!third!beat!is!aberrant!
o Quadrigeminal:!every!fourth!beat!is!aberrant!
o (If!every!fifth!or!more!beat!is!abnormal!!!call!‘occasional’)!

Bradycardia0
+ Sinus!bradycardia!
+ Junctional!escape!rhythm!
+ Ventricular!escape!rhythm!
+ 2nd!/!3rd!degree!heart!block!
+ AF!/!atrial!flutter!with!slow!ventricular!rate!
!
Indication!for!immediate!treatment!!
+ Ventricular!asystole!
+ Symptomatic!heart!block:!type!II!2°/3°!HB!with!narrow!complex!escape!rhythm!
+ Symptomatic!sinus!bradycardia:!hypotension,!ischemia,!escape!ventricular!arrhythmia!
!
Treatment!
+ Atropine:!IV!0.6mg!(usually!NOT!effective!in!complete!HB)!
+ Isoproterenol!(caurtion!in!IHD)!!
+ Epinephrine:!esp!in!severe!hypotension!
+ Pacing!(transcutaneous!/!epicardial!/!transvenous)!
o Indications!for!urgent!transcutaneous!pacing!
" Asystole!
" Symptomatic!sinus!bradycardia!(SBP!<80)!unresponsive!to!drug!therapy!
" Type!II!2°/3°!HB!
" Bilateral!BBB!(alternating!BBB!/!RBBB!with!alternating!LAFB/LPFB)!
" Bifascicular!block!with!1°!HB!
o Transvenous!pacing!is!preferred!if!likely!require!on+going!/!long+term!pacing!

!
!
Cardiology!+!66!
Sinus0bradycardia0
Etiology!
! Hypothyroidism!
! Hypothermia!
! Athletics!!
! Sick!sinus!syndrome!
! Drugs:!B!blocker!or!CCB!
!
Management!
! Atropine!during!acute!symptomatic!episode!
! Remove!drug!if!iatrogenic!

Sinus0block0/0pause0/0arrest0
Sinus!block!
! SA!block!
! A!complete!block!/!failure!of!sinus!node!to!depolarize!the!atria!
! The!block!can!last!≥1!cardiac!cycles!&!is!a!multiple!of!normal!P+P!interval!
!
Sinus!pause!
! A!delay!in!the!formation!of!a!sinus!impulse!in!the!SA!node,!resulting!in!a!temporary!pause!
(usually!>3!sec)!
!
Sinus!arrest!
! A!longer!delay!in!the!formation!of!a!sinus!impulse!in!SA!node!
! Pause!lasts!greater!than!3x!!the!normal!P+P!interval!
!
Escape!beats!/!rhythm!may!occur!
! Atrial!escape:!P!waves!with!abnormal!morphology!
! Junctional!escape:!P!waves!not!seen,!or!follow!the!QRS!(retrograde!P),!rate!40+60!bpm!
! Ventricular!escape:!no!P!wave;!wide,!abnormal!QRS;!slow!rate!20+40!bpm!

Junctional0bradycardia0
Causes!
+ Sick!sinus!syndrome!
+ RCA!infarct!(inferior!MI):!give!the!nodal!branch!(but!more!commonly!cause!heart!block!than!
junctional!brady)!
+ Electrolyte!imbalance,!e.g.!K!
+ Drug+induced!
+ **!Need!to!differentiate!reversible!Vs!irreversible!cause!!
o Different!Mx:!if!degenerative!change!!!need!pacemaker!

Sick0sinus0syndrome0/0BradyTtachy0syndrome0
+ Common!in!elderly!

!
Symptoms!
+ Usually!present!as!AF,!treated!with!low!dose!BB/CCB!!!develop!bradycardia!even!pause!
+ Stokes+Adams!attacks:!sudden,!transient!episode!of!syncope!due!to!lack!of!cardiac!output!
+ Dizziness!
!

Cardiology!+!67!
!
Treatment!
+ If!symptomatic!!!block!&!pace!!
o BB/!CCB!±!digoxin!for!tachycardia!
o Symptomatic!=!class!1!indication!for!pacemaker:!use!conventional!(dual!chamber)!
pacing!!!↑!AV!synchrony!
+ If!asymptomatic!but!pause!>3s!!!can!still!consider!block!&!pace!
o Although!this!is!not!class!1!indication!but!class!2a/b!
Heart0block0
Causes!
! Degeneration!
! Idiopathic!conduction!pathway!fibrosis!
! AMI:!inferior!&!anterior!
! Surgery!!
! Infection!e.g.!myocarditis,!aortic!root!abscess,!syphilis!
! Infiltrative!e.g.!amyloidosis,!hemochromatosis!
! Neuromuscular!e.g.!dystrophia!myotonica!
! Drugs!e.g.!BB,!digoxin,!amiodarone,!diltiazem!
! Hypothyroidism!!
!
Types!
! First+degree:!constant!prolonged!PR!(AV!node!problem)!
! Second+degree!(problem!below!AV!node!!!normal!PR!interval)!
o Morbitz!type!I!(Wenckebach)!=!progressive!lengthening!of!successive!PR!interval!
o Morbitz!type!II!=!constant!PR,!some!P+waves!not!conducted!
o */In/2:1/AV/block,/we/cannot/distinguish/the/subtypes!
! Third+!degree:!complete!AV!dissociation!
! **!1st!degress!&!Wenckebach!=!low,!Morbitz!type!II!&!3rd!degree!=!high!
!
Clinical!presentations!
! Dizziness,!exercise!intolerance!
! Syncope!(Stokes2Adams2attacks)!
o Found!in!morbitz!type!II!2nd!degree!heart!block!/!complete!heart!block!
o Episodes!of!ventricular!asystole!!!recurrent!syncopes!
o Sudden!LOC!with!deathlike+pallor,!rapid!recovery!with!flushing!
! **!Should!be!asymptomatic!in!1st!degress!/!Wenckebach!
!
Management!
! Heart!block!in!AMI!
o Inferior/MI!
" Due!to!vagal!tone!increase,!usually!TRANSIENT/(resolve/in/7M10/days)!
" If!symptomatic!!!atropine,!temporary2pacing!
o Anterior/MI!
" Due!to!inschemic!damage!to!conduction!system,!usually!PERMANENT!
" Permanent!pacing!needed!
+ Chronic!heart!block!
o Permanent2pacemaker2if!symptomatic!

Wenckebach0(second0degree,0Mobitz0type0I)0
+ Progressive!prolongation!of!successive!PR!interval!
!
Investigation!
!

Cardiology!+!68!
+ Treadmill!
o If!fixed!AV!node!problem!(pathological)!!!when!HR!↑!!!block!more!frequent!(fixed!
block)!
o If!fue!to!autonomic!problem!(benign)!!!when!sympathetic!tone!↑!!!improve!(less!
frequent!block)!
" AV!node!is!regulated!by!autonomic!nerves,!HB!become!worse!when!vagal!tone!is!
high!(∴!common!to!have!syncope!after!micturation)!
!
Management!
+ Depend!on!clinical!picture:!e.g.!any!syncope!
+ If!yes!!!Holter!to!look!for!long!pause!/!transformation!to!other!degree!of!heart!block!!
o Heart!block!is!dynamic,!may!change!to!diff!degree!throughout!the!day!
+ May!need!pacing!if!symptomatic!
+ Avoid!AV!blocking!agent!
o But!if!MI!/!tachy+brady!which!need!beta+blocker!!!do!block!&!pace!

Complete0heart0block0
Causes!
+ Degeneration!of!the!conduction!system:!commonest!
+ HyperK,!digoxin!toxicity!
+ Endocarditis,!acute!MI!
+ Lyme!disease:!infection!of!Borrelia!
+ Congenital!heart!block!
!
ECG!
+ Prefunded!bradycardia!
+ Atrioventricular!dissociation:!QRS!complex!not!associated!with!P!waves!
+ *!In!a!patient!with!AF!+!complete!heart!block!!!RR!will!be!regular!
o In!complete!heart!block!!!AV!dissociation!!!there’ll!be!escape!beat!below!(junctional!/!
ventricular),!which!are!not!affected!by!AF!!!regular!beats!
WolffTParkinsonTWhite0(WPW)0Syndrome0
Pathology!
+ Presence!of!a!strip!of!accessory!tissue!that!allow!signals!to!bypass!the!AV!node,!leading!to!
ventricular2preexcitation!
+ In/sinus/rhythm!!!
o Manifest2accessory2pathway!50%!
" Signals!passing!through!both!AV!node!&!accessory!pathway!(with!preexcitation)!
" Short!PR!interval!+!broad!QRS!complex!+!slurred!upstroke!(delta!wave)!
" May!have!L/RBBB!pattern,!depending!on!the!location!of!accessory!pathway!
• E.g.!pathway!in!L!side!!!look!like!RBBB!
" May!have!pseudo+infarction:!e.g.!Q!wave!in!lead!III!!!due!to!abnormal!pathway!
leading!to!strange!axis!of!the!heart!

Cardiology!+!69!
 " !
o Concealed2accessory2pathway!50%!
" Accessory!pathway!only!allow!retrograde!transmission!!!
" Normal!ECG!in!sinus!rhythm!!
+ In/AVRT!
o Orthodromic2tachycardia!!!
" Reentry!taken!part!retrogradely!via!accessory!pathway!&!anterogradely!via!AV!
node!!!
" Ventricules!depolarized!through!the!AV!node!as!usual,!ECG!findings!are!
indistinguishable!from!other!AVNRT!(a/subtle/finding/=/P/wave/occuring/visibly/
after/QRS/complex!)!
o Antidromic2tachycardia!!!
" Reentry!taken!part!ANTEROGRADELY!via!accessory!pathway!and!
RETROGRADELY!via!AV!node!!!
" Ventricles!depolarized!through!the!accessory!pathway,!creating!a!broad!complex!
tachycardia!
" Only!seen!in!WPW,!other!accessory!pathways!can!only!conduct!from!ventricle!to!
atrium,!not!from!A!to!V!
+ In/AF!
o All!signals!passes!through!the!accessory!pathway!!!
o Giving!a!life!threatening!broad!complex!irregular!tachycardia!(preexcited2AF)!!
" Every!atrial!depolarization!is!delivered!to!ventricle!leading!to!dangerous!rapid!
ventricular!rate,!need!urgent!DC!cardioversion!
!
Management!
+ Cannot!give!betablockers,!CCB,!Digoxin:!if!we!delayed!the!AV!nodal!transmission,!it!precipated!
a!pre+excitation!AF!(all!signals!from!SA!node!can!conduct!to!ventricle!via!accessory!pathway)!
+ Management!based!on!risk!straification!(risk!of!Pre+excitation!AF)!
o Symptomatic!
o Antidromic!WPW!(where!accessory!pathway!can!transmit!anterogradely)!
o Programmed!electrical!stimulation!show!fast!rate!of!electrical!propagation!through!
accessory!pathway!
+ Management!choice!
o Observe!+!educate!vagal!manuver!+!avoid!certain!drugs!
o Prophylactic!Class!I/II!antiarrhymics!in!symptomatic!patients!
o Catheter!ablation!of!accessory!pathway!
Long0QT0syndrome0
+ Prolonged!QT!interval!with!delayed!repolarization!
o *!Normal!QT!interval!varies!inversely!with!HR!!!should!correct!with!HR!
o QTc!=!QT!/!square!root!of!RR!(Bazett's!formula)!
+ May!degenerate!into!Torsades2de2pointes2/!ventricular!fibrillation!
!

Cardiology!+!70!
!
Causes!
+ Congenital!channelopathy!
+ Acquired!
o Electropyte!abnormalities:!hypoK,!hypoMg,!hypoCa!
o Hypothermia!
o Metabolic:!hypothyroidism,!DM!
o Drugs!
" Anti+arrhythmics:!class!1!(lignocaine,!quinidine)!&!3!(amiodarone,!sotalol)!
" Antibiotics:!e.g.!macrolide!(erythromycin,!clarithromycin),!quinolones!
(moxifloxacin),!antifungals!(ketoconazole)!
" Anti+malarials:!quinine!
" Anti+histamine:!terfenadine,!diphenhydramine!
" TCA!(amitriptyline:!suicidal!attempt),!Antipsychotics!(chlorpromazine)!
" Anti+migraine:!+triptans!
" Cisapride!(gastroprokinetic!agent)!
" Protease!inhibitor!(anti+HIV)!
o Organophosphates!
o Neurological!disorder:!stroke,!trauma,!SAH!
o Cardiac!disorder:!IHD,!eart+block!with!bradycardia!
o Anti+Ro!antibody!
!
Treatment!
+ Can!give!BB!to!prevent!syncope!
o After+depolarizations!(the!cause!of!arrhythmia!in!LQTS)!↑!in!states!of!adrenergic!
stimulation!
o BB!↓!risk!of!stress+induced!arrhythmias!
+ ICD!
Brugada0syndrome0
Introduction!!
+ Autosomal!dominant!
+ Inherited!Na!channelopathy!!
o Mutation!on!gene!of!Na!channel!of!myocytes!(SCN5A!mutation)!
o !!premature!repolarization!of!epicardial!myocytes!!
o !!potential!gradient!b/w!epi!&!endocardial!myocytes!!
o !!ST+elevation!in!R!chest!leads!&!may!cause!reentrant!tachyarrhythmia!
+ Usually!in!young!males!
!
Clinical!presentation!
+ Unexplained!syncope!
+ Predisposes!to!fatal!arrhythmias!(polymorphic!VT/!VF)!!!sudden!death!
!
Diagnosis!
+ ECG!
o RBBB!
o ST+elevation!in!V1+V3!with!unusual!morphology!
" Type!1:!coved+type!ST!elevation!/!downward!sloping!ST!elevation!
• Elevated!take+off!point,!desending!into!–ve!T!wave!with!little/!no!
isoelectric!separation!
" Type!2:!saddle!shape!ST!elevation!
• Vs!pericarditis:!more!widespread!
!

Cardiology!+!71!
 " Type!3:!coved+typed!/!saddle+shaped!with!<!2mm!J+point!elevation!(Type!1!&!2!
have!>2mm!J+point!elevation)!
o *!Resting!ECG!can!be!normal!
o *!Need!to!correlate!with!clinical!(e.g.!history!of!syncope):!if!only!Brugada!features!on!
ECG!without!symptoms!!!not!Brugada!syndrome!
+ Confirmation!test:!!
o Flecainide!/!Ajmaline!provocation!test!!
" Only!indicated!in!symptomatic!pt!(not!incidental!ECG!finding)!
" Flecainide,!Ajmaline:!class!Ic!antiarrhythmic!drug!(block!Na!channels)!!!
unmask!ECG!abnormality!
" Flecainide!dose:!2mg/kg!(<75!kg),!150mg!(≥75kg)!
" Prepare!defibrillator!during!the!test!in!case!of!converting!into!VF/VT!
" Antidote:!isoproterenol!if!VF!/!VT!occurs!
" +ve!if!covered+type!elevation!(≥2mm)!in!≥2!chest!leads!
+ Genetic!sequencing!
o SCN5A!locus!with!R367H!missense!mutation!
!
Treatment!
+ Prophylactic!implantable!cardioverter+defibrillator!(ICD)!
o Continuously!monitors!heart!rhythm,!if!ventricular!fibrillation!is!noted!!!defibrillate!!
o Only!indicated!in!symptomatic!(e.g.!syncope)!/!strong!FHx!(e.g.!FHx!of!sudden!death):!as!
ICD!is!expensive!($25,000)!&!have!limited!lifespan!
Dilated0cardiomyopathy0
+ Dilated,!poorly!contractile!ventricle!
+ Systolic!heart!failure!
!!
Causes!!!
+ 30+40%!genetic!!
o Usually!autosomal!recessive!!!
o Mutation!in!sarcomere,!cytoskeleton!(e.g.!dystrophin!in2Duchenne2muscular2
dystrophy),!nuclear!envelope,!mitochondria!!!
+ Postviral!myocarditis!
+ Autoimmune!process!(Ab!to!myosin!and!lymphocytes)!
+ Alcohol!/!Cobalt!toxicity!
+ Selenium!(Keshan's2disease)!!/!Thiamine!deficiency!(beriberi)!!!
+ Peripartum!cardiomyopathy!!!
o 1+6!month!after!delivery!
o ?!Due!to!fluid!overload!(with!high!salt!content!soup!postpartum)!
o Corticosteroid!and!azathioprine!
!!!!!
Clinical!manifestations!!!
+ Heart!failure!!!!
+ Atrial!fibrillation!!!
+ Thromboembolism!!!
+ Sudden!death!!!
!!
Physical!signs!
+ Diffuse!displaced!apex!beat!
+ Third!heart!sound!
+ Function!regurgitation!
!!
!

Cardiology!+!72!
Management!
+ Beta!blockers!
+ Anticoagulation!
Hypertrophic0cardiomyopathy0(HCM)0
+ Genetically!determined!(beta+myosin,!troponin,!myosin!binding!protein!C)!
+ Thicked!left!ventricular!septal!wall!with!small!cavity!
o Impaired!diastolic!filling!
o Dynamic!outflow!obstruction!
o Functional!mitral!regurgitation!
+ Apical2HCM!
o More!common!in!Asia!
o No!outflow!tract!gradient,!asymptomatic,!benign!condition!
+ Commonest!CV!Cx:!AF!
!!
Symptoms!
+ Asymptomatic!
+ SOB,!chest!pain,!syncope!
+ Heart!failure!
+ Sudden!death:!due!to!↑!arrhythmia!risk!–!patchy!fibrosis!of!myocardium!affecting!conduction!
pathway!
!!
Physical!signs!
+ Jerky!pulse:!rapid!upstroke!and!fall!of!pulse!
+ Giant!a!wave!in!JVP!(noncomplaince!of!RV)!
+ Displaced,!double!strong!apex!pulse!
+ Murmur!
o Ejection2systolic2murmur!at!the!left!sternal!edge!and!apex!(outflow!obstruction)!
o Pansystolic2murmur!at!apex!(from!functional!MR:!valve!pulled!anteriorly!by!Venturi!
effect!from!high!flow)!
o *!Murmur!enhanced!by!Valsalva!manoeuver,!as!the!forced!expiration!decrease!the!blood!
flow!into!LV,!when!preload!↓!!!↑!outflow!obstruction!!
" That’s!why!don’t!give!TNG!to!HCM!although!the!presentation!may!mimic!angina!
• Also!C/I!for!ACEI,!ARB!&!nifedipine:!vasodilatation!(BB,!verapamil!&!
diltiazem!still!ok)!
!
Investigations!
+ ECG:!prominent!LVH!with!strain!(despite!normotensive),!PVC!/!non+sustained!VT!
+ CXR:!large!heart!
+ Echocardiogram:!asymmetrical!septal!hypertrophy!(ASH),!outflow!tract!gradient,!MR,!systolic!
anterior!motion!(SAM)!
!!
Managemnt!
+ Non+pharmacological!
o Avoid!strenous!exercise,!dehydration!
+ Pharmacolgical!
o Betablockers2for!chest!pain!and!SOB!
o Treat!all!arrhythmias!esp!AF!(the!stiff!ventricular!relies!on!atrial!contraction!for!filling)!
+ Surgical!
o Dual!chamber!pacing!
o Ethanol!injection!on!septum!to!induce!infarction!
!
!

Cardiology!+!73!
Prognostic!factors!
+ Septal!thickness!
+ PVC!/!non+sustained!VT!
Restrictive0cardiomyopathy0
Causes!!!
+ Endomyocardial2fibrosis!!!
o African!children!!!
o Ventricular!subendocardial!fibrosis!!!
o Reduced!ventricular!chamber!volume!!!
+ Loeffler2eosinophilic2endocarditis!!!
o Termperate!ones!!!
o Peripheral!eosinophilia!and!esosinophilic!infiltration!of!multiple!organs!!!
o Rapidl!fatal!!!
+ Endocardial2fibroelastosis!!!
o Usually!<2!years!old!!!
o Diffuse!fibroelastic!thickening!of!endocardium!!!
+ Other!infiltrative!diseases:!amyloid,!hemochromatosis,!glycogen!storage!diseases!!!
!!!!
Morphology!!!
+ Restriction!of!ventricular!filling!leading!to!reduced!cardiac!output!!!!
+ Interstitial!myocardial!fibrosis!!!
Arrhythmogenic0Right0Ventricular0Cardiomyopathy0(dysplasia)000
+ Familial!disorder!!!
+ Predominantly!right!heart!failure!with!VT!&!sudden!death!!!
+ Right!ventricular!wall!severely!thinned!with!profound!fibroadipose!tissue!infiltration!!!
disturb!conductive!system!!!arrhythmogenic!
Tetralogy0of0Fallot0(TOF)0
+ A!type!of!R!to!L!shunt!(cyanotic!lesion)!
+ Tetralogy!
o Pulmonary!infundibular!stenosis!
o Overriding!aorta!
o Ventricular!septal!defect!(VSD)!
o Right!ventricular!hypertrophy!
!
P/E!
+ Clubbing!
+ Cyanosis!!
!
Investigation!!
+ CXR:!‘coeur+en+sabot’!(boot+like)!appearance!
+ ECG:!RVH:!right!axis!deviation,!tall!R!in!V1,!deep!S!in!V6!±!RBBB!
!
Treatment!
+ Blalock+Taussig!shunt:!R!subclavian!artery!!!pulmonary!artery!
+ Waterston+Cooley!shunt:!ascending!aorta!!!pulmonary!trunk!
Ebstein’s0anomaly0
+ Downward!displacement!of!TV!
+ Related!to!lithium!intake!during!pregnancy!
+ Tattering!effect!!!incomplete!closure!of!TV!!!TR!
+ Volume!overload!!!RVH!!!risk!of!arrhythmia!(atrial!flutter)!
!

Cardiology!+!74!
+ Ix:!Holter,!Echo!
Dyslipidemia0
Target!LDL+C!level!
+ Depend!on!overall!cardiovascular!risk!
+ 0+1!risk!factor:!<4.2mmol/L!(160mg/dL)!
+ 2+!risk!factors:!<3.4!mmol/L!(130!mg/dL)!
+ CHD/risk!equivalent!(e.g.!DM):!<!2.6!mmol/L!(100!mg/dL)!
+ Very!high!risk:!<1.8!mmol/L!(70!mg/dL)!
o Established!atherosclerotic!CVD!with!multiple!risk!factors!(esp!DM)!+!severe!&!poorly!
controlled!risk!factors!(e.g.!smoking)!+!ACS!
!
FU!in!OPD!
+ HBPM,!diet!
+ Drug!compliance,!S/E!(muscle!pain),!allergy!
+ Chest!pain!(TNG!need),!stomach!pain!
+ Exercise,!smoking!
+ Last!FU,!last!blood!taking!
o Lipid!level,!LFT!(statin!may!induce!↑!ALT),!CPK!(statin!!!muscle!damage)!
Cardiac0arrest00
Condition!associated!(death!mediated!by!VT/VF)!
+ Coronary!artery!disease!
+ Dilated!cardiomyopathy!
+ Hypertrophic!cardiomyopathy!
+ Long!QT!syndrome!
+ Brugada!syndrome!
+ Arrhythmogenic!right!ventricular!dysplasia/cardiomyopathy!
+ Atrial!fibrillation!with!WPW!
!
Resuscitaion!!
+ Consciousness!
+ Call!help!!
+ Wear!PPE!
+ Primary!ABCD!
o Airway!(clear!obstruction,!HT/CL,!OP!airway)!
o Breathing!(Oxygen!mask,!2!rescue!breath/2+4s)!
o Carotid!pulse!5+10s!and!CPR!30:2!
o Defibrillation!(360J!for!mono,!200J!for!Bi)!
+ Secondary!ABCD!
o A:!Airway!device!±!Intubation!
o B:!Maintain!ventilation,!Primary!confirm!(5!pt!auscultation),!Secondary!confirm!
(ETCO2,!esophageal!detector!device)!
o C:!Circulation!IV!access!
o D:!DDx!
" Consider!causes:!hypoxia,!hyper/hypoK,!acidosis,!drug!overdose,!hypothermia!
+ Transcutaneous!pacing!if!indicated!
+ Drug!
Drug! Amount! Time! Indication!
Adrenaline! 1mg!(10ml!1:10000)! IV!Q3+5min! !!
Atropine! 1mg!up!to!a!total!of! IV!Push!! !!
0.04mg/kg! Q3+5min!
Vasopressin! 40!IU/ml! IV!push! !!
!

Cardiology!+!75!
 Lignocaine! 1mg/kg! IV!bolus! !!
! 1+4mg/min! Infusion! !
Amiodarone! 300mg!mixed!in!20!ml! Rapid!infusion! Pulseless!VT!
NS/D5!! VF!
! 150mg!! 10!min! !
! 1mg/min! Infusion!x!6!hrs! !
! 0.5mg/min! !! !
CaCl2!(10%)! 5+10ml! IV!slow!push! Hyper!K!
CCB!toxicity!
NaHCO3!(50ml!8.4%)! 1mEq/kg!initially! !! Hyper!K!
MgSO4! 5+10mmol! IV! Torsades!de!point!
o Tracheal!Drug!(LEAN)!
" Lignocaine,!Epipneprhine,!Atropine,!Naloxone!
" Double!dose!
" Dilute!in!10ml!NS/D5!
" Inject!quickly!in!ETT!!!Quick!insufflation!
" Withhold!chest!compression!
+ *!Consider!to!stop!CPR!in!those!who!continue!in!asystole!for!>10mins!with!no!potential!
reversible!cause!despite!successful!deployment!of!advanced!interventions!
!
Post!CPR!care!
+ Hypoxia:!100%!O2!
+ Hypercapnia:!mechanical!ventilation!
+ Keep!Anti+arrhythmic!
+ Hypotension:!volume!expander/vasopressor!
+ Seizure:!AED!
+ Blood!glucose!
+ X!routine!NaHCO3!
!
Management!after!resuscitation!
+ Left!ventricular!function!NORMAL!
o Ischemia!!!revascularisation!
o No!ischemia!!!electrophysiological!assessment!!!RFA!or!ICD!
+ Left!ventricular!dysfunction!
o AMI!!!ICD!
o No!ischemia!!!ICD!
o Ischemia!!!revascularization!
" EF!<30%!!!ICD!
" EF!>30%!!!EPS!!!abnormal!!!ICD!
Pulseless0electrical0activity0(PEA)0(Electromechanical0dissociation)0
+ ECG!activity!present!but!no!pulse!
+ **!During!resuscitation,!if!patient’s!cardiac!mon!shows!some!waves!!!need!to!palpate!pulse!to!
differentiate!any!rhythm!from!PEA!
!
DDx:!6!‘H’s!&!5!‘T’s!
+ Hypovolemia! + Tension!pneumothorax!
+ Hypoxia!! + Tamponade!
+ HypoK/hyperK! + Toxins!or!drugs!!
+ Hydrogen!ion!(acidosis)! + Thromboembolic!event!(coronary!/!PE)!!
+ Hypothermia! + Trauma!!
+ Hyper/hypoglycemia!
!

Cardiology!+!76!
!
Management!
+ Primary!&!secondary!ABCD!
+ Adrenaline!1mg!IV!(10ml!of!1:10000),!Q3+5mins!
+ If!PEA!rate!<60/min!!!atropine!1mg!IV!Q3+5min!to!a!total!dose!of!0.04mg/kg!
Treadmill0(Exercise0ECG)0
+ Sensitivity!70%,!specificity!80%!
!
Indications!!
+ Diagnosis!of!IHD!
o Only!do!in!intermediate!risk!(otherwise!high!false!+ve!or!+ve)!
" E.g.!atypical!pain!with!risk!factors!/!typical!pain!but!no!risk!factor!
" In!high!risk!!!directly!do!coronary!angiogram!
o May!be!used!in!post+MI!patients!who!haven’t!done!PCI:!see!whether!there’s!other!vessel!
problem!
" But!now!usually!go!straight!to!do!coronary!angiogram!&!PCI!in!post+MI!
+ Stress!for!exercise+induced!arrhythmia!/!HR!response!
o E.g.!for!patient!with!exertional!palpitation!/!chest!discomfort!
+ Test!for!exercise!tolerance!at!baseline!
+ After!therapeutic!intervention!
!
Contraindications!
+ Unable!to!exercise!sufficiently!
o E.g.!leg!claudication,!arthritis,!uncontrolled!symptomatic!HF,!resp!failure,!asthma,!DVT,!
MR!leading!to!inability!to!coorperate…!
o !!Do!pharmacologic!stress!ECG!
+ With!non+interpretable!baseline!ECG!
o E.g.!LBBB/RBBB,!high!degree!AV!block,!pacemaker,!>1mm!ST!depression!/ST!elevation!
(LV!aneurysm)!at!rest,!baseline!LV!strain,!digoxin!(reverse!tick!sign)!!
o !!Do!exercise!Echo/rMPI!!
+ Hemodynamic!unstable!!
o E.g.!uncontrolled!HT,!unstable!angina,!severe!AS,!HOCM,!AMI!(within!3+5days),!active!
endocarditis/myocarditis/pericarditis,!acute!PE!
+ Non+sinus!rhythm,!e.g.!AF!
!
Test!procedure!
+ Change!/!stop!anti+hypertensive!drugs!on!the!day!of!test!esp.!BB!&!diltiazem/verapamil!
o They!prevent!good!HR!response!for!diagnosing!IHD!
+ Usually!use!Bruce!protocol:!7!stages!of!exercise!
+ Monitor!HR,!BP!&!ECG!changes!
+ Exercise!perform!until!
o Target!heart!rate!reached:!HR!=!(220+age)!x!80%!
o Patient!become!symptomatic!!
o Develope!ST+changes!!
+ Abnormal!=!
o Horizontal!ST!depression!of!≥1mm!throughout!≥1!lead!
" More!severe:!more!deep!of!the!horizontal!ST!depression!!!downward!sloping!
ST!depression!!!ST!elevation!
" If!up+sloping!ST!depression:!normal!
o Onset!of!ischemia!at!low!workload!!
o Ventricular!tachycardia!!
!
o Hypotension!
Cardiology!+!77!
 o *!Keep!monitoring!in!the!recovery!phase:!~30%!of!ischemic!changes!happened!during!
the!recovery!phase!!
!
Conclusion!!
+ Exercise!capacity!
o Need!to!look!at!MET,!if!not!achieve!target!MET!!!inconclusive!treadmill!
" MET!=!metabolic!equivalent:!use!age,!sex…!to!calculate!a!exercise!capcity!
o MET!achieved!is!inversely!proportional!to!mortality!
" If!patient!can!achieve!13!MET!!!very!good!prognosis!irrespective!to!coronary!
vessel!condition!
+ Ischemia!
o No!chest!pain!/!ECG!change!!!no!
o Chest!pain!but!no!ECG!change!!!possible!
o ECG!change!but!no!chest!pain!!!probable!
o ECG!change!&!chest!pain!!!definite!
o *!In!ischemia,!sequence!of!change:!cellular!level!!!regional!wall!(seen!by!Echo)!!!ECG!
change!!!chest!pain!
+ Calculated!the!Duke2Treadmill2Score2(annual!mortality!&!5+year!survival)!
o High!risk!(annual!mortality!≥4%)!!!coronary!angiography!
o Intermediate!risk!(2+3%)!!!coronary!angiography!if!additional!risk!factors,!otherwise!
medical!management!
o Low!risk!(<1%)!!!Medical!management!!
!
Alternative!types!of!measures!in!stress!tests!
+ Echocardiography:!look!at!wall!motion!abnormality!(allow!localization!of!ischemia)!
+ Radionuclide!ventriculography!(RVG)!!
o A!perfusion!scan!using!Technetium+99m:!look!at!pumping!function!of!the!heart!
+ Radionuclide!myocardial!perfusion!imaging!(rMPI):!look!at!perfusion!defects!(allow!
localization!of!ischemia)!
!
Complication!(1!in!3000!or!3!in!10,000)!
+ Cardiac!
o Bradyarrhythmia:!sinus,!AV!junctional,!ventricular,!AV!block,!asystole!
o Sudden!death!(VT/VF)!
o MIHF!
o Hypotension!&!shock!
+ Non+cardiac!
o Musculoskeletal!trauma!
+ Ill+defined!&!miscellaneous!
o Severe!fatigue!(may!persist!for!days),!dizziness,!fainting,!body!ache,!delayed!feelings!of!
illness!
!
Alternative!!
+ Pharmacological!stress!ECG!!
o Vasodilators:!adenosine,!dipyridamole!(C/I!in!asthma)!
" Causes!vasodilation!when!given!at!high!doses!over!a!short!time!
o Inotrope:!dobutamine!
o *!For!patients!not!able!to!do!exercise!
+ Stress!echo/rMPI,!cardiac!MRI!!!look!for!functional!ischemia!
o For!patient!with!non+interpretable!ECG!!
" Preexcitation!syndrome!
" >1mm!ST!depression!at!rest!
!

Cardiology!+!78!
 " Taking!digoxin!
" LVH!criteria!
+ Coronary!angiography,!CT!angiogram!!!look!at!coronary!artery!(anatomical!not!functional)!
CT0angiogram0
+ Anatomical!test,!not!functional!
o May!have!poor!correlation!of!result!to!function!status!of!patient!!
+ Very!high!negative!predictive!value!
o Good!for!patients!with!low!pretest!probability:!+ve!test!can!rule!out!coronary!problem!!
o If!high!pretest!probability!!!should!do!coronary!angiogram!directly!
+ Considerable!dose!of!radiation!used!!
+ Why!CT!angiogram!is!only!available!in!the!recent!years!when!CT!scan!is!here!for!long!time?!
o Coronary!arteries!are!very!thin:!~2.25+4mm!
o Coronary!arteries!are!moving!all!the!time!!!need!very!quick!imaging!during!diastole!
o ∴!Need!advanced!techonology!
+ Prerequisites!for!CT!angiogram!
o Able!to!control!respiration:!need!to!hold!breath!!!C/I!in!COPD!pt!with!resp!distress!
o Sinus!rhythm!
o Not!too!old:!too!much!calcification!may!block!view!
o Can!tolerate!BB:!need!to!control!HR!to!~50!!
Cardiac0catheterization0
+ Any!procedure!requiring!putting!catheter!through!the!vessel!to!the!heart!
+ Can!be!doing!angiogram,!PCI!or!monitoring!pressure!

Coronary0angiogram0
Anatomy!of!the!heart!
+ LAD:!have!constant!territory!
o Towards!the!apex,!give!out!diagonal!(to!lateral)!&!septal!(to!septum)!branches!
+ Circumflex:!variable!territory,!compete!with!RCA!
o Give!rise!to!obtuse!marginal!(OM)!artery!1&2!!
!
Procedure!
+ Fast!at!least!4!hours!before!procedure!
+ Takes!~15+20mins!(Vs!PCI:!1!hour)!
+ Bed!rest!for!4+6!hours,!usually!discharge!same!day!
!
Risk/complications!(low!risk!procedure)!
+ Nausea!5%!
+ Wound!infection!/!hemorrhage!1%!
+ Mild!allergic!reactions!to!contrast,!e.g.!rash!2%!
+ Severe!allergic!reaction!to!contrast!0.007%!
+ MI!0.07%!
+ Stroke!0.2+0.4%!
+ Sudden!death!0.1%!
+ Rarely!subclinical!hyperthyroidism:!contrast!contain!iodine!

Percutaneous0Coronary0Intervention0(PCI)0
Introduction!
+ In!the!past!!
o Conventional!PTCA:!problems!of!elastic!recoil,!intimal!dissection!with!abrupt!closure!of!
dilated!segments,!restenosis!30+40%!within!6!months)!
o PCI!is!limited!to!proximal,!discrete,!subtotal,!concentric,!noncalcified!lesions!!
!

Cardiology!+!79!
+ Now!!
o More!advanced!techniques!(e.g.!stents,!rotational!atherectomy)!
o Improvement!in!adjunctive!pharmacotherapy!!
!
Indications!&!C/I!
+ Larger!vessels:!do!stenting!if!occlude!>70%!
+ Vessel!of!<2mm!!!cannot!put!stent,!use!balloon!only!
o New!technology:!drug+elluting!balloon:!balloon!that!release!drug!
+ Relative!C/I:!unexplained!anemia!(dual!anti+platelet),!renal!impairment!(contrast!
nephropathy)!
!
Technology!!
+ Balloon2angioplasty2!
o Elastic!recoil!
o Cx:!local!intimal!dissection,!which!may!!!complete!closure!of!artery!
o 30+40%!overall!restenosis!rate!!
+ Bare2metal2stent2!
o Usually!made!of!stainless!steel!/!cobalt+chromium!alloy!!
o Mechanical!framework!to!maintain!artery!opens,!Vs!PTCA!alone:!!
" No!elastic!recoil!
" No!local!intimal!dissection!
" 15%!overall!stent!restenosis!(treat!with!balloon!dilatation!and/or!
brachytherapy)!!
o Problem:!higher!risk!of!early2stent2thrombosis,!restenosis!due!to!hyperplasia!caused!
by!vessel!trauma!during!atent!implantation!
" ∴!Need!double!antiplatelet!for!1!month!!
+ Drug2eluting2stent2(DES)!
o Anti+proliferative!drugs!to!reduce!neointimal!hyperplasia!(zotarolimus,!sirolimus,!
everolimus,!paclitaxel)!!!↓!rate!of!in+stent!restenosis!(to!5%)!
o Problem:!late2stent2thrombosis2(0.6%!per!year)!–!delayed!endothelialization!
" ∴!Need!double!antiplatelet!for!122months22
• In!fact!the!risk!of!very!late!stent!thrombosis!exist,!so!double!antiplatelet!
can!be!lengthened!in!high!risk!pts!
o Considered!the!first!line!stent!unless:!!
" $$$!problem!
" Patient!cannot!tolerate!prolonged!double!antiplatets!
" Coronary!anatomy!with!long!small!caliber!artery!!!high!chance!of!restenosis!!
+ Bio+engineered!stent!
o Coated!with!antibodies,!which!rapidly!capture!circulating!endothelial!progenitor!cells!in!
blood!stream,!accelerating!the!natural!healing!process!
o Lower!thrombotic!risk!than!bare!metal!stent!/!drug!eluting!stent!
o Need!double!antiplatelet!for!1!month!
+ Other!technologies!!
o Atherectomy!catheter:!used!in!heavily!calcified!lesion!to!improve!compliance!for!
balloon!dilatation!!
o Thrombectomy!devices!
o Embolic!protection!devices!!
!
Vascular!access:!femoral!vs!radial!artery!
+ Femoral!artery!is!end!artery!
o If!damage!!!no!blood!supply!to!lower!limb!(though!risk!of!damaging!it!is!low!as!it’s!
large)!
!

Cardiology!+!80!
 o Vs!radial!artery:!if!damage!!!still!have!ulnar!artery!
+ Less!access!complications!in!radial!artery!
o Femoral!a!only!have!one!site!against!femur,!other!are!muscle!/!soft!tissue!which!are!
difficult!to!compress!to!stop!bleeding!!!may!develop!hematoma,!pseudoaneurysm,!
even!retroperitoneum!bleed!(fatal)!
" If!femoral!bleeding!!!compress!slightly!above!the!skin!wound,!as!the!needle!
enter!obliquely!
o Radial!a!is!against!radial!bone!!!can!be!compressed!easily!
+ Technically!more!difficult!to!perform!in!radial!artery!as!it’s!thinner!
o If!thick!instrument!is!needed!in!more!complicated!cases!!!need!to!use!femoral!
+ Radial!artery:!L!side!is!preferred!as!the!route!is!better!
o But!usually!use!R!side!due!to!limitation!of!the!setting!
!
Procedure!!
+ 60+90min!
+ Achieve!anticoagulation!(UFH/!LMWH/!bilvalirudin)!
+ Aspirin!pretreatment!300mg!
+ Clopidogrel!preloading!300+600mg!±!glycoprotein!IIb/IIIa!antagonists!(if!many!clots)!
+ Coronary!angiography!
+ Catheter!inserted,!a!steerable!0.4mm!guidewire!advanced!across!target!lesion!
+ Balloon!dilatation!(6+16atm)!±!rotational!athrectomy!
+ Stent!placement!±!intraenous!ultrasound!
+ Stop!anticoagulation!
+ Wound!pressure!
o Close!femoral!artery!using!Angioseal:!a!new!method!to!close!the!vessel!endocascularly!
in!order!to!stop!bleeding!(disadvantage:!cannot!puncture!that!vessel!again!within!3!
months)!
!
*!Cannot!do!all!3!vessels!at!one!go!(need!stage!procedure)!
+ Need!contrast!during!procedure!(~200ml/procedure)!
+ If!do!all!3!vessels!!!need!too!much!contrast!!!high!risk!of!nephropathy!
+ Also!if!duration!of!procedure!too!long!!!too!high!radiation!exposure!&!machine!get!overheat!
+ So!do!the!most!critical!ones!then!do!stage!procedure!
!
Complications!(1%)!
+ General:!catheter!sites!bleeding,!hematoma!formation,!infection,!pain,!death!
+ Specific:!injury!to!nearly!organ/tissue!
o Contrast!allergy,!contrast!nephropathy!
o AMI!
" Stroke!(cardiac!emboli!Vs!hemorrhagic!due!to!dual!anti+plt)!
• Echo:!if!have!mural!thrombus!!!warfarin!for!3+6m!(INR2+3)!
o Arrhythmia!
" If!catheter!enter!LA!!!e.g.!atrial!ectopic,!even!VT,!VF!
o Coronary!artery!dissection!/!perforation!
" When!put!in!balloon!!!risk!of!dissection!
" When!put!in!stent!!!risk!of!stent!edge!dissection!if!stent!edge!land!on!a!diseased!
(stenosed)!region!
" If!stent!size!is!too!large!!!risk!of!vessel!perforation!
o Stent!malposition!
o Acute!stent!thrombosis!
" Acute!occlusion!of!stent,!due!to!clot!formation!on!the!not+yet+endothelialised!
stent!!
!

Cardiology!+!81!
 " Higher!risk!in!drug!eluting!stent,!so!need!to!take!longer!anti+platelet!
o Aortic!dissection,!arterial!puncture!(hemoperitoneum,!hemothorax)!!
o Pseudoaneurysm!/!dissection!of!access!blood!vessel!/!aorta!
o Emboli!
" Cholesterol!emboli!!!renal!function!↓!(Rx:!high!dose!statin)!
" Platelet!emboli:!plt!clot!on!the!catheter,!when!remove!it!!!clots!fall!off!from!
catheter!&!left!in!the!vessel!
" Content!of!atherosclerosis!
o Ventricular!pseudoaneurysm!
o Cardiac!tamponade!
" Hemopericardium!due!to!puncture!of!myocardium!
" Post+pericardiotomy!syndrome!(PPS):!pericardial!effusion!due!to!secondary!
pericarditis!(inflam!markers!activated)!
• Less!common!in!PCI,!more!common!in!surgery!that!involves!opening!of!
pericardium!
• Vs!Dressler's!syndrome:!complication!of!MI!
o Re+stenosis!
" MI!risk!after!PCI!is!still!higher!than!normal!population:!2+3%!Vs!1%!!
" A!chronic!insidious!process!of!stent!stenosis!(Vs!stent!thrombosis:!acute),!due!to!
neointimal!hyperplasia!!
• !Acute=!<24hour;!subacute!=!<1week;!late!=!<1year;!very!late!=!>1year!!
o Risk!of!dual!anti+platelet!
" Extra+bleeding!risk!in!future!operation!if!any!
+ **!Any!complications!happened!!!may!convert!to!urgent!CABG!
!
Use!of!antiplatelet!agents!in!patients!undergoing!PCI!!
+ Development!history!!
o Aspirin!
o Aspirin!+!ticlopidine!(neutropenia)/!
o Aspirin!+!clopidogrel!
o Aspirin!+!prasugrel/ticagrelor!!
+ Current2choice2for!drug!eluting!stent!=!aspirin2+2clopidogrel2!
o Loading!clopidogrel!of!300mg!stat,!followed!by!75mg!daily!
Coronary0Artery0Bypass0Surgery0/0Graft0(CABG)0
CABG!preferred!(over!PCI)!if!
+ Disease!of!L!main!coronary!artery!(LMCA)!
o L!main!trunk!supply!lots!of!myocardium,!during!PCI,!may!↓!blood!flow!!!higher!risk!of!
cardiac!arrest!
+ Disease!of!all!3!coronary!vessels!(LAD,!LCX,!RCA)!
o Each!stent!inserted!carry!risk!of!20+30%!of!re+stenosis,!so!risk!of!re+stenosis!↑!if!many!
stents!are!needed!
+ Diffuse!disease!not!amenable!to!Rx!with!a!PCI!
!
CABG!Vs!PCI!
+ CABG!is!more!durable!
o More!immediate!complication!
o Less!re+stenosis!rate!
o Similar!survival!for!2+vessel!disease!
+ PCI:!procedure!done!when!the!heart!is!beating!!!higher!mortality!/!complication!rate!during!
procedure!in!high!risk!patient!

Cardiology!+!82!
 o If!any!complications!occurs!(e.g.!dissection…)!during!the!procedure!that!affect!blood!
flow!leading!to!cardiac!arrest!!!may!die!on!table!
o Vs!CABG:!have!mechanical!bypass,!less!risk!of!complication!during!procedure,!but!
higher!complication!rate!after!the!procedure!(due!to!clamping!of!vessels,!accumulation!
of!toxin…)!
!
Complications!
+ See!CT!notes!
!
Post+op!need!high!dose!aspirin!for!≥1!year!
Prosthetic0valve0replacement0
Types!
+ Mechanical!valves!(percutaneous!/sternotomy/thoracotomy!implantation)!
o Can!last!indefinitely!
o But!need!lifelong!anticoagulant!(need!regular!blood!test!monitoring)!
+ Tissue!(biological)!heart!valves!(allograft/isograft,!xenograft:!usu!pig!valve)!
o No!need!anticoagulant!
" Improved!blood!flow!dynamics!resulting!in!less!red!cell!damage!and!hence!less!
clot!formation!
o Limited!lifespan!(~15!years)!!!not!preferred!in!young!patients!
!
Before!procedure!
+ Do!Echo!to!assess!severity!of!valvular!lesion!
o For!mixed!valve!lesions:!not!replace!both!valve!if!possible:!higher!risk!for!dual!valve!
replacement!
+ Do!coronary!study!to!r/o!CAD!
o If!present,!do!CABG!at!the!same!time!
!
Complications!
+ Paravalvular!leak!
o Murmur!!
o May!!!hemolytic!anemia!
+ Thrombosis!!
+ Infective!endocarditis!
o Even!mild!fever!in!patient!with!prosthetic!heart!valve!!!need!to!investigate,!less!
worrying!if!2!blood!cultures!are!negative!
!
Long+term!warfarin!
+ As!prosthetic!valve!is!prothrombotic!
+ INR!aim!at!2+3!except!mitral!/dual!valve!replacement:!INR!2.5+3.5!(M!=!low!flow!system!!!
more!stasis!!!↑!risk!of!thrombus!formation!!!aim!higher)!
+ If!underwarfarinisation!!!may!need!heparin!cover!when!titrating!the!warfarin!dose!
o In!MVR:!use!UH!because!it!can!be!monitored,!off!heparin!when!INR!≥2,!continue!to!
titrate!warfarin!until!reach!target!of!2.5+3.5!
o In!AVR:!can!use!LMWH!(due!to!lower!thrombotic!risk)!
+ Need!to!change!from!warfarin!to!heparin!before!surgery!(bridging!therapy)!
o Vs!patient!with!DVT:!no!need,!just!stop!warfarin!is!OK!
" Indication!depends!on!estimated!risk!of!ischemic!stroke!
+ **!Cannot!use!dabigatran!
o Newest!evidence!in!NEJM!2013!showed!that!dabigatran!is!inferior!to!warfarin!in!terms!
of!thromboembolic!risk!&!bleeding!risk!in!mechanical!heart!valve!
!

Cardiology!+!83!
External0Defibrillation0/0Synchronized0DC0cardioversion0
Defibrillation!!!no!synchronization!
+ Use!in!VF/!pulseless!VT!
+ If!used!in!other!circumstances,!risk!of!R!on!T!phenomenon!!!ventricular!stimulus!in!
repolarization!phase!!!develop!VT/VF!!!sudden!death!
!
Synchronized!DC!cardioversion!!!synchronized!with!R!wave!to!shock!!
+ Have!time!lag!so!not!in!above!condition!
+ Use!in!pulse+present!VT!
o Hemodynamically!stable!VT!(±!analgesics!e.g.!morphine/midazolam,!because!
cardioversion!cause!pain)!
" May!also!try!IV!amiodarone!but!less!preferred!
o Hemodynamically!compromised!VT!
+ Modes!
o Monophasic:!not!exist!anymore,!don’t!say!in!exam!!!
o Biphasic:!more!effective,!maximum!100J!(=200J)!
" Easily!cardioverted!(SVT,!atrial!flutter):!start!by!50J!biphasic!
" Difficult!to!cardiovert!(AF,!VT):!start!by!100J!biphasic,!then!escalate!to!150,!200J!
!
Mechanisms!
+ Passing!a!sufficiently!large!electrical!current!through!the!heart!to!completely/depolarize!it!!
+ Create!a!brief!period!of!asystole!which!usually!followed!by!the!resumption!of!sinus!rhythm!
+ *Current!external!defibrillators!also!have!functions!of!transcutaneous/pacing!!
+ When/used/to/treat/organised/rhythms/!
o Shock!should!be!synchronised!with!ECG!!
o Given!0.02s!after!peak!of!R!wave!!
o If!shock!on!peak!of!T!wave!!!provoke!ventricular!fibrillation!(RMonMT/phenomenon)!
+ When/used/to/treat/ventricular/fibrillation/!
o Precise!timing!is!not!important!!
!!!
Procedure!
+ Gel!pads!placed!on!right!upper!sternal!border!+!apex!
+ In!emergency!setting,!first!shock!should!be!100J,!followed!by!150J!!
+ In!elective!cardioversion!!
o Requires!GA!/!sedation!
o Can!start!from!low+amplitude!shock!eg!20+30J,!to!prevent!postoperation!chest!pain!!
o Withhold!digoxin!24hours!before!elective!cardioversion!!
o Start!warfarin!4!weeks!prior!to!cardioversion!for!atrial/arrhythmias!
Pacemaker0
Temporary0pacemakers0
Indications!
+ Transient!bradyarrhythmias!(e.g.!inferior!MI,!electrolytes!or!metabolic!disturbances)!
+ Prelude!to!permenant!pacing!
!
Types!!
+ Transcutaneous!pacing!
o Usually!incoporated!with!external!cardiac!defibrillators!!!
o Significant!discomfort!as!it!induces!forceful!pectoral!&!intercostal!muscles!contractions!!
+ Transvenous!pacing!
o Catheters!enter!from!internal!jugular,!subclavian!and!femoral!veins!!!
!

Cardiology!+!84!
 o Positioned!at!the!right!ventricular!apex!!!
o ECG:!broad!QRS!complex!with!LBBB!pattern!

Permenant0pacemakers0
Indications!
+ Bradycardia!!
o Daytime!mean!HR<40!/!symptomatic!/!long!pause!>5s!if!asymptomatic!
+ Heart!block!
o Symptomatic!T1!2nd!degree!HB!/!T2!2nd!degree!HB!/!3rd!degree!HB!(symptomatic!/!
asymptomatic)!
+ Drug+resistant!tacharrhythmias!
!
Considerations!
+ Symptom:!e.g.!syncope,!dizziness!
+ Age:!balance!risk!&!benefit!
+ LV!function:!low!LV!Fx!is!a/w!risk!of!VT/VF,!as!pacemaker!trigger!ventricle!
!
Mechanism!
+ Pulse!generator!implanted!under!the!skin!
+ Programmable!by!telemetry!system,!to!control!heart!rate,!pacing!mode!and!output!
!
Procedure!of!insertion!
+ Via!cephalic!vein!(preferred,!no!need!venogram+guided)!or!axillary!vein!(need)!
+ Require!contrast!in!the!procedure!!!risk!of!contrast!nephropathy!/!allergy!
+ Put!on!left!subclavicular!region!!
o If!in!R!side!!!may!limit!movement!of!R!upper!limb!
o Easier!for!surgeon!to!put!it!in!L!side:!the!wire!only!need!1!curve!(vs!R+side:!the!wire!
need!to!be!S+shape)!
!
Code!
+ 1st!letter:!chamber!paced!(A,!V,!D)!
+ 2nd!letter:!chamber!sensed!(A,!V,!D,!0)!
+ 3rd:!pacemaker!reponse!
o T:!trigger!
o I:!inhibited!
o D:!dual!
o R:!rate!response!
" A!sensor!that!triggers!a!↑!in!HR!in!response!to!movement!or!↑!respiratory!rate!
+ 4 !letter:!P!=!programmable,!M!=!multiprogrammable!
th

+ 5th!letter:!P!=!pace!when!tachycardic,!S!=!shock!when!tachycardic,!D!=!dual!ability,!0!=!none!
!
Types!!
+ Single!chamber!pacemaker:!RV!pacing!
o VVI!/!VVIR!mode:!for!chronic2AF!
" Ventricular!"on!demand"!pacing!!!wide!complex!in!ECG!
" No!synchronization!with!the!atrial!beat!is!required!
• No!atrial!contraction!!!no!pacemaker!syndrome!
" Lead!on!outflow!track!(near!bundle!of!His!!!more!physiological)!
" VVIR:!with!automatic!rate!adjustment!for!exercise!
o AAI!/!AAIR!mode:!for!sinus2node2disease!(SND)!/!sick2sinus2syndrome!
" Similar!to!VVI!/!VVIR!but!with!atrial!pacing!
" Intact!AV!conduction!!!narrow!complex!in!ECG!
!

Cardiology!+!85!
 o VDD!mode:!for!AV2block!
" Single!pacing!lead!with!electrodes!in!RA!(to!sense)!&!RV!(to!sense!&!pace)!
" Detect!atrial!beat!!!trigger!ventricular!beat!after!a!normal!delay!(0.1+0.2s),!
unless!it!already!happened!
" Allow!ventricular!rate!to!increase!together!with!atrial!rate!during!exercise!/!
stress!(because!the!SA!node!firing!will!change)!&!avoid!pacemake!syndrome!
+ Dual!chamber!pacemaker!/!Biventricular!pacemaker!(BVP)!
o Implanted!cardiac!resynchronization!device!(ICR)!!
" A!device!used!in!CRT!(cardiac!resynchronization!therapy)!
" 1st!lead:!RA!!!facilitate!synchrony!with!atrial!contraction!
" 2nd!lead:!RV!!!stimulate!septum!
" 3rd!lead:!coronary!sinus!!!pace!lateral!wall!of!LV!
• Cannot!put!the!lead!into!LV!because!LV!has!too!high!pressure,!lead!can’t!
stay!inside!
o For!refractory2HF2with2ventricular2dysynchrony2with2poor2EF!
" Clinically!HF,!ECG!show!widen!QRS!(>150ms)!&!Echo!showed!poor!EF!
o Synchronize!A!&!V,!and!septal!&!lateral!walls!of!LV!!!avoid!HF!due!to!dyssynchrony!
o Also!more!superior!than!conventional!pacing!for!heart!block!!
" Conventional:!pace!RV!!!like!having!a!LBBB!!!long!term!will!cause!LVH!&!↓!in!
LV!function,!CRT!is!better!as!it!improve!synchronization!
o CRT!defibrillators!(CRT+D):!capable!of!delivering!electrical!shocks!for!dangerously!fast!
abnormal!ventricular!rhythms!
+ Rate+responsive!pacemaker!
o Have!sensors!that!detect!changes!in!physical!activity!!!automatically!adjust!the!pacing!
rate!to!fulfill!metabolic!needs!
!
ECG!morphology!
+ Pacemaker!spike!then!widen!QRS!with!LBBB!morphology!
!
Clinical!monitoring!
+ Put!a!magnet!over!the!pacemaker!!!change!the!mode!of!pacemaker!!!not!detect!intrinsic!
heart!rate!&!pace!at!its!own!rhythm!(e.g.!60/min)!
+ Some!pacemaker!have!battery!dependent!rate!!!can!used!to!check!amount!of!battery!left!
!
Complications!
+ Perioperative:!wound!infection,!hematoma,!pneumothorax,!heart!perforation!
+ Pacemaker!syndrome!in!VVI!
o Due!to!atrioventricular!asynchrony:!concomitant!contraction!of!RA!&!RV!!!atrium!
contract!against!closed!valve!!!↑!ANP!release,!hypotension!
o Signs!&!symptoms!
" Dyspnea!
" Dizziness!!
" Cannon!A!waves!
" Sensation!of!engorgement!of!the!neck!
+ Pacemaker!induced!tachycardia!in!DDD!
+ Lead!fracture!and!dislodgement!
+ Limited!longeivity!(wearing!of!pacemaker)!
Implantable0cardioverter0defibrillator0(ICD)0
Mechanism!
+ A!rhythm!sensor!+!Generator!+!intracardiac!leads!
+ Functions!
!

Cardiology!+!86!
 o Pacemaker!for!bradyarrhymias!
o Overdrive!pacing!for!VT!
o Synchronised!cardioversion!for!VT!
o Defribrillation!for!VF!
!!
Indications!
+ Primary/prevention!
o Class!III/IV!heart!failure!with!low!ejection!fraction!
o Long!QT!syndrome!
o Hypertrophic!cardiomyopathy!
+ Secondary/prevention!
o Previous!potentially!life!threatening/!symptomatic!arrhythmias!
!
In!CXR!
+ Have!double!coil!(bigger!insulated!leads)!shown!in!CXR!
o One!at!SVC,!one!at!RV!!
o Vs!pacemaker:!same!thickness!of!the!whole!lead!
Physical0examination0(Cardiovascular0exam)0
OSCE!
+ MS,!AR,!MR!
+ Infective!endocarditis:!clue:!on!IV!antibiotics!
+ Valve!replacement!with!residual!regurgitation!/!murmur!
+ Valve!replacement!with!warfarin!complications,!e.g.!overwarfarinization,!stroke!
!
General!inspection!
+ Stigmata!of!infective!endocarditis!
o Splinter!hemorrhage!
o Oshler’s!nodes:!red,!raised,!tender!nodules!on!pulps!of!fingers!
o Janeway!lesions:!non+tender!erythematous!maculpopapular!lesions!on!palms!/!pulps!of!
fingers!
+ Radial!pulse!
o *!Sometimes!use!radial!artery!for!PCI,!so!radial!pulse!may!be!absent!
o *!If!cannot!palpate!radial!pulse!!!SBP!should!be!<70!
" Perfusion!pressure!of!radial!artery:!70;!lower!limb!90,!carotid!60+70mmHg!
o AF!
" If!have!history!of!stroke!!!look!for!regularity!of!pulse:!AF!
" Stroke!volume!of!each!pulse!is!different!!!don't!say!character!of!carotid!pulse!is!
normal,!just!skip!it!
" Look!for!features!of!thyrotoxicosis!!
" Especially!look!for!MR!(pansystolic!murmur)!/!MS!(use!bell!&!turn!patient!to!L!
lateral)!later!
• If!no!murmur!!!consider!ASD!!!look!for!fixed!splitting!at!sternum!(ask!
patient!to!take!deep!breathe)!/!parasternal!heave!/!flow!murmur!over!P!
area!
o ASD!patients!usually!develop!AF!when!get!old!
" Look!for!complications!
• Stroke!(thrombosis):!screen!muscle!power!/!ask!patient!left!up!both!arms!
(hemiperasis)!&!facial!symmetry!
• Pulmonary!embolism!
• Overwarfarinization!!

Cardiology!+!87!
 o Valvular!AF!!!patient!should!be!on!warfarin!∴!look!for!bruises!
over!bony!prominence!&!cubital!fossa!around!site!of!blood!taking!
o Radial+radial!pulse!
" RR!delay:!subclavian!artery!stenosis!
• Commonest!site!of!coarctation!is!just!distal!to!L!subclavian,!∴!no!RR!delay!
in!CoA!
" Pulse!discrepancy!(different!in!volume)!
• Aortic!dissection:!false!lumen!may!encroach!the!ostium!of!subclavian!
artery!
o Radial+femoral!delay:!coarctation!of!aorta!
o Collapsing!pulse:!feeling!hand!should!not! ,!use!another!hand!to!left!up!the!arm!
" In!AR,!when!you!lift!up!the!arm,!blood!regurgitate!from!artery!back!to!heart!!!
next!beat!have!higher!volume!due!to!starling’s!law!
+ Xanthoma!(tendon)!&!xanthelasma!(eyelid)!
+ Conjunctival!pallor!
o Non+sensitive!test:!clinically!detectable!only!when!Hb!<8!
o May!be!present!in!microangiopathic!hemolytic!anemia!in!valve!replacement!
+ Mitral!facies:!in!severe!MS!!!↓!CO!
o Rosy!cheeks,!whilst!the!rest!of!the!face!has!a!bluish!tinge!due!to!cyanosis!
+ JVP!
o JVP!Vs!carotid!pulse!
" Apply!pressure!at!the!root!of!neck!!!JVP!will!disappear!
" Apply!hepatojugular!reflux:!apply!a!sustained!pressure!
" If!there’s!distended!external!jugular!vein!on!neck!!!likely!also!have!↑!JVP!
o Different!waveform!
" Palpate!contralateral!carotid!at!the!same!time!!!the!wave!coincide!with!carotid!
is!the!v!wave!
o If!elevated!!!look!for!signs!of!heart!failure!
" O2!supplement,!ankle!edema,!basal!creps,!breath!with!accessory!muscles!
" Also!ask!for!CXR!
o AF!!!never!has!2!waveforms!!!(No!atrial!contraction!!!no!a!wave)!
+ Carotid!pulse!
o Character!
" Low!volume!pulse!!!AS!/!MS!(if!regular!pulse!!!likely!AS)!
o Corrigan's!sign!
" Carotid!pulsation!(anterior!to!SCM),!bilateral,!very!forceful!(contrast!to!JVP)!
" Suggest!AR,!should!have!other!signs!of!AR,!e.g.!displaced!apex!beat,!early!
diastolic!murmur...!
!
Examination!of!the!precordium!
+ Scars!
o Mid+sternotomy!scar!
" Valve!replacement,!CABG!
• CABG:!use!internal!thoracic!artery/!radial!artery/!great!saphenous!vein!
as!graft!
• Look!for!saphenous!scar!(medial!side!of!leg,!usually!take!10+20cm!of!vein!
distally)!
o Submammary!scar!
" Transventricular!mitral!valvotomy:!for!MS,!seldomly!done!now!
+ Pacemaker!/!ICD!(implantable!cardioverter!defibrillator)!
o Pacemaker!is!smaller!while!ICD!is!larger,!but!don’t!comment!on!it,!just!say!a!‘device!
!
below!the!clavicle’!
Cardiology!+!88!
+ Hickman!catheter!!!think!of!IE!(IV!antibiotics)!
+ Listen!for!metallic!click!when!doing!inspection/!palpation!&!listen!for!metallic!heart!sound!
when!auscultate!
o Easier!to!differentiate!1st!/!2nd!HS!is!metallic!with!ear!without!stethoscope!∴!hear!
carefully!with!palpating!carotid!pulse!
+ Apex!beat!
o If!cannot!feel!apex!beat!!!tell!patient!to!sit!up!&!lean!forward!
o If!still!can't!feel!!!turn!patient!to!left!lateral!position:!will!displace!apex!beat,!but!at!
least!can!feel!for!character!
o Site!
" Displaced!!!suggest!LVH!(caused!by!HT,!AS,!cardiomyopathy)!
• Initial!!!forceful!apex!beat!only,!not!displaced!
• Later!because!supply!not!match!demand!(hypertrophy!!!ventricular!
volume!↓)!!!remodeling!!!dilated!!!displaced!apex!beat!
o Character!(use!palm!/!palmer!surface!of!fingers!to!palpate)!
" Hyperdynamic!(sustained!/!heaving):!pressure!overload!–!ventricular!
hypertrophy!
• Pressure!like!a!fist!on!your!palm!(more!localized),!sustained!
• AS!
" Hypervolemic!(thrusting):!volume!overload!–!ventricular!dilatation!
• Like!a!balloon!hitting!on!you!and!go!away,!more!diffused,!also!displace!
• AR,!MR!
" Tapping!apex!beat!(palpable!S1)!
• MS!
• Mechanical!heart!valve!feel!like!tapping!apex!beat!
" Double!impulse!
• Two!impulses!felt!during!systole!
• Hypertrophic!cardiomyopathy:!when!atrium!pump!blood!into!stiff!LV!!!
4th!HS!
" Dyskinetic!apex!
• Uncoordinated,!dyskinetic!movements!of!infarcted!myocardium!!
• MI!!
+ Parasternal!heave!
o RVH!/!LAH!
" Pul!HT,!PS!(giant!a!wave)!/!TR,!CHF!(giant!v!wave)!
o *!Ask!the!patient!to!expire!slowly!!!not!affect!by!breathing!movement!
+ Palpate!for!palpable!P2!(indicate!pul!HT)!
+ Palpate!for!thrills!
o Present!!!murmur!≥!grade!4!
+ Auscultation!
o Bell!@!apex!!!MS!
o Bell!@!apex!+!left!lateral!position!!!subtle!MS!murmur!
" Have!to!palpate!for!apex!beat!before!auscultate!again!after!turning!because!apex!
beat!change!position!
o Diaphragm!@!apex!!!MR!
" If!have!PSM!!!axillary!radiation!
o Diaphragm!@!tricuspid!area!!!TR!
o Diaphragm!@!aortic!area!!!AR!/!AS!
o Bell!@!neck!!!carotid!bruit!&!AS!radiation!
o Diaphragm!@!left!lower!sternal!border!(3rd!/!4th!ICS)!!!AR!/!VSD!
o +!lean!forward!&!hold!breath!at!full!expiration!!!exaggerate!AR!
!

Cardiology!+!89!
 o Listen!for!lung!base!when!patient!lean!forward!&!look!for!sacral!edema!(esp.!in!elderly!
lying!on!bed!all!the!time!(may!be!more!prominent!than!ankle!edema!)!
o *!If!suspect!PDA!!!can!listen!below!clavicle!
o *!Be!systematic:!1st!differentiate!1st!&!2nd!HS,!then!hear!for!any!loud!/!soft!HS,!then!
murmur!etc!
+ Palpate!for!pulsatile!liver!
o Can!feel!on!costal!margin!/!through!rib!cage!
!
In!cases!of!prosthetic!valve!replacement!
+ May!palpate!click!of!the!metallic!valve,!but!no!need!to!comment!it!
+ Metallic!heart!sound:!1st!/!2nd!HS?!!!Compare!with!carotid!pulse!
o No!need!to!say!best!heard!in!which!area!
+ If!metallic!1st!heart!sound!(MVR)!!!no!need!to!auscultate!in!L!lateral!position!as!metallic!valve!
won't!have!stenosis!
+ May!have!short!(ejection)!systolic!murmur!(flow!murmur):!normal!
+ If!hear!pansystolic!murmur!with!radiation!!!valve!is!failing!&!need!replacement!
+ Also!look!for!evidence!of!HF,!pulmonary!hypertension,!TR2(common!to!have!2°!TR!due!to!2°!
pulmonary!HT!due!to!severe!valvular!disease),!AF,!Cx!of!prosthetic!valve!e.g.!paravalvular!leak,!
old!stroke,!overwalfarinization!

Finish!the!examination!by!
+ Ask!for!BP:!wide!/!narrow!pulse!pressure!
+ Feel!for!pulse!at!lower!limb!at!the!end!of!exam!
+ CXR:!cardiomegaly!
+ Echocardiogram!!
+ Temperature!chart,!splenomegaly,!urine!stix!(microscopic!hematuria)!if!suspected!IE!
!
DDx!
+ Irregularly!irregular!pulse!
o AF!
o Atrial!flutter!with!variable!block!
o Multifocal!atrial!tachycardia!(MAT)! Young:!MVP,!VSD,!
" Common!in!COPD,!also!in!acute!MI,!hypokalemia!&! ASD!
hypomagnesemia! Middle!age:!MR,!MS!
" ECG:!≥!3!P+waves!of!variable!morphology,!varying! Old:!MR,!AS!
PR!intervals!&!HR!>!100!with!narrow!QRS!
complexes!!
+ Pulse!character!
o Bounding:!CO2!retention,!liver!failure,!sepsis!
o Collapsing:!AR,!AVM,!PDA!
o Small!volume:!AS,!shock,!pericardial!effusion!
o Slow!rising!(anacrotic):!AS!
o Bisferiens:!AS!+!AR!
o Pulsus!alternans!(strong/weak!pulse):!LVF,!cardiomyopathy,!AS!
o Jerky!pulses:!HOCM!
o Pulsus!paradoxus!(SBP!↓!in!inspiration!by!>10mmHg):!severe!asthma,!pericardial!
constriction,!cardiac!tamponade!
+ JVP!
o ↑!JVP!with!normal!waveform:!fluid!overload,!RHF!
o ↑!JVP!with!absent!pulsation:!SVCO!
o Large!a!wave:!pul!HT,!PS!
!

Cardiology!+!90!
 o Cannon!a!wave!(RA!contract!against!closed!TV):!complete!heart!block,!single!chamber!
ventricular!pacing,!ventricular!arrhythmia/ectopics!
o Absent!a!wave:!AF!
o Large!systolic!v!wave:!TR!
o High!plateau!of!JVP!with!deep!x!&!y!desent:!contrictive!pericarditis!
o Absent!JVP:!dehydration,!hemorrhage!
+ Parasternal!heave!+!loud!P2!!!listen!for!fixed!spitting!&!pan+systolic!murmur!(ASD)!/!early!
diastolic!murmur!at!P!(PR!due!to!pul!HT)!
+ Pansystolic!murmur!in!LLSB!
o TR!!!look!for!c+v!wave!
o VSD!
" Loudest!at!3rd+4th!ics!(muscular:!
lower;!membranous:!upper)!
" L+to+R!shunt!Vs!R+to+L!shunt!
(cyanosis)!
• Eisenmenger!(pul!HT):!RVH,!
heave,!giant!v!wave,!loud!P2!
• TOF!no!pul!HT,!but!have!↑!
JVP!(no!giant!v!wave)!
+ Loud!2nd!heart!sound!(mechanical!heart!sound)!
but!no!mid!sternotomy!scar!
o Transcatheter!aortic!valve!implantation!
(TAVI)!
" For!treating!severe!AS!
" May!not!be!able!to!hear!click!sound!
without!stethoscope!
" Transfemoral!/!transapical!(small!
incision!just!below!left!nipple)!
+ Splitting!of!2nd!heart!sound!
o Normally!↑!in!inspiration,!A2!then!P2!
o Wide!splitting:!RBBB,!PS,!deep!inspiration,!
MR,!VSD!
o Wide!fixed!splitting:!ASD!
o Reversed!splitting:!AS,!LBBB,!PDA,!RV!pacing!
o Single!S2:!TOF,!severe!AS/PS,!pul!atresia,!Eisenmenger,!large!VSD,!HT!
+ Splitting!of!1st!heart!sound!
o Uncommon:!maybe!due!to!BBB!
+ 3rd!heart!sound!
o Low!pitch,!gallop!rhythm!
o Due!to!rapid!LV!filling!in!dilated!LV!
o Occur!in!HF!with!poor!LV!Fx!(usually!with!tachycardia)!
o Can!be!physiological!(pregnancy!/!<30y.o.)!
+ 4th!heart!sound!
o High!pitch,!atrial!effective!contraction!against!ventricle!
o Not!in!AF!
+ Carotid!bruit!
o Carotid!stenosis!
o Severe!MR!/!PS!may!also!give!soft!carotid!bruit!
" Differentiate!by!moving!stethoscope!down!the!chest!wall,!if!bruit!disappear!!!
likely!from!carotid!
!
!

Cardiology!+!91!
ECG0(electrocardiography)0
Methods!to!slow!down!HR!to!make!P!&!QRS!complex!more!clearly!in!ECG!
+ Vagal!maneuver:!↑!ACh!act!on!SA!node!/!AV!node!!!↓!HR!
o Carotid!massage!
o Cardiac!massage!
o Hold!breath!&!immerse!head!into!water!
+ Valsalva!maneuver:!expired!against!a!closed!glottis!
o Can!arrest!episodes!of!supraventricular!tachycardia!
+ Pharmacological!
o Adenosine!
o Amiodarone!
o Calcium!channel!blocker!
!
Systematic!review!of!ECG!
+ Low!voltage:!peak+to+peak!QRS!amplitude!<!5!mm!(limb!leads)!&/or!<!10!mm!(chest!leads)!
o Pericardial!effusion!
o Thick!chest!wall:!obesity,!pleural!effusion,!subcutaneous!emphysema!
o Severe!hypothyroidism!!
o Massive!myocardial!damage/infarction!
o Infiltrative/restrictive!diseases!e.g.!amyloid!cardiomyopathy!
+ Pacemaker!spikes!
+ Rate!&!rhythm!
o Sinus!/!atrial!/!junctional!/!ventricular!
" Definition!of!sinus!rhythm!
• Every!P!wave!is!followed!by!one!QRS!
• Polarity!of!P!wave:!upright!at!II,!III,!aVF!(inf!leads)!&!inverted!in!V1!!
o Atrium!depolarize!from!superior!to!inferior,!from!right!to!left!
o **!Important!to!differentiate!atrial!tachy!vs!sinus!tachy!
" In!atrial!tachycardia:!P!wave!at!wrong!direction!
• *!1st!degree!HB!can!be!sinus,!but!not!2nd!/!3rd!degree!HB!
" Sinus!tachycardia!!!must!look!for!SIQIIITIII!!!!!!
o Escapes!/!premature!beats!
o Regularly!irregular!
" Sinus!arrhythmia!
• Need!long!lead!II!(e.g.!30s)!to!make!this!comment!!
" Mobitz!type!II!2nd!degree!HB:!regular!rate!with!regular!dropped!beat!
o Irregularly!irregular!
" AF!
" Atrial!flutter!with!variable!block!
" Multifocal!atrial!tachycardia!(MAT)!
• Common!in!COPD,!also!in!acute!MI,!hypokalemia!&!hypomagnesemia!
• ≥!3!P+waves!of!variable!morphology,!varying!PR!intervals!&!HR!>!100!
with!narrow!QRS!complexes!
+ Axis!deviation!
o Normal:!+30°!to!+90°!(both!lead!I!&!II!+ve)!
o *!Lead!aVR!must!be!–ve,!otherwise!!!wrong!leads!(L/R!reversed)/!VT!
o Left!axis!deviation:!L!anterior!fascicular!block,!previous!MI,!LVH,!WPW!
" If!see!RBBB!with!left!axis!deviation!!!bifascicular!block!
• Both!R!bundle!branch!&!L!anterior!fascicle!are!blocked!
• RBBB!won’t!affect!cardiac!axis!

Cardiology!+!92!
 • Indicate!for!pacing!because!if!all!3!branches!block!!!complete!heart!
block!
o Right!axis!deviation:!L!posterior!fascicular!block,!RVH,!PE,!cor!pulmonale,!TOF!
o *!Trifascicular!block:!left!anterior!/!posterior!fascicular!block!+!RBBB!+!1st!degree!HB!
+ P!wave!
o Normal:!≤2.5mm!tall!&!≤120ms,!+ve!in!I,!II,!aVF,!V4+6!
o No!p!wave!!!ventricular!/!junctional!escape!/!AF!
o Abnormal!P+wave!axis!!!atrial!tachycardia!/!atrial!flutter!
o Peaked!P!wave!in!lead!II,!III,!aVF!!!RA!enlargement!
" V1:!biphasic!P!wave:!initial!+ve!portion!>!terminal!–ve!portion!
o I!Bifid!wide!P!wave!(P!mitrale)!in!lead!II,!III,!aVF!!!LA!hypertrophy!!
o Biphasic!P!wave!in!V1+2:!terminal!–ve!portion!>40ms!&!>1mm!!!LA!dilatation!
o Compare!with!previous!ECG!!E.g.!previous!one!have!P,!now!no!P!but!have!S!in!V1!!!may!
be!retrograded!P!(junctional!rhythm)!
+ QRS!complex!
o Q!wave!
" Normally!have!small!Q!wave!in!left!leads:!I,!aVL,!V6!(septal!Q!waves)!
" Pathological!Q:!>1!small!square!(0.04s)!in!width!&!>!2mm!deep!
• DDx!
o STEMI:!10%!of!pathological!Q!wave!will!resolve!!
" NO!Q!wave!in!NSTEMI!(NSTEMI!=!non+Q!wave!infarct)!
o WPW!syndrome:!+ve!delta+waves!over!inferior!leads!
o LBBB:!QS!pattern!over!V1+4!
o COPD:!Q!waves!over!inderior!leads!with!poor!R!wave!progression,!
P!pulmonale,!low!voltage!QRS!
o Hypertrophic!cardiomyopathy:!septal!hypertrophy!with!Q!wave!
over!I,!aVL,!V4+6!
o PE:!Q!wave!over!lead!III!&!aVF!(not!in!lead!II:!vs!inferior!MI)!
o Widen!QRS!(>120ms)!!!BBB!/!ventricular!rhythm!
" Ventricular!rhythm!(Vs!BBB)!
• AV!dissociation!with!independent!P!wave!
• Capture!beat:!capture!the!beat!from!atrium!(normal!atrial!beat!in!the!
middle!of!many!ventricular!beats)!
• Fusion!beat!
o Concurrent!activation!of!same!chambers!by!2!stimuli:!ventricular!
beat!coincides!with!sinus!beat!/!ventricular!ectopic!beat!/!
junctional!beat!
o E.g.!sinus!+!V!beat!
• Taller!left!rabbit!ear!in!lead!V1!(Vs!RBBB:!R!taller)!
" If!have!RR’!complex!but!<120ms!!!incomplete!BBB!
" If!QRS!>150ms!!!have!extra!implication:!CRT!only!useful!for!QRS!>150ms!
o Tall!QRS!!!ventricular!hypertrophies!(may!also!have!axis!deviation)!
" R!in!V5/6!+!S!in!V1!>!35mm!!!LVH!
" Tall!R!in!V1!&!R!axis!deviation!±!RBBB!!!RVH!(e.g.!cor!pulmonale)!
o R!wave!in!V1!(normally!no!R!wave!in!V1)!
" RVH!
" Posterior!MI!
" RBBB!
" PWP!type!1!
" Dextrocardia!!
!
!

Cardiology!+!93!
+ T!wave!
o Usually!have!same!direction!as!QRS!complexes!
o Because!repolarizaion!is!from!epicardium!to!endocardium!(VS!depolarization:!
endocardium!to!epicardium)!
o Tented!T!wave!
" >5mm!in!limb!leads!&!>10mm!in!chest!leads!OR!!
" ≥2/3!of!height!of!R!
" DDX:!hyper+acute!T!wave!in!MI,!HyperK!
• Symmetrical!tented!T!wave!!!more!likely!hyperK!/!ischemia!
• If!not!symmetrical!!!may!be!normal!varient!
o Flatted!T!wave!
" HypoK,!hyperthyroidism,!pericardial!effusion!
o T+wave!inversion!
" Myocardial!ischemia,!PE!(V1+3),!LVH,!LBBB!(V1+4),!RBBB!(V1+3),!RH!strain,!
cardiomyopathy,!pacemaker!rhythm!(ventricular),!Wellens'!syndrome,!WPW,!
hypothyroidism,!hyperventilation,!subarachnoid!hemorrhage,!MVP,!normal!
variant!
" DDx!of!diffuse!TWI:!Wellen’s,!SAH,!apical!HOCM!
+ U!wave!
o Origin!
" Repolarization!of!papillary!muscles!/!Purkinje!fibres!
" M!cells!(in!mid+myocardium):!ventricular!myocytes!with!long!action!potential!
o U!wave!can!be!normal!/!hypoK!
+ PR!interval!
o Beginning!of!P!to!beginning!of!QRS!
o Normal:!120+200ms!(3+5!small!squares)!
o Heart!blocks!
" Mobitz!type!I!(Wenckebach!type):!progressive!prolongation!of!PR!interval!
• Be!careful!that!some!p!waves!may!be!hided!inside!QRS!
" Mobitz!type!II:!sudden!non+conducted!P!wave!
o PR!depression:!pericarditis!
+ J+point!
o J+wave!(Osborn!wave):!positive!deflection!at!J!point!(+ve!in!aVR!&!V1)!
" Height!roughly!proportional!to!degree!of!hypothermia!
+ ST!segment!
o ST!elevation:!significant!when!>!1mm!(limb!lead)/!2mm!(chest!lead)!
" STEMI:!convex!
• More!localized!
• Presence!of!reciprocal!ST!depression!over!other!leads!!
" Pericarditis:!concave!(also!called!‘saddle+shape’!(QRS!+!ST!look!like!saddle):!
different!from!that!of!Brugada!(ST!alone!is!saddle))!
• Typically!widespread!in!all!leads!except!aVR!
• Presence!of!PR!segment!depression!
o ST!depression!
" Subendocardial!ischemia,!hypoK,!digoxin,!ventricular!hypertrophy!
o If!ST!elevation!seen!in!inferior!leads!(II,!III,!aVF)!!!right!coronary!artery!territory!
affected!!!might!also!affect!SA!node!!!need!to!look!for!bradycardia!
ST!elevation!/!depression!
+ In!fact,!it!is!the!shift!in!TP!segment!instead!of!ST!segment!
+ In!MI,!↓!Na/K+ATPase!activity!(which!maintain!K+!gradient)!!!↓!resting!
membrane!potential!
+ Injured!cells!become!partially!depolarized!!!dipole!!!artefactual!shift!of!TP!
!

Cardiology!+!94!
 segment!!!apparent!elevation!/!depression!of!ST!segment!
+ ST!segment!correspond!to!plateau!phase!of!AP!of!both!injured!&!normal!tissues!!!
no!dipole!!!true!zero!isoelectric!line!
+ QT!interval!
o Normal:!<460ms!(F)!/!450ms!(M)!
o Normal!QTc!(corrected!QT!interval:!QT!interval!/!square!root!of!RR!interval):!<440ms!
o Or!prolonged!if!QT!>!½!of!RR!interval!(not!applicable!if!brady!<50)!
o Prolonged!QT:!long!QT!syndrome,!drug!causes,!HCM,!hypoCa/K/Mg!
o Short!QT:!digitalis,!hyperCa!
!
James’s!tutorial:!
+ No!need!to!look!at!lead!aVR,!because!no!pathology!there!
+ There!are!2!ways!of!presenting!the!findings!
o 1.!Say!the!diagnosis!1st!then!as!evidence!by…!
o 2.!Systematically!review!the!ECG!(same!as!CXR),!finally!say!top!DDx!
o Usually!use!2,!unless!it’s!emergency!
" E.g.!this!electrocardiogram!shows!an!acute!inferoloateral!ST!elevation!
myocardial!infarction,!which!is!a!medical!emergency.!This!is!evidence!by…!

Electrical0alternan0
+ Alternation!of!QRS!complex!amplitude!or!axis!between!beats!
+ Seen!in!cardiac!tamponade!&!severe!pericardial!effusion!
+ Heart!move!in!fluid!filled!precardial!sac!!!changes!in!ventricular!electrical!axis!

Ventricular0tachycardia0
+ Monomorphic!ventricular!tachycardia!
o Arise!from!an!irritable!ventricular!focus!
o Consecutive!wide!QRS!with!same!appearance,!no!distinguishable!T!wave!

o !
+ Polymorphic!ventricular!tachycardia!
o Beat+to+beat!variation!in!QRS!morphology!
o E.g.!Torsades!de!Pointes!(twisting!of!the!points)!

o !
+ Ventricular!fibrillation!
o Arise!from!multiple!ventricular!foci!
o No!organized!QRS!complexes!are!seen!

o !
Hyperkalemia0
+ 1.!Tall!tented!T!wave!
+ 2.!PR!interval!↑,!small!P!waves,!wide!QRS!complex!
+ 3.!Sinusoidal!wave:!QRS!complexes!merge!with!T!waves!

Cardiology!+!95!
Hypokalemia0
+ Flattened!/!inverted!T!wave,!prominent!U!wave,!ST!segment!depression,!long!QT!

Hyper/hypoMg0
+ Similar!to!hyper/hypoK!

Hypercalcemia0
+ Shortened!QT!interval!
+ Prolonged!PR!interval!!
+ At!very!high!level!!!lengthen!QRS,!flatten!/!invert!T!waves!&!variable!degree!of!heart!block!!
+ Digoxin!effect!amplified!

Hypocalcemia0
+ Prolonged!QT!interval!

Digoxin0
+ ST!depression:!scooping!appearance!(A)!/!reversed!tick!(B)!!
o *!Reverse!tick!is!feature!of!digoxin!use,!not!toxicity!
+ Toxicity!!!any!kind!of!arrhythmia!
o Tachy!/!bradyarrhythmia!or!combination!
o Bidirectional2VT:!commonest!

Class0IA0antiTarrhythmic0(e.g.0quinidine,0procainamide,0disopyramide)0
+ Widen!QRS,!prolonged!QT!±!U!wave!
+ May!cause!Torsades!de!pointes!

Class0III0antiTarrhythmic0(e.g.0amiodarone,0sotalol)0
+ ↑!PR,!QRS!&!QT!intervals!
+ May!cause!Torsades!de!pointes!&!bradyarrhymias!

Pulmonary0embolism0(PE)0
+ SIQIIITIII!
o Deep!S!wave!in!lead!I,!pathological!Q!&!inverted!T!wave!in!lead!III!
+ Sinus!tachycardia,!atrial!&!ventricular!ectopics!
+ R!axis!deviation!
+ R!ventricular!strain!pattern:!inverted!T!in!R!chest!leads!
+ RBBB:!incomplete!/!complete!
+ Slow!R!wave!progression!in!chest!leads!

AF0
+ No!discernible!P!wave!
+ Fine!Vs!Course!
o Fine:!smooth!baseline!
o Course:!sawtooth!appearance!
This!is!an!electrocardiogram!of!ABC!taken!on!today.!There!is!irregularly!irregular!rhythm!with!
approxiamate!rate!of!100!bpm.!There’s!borderline!L!axis!deviation.!There’s!no!discernible!P!
waves!and!narrow!QRS!complex.!There!is!no!pathological!Q!wave!(Important!to!say!!)!and!no!ST!
changes.!(James:!usually!won’t!say!QT!interval!as!it!needs!calculation).!!
In!summary,!this!is!an!ECG!of!atrial!fibrillation.!

Hypothermia0
+ Bradyarrhythmias!!
+ Osborne!Waves!(J!waves)!
!

Cardiology!+!96!
+ Prolonged!PR,!QRS!and!QT!intervals!
+ Shivering!artefact!
+ Ventricular!ectopics!
+ Cardiac!arrest!due!to!VT,!VF!or!asystole!
Echocardiogram0
Indications!
+ Murmur!
+ Hypotension!
o Volume!status,!tamponade,!myocardial!dysfunction,!valvular!stenoesis!&!insufficiency…!
!!can!all!happen!in!trauma!patient!!(blood!loss,!cardiac!contusion…)!
+ Pericardial!fluid!
+ Atrial!fib!/!flutter!(thrombus)!
o Should!use!TEE!to!look!for!clots!in!L!atrial!appendage!!
+ Aortic!dissection!
+ Shunts!
+ Volume!status!
+ Dyspnea!!
!
Useful!in!the!following!
+ Myopathy!
o Dilated!cardiomyopathy!
o Restrictive!cardiomyopathy!
+ Valvular!lesion!/!valvular!heart!disease!
o Infective!endocarditis!
+ Pericarditis:!chronic!/!constrictive!
+ Congenital!heart!disease!
o Coarctation!of!aorta!!
o Tetralogy!of!Fallot!!
o ASD,!VSD!
+ Aortic!dissection!!
+ Functional!
o Ejection!dysfunction!&!diastolic!dysfunction!
+ NSTEMI!
o Look!at!muscle!for!scarring!&!ischemia!
o Ejection!fraction!=!stroke!volume!/!end!diastolic!volume!=!(end!diastolic!volume!–!end!
systolic!volume)!/!end!diastolic!volume!
" End!systolic!volume:!measured!just!after!QRS!
" End!diastolic!volume:!measured!just!before!P!wave!
+ Stroke!
o Do!ECHO!to!look!for!thrombus!in!L!atrial!appendix!

Transthoracic0Echocardiogram0(TTE)0
3!windows!
+ Parasternal!window!(lie!left!lateral!with!arm!extended!over!shoulder!to!open!up!ribs)!
o Parasternal!long!axis:!LA,!LV,!LVOT,!RV;!M!&!A!valves!
" Probe!right!next!to!the!sternum,!around!the!4th!ICS,!maker!points!toward!R!
shoulder!
• No!too!far!away!from!sternum!(heart!is!midline!structure!)!
• Can’t!put!on!top!of!sternum!/!ribs!as!USG!won’t!go!through!bones!
" Calculate!EF,!LA!size,!Doppler!to!look!for!MR/AR!
o Parasternal!short!axis!(90!degree!turn!from!long!axis)!
" Mitral!valve!level:!RV,!LV;!M!valve!
!

Cardiology!+!97!
 • Same!place,!with!marker!points!towards!L!shoulder!
" Aortic!valve!level:!LA,!RA,!RVOT;!A,!P!&!T!valves;!descending!aorta!(can!look!for!
aortic!dissection)!
• Probe!tilt!upward!
" Papillary!muscle!level!(mid+ventrocle):!RV,!LV,!papillary!muscles,!IV!septum!
• Probe!tilt!downward!
• Look!at!contractility!of!LV,!symmetrical!or!not,!thickness!of!septum!
+ Apical!window!(lie!left!lateral!with!arm!extended!over!shoulder)!
o Probe!at!apex,!marker!points!towards!L,!tilt!towards!thorax!
o Apical!4+chamber:!RA,!RV,!LA,!LV;!M&T!valves!
" Apex!is!at!the!tip!of!the!image!(closest!to!the!probe)!
o Apical!5+chamber:!RA,!RV,!LA,!LV,!aorta;!A,!M&T!valves!
" Look!for!any!septal!defect,!e.g.!patent!foramen!ovale!(PFO)!
+ Subcostal!window!(lie!flat)!
o Subcostal!4+chamber:!RA,!RV,!LA,!LV;!M&T!valves!
" The!marker!point!towards!L,!tilt!probe!at!~45°!!ask!the!patient!to!inspire!to!
descend!the!heart!!
o Subcostal!IVC:!RA,!IVC!
" Maker!points!toward!the!head,!vertical!probe!!!see!aorta,!tilr!slightly!to!right!!!
IVC!
+ **!In!parasternal!&!apical!window,!if!the!views!are!not!good!!!ask!the!patient!to!breath!out!&!
hold!breath!to!↓!air!for!better!view!
!
Color!Doppler!!
+ Colour:!blue!=!flow!away!from!probe!(downward),!red!=!flow!towards!(upward)!–!‘BART’!
o But!when!flow!is!too!fast,!may!color!flow!reversal!(problem!in!calculation!of!the!
machine)!
+ Have!turbulent!flow!in!!!have!mosaic!of!color:!neither!blue!nor!red!!
o Distal!to!valvular!stenosis,!&!happen!during!contraction!
o Proximal!to!regurgiatation,!&!happen!during!relaxation!
+ *!Regurgitation:!Dx!by!Doppler!color!
+ *!Stenosis:!Dx!by!Doppler!flow!
!
Procedure!
+ Patient!lie!on!left!lateral!position!&!connected!to!ECG!
!
Parameters!
+ Ejaction!fraction!(EF):!normal!=!55+60%!
+ LA!size:!normal!<4.0cm!
+ IV!septum!thickness:!>1.2cm!!!LVH!
+ Mean!pressure!gradient!over!AV:!calculate!right!after!QRS!complex!
o Normally!~7mmHg!
o Mild!AS:!<25;!moderate:!25+40;!severe:!>40mmHg;!critical!AS:!>70!
+ EA!ratio:!transmitral!flow!
o E:!LA!to!LV!during!diastole;!A:!LA!to!LV!during!atrial!contraction!
o Area!under!the!curve!(AUC):!LV!filling!volume,!i.e.!stroke!volume!
o Normally!E>A:!more!blood!enter!LV!during!diastole!than!atrial!contraction!
o In!diastolic!dysfunction:!reversed!EA!(E<A)!
" Diastolic!dysfunction!!!more!depend!on!atrial!contraction!
o In!very!severe!diastolic!dysfunction:!raised!EA!(E>A!again)!
" Ventricle!become!stiff!(fibrosed),!∴!once!blood!flow!in!!!pressure!shoots!up!!!
E↑↑;!conversely,!A↓!as!pressure!inside!LV!already!very!high!
!

Cardiology!+!98!
 " But!AUC!↓!although!E↑,!so!stroke!volume!also!↓!
+ IVC!diameter!(take!the!largest!value)!
o Estimate!volume!status!(may!replace!central!line)!
" Sniff!test:!!
• E.g.!originally!IVC!diameter!<!1.5cm!!!if!IVC!collapse!with!sniff!!!RA!
pressure!estimation!is!0+5mmHg!!!hypovolemia!!!!!should!give!fluid!
• E.g.!originally!>2.5cm!&!no!change!with!sniff!!!RA!pressure!>20mmHg!!!
already!volume!overload!!!should!do!inotrope!
o R/o!right!heart!failure!
!
Uses!!
+ Ischemic!heart!disease!
o See!which!part!of!muscle!contract!less!!!find!out!which!vessel!is!involved!
+ Pericardial!effusion!
o Rim!of!black!around!the!heart,!end!before!fescending!aorta!(otherwise!!!pleural!
effusion)!
o Also!look!for!collapsed!RV:!suggest!pericardial!effusion!than!pleural!effusion!
o Can!be!seen!in!subcostal!window!
+ LV!aneurysm!
o Grossly!dialted!LV!
o May!have!stasis!of!blood!(spontaneous!echo!signal)!or!even!clots!inside!LV!due!to!
stagnant!flow!
+ Mitral!stenosis!
o Left!atrial!enlargement,!thick!&!calcified!mitral!valve!with!narrow!&!‘fish+mouth’+
shaped!orifice!!
o Look!for!any!enlarged!LA:!e.g.!no!LA!enlargement!in!acute!IE!(acute!thickening!of!MV!
only)!
Transesophageal0echocardiogram0(TEE)0
Indication!
+ Valvular!lesions!
o TEE!can!see!the!valves!more!clearly,!even!can!see!individual!leaflet!
+ Before!PTMC!in!MS!
o Rule!out!concomitent!MR:!anything!more!than!mild!MR!!!C/I!to!PTMC!
o Rule!out!LAA!clots!(C/I!to!PTMC)!
o Look!at!the!morphology!of!MV:!if!MV!too!thick/calcified!or!subvalvular!apperatus!too!
thick!!!C/I!to!PTMC!
+ Septal!defect!
o Cannot!be!seen!clearly!in!TTE!
Drugs0
Amiodarone0
+ Ultra+long!t½:!30+120!days!
+ Check!TFT!before!prescription:!amiodarone!contain!iodine!content!!!may!lead!to!thyroditis!!!
further!↑!thyroid!hormone!transciently!!!worsen!arrhythmia!
!
Side!effects!
+ Lung:!interstitial!lung!disease!(pulmonary!fibrosis)!–!lower!lobe!
+ Thyroid!
o Amiodarone!contain!iodine!content!&!structurally!similar!to!thyroxine!
o TSH!should!be!checked!every!6!months!
o Hypothyroidism:!more!common!
!
" Slowing!of!thyroid,!due!to!Wolff+Chaikoff!effect!
Cardiology!+!99!
 • Autoregulatory!phenomenon:!↑!blood!levels!of!thyroglobulin!bound!
iodide!inhibit!further!binding!of!iodide!by!thyroid!gland!
o Hyperthyroidism:!less!common!
" Jod+Basedow!Effect!
• Iodine+induced!hyperthyroidism!
" Toxic!to!thyroid!!!inflam!&!release!hormone!
• Rx:!steroid,!NSAIDs!
+ Eye:!corneal!micro+deposits!
+ Skin:!photosensitiviy!
+ GI:!Abnormal!liver!enzyme!
+ Other:!ataxia!
!!Not!use!for!loner!than!3+5!years!

Digoxin0
+ Block!Na/K!ATPase!!!↓!Na/Ca!transporter!
+ +ve!chronotropic!effect!but!+ve!inotropic!effect!
o ↑!vagal!activity!!!slowing!SA!node!rate!&!AV!conduction!
+ Very!slow!onset!
o Need!3!loading!dose!!!the!fastest!still!need!half!day!to!have!effect!
+ Half+life:!36+48!hours!(3.5+5!days!in!renal!impairment)!
+ Narrow!therapeutic!index!
o HypoK!can!induce!toxicity:!K!compete!for!same!binding!site!on!Na+/K+!ATPase!!
o Amiodarone!also!↑!risk!of!digoxin!toxicity!
+ S/E:!N&V!&!D,!blurred!vision,!confusion,!insomnia,!nightmare,!depression!
+ Toxicity:!psychosis,!convulsion,!VT,!VF,!heart!block!
!
Management!of!digoxin!toxicity!
+ Stop!digoxin!
+ Cardiac!monitoring,!ICU!/!CCU!care!
+ Activated!charcoal!within!2!hours!on!infection!in!acute!toxicity!
+ Keep!K!>4.0!as!hypoK!↑!digoxin!effect!
+ Assess!hemodynamic!status!
o VT/VF!!!anti+digoxin!FAb,!hemodialysis!
o *!BB!/!transvenous!pacing!should!be!avoided:!may!trigger!more!serious!arrhythmia!

Nitroprusside00
+ IV!vasodilator!
+ Vasodilation!!!tigger!baroreceptor!!!reflex!tachycardia!
+ Need!A+line!monitoring,!due!to!very!fast!action!
+ Risk!of!cyanide!poisoning!!!rarely!used!
+ Photodegradation!!!need!to!wrap!by!black!cloth!

ACEI0
Contraindication!
+ Bilateral!renal!artery!stenosis:!may!lead!to!acute!renal!failure!!
+ HyperK!
+ Hx!of!angioedema!
+ *!Not!contraindicated!in!renal!insufficiency,!but!need!close!monitoring!
o Generally!protect!kidney,!esp!in!diabetic!nephropathy!by!↓!renal!plasma!flow!
!
Side!effect!
+ General:!N&V,!hypersensitivity,!dizziness!
!

Cardiology!+!100!
+ Specific:!!
o Cough:!20+40%,!due!to!accumulation!of!bradykinin!
" Alternative:!ARB!(less!but!still!may!cause!coughing)!
o Angioedema!
o Renal!failure!(bilateral!renal!artery!stenosis)!
o HyperK!(fatal!within!days!!)!due!to!↓K!removal!by!kidney!
o 1st!dose!hypotension!
o Confusion,!esp!eldery!
o Taste!disturbance,!esp!elderly!
o Agranulocytosis:!very!rare!

Labetalol0
+ Non+selective!BB!
+ Given!by!IV!bolus!followed!by!infusion!
+ For!hypertensive!emergency!
o Alternative!hydralazine!
" Give!by!bolus!!!easier!titration!
" C/I!in!dissecting!aneurysm!as!it!causes!laminar!flow!which!worsen!it!!
" Tends!to!be!used!in!pre+eclampsia/!eclampsia!(though!same!effect!&!outcome)!

Calcium0channel0blocker0(CCB)0
Dihydropyridine:!–dipine,!e.g.!Amlodipine!(Norvasc),!nifedipine!(Adalat)!
+ Affect!peripheral!vasculatures!!!↓!systemic!vascular!resistance!
+ Vasodilation!&!hypotension!!!reflex!tachycardia!∴!not!used!to!treat!angina!
!
Non+dihydropyridine!(rate!limiting!CCB)!
+ Block!AV!node!!!used!as!anti+arrhythmics!
+ Phenylalkylamine:!verapamil!
o Myocardial!selective!!
" Negative!inotropic!effect!!!↓myocardial!O2!demand!!
" Reverse!coronary!vasospasm!!
" Minimal!vasodilatory!effects!!!cause!less!reflex!tachycardia!!
o ∴!Used!to!treat!angina!
+ Benzothiazepine:!diltiazem!
o Have!both!cardiac!depressant!&!vasodilator!actions!!!↓!arterial!pressure!without!
producing!reflex!tachycardia!!

Lasix0(Furosemide)00
+ Loop!diuretic!
+ Weaker!action!as!distal!tubule!reabsorb!more!to!compensate!
o ∴Can!add!thiazide!to!potentiate!its!action,!but!both!can!cause!hypoK!
+ Usually!give!with!Slow!K!(Potassium!Chloride)!!

Spironolactone0(Aldactone)0
Side!effects!
+ High!K!
+ Anti+androgenic!effects!
o Painful!gynecomastia!
o Loss!of!libido!and!erectile!dysfunction!
o *!Newer!drug!(Eplerenone!(Inspra):!also!aldosterone!antagonist)!!!less!progesterone!&!
androgen+receptor!effects!!!for!patient!developing!gynecomastia!after!taking!
spironolactone!
!

Cardiology!+!101!
Heparin0
Unfractionated!heparin!(UFH)!
+ Activated!anti+thrombin!III!!!inhibit!thrombin,!factor!IXa,!Xa!&!XIa!
+ Not!affected!in!renal!impairment,!because!its!dosage!is!titrated!according!to!APTT!anyway!
+ How!to!give?!
o Check!baseline!APTT!&!confirm!no!C/I!(eg.!ICH)!
o IV!bolus!of!3000+5000IU!(80IU/kg)!
o Continuous!infusion!of!500+900IU/hour!(15+25IU/kg/hr)!
o Check!APTT!every!4+6!hours!
" 4+6!hours!because!t½!of!UH!=!60+90min!!!measure!after!4!x!t½!=!almost!
(~93%)!reach!steady!state!
o Titrate!dose!according!to!APTT:!aim!1.5+2!x!upper!normal!limit!(~60+80s)!
+ Uses!
o During!PCI!
" Predictable:!can!be!monitored!by!APTT!
" Reliable!absorption!(IV,!Vs!LMWH:!SC,!absorption!affected!by!shock!/!
dehydration)!
" Can!be!reversed!by!protamine!
o During!invasive!procedure!in!patients!with!prosthetic!heart!valve!
" LMWH!↑!mortality!in!this!group!of!patients!
o Other!conditions!can!use!LMWH!
+ Complication!
o Bleeding!
" If!massive!bleeding!occur!!!can!reverse!effect!in!4!hours!(vs!LMWH:!12hr)!
o HIT!(heparin+induced!thrombocytopenia!with!thrombosis):!up!to!5%!
" Heparin!binds!to!the!circulating!platelet2factor24,!this!complex!induces!the!
formation!of!an!antibody,!which!causes!platelet!activation!&!clumping!
" Need!to!check!platelet!count!regularly!
" Cause!a!fall!of!platelet!count!>50%!≥!5!(usu!5+7)!days!after!initiation!of!heparin!
therapy!(time!for!Ab!to!form)!
• S/S!starts!at!only!1+2!days!after!heparin!infusion,!in!those!previously!
sensitized!with!pre+formed!antibodies,!thus!a!quick!immune!reaction!
" Clinical!presentations!
• Asymptomatic!
• Increased2/2new2thrombotic2events!(could!be!arterial!or!venous)!
• Biochemically,!thrombocytopenia!
" Treatment!
• Stop!heparin!immediately2!2switch!to!direct2thrombin2inhibitor!(e.g.!IV!
argatroban!/lepirudin)!
• Not!switch!to!LMWH,!as!there’s!cross+reactivity!of!Ab!
o Vs!HAT!(heparin+associated!thrombocytopenia)!
" Platelet!>100,!self+limiting,!no!need!Rx!
" Occur!24+72!hours!after!initiation!
!
LMWH!
+ Low!molecular!weight:!~5kDa!(vs!UH:!~12+15kDa)!
+ Inhibit!factor!Xa!
+ Vs!UFH!
o Subcutaneous!injection!
o Lower!risk!of!HIT,!bleeding!&!osteoporosis!
o No!need!monitoring!
" Very!difficult!to!monitor:!need!to!check!factor!Xa!level!!!not!easily!available!
!

Cardiology!+!102!
 " May!need!monitoring!in!anti+thrombin!3!deficiency!/!pregnancy!for!tighter!
dosage!adjustment,!due!to!high!risk!of!thrombosis!
o No!antidote!
o Longer!t½:!8+12!hours!(vs!UH:!2+4hours)!!!give!Q12H!(?)!
+ Need!to!↓!dose!in!renal!impairment,!C/I!if!CrCl!<30!
+ Uses!
o During!invasive!procedure!in!patients!with!MS!+!AF!
" Atrium!size!is!large!!!prone!to!clot!formation!&!stroke,!∴!better!cover!with!
LMWH!

Warfarin0
+ Block!factor!2,!7,!9,!10,!protein!C,!protein!S!(vit!K!dependent!clotting!factors)!
+ Onset!36+72!hours,!t½!=!2.5!days!(20+60!hours)!
+ Racemic!mixture!of!2!isomers:!S+!and!R+!(S+warfarin!is!5!times!more!potent)!
+ Preparation:!brown!1mg,!blue!3mg,!red!5mg!
+ Average!dose!of!warfarin!needed!to!maintain!therapeutic!INR:!~3mg!in!HK!(Vs!~6mg!in!West)!
o Polymorphism!in!CYP!2C9:!Asian!have!more!poor!metabolisers!!
o Polymorphism!in!VKOR!C1!(Vitamin!K!epoxide!reductase!complex!subunit!1:!the!target!
of!warfarin):!variant!produce!less!VKOR!C1!!!lower!dose!of!warfarin!is!needed!
!
Indications!!
+ Already!have!thrombus!
o PE,!DVT,!atrium!/!ventricle!thrombus!
o Use!heparin!/!LMWH!to!bridge!
+ No!thrombus,!prophylaxis!
o AF,!SLE:!can!give!warfarin!right!away!
o Mechanical!valve!prosthesis:!also!need!heparin!bridge!
!
Contraindication!
+ History!of!fall!
+ Severe!GI!bleeding!
+ Inability!to!obtain!regular!INR!
!
Initiation!
+ Start!10mg!stat,!with!heparin!cover!for!5!days!and!until!INR!reach!target!therapeutic!range!
o Need!heparin!cover:!wardarin!has!initial!prothrombotic!effect,!may!cause!skin!necrosis!
+ Take!INR!16h!after!first!dose!
o <1.8!give!second!dose!5+10mg!
o >1.8!give!second!dose!0.5mg!(warfarin!sensitivity)!
+ INR!daily,!continue!to!titrate!
+ **!Start!to!have!effect!since!INR=1.8!
!
Complications!
+ Bleeding!
o Presentation!!
" GIB,!intracranial,!subcutaneous!
" Also!don’t!forget!retroperitoneal!bleeding:!Cullen’s!sign,!Grey!Turner's!sign!
o Most!dangerous!bleeding!
" Upper!airway!!!obstruct!airway!
" Intracranial!hemorrhage!
" Inguinal!area:!compress!on!neurovascular!bundle!&!bleed!into!retroperitoneal!
o Hx!&!P/E:!look!for!bruising!(esp!near!drip!site),!gum!bleeding!
!

Cardiology!+!103!
 o Etiology!!
" Interference!with!platelet!functions:!anti+platelets,!SSRI!
" Disrupt!GI!mucosa:!NSAIDs!
" Inhibit!hepatic!metabolism:!cotrimoxazole,!metronidazole,!antifungal,!
amiodarone!
" Reduce!GI!Vitamin!K!synthesis:!antibiotics!
+ Terotogenicity:!safe!in!2nd!trimester!(alternative:!LMWH)!
o 1st!trimester!!!fetal!warfarin!syndrome!(FWS):!nasal!hypoplasia,!soliosis,!
brachydactyly,!low!borth!weight,!developmental!disabilities!
o Around!delivery!!!risk!of!bleeding!
+ Osteoporosis!!
+ Warfarin!necrosis!
o Particular!in!patient!with!protein+C!or!protein+S!deficiency!
o In!the!prothrombotic!phase,!the!scarce!protein+C!in!body!are!inactivated!prior!to!the!
clotting!factors,!which!then!lead!to!severe!skin!necrosis!and!limb!gangrene!
+ Purple!toe!syndrome!(cholesterol!embolism)!
!
Drug+drug!interaction!
+ Antibiotics!!
o Augmentin!kill!Vit+K!producing!bacteria!!!↑!INR!
o Levofloxacin:!even!more!interaction!!!↑!INR!
o Clarithromycin:!interact!with!warfarin:!both!metabolized!by!CYP3A4!in!liver!!!↑!INR!
" Use!azithromycin!instead!if!need!macrolide!
+ Amiodarone:!CYP2C9!inhibitor!!!↑!INR!
o Should!reduce!warfarin!dose!by!½!if!on!amiodarone!
+ Anticonvulsants!!
o Phenytoin,2carbamazepine:!CYP2C9!inducer!!!↓!INR!
o Valproic2acid:!CYP2C9!inhibitor!!!↑!INR!
o !!use!other!choice,!e.g.!gabapentin,!?lamotrigine!!
+ Rifampicin:!CYP2C9!inducer!!!↓!INR!
+ Diltiazem:!CYP1A2!inhibitor!!!↑!risk!of!bleeding!
+ Danshen! (for!Rx!of!CVS!disease):!↑!risk!of!bleeding!
!
Management!of!Over+warfarinization!(narrow!therapeutic!range)!
+ Stop!warfarin!
+ Check!for!major!bleeding,!resuscitation!
+ If!no!major!bleeding!!!1mg2oral2Vit2K12(preparation!is!10mg,!may!need!dilution)!!
o **!Remember!to!use!this!dose,!if!high!dose!used,!the!high!body!load!of!Vit!K!can!cause!
prolonged!resistance!to!warfarinization,!affect!subsequent!titration!of!warfarin!
o Give!1+2!doses!as!stat,!not!as!regular!drug,!otherwise!prolonged!warfarin!resistance!
o Vit!K1!start!to!have!effect!after!6+8!hours!(liver!start!making!factor!2,7,9,10),!peak!effect!
at!24!hours!
o *!Give!oral!/!IV!Vit!K1!NOT!IM!
o *!Have!Vit!K1+4:!if!you!write!Vit!K!!!vit!K4!will!be!given!
o *!Vit!K3!&!4!is!available!&!cheapest!but!ineffective!because!need!to!metabolise!in!body!
to!become!Vit!K1!active!form!
+ If!major!bleeding!!!10mg2IV2Vit2K12+!prothrombin2complex2concentrate/2FFP!
o FFP!just!replace!the!factors!(factor!7!has!t½!only!6!hours,!but!warfarin!t½!is!long,!need!
to!wait!5+7!days!for!effect!to!diminished),!so!INR!will!rebound!
o If!just!repeat!FFP!!!pulmonary!edema!
o Prothrombin!complex!concentrate:!for!HF,!due!to!smaller!volume!
!

Cardiology!+!104!
 o Vit!K1!10mg!total!correction!but!difficulty!in!titration!and!long!term!problem!in!months,!
may!need!to!titrate!!
+ Recheck!INR!in!24!hours!
+ Find!out!the!cause!
o Adherence!
o Drug+drug!interaction!
o Food+drug!interaction!
+ When!INR!<2!!!start!LMWH!!
!
ASTH recommendations for patients on warfarin with a high INR but no bleeding
Clinical setting Recommendations
INR higher than the • Reduce or omit the next warfarin dose
therapeutic range but < • Resume treatment at a lower warfarin dose when the INR approaches the
4.5 and no bleeding therapeutic range
• If the INR is only minimally above the therapeutic range (up to 10%), dose
reduction is generally not necessary
INR 4.5–10.0 and no • Stop warfarin treatment: consider reasons for elevated INR and patient-
bleeding specific factors. Vitamin K1 is usually not necessary
If bleeding risk is high:
• Consider vitamin K1 1.0–2.0 mg orally or 0.5–1.0 mg IV
• Measure INR within 24 hours
• Resume warfarin at a lower dose when the INR approaches the
therapeutic range
INR >10 and no bleeding • Stop warfarin treatment
• Administer 3.0–5.0 mg vitamin K1 orally or IV
• Measure INR in 12–24 hours, monitor INR daily or every second day over
the next week
• Resume warfarin at a lower dose when the INR approaches the
therapeutic range
If bleeding risk is high:
• Consider Prothrombinex-VF, 15–30 IU/kg
• Measure INR in 12–24 hours and monitor closely over the next week
• Resume warfarin at a lower dose when the INR approaches the
therapeutic range
!
!
Management!of!bleeding!(within!therapeutic!range!/!overwarfarinization)!
ASTH recommendations for patients on warfarin experiencing bleeding
Clinical setting Recommendations
INR ≥ 1.5 with life-threatening Stop warfarin and administer:
(critical organ) bleeding, including - Vitamin K1 5.0–10 mg IV
intracranial bleeding - And Prothrombinex-VF 50.0 IU/kg IV
- And fresh frozen plasma 150–300 mL
- If Prothrombinex-VF is unavailable, administer FFP 15mL/kg
INR ≥ 2.0 with clinically significant Stop warfarin and administer:
bleeding (not life threatening) - Vitamin K1 5.0–10 mg IV
- And Prothrombinex-VF 35.0–50.0 IU/kg IV, according to INR
- If prothrombinex-VF is unavailable, administer FFP 15 mL/kg
Any INR with minor bleeding Omit warfarin. Repeat the INR measurement the following day
and adjust the warfarin dose to maintain a therapeutic INR
Consider vitamin K1 1.0–2.0 mg orally or 0.5–1.0 mg IV if
bleeding risk is high or INR is > 4.5
!
!
!

Cardiology!+!105!
Management!in!surgery!
+ Stop!warfarin!5!days!before!procedure!
+ INR!usually!return!to!sub+therapeutic!range!in!2+3!days,!aim!INR!<1.2!
+ Start!heparin!(IV)!/!LMWH!(SC)!to!prevent!thrombotic!risk!
o Heparin:!bolus!+!maintenance!!
" Bolus!500!unit!!!take!blood!at!6+8h!!!give!maintenance!according!to!APTT!(60+
80s)!!!regular!blood!taking!for!APTT!monitoring!
+ For!high!risk!patient:!stop!4+6!hours!before!surgery!
o Aortic!valve!less!risk!of!thrombosis!than!mitral!valve!
+ Post+op:!start!heparin!+!warfarin!when!patient!is!no!longer!bleeding!
o Warfarin!start!effect!in!2+3!days!∴!need!heparin!cover!

Direct0thrombin0inhibitors0
+ Bivalent:!Lepirudin,!Bivalirudin!!!For!heparin!induced!thrombocytopenia!(injections)!
+ Monovalent:!(Ximelagatran),!Dabigatran!!!As!warfarin!substitutes!(oral)!
Dabigatran0
+ Direct!thrombin!inhibitors!
+ Fixed!dose:!no!need!to!monitor!INR!
o Give!lower!dose!in!elderly!&!low!BW!patients!
+ APTT!
o If!normal!APTT!!!no!anti+coagulation!effect!
o If!high!APTT!!!have!anti+coagulation!effect!but!don’t!know!how!mouch!(insensitive!to!
monitor!effect!of!dabigatran)!
+ Vs!warfarin!
o #!
" No!antidote!!
• If!life+threatening!bleeding!!!give!prothrombin!complex!concentration!
(PCC!=!concentrated!FFP)!/!hemodialysis!(low!protein!bound)!
• But!shorter!t½,!not!last!long!!
" Need!dose!adjustment!/!change!to!warfain!if!renal!impairment!(C/I!when!eGFR!
<30)!
" Expensive:!self!financed!item!~$20+30/day!!
" Coated!with!acidic!substance,!may!cause!esophagitis!!
o ☺!
" No!need!INR!monitoring!!
" No!dietary!restriction!!
" Faster!onset,!shorter!half+life!(12+17hr!Vs!40hr)!!
" Less!drug+drug!interaction!!
" More!stable!&!predictable!pharmacokinetics!!
" Less!bleeding!risk!&!better!efficacy!!
+ Need!to!stop!1!day!before!invasive!procedure!
+ Indication!
o Non+valvular!AF!
+ Contraindications!!
o Severe!renal!impairment:!CrCl!<30!
o Recent!bleeding!/!bleeding!tendency!
o Prosthetic!heart!valve!
o On!anti+fungal!!
+ S/E:!GI!upset,!esophagitis!(acid!coating),!MI!

Cardiology!+!106!
0

Factor0Xa0inhibitor0(Txaban)0
+ Apixaban!
+ Rivaroxaban!!
o t½:!5+9!hours!
o S/E:!mild!ankle!edema!
o Need!good!compliance!(need!to!be!taken!at!same!time!everyday)!
+ Fondaparinux!!
Treatment!for!overdose!
+ No!use!for!hemodialysis:!heavy!protein!bound!

Aspirin0
+ t½!short,!but!action!last!for!7!days!
o Due!to!irreversible!binding!!!action!last!for!lifespan!of!platelet!
!
Usage!!
+ Low!dose!(80mg):!for!MI!(↓risk!of!GIB)![antiplatelet]!
+ High!dose!(300mg):!for!pain!relief!(usu!added!GI!protective!drugs!to!↓!risk!of!GIB,!if!no!!!very!
bad!drug)![antipyretic!&!analgesic]!
+ *!Oral!route!!!make!use!of!1st!pass!effect!
o Act!on!platelet!in!portal!vein!!!have!effect!on!platelet!even!low!dose!
o Then!wash!out!by!liver!!!only!small!amount!in!systemic!circulation!!!low!dose!have!
no!pain!relief!effect!which!act!on!brain!
!
Before!prescription!
+ Must!rule!out!GI!bleed!before!prescription:!!
o Recent!Hb!drop!!!withhold!
o Urea↑!unproportional!to!creatinine:!upper!GI!bleed,!due!to!breakdown!of!protein!
+ Also!need!to!look!for!renal!function!
o Prostaglandin!dilate!afferent!arteriole,!so!aspirin!!!↓!renal!plasma!flow!!!↓GFR!!!↓!
renal!function!
Side!effect!
+ General:!N&V,!hypersensitivity,!GI!upset!(as!it!is!an!oral!drug)!
+ Specific!
o GIB,!PU!!
" Risk!of!GIB!is!highest!in!1st!month!(not!yet!gastric!mucosal!adaptation)!
• Mechanism:!direct!mucosal!injury,!COX1!inhibition,!anti+platelet!effect!
o Gout,!ototoxic,!bleeding!tendency!(!!hematuria,!epitaxis),!renal!failure!

Clopidogrel00
+ A!PRODRUG,!it!requires!a!2!steps!activation!to!its!active!form!(ADP!antiagaonist)!
+ Problem!!
o Slow!onset!of!effectiveness!!
o Interpersonal!response!variability!(genetic!variation)!
" 12%!accountable!by!CYP2C19!enzyme!polymorphism!
" 50%!of!Chinese!are!heterozygotes!for!this!polymorphism,!15%!are!poor!
metabolizer!(0!gene)!!!↓!ability!to!produce!active!metabolite!(↑!risk!of!stent!
thrombosis!in!post+stenting!individuals)!
o Drug+drug!interactions!(omeprazole,!statin)!!
" Clopidogrel!is!converted!to!active!drug!by!CYP2C19,!omeprazole!will!decrease!
the!conversion!!!use!pantoprazole!/!lanzoprazole!instead!
!

Cardiology!+!107!
 • But!still!conflicting!evidence!
• This!study!is!retrospective!and!there!is!selection!bias!(the!group!of!patient!need!to!consume!PPI!already!has!
higher!bleeding!risk)!!
• Recent!paper!(AHA)!prospective!study!show!that!there!is!no!decreased!effectiveness!of!clopidogrel!and!
decreased!GIB!(however,!the!size!of!sample!is!small!and!duration!is!not!long)!!
o Comparatively!mild!antiplatelet!effect!!
+ What!to!do!with!the!interpersonal/response/variability?/!
o Increase!dose!of!clopidogrel!!
o 600mg!loading!BETTER!than!300mg!
o 150mg!maintenance!slightly!BETTER!than!75mg!in!term!of!restenosis!
o BUT!increase!risk!of!bleeding,!and!still!some!patients!don’t!achieve!adequate!activity!!
+ Genetic!or!platelet!function!test!guided!therapy!!
o Antiplatelet!therapy!resistant!!!failure!to!inhibit!target!platelet!Fx!!
o But!no!standard!lab!test!for!ontreatment2platelet2activity,!still!controversial!!
o CYP2C19!rapid2genetic2test2for!polymorphism!
BUT!in!non+responder,!up!to!2400mg!clopidogrel!is!still!8%!no!response!!!
+ Alternative!antiplatet!therapy!!
o Prasugrel!
" More!efficiently!metabolised!by!2C19,!1!step!only!quicker!to!effect!!
" More!potent!antiplatelet!effect,!translate!to!lower!event!rate!in!head!to!head!trial!
with!plavix!
" BUT,!higher!risk!of!bleeding,!so!not!suitable!for!three!subgroups:!stroke!history,!
<60kg!(switch/from/10mg/to/5mg),!>70!years!old!!
o Ticagrelor2!
" Reversible!ADP!antagonist,!so!takes!only!2!days!to!wear!out!effect!!
" Active!drug,!not!a!prodrug,!direct!antiplatelet!effect!!
• Not!affected!by!genetic!variation!/!interact!with!PPI!
" Quicker!to!effect!
" More!potent!than!clopidogrel!!
" BUT!still!increase!bleeding!!

Statin0
New!NCEP!ATP!III!guideline!2013!
+ Statin!should!be!given!for!everyone!with!increased!CV!risk!
o High!dose:!for!high!risk!patients!
" Atorvostatin!
o Medium!dose!for!medium!risk!patients!
o Low!dose:!for!low!risk!patients!
" Simvastatin!10mg!
+ Aim!
o Reduce!LDL!by!50%!
o High!risk!patients:!<1.8!
!
Administration!!
+ Nocte:!take!at!night!
o Inhibit!endogenous!synthesis!of!cholesteral,!which!is!mainly!at!night!
!
Simvastatin!
+ A!prodrug,!convert!to!acid!from!lactone!in!body!
+ Not!used!simvastatin!80mg!
o Risk!of!myopathy!=!2%!!!too!high!
+ Metabolized!by!CYP3A4!(account!for!>50%!of!CYP!enzyme!in!gut!&!liver)!

Cardiology!+!108!
 o Extensive!metabolized!in!body,!only!5%!of!drug!left!(if!inhibit!CYP3A4!!!20!times!
higher!concentration!in!body)!
o Drug!interaction!with!enzyme!inhibitor:!
" Macrolide!!
• Clarithromycin!for!Hp!/!pneumonia,!erythromycin!but!not!used!
commonly!due!to!GI!S/E!
• !!need!to!stop!simvastatin!temporarily!!!
o Erythromycin!is!strong!enzyme!inhibitor!!!↑!simvastatin!to!4+5!
times!higher!
• *Azithromycin!not!inhibit!CYP3A4!that!much!
" Azole!anti+fungal!
• Ketoconazole!
o Cause!liver!damage!in!1%!of!patient!
o Should!stop!simvastatin!temporarily!too!!!
o Have!mild!effect!on!cholesterol!lowering!effect!
" Amiodarone!
• Inhibit!a!whole!range!of!CYP!enzyme!
• ↑!simvastatin!dose!by!3+4!times,!should!↓!dose!of!simvastatin!to!10mg!
" Non+dihydropyridine!CCB!(diltiazam,!verapamil)!
• ↑!simvastatin!dose!by!~4!fold,!but!can’t!increase!effect!of!simvastatin,!
maybe!the!metabolites!are!active!also,!so↓!metabolism!only!↑!risk!but!not!
↑!risk!
• ↓!dose!to!10mg!
" Amlodipine!
• Limit!dose!to!20mg!
" Grapefruit!juice!
• Should!not!drink!<1L!within!4!hours!of!taking!simvastatin!
" Valproate!
• Not!interact!with!3A4!very!much!

Fibrate0
+ Gemfibrazil!(lopid)!
o Inhibit!CYP2C8!&!CYP2C9!!!cause!drug!interaction,!e.g.!warfarin!
!
!
!
!
!
!
!
!
!
!
!
!
!
!
!
!
!
!
!

Cardiology!+!109!
Dermatology!
Bulla-Eruption:-Pemphigus-/-Pemphigoid ........................................................................................1!
Psoriasis..........................................................................................................................................2!
Erythroderma-(exfoliative-dermatitis) .............................................................................................4!
Erythema-multiforme......................................................................................................................4!
StevensBJohnson-syndrome-(SJS)-/-Toxic-epidermal-necrolysis-(TEN) ...............................................4!
Erythema-nodosum.........................................................................................................................5!
Pyoderma-gangrenosum .................................................................................................................5!
Necrobiosis-lipoidica-(diabetocorum) ..............................................................................................6!
Campbell-de-morgan-spot-(Cherry-angioma-/-senile-angioma).........................................................6!
!
Bulla-Eruption:-Pemphigus-/-Pemphigoid-
Bulla!Vs!vesicle!
, Bulla:!diameter!>!0.5!cm!!
, Vesicle:!<!0.5!cm!!
!
Pemiphugus!vs!pemiphigoid!
! Pemphigus!! Pemphigoid!!
Layer!! Intra,epidermal!! Sub,epidermal!!
Involvement!! Skin!and!mucosa!! Skin!!
✓!rupture!(usually!can’t!see! x!rupture!(deeper!layer!!!more!
Blister!!
blisters,!see!skin!eruption!instead)! resistance!to!pressure)!
Nikolsky's!sign*! +ve! ,ve!!
Auto,Ab! Anti,desmoglein! Anti,BP180!
Precipitating!factor!! Captopril,!frusemide,!penicillin!
, *Nikolsky's!sign:!slight!rubbing!of!the!skin!results!in!exfoliation!of!the!outermost!layer,!
forming!a!blister!within!minutes!(skin!splitting!conditions)!
o Also!+ve!in!TEN!(toxic!epidermal!necrolysis)!
!
DDx!of!bullous!disorder!
, SSSS!(Staphylococcal!scalded!skin!syndrome)!
, Bullous!impetigo!
, HSV,!VZV!
, Inflammatory!dermatitis:!e.g.!acute!dermatitis,!severe!eczema!
, Erythema!multiformin!
, TEN,!Steven,Johnson!Syndrome!
, Eczema!(usu!not!in!extend!of!bullae,!mostly!vesicles)!
, ***!Remember!to!ask!for!drug!Hx:!DDx!=!drug!eruption!
!
Investigation!
, Punch!biopsy!
o Look!at!the!histology!
o Do!direct!IF!staining!to!stain!the!Ab!!!look!at!Ab!deposition!on!skin!(on!which!layer)!
" Pemphigoid:!dermal,epidermal!junction!
, Anti,skin!antibody!
, Wound!swab!and!C/ST!
!

Dermatology!,!1!
, LFT:!albumin!level!!
o Decreased!appetite!because!of!oral!ulcer!!!malnutrition!
, HBsAg!!
o Treatment!may!cause!flare!up!!
!
Management!
, General!
o Administer!IVF!(ensure!adequate!hydration)!
o Barrier!dressing!
o Isolation:!risk!of!secondary!bacterial!infection!
o Refer!to!nutrition!(supplement)!+/,!Nasogastric!tube!feeding!
, Specific!
o Antibiotic!!
o Prednisolone!(1st!line)!
o Immunosuppressant,!e.g.!azathioprine,!MMF!
o Tetracycline:!prophylactic!A/B!
Psoriasis--
Clinical!presentation!!
, Skin!lesions!
o Well!dermacated!red!plaques!with!silvery!scales!
o Very!itchy:!DDx:!scabies!(∴better!to!take!precaution,!e.g.!wear!gloves)!
o Koebner's!phenomenon:!new!skin!lesions!at!sites!of!trauma!!
" DDx:!lichen!planus,!molluscum!contagiosum,!vitiligo!
o Auspitz's!sign:!capillary!bleeding!when!scales!are!plucked!off!!
, Nail!pitting!(>5!per!nail),!onycholysis,!onychodystrophy,!sunungual!hyperkeratosis,!splinter!
hemorrhage!
o Oil!drop!sign:!translucent!discolouration!in!the!nail!bed!that!resembles!a!drop!of!oil!
beneath!the!nail!plate!
, Alopecia!
, Psoriatic!arthropathy:!~1%!
, *Dactylitis!!
!
History!taking!
, PMH:!HT!(ACEI,!BB,!diuretics!may!cause!flare)!
!
Physical!examination!
, Scalp,!nail,!joint!(deformity,!swelling,!tenderness)!involvement!
o *!Patients!with!nail!involvement!have!higher!chance!of!having!joint!involvement!!!
need!to!look!for!joint!involvement!(need!early!detection!before!irreversible!joint!
destruction)!
, Skin!lesion!(extensor!surface!of!limbs,!hairline,!back!of!ear):!any!pustules!
, %!of!body!surface!area!involvement!(by!rule!of!nines):!if!>90%!!!erythroderma!
!
Types!
, Plaque!psoriasis!!
o Most!common!type!80%!!
o With!red!plaque!plus!silvery!scales!in!elbows,!knees,!scalp!and!buttocks!!
, Flexural!psoriasis!(inverse!psoriasis)!
o SMOOTH!lesions!found!on!skin!folds!(inframamillary!lines,!armpits,!behind!ears,!
genitals)!with!minimal!plaques!!
, Guttate! psoriasis!!
!

Dermatology!,!2!
 o Most!often!in!children!and!teenagers!
o Numerous!small!papular!lesions!with!silvery!scaling!evolve!suddenly!all!over!the!
body!!
o Ofter!appear!about!2!weeks!after!beta,streptococcal!infections!
o Usually!self!settle!in!3!months!!
, Pustular!psoriasis!!!
o Rapid!onset!of!raised!bumps!that!are!filled!with!non,infectious!pus!!
o Often!unwell,!achy!and!febrile!
o May!be!precipitated!by!concurrent!infection!or!rapid!withdrawal!of!steroids!!
, Erythrodermic!psoriasis!!
o May!be!precipitated!by!concurrent!infection!or!rapid!withdrawal!of!steroids,!use!of!
coal!tar!in!pustular!psoriatsis,!antimalarial!therapy,!hypocalcemia!!
o Life!threatening!general!erythema!and!scaling!!
" DDx:!TENS,!SSSS!
o Progress!to!erythroderma!(exfoliative!dermatitis)!(=skin!failure)!!
" Involve!>90%!of!body!surface!area!(BSA)!
o Poor!temperature!regulation,!dehydration,!negative!nitrogen!balance,!secondary!
infection!
o Management!
" CBC!d/c,!LRFT,!CaPO4,!RG,!INR!/APTT!
" Blood!culture!+!skin!swap!x!C/ST!
" MSU!x!C/ST,!multistix!
" Sputum!x!C/ST!
" Empirical!A/B!(cover!G+ve,!e.g.!Augmentin)!
!
Exacerbating!factors!
, Emotional!stress!
, Cold!weather!
, Smoking,!alcohol!
, Drugs:!Lithium,!antimalarials,!ACEI,!BB,!diuretics,!NSAIDs!!
, Infections:!streptococcus!
!
Treatment!for!skin!lesions!
, Avoid!exacerbating!factors!
, Selecting!the!base:!
o Ointment!for!broad!skin!areas!because!they!are!occlusive!
o Cream!for!haired!or!flexural!areas!
, Topical!
o Emollients!(e.g.!paraffin)!
o Corticosteroids!
" Often!potent!agents!needed!
" Takes!time!to!work!!
o Calcipotriol!(Vitamin!D3!analogue)!
" Better!if!combined!with!steroids!(not!with!salicylates!as!it!will!degrade!
calcipotriol)!!
" S/E:!hypercalcemia,!25%!skin!irritation!
o Coal!tar!
" Smelly,!stain!clothes!
" Not!used!in!unstable!pustular!psoriasis,!which!may!exacerbate!erythroderma!!
o Salicylic!acid!
" Keratolytic!agent!that!removes!scale!
" Beware!of!systemic!salycilism!!
!

Dermatology!,!3!
 o Dithranol!
" Inhibits!DNA!synthesis!and!epidermal!turnover!
" Stains!clothes!!
o Tazarotene!
" Retinoid!that!normalize!keratinocyte!proliferation!and!differentiation!
" Teratogenic,!contraindicated!in!pregnancy!!
, Intralesional!steroids!
, Phototherapy!
o Narrow!band!UVB!
o Starts!short!time!and!escalate!gradually!
o S/E:!sunburn,!hyperpigmentation,!skin!cancers!
, Oral!(systemic)!
o Retinoid:!Acitretin!
o Steroid!!
o Methotrexate!±!folic!acid!(not!take!at!the!same!time/day!as!MTX,!otherwise!MTX!not!
effective)!
o Cyclosporin!
o Other!immunosuppresants!
, Biologic!agents!
o Anti,TNF!agents!
o Anti,T!cell!therapy:!alefacept,!abatacept!
Erythroderma-(exfoliative-dermatitis)--
Introduction!
, Skin!failure,!involve!>90%!of!body!surface!area!(BSA)!
, A!dermatological!emergency!
, Poor!temperature!control,!negative!nitrogen!balance!
, High!risk!of!dehydration,!secondary!infection,!electrolyte!disturbance!
!
Management!
, High!protein!diet,!IVF!
, Moisturizer,!warm!room!
, Prophylactic!antibiotics!
Erythema-multiforme-
, Usually!maculopapillar!rash!initially,!then!develop!into!target!lesions!
, Erythema!multiforme!minor:!typical!targets!/!raised,!edematous!papules!distributed!acrally!
, Erythema!multiforme!major:!with!involvement!of!≥1mucous!membranes;!epidermal!
detachment!involves!<10%!of!total!body!surface!area!(TBSA)!
Drug!causes!
, Allopurinol,!carbamazepine,!cephalosporin,!ciprofloxacin,!co,trimoxazole,!NSAIDs,!celecoxib,!
penecillins,!rifampicin,!sulfasalazine,!vancomycin!
StevensBJohnson-syndrome-(SJS)-/-Toxic-epidermal-necrolysis-(TEN)-
Clinical!features!
, 2!mucosal!involvement!
, Epidermal!detachment:!SJS:!<10%,!TEN:!>30%!(Overlap:!10,30%)!!
o TEN:!appearance!is!similar!to!2nd,degree!burns!
, Nilkosky’s!sign!
!
Causes!!
, Drug!eruption!(common!cause)!
o Carbamazepine!(HLA,B*1502),!allopurinol!(HLA,B*5801),!sulphonamide!group!a/b,!
NSAIDs,!penicillin,!lansoprazole!
!

Dermatology!,!4!
 o Occur!~7,21!days!after!taking!the!medications!&!may!not!immediately!resolve!with!
drug!cessation!(idiosyncratic!reaction)!
" Vs!urticaria:!type!1!hypersensitivity!!!onset!within!min/hr!but!disappear!
with!cessation!of!drugs!
o Due!to!drug!metabolites!which!are!toxic!to!keratinocytes!
, Infection!
!
Management!
, Stop!offending!agent!
, Steroid:!a!Rx!option!for!SJS!only!
o NOT!used!in!TEN:!it!↑!mortality!due!to!infection!
, For!TEN:!treat!before!biopsy!result!come!back:!it’s!life!threatening!!
, IVIg!if!severe!
, Give!drug!allergy!card!&!never!re,challenge!!
, *!Cannot!treat!as!2˚!burn!(skin!graft):!autoimmunity!against!skin!!!no!use!even!graft!a!skin!!
Erythema-nodosum--
Pathology!!
, A!type!of!panniculitis!(inflammation!of!subcutaneous!fat)!
, Painful!blue!red!raised!nodular!lesions!on!anterior!shin!!
!
Etiology!!
, Sarcoidosis!
, Drugs!!
o Sulfonamides,!OCP,!penicillin!
, Infections!
o Infectious!mononucleosis,!Streptococcus,!TB,!Leprosy,!Yersinia,!leptospirosis!
, Inflammatory!bowel!disease!
, Behcet’s!disease!
Pyoderma-gangrenosum-
, A!condition!that!causes!tissue!to!become!necrotic,!causing!deep!ulcers,!can!lead!to!chronic!
wounds!
!
Presentation!!
, Usually!initially!look!like!small!bug!bites/papules!!!progress!to!larger!ulcers!
, Cause!pain!&!scarring!
, Classic!pyoderma!gangrenosum!
o Begin!as!a!nodule!/!sterile!pustule!progressing!to!a!necrotic!&!purulent!ulcer,!with!n!
edematous,!blue,black!expanding!border!
o Commonly!on!legs!(shin)!

o !
, Atypical!pyoderma!gangrenosum!
o Have!a!‘juicy’!vesiculopustular!component!at!the!border,!erosive!/!superficially!
ulcerated!
o Usually!on!dorsum!of!hands,!extensor!surface!of!forearms!/!face!
!

Dermatology!,!5!
 o !
!
Cause!
, Immune!system!dysfunction,!particularly!improper!function!of!neutrophils!
o Related!to!autoimmune!disease!(same!as!erythema!nodosum)!
!
Association!
, IBD:!UC,!Crohn's!Disease!
, Arthritis:!RA,!seronegative!symmetrical!polyarthritis!
, Hematological!disease:!MM,!paraproteinemia,!hairy!cell!leukemia,!myelofibrosis,!myeloid!
metaplasia,!monoclonal!gammopathy!
, Autoinflammatory!Disease:!PAPA!syndrome!(pyogenic!sterile!arthritis,!pyoderma!
gangrenosum,!and!acne!syndrome)!
, Wegener's!Granulomatosis!
!
Treatment!(basically!same!Rx!as!IBD)!
, Wound!care!&!dressings!
, Send!for!culture,!antibiotics!
, Treat!the!underlying!cause!
, Superpotent!topical!steroid,!cromolyn!sodium!2%!solution,!nitrogen!mustard,!5,
aminosalicylic!acid!
, Topical!tacrolimus,!pimecrolimus!
, Systemic!immunosuppressants!
o 1st!line:!predinisolon!/!methylprednisolone!(for!acute!setting)!
o Maintenance:!steroid!sparing!drugs!
" Cyclosporin6A,!thalidomide,!MMF,!dapsone,!tacrolimus,!cyclophosphamide,!
anti8TNF!
" Thalidomide:!this!drug!is!not!for!IBD!due!to!S/E!!
• Teratogenic:!initially!this!drug!is!marketed!as!anti,nausea!&!used!by!
pregnant!women,!then!found!that!many!fetus!got!congenital!defects!
• Peripheral!neuropathy:!dose!dependent,!uncommon!for!<100mg!daily!
• Drowsiness!!!∴!take!at!night!
" Cyclosporin!
• Need!to!monitor!BP!(HT),!lipid!(hyperlipidemia),!RFT!(renal!toxicity),!
gum!hypertrophy!
o *!Azathioprine!is!not!so!useful!
Necrobiosis-lipoidica-(diabetocorum)-
, Idiopathic!granulomatous!skin!disorder,!a/w!DM!
, Typically!over!the!shins!
, Erythematous!patch!with!yellowish!hue!that!becomes!progressively!atrophic!
, Rx:!better!glycemic!control,!corticosteroid,!pentoxifylline!
Campbell-de-morgan-spot-(Cherry-angioma-/-senile-angioma)-
, Red!papules!(elevated),!common!in!elderly!
!
!

Dermatology!,!6!
Endocrine!
Thyrotoxicosis.................................................................................................................................... 1!
Graves’!disease............................................................................................................................................................................................ 5!
Iodine*induced!hyperthyroidism!(IIHT) ......................................................................................................................................... 6!
Thyroid!storm ............................................................................................................................................................................................. 7!
Thyrotoxic!periodic!paralysis............................................................................................................................................................... 8!
Hypothyroidism ................................................................................................................................. 9!
Primary7hyperparathyroidism .......................................................................................................... 10!
Familial7hypocalciuric7hypercalcemia7(FHH)...................................................................................... 12!
Neonatal7severe7hyperparathyroidism7(NSHPT) ............................................................................... 12!
Hypoparathyroidism ........................................................................................................................ 12!
Pseudohypoparathyroidism ............................................................................................................. 12!
Pseudopseudohypoparathyroidism7(Albright's7hereditary7osteodystrophy) ..................................... 12!
Diabetes7Mellitus7(DM) .................................................................................................................... 13!
DM!nephropathy ..................................................................................................................................................................................... 21!
Diabetic!neuropathy .............................................................................................................................................................................. 22!
Diabetic!retinopathy.............................................................................................................................................................................. 22!
Diabetic!foot .............................................................................................................................................................................................. 23!
Hyperosmolar!hyperglycemic!state!(HHS).................................................................................................................................. 24!
Diabetic!ketoacidosis!(DKA) .............................................................................................................................................................. 25!
Hypoglycemia .................................................................................................................................. 27!
Metabolic7syndrome ........................................................................................................................ 29!
Hyperlipidemia ................................................................................................................................ 29!
Hyperprolactinemia ......................................................................................................................... 30!
Acromegaly...................................................................................................................................... 31!
Hypopituitarism............................................................................................................................... 33!
Adrenal7incidentaloma..................................................................................................................... 35!
Cushing7syndrome ........................................................................................................................... 37!
Primary7Hyperaldosteronism ........................................................................................................... 40!
Pheochromocytoma......................................................................................................................... 41!
Sex7hormone7secreting7tumor .......................................................................................................... 43!
Addison’s7disease7(Primary7Adrenal7Insufficiency)............................................................................ 43!
Addisionian!crisis ................................................................................................................................................................................... 45!
Congenital7adrenal7hyperplasia........................................................................................................ 46!
Multiple7endocrine7neoplasm7(MEN)7syndromes.............................................................................. 46!
!

7
Thyrotoxicosis7
Introduction!to!thyroid!hormone!
* T3,!T4:!99%!bound!to!hormone*binding!proteins!
o T4!TBG!>!transthyretin!>!albumin!
o T3!binds!less!firmly!by!TBG,!not!by!TTR!!
!

Endocrine!*!1!
* Change!in!TBG!
o ↑!in!pregnancy,!OCP,!oestrogens,!Tamoxifen,!Hep!A,!chronic!active!hepatitis,!biliary!
cirrhosis!
o ↓!by!androgens,!high!dose!glucocorticoids,!Cushings,!chronic!liver!disease,!severe!
systemic!illness,!active!acromegaly,!nephrotic!syndrome,!drugs!e.g.!phenytoin!
o **!Affect!total!T4,!T3,!but!not!free!T4/!fT3!
!
Etiology!!
* Graves'disease'
* Toxic'multinodular'goiter''
* Toxic!solitary!adenoma!(uncommon)!
* Acute!thyroiditis!
* Exogenous!thyroxine,!e.g.!weight!reduction!drugs!
* Drug!induced:!amiodarone!
* Ectopic!thyroxine!(struma!ovarii!–!ovarian!tissue!producing!thyroid!hormone,!
choriocarcinoma)!!
* Hyperemesis!gravidarum!(hCG)!!
* Iodine*induced!hyperthyroidism!
!
Clinical!presentations!!
* Weight!loss,!good!appetite,!diarrhea!!
* Sweating,!heat!intolerance,!tremor,!palpitation,!angina!
* Oligomenorrhia,!infertility!
* Muscle!weakness!
* Anxiety,!irritability,!poor!concentration,!psychosis!
* Pretibial!myxedema,!diplopia!
* In!elderly:!
o Apathetic,!anorexia,!weight!loss!&!persistent!constipation!
o Symptoms!of!sympathetic!overactivity!is!less!common!
o Only!2/3!of!patients!have!symptoms!similar!to!those!in!younger!patients!
o Tachycardia!is!absent!in!40%:!primarily!to!co*existent!conduction!system!disease!
!
Physical!examination!!
* Sweaty!warm!palm,!fine!tremor,!palmar!erythema!
* Tachycardia,!AF!±!HF!
* Proximal!myopathy,!hyperreflexia!!
* Lid!lag,!lid!retraction!(symptoms!of!sympathetic!overtone,!not!Grave’s!ophthalmopathy)!
* Diffuse!goiter!±!bruit!
* Diffuse!alopecia!
* Grave:!ophthalmopathy,!pretibial!myxedema,!thyroid!acropachy,!lymphoid!hyperplasia!(LN,!
thymus,!spleen),!associated!autoimmune!disease!
!
Major!complications!
* Thyroid!heart!disease!
* Osteoporosis!!
!
Investigations!!
* Blood!tests!!
o TSH,!fT3,!fT4!!
o Autoantibodies!!
! Anti*thyroglobulin!(ATG)!
• Found!in!Hashimoto’s!thyroiditis,!myxoedema!and!normal!subjects!!
!

Endocrine!*!2!
 ! Anti*microsomal!antibody!(AMC):!also!known!as!the!anti*TPO!antibody!!
• Found!in!Hashimoto’s!thyroiditis,!myxoedema!and!normal!subjects!!
! IgG!Thyroid!stimulating!antibody:!not!always!available!in!every!lab!
• Found!in!Grave’s!disease!
o CBC!(anemia,!leucopenia)!!
o ESR!
o LFT!!
! Directly!due!to!thyrotoxicosis!
! Thyrotoxic!congestive!heart!with!congested!liver!!
! Idiosyncratic!reaction!with!antithyroid!agents!
! Associated!autoimmune!hepatitis,!primary!biliary!cirrhosis!!
o Calcium!!
o Red!cell!zinc:!low!if!chronic!thyrotoxic!state,!normal!if!acute!
* Imaging!!
o USG!
o Radioactive!iodine!uptake!if!toxic!solitary!nodule!!
!
Treatment!
Grave’s!disease! Antithyroid!drugs/!RAI!/!surgery!(~50%!relapse!after!ATD)!
Toxic!MNG! Total!thyroidectomy!(after!drug!control)!(100%!relapse!after!ATD)!
Toxic!adenoma! Subtotal!thyroidectomy!(after!drug!control)!
* Symptomatic!relief!
o Propranolol!40mg!Q6H!(as!propranolol!also!acts!in!brain!so!for!nervousness!symptoms)!
* Anti*thyroid!drugs!(ATD)!
o Thionamides:!Carbimazole!(CBZ)!(prodrug),!propylthiouracil!(PTU)!
! Thyroid'peroxidase'inhibitor!
! Pharmacological!effect!is!quick,!but!clinical!effect!is!delayed!to!6!weeks,!due!to!
time!needed!to!deplete!stored!thyroxine!!
o Choice!
! Carbimazole!(CBZ)!(prodrug):!max!20mg!TDS!
! Propylthiouracil!(PTU):!100*200mg!TDS!
! Methimazole:!15*30mg!BD!
! *!Generally!prefer!carbimazole!over!propylthiouracil!!
• More!potent!
• Less!bitter!in!taste!
• Longer!half*life!thus!convenient!dosing!
• Less!S/E,!esp!liver!toxicity!(hepatitis!&!cholestasis)!
! *!But!we!prefer!PTU!when!!
• Pregnancy!
o Less!pass!through!placenta!(fetal!thyroid!produces!thyroxine,!
important!for!growth)!
o Carbimazole!has!be!associated!with!aplasia!cutis!!
• Thyroid!storm!(it!blocks!also!peripheral!conversion!of!T4!>!T3)!!!!
o Indication!
! Young!patients!with!Graves!thyrotoxic!crisis!
! Preparation!for!surgery!/!RAI!!
! Pregnancy!
o Contraindication!!
! Allergy!/!agranulocytosis!
o S/E!
! Common:!rash!(5%),!urticaria,!arthralgia,!fever!and!malaise!
! Uncommon:!GI,!abnormal!taste/smell,!arthritis,!agranulocytosis!(0.1%)!
!

Endocrine!*!3!
 • Advice!to!seek!medical!advice!onve!have!sore!throat!/!fever!
• Management!of!agranulocytosis!
o Stop!all!anti*thyroid!drugs,!usually!spontaneously!resolves!within!
1*2!weeks!of!stopping!the!drug!
o Reversed!barrier!nursing,!board!spectrum!A/B,!G*CSF!
o Can!use!lithium!to!treat!thyroid!storm!by!temporarily!inhibit!
thyroid!hormone!synthesis!&!secretion!
! Very!rare:!thrombocytopenia,!aplastic!anaemia,!cholestatic!hepatitis,!lupus*like!
syndrome/!ANCA!disease,!vasculitis,!hypoglycaemia!(autoimmune)!
o One!course:!12*18!months!(not!recommended!as!long*term!Rx)!
o 50%!relapse!after!stopping,!may!proceed!to!RAI!(but!need!medical!Rx!to!↓!thyrotixic!
1st)!
o Pros:!outpatient!therapy,!no!permanent!hypothyroidism!!
o Cons:!S/E!of!drugs,!highest!relapse!rate,!take!at!least!3!weeks!to!control!toxic!symptoms!!
* Radioactive!iodine!(RAI:!iodine*131)!–!definitive!Rx!for!hyperthyroidism!
o Single!oral!dose!of!131*I!causes!direct!radiation!damage!to!the!replication!mechanisma!
of!thyroid!follicular!cells!
o Indication!
! Grave’s!disease!with!!
• Relapse!or!failed!antithyroid!drugs/!surgery!(used!as!2nd!line)!
• Cx!from!thyrotoxicosis:!TTP,!CHF,!fast!AF,!cardiac!problems,!psychosis!
• Concomitant!disease!(e.g.!DM…)!where!we!don’t!want!relapses!!
! Toxic!nodular!goiter!
! Established!hyperthyroidism!with!age>!50!
! Post*thyroidectomy!
o Contraindications!!
! Child!bearing!age,!pregnancy!(need!contraception!for!≥6m),!breastfeeding!!
! Allergic!to!iodine!
! Retrosternal!goiter!(radiation!thyroiditis!"!edema)!
! Severe!eye*signs!!
! Thyrotoxic!crisis!
o S/E!
! Short!term!
• Transient!thyroiditis!(swelling!(~10ml)!↑!compressive!Sx,!pain)!
• Transient!hyperthyroidism!!
• Worsen!eye!signs!
• ↓!taste,!nausea!
• Salivary!gland!may!have!small!uptake!causing!pain!&!swelling!!
• Radiation!gastritis!
• Teratogenic!if!pregnant!!
! Long!term!
• Hypothyroidism!(~100%!will!become!hypothyroidism!eventually)!
• ↑!miscarriage!rate!in!the!future!!
• (No!evidence!show!↑!risk!of!secondary!cancer)!
o Regime!
! Stop!ATD!2!weeks!before!RAI:!↑!uptake!of!RAI!
! Give!1!dose!of!RAI!
• Dosage!depends!on!body!weight!/!size!of!goiter!!
o Upper!limit:!10MCI!(radioactive)!
! May!need!ATD!cover!in!elderly!/!cardiac!disease!as!RAI!need!2!months!to!work!
• Start!ATD!1!week!after!RAI,!until!TFT!normalized!

Endocrine!*!4!
 o Pros:!outpatient!therapy,!rapid!control!of!toxic!symptoms!(~2*3!weeks),!can!normalize!
thyroid!size!within!1!year,!minimal!side!effects!☺!
o Cons:!radiation!hazards,!can!worsen!ophthalmopathy,!most!result!in!permanent!
hypothyroidism!$!
* Subtotal!thyroidectomy!!
o Indications!!
! Malignant/!suspected!malignant!goiter!(usu!euthyroid)!
! Pressure!symptoms!
! Cosmetic!reason!!
o Contraindication!!
! Uncontrolled!thyrotoxic!state!!
! Patients!rely!on!voice!!
! Relapse!!
o S/E!
! Keloid,!reactive!hemorrhage,!hypothyroidism,!transient/!permanent!
hypocalcemia,!recurrent!laryngeal!nerve!damage,!external!branch!of!superior!
laryngeal!nerve,!laryngomalacia!!
o Pros:!no!radiation!hazard,!immediate!control!of!toxic!symptoms,!immediate!
normalization!of!thyroid!size,!lowest!relapse!rate!☺!
o Cons:!inpatient!therapy,!surgical!/!GA!risks,!inevitable!permanent!hypothyroidism!$!
!
FU!in!OPD!
* Assess!symptoms!
o Weight,!palpitation,!sweating,!tremor!
* Drug!compliance,!S/E,!recent!change!of!dosage!/!drug!
* Monitor!fT4!instead!of!TSH!if!2°!thyroid!problem!/!on!anti*thyroid!drugs!(TSH!need!time!to!
recover)!

Graves’7disease7
Epidemiology!
* F>M:!7:1!
* Peak!age!of!onset:!30*40s!
* May!be!a/w!other!autoimmune!diseases!(e.g.!pernicious!anemia,!Hashimoto)!
!
Pathophysiology!
* Defect!in!T*suppressor!cells!
* B!lymphocytes!produce!TSI!that!bind!to!TSH!receptor!
* Immune!response!can!be!triggered!by!pregnancy!(esp.!postpartum),!iodine!excess,!lithium!
therapy,!viral/bacterial!infections,!steroid!withdrawal!
!
Diagnosis!
* Hyperthyroidism!
* Diffuse!enlarge!thyroid!
* Extra*thyroidal!manifestation!
o Ophthalmopathy,!e.g.!exophthalmos!
o Pretibial!myxedema!
* **!Auto*antibody!NOT!diagnostic!!
!
Presentation!
* Diffuse!thyroid!goiter!±!thyroid!bruit!
* Ophthalmopathy!

Endocrine!*!5!
 o Proptosis,!lid!lag,!lid!retraction,!diplopia,!characteristic!stare,!conjunctival!injection,!
periorbital!edema!
! Proptosis:!view!from!above!
! Lid!retraction:!eye!white!present!above!the!iris!
! Exophthalmos:!eye!white!present!below!the!iris!
! Ophthalmoplegia:!impaired!up!and!lateral!gaze!(infiltrate!most!severe!in!inferior!
rectus!&!medial!rectus)!
o Due!to!glycosaminoglycan!deposition!&!Ab!against!extraocular!muscle!Ag!with!
lymphocytic!infiltration!
o Periorbital!edema!due!to!impaired!venous!drainage!&!herniation!of!retrobulbar!tissue!
o *!May!need!to!do!Orbit!CT:!to!look!for!compression!of!optic!nerve!by!swollen!
extraoccular!muscle!which!can!cause!blindness!!
! Optic!nerve!compression!(which!is!due!to!swollen!retroorbital!structure)!may!
occur!even!if!no!obvious!ophthalmopathy!seen!externally!!
! Rx:!steroid,!orbital!radiotherapy,!even!decompression!by!surgery!(remove!a!part!
of!bone)!
* Dermopathy!(rare)!
o Pretibial!myxedema!(thickening!of!dermis!that!manifests!as!non*pitting!edema,!orange!
skin!appearance)!
o Related!to!cutaneous!glycosaminoglycan!deposition!
* Acropachy:!clubbing!&!thickening!of!distal!phalanges!
* Lymphoid!hyperplasia!(LN,!thymus,!spleen)!
* Associated!autoimmune!disease!
!
Investigations!
* Low!TSH!
* Increased!fT4!
* Positive!TSI!
!
Treatment!
* For!ophthalmopathy!
o High!dose!pulse!steroid:!methyprednisolone!IV!
o ±!Methotrexate!(immunosuppressant!used!as!it’s!autoimmune!disease)!
o Surgical!decompression!

IodineRinduced7hyperthyroidism7(IIHT)7
Cause!
* Contrast*induced!thyrotoxicosis!
o Non*ionic!contrast!contain!free!iodide,!e.g.!in!CT,!coronary!angiogram!
o High!risk!in!!
! Graves’!disease!
• TSI!enhance!iodine!uptake!&!thyroid!hormone!synthesis!
! Autonomous!tissue!in!thyroid!autonomy!
• The!nodule!s!not!under!control!of!TSH,!when!subjected!to!high!iodine!
loads!"!produce!&!secrete!excessive!thyroid!hormone!with!/!without!a!
concomitant!decrease!in!TSH!
! Iodine!deficient!area!
! Elderly!
o Presentation!could!be!up!to!18!weeks!post!contrast!
o Mostly!self*limiting!
* Disinfectants!
* Secretolytic!agents!
!

Endocrine!*!6!
* Anti*arrhythmic:!amiodarone!
* Eye!drops!&!ointments!
* Seaweed,!multi*vitamin!preparations!
* Skin!ointment,!toothpaste!
!
Iodine!toxicity!
* Jod*Basedow!phenomenon!
o People!with!background!of!iodine!deficiency!that!ingest!excess!aount!of!iodine!leading!
to!hyperthyroidism!
* Wolff*Chaikoff!effect!
o Excess!uptake!of!iodine!by!the!thyroid!leading!to!inhibition!of!thyroid!hormone!
synthesis!
o Iodine!toxicity!can!eventually!cause!iodide!goiter,!hypothyroidism!or!myxedema!
* Acute!toxicity!
o Burning!of!the!mouth,!throat!&!stomach!
o Fever,!N&V,!diarrhea,!weak!pulse,!coma!

Thyroid7storm7
Clinical!presentations!!
* Severe!thyrotoxic!symptoms!
* General:!fever,!profuse!sweating,!poor!feeding!&!weight!loss,!resp!distress,!fatigue!
* Cardi:!heart!failure,!fast!AF,!arrhythmia!!
* GI:!N/V/D,!abdominal!pain,!jaundice!
* Neurological:!anxiety,!altered!behavior,!seizure,!psychosis,!coma!
* *!Mortality!30%!despite!treatment!
!
Initial!investigation!!
* TFT!
* Potassium,!Calcium!!
* ECG!!
!
Management!outline!!
* Stabilize!the!patient!(temperature,!hydration,!mental!state,!heart!rate)!!
* Correct!thyrotoxic!state!
* Identify!precipitant!and!treat!it!!
!
Management!!
* To!ICU!for!close!monitoring!&!organ!support!
* Close!monitoring!of!fluid!balance!and!vitals!!
* ±!CVP/Swan*Ganz!(R!heart!catheterization)/cardiac!monitor!
* Symptomatic!!
o Paracetamol'±'tepid'(slightly!warm)'sponging'(external!cooling):!for!fever!!
o Hydration:!replace!fluid!from!vomiting!&!diarrhea!!
o Sedation:!for!agitation!
o Treat!heart!failure!(Oxygen,!diuretics)!!
o Treat!AF:!digoxin!
! Avoid!amiodarone!if!possible:!because!it!contains!iodine!component!"!
thyroiditis!"!further!release!thyroid!hormone!
* Specific!!
o High!dose!Propylthiouracil:!300mg!Q6H!by!N/G!tube!
! Block!new!hormone!synthesis!
! PTU!also!help!block!peripheral!T4/T3!conversion!
!

Endocrine!*!7!
 o Followed!by!Lugol's'iodine'solution'1!hour!later!(8!drops!Q6H,!continue!for!1!week)!!
! Block!the!release!of!thyroid!hormone!
! Iodinated!radiocontrast!agent!(if!available):!inhibit!peripheral!conversion!of!T4!
to!T3!
o Propranolol'IV/PO!40mg!Q4H!
! Control!symptoms!induced!by!increased!adrenergic!tone!
! C/I!in!acute!HF!!
o Steroid'IV/PO!(Dexamethasone!2mg!Q6H)!
! ↓!peripheral!T4*to*T3!conversion!and!possibly!treat!the!autoimmune!process!in!
Graves’!disease!
o (NaI!infusion)!(Lithium!carbonate)!(Plasmapheresis)!(Charcoal!hemoperfusion)!!
* Find!the!precipitant!!
o Infection"!antibiotics!!
o Post!thyroid!surgery!/!RAI!!
o MI/!stroke!!
o Excessive!thyroxine!replacement!!

Thyrotoxic7periodic7paralysis7
* 1.8%!of!all!thyrotoxic!patient,!much!high!than!the!West!
* Super!high!MALE!predominance!(60:1)!
!
Pathogenesis!!
* Enhanced!Na/K!ATPase!in!thyrotoxic!state!"!influx!!
o *!Na/K!ATPase!also!controlled!by!catecholamines,!∴!sometimes!may!have!hypoK!in!
pheochromocytoma!
* Exaggerated!insulin!response!to!glucose!load!in!thyrotoxic!state!"!↑!Na/K!ATPase!activity!"!
influx!!
!
Precipitating!factors!!!
* High!carbohydrate!load!
o ↑!inulin!secretion!which!stimulate!Na/K!ATPase!
* Strenuous!exercise!!
o Increase!in!catecholamines!which!stimulate!Na/K!ATPase!
o With!increase!potassium!loss!in!sweat!(?)!
* Insulin!
* Trauma!
* Cold!exposure!
* Infection!!
* Emotional!stress!!
!
Clinical!presentation!!
* Severe!proximal!paralysis!(LL!>>!UL)!with!preserved!reflexes!(Vs!GBS)!
* No!CN!involvement!
* Occurs!only'in'thyrotoxic'states,'but!severity!correlates!poorly!!
* Typically!occurs!in!the!RESTING!period!after!exercise,!and!vigorous!movements!often!abort!an!
mild!attack!
* Usually!recover!in!24!hour!!
!
DDx!
* GBS!
* Acute!cord!compression!!
* Transverse!myelitis!!
!

Endocrine!*!8!
* Other!cause!of!periodic!paralysis!
o HypoK:!familial,!primary!hyperaldosteronism,!thyrotoxic!
! Primary!hypokalemic!periodic!paralysis!
• Autosomal!dominant!condition!with!incomplete!penetrance!!
• Type!1!=!90%,!defect!in!voltage!sensitive!Ca!channel!gene!(CALCL1A3)!!
• Type!2!=!10%,!defect!in!voltage!sensitive!sodium!channel!gene!(SCN4A)!
o NoromoK:!von!Eulenberg’s!disease!
o Hyper:!Gamstorp’s!disease!
!
Treatment!!
* Admit!to!HDU!/!ICU!with!ECG!monitoring!
* Frequent!checking!of!RFT!
* Potassium!supplement!
o Slow!infusion!of!IV!NS!with!KCl!supplement!/!oral!potassium!supplement!(not!given!in!
glucose!solution!)!
o Recheck!RFT!after!supplement!given,!repeat!slow!infusion!if!required!!
o Stop!if!K!improved!to!avoid!rebound'hyperK!
! Body!store!of!K!is!not!low!!Just!due!to!transcellular!shift,!so!don’t!give!too!much!
* Propranolol:!↓!transcellular!shift!of!K!
* Treat!the!hyperthyroidism!to!prevent!further!attacks!
* If!persistent!hyperthyroid,!use!BB'!
Hypothyroidism7
Cause!
* Primary!hypothyroidism!!
o Thyroid!agenesis/!dysgenesis/!atrophy!!
o Thyroid!gland!destruction!!
! Post'RAI/'thyroidectomy!
! Hashimoto'thyroiditis!
! Subacute!granulomatous!(De!Quervain)!thyroiditis:!transient!!!
! Subacute!lymphocytic!thyroiditis!
! Riedel's!thyroiditis!(fibrosis)!!
o Hormone!synthesis!disorder!!
! Iodine!deficiency!!
! Drugs'!
• Amiodarone:!t½=100!days,!∴!hypothyroid!may!persist!for!a!while!
despite!withdrawal!
• Lithium,!iodide,!antithyorid!drugs!
! Dyshormonogenesis!!
* Secondary!hypothyroidism:!hypopituitarism!
o Post*NCP!RT,!NPC!invasion,!mass!effect!of!pituitary!tumor!
* Tertiary!hypothyroidism:!hypothalamus!disorder!
* Generalized!/!peripheral!thyroid!hormone!resistance!
!
Clinical!presentations!!
* Tiredness,!lethargy,!muscle!aching!&!cramps!
* Depression,!dementia,!memory!loss!
* Cold!intolerance!!
* Weight!gain!!
* Constipation,!menorrhagia!!
* Husky!voice,!goiter!!
* Coarse,!yellowish!skin,!facial!&!hand!puffiness,!thinning!hair,!loss!of!lateral!1/3!eyebrow!
!
!

Endocrine!*!9!
Associated!disease!!
* Type!1!DM!!
* Pernicious!anemia!!
* Addison's!disease!!
* Viltiligo!!
!
Associated!syndrome!!
* Turner's!syndrome!!
* Down's!syndrome!!
* POEMS!syndrome!!
* Pendred!syndrome!!
!
Investigations!!
* TFT!
* Anti*!thyroid!peroxidase!(TPO)!antibody!/!anti*microsomal!(AMC)!antibody!
* Anti*thyroglobulin!(ATG)!antibody!!
* CPK,!lipid!profile,!RFT!(low!Na)!!
* If!cannot!find!obvious!cause!of!hypothyroidism!like!Hashimoto!"!may!do!LDSST!to!rule!out!
concomitant!adrenal!insufficiency!before!replacing!thyroxine!
!
Management!!
* Replace!thyroxine!(L*thyroxine)!
o 50/100mcg!daily!usually!enough!!
o Beware:!!
! Rule!out!ischemic!heart!disease,!start!low!(↑!HR!"!↑!risk!of!ischemia)!
! Rule!out!concomitant!adrenal!insufficiency,!replace!steroid!first!!
• Thyroxine!↑!metabolism!"!need!even!more!cortisol!support!"!worsen!
adrenal!insufficiency!
o Drug!interactions!
! Fe/Ca!supplement:!chelate!thyroxine!"!prevent!absorption!!
! Enzyme!inducers!(e.g.!PPI):!↑!thyroxine!metabolism!in!liver!!
* Monitor!TSH!level!after!4!weeks!(thyroxine!half*life!around!7!days)!
* Surgery!is!not!indicated!unless!with!pressure!symptoms!
Primary7hyperparathyroidism7
Etiology!!
* Adenoma!80%!
* 4!x!Hyperplasia!20%!!
* Carcinoma!(*MEN1,!2a)!!
!
History!taking!
* Symptoms!of!hyperCa:!polydipsia,!polyurea,!constipation,!abdominal!pain,!bone!pain,!
neuropsychiatric,!fatigue,!proximal!muscle!weakness…!
* Complications!of!hyperCa:!renal!stone,!osteoporosis,!bone!fractures!
* Hx!of!TB,!malignancy,!renal!impairment!
* Dietary!Ca,!Vit!D!intake!
* Hx!of!other!hormonal!problem!esp.!pituitary,!pancreas,!thyroid,!phaeo!(MEN)!
* FHx!of!hormonal!problem!(MEN)!
!
Physical!examination!
* Corneal!calcification!(usually!asymptomatic)!
o Sign!of!chronic!hyperCa!
o Start!at!equator!(horizontal):!vs!Arcus!senilis:!start!at!upper/lower!pole!
!

Endocrine!*!10!
Investigations!!
* Ca!↑,!PO4!N/↓!
o Sometimes!may!have!↑!PTH,!↑!ALP!but!normal!Ca!in!1°!hyperPTH!"!due!to!
concomitant!vit!D!deficiency!
* Paired!PTH!N/↑!
* ALP!↑!
* RFT:!normal!
o Cl!↑!in!1°!hyperPTH!(↑!chloride/phosphate!ratio),!but!↓!in!other!causes!of!hyperCa!
* ABG!(hyperchloremic!metabolic!acidosis)!!
* 24h!urine!calcium!!
* Preoperative!localization!by!USG,!CT,!MRI,!MIBI!scan!(functional!scan)!
o Not!diagnostic:!diagnosis!by!surgical!excision!of!adenoma!
* DEXA:!if!osteoporosis!"!indicated!for!surgery!

!
!
Medical!Treatment!!
* Adequate!hydration!
* Avoid!thiazide,!lithium!
* Ambulatory!lifestyle!
* Moderate!calcium!and!vitamin!D!intake!!
o Avoid!excessive!intake!of!high!Ca!food,!e.g.!diary!products!
* Bisphosphonates'!
o Mechanism!
! Osteoclast!inhibitors!
! Increase!vitamin!D!synthesis!!
! Reduce!renal!calcium!excretion!
o Beneficial!to!bone!density!
o Indication!!
! For!patient!not!plan!/!not!fit!for!OT,!e.g.!elderly!already!having!osteoporosis!
! In!hyperCa!emergency!(>3.2):!give!IV!pamidronate!/!zoledronate!
• Bring!down!Ca!level!in!1*2!days!
• But!effect!just!last!for!few!weeks:!not!long*term!
* Cinacalcet'!
o A!calcium!mimic!that!activate!CaSR,!suppress!PTH!production!!
o For!uncontrolled!1°/!2°hyperPTH!/!parathyroid!CA!
!
Surgical!management!!
* Indications!!
o Hypercalcemia:!>0.25mmol/l!more!than!upper!limit!of!normal!!
o Hypercalciuria:!>10mmol/day!NO!LONGER!AN!INDICATION!!
o Renal!impairment:!CrCl!<30%!predicted!
o Osteoporosis:!T*score<2.5!
o <50!years!old!
o Complication!arise:!recurrent!renal!stone!
!

Endocrine!*!11!
 o Symptomatic!hyperCa!
o CA!parathyroid!
o Difficult!follow!up!
* Post*op:!need!to!measure!Ca!again!
o Before!excision,!other!3!glands!suppressed!∴!usu!keep!in!hospital!for!few!days!to!wait!
for!their!recovery!
Familial7hypocalciuric7hypercalcemia7(FHH)7
Introduction!
* Heterozygous!hypofunction!of!CaSR!(calcium!sensing!receptor)!"!mild!hyperCa,!usually!
asymptomatic!
* AD!"!young!onset!
o HyperCa!since!birth,!so!normal!Ca!in!previous!report!point!towards!1°!
hyperparathyroidism!more!than!FHH!
!
Investigations!
* Serum!Ca!↑,!PTH!↑!
* Fraction!excretion!of!Ca!<1%!(Vs!1°!hyperparathyroidism!>1%)!
o Calculated!by!spot!urine!Ca!to!Cr!ratio!
o Not!look!at!the!absolute!amount!of!Ca!excreted!as!it!is!affected!by!the!amount!of!urine!
excreted!
Neonatal7severe7hyperparathyroidism7(NSHPT)7
* Hypofunction!of!CaSR!(inactivating!mutation)!
* Severe!hyperCa!
Hypoparathyroidism77
Causes!!
* Autoimmune!(*!Autoimmune!polyendocrine!syndrome!type!1)!!
* Congenital!(DiGeorge!syndrome)!
* Surgery!
* Radiation!!
* HypoMg!!
!
Treatment!!
* Calcium!supplement:!Ca!1*2g/day!
* Vitamin!D!supplement:!calciferol!(vit!D2)!/!alfacalcidol!
Pseudohypoparathyroidism77
* End!organ!resistance!to!PTH!
Clinical!features!
* Moon!face,!short!stature,!Mentally!retarded!!
* Short!4th!and!5th!metacarpals!
Investigations!!
* High/normal!PTH,!but!low!Ca!
* Ellsworth'Howard'test'!
o Infusing!PTH!
o Measure!urinary!phosphate!and!cAMP!!
Pseudopseudohypoparathyroidism7(Albright's7hereditary7osteodystrophy)77
* Deficiency!of!Gsa!protein!!
* Similar!morphology!to!pseudo!!
* Normal!PTH!&!Ca!!

Endocrine!*!12!
7
7
Diabetes7Mellitus7(DM)7
Causes!!
* Type!I!*!insulin!deficiency!
* Type!II!*!insulin!resistance!+!insulin!deficiency!!
* Others!!
o Maturity!onset!diabetes!of!the!young!(MODY):!dominantly!inherited,!monogenic!defects!
of!insulin!secretion!occurring!at!any!age!
o Gestational!diabetes!!
o Exocrine!pancreas!diseases!!
! Chronic!pancreatitis,!hemochromatosis,!cystic!fibrosis!
o Endocrine!disorders:!acromegaly,!Cushing's,!hyperthyroidism,!pheochromocytoma,!
glucagonoma!
o Drugs:!diuretics,!steroids!
!
Brittle!DM!
* Fluctuation!of!hyper!&!hypoglycemia!
* Risk!of!neurohypoglycemia!&!DKA!
* Difficult!to!titrate!drugs!&!insulin!
* May!need!to!split!insulin!dose!&!adjust!t½!of!insulin!
* Need!close!monitoring:!H’stix!at!least!4!times/day!
!
Diagnosis!!
* DM!!
o Fasting!(>8h)!plasma!glucose!≥7.0mmol/l!!
o OGTT!2!hour!plasma!glucose!≥11.1mmol/l!!
o Random!plasma!glucose!≥11.1mmol/l!+!polydipsia/!polyuria/!polyphagia/!unexplained!
weight!loss!!
o HbA1c!≥6.5%!
* Impaired!fasting!glucose:!fasting!plasma!glucose!≥6.1!(WHO)!/!5.6!(ADA)!mmol/l!
* Impaired!glucose!tolerance:!OGTT!2!hour!plasma!glucose!≥7.8mmol/l!!
* How!to!do!a!OGTT!!
o 3!days!of!normal!diet!and!normal!physical!activity!!
o Fasted!overnight!
o Start!test!at!9am!
o 75g!anhydrous!glucose!in!300ml!water,!finish!in!5min!!
o Blood!taken!at!0h!and!2h!!
o Free!water!intake!in!between!
!
When!to!screen?!(Every!3!yearly;!fasting!glucose!"!if!IFG!go!for!OGTT)!!
* For!>45yo!!
* Overweight!BMI!>23!!
* Any!of!the!followings!!
o First!degree!relatives!
o Physical!inactivity!
o Previous!IGT/!IFG/!GDM/!macrosomia!!
o HT;!HDL!<0.9mmol/l;!TG!>2.8mmol/l!!
o PCOS/!acanthosis!nigricans!
o CVD/!CVA!!
!
!

Endocrine!*!13!
Complications!!
* Microvascular!
o Neuropathy!
! Peripheral!neuropathy!
! Sensory!neuropathy!
! Motor!neuropathy!
! Autonomic!neuropathy!
! Mononeuritis!multiplex:!isolated!nerve!problem!
! **!DDx:!subacute!combined!degenration!of!cord!due!to!B12!defiency!due!to!long!
term!metformin!"!test!dorsal!column!
o Nephropathy!
! May!"!UTI,!but!due!to!neuropathy,!may!not!have!dysuria!∴!do!urine!stix!
! On!the!other!hand,!UTI!may!lead!to!poor!control!of!DM!
! Decrease!in!erythropoietin!production!"!anemia!"!↓O2!supply!(together!with!↓!
glucose!into!cells!due!to!DM)!"!↓!ATP!"!risk!multiplier!for!IHD,!may!lead!to!
acute!exacerbation!of!heart!failure!
o Retinopathy!
o Dermatopathy!(necrobiosis!lipiodica!diabeticorum)!!
! Shiny,!red*brown!lesion!most!commonly!in!tibia!!
! Progressively!become!yellow!and!atrophic!!
! Prone!to!trauma!and!may!then!ulcerate!!

! !
* Macrovascular!
o Stroke!
o Ischemic!heart!disease!
o Peripheral!vascular!disease!
* Cancers:!2!cases!in!every!10!DM!patients!
* Lifespan:!10!years!less!than!non*DM!
!
P/E!
Aim!
* Look!for!causes:!obesity,!endocrine…!
* Look!for!signs!of!complication!
* General!
o Cushingoid!features,!acromegaly!
o Skin!ulcers,!acanthosis!nigricans,!necrobiosis!lipiodica!diabeticorum!
o Whitish!chalky!materials!(ectopic!calcifications!due!to!3°!hyperPTH)!
* Foot!
o Ankle!edema!(nephropathy),!pes!cavus!(neuropathy)!
o Deformity!(callus),!ulcers,!amputation,!fungal!infection!
o Peripheral!nerve!sensory!loss!(monifilament,!vibration)!
o Capillary!refill,!atrophic!changes,!pulse!
! If!loss!of!dorsalis!pedis!pulse!(also!carotid!bruit)!"!signify!significant!
atherosclerosis!"!high!risk!of!coronary!artery!disease!/!stroke!
!
!

Endocrine!*!14!
* Neurological!
o Power,!sensation,!CN,!proximal!muscle!weakness!(diabetic!amyotrophy),!small!hand!
muscle!wasting!(neuropathy)!
* Eye!
o Visual!acuity,!papillary!reflex!(cataract)!
o EOM!(mononeuritis!multiplex)!
o Fundi!(DM!proliferative!retinopathy,!maculopathy)!
* Cardiovascular!!
o Basal!creps!(HF),!carotid!bruit!
* Abdomen:!insulin!injection!site!(lipodystrophy),!!
* Finished!by!
o BP,!postural!BP!(autonomic!neuropathy)!
o Body!weight,!BMI!
o Urine!dipstix!!
!
Treatment!
* Key:!empower!patient!for!his!responsibility!&!allow!autonomy!in!decision*making!!
* Aim:!
o Depend!on!Age,!Body!weight,!Complications,!Disease!duration!
o Fasting!blood!glucose:!5*6!
o Post*prandial:!7*8!
o BP!<!130/80!
o HDL!>!1!
o Triglyceride!<!2!
o LDL!<!3!
* 4!ways!to!↓!vascular!risk!(cerebral,!cardiac,!lower!limb)!
o HbA1C!
o BP!
o Cholesterol!level!
o Weight!
* Lifestyle!modification!!
o Smoking!cessation!
o Limit!alcohol!intake!to!<2!unit!(M)/!<1!unit!(F)!
o Weight!reduction!
o DM!diet!by!dietitian:!low!carbohydrate,!low!fat!(<7%!saturated!fat,!no!trans!fat)!!
o Regular!moderate!intensity!aerobic!exercise!at!least!150min!a!week!!
* Lowering!blood!glucose!!
o Start!OHA/'insulin'!
! Meformin!
! Meformin!+!sulphonylurea!
! Meformin!+!sulphonylurea!+!glitazone/exenatide/insulin!!
! *!Eventually!40%!of!T2DM!patients!need!insulin,!if!really!need!"!start!early!
o Warn!S/E,!educate!what!to!do!if!hypoglycemia!!
* Glucose!monitoring!!
o Self!H'stix!!
! 2!times!a!weeks,!3!times!a!day!(morning!fast,!pre*lunch,!pre*dinner);!adjust!
according!to!control!
• Fasting!4*6mmol/l!
• Postprandial!7*10mmol/l!!
! Most!ideal:!H’stix!before!meal!as!all!DM!patients!are!bound!to!have!post*prandial!
hyperglycemia!!
! Educate!what!to!do!if!sky*high!/!low!with!symptoms!!
!

Endocrine!*!15!
 o HbA1c!!
! 2!times!a!year!for!stable!control,!4!times!a!year!for!poor!control!!
! Aim!<7%!(young!patients:!~6.5%):!reduce!microvascular!complications!!
• More!stringent!if!short!duration!of!DM,!long!life!expectancy!!
• Less!stringent!if!old!age/!history!of!severe!hypoglycemia!!
! Not!accurate!in!thalassemia,!aplastic!anemia,!previous!transfusion…!
* Complication!screening!&!treatment!
o Nephropathy!!
! Annual!spot!urine!albumin!to!creatinine!ratio!
! Annual!serum!creatinine!for!eGFR!
! If!microalbuminuria:!start!ACEI/ARB,!check!K!and!RFT!!
o Retinopathy!!
! Annual!ophthalmologist!examination!!
! If!retinopathy:!laser!photocoagulation!!
o Neuropathy!!
! Annual!examination!for!distal!symmetrical!sensory!polyneuropathy!and!postural!
hypotension!!
o Foot!care!!
! Annual!comprehensive!foot!examination!(inspection,!pulses,!sensation)!!
! Provide!general!foot!care!education!!
* Control!other!cardiovascular!risk!factors!!
o Hypertension:!<130/80,!use!ACEI/ARB,!monitor!K!!
o Hyperlipidemia:!statin!usage!!
! LDL!<2.6mmol/l!(<1.8!for!CVD!/!high!risk)!!
! HDL!>1.0!(M);!>1.3!(F)!
! TG!<1.7!!
o Aspirin!for!CVD!/!high!risk!
! Balance!CVD!risk!(Framingham!risk!score)!&!bleeding!risk!!
Follow!up!
* Q3M:!Fasting!glucose,!BP,!Body!weight!
* Q6M:!Lipid!profile,!HbA1c!
* Q12M:!Eye,!foot,!neuro,!eGFR,!microalbuminuria,!review!technique!!
!
Aim!of!glycemic!control!!
* UKPDS:!8%!vs!7%!!
o Tight!glycemic!control!for!MICROVASCULAR!DISEASES!!
! Each!%!drop!lead!to!reduced!risk!with!no!threshold!effect!
o Tight!glycemic!control!for!MACROVASCULAR!DISEASES!!
! For!longstanding!type!2!DM!
• No!RCT!show!beneficial!effect!on!macrovascular!outcome!!
! For!newly!diagnosed!type!2!DM!(UKPDS)!!
• Lower!risk!of!MI,!DM*related!deaths,!overall!deaths!
o **SO,'intense'control'<7.0'may'be'beneficial'when'used'early''
* ACCORD:!7%!vs!6%!!
o Terminated!prematurely!due!to!high!incidence!of!weight!gain,!hypoglycemia!and!
mortality!!
o (Despite!benefit!on!microvascular!complications!demonstrated)!!
* Overall!recommendation!!
o In!general,!aim!HbA1c!<7.0%!!
o Individualize'the'goal'by'balancing'
(i)'Risk'of'hypoglycemia'
(ii)'Benefit'of'microvascular'complication'reduction'!
!

Endocrine!*!16!
 o Looser!threshold!for!!
! Previous!severe!hypoglycemia!limited!life!expectancy!
! Poor!comorbid!!
! Already!have!establiched!microvascular!complications!&!have!limited!life!
expectancy!
• Main!concern!is!to!prevent!acute!DM!complications:!hypoglycemia!&!
HHNS/DKA!
* Titration!of!drug!dose!
o If!hyperglycemia!before!meal!"!give!short!acting!insulin!
o If!early!morning!hypoglycemia!"!↓!dose!of!night!insulin!/!have!a!snack!(e.g.!biscuits)!
before!sleep!
o If!morning!hyperglycemia!!
! DDx:!
• Inadequate!drug!dosage!
• Nocturnal!hypoglycemia!"!rebound!hyperglycemia!(Somigyi!effect)!
o Fasting!glucose!&!HbA1c!↑!(HbA1c!capture!the!peak!glucose!level,!
masking!the!nocturnal!hypogly∴!need!to!monitor!glucose!profile!
i.e.!HBGM!also)!"!doctor!will!↑!nocturnal!dose!of!medication!"!
vicious!cycle!
o Usually!suspect!this!when!↑!drug!dosage!but!worsening!of!
morning!hyperglycemia!
o Can!ask!patient!to!check!H’stix!at!midnight!to!differentiate!
o If!recurrent!hypoglycemia!"!↓!insulin!dose!by!20*30%,!want!to!aim!high!normal!1st!!
! No!need!to!stop!metformin!as!metformin!won’t!cause!hypogly!!!Unless!renal!
impairment,!then!need!to!↓!dose!to!prevent!lactoc!aidosis!
o *!Titrate!the!dose!of!insulin!slowly,!e.g.!every!3!days!
!
Oral!hypoglycemic!agents!(OHA)!!
* Metformin!(belongs!to!Biguanide):!1st!line!
o Mechanism!!
! ↑ insulin!sensitivity!of!peripheral!tissue!+!↓!hepatic!gluconeogenesis!
! Work!mostly!on!fasting!glucose!!
o *Taken!WITH!FOOD!to!↓!GI!S/E!(Vs!sulphonylurea:!take!30MIN!BEFORE!FOOD)!
o Stop!when!!
! Cr!>150umol/l!or!GFR!<30!due!to!risk!of!lactic!acidosis!
! Tissue!hypoxia!(MI,!sepsis,!severe!liver!disease,!alcoholism)!!
! Before!GA!/!radiocontrast!!
o Advantage!!
! Mild!weight!loss!/!no!weight!gain!(↓!weight!by!↓!appetite)!
! No!hypoglycemia!!
o Side!effects!
! GI!disturbance:!anorexia,!diarrhea,!dyspepsia,!N&V,!flatulence,!weight!loss!
• If!used!with!insulin:!weight!loss!caused!by!metformin!"!↑!insulin!to!body!
weight!ratio!"!may!lead!to!hypoglycemia!
! Lactic!acidosis,!esp!in!renal!/!cardiac!/!liver!failure!
! Vit!B12!deficiency!(in!chronic!high!dose):!due!to!inhibited!terminal!ileum!B12!
absorption!
• It’s!a!vascular!risk!factor!due!to!↑!in!homocysteine!(B12!is!involve!in!its!
metabolism)!which!is!toxic!to!vasculature,!can!give!oral!B12!supplement!
when!B12!<300!(no!need!to!wait!until!not!in!normal!range!to!start!Rx)!
!
!
!
Endocrine!*!17!
* Sulphonylurea'!
o Mechanism!!
! Insulin!secretagogues,!they!depend!on!pancreatic!insulin!reserve!for!action,!so!
effectiveness!tends!to!decrease!over!time!!
o Drug!choice!!
! Short!acting:!tolutamine!!
! Intermediate!acting:!gliclazide!(Diamicron),!glipizide!
! Long!acting:!chlorpropamide,!glibemclamide!(Daonil)!"!risk!of!hypoglycemia!!
o Advantage!!
! Rapidly!effective!!
o Side!effects!!
! Weight!gain,!hypoglycemia!!
* Meglitinides'!
o Repaglinide,!Nateglinide!!
! Repaglinide!is!superior!to!nateglinide:!hepatic!metabolized!(suitable!in!renal!
patients)!&!more!effective!in!lowering!A1c!
o Mechanism!!
! Insulin!secretagogues!–!sulfonylurea!receptor!binders!
! Action!similar!but!pharmacologically!distinct!from!sulphonylurea!!
! Target!post*prandial!hyperglycemia!(vs!metformin:!fasting!glucose)!
o Advantage!!
! Very!rapidly!effective!with!short!half*life!"!good!for!those!irregular!meals!!
o Side!effects!!
! Weight!gain!!
! Hypoglycemia!(less!than!that!in!sulphonylurea)!!
* Thiazolidenedione'(rarely!used!now)!
o Drug!choice!
! Troglitazone:!WITHDRAWN!(severe!idiosyncratic!hepatic!injury!in!~1%)!
! Rosiglitazone:!WITHDRAWN!(increase!risk!of!ischemic!event),!now!start!to!use!
again!in!US!due!to!wrong!data!in!previous!study!(?)!
! Pioglitazone!
o Mechanism!!
! PPAR*gama!agonist!
• Enhance!insulin!sensitivity!
• Enhance!muscle!glucose!uptake!!
• Reduce!hepatic!gluconeogenesis!!
o Side!effects!
! Weight!gain!
! Reduced!bone!density!"!osteoporosis!
! Fluid!retention!(dose*dependent)!"!NOT!USED!in!heart!failure/renal!failure!
! May!↑!risk!of!bladder!cancer!(controversial)!!
o Drug!interaction!
! CYP!2C8:!fibrate!inhibit!CYP2C8!"!↑!fluid!retention!!
o Advantage!(for!pioglitazone)!!
! Improve!lipid!profile!(HDL!and!TG)!!
! Potential!decrease!MI!!
* Dipeptidyl'peptidase'IV'inhibitors'(DPPWIV'inhibitors)!
o Sitagliptin,!Saxagliptin,!Vildagliptin!(Galvus)!
o Mechanism!!
! Blocks!this!enzyme!which!degrades!incretins!"!↑!incretin!levels!
• GLP*1:!Glucagon!like!peptide!1,!GIP:!gastric!inhibitory!polypeptide!
! Potentiate!glucose*stimulated!insulin!secretion!during!meal!time!(this!needs!the!
!

Endocrine!*!18!
 presence!of!glucose!∴low!risk!of!hypogly)!
! Inhibit!glucagon!secretion!
! Retard!gastric!emptying!
! Reduce!appetite!
o Benefit!!
! Weight!neutral!!
! Minor!S/E,!low!risk!of!hypoglycaemia!
o Side!effects!!
! ?Pancreatitis!!
o Indication!
! Failed!/!intolerant!to!metformin!&!SU!
• Lower!efficacy!than!metformin/SU!(↓!HbA1c!by!~0.8%!vs!1*2%)!
! Poor!DM!control!but!don’t!want!insulin!injection!
! "!trial!of!6*8!months,!if!still!fail!"!need!insulin!
o *!Need!to!↓!dose!if!renal!impairment!
* GLPW1'receptor'agonist'!
o Exenatide!(from!lizard!saliva!),!Liraglutide!!
o Mechanism!!
! Directly!act!on!GLP*1!receptor!"!↑!incretin!levels!(same!effects!as!DPP*4i)!
o Benefit!!
! Weight!loss!!
o Side!effects!!
! Nausea!!
o Vs!DPP*IV!inhibitors!
! Need!sc!injection!!
! More!GLP!elevation,!HbA1c!reduction,!weight!loss,!likely!B*cell!protection!!
* Alpha'glucosidase'inhibitor'!
o Acarbose,!Miglitol!!
o Mechanism!!
! Inhibitor!this!intestinal!enzyme!"!no!hydrolysis!from!dissaccharides!to!glucose!
"!↓!intestinal!absorption!!
o Benefit!!
! Weight!neutral!!
o Side!effects!!
! Abdominal!bloating,!flatulence!&!cramps!!
* Sodium'glucose'transporterW2'inhibitors'!
!
Insulin!!
* Types!(all!at!a!concentration!of!100units/ml)!!
o Ultrafast!acting:!onset!15mins,!inject!at!start!of!meal,!last!4!hour!!
! Insulin!aspart!(Novorapid)!!
! Insulin!lispro!(Humalog)!
o Soluble!insulin:!inject!~30min!before!meal,!last!8!hour!!
! Actrapid'!
! Humulin'R'!
o Intermediate:!last!16!hour,!have!peak!action!time!(up!&!down!slope)!
! Human!isophane!(Protaphane)!!
! Human!isophane!(Humulin'N)!
o Long!acting:!rapid!onset,!last!24!hour,!no!peak!action!time!(↓!risk!of!hypo)!
! Insulin!glargine!(Lantus)!!
! Insulin!detemir!(Levemir)!!

Endocrine!*!19!
 ! Used!once!at!bedtime,!soluble!at!acidic!pH,!but!precipitates!in!subcutaneous!
tissue!and!is!slowly!released!from!a!depot!!
o Premixed!
! NovoMix'30!
! Humulin'70/30'HM:!premix!of!70%!humulin!R!+!30%!humulin!N!!
! Mixtard'30H'!
* Regime!(start!at!a!total!daily!dose!of!1U!insulin!every!unit!of!BMI)!!
o Night!time!add*on!regime!!
! Add!a!intermediate/long!action!insulin!at!bedtime!!
• Starting'dose'~0.2W0.5unit/kg!
! Continue!oral!hypoglycemic!agents!as!usual!!
! Can!↑!patient's!acceptance!to!insulin,!while!offer!a!better!control!of!fasting!
glucose!level,!as!well!as!a!smoother!transition!to!full!insulin!regime!!
! If!already!maximum!tolerated!dose!but!still!unsatisfactory!HbA1c!"!!
• Introduce!a!rapid*acting!insulin!analogue!at!mealtimes!OR!
• Switch!to!twice*!/!thrice*!daily!insulin!analogue!mixtures!
! *!Doses!of!basal!insulin!>0.5U/kg/day!can!cause!weight!gain!/!↑!risk!of!
hypoglycemia!
o BD'regime'(mixtures)!
! Premixed!insulin!/!intermediate!insulin!x!2!
! 2/3!dose!before!breakfast,!remaining!1/3!before!dinner!
! Always!keep!metformin!(unless!C/I),!but!stop!SU!
• Metformin!↑!sensitivity!of!insulin!"!can!use!lower!dose!of!insulin!
• Metformin!also!↓!risk!of!CV!events!&!cancers!
• SU!may!over*stress!the!pancreas!when!it!already!not!function!well!
• Also,!if!give!both!SU!&!insulin!and!hypoglycemia!occurs!"!don’t!know!
whether!it’s!caused!by!SU!or!insulin!
! *Can!lead!to!nocturnal!hypoglycemia!&!morning!hyperglycemia!(rebound)!!
! Simple,!good!prandial!&!fasting!control!☺!
! Compromise!for!dose!adjustment!$!
• For!patient!with!regular!life*style,!regular!meals,!less!motivated!for!blood!
glucose!monitoring!&!insulin!dose!adaptation!
o Basal'bolus'regime'!
! Before!meals!ultrafast/soluble!insulin!+!bedtime!long!acting!insulin!(baseline)!
! More!for!type!I!diabetes:!can!adjust!the!pre*meal!dose!according!to!meal!sizes!!
! Close!to!physiology!☺!
! Good!for!post*prandial!hyperglycemia!☺!
! Need!extensive!patient!education!&!multiple!daily!home!glucose!monitoring!$!
• For!young,!active!&!motivated!patients!!
* *!During!intercurrent!illness!!
o Maintain!calories!intake!
o Requirement!may!increase!due!to!catabolic!effect!of!infection!!
o Requirement!may!decrease!due!to!loss!appetite!
o Check!H'stix!4!times!a!day!and!adjust!insulin!accordingly!!
o In!critically!ill!patients,!need!tight!glucose!control!(otherwise!↑!mortality)!
! Use!DKI!if!no!fluid!overload,!otherwise!use!insulin!pump!(lower!volume)!
!
FU!in!OPD!
* Assess!control!
o HBGM,!HBPM!
o Hypoglycemic!Sx!
!
!

Endocrine!*!20!
* Drug!
o Compliance,!S/E!(e.g.!hypoglycemic!symptoms,!GI!disturbance)!
* Check!complication!
o Chest!pain!after!exercise,!use!of!TNG!(IHD)!
o Claudication!(PVD),!amoureux!fugax!(TIA),!foot!ulcers!
o Arrange!complication!screening!if!not!yet!done!
* Assess!overall!CV!risk!
o Smoking,!alcohol,!diet,!exercise!
o PMH:!HT,!dyslipidemia!
o FHx:!CVS,!DM!
* P/E!
o Monofilament,!peripheral!neuropathy!
o Foot!ulcer,!sensation!
o Muscle!power!(old!stroke)!
o Eye:!visual!acuity,!EOM,!fundi!
o BP!
* Counsel!quite!smoking,!diet!(refer!to!dietitian),!exercise,!importance!of!drug!compliance!
!
Complication!screening!!
* Questionnaire!
o Occupation:!affect!diet!habit!
o FHx:!1°!relative!
o Renal!disease,!premature!CVD!(F<60,!M<50),!cancers:!risk!↑!
* Education!by!dietitian,!podiatrist,!nurses!(teach!them!self!monitoring)!
o 8765!theory:!365.25!days!x!24hr!=!8766!hr/year,!4!FU/year!&!15min/time!"!8765hr!
on!their!own!∴!important!to!have!patient’s!participation!/!self!control!
* DM!foot!
o Pulse!
o Sensation:!monofilament,!vibration!
* Ankle*brachial!index!(ABI):!<0.9!"!PVD!
* HbA1C,!fasting!blood!glucose,!lipid!level,!L/RFT!
* Urine:!albuminuria!(also!check!nitrite!to!r/o!UTI:!which!may!cause!proteinuria)!
* Visual!acuity,!fundus!camera!
* Body!weight,!wrist!circumference!
**!When!should!start!complication!screening?!
* Type!2!DM:!gradual!onset,!may!be!asymptomatic!at!1st,!so!start!Cx!screening!once!diagnosed!
* Type!1!DM:!acute!onset,!e.g.!acute!DKA!"!Cx!screening!later,!e.g.!after!5!years!of!Dx!

DM7nephropathy7
Microalbuminuria!
* Definition!!
o 24h!urine!albumin!30*300mg!!
o Albumin:!creatinine!ratio!>!2.5*3.5mg/mmol!
o **!If!proteinuria!reach!nephrotic!range!"!need!renal!biopsy!to!r/o!other!causes!
* Clinical!significance!!
o It!is!the!earliest!sign!for!DM!nephropathy!
o Risk!stratification:!independent!risk!factors!for!cardiovascular!disease,!renal!
impairment!&!mortality!
o Modifier!for!effective!ACEI!renoprotective!property!
* Management!
o Better!glycemic!control!
o Better!hypertension!treatment!
!

Endocrine!*!21!
 o Consider!ACEI!
! Mechanism:!Inhibit!ACE!2!which!is!the!potent!constrictor!
! Cause!vasodilation!of!efferent!arteriole!>!afferent!arteriole!
! Tolerate!15*30%!increased!Cr!level!after!ACEI!prescription!!
!
Choice!of!medication!affected!by!poor!renal!function!
* Prefer!SU!/!DDP*4!inhibitor,!avoid!metformin!(when!eGFR<30!/!Cr!>150)!/!glibenclamide!(SU)!
* Use!shorter!acting!drugs!
o High!risk!of!hypoglycemia!due!to!↓!excretion!of!drugs!
* Not!necessary!to!use!insulin,!only!if!poor!control,!e.g.!originally!taking!combinations!of!drugs,!
but!now!metformin!is!C/I!
* Some!patients!may!lose!weight!after!having!renal!impairment!"!may!improve!insulin!
sensitivity!"!may!need!less!drugs!
* Glucose!control!is!worse!after!dialysis!
o Dialysate!contain!high!sugar!content!
!
Prognosis!!
* Survival!rate!in!patient!>!65!years!after!dialysis!=!50%!in!2!years!
o Usually!die!of!CV!events,!also!due!to!IC!state!

Diabetic7neuropathy77
Sensory!neuropathy!!
* Patients!tend!to!lose!their!sense!of!VIBRATION!AND!PROPRIOCEPTION!first!!!
* Distal!glove!and!stock!numbness!"!neuropathic!ulcers!!
* Tingling!pain!often!worse!at!night!
* Rx:!paracetamol!>>!TCA!>>!gabapentin!!
!
Mononeuritis!multiplex!!
* CN!III/VI!palsy,!median!nerve,!common!peroneal!nerve!palsy!!
* Rx!(if!severe):!steroids,!IVIg,!cyclosporin!!
!
Diabetic!Amyotrophy!!
* Painful!asymmetrical!wasting!of!quadriceps!&!pelvifemoral!muscles,!often!recover!
spontaneously!!
* Rx!(if!severe):!IVIg!!
!
Autonomic!neuropathy!!
* Postural!hypotension!(fludrocortisone),!loss!of!beat!to!beat!variation!
* Urinary!/!fecal!retention!
* Sexual!dysfunction!
* Esophageal!dysmotility,!gastroparesis!(prokinetic!agents),!diarrhea,!constipation!!
* Gustatory!flushing!or!sweating!!

Diabetic7retinopathy7
* **!DM!is!the!most!common!cause!of!blindness!in!middle!age!patient!in!developed!countries!
!
Proliferative!diabetic!retinopathy!(PDR)!
* DM!damage!small!vessels!"!closure!of!retinal!capillaries!
"!hypoxia!of!retina!"!compensatory!mechanism!of!
neovascularization,!forming!of!fragile!and!leaky!vessels!
along!surface!of!retina,!and!they’re!disrupted!easily!by!
vitreous!traction!"!bleed!into!vitreous!cavity!/!
preretinal!space!
!

Endocrine!*!22!
* Neovascularization!also!a/w!fibrous!tissue!formation!adhere!to!retina,!when!vitreous!
contracts,!may!exert!tractional!forces!on!retina!"!traction!retinal!detachment!(end*stage!
retinopathy)!
!
Fundoscopy!!
* Red!reflex:!no!cataract!if!present!
* Optic!disc:!see!vascular!bundle!(vein:!darker!&!thicker!vs!artery)!
* Hard!exudates:!look! d!
o Lipid!deposit!(lipid!leaked!from!vessels!&!engulfed!by!macrophages),!may!have!
hemorrhage!before!
* Soft!exudates:!like!cotton!wool,!more!‘blurred’!
o Mostly!caused!by!HT!
* Laser!mark:!lighter!color,!round,! ,!if!at!macula!"!
blurred!vision!
* Dot!hemorrhage:!small!hemorrhage!
* Asteroid!hyalosis:! in!ophthalmoscope!but!not!affect!
vision!"!no!need!Rx!
o Small!white!opacities!in!vitreous!humor!
* Proliferative!diabetic!retinopathy!(PDR)!
o Neovascularization:!vessels!that!are!1!pat ,!unlike!
normal!vessels!very!clear!
o Very!brittle,!prone!to!hemorrhage!!
o Higher!risk!in!high!serum!triglyceride!level!
o Need!urgent!referral!to!ophthalmologist!
o Rx:!laser!after!blood!resorbed!
* Retinal!detachment:!higher!risk!if! !
* Central!venous!occlusion:!many!hemorrhage,!usually!unilateral!
* *!Not!the!type!of!abnormalities!present!but!the!location!of!them!counts!!Even!hemorrhage,!if!
not!affect!macula!"!still!OK!
o If!abnormality!at!macula!/!~1!optic!disc!length!around!macula!"!need!referral!to!
ophthalmologist!
!
Treatment!!!
* Panretinal!photocoagulation!
o Create!1,600!*!2,000!burns!in!retina!"!↓!retina's!O2!
demand!"!↓!ischemia!
o May!sacrifice!some!of!the!peripheral!vision,!but!usu!not!
noticeable!by!patient!

Diabetic7foot7
* Ulcer,!gengrene!and!infection!of!foot!!
!
Etiology!!
* Peripheral!sensory!neuropathy!!
* Muscle!weakness!
* Peripheral!vascular!disease!!
* Prone!to!infections!!
!
Risk!factors!
* Absence!of!protective!sensation!due!to!peripheral!neuropathy!
* Arterial!insufficiency!
!

Endocrine!*!23!
* Foot!deformity!(claw!feet,!hammer!toes,!bunions)!&!callus!formation!"!focal!areas!of!high!
pressure!
* Skin!changes:!healed!ulcers,!acute!ulcers,!gangrene,!dry!skin,!fissures,!fungal!infection!
* Autonomic!neuropathy!"!↓!sweating!&!dry,!fissured!skin!
* Limited!joint!mobility!
* Obesity!
* Impaired!vision!
* Poor!glucose!control!"!impaired!wound!healing!
* Poor!foot!wear!that!causes!skin!breaksown!/!inadequately!protect!the!skin!from!high!pressure!
and!shear!forces!
* History!of!foot!ulcers!/!LL!amputation!
!
Prevention!
* Educate!on!foot!care!
o Daily!foot!inspection!by!patient!/!caretaker!!
o Gentle!cleansing!with!soap!&!water,!followed!by!application!of!topical!moisturizers,!
helps!to!maintain!healthy!skin!that!can!better!resist!breakdown!&!injury!
* Wear!an!athletic!shoes!which!fit!well!and!have!adequate!support,!with!thick,!absorbent!socks!
* Minor!foot!injuries!&!infections!(e.g.!cuts,!scrapes,!blisters!and!tinea!pedis):!treated!by!gentle!
cleansing!&!application!of!topical!antibiotic!to!maintain!a!moist!wound!environment!which!
help!to!prevent!ulcer!formation!
o Avoid!hot!soaks,!heating!pads!and!harsh!topical!agents!such!as!hydrogen!peroxide,!
iodine!(e.g.!Betadine)!and!astringents!(e.g.!witch!hazel).!!
o Inspected!by!physicians!for!any!minor!wound!that!does!not!heal!rapidly!
* Closely!monitor!foot!condition,!neuropathy!and!PVD!
* Good!glycemic!control,!HT,!hyperlipidemia!and!aspirin!!

Hyperosmolar7hyperglycemic7state7(HHS)77
Introduction!
* Previously!termed!hyperosmolar!hyperglycemic!nonketotic!coma!(HHNC)!
o Changed!because!coma!is!found!in!<20%!of!patients!with!HHS!
* Mortality:!~10*20%,!higher!than!DKA!
!
Diagnosis!
* Plasma!glucose!>33mmol/L!
* Effective!serum!osmolality!>320mOsm/kg!!
* Profound!dehydration,!up!to!an!average!of!9L!
* Serum!pH!>7.30!
* Bicarbonate!>15!mEq/L!
* Small!ketonuria!&!absent/low!ketonemia!
* Some!alteration!in!consciousness!
* Normal!anion!gap!
!
Trigger!
* Inadequate!administration!of!insulin!
* Infection:!pneumonia,!UTI,!GE,!sepsis!
* Infarction:!cerebral,!coronary,!mesenteric,!peripheral!
* Use!of!other!drugs:!steroid,!diuretics,!α/β!blocker!
* Chronic!disease:!renal,!heart!
!
!
!
!

Endocrine!*!24!
Presentation!
* Weight!loss,!polydipsia,!thirst,!lethargy,!fever!
* Dehydration,!tachycardia,!hypertension!(vs!DKA:!hypotension)!
* K!may!be!high!due!to!acute!renal!failure!
!
Management:!similar!to!DKA!
* Rehydration!
o Usually!required!6*10L!fluid!replacement,!as!patient!is!usually!very!dehydrated!
o If!plasma!Na!≥150,!start!with!0.45%!saline!
o Serum!urea!is!the!best!prognostic!factor!
* Insulin!
o Insulin!dosing!on!sliding!scale,!↓!by!half!of!that!for!DKA!
o Avoid!rapid!normalization!of!blood!glucose!in!1st!24!hours!to!↓!risk!of!cerebral!edema!
o Resume!oral!hypoglycemic!agents!when!patient!is!out!of!HHS!

Diabetic7ketoacidosis7(DKA)7
Presentation!
* 3!cardinal!signs:!dehydration,!overbreathing!(Kussmaul!breathing),!ketones!('fruity')!on!breath!
* Osmotic!symptoms:!thirst,!polydipsia,!polyuria!
* Abdominal!pain:!dull!persistent!discomfort!usually!centred!on!umbilicus!
* Vomiting!±!diarrhea,!anorexia!
* Confusion!±!shock!
* Signs!of!DM!&!complications!
!
Trigger!
* Infection!
* Missed!insulin!treatment!
* The!onset!of!previously!undiagnosed!diabetes!
* Severe!medical!illness!(e.g.!MI,!CVA)!/!psychological!stress!
!
Initial!investigations!!
* Plasma!glucose!!
* Urinalysis:!glucose,!ketones!
* ABG!
* CBC,!RFT!
* (CXR,!urine!micro/C/ST,!blood!culture)!!
!
Diagnosis!!
* Arterial!pH!<7.3!
* Plasma!glucose!>!14mmol/L!
* Bicarbonate!<15mmol/L!(high!anion!gap)!
* Moderate!ketouria!/!ketonemia!
!
Management!!
* Monitoring!!
o Glucose,!RFT,!ABG!hourly!!
o BP/P,!U/O,!RR,!conscious!level!hourly!!
o Wide!bore!NG!tube:!gastroparesis!is!common!
* Correction!!
o Fluid:!1L!NS/hour!initially!until!BP/P!stable,!then!100ml/hr!(titrate!against!urine!flow)!
!

Endocrine!*!25!
 ! If!serum!Na!>150mmol/l,!switch!to!0.45%!NS!
! If!serum!Na!<150mmol/l,!continue!0.9%!NS!
! When'plasma'glucose'drops'<14mmol/l,'switch'to'D5'!
o Insulin!!
! Initial!0.1*0.15U/kg!as!IV!bolus,!followed!by!infusion!
! Set!up!insulin!pump,!infuse!at!rate!of!0.1unit/kg/hour!!
! Aim!decrease!at!rate!of!3*4mmol/l/h!glucose!!
• If!no!decrease!in!glucose!in!1st!hour,!double!the!dose!to!achieve!this!rate!
• Excessively!rapid!correction!of!hyperosmolality!"!cerebral!edema!
! When'plasma'glucose'drops'<14mmol/l'"'0.05W0.1'unit/kg/hour!
• Adjust!dose!to!!maintain!blood!glucose!between!8*12mmol/L!
! When'plasma'glucose'<10mmol/l'"'start'IV'glucose!
! When!patient!is!fully!conscious!&!normal!diet!resumed,!start!twice!daily!
combination!of!short!&!intermediate!acting!insulin!/!multiple!daily!dose!
• Overlap!with!insulin!infusion!1*2!hours!before!sc!insulin!take!effect!
o K!replacement!!
! *!Common!to!have!normal!K!at!presentation!due!to!insulin!deficiency!&!acidosis!
! Add!20*40mmol!of!K!into!each!liter!of!IVF!if!have!good!urine!ouput!
! Monitor!K!hourly!then!2!hourly!
! If!<3.3mmol/l!"!stop!insulin,!give!40mmol!K!until!>3.3mmol/l!!
! If!>5.5mmol/l!"!stop!K!supplement!until!drops!
! Aim!serum!K!4*5mmol/l!!
o Bicarbonate!replacement!!
! Not!indicated!when!pH!>7.0!
• Precipitate!rapid!intracellular!K+!shift!with!hypokalemia!
• Tissue!anoxia!due!to!shift!of!O2!dissociation!curve!
• Cerebral!acidosis!due!to!decreased!pH!in!the!CSF!
• Sodium!overload!!
! If!pH<7.0,!give!50mmol!NaHCO3!over!1hour!(if!<6.9!"!100mmol!over!2!hours)!
! Repeat!ABG!after!infusion,!repeat!infusion!every!2!hours!until!pH!>7!
! *!Monitor!K!closely!as!alkali!shift!them!into!cells!!!
* DVT!prophylaxis!!
o Consider!5000U!heparin!Q8H!SC!in!comatose,!elderly!or!obese!patients!
o Should!be!continued!until!patient!is!mobile!with!no!evidence!of!dehydration!/!↑!in!
serum!osmolarity!
* Find!the!underlying!cause!!
o Infection,!treat!accordingly!!
o Medication!non*compliance!!
o Wrong!insulin!dosing!!
o Recent!surgery!or!MI!!

Endocrine!*!26!
 !
Hypoglycemia7
* Definition:!blood!glucose!<3.9!=!low!but!not!necessary!have!Sx,!<2.8!=!symptomatic!(Prof!R!Ma)!
!
Clinical!presentations!!
* Neuroglycopenic!symptoms:!drowsiness,!confusion,!seizure,!coma!!
* Sympathetic!overactivity:!sweating,!anxiety,!agitation,!palpitation,!hunger,!tremor!!
o Beware!of!masking!by!concurrent!beta*blockers!!!
!
!

Endocrine!*!27!
Whipple’s!triad!
* Symtpoms!known!/likely!to!be!caused!by!hypoglycemia:!sympathoadrenal,!neuroglycopenic!
* A!low!plasma!glucose!measured!at!the!time!of!symptoms!
* Relief!of!symptoms!when!glucose!is!raised!to!normal!
!
Etiology!!
* Fasting!hypoglycemia!(EXPLAIN)!
o EXogenous!drugs!(insulin,!OHA,!contaminated!viagra,!Alcohol,!aspirin!poisoning,!
pentamidine)!!
! In!DM!on!OHA/insulin:!hypogly!may!be!triggered!by!
• Poor!oral!intake!
• Vigorous!exercise!
• Inappropriate!insulin!/!drug!dose!
• New!injection!site!(inject!to!muscle!rather!than!skin!"!↑!absoprtion)!
• Concomitant!/!preceding!illness!
o Infection!commonly!cause!hyperglycemia!too!∴need!more!
frequent!H’stix!monitoring!
• Renal!failure:!↓!excretion!of!drugs!
o Pituitary!insufficiency!
o Liver!failure!
o Addison's!disease!
o Insulinoma,!Immune!hypoglycemia!
o Non*pancreatic!neoplasms!(retroperitoneal!fibrosarcomas,!hemangiopericytomas)!!
* Postprandial!hypoglycemia!!
o Early!DM!
o Dumping!syndrome!!
!
Investigations!!
* Plasma'ketones!
* Urine'sulphonyureas!
* Short'synacthen'test:!for!Addison’s!!
* Prolonged!fasting!test:!for!insulinoma!
o Fasting!for!72!hours,!vigorous!exercise!for!20min!at!72!hours!!
o H'stix!Q4H!+!symptomatic!
o Glucose,'insulin,'CWpeptide'at!Q24H!+!H'stix<2.2!!
o Terminate!when!H'stix!<2.2!!
* In!DM!patients!
o CBC:!WCC!–!systemic!infection!causing!hypoglycemia!even!increased!stress!level!
o RFT:!electrolyte!imbalance!
o Cardiac!Enzyme!!
! Silent!MI!in!the!long!standing!DM!patient!with!stress!caused!by!hypoglycemia!!
o Septic!workup:!↑!risk!of!UTI!and!pneumonia!in!DM!!
!
Management!outline!!
* Treat!the!hypoglycemia!
* Identify!and!treat!underlying!etiology!
* Education!if!patient!is!DM!(correct!usage!of!drugs,!avoid!missing!meals)!!
!
Initial!management!!!
* Conscious!patient!!
o Oral!syrup!!
* Decreased!consciousness!!
!

Endocrine!*!28!
 o Establish!iv!line!!
! D50'40ml'IV'stat'using!LARGE!VEIN!with!SALINE!FLUSH!!
• In!newborn:!use!D10!(5mg/kg)!instead!
! Followed!by!D10'drip'(followed!by!D5!or!D10!according!to!severity!of!
hypoglycemic!attack!and!previous!regimen!by!V!Wong)!!
o If!IV!line!cannot!be!established!!
! IM!glucagon'1mg'(does!not!work!in!DRUNK!/!starved!patient!)!/!oral'glucose'
after'airway'protection'!
* Monitor!!
o H'stix!every!1*2hrs!until!stable,!esp!if!cause!is!long*acting!insulin/OHAs!
o Then!review!the!drug!chart!to!stop!offending!drug!esp.!renal!impairment!(OHA)!!
!
Further!management!!
* After!single!episode!of!hypoglycemia,!explore!the!risk!factor!of!hypoglycemia!and!provide!the!
DM!education!to!patient!and!family!accordingly!!
Metabolic7syndrome7
Definition:!
* Central!obesity!
o BMI!>23!or!waist!circumference!>80cm!(F)!/!90cm!(M)!
* And!any!2!of!the!below!
o High!TG!>1.7mmol/L!(150mg/dL)!
o HDL*C!<1.0(M)!/!1.3(F)!mmol/L!(40mg/dL)!
! HDL!=!total!choleseterol!–!LDL!–!triglyceride!/!5!
o BP!>130/85mmHg!
o Impaired!glucose!regulation:!FPG!>5.5mM!
Consequence!
* 2*3x!↑!risk!of!premature!CVD!
* 4*5x!↑!risk!of!DM!
Hyperlipidemia7
Primary!hyperlipidemia:!genetic!causes!
!
Secondary!hyperlipidemia!
* Environmental:!diet!
* Other!disease!&!drugs!
! TG! Chol! HDL!
DM! ↑! ! ↓!
Obesity! ↑! ±! ↓!
Nephrotic!syndrome! ! ↑! !
Chronic!renal!dailure! ↑! ±! ↓!
Liver!disease! ! ↑! !
Hypothyroidism! ±! ↑! !
Alcohol!abuse! ↑! ! ↑!(small!dose),!↓!(large!dose)!
Thiazide! ↑! ±! !
Beta*blocker! ↑! ! ↓!
Steroid! ! ↑! !
Oral!contraceptive! ↑! ! !
Cyclosporine! ! ↑! !
Retinoid!(vit!A)! ↑! ! !
Phenytoin! ! ! ↑!
!
Treatment!
* For!hypercholesterolemia!
!

Endocrine!*!29!
 o Statin!(HMG!CoA!reductase!inhibitors)!
o Plant!stanols!
o Bile!acid!sequestrants!
o Ezetimibe:!inhibit!intestinal!cholesterol!absorption!
* For!hypertriglyceridemia!
o Fibrates:!clofibrate,!gemfibrozil,!bezafibrate,!fenofibrate,!ciprofibrate!
o Nicotinic!acid!
o Fish!oil!
Hyperprolactinemia7
Causes!!
* Physiological!
o Pregnancy!!
o Lactation!
o Nipple!stimulation!!
o Stress!!
* Pathological!
o Prolactinoma!(level!correlates!with!size)!!
o Pituitary!stalk!compression!(level!rarely!>2000)!!
o Chronic!renal!failure!
o Hypothyroidism!
o Liver!cirrhosis!!
* Drugs!!
o Antipsychotics!(phenothiazines,!risperidone,!clozapine)!!
o Antiemetics!(metochlorpramide,!prochlorperazine,!domperidone)!
! An!interesting!fact!is!that,!domperidone!does!not!cross!BBB,!but!mind!you,!
pituitary!HAS!NO!BBB!!!So!yes,!domperidone!causes!no!extrapyramidal!side!
effect!hence!its!use!in!Parkinson’s!disease!for!peripheral!dopamine!blockade,!but!
hyperprolactinemia!is!definite!!
o Dopamine!depleting!agents!(reserpine,!methyldopa)!!
o High!dose!estrogen!
o Verapamil!
o Cimetidine!!
!
Clinical!presentations!
* Mass!effect:!frontal!headache,!visual!field!defect,!CN!palsy!
* F:!galactorrhea!(30*80%),!oligo/amenorrhea,!infertility,!hirsutism,!acne,!dry!vagina!
o Famale!usually!presents!earlier!due!to!menstrual!disturbances!
* M:!loss!of!libido,!erectile!dysfunction,!gynaecomastia!(mild),!loss!of!hair,!galactorrhea!(<30%)!!
* Other!hormones!deficiency!in!macroadenoma!
!
Investigations!!
* Pregnancy'test!
* Serum'prolactin'level!(*send!for!both!diluted!and!undiluted!sample)!!
o Normal!!
! MALE!=!<375mU/l!!
! FEMALE!=!<625mU/l!!
o Macroprolactinemia:!a!polymeric!form!of!prolactin*antibiody!complex,!biologically!
inactive!but!assayed!
! ∴If!normal!clinical!feature!"use!other!assay!method!e.g.!PEG!precipitation!
o Hook'Effect:!very!high!prolactin!level!(e.g.!in!giant!prolactinoma)!will!paradoxically!
give!a!negative!immunoassay,!as!it!hinders!the!formation!of!a!antibody*sandwich!
! Overcome!by!serial!dilution!!
!

Endocrine!*!30!
* MRI!pituitary!
* RFT,!LFT,!TFT!
* Other!pituitary!hormone!assays!!
* Perimetry!!
!
Management!!
* Dopamine!agonist:!bromocriptine,'carbergoline,!Pergolide!(withdrawn!in!2007!due!to!heart!
valve!damage)!
o Carbergoline!is!superior:!better!control!of!hyperprolactinema,!better!shrinkage,!longer!
half*life!(convenient!dosage)!
o Withdrawal!of!drugs!can!be!considered!
! After!4!years!of!treatment!!
! No!MRI!tumor/!shrinkage!>50%!
! *!Need!at!least!2!years!monitoring!
o Dose!used!in!prolactinoma!much!less!than!in!parkinsonism,!no!report!of!fibrosing!
valvular!diseases!!
* Transphenoidal'hypophysectomy'±!post*op!adjuvant!radiation!!
o Indications!(*visual!disturbance!per!se!is!not!one)!!
! Intolerant!/!non*responsive!to!medical!treatment!!
! Apoplexy!
! CSF!rhinorrhea!!
o Complications!!
! Hypopituitarism,!cranial!DI!
! CSF!leakage,!bleeding!!
!
Prolactinoma!in!pregnancy!!
* Basics!!
o No!documented!fetal!risk!of!bromocriptine!!
o Microprolactinoma!5%!enlarges!!
o Macroprolactinoma!35%!enlarges!!
* Microadenoma!!
o Stop!bromocriptine,!MRI!if!sympatomatic!visual!problem!(don’t'be'stupid'to'monitor'
prolactin!)''
* Macroadenoma!!
o Stop!bromocriptine,!MRI!if!sympatomatic!visual!problem!!
o Prepranancy!transphenoidal!debulking!!
o Continue!bromocriptine!!
Acromegaly7
Causes!!
* Pituitary!growth!hormone!secreting!tumor!(>95%)!
* Hypothalamus!GHRH!tumor!
* Ectopic!GH/GHRH!(eg!Carcinoid)!!

Clinical!features!!
* Excessive!soft!tissue!growth!!
o Prominent!supraorbital!ridge!!
o Prognathism:!pronounced!lower!jaw!protrusion!due!to!mandibular!overgrowth!
o Wide!spaced!teeth!!
o Macroglossia!!
o Hoarseness!/!thick!&!deep!voice:!soft!tissue!swelling!of!the!vocal!cord!
o Large!palm!and!sole,!spade!like!hand,!thickened!heel!pad!!
o Increased!ring!and!shoe!size!!
!

Endocrine!*!31!
 o Increased!sweating!(sweaty!palm:!indicate!active!disease)!
o Axillary!skin!tags!(acrochordon)!
o Goiter,!hepatosplenomegaly!
o Oily!skin!
o **!Ask!for!old!photos!for!comparison!!!
* Pituitary!compression!!
o Bitemporal!hemianopia!!
! 70*80%!is!big!tumor!"!commonly!affect!visual!field!∴must!test!visual!field!!
• Vs!Cushing’s:!usually!small!tumor!
! Loss!of!temporal!visual!field!
• May!not!be!complete!bitemporal!hemianopia,!may!be!unilateral!/!only!
upper!/!lower!quadrant!
o Frontal!headache!!
o Hypopituitarism:!menstrual!irregularity!
!
Complications!!
* Cardiovascular:!commonest!cause!of!premature!death!
o HT,!LVH,!↓!EF!during!exercise,!HF!
* Respiratory!
o Obstructive!sleep!apnea!!
* Neoplastic!!
o Colonic!poly!and!CA!!
* Endocrine!!
o Diabetes,!hypercalcmia!(usually!due!to!coexistent!1°!hyperPTH),!MNG!
* Musculoskeletal!!
o Carpel!tunnel!syndrome,!arthropathy!(narrowed!joint!space),!2°!OA,!proximal!
myopathy!
!
Associations!
* MEN*1!(5%!of!acromegaly)!
o Pituitary!tumors,!hyperparathyroidism,!pancreatic!tumors!
* Carney!complex!!
o Spotted!skin!pigmentation!
o Cardiac!myxoma!
o Pituitary/thyroid/testicular!tumors!
o Primary!nodular!adenocortical!disease!with!ACTH*independent!Cushing!syndrome!
* McCune!Albright!syndrome!!
o Fibrous!dysplasia!!
o Cafe*au*lait!spots!!
o Precocious!puberty!!
o Acromegaly/!Cushing's!
!
Investigations!!
* Serum'IGF'!
o Reflect!the!integrate!effect!of!GH!
o For!screening,!if!normal:!active!acromegaly!ruled!out!!
* *!Growth!hormone!level!alone!is!not!useful!because!
o Fluctuate!by!sleep,!exercise,!fasting,!stress!!
o Fluctuate!by!short!half!life!20min!!
o But!undetectable!random!GH!"!very!unlikely!acromegaly!
* 75g'extended'OGTT'with'measurement'of'glucose'&'GH'for'3'hours'period!
o Failure!of!GH!suppression!to!<1!mU/L!!
!

Endocrine!*!32!
 o Look!for!coexisting!DM!!
* MRI'pituitary'with!contrast!
* Screen!for!complications!!
o Other!pituitary!hormonal!assay!!
o Perimetry!
o ECG!+!echocardiography!!
o Colonoscopy!!
o Serum!Ca!level!!
o DEXA!!

Management!!
* Transphenoidal'transphenoidal'hypophysectomy'(1st!line)!
o Cure!rate!90%!for!microadenoma!!
! Cure!=!IGF*1!normalized!/!OGTT*GH!suppression!to!<2ng/ml!
o Cure!rate!50%!for!macroadenoma!!
* Post*op!adjuvant!radiation!!
o External!beam!radiation!
o Highly!focused!stereotactic!radiotherapy!!
o S/E:!panhypopituitarism!!
* Drugs:!for!patient!not!fit!for!/!unwilling!to!have!OT!
o Dopamine!agonists!(bromocriptine,!carbergoline)!
! 30%!responsive,!but!cheap,!so!sometimes!as!first!line!trial!!
! S/E:!N&V,!constipation,!nasal!congestion,!postural!hypotension,!psychosis,!
restrictive!vavular!disease,!retroperitoneal!fibrosis!!
o Somatostatin!analogue!(Octreotide,!lantrotide)!
! 60%!responsive!
! S/E:!nausea,!vomiting,!gallstones,!impaird!glucose!tolerance!!
o GH!antagonists!(pegvisomant)!
! 95%!responsive!(only!stop!downstream!effect,!GH!level!may!not!↓,!may!even!↑)!
! S/E:!hepatitis!
! *!Monitor!by!serum!IGF*1!only!(not!GH!)!!
Hypopituitarism7
Causes!!
* Space!occupying!lesions!!
o Pituitary:!secreting!/!non*secreting!adenoma!!
o Adjacent:!craniopharyngioma,!optic!nerve!glioma,!meningioma,!carotid!aneurysm!
* Iatrogenic!!
o Radiation,!e.g.!post*NPC!RT!
o Surgery!!
* Infiltration!!
o Metastasis!!
o Hemochromatosis,!histoplasmosis,!sarcoidosis!!
* Infection!!
o Tuberculosis,!pyogenic!abscess!!
* Vascular!!
o Sheehan!syndrome:!massive!post*partum!hemorrhage!"!infarction!due!to!
vasoconstriction!
! Presentation:!unable!to!lactate!&!amenorrhea!!
o Pituitary!apoplexy!(bleeding!or!infarction)!!
* Congenital!!
o Kallman!syndrome!
o Cerebellar!ataxia!and!retinitis!pigmentosa!!
!

Endocrine!*!33!
!
Presentations!!
* Hormone!deficiency!
o Prolactin:!none!
o Growth!hormone:!puberty!cessation,!fine!wrinkles,!obesity,!muscle!weakness!
o Sex!hormone:!loss!of!libido,!infertility,!oligomenorrhea,!loss!of!body!hair,!osteoporosis
!
! The!1st!axis!to!be!affected,!because!it’s!not!essential!to!life!
! But!long*term!deficiency!"!still!have!Cx:!osteoporosis,!↓!muscle!bulk…!
! May!replace!testosterone!in!M!(S/E:!CA!liver:!anabolic)!
o Cortisol:!anorexia,!malaise,!nausea,!abdominal!pain,!postural!hypotension,!dizziness,!
hypoglycemia! !
o Thyroid:!weight!gain,!↓!appetite,!cold!intolerance,!constipation,!menorrhagia,!
depression! !
o ADH:!polyuria,!polydipsia,!confusion!!
* Mass!effect!!
o Bitemporal!hemoanopia!!
o Frontal!headache!!
o CN!palsy!(CN!3,!4,!6,!V1,!V2)!–!cavernous!sinus!
!
Investigations!!
* Hormonal!function!assay!!
o Prolactin!
o Free!T4!not!TSH!!
o LH,!FSH,!testosterone,!estradiol!
o Short!synacthen!test!
o Serum!sodium!and!osmolarity,!urine!osmolarity!!
o (IGF*1)!!
* Etiology!!
o MRI!pituitary!
! Normal:!posterior!pituitary!hyperintense!in!T1!!
!
Hormone!replacement!in!hypopituitarism!!
* Hydrocortisone'!
o 20*30mg/day!in!2!divided!dose!(low!dose,!compared!to!high!dose:!1000mg!BD!for!acute!
exacerbation!of!asthma!/!COPD!/!IBD)!
! 10mg!BD!or!20mg!OM!+!10mg!PM!(less!at!night!to!avoid!insomnia)!
o Increase!dose!in!stress!state!or!intercurrent!illness:!otherwise!may!have!Addisonian!
crisis!
! Stress!dose:!~40mg/day!(double!dose):!20mg!BD!
* Thyroxine'!
o 2ug/kg/day,!after!resuming!cortisol!axis!!
o Start!at!low!dose!in!elderly,!CV!disease!
* (Human!growth!hormone)!!
o Only!if!symptomatic!after!other!hormonal!replacement,!or!for!puberty!growth!!
* (Sex!hormones)!!
o GnRH/hCG!±!FSH!only!if!for!fertility!!
o Testosterone/!Estradiol!for!puberty!!
* DDAVP'!
o If!cranial!DI!present!
o Nasal!route!!!
! Not!oral!as!it’s!peptide!
!

Endocrine!*!34!
 ! Not!IV!otherwise!t½!is!very!short!
! But!nasal!route!is!also!not!so!reliable!as!absorption!variable!(e.g.!↓!when!nasal!
congestion)!
! New!drug:!sublingual!!
* **!Tell!patient!to!↑!replacement!in!times!of!stress!
!
Assessing!replacement!!
* Cortisol:!24h!urine!free!cortisol!
* Thyroid:!free!T4!
* (Growth!hormone):!IGF*1!
* (Sex!hormones):!free!testosterone!in!male;!clinical!in!female!!
* ADH:!serum!and!urine!osmolality!!
Adrenal7incidentaloma7
What!we!need!to!know!
* Functioning!vs!non!functioning!
* Any!malignant!potential!
!
Anatomy!
* Cortex:!mineralocorticoid!(zona!glomerulosa),!glucocorticoid!(z.!fasiculata),!sex!hormone!(z.!
reticularis)!
* Medulla:!catecholamine!
!
DDx!
* Functioning!(benign)!
o Adenoma!(52%)!
! Aldosterone*producing!(Conn’s),!cortisol*producing!(Cushing’s)!
o Pheochromocytoma!(11%)!
* Benign!non*functioning!!
o Cyst!(5%),!myelolipoma!(8%;!fat!+!bone!marrow),!hemangioma,!granuloma,!hematoma,!
amyloidosis,!ganglionueuroma!(4%)!
* Malignant!!
o Primary:!adrenocortical!carcinoma!(12%;!including!sex*hormone!producing),!
malignant!phaeochromocytoma,!neuroblastoma!(child)!
o Secondary:!metastatic!disease!(2%)!
* Pseudo*adrenal!!
o Renal,!pancreas,!spleen,!liver!
!
History!taking!
* Prior!malignancy!
* Young!onset!HT!
* S/S!of!excess!cortisol,!mineralocorticoid,!catecholamines,!sex!hormones!
!
Physical!examination!
* Look!for!cushingoid!features!
!
Investigation!
* Screen!for!functioning!tumor!
o Overnight!1mg!dexamethasone!test!"!Cushing’s!
o Increase!aldosterone!to!renin!ratio!(ARR)!"!renin!(low),!aldosterone!(high)!"!Conn’s!
o 24!hr!urine!catecholamines!(adrenaline,!noradrenaline,!dopamine),!metanephrine,!
normetanephrine,!VMA"!pheochromocytoma!
o Blood!DHEAS!(↑),!testosterone,!E2,!FSH!(↓),!LH!"!sex!hormone!producing!tumor!
!

Endocrine!*!35!
 o RFT!for!hypokalemia!"!Conn’s,!Cushing’s!
* Fine!needle!aspiration!
o Only!useful!to!rule!out!metastasis!
o MUST!exclude!pheachromocytoma!first!!!!
! Can!provoke!hemodynamic!instability!&!death!
* Imaging!!
o Look!for!size,!local!infiltration,!LN!enlargement,!characteristic!(well*/ill*defined)!
! Benign:!homogenous,!smooth!border!
! Malignant:!bilateral,!large!size,!heterogenous!attenuation,!central!necrosis,!
irregular!border,!local!invasion,!vascular!invasion,!regional!lymphadenopathy,!
distant!metastasis,!calcification!20*30%!
o **!Also!look!for!primary!tumor:!adrenal!tumor!may!be!metastasis!!
o Non*contrast!CT!scan!
! High!lipid!content,!low!attenuation!(<10HU)!"!confirm!adenoma!(in!70%!of!
adenoma)!
! 30%!of!adenoma!have!not!enough!lipid!to!show!low!attenuation,!i.e.!>10HU!
(lipid!poor)!"!do!contrast!CT!with!adrenal!protocol!
o Contrast!CT!with!adrenal!protocol!
! Calculate!adrenal!enhancement!washout!
! If!density!decrease!for!>50%!"!adenoma!
! If!<50%!"!may!be!malignant:!do!MRI/!biopsy!(must!rule!out!
pheochromocytoma!1st!to!avoid!HT!crisis!triggered!by!Bx)!
o MRI!
! Chemical!shift!MRI!=!adenoma!(signal!intensity!in!out*of*phase!decrease!>20%!
than!in*phase)!"!intensity!compared!with!spleen!not!liver!because!steatosis!!
o PET*CT!
! High!sensitivity!and!specificity!to!differentiate!benign!vs!malignant!adrenal!
lesion!
! Compare!SUV!(standard!uptake!value)!with!that!of!liver!
• Normal!adrenal!gland!SUV!=!0.95*2.46;!liver!1.5*2.0!
• Malignant!if!intensity!of!adrenal!gland!>!liver!!
! Increase!uptake!in!!
• Primary!malignancy!
• Secondary!tumor:!metastasis!
o Most!common!sites:!lung,!breast,!skin!(melanoma),!kidney,!
thyroid,!colon!!
• Pheochromocytoma:!false!+ve!
!
Management!
* Adrenalectomy!
o Indications!
! Hormone!secreting!(functional)!
! Malignancy!
• For!multiple!metastases!"!not!indicated!for!surgery,!for!conservative!
instead!
! Large!(>6cm,!optional!if!>4cm!(e.g.!fast!growing))!
Size'of'tumor' Risk'of'cancer' Recommendation'
<4cm! 2*3%! Observation!
4*6cm! 7%! Adrenalectomy!(if!pt!is!healthy)!
>6cm! 25%! Adrenalectomy!!
• Large!tumor!has!risk!of!hemorrhage!&!malignancy!
! Growing!tumor!on!serial!imaging!(repeat!6*12!months)!
!

Endocrine!*!36!
 o Approach!
! Adenoma:!laparoscopic!/!open!
! Carcinoma:!open!preferred!(may!need!en!bloc!resection!of!nearby!/!invaded!
organs)!
* FU!for!non*removal!incidentaloma!
o Repeat!imaging!3*6months!to!look!for!interval!change!
! USG!or!CT!with!contrast!
! Grow!>1!cm!"!surgery;!if!no!growth,!no!need!rescan!
o Repeat!hormone!test!every!12!months!x!4!yrs!
o 5*25%!grow,!3*4%!shrink,!20%!become!functional!
Cushing7syndrome7
Definition!
* Increased!free!circulating!glucocorticoid!
!
Etiology!!
* ACTH!dependent!(Cushing’s!disease)!
o Pituitary!adenoma!/!carcinoma!
o CRH!secreting!tumour:!hypothalamic,!ectopic!(e.g.!medullary!CA!thyroid,!prostate)!
o Ectopic!ACTH!producing!tumors!!
! Small!cell!lung!cancer!
! Bronchial!carcinoid!
! Medullary!thyroid!carcinoma!
! Pancreatic!carcinoma!
! Phaeochromocytoma!
* ACTH!independent!!
o Exogenous!steroids!
o Adrenal!adenoma!(60%)!/!CA!(40%)!!
o Adrenal!hyperplasia!(Carney!complex,!macronodular!adrenal!hyperplasia,!McCune!
Albright!syndrome)!!
!
Pseudocushings!(a!hypercortisolism!state)!!
* Depression,!eating!disorder,!stress!
* Obesity!
* Alcohol!excess!
* Liver!enzyme!inducer!(phenytoin,!carbamezepine,!phenobarbital,!rifamipcin)!!
o ↑!metabolism!of!dexamethasone!"!↓!suppression!effect!
* Increased!CBG!(estrogen,!pregnancy)!!
!
History!taking!
* Weight!gain!
* Growth!arrest!in!children!
* Polyuria,!polydypsia!(due!to!nephrogenic!DI!due!to!hypoK,!which!caused!by!the!
mineralocorticoid!activity!of!cortisol)!
* Loss!of!libido,!amenorrhoea!/!oligomenorrhoea!
* Insomnia,!depression,!psychosis!
* Muscular!weakness!
* Backache!(?!vertebral!collapse!due!to!osteoporosis)!
!
Physical!examination!(bold!=!more!pathological!signs)!
* Moon!face,!facial'plethora,!acne,!hirsutism,!frontal!balding!
o Hirsutism:!due!to!androgen!excess,!∴!not!seen!in!cases!due!to!excess!steroid!intake!
* Buffalo!hump,!supraclavicular!fat!pad!!
!

Endocrine!*!37!
* Truncal!obesity!with!thin!limbs:!‘orange!on!stick!appearance’!
* Purplish'striae!over!upper!arms,!thighs!&!abdomen!(>1cm!wide)!
o Weaken!skin!"!elastin!break!even!by!normal!stretching!"!depressed!purple!scars!on!
healing!
* Thin!skin,!bruising,!skin!infection,!poor!wound!healing,!edema!
* Proximal'muscle'weakness''
* Fractures:!vertebrae,!ribs!
* Hyperpigmentation!in!ACTH!excess!
* Look!for!clues!that!may!suggest!use!of!steroid,!e.g.!renal!Tx,!asthma!
* End!by:!BP!(HT),!urine!glucose!/!H’stix!(DM!/!glucose!intolerance)!!
!
Complication!
* Cardiovascular:!HT,!fluid!retention!(mineralocorticoid!activity)!
* Metabolic!risk:!DM/!glucose!intolerance,!central!obesity,!hypercholesterolemia,!hypoK!
* MSK:!osteoporosis,!proximal!muscle!weakness!
* Soft!tissue:!thinning!of!skin,!bruises!&!striae!
* Immune!system:!immunosuppression!with!risks!of!opportunistic!infection,!easy!infection,!poor!
wound!healing!
* Psychiatric:!irritability,!depression,!anxiety,!psychosis!
* Reproductive!disorders,!e.g.!amenorrhea!(F),!decreased!fertility!(M)!
* Renal!stone!
* Androgen!excess!(not!in!exogenous!Cushing’s):!acne,!hirsutism!
* For!iatrogenic!Cushing’s!(rare!in!endogenous!Cushing’s):!avascular!necrosis,!glaucoma,!
posterior!subcapsular!cataract!!
!
Investigations!
* **!Never!image!before!biochemical!confirmation!
o Incidentaloma!common!in!both!adrenal!and!pituitary!gland!!
o MRI!detects!only!70%!of!microadenomas!
* Screening!
o Overnight!dexamethasone!suppression!test!!
! 1mg!at!11pm,!cortisol!at!8*9am!!
! Cutoff:!50!nmol/l!!
! False!+ve!in!pseudocushings!(∴!stop!liver!enzyme!inducing!drugs!before!test)!
o 24!hour!urine!free!cortisol!x!3!
! Cutoff:!>280nmol/24h!
o Late!night!(2300*2400)!salivary!cortisol!(for!loss!of!normal!nadir):!cutoff!4nmol/L!!
o Midnight!cortisol!(for!loss!of!normal!nadir):!sleeping!<50,!awake!<207nmol/L!
* Confirmation!
o Low!dose!dexamethasone!suppression!test!(LDDST)!
! 0.5mg!Q6H!for!8!doses!(2!days)!
! Cutoff!level:!<50!nmol/L!!
* Discrimatory!
o Plasma!ACTH!level!
o High!dose!dexamethasone!suppression!test!!
! 2mg!Q6H!for!8!doses!(2!days)!
! Cortisol!suppressible!in!pituitary!disease,!not!in!adrenal!Cushing!/!ectopic!ACTH!
o CRH!(corticotrophin!releasing!hormone)!stimulation!test!!
! 100ug!CRH!IV,!cortisol!at!2!hour!
! Normal:!↑!above!baseline!of!plasma!ACTH!of!>50%!&!cortisol!of!>20%!
! Exaggerated!ACTH!/!cortisol!response!suggests!pituitary!dependent!disease!
! Ectopic!sources!do!not!respond!!
!

Endocrine!*!38!
 o Bilateral!inferior!petrosal!sinus!sampling!!
! Confirmation!(ACTH!C:P>2:1,!or!CRH!C:P>3:1)!&!localization!of!ACTH*producing!
pituitary!adenoma!
* Anatomical!
o CT/MRI!adrenals!!
! Adrenal!veins!sampling!/!adrenal!scintigraphy!(radiolabeled!cholesterol!
derivatives)!!
o MRI!pituitary!(FN=!40%!absent)!
o CXR!(look!for!lung!cancer)!

!
!
Management!
* Depends!on!the!etiology!causing!Cushing’s!syndrome!
* Exogenous!!
o Stop!(slowly)!and!perform!LDSST!(back!to!normal,!cortisol!should!be!suppressed!by!
LDSST)!
* Cushing's!disease!!
o Transphenoidal!microadenomectomy!±!radiotherapy!
o Bilateral!adrenalectomy:!as!a!last!resort!
! With!pituitary!RT!to!prevent!Nelson’s!syndrome!(rapid!enlargement!of!pituitary!
adenoma!/!development!of!a!locally!invasive!pituitary!tumor!secreting!high!
ACTH!level!after!removal!of!both!adrenal!glands,!resulting!in!pigmentation)!
* Adrenal!tumor!
o Laparoscopic!unilateral!adrenalectomy!!
! Good!for!adenoma,!very!poor!for!carcinoma!
o Adrenal!enzyme!inhibitor:!metyrapone!(GI!upset,!easy!breakthrough!of!Cushing’s),!
ketoconazole!(synergistic!with!metyrapone,!inhibit!adrenal!steroidogenesis,!S/E:!skin!
rash,!hepatotoxic!"!check!LFT),!etomidate!
o Adrenolytic!agents:!mitotane!(oPDDD,!palliation!of!adrenal!CA)!
o Glucocorticoid!antagonists:!mifpristone!(RU486)!
o Somatostatin!analogues:!octreotide,!pasireotide!
!

Endocrine!*!39!
 o Radiotherapy!for!CA!adrenal!
* Ectopic!ACTH!
o Excision!of!the!secreting!tumor!
o Bilateral!adrenalectomy!(need!lifelong!replacement!afterwards!&!pituitary!RT!to!
prevent!Nelson’s!syndrome)!
Primary7Hyperaldosteronism7
Etiology!
* Aldosterone'producing'adenoma'(Conn's'syndrome)'80%!
* Bilateral'adrenal'hyperplasia!20%!
* Adrenocortical!CA!
* Familial!hyperaldosteronism!type!1!(Glucocorticoid!remediable!aldosteronism,!GRA)!
o Autosomal!dominant!
o Fusion!of!2!proteins:!11B*hydroxylase!&!aldosterone!synthase!during!crossing!over!in!
meiosis!"!share!the!same!ACTH*dependent!promoter!
o Treatable!by!steroid!
* Familial!hyperaldosteronism!type!2!
o Autosomal!dominant!
o Exact!mechanism!unknown!!
o Not!treatable!by!steroid!
!
DDx!
* Liddle’s!syndrome!(pseudoaldosteronism)!
o AD,!ENaC!not!degraded!"!↑!Na!reabsorption!&!K!loss!
* Syndrome!of!apparent!mineralocorticoid!excess!
o AR,!inactivated!enzyme!in!kidney!"!↑!local!conc.!of!cortisol!"!high!level!of!cortisol!
cross*react!&!activate!mineralocorticoid!receptor!
!
Diagnosis!
* High!Na,!low!K,!alkalosis,!low!Cl!
o K!level!can!be!normal!"!not!sensitive!enough!as!screening!
o Urine!K:!>20mmol/L!"!renal!loss!
* Screening!
o Indications!
! Young!HT!(e.g.!onset!<40/45!years),!HT!with!hypoK,!resistant!HT,!HT!requiring!
multiple!medications!
o Not!on!ACEI,!BB,!diuretics,!steroids,!K!for!4*6!weeks!
o Spot!aldosterone!to!renin!ratio!(ARR)!
! High!ARR!(cutoff!=!555)!in!primary!hyperaldosteronism!
• >!1000!"!pathologomic!!
! ↑renin,!↑aldosterone:!
• Renovascular'hypertension!e.g.!Renal!artery!stenosis!
• Diuretics'
! ↓renin,!↑aldosterone!(negative!feedback!on!renin):!
• Primary'hyperaldosteronism'
! ↓renin,!↓aldosterone:!
• Exogenous'mineralocorticoids'
• Cushing’s'syndrome:'if'features'do'overnight'dexamethasone'
suppression'test'for'screening!
• Liquorice!
• Liddle’s!syndrome,!syndrome!of!apparent!mineralocorticoid!excess!
• Pheochromocytoma!
* Confirmatory!!
!

Endocrine!*!40!
 o Salt!loading!test!(measure!ARR)!
! Inappropriately!non*suppressed!aldosterone!level!in!hypervolemia!state!
* Discriminatory!
o Balance!study!(discriminates!between!adrenal!hyperplasia!+!adrenal!adenoma)!
! Principle:!↑!salt!load!the!patient!–!normally!aldosterone!should!be!suppressed!
! Day!0*2:!Salt!loading!2g!tds!+!replace!K!deficit!!
• To!rule!out!dehydration!causing!hyperaldosteronism!
! Day!3!
• Admit,!ensure!normokalemia!
• Send!spot!urine!Na!&!K!to!ensure!sufficient!salt!loading!(so!should!be!↑Na!
in!urine!because!excess!Na!excreted!in!urine)!
o Make!sure!normokalemia!
! Day!4!
• 9am:!supine!renin!and!aldosterone!!
• Ambulate!for!4!hours!
• 1pm:!erect!renin!and!aldosterone!
o If!hyperplasia!"!aldo!↑!when!upright!
! Sensitive!to!postural!change!(angiotensin)!like!normal!
o If!adenoma!"!paradoxical!drop!in!erect!aldosterone!!
! Still!respond!to!ACTH!drive!∴!lower!in!noon!(diurnal!rhythm)!
* Localization!studies!
o CT/!MRI!of!adrenals!–!anatomic!imaging!
o Adrenal!vein!sampling!
o Adrenal!scintigraphy!(iodocholesterol!scan)!–!functional!imaging!
!
Treatment!
* Adenoma!"!laparoscopic!adrenectomy,!with!4*week!pre*op!spironolactone!
o BP!may!persist!in!40*65%!of!cases!due!to!!
! Nephrosclerosis!after!prolonged!uncontrolled!HT!
! Underlying!essential!HT!
o BP!response!to!spironolactone!pre*op!usu.!predict!response!to!surgery!!
* Hyperplasia!"!medical!Rx!
o Spironolactone!/!eplerenone!(mineralosorticoid!receptor!antagonist)!
o Amiloride!(K*sparing!diuretics)!
o *!Not!do!surgery!for!bilateral!problem!(excision!will!lead!to!adrenal!crisis)!
* Glucocorticoid!remediable!aldosteronism!"!Dexamethasone!!
Pheochromocytoma77
* Pheachromocytoma!=!Dusky!color!when!stained!under!chromium!salt!
* A!neuroendocrine!tumor!of!the!medulla!of!adrenal!glands!(originating!from!chromaffin!cells)!
* Secrete!high!amounts!of!catecholamine,!most!commonly!noradrenaline!(α1!"!
vasoconstriction)!&!adrenaline!(α1,!β1,!β2!"!bronchospasm)!
!
10%!rule!
* Malignant!!
o Presence!of!metastasis!(in!place!where!neuroectodermal!tissue!not!normally!found)!/!
local!invasion!
o NOT!differentiated!from!histology!
* Extra*adrenal:!paraganglioma!(originate!in!ganglia!of!sympathetic!nervous!system)!
* Bilateral!!
* Familial!!
o The!familial!cases!are!more!insidious!onset!than!the!non*familial!ones!
!

Endocrine!*!41!
 o 24hr!urine!catecholamine!test!for!adrenaline/noradrenaline!may!be!only!slightly!
higher,!may!need!more!sensitive!test,!e.g.!metanephrine!/!normetanephrine!
* Multiple!
!
Clinical!presentations!
* Clinical'triad:'sweating,'headache,'palpitation''
o Headache:!intermittent,!episodic,!sustained'
* Fluctuating'HT'
* Postural!hypotension!/!dizziness!
o Excessive!catecholamine!secretion!"!!
! Down!regulation!of!adrenoceptor!
! Constant!vasoconstriction!
! Depleted!intravascular!volume!
o "!loss!of!auto*regulation!when!standing!up!
* Flushing,!pallor!
* Abdominal!pain,!nausea,!constipation!!
* Anxiety!
* Fatal!reason:!HF,!MI!due!to!coronary!artery!dissection!
!
DDx!
* OSA:!↑!adrenaline!
* Hyperthyroidism!
!
Associations!
* MEN!2a:!thyroid!medullary!CA,!parathyroid!hyperplasia!
* MEN!2b:!thyroid!medullary!CA,!mucosal!neuroma,!marfarnoid!
* Neurofibromatosis!
* Von!Hippel!Lindau!Syndrome:!RCC,!retinal/cerebellar!hemangioblastoma,!pancreatic!
neuroendocrine!tumor!(autosomal!dominant)!
* *!Do!genetic!study!if!young!"!RET!oncogene!(MEN),!succinate!dehydrogenase!gene!
(SDHB/SDHD),!(+/*!NF1,!VHL)!
!
Diagnosis!
* Screening!&!confirmatory!(by!Shirley!Liu)!
o 24h!urine!catecholamines/metacholamines/VMA!for!3!times!!
! Switch!anti*HT!to!CCB!/!alpha!blockers!/!hydralazine!
• Avoid!BB:!↓!central!symp!activity!
• Avoid!ACEI:!↓!degradation!of!bradykinin!"!↓!symp!
! Norepinephrine!metabolized!to!normetanephrine!and!VMA!(vanillylmandelic!
acid)!
! Measure!dopamine!is!not!very!useful!because!most!urinary!dopamine!derived!
from!renal!extraction!
* Confirmatory!(if!24!hours!CAT!borderline!results:!Shirley!Liu)!
o Clonidine!suppression!(observe!for!drop!in!plasma!catecholamines!3!hours!oral!drug)!
o Serum!chromogranin!A!(co*release!from!adrenals)!!
* Discriminatory!
o CT/!MRI:!for!adrenal!
o MIBG!(metaiodobenzylguanidine)!scan!(Schintigraphy)!
! A!radiolabeled!molecule!(iobenguane)!similar!to!noradrenaline!
! For!detecting!extra*adrenal!/!multiple!tumors!
o Adrenal!vein!sampling!
!
!

Endocrine!*!42!
Management!!
* Pre*op!preparation!
o Localization,!malignant!/!benign,!related!to!MEN!
o Normalize!HR!&!BP:!start!α!blocker!2!weeks!before!OT!
! Very!important!!Intra*operative!hemodynamic!fluctuation!is!lethal!!!
! Alpha!blockade!first!!!
• Avoid!hypertensive!crisis!due!to!unopposed!alpha!stimulation!by!beta!
blockade!
o β!blocker!"!↓!HR!&!contractility!but!afterload!still!high!"!HF!
• Phenoxybenzamine!(irreversible!non*selective!α!blocker)!
/phentolamine!(reversible!non*selective!α!blocker)!/!labetolol!(α/β!
blocker)!x!2!days!!
• How!to!identify!adequate!alpha!blockade?!Postural!hypotension,!
dizziness,!nasal!congestion,!SBP!80*160!
! Then!β!blocker!(propranolol)!
! Volume!repletion:!Hct!from!high!return!to!normal!
* Excision:!adrenalectomy!
o Intra*op!
! Must!ligate!vein!before!resection!
! Reduce!manipulation!of!adrenal!gland,!otherwise!leak!into!vein!"!crisis!
o Post*op!need!ICU!admission!with!BP!monitoring!
* **!Bilateral!"!subtotal!adrenectomy!to!preserve!cortical!function!
* FU!patient!after!excision!for!recurrence!"!yearly!urine!metanephrine!(for!10!years)!
Sex7hormone7secreting7tumor7
* Extremely!rare!
* Mostly!are!virilizing!(vs!feminizing)!
* Malignant!until!proven!otherwise!
o Virilizing:!about!1/3!
o Ferminizing:!almost!100%!
* Biochemical!diagnosis:!24!hour!urine!testosterone!&!androgens!
o Pulsatile!secretion!"!need!24!hour!urine!collection!
* Rx:!adrenalectomy!(to!exclude!adrenocortical!CA)!
Addison’s7disease7(Primary7Adrenal7Insufficiency)7
Causes!of!adrenal!insufficiency!
* Primary'!
o Autoimmune!80%!!
o Infections!
! TB!20%!
! HIV!opportunistic!infection:!CMV,!fungal,!Mycobacterium!avium*intracellulare!
! Histoplasmosis!
o Congenital!
! Congenital!adrenal!hyperplasia!(CAH)!
! Polyglandular!syndrome!(autoimmune!polyendocrine!syndrome)!
! Adrenoleukodystrophy!
o Hemorrhage!
! Waterhouse!Friderichsen!syndrome:!fulminant!meningococcemia!
! Bleeding!tendency!!
! Physical!trauma!
o Iatrogenic!
! Bilateral!adrenectomy!
! Radiation!!
!

Endocrine!*!43!
 o Infiltrative!
! Malignancy:!lung,!breast,!stomach,!colon!cancer,!melanoma,!lymphoma!
! Sarcoidosis,!amyloidosis!!
! Hemochromatosis!
o Drugs!!
! Exogenous'steroid'
! Ketoconazole,!aminogluthemide,!metyrapone,!opDDD!!
* Secondary:!hypopituitarism!(rare)![NOT!Addison’s]!
!
Clinical!presentations!
* Fatigue,!lethargy,!malaise,!weight!loss,!anorexia,!low!grade!fever!!
* Generalized'weakness'
* N&V,!abdominal!pain,!diarrhea,!constipation,!salt!craving!
* Hypotension,!postural!hypotension!(hypovolaemia!in!mineralocorticooid!deficiency,!loss!of!
vascular!tone!in!glucocorticoid!deficiency),!shock!
* Hypoglycemic!symptoms!
* (Pigmentation,!dehydration,!pituitary!compression!symptoms)!!
!
Associations!
* Autoimmune!hypothyroidism!!
* Type!I!DM!
* Pernicious!anemia!
* Vitiligo!
!
Primary!Vs!secondary!
* Primary!more!hypoK!and!hypotension!(loss!of!aldosterone!activity)!
* Pigmentation!if!chronic!primary!
* No!frontal!headache,!visual!disturbances!
!
Investigation!
* Biochemistry!!
o RFT:!low'Na,!high!K!
o VBG!
o Hypoglycemia!
o Hypercalcemia!
o Eosinophilia,!neutropenia,!ormochromic!normocytic!anemia!
* Screening!endocrine!test!
o Short!Synacthen!test!
! 250ug!synacthen!IV/IM!
! Plasma!cortisol!at!0,!30min!
! Addison!excluded!if!peak!>550nmol/l!&!>200nmol/l!increment!
o Low!dose!short!synacthen!test!
! More!sensitive,!but!require!accurate!dilution!of!the!vial!!!
! 1ug!synacthen!IV!(diluted!by!adding!into!a!250ml!NS,!and!withdraw!1ml)!!
! Plasma!cortisol!at!0,!(20),!30min!
• 20!is!for!some!early!peaking!individuals!!
! Addison!excluded!if!peak!>550nmol/l!+!>200nmol/!increment!!
o Random!cortisol!NOT!useful!(but!tested!during!addisonian!crisis)!
! Even!cortisol!is!‘normal’,!e.g.!600,!it!may!already!be!maximally!stressed,!so!when!
do!LDSST!"!inadequate!response!(e.g.!rise!just!from!600!to!700)!
* Confirmatory!endocrine!test!!
o Insulin!tolerant!test!(ITT)!!
!

Endocrine!*!44!
 o Glucagon!stimulation!test!!
* Discrimatory!endocrine!test!!
o Morning!9am!ACTH'!
! Raised!in!primary!Addison’s!(>300nmol/l)!!
! Low!in!secondary!cause!!
o Long'synacthen'test:!for!equivocal!case!
! 1mg!depot,!0,6,24!hours!
! Delayed!rising!in!secondary!Addison’s!(e.g.!prolonged!exogenous!steroid!use)!
after!10!hours!
! Remain!low!in!primary!Addison!!
* Anatomical!!
o CT!adrenal!
o CXR/AXR!for!calcification!in!TB!!
o MRI!pituitary!!
* 21*OH/17*OH/P450scc!adrenal!autoantibodies!
* Aldosterone!to!renin!ratio!(for!detecting!aldosterone!deficiency)!!
* Etiological!
o TB!workup:!early!morning!sputum!x!3!for!TB!smear,!AFB!stain,!PCR!if!high!suspicion,!
CXR!
o Autoimmune!workup:!fasting!blood!glucose,!serum!B12,!RBC!folate!if!macrocytic!
anaemia!
!
Treatment!!
* Replace!volume!!
* Replace!hydrocortisone!!
o 15*30mg!daily,!in!2*3!divided!dose,!but!avoid!giving!at!evening!leading!to!insomnia!!!
o Depend!on!results!of!LDSST!
! If!500*550!"!no!need!maintenance!dose!"!HC!10mg!BD!for!stress!cover!
! <500!"!required!HC!10mg!BD!maintenance!dose!&!20mg!BD!stress!cover!
o Can!teach!to!self!double!the!dose!if!febrile!illness,!injury,!stress!or!strenuous!exercise!!
o (Dexamethasone!is!stronger!that!prednisolone!stronger!than!hydrocortisone)!
* Replace!fludrocortisones:!0.1mg/day!
o Only!start!after!tapered!to!replacement!dose!of!glucocorticoid!
o Lower!dose!with!hydrocortisone!(which!has!mineralocorticoid!activity)!
o Monitor!plasma!renin!activity!

Addisionian7crisis77
Who?!
* Previously!undiagnosed!Addison’s!disease!
* Disease!suddenly!affecting!adrenal!function,!e.g.!adrenal!hemorrhage!
* Known!Addison’s!with!intercurrent!problem,!e.g.!infection,!trauma!
!
High!risk!of!adrenal!suppression!for!long!term!steroid!
* >3!weeks!
* Daily!dose!prednisolone!>20mg!
* Cushoigoid!features!
* Night!time!dose!
!
Presentation!
* Severe!vomiting!&!diarrhea!"!dehydration!
* Low!BP!
* Syncope,!confusion,!slurred!speech,!severe!lethargy!
* Hypoglycemia!
!

Endocrine!*!45!
* HypoNa,!hyperK,!hyperCa!
* Psychosis,!convulsion!
* Sudden!penetrating!pain!over!legs,!lower!back!/!abd!
!
Management!!
* Fluid!resuscitation!with!NS!if!shock!
* Blood!x!RFT,!ABG,!glucose,!random!cortisol!
* Replacement!hydrocortisone!100mg!Q6H!±!fludrocortisone!!
* Monitor!BP/P/K/H'stix!
* Treat!precipitating!factors!(e.g.!infection,!AMI)!if!any!!
Congenital7adrenal7hyperplasia77
* Autosomal!recessive!
!
21*hydroxylase!(21*OH)!deficiency!!
* 90%'of'all'CAH'!
* Presentation!
o Ambiguous!genitalia!+!precocious!puberty!with!virilisation!(↓!E2,!↑!androstenedione!&!
testosterone)!!
o Salt!losing!(↓!aldosterone!
&!DOC)!
o Addison's!disease!(↓!
cortisol,!↓!adrenaline)!
* Investigation!!
o High!ACTH!
o High!17WOH'
progesterone'!
o Young!bone!age!!
!
3β*hydroxysteroid!dehydrogenase!(3β*HSD)!deficiency!!
* Gonadal!ambiguity!in!both!sexes!!
* Survival!rare!!
!
11β*hydroxylase!(11β*OH)!deficiency!!
* Ambiguous!genitalia!+!precocious!puberty!with!virilisation!
* Hypokalemic!hypertension!(↑!DOC)!
* Addison's!disease!(↓!cortisol)!
!
17α*hydroxylase!(17α*OH)!deficiency!!
* Famale!genitalia!(prototype),!failure!of!puberty!(↓!androgen!&!estrogen)!
* Hypokalemic!hypertension!(↑!DOC!&!corticosterone)!
Multiple7endocrine7neoplasm7(MEN)7syndromes77
Features!!
* Can!be!hyperplasia!/!adenoma!/!CA!
* Younger!age!of!onset,!more!aggressive!&!commonly!recur!
* Multi*focal!involvement!within!a!gland!
* Synchronous!/!metachronous!involvement!
!
Types!!
* MEN*1!!
o Parathyroid!+!Pituitary!+!Pancreatic!!
o Autosomal!dominant,!MEN1!tumor!suppressor!gene!
!

Endocrine!*!46!
* MEN*2:!activatin!mutation!of!RET!
o MEN*2a!(Sipple!syndrome)!
! Thyroid!medullary!CA!(100%)!+!pheochromocytoma!(20%)!+!parathyroid!
(50%)!
o MEN*2b!(William!syndrome)!
! Thyroid!medullary!CA!+!pheochromocytoma!+!Marfanoid!/!Mucosal!neuroma!!
o Familial!medullary!CA!of!thyroid!
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Endocrine!*!47!
Geriatrics)
History)taking .................................................................................................................................... 1!
↓)GC .................................................................................................................................................. 1!
Fall..................................................................................................................................................... 1!
Malnutrition ...................................................................................................................................... 3!
Dysphagia .......................................................................................................................................... 4!
Tube)feeding...................................................................................................................................... 5!
NG!tube!feeding .......................................................................................................................................................................................... 6!
Percutaneous!endoscopic!gastrostomy!(PEG) .............................................................................................................................. 6!
!

History)taking))
) Premorbid!status!
) Caring:!self!care,!food,!medication!
) Ambulation:!dementia!features!
) ADL:!
o Basic:!feeding,!grooming,!dressing,!transfer,!toileting,!bathing,!ambulation,!continence!
o Instrumental:!writing,!reading,!cooking,!cleaning,!shopping,!management!meds!/money,!
travelling!!
) Fall!history!!
) Carer!distress/carer!issue!
) Social!support:!any!MSW!visit!regularly!
↓)GC)
DDx!
) Infection,!sepsis!
) CVS:!MI!(hypoxia!&!↓!CO)!
) CNS:!stroke,!infection,!head!injury!
) Endocrine!&!metabolic:!electrolytes,!hypoglycemia!
) Respiratory:!respiratory!failure,!CO2!retention!
) Drug!&!toxin!
) **!Depression!!
Fall)
In!order!to!walk,!you!need:!
) Sensory!
o Vision,!cerebellum,!proprioception!
) Central!processing!
o Good!nutrient!supply:!O2,!blood,!glucose!
) Motor!
o Bone,!joint,!muscle,!coordination!
!
DDx!
) Sensory!
o Visual:!cataract,!glaucoma!(↓!visual!field)!
o Inner!ear!problem!
o Proprioception:!degenerative!
) Central!!
o Drugs:!e.g.!sedative,!CNS!suppression,!drugs!causing!postural!hypotension…!
o Seizure,!dementia!
o MI,!arrhythmia,!HF!
o Vasovagal,!orthostatic!hypotension,!carotid!hypersensitivity!
!

Geriatric!)!1!!
 o Hypoglycemia,!anemia!
o Sepsis,!e.g.!UTI!
) Motor!
o Stroke:!weakness,!spasticity!(most!common!),!hemineglect,!sensory!loss!
o Parkinson!!
o MSK:!arthritis,!contracture,!muscle!wasting,!myopathy!(e.g.!statin),!proximal!leg!
weakness!(steroid)!
!
History!taking!
) LOC,!convulsive!features!
) Prior!palpitation!/!chest!pain!/!chest!discomfort!
) Limb!weakness!
) Vertigo,!postural!dizziness!
) HI!
!
Physical!examination!
) GCS,!external!head!injury!
) Visual,!cataract!
) Upper!limb!
o Power!
o Parkinsonism!
o Cerebellar!sign!
o Pronator!drift:!the!most!sensitive!sign!to!test!for!old!stroke!(UMNL)!
! Flex!the!arm!at!shoulders,!supinate!forearms,!close!his!eyes!&!hold!the!position!
! Tapping!palm!of!out!stretched!hands!"!↑!effect!
! Positive!result!=!unable!to!maintain!supination!
• Indicate!spasticity!including!UMNL!
• Forearm!pronates!"!contralateral!pyramidal!tract!lesion!
• Drift!upwards!(overshoot)!"!cerebellar!lesion!
) Lower!limb!
o Tone!!
o Jerks!(brisk!"!old!stroke),!plantar!reflex!
o Power,!muscle!atrophy!
o Joint!arthritis!(warmth),!contracture!
o Leg!length!discrepancy!
o Proprioception!
) Gait!
) Neck:!carotid!bruit!
) Postural!BP!
!
Investigation! Avoid!anti)cholinergic!in!elderly!(e.g.!
) CBC,!L/RFT,!TFT! cough!syrup,!anti)histamine)!due!to!
) B12,!folate! various!S/E!
) Blood!glucose! ) Acute!glaucoma!
) Urinestix!! ) Constipation!
) ECG,!CT!brain! ) Urine!retention!
) Pelvic!XR,!C!spine!XR! ) ↓!cognition!
) MMSE! ) "!↑!risk!of!fall!!!
) Bladder!scan!(test!for!residual!volume)!
o BPH/constipation:!↓!venous!return!to!heart!during!straining!"!common!to!have!AMI!or!
cardiac!events!after!going!to!the!toilet!
!
!

Geriatric!)!2!!
Management!
) Primary!/secondary!prevention!(↓!incidence!/!prevent!recurrence)!
o Correct!reversible!causes!
! Stop!offending!drug!
! Remove!cataracts!!
o Environmental!modification:!lighting,!clear!obstacles!in!aisle!
o Strengthen!muscle!by!physical!exercise!under!supervision!
o Spasticity!"!prime!relaxation!before!moving!(nervousness!will!cause!associated!
spasticity)!
o More!supervision:!more!surveillance!rather!than!physical!restraints!is!required!
) Tertiary!prevention!(minimize!ill!effect!of!falls!&!fractures)!
o Treat!osteoporosis,!hip!protector,!floor!mat!
o Teach!patient!how!to!fall!properly!(e.g.!land!on!hip)!&!how!to!get!up!after!fall!
Malnutrition))
High!risk!in!elderly!
) Physical!
o Impaired!regulation!of!appetite!
o Rigid!stomach!
o No!teeth!
o Malabsorption!
o Disease:!drugs,!chronic!disease,!dysphagia!
) Psychological:!depressed,!dement!
) Social:!isolation,!poverty,!OAH,!habit!
!
Significance!!
) ↑!mortality:!e.g.!surgery,!sepsis!
) Impaired!immunity:!protein,!vit!A,!C,!Fe,!Zn,!selenium!
) Impaired!healing:!protein,!vit!C,!Zn!
) Cognitive!impairment:!Vit!B,!C!
) Muscle!weakness,!osteoporosis!"!fall,!#!
) Anemia:!Fe,!folate,!Vit!B12!
) Constipation!
!
History!
) Weight!change:!10%!in!6!months!
o No!matter!how!fat!originally,!if!weight!↓!for!10%!=!malnutrition,!a/w!↑!mortality!
o Loss!of!muscle!mass!due!to!restricted!calories,!prone!to!micronutrient!deficiency!
) Appetite!
) Stomach!pain/diarrhea!
) Disability!
!
Physical!examination!
) Loss!of!subcutaneous!fat:!face,!Below!clavicle,!rib!cage,!upper!arms!
) Muscle!wasting:!thighs,!arms!
) Edema!
) Ankle,!face,!hands!
!
Causes!
) Neurological!dysphagia!!
o Choke!/!cough!on!liquid!(vs!mechanical!dysphagia:!solid!food!get!stuck),!slow!to!eat!
(take!long!time!to!swallow)!
o Causes:!dementia,!stroke,!Parkinsonism!!
!

Geriatric!)!3!!
) Refusal!to!eat!
o Depression!
o Advanced!dementia!
! Loss!of!appetite!(vs!early!dementia:!↑!appetite,!eat!whatever!they!see)!
! Altered!taste!
! Impaired!recognition!of!food!!
! Eating!apraxia:!don’t!know!how!to!chew!/!swallow!
! Dysphagia!
! Pain!in!mouth:!aphthous!ulcers,!bitten!tongue!!
!
Management!
) Neurological!dysphagia!
o Food!texture:!soft,!blenderized!(semi)solid!is!the!best!texture,!put!in!thickener)!
o Sit!up!posture!
o Chin!down:!protect!larynx!–!food!is!less!likely!to!enter!larynx!
o Patience,!feed!slowly!
o Tube!feeding:!last!resort!!
) Refusal!to!eat!
o Increase!appetite!
! Stop!dietary!restrictions:!e.g.!DM!patients!
! Appetizer!
! Social:!dining!room,!activities,!exercise,!OAH!management!
! Medical!
• Depression!
• Vitamins!(B!&!C),!zinc!
• Stop!drugs!that!affect!appetite!
• Appetite!stimulant!
o Megestrol!acetate!(Megace®):!but!risk!of!DVT!in!long)term!use!
(antiestrogenic!effect)!
o Small!frequent!feeds!
o Environmental!clues!for!feeding!
o Supplement!
! Increase!nutritional!density!
! More!flavor!
! Vitamin!&!mineral!supplement!
! Oral!supplement!in!between!meals!
! Enteral!feed!
o Supervise!feeding,!feeding!assistance!
Dysphagia))
Factors!needed!for!swallowing!
) Conscious!to!swallow!"!do!GCS!
) Cerebellum:!coordination!of!muscles!during!swallowing,!e.g.!epiglottis!
) Bulbar!nerves:!CN9,!10!"!gag!reflex!(both!movement!&!sensory)!
o Soft!palate!paralysis!"!every!time!drink!fluid!"!come!out!from!nose!(nasal!escape)!
o Bulbar!palsy:!lower!motor!neuron!lesion!
o Psudobulbar!palsy:!due!to!recurrent!stroke,!upper!motor!neuron!lesion!"!jaw!jerk!
normal!
) Patent!aerodigestive!tract!"!sensory!of!obstruction,!e.g.!foreign!body,!tumor!
!
Dysphagia!Vs!odynophagia!
) Dysphagia:!worse,!may!be!CA!
) Odynophagia:!pain!when!swallow,!more!likely!inflammation,!less!likely!CA!
!

Geriatric!)!4!!
 o Fungal!esophagitis:!immunocomprimised!
o RT)induced!esophagitis:!NPC/!oropharynx!
!
Complication!
) Malnutrition!
) Aspiration!(food!/!saliva)!"!Pneumonitis!"!Pneumonia!
o Poor!oral!hygiene!"!if!aspirate!saliva!"!higher!risk!of!infection!
) Bronchiectasis!after!recurrent!pneumonia!
) Increased!mortality!
!
Swallowing!test!
) Bedside!swallowing!test!(by!nurse:!screening)!
o Nurse!will!do!a!preliminary!swallowing!test:!try!1)5ml!of!water!on!teaspoon!&!observe!
for!any!choking!
o If!ok!"!give!puree!diet!1st,!wait!for!ST!to!perform!a!formal!swallowing!test!
) Bedside!swallowing!test:!50!ml!of!water/puree!"!observe!for!swallowing!(look!for!swallowing!
effort!externally)!&!choking!(if!cough!"!fail)!
o Silent!aspiration:!no!choking!(no!cough!reflex)!even!if!food!go!into!larynx!
o Puree!is!more!easy!to!swallow!as!it!forms!food!bolus!easier!
o Use!water!as!screening!test!in!stroke!patients!
) Fibreoptic!endoscopic!evaluation!of!swallowing!!
o See!via!endoscopy!while!patient!swallow!puree!!
) Videofluoroscopic!swallowing!study!(VFSS):!definitive!test!for!aspiration!risk!
o Swallow!liquid!barium,!see!whole!motion!from!oral!cavity!to!esophagus!
o Can!try!different!maneuvers!(e.g.!posture)!&!texture!of!food!to!assess!whether!they!↓!
risk!(can!look!at!the!extent!of!aspiration)!
!
Feeding!methods!
) Thickener!"!NG!tube!"!gastrostomy!(PEG)!"!TPN!
Tube)feeding)
Indications!
) Dysphagia:!commonest!cause!
) Poor!oral!intake!
) Impaired!consciousness!
) Malnutrition!
!
Mode!of!milk!delivery!
) Intermittent!bolus!by!gravity!
) Continuous!pump!feeding!!
o May!be!safer!in!bedbound,!unconscious!patients!
o No!evidence!that!it!↓!incidence!of!aspiration!/!diarrhea!
!
Complication!
) Electrolyte!alterations!(46%):!low!calcium,!sodium,!potassium!
) Hyperglycemia!(35%):!esp!in!DM,!as!whole!body!is!not!prepared!for!food!(lack!of!cephalic!
phase!in!eating)!
) Diarrhea!(33%)!/!constipation!!(30%)!
o Diarrhea!due!to!infected!milk,!lactose!intolerance,!osmotic!load,!gastrocolic!reflex!!
) Vomiting!(20%):!if!milk!enter!too!quickly!
) Tube!clogging!(13%)!
) Aspiration!Pneumonia!
o Causes!
!

Geriatric!)!5!!
 ! Improper!administration!
! Relaxation!of!esophageal!gastric!junction!"!reflux!!
! Reduced!cough!reflex!
! Foreign!body:!bacteria!colonize!the!tube!
! Neglect!of!oral!hygiene!
o Prevention!
! Tube!feeding!ensures!nutritional!intake,!but!does!not!prevent!AP!
! Safe!administration!–!propped!up,!slow!delivery!speed!!
! Reduce!feeding!volume!
! Oral!hygiene!!
) Psychological:!confusion,!depression,!physical!restraint!
) Malpositioning!(15%):!if!stay!in!eso!but!not!enter!stomach!(fine!Entriflex!may!curl!up!during!
insertion!and!not!entering!stomach)!"!aspirate!(∴!check!by!pH!/!gurgling!/!CXR!before!feed)!
) Poor!oral!hygiene:!↑!risk!of!aspiration!pneumonia!!
) Gastrointestinal!bleeding!
o Esophagitis:!laxity!of!esophageal!junction!(NG!tube),!gastric!acid!reflux!(PEG)!
o Gastritis!(usually!a/w!infection)!"!coffee!ground!aspirate!!

NG)tube)feeding)
) NG!tube!↓!risk!but!not!prevent!aspiration!pneumonia!
o Still!have!upper!respiratory!secretion!"!may!still!need!frequent!suction!
) After!withholding!RT!feeding,!start!slowly!
o If!feed!too!much!in!the!beginning!"!stimulation!"!↑!respiratory!secretion!"!worsen!
respiration!
o Can!use!milk!pump!feeding!rather!than!bolus!(just!let!the!milk!fall!by!gravity)!to!slower!
rate!of!feeding!
) Long!term!NG!tube!may!cause!a!lot!of!Cx,!e.g.!
o Impair!swallowing!coordination!
o Induce!nasal!&!pharyngeal!secretion!"!nasal!congestion!
o Risk!of!aspiration:!eso!sphincter!cannot!close!
) **!In!bed!bound!RT!elderly:!need!to!check!oral!hygiene!&!sacral!sore!from!time!to!time!

Percutaneous)endoscopic)gastrostomy)(PEG))
Indication!
) Dysphagia,!e.g.!post)NPC!RT!(in!these!patients:!need!to!check!whether!they!can!open!mouth!
wide!enough!for!OGD,!due!to!radiation)induced!fibrosis)!
!
Vs!NG!tube!
) ☺!Better!tolerated!(recommended!for!long!term!tube!feeding)!
) ☺!Less!tube!blockage:!higher!diameter!
) ☺!Less!frequent!replacement!
) ☺!Lower!aspiration!risk!
o *!Still!can’t!prevent!all!aspiration!pneumonia:!caused!by!upper!airway!secretion!
) No!difference!in!incidence!of!pneumonia!
) $!Invasive!"!operative!risk!
) $!Local!sepsis!
) $!Leakage!
) $!Esophagitis:!cause!gastric!acid!reflux!!
) $!Difficult!to!replace!
) $!High!risk!if!patient!self)remove!it!(e.g.!demented!patient)!before!fistula!formation!"!
peritonitis!∴!patient!selection!is!very!important!!!
!

Geriatric!)!6!!
GI!
Parotitis ..........................................................................................................................................2!
Dyspepsia .......................................................................................................................................2!
Functional!dyspepsia...........................................................................................................................................................................3!
Gastroesophageal3reflux3disease3(GERD) .........................................................................................3!
Barrett's3esophagus ........................................................................................................................7!
Esophageal3motility3disorders .........................................................................................................7!
Achalasia ...................................................................................................................................................................................................7!
Scleroderma.............................................................................................................................................................................................8!
Diffuse!esophageal!spasm..................................................................................................................................................................8!
Upper3GI3Bleeding ...........................................................................................................................8!
Peptic3Ulcer3(PU) .............................................................................................................................9!
Managements!of!dyspepsia............................................................................................................................................................10!
Management!of!bleeding.................................................................................................................................................................10!
Management!of!perforated!peptic!ulcer...................................................................................................................................12!
Management!of!Gastric!outlet!obstruction..............................................................................................................................13!
NSAIDs!induced!Peptic!ulcer!diseases ......................................................................................................................................13!
Helicobacter3pylori3infection .........................................................................................................14!
Acid3suppression3therapy ..............................................................................................................16!
Middle3GIB....................................................................................................................................16!
Obscure3bleeding ..........................................................................................................................16!
Deranged3liver3function.................................................................................................................17!
Cholestasis....................................................................................................................................17!
Acute3hepatitis..............................................................................................................................17!
Hepatitis3A ....................................................................................................................................18!
Hepatitis3B ....................................................................................................................................19!
Chronic!Hepatitis!B!infection ........................................................................................................................................................20!
Hepatitis3C ....................................................................................................................................24!
Hepatitis3D ....................................................................................................................................27!
Hepatitis3E.....................................................................................................................................27!
Alcoholic3liver3disease ...................................................................................................................27!
Alcoholic!complication.....................................................................................................................................................................28!
NonQalcoholic3Fatty3liver3Disease...................................................................................................29!
Cirrhosis........................................................................................................................................29!
Ascites ..........................................................................................................................................32!
Spontaneous3bacterial3peritonitis3(SBP) ........................................................................................35!
Esophageal3variceal3bleeding ........................................................................................................36!
Portal3hypertensive3gastropathy ...................................................................................................38!
Liver3failure...................................................................................................................................38!
Hepatorenal!syndrome!(HRS) ......................................................................................................................................................39!
!

GI!$!1!
Hepatic!encephalopathy!(HE).......................................................................................................................................................40!
Hepatopulmonary-syndrome .........................................................................................................................................................41!
Paracetamol3overdose ..................................................................................................................42!
Vascular3problem3in3liver ..............................................................................................................42!
Ischemic!hepatitis ..............................................................................................................................................................................42!
Cardiac!cirrhosis.................................................................................................................................................................................42!
Budd!Chiari!syndrome .....................................................................................................................................................................43!
Venoocclusive!disease!(Hepatic!sinusoidal!obstruction!syndrome) ...........................................................................43!
Autoimmune3hepatitis ..................................................................................................................43!
Primary3biliary3cirrhosis3(PBC) .......................................................................................................44!
Primary3Sclerosing3Cholangitis3(PSC) .............................................................................................45!
Wilson's3disease3(hepatolenticular3degeneration) .........................................................................46!
Primary3hemochromatosis ............................................................................................................47!
AlphaQ13antitrypsin3deficiency.......................................................................................................48!
Liver3transplantation.....................................................................................................................49!
Porcelain3gallbladder ....................................................................................................................49!
IgG4Qrelated3systemic3disease .......................................................................................................49!
Autoimmune!pancreatitis!(AIP)...................................................................................................................................................50!
Constipation .................................................................................................................................50!
Diarrhea........................................................................................................................................50!
Constipations ................................................................................................................................51!
Inflammatory3Bowel3Disease3(IBD) ................................................................................................51!
Ulcerative!colitis!(UC).......................................................................................................................................................................53!
Crohn’s!disease!(CD).........................................................................................................................................................................56!
Splenic3abscess..............................................................................................................................61!
Splenic3infarct ...............................................................................................................................61!
Esophagogastroduodenoscopy3(OGD) ...........................................................................................61!
Physical3examination3(Abdominal3exam).......................................................................................64!
Drugs ............................................................................................................................................68!
Proton!pump!inhibitor!(PPI) .........................................................................................................................................................68!
Biologics!(E.g.!Infliximab!for!IBD)...............................................................................................................................................68!
!
Parotitis3
Approach!to!facial!swelling!
$ Look!at!opening!of!the!parotid!duct:!any!discharge,!stone!
$ Examine!for!any!facial!nerve!palsy!
$ Test!for!serum!amylase:!↑!in!parotitis!
$ USG!/!XR:!any!stone!@!parotid!duct!
Dyspepsia33
Causes!!
$ Functional!dyspepsia!!
$ Peptic!ulcers!
$ GERD!
!

GI!$!2!
$ Gastric!cancer!!
$ **!The!reason!for!having!dyspepsia!is!not!due!to!production!of!more!gas,!but!due!to!motility!
problem!affecting!the!removal!of!gas!from!stomach!

Alarming!features!!
$ Age!>45!
$ Nocturnal!attacks!
$ Vomiting!
$ Weight!loss!
$ GIB!
$ NSAID!usage!
$ Family!history!of!gastric!cancer!!
!
Management!protocol!!
$ Age!>40!/!alarming!features!!!straight!to!endoscopy!!
$ Age<40!&!no!alarming!features!!
o Test!and!treat!
o If!not,!PPI!trial!
o If!not,!endoscopy!(make!the!diagnosis!of!functional!dyspepsia)!!

Functional3dyspepsia3
Rome!III!criteria!
$ >1!of!the!following!!
o Bothersome!postprandial!fullness!!
o Early!satiation!
o Epigastric!pain!
o Epigastric!burning!!
$ No!evidence!of!structural!disease!that!explain!symptoms!!
$ Last!>3!months!
$ Onset!for!>6!months!ago!!
!
Management!!
$ Reassure!patient!!Look!for!psychological!stressors!
$ If!HP!positive!!!triple!therapy!!
$ Anti$secretary!agents!!
o Antacid:!minimal!usefulness!!
o H2!blocker!
o PPI!!
$ Prokinetic!agents:!minimal!usefulness!!
o Domperidone!(D2!antagonist)!
o Metochlorpramide!(D2!antagonist)!
o Itopride!(D2!antagonist!+!acetylcholineseterase!inhibitor)!
o S/E:!hyperprolactinemia,!extrapyramidal!side!effects,!affect!other!drug!absorption!!
Gastroesophageal3reflux3disease3(GERD)3
Definition!
$ Reflux!of!gastroduodenal!content!back!to!esophagus!
o Not!necessary!acid,!anything!is!ok)!
!
Introduction!!
$ Reflux!is!normal!when!postprandial,!there!is!tLESR!(transient!lower!esophageal!sphincter!
relaxation)!letting!gas!to!be!released!
$ Pathological!when!causing!symptoms!or!complications!
!

GI!$!3!
$ GERD!is!more!a!western!disease!(~10%!vs!30%),!but!trend!in!Asia!increasing!!
$ Severity!of!disease!is!determined!early!and!patients!tend!to!continue!with!that!phenotype!!
!
Protective!mechanism!!
$ Esophagus!!
o Saliva!!
o Esophageal!peristalsis!(disease:!scleroderma,!prolonged!reflux!with!scaring)!!
" Secondary!peristalsis!to!clear!the!food!content!from!esophagus!
$ OGJ!!
o LES!
" Pressure!>6mmHg!
" Length!>2cm!!
" Intra$abdominal!length!>1cm!!
o Phrenico$esophageal!ligament/!angle!of!His!(distended!fundus!push!to!OGJ)!!
" Normally!oblique!!!ball!valve!effect!
o Crural!muscle!(when!abdominal!pressure!increase)!!
$ Stomach!!
o Rosette!gastric!rugae!!
o Gastric!emptying!!
!
Cause!of!reflux!
$ Increase!frequency!of!tLESR!
$ Shorten!high!pressure!zone!(normally!4cm!!!2$3cm)!
o Have!a!habit!of!eating!rapidly!and!large!amount!of!high!fatty!content!food!!!gastric!
stasis!!!back!pressure!at!LES!!!damage!LES!
$ Damage!to!other!anti$reflux!mechanisms!
o E.g.!hiatus!hernia!
" LES!is!above!esophageal!hiatus!!!thoracic!cavity!is!–ve!pressure!during!
inspiration!(vs!intra$abd!is!always!+ve)!!!acid!reflux!up!&!form!a!pocket!

Risk!factors!!
$ Obesity!
o Weakened!connective!tissue!!!↑!risk!of!hiatus!hernia!
o Tend!to!eat!large!amount!of!high!fatty!food!!!shorter!high!pressure!zone!
$ Smoking,!alcohol,!coffee,!chocolate!
$ Genetic!factor!
$ *!Hp!infection!is!PROTECTIVE!!(esp!in!Asians)!!
!
Clinical!presentation!!
$ Acid!regurgitation!(more!common!in!Chinese:!60%)!
o Esophagus!is!more!resistant!to!alkaline!/!bile!content,!so!less!symptoms!caused!by!
things!other!than!acid!
o Study!showed!that!there’s!an!acid!pocket!on!top!of!the!food!content!in!the!stomach!
(food!more!distal,!acid!layer!on!top),!so!reflux!acid!after!meal!
$ Retrosternal!/!epigastric!heartburn!20%!(Ill$defined!in!non$English!speaking!population)!
$ Laryngeal!irritation!
$ Asthma,!chronic!cough,!sleep!apnea,!aspiration!!
!
Complications!!
$ Erosion,!ulcer,!bleeding!
$ Stricture!
$ Barrett!esophagus,!adenoCA!(1%!per!year!from!Barrett)!!
!

GI!$!4!
!
Investigations!!
$ PPI#inhibition#test#(therapeutic#trial)#!
o Omeprazole!20mg!or!40mg!(doubled)!bd!x!2!wks!!
o Good!sensitivity!and!specificity,!only!after!pH!study!!
$ OGD#!
o Not!sensitive:!only!25%!of!patients!have!erosion,!most!are!NERD!(75%)!!
o Indications!
" Atypical!/!alarming!symptoms!!
" Not!responsive!to!PPI!trial!!
" **!Should!be!done!in!every!GERD!patient!in!HK,!as!the!prevalence!of!upper!GI!
cancer!is!high!(‘scope!&!treat’!in!HK!vs!‘test!&!treat’!(test!Hp)!in!the!West)!
o Los#Angeles#classification#!
" Grade!A:!mucosal!break!≤5!mm!long,!not!continuous!between!mucosal!folds!
" Grade!B:!mucosal!break!>5mm!long,!not!continuous!between!mucosal!folds!
" Grade!C:!mucosal!break!continuous!between!2!mucosal!folds!
" Grade!D:!mucosal!break!≥75%!of!esophageal!circumference!
o Savary#and#Miller#(1978)#Classification#of#reflux#esophagitis#!
" Grade!I:!≥1!non!confluent!lesion!with!erythema!and!edema!
" Grade!II:!superficial!mucosal!erosion!
" Grade!III:!circumferential!erosion!with!luminal!narrowing,!islands!of!
edematous!squamous!mucosa!(cobblestone!esophagitis)!!
" Grade!IV:!esophageal!ulcer,!Barrett!́s!epithelium,!strictures!
$ 24#hour#esophageal#pH#study#(gold!standard:!most!SN!&!SP,!but!invasive!and!not!readily!
available)!!
o Indications!
" When!diagnosis!is!equivocal!!
" For!preoperative!assessment!!
o Procedure!!
" Catheter!placed!at!5cm!above!LES!!
" Event!button!to!record!symptoms,!body!position!and!meals!!
o Results!
" DeMeester#score#!
• A!score!of!>14.72#shows!significant!reflux!(2!SD)!!
o But!may!still!have!severe!S/S!even!<14.72!in!HK!patients!
• 6!Parameters!(in!comparison!to!mean!values!in!normal!subjects)!!
o Percent!total!time!pH<4!
o Percent!Upright!time!pH<4!
o Percent!Supine!time!pH<4!
o Number!of!reflux!episodes!!
o Number!of!reflux!episodes!≥!5!min!
o Longest!episode!(min)!
" Fraction#time#pH<4#>4%#!
" (Philip#Chiu:#%#of#total#time#pH<4#>5%)!
$ Esophageal#Manometry#!
o Indications!!
" Preoperative!assessment!!
" To!exclude!achalasia!/!other!esophageal!motility!disorder!
" Can!also!locate!the!LES!to!aid!the!placement!of!pH!probe!for!pH!study!
o Defective!LES!if!any!of!the!followings!occur!
" Pressure!<!6mmHg!!
" Overall!lengths!<2!cm!!
!

GI!$!5!
 " Abdominal!length!<1cm!!
o May!also!show!impaired!esophageal!motility!(IEM)!due!to!chronic!reflux!
!
Management!outline!!
$ Clinical!diagnosis!made!+!Endoscopy!for!alarming!features!!
$ Lifestyle!modifications!
$ Standard!dose!PPI!once!daily!for!4$8!weeks!!
o If!symptom!resolves,!try!to!step!down!!
o If!symptom!persists,!endoscopy!if!not!done,!think!about!reasons!(poor!compliance,!
inadequate!dosing,!nocturnal!acid!breakthrough,!non$acid!reflux,!wrong!diagnosis!e.g.!
achalasia)!
$ Surgical!therapy!when!indicated!(*considered!equivalent!to!long$term!PPI)!
!
Management!details!!
$ Life!style!modification!(virtually!minimal!effect!on!reflux,!but!they!confer!WIDER!benefits,!so!
recommend)!!
o Weight!reduction!
o Smoking!cessation!
o Avoid!acidic!/!irritative!food!
o Avoid!food!that!causes!reflux!(fatty,!caffeine,!chocolate,!mint)!
o Night!time!symptoms!!!avoid!eating!<3!hour!before!bed,!bed!elevation!!
o Postprandial!symptoms!!!small!frequent!meal,!avoid!lying!down!after!meal!!
$ Initial!treatment!!
o Proton#pump#inhibitor#(esomeprazole,!rabeprazole,!lansoprazole)!!
" Once!daily!for!4$8!weeks!!
" S/E!
• Nausea,!diarrhea,!headache,!dizziness!
• Increased!risk!of!pneumonia!
• Increased!risk!of!GE!&!clostridium!difficile!infection!!
• Increased!risk!of!osteoporosis!
• Affect!thyroxine!&!clopidogrel!absorption!and!effect!!
o H2#blockers#!
" Also!effective!when!compared!with!placebo,!but!inferior!to!PPI!!
$ Maintenance!treatment!(usually!needed!because!most!patients!with!GERD!relapses!after!
stopping!initial!treatment)!!
o Contraindication!to!step!down!Rx!(need!continuous!lifelong!standard!dose!PPI)!
" Severe!esophagitis!!
" Complications:!bleeding,!dysplasia,!stricture!!
o Step!down!!
" To!continuous!low$dose!PPI!
" To!continuous!H2!blockers!
" To!on!demand!PPI!
" To!on!demand!H2!blockers!(rapid-TOLERANCE!)-!
$ Endoscopic!(NOT!in!any!current!guidelines,!still!under!investigations)!!
o Endoscopic#suturing#devices#!
" Insert!stitches!in!gastric!cardia!to!strength!LES!!
" Technically!demanding!and!long!time!needed!!
" Reduce!tLESR!!
o Radiofrequency#!
" RF!directed!to!8!points!in!cardia!!
o Injection#of#bulking#agents#!
$ Surgical:!open!/!lap!!
!

GI!$!6!
 o Indication!!
" Patients!with!GERD!responsive!to!PPI,!but!refuse/intolerant!to!medications!
• Patient!who!are!not!responsive!to!PPI!may!have!wrong!diagnosis,!need!
further!investigations!!
" To!prevent!dysplasia!&!adenoCA,!to!induce!regression!of!Barrett's!!
o Types!
" Nissen#Fundoplication#(complete!/!total)!
• 3!steps:!reduce!hiatal!hernia!if!any,!repair!crural!defect!&!360°!wrap!
around!esophagus!by!fundus!!
• After!meal,!stomach!distends,!and!the!intragastic!pressure!transmit!to!
lower!esophagus,!acting!as!a!sphincter!!
" Tourpet#Fundoplication#(posterior!partial:!posterior!270°)!
• Longer!OT!duration!&!higher!recurrence!rate!!
• But!less!post$op!dysphagia!!
" Dor#fundoplication#(anterior!partial:!anterior!180$200°)!
• The!preferred!way!as!it!causes!less!dysphagia!(though!the!data!failed!to!
demonstrate!statistically!significant!results)!
o Complications!!
" Complication!rate!is!not!high,!peri$op!mortality!only!<0.5%!
• But!very!difficult!to!adjust!technically!
o Too!loose!!!recurrence!of!symptoms!
o Too!tight!!!dysphagia!
" Vagus!nerve!injury!during!dissection!of!crus!muscle!!!gastroparesis,!GOO!
(pylorus!not!relax)!
o Success!rate:!83%!symptomatic!control!(asymptomatic!not!require!PPI)!in!2!years,!
75%!in!5!years!
Barrett's3esophagus3
$ Endoscopically!visible!columnar!epithelium!
o Vs!sliding!hernia:!not!have!rugae!in!the!part!with!gastric!mucosa!
$ Glandular!metaplasia!under!histological!examination!
!
Prague!classification!of!Barrett!esophagus!(by!OGD)!
$ The!Prague!C!(circumferential)!and!M!(maximal!extent)!criteria!
o M:!maximal!length!(including!tongues)!of!Barrett!esophagus!
o C:!length!of!the!circumferential!Barrett!segment!!
!
Management!!
$ Long!term!PPI!
$ Regular!surveillance!of!CA!eso!
o If!low!grade!dysplasia!!!need!to!see!whether!it’s!active!esophagitis,!because!active!
inflammation!may!be!misinterpreted!as!low!grade!dysplasia.!∴!Need!to!repeat!biopsy!
after!esophagitis!heal!
o If!high!grade!!!high!risk!of!adenoCA!!!need!Rx,!e.g.!submucosal!dissection,!RFA!
!
Esophageal3motility3disorders33
Achalasia33
$ Dysphagia!of!liquid!and!solid!food,!sometimes!regurgitation!
$ BE:!beaklike!appearance!of!distal!esophagus!
$ Definitive!diagnosis!by!manometry!
$ Treatment!
!

GI!$!7!
 o Can!try!nitrates,!calcium!channel!blockers!!
o Endoscopic!dilatation,!botox!!
o Heller's!myotomy!!

Scleroderma33
$ Atrophy!of!smooth!muscles!of!lower!2/3!of!esophagus!!
$ BE:!dilation!of!distal!esophagus!with!loss!of!peristaltic!contractions!!

Diffuse3esophageal3spasm33
$ Disorganised!non$peristaltic!contractions,!due!to!dysfunction!of!inhibitory!nerves!!
$ Sharp!substernal!chest!pain!radiating!to!arm,!chest!and!jaw!(mimics!heart!disease)!lasting!
from!sec!to!mins!(always-need-to-rule-out-cardiac-pain!!),!dysphagia!coexist!!
$ BE#=!loss!of!normal!peristaltic!contractions!below!level!of!aortic!arch,!with!numerous!
uncoordinated!simultaneous!contractions,!the!corkscrew#esophagus!
$ Rx:!nitrates/!calcium!channel!blockers!!
Upper3GI3Bleeding3
DDx!of!coffee!ground!vomiting!
$ GI:!PU,!bleeding!varices,!gastritis,!gastric!CA,!pancreatitis,!cholangitis!
$ Resp!(hemoptysis):!pneumonia,!PE,!bronchiectasis,!lung!CA,!TB!
!
Presentation!
$ Coffee!ground!vomiting!/!hematemesis!
o Non$specific,!e.g.!long$term!NG!tube!!!esophagitis!!!coffee!ground!aspirate!
o Should!also!look!at!other!evidence,!e.g.!↑!urea,!↓!Hb!
$ Melena!/!tarry!stool!/!hematochezia!
o Blood!is!a!good!laxative,!∴!if!continuous!UGIB,!should!have!melena!(have!tarry!stool!
in!PR)!!
o Blood!Fe2+!!!Fe!3+!(black)!
$ Orthostatic!hypotension!
$ Syncope!!
!
History!
$ Drug!history!
o NSAID,!aspirin,! ,! (salisylate)!
!
Investigation!
$ CBC!d/c!!!Hb!
$ LFT!!!liver!derangement!in!cirrhosis!
$ RFT!!!↑!in!urea!(DDx:!hypovolemia)!
$ CaPO4!
$ Clotting!
$ T&S!
$ Amylase!
$ Sputum!x!C/ST,!urine!x!C/ST,!stix!
$ ECG!
$ CXR±!AXR!!!bowel!perforation!
!
Management!
$ Blood!transfusion:!aim!Hb!≥7!&!~9!if!have!co$morbidities!e.g.!CAD!
$ Risk!stratification!
o Rockall!score:!base!on!age,!shock,!co$morbidity!&!endoscopic!findings!(not!count!Hb!)!
!

GI!$!8!
 ! Score!0! Score!1! Score!2! Score!3!
Age! <60! 60$79! >80! !
Shock! None! Pulse!>100,! SBP<100! !
SBP!>100!
Co$ None! $! Cardiac!disease! Renal,!liver,!
morbidity! malignancy!
Diagnosis! Mallory$Weiss! All!other! Upper!GI! !
tear!/!no!lesion! diagnosis! malignancy!
Signs!of! None!/!black! $! Blood!in!lumen,! !
recent!bleed! spots! active!
" Predict!mortality!
o Blatchford!score:!base!on!urea,!Hb,!SBP,!pulse,!melena,!syncope,!liver!disease!&!HF!
!
Management!if!patient!on!anti$platelet!/!anti$coagulant!
$ Warfarin!!!stop!warfarin!immediately!
o When!GIB!stopped,!don’t!give!warfarin!immediately!
o Give!aspirin!within!1st!week!!!have!survival!benefit:!↓!CV!risk!
$ Aspirin!!!best!resume!aspirin!at!day!3$7!
o Aspirin!t½!~!1week!!!if!resume!aspirin!within!1!week!!!action!of!aspirin!not!yet!
lost!
$ If!ACS!risk!is!high!!!start!aspirin!with!high!dose!PPI!
!
In!cases!of!massive!GIB!with!multiple!endoscopy!done,!monitor!for!
$ Rebleeding:!melena,!hematemesis,!Hb!↓,!urea!↑,!BP!
$ Aspiration!due!to!UGIB!
$ MI!/!ischemia!due!to!stress!&!anemia:!do!ECG,!serial!TnT,!chest!pain!
$ Stroke!due!to!stress!&!anemia!
$ Acute!renal!failure:!monitor!urine!output,!Cr!level!
!
Case:!CA!breast!with!liver!met,!taking!NSAID!for!pain!control,!now!UGIB!
$ GU!due!to!NSAID!+!eso!varices!due!to!portal!vein!thrombosis!
$ Management!
o High!dose!PPI!+!octreotide!infusion!post$OGD!
o Long$term:!cover!NSAID!with!PPI!or!change!to!COX$2!(best:!COX$2!+!PPI!!!GU!~0%)!
Peptic3Ulcer3(PU)3
Definition!!
$ Erosion!=!mucosal!break!<5cm!!
$ Ulcer!=!muscosal!break!>5cm!!
!
Etiology!!
$ H.!pylori!infection!!
$ NSAID!related!!
$ Others!!
o Cushing's!(↑!in!ICP!!!irritate!vagal!nuclei!!!stimulate!stomach!to!overproduce!acid)!
o Curling's!(ulcers!found!after!severe!burns,!due!to!hypoperfusion!of!mucosa)!!
o Hypercalcemia!
o Zollinger!Ellison!Syndrome:!usually!cause!DU!(D2/3!involvement)!
o G$cell!hyperplasia!
o Crohn's!disease!!
!
Location!
!

GI!$!9!
$ Gastric:!lesser!curvature,!all!other!locations!!
$ Duodenum:!bulb!(from!pylorus!to!neck!of!gallbladder,!~5cm)!
o *!If!found!in!distal!duodenum,!consider!!
" Crohn's!disease!!
" Ischemia!!
" Zollinger$Ellison!syndrome!!
!
Clinical!presentations!!
$ Dyspepsia:!food!bad!in!GU;!food!good!in!DU!
$ Upper!GIB:!coffee!ground!vomiting,!hematemesis,!tarry!stool,!fresh!PR!bleed,!anemia!!
$ Perforation:!sudden!onset!of!pain,!toxic!looking,!rigidity!!
$ Gastric!outlet!obstruction!(GOO):!wax!and!wanes!pain,!repeated!projectile!vomiting!!

Managements3of3dyspepsia33
$ Smoking#cessation#
$ Risk!stratification#
o If!uncomplicated!!!test#and#treat!(see!above)!!!PPI!trial!!!OGD#
o If!complicated!or!old!age!!!OGD#
$ If!Test!and!Treat$FAILURE,!think!!
o Compliance!
o H!pylori!resistance!
o NSAID!
o CA!stomach,!Crohn's,!ZES!!
$ Elective!surgery!as!last!resort:!(rarely!indicated!now)!!
o Duodenal!ulcer!!
" Truncal!vagotomy!with!pyloroplasty!
" Truncal!vagotomy!with!Billroth!I!(GDstomy)!/!Billroth!II!(GJstomy)!
antrectomy!!
" Highly!selective!vagotomy!!
$ Gastric!ulcer!!
o Wedge!resection!!
o Antrectomy!!

Management3of3bleeding33
$ Resuscitation!+!Assess!severity!(BP/P,!Hb,!Urea)!and!indication!for!urgent!OGD!!
$ Pre$endoscopy!management!!
o NPO,!IVF!
o Crossmatch,!CBC,!LFT,!RFT,!clotting!!
o Transfuse!up!to!Hb!7!(not!too!high),!correct!coagulopathy!!
o Close!monitor!of!vitals!!
o IV#PPI:!omeprazole!bolus!followed!by!infusion!!
" Maintain!high!pH!in!stomach!!!stabilize!blood!clot,!improve!platelet!
aggregation!
" ↓!need!for!endoscopic!treatment,!but!NOT!↓!hospital!stay!/!mortality!
" ↓!actively!bleeding!ulcers!&!stigmata!of!hemorrhage!
• ∴Not!routinely!used!in!PWH!(because!emergency!OGD!is!available),!
only!used!if!OGD!is!not!readily!available!
$ Localization!by!OGD#+#biopsy#(for!histology!&!rapid!urease!test)!!
o Indication!for!emergency!OGD!(even!in!the!middle!of!the!night)!
" Large!amount!(>100ml)!fresh!hematemesis!
" Persistent!hypotension!despite!fluid!resuscitation!
o Forrest's!classification!!
!

GI!$!10!
 Forrest#class! Type#of#lesion! Risk#of#rebleeding#if#untreated!
IA!! Arterial!spurting!bleeding!! 90%!!
IB!! Arterial!oozing!bleeding!! 50%!!
IIA!! Non$bleeding!visible!vessel!! 30%!!
IIB!! Adherent!clot!! 20%!!
IIC!! Pigmented!flat!spot! <5%!!
III! No!stigmata!of!hemorrhage!! <5%!
$ Hemostasis!(COMBINED#endoscopic#treatment,!as!it!reduces!rebleeding)!!
o Mechanical!clips!!
" Difficult!for!flat,!difficult!positioned!or!multiple!ulcers!!
" Better!for!visible!vessels!
" (Not!rubberband!ligation!as!the!ulcer!cannot!be!sucked!up)!!
o Adrenaline!injection!(1:10,000)!(0.5$1ml!up!to!10ml)!!
" Local!tamponade!!
" Vasoconstriction!(can!see!mucosa!become!white)!
" Platelet!aggregation!!
o Sclerosant!injection!!
" Ethanol,!ethanolamine,!STD,!fibrin!glue,!thrombin!!
" Now!rarely!used!as!it!may!induce!necrosis!leading!to!bigger!ulcers!
o Thermocoagulation!!
" Heater!probe!/!bipolar!coagulation!probe!!
" May!be!difficult!if!vessel!too!large!!
o (Laser!coagulation)!!
$ Post$endoscopy!!
o NPO,!IVF!for!3!more!days!
o Post$endoscope!high#dose#IV#PPI#infusion#for!72!hours!for!Forrest!class!IA,!IB,!IIA!&!
IIB!(IIC!&III!!!oral!PPI)!
" Pantoprazole!/!esomeprazole!80mg!stat!then!8mg/hr!
" Maintain!neutral!gastric!pH!!!stabilize!blood!clots!!↓!rebleeding!in!1st!3!days!
" Not!for!ulcer!healing!in!acute!phase!
o Monitor!BP/P,!U/O,!signs!of!rebleeding!
o Monitor!for!OGD!complications!(perforation,!aspiration)!!
$ Long!term!management!!
o Consider!second!look!endoscopy!in!all!GU!&!high!risk!patients!with!DU!!
" All!GU!need!re$scope!to!r/o!malignancy!in!6$8!weeks!
" If!rescope!show!persistent!ulcer,!but!down$sized!!!still!need!to!repeat!OGD!&!
biopsy!until!ulcer!heal!
• As!early!gastric!cancer!may!behave!like!GU,!may!downsized!by!PPI!
o HP!eradication!after!all!acute!management!!
!
Rebleeding!
$ High!risk!group!!
o Shock!on!admission!!
o High!rank!Forrest!class!!
o Ulcer!>2cm!!
$ Reduction!of!this!risk!!
o Combined!endoscopic!treatment!
o High!dose!PPI!infusion!for!72!hours!(stabilize!coagulation,!less!platelet!disaggregation!
in!higher!pH)!!
o Second!look!endoscopy!!
o **!No!role!for!HP!eradication!at!acute!stage!!
$ Features!suggesting!rebleeding!
!

GI!$!11!
 o BP!drop,!increase!in!urea!
" Hb!drop!may!be!due!to!hemodilution!(due!to!↓!in!intravascular!volume!during!
bleeding)!
o Fresh!melena!or!melena!with!normal!stool!in!between!!
" Old!melena!itself!doesn’t!signify!rebleeding!!
$ Choice!of!treatment!!
o Repeat!endoscopy!&!endotherapy!!
o Angiographic!embolisation!!
o Salvage!surgery!!
!
Angiographic!embolisation!!
$ If!cannot!identify!the!bleeding!site!!!can!do!prophylactic!emboliation!@!gastroduodenal!
artery!(GDA)!!!↓!rebleeding!risk!from!16%!to!4%!
$ Can!leave!the!sheath!in!situ!if!high!risk!of!rebleeding!requiring!angiography!again!
$ Complications!
o Acute!renal!failure!(contrast!nephropathy)!
o Pseudoaneurysm!(esp!if!patient!have!coagulopathy)!
!
Salvage!surgery!!
$ Indications!!
o Failed!primary!endoscopic!hemostasis!
o Rebleeding!in!hospital!±!angiographic!embolisation!failure!!
o Ongoing!transfusion!>8!units!!
$ Choices!!
o Small!ulcer!!
" Plication!of!vessel!!
" Exclusion!of!ulcer!!
o Large!ulcer!!
" Distal!!!distal!partial!gastrectomy!!
" Proximal!!!ulcer!excision!+!vagotomy!!
" Unstable!!!ulcer!excision!!

Management3of3perforated3peptic3ulcer33
$ Resuscitation!!
$ NPO!with!IVF,!NG!tube!inserted!!
$ Close!observation!!
$ Investigations!!
o CXR#!
" Free!gas!under!diaphragm:!SN!70%!
" If!unsure!!
• Decubitus!film!!
• CT#abdomen#!
• (Inject!air!via!NGT!and!CXR!again)!!
o Crossmatch,!CBC,!RFT,!amylase!!
$ IV#cefuroxime#+#metronidazole#!
$ IV#bolus#PPI!
$ Surgery!!
o Omental!patch!repair!+!peritoneal!lavage!(>6L!NS)!!
o Laproscopic:!less!post!op!pain,!not!feasible!if!ulcer!>1cm!!
$ HP!eradication!after!all!acute!management!!

GI!$!12!
Management3of3Gastric3outlet3obstruction33
$ Resuscitation!!
$ NPO!with!IVF,!NGT!inserted!!
$ Investigations!!
o Crossmatch,!CBC,!RFT!(hypoK),!chloride,!ABG!(hypochloremic!metabolic!acidosis)!!
o Urine!pH!!
o Water!soluble!constrast!
" 1st!part!obstruction!=!GOO!
" 2nd!part!obstruction!=!periampullary!CA!
" 3rd!part!obstruction!=!SMA!compression!/!food!bolus!!
$ Replace!K!!
$ OGD#+#biopsy#(GU!has!risk!of!malignancy)!
$ Surgery!!
o Endoscopic:!balloon!dilatation,!50%!recur,!reserved!for!poor!risk!patients!!
o Surgical:!gastrojejunostomy!+!vagotomy!(prevent!ulcer!at!anastomosis)!!
$ HP!eradication!after!all!acute!management!!

NSAIDs3induced3Peptic3ulcer3diseases33
Role!of!acid!in!ulcerogensesis!!
$ Exacerbates!existing!mucosal!lesions!to!produce!deeper!injury!!
$ Interfering!with!platelet!aggregation!
$ Impair!ulcer!healing!!
!
Mechanism!!
$ Suppression!of!gastric!prostaglandin!synthesis!via!COX$2!!
$ Topical!injury!by!ion$trapping!!
!
Risk!factors!!
$ History!of!ulcer!
$ HP!infection!
$ Old!age!
$ Co$morbidities!
$ High!dose!NSAIDs!
$ Corticosteroids!(it!per!se!is!not!ulcerogenic,!but!magnify!the!action!of!NSAIDs)!!
$ Aspirin!!
$ Anticoagulation!!
!
Key!!
$ COX$2!inhibitor!reduces!but!not!clear!ulcer!risk!!
$ Very$low$dose$aspirin!still!have!ulcer!risk!!
!
Management!of!NSAIDs!induced!ulcers!!
$ Stop!culprit!drug!if!possible!
$ PPI!for!4$8!weeks!!
!
Prevention!of!NSAIDs!induced!ulcers!!
! No!GI!risk!! 1!or!2!GI!risk*!! High!GI!risk/!previous!ulcers!!
Low!CVS!risk! NSAID!+!PPI/!misoprostol!!
(low!dose!aspirin! NSAID!! Or!! COX$2!+!PPI/misoprostol!!
not!needed)!! COX$2!!
High!CVS!risk! Naproxen!+!PPI/! Naproxen!+!PPI/! Avoid#if#possible#!
!

GI!$!13!
(low!dose!aspirin! misoprostol!! misoprostol!! High!CVS!risk:!Naproxen!+!
needed)!! ! PPI/misoprostol!!
High!GI!risk:!Low!dose!COX$2!+!
PPI/misoprostol!!
$ Rationale!
o COX$2!inhibitors!=!NSAID!+!PPI/misoprostol!
o High!CVS!risk!!!use!naproxen!instead!of!COX$2!
" Only!full$dose!neproxen!NOT!with!increased!cardiothrombotic!risk!!
o Cardiothrombotic!risk!of!COX$2!inhibitors!is!dose$dependent!!
o Aspirin!+!PPI!better!than!clopidogrel!alone!
o **!Misoprostol!(synthetic!analog!of!prostaglandin!E1):!S/E!=!miscarriage!(it’s!the!drug!
used!for!TOP!&!labour!induction),!diarrhea!!
Helicobacter3pylori3infection33
Basic!!
$ Infection!usually!contracted!at!first!few!years!of!birth,!tend!to!persist!indefinitely-!
$ 50%!of!world!population!are!infected,!among!which!!
o 1$10%!have!peptic!ulcers!!
o 1%!have!gastric!cancer!!
o 0.01%!have!MALT!lymphoma!!

Pathogenesis!!
$ Gastric!ulcer!!
o Direct!damage!to!acid#producing#body#!!atrophic!gastritis!(paradoxically!low$acid!
secreting!)!!
$ Duodenal!ulcer!!
o Inflammation!of!non^acid#secreting#antral#region#!!↑!gastrin!release!!!stimulate!
excess!acid!secretion!from!proximal!stomach!!!acid!load!damages!the!duodenal!
mucosa,!causing!ulceration!&!gastric!metaplasia!!
o H.!pylori!can!then!colonise!and!lead!to!direct!damage!!
$ Gastric!cancer!!
o Associated!with!non^cardia#gastric#cancers#!
o Higher!risk!in!!
" Inflammation!of!BOTH!antrum!&!fundus!!
" Mucosal!atrophy!
" Intestinal!metaplasia!!
o *!Eradication!cannot!reverse!atrophy!/!metaplasia,!?!reduce!risk!of!cancer!
$ Gastric!MALToma!!
o Association!demonstrated!!
o *!Eradication!CAN#lead!to!regression!of!localized!tumors!!
$ Non$ulcer!dyspepsia!!
o Constitute!50%!of!patients!with!upper!GI!symptoms!undergoing!endoscopy!
o Among!these!H!pylori!is!found!in!biopsy,!but!eradication!does!not!confer!any!
significant!improvement!in!symptoms!!

Indication!for!HP!testing!!
$ Endoscopically!confirmed!peptic!ulcers,!gastric!MALToma!!
$ After!gastric!CA!resection!!
$ The#test^and^treat#approach#!
o For!patient!with!uninvestigated!uncomplicated!dyspepsia!+!younger!age!+!no!NSAIDs!
o Rationale!!
" Some!patients!with!dyspepsia!have!underlying!H#pylori#induced#ulcers#!
!

GI!$!14!
 " Using!a!non$invasive!diagnostic!test,!treat!all!+ve!patients!!
" For!patients!with!ulcers!!!they!benefit!from!avoiding!endoscopy!
" For!patients!without!ulcers!!!only!20%!benefit,!80%!suffer!from!$$!and!S/E!
" NNT!~!7!!
o Unlikely!to!be!cost$effective!if!H#pylori#infection#prevalence#<20%#!
" HK:!Hp!prevalence!≥10%!∴!Hp!test!&!treat!!!PPI!trail!!!endoscopy!
!
Tests!for!HP!infection!!
$ Non$endoscopic!
o Serology!(SN!85%,!SP!80%)!
" Test!for!IgG!
" Remained!positive!months!to!years!after!eradication,!cross$reactive!with!
Salmonella!
o Urea!Breath!Test!(95%,!95%)!
" Drink!C13!/!C14!labeled!urea!
" Measure!the!level!of!labeled!exhaled!carbon!dioxide!!
" Need!to!stop!antibiotics!4!weeks;!PPI!2!weeks;!H2B!1!day!!
o Faecal!antigen!test!(95%,!95%)!
" Need!to!stop!antibiotics!4!weeks;!PPI!2!weeks;!H2B!1!day!!
$ Endoscopic!!
o Rapid!urease!test/!CLO!test!(Campylobacter$like!organism!test)!(90%,!95%)!
" Immerse!biopsy!specimen!in!urea!solution!&!look!for!pH!!
• Test!the!ability!of!Hp!to!secrete!urease,!which!catalyzes!urea!to!
ammonia!&!carbon!dioxide!
" +ve:!yellow!!!red!
" False#negatives!
• Blood#in#stomach:!blood!is!a!buffer!!!↓!sensitivity!of!pH!change!
• Acid!suppression:!PPI#!
" Need!to!stop!antibiotics!4!weeks,!PPI!2!weeks,!H2B!!
o Histology!!
" For!all!to!avoid!false!negatives!in!rapid!urease!test!!
o Culture!!
" For!antibiotic!sensitivity!testing!!
!
Treatment!!
$ First!line!!
o Levofloxacin!/!clarithromycin!+!metronidazole!/!amoxicillin!+!PPI!x!10$14!days!
" Levofloxacin:!1st!line!as!resistance!rate!is!lower!
" Clarithromycin!frequently!cause!GI!upset!!!poor!compliance!is!the!
commonest!cause!of!Rx!failure!
" Triple!therapy!efficacy!is!95%!(but!now!increased!resistance)!!
" Increase!gastric!pH!by!high!dose!PPI!(Nexium!40!mg!BD)!to!↑!efficacy!!
o PPI!+!bismuth!+!tetracycline!+!metronidazole!x!10$14!days!!
" For!clarithromycin$resistant!prevalent!areas!
o Sequential!therapy!for!repeated!prior!exposure!to!clarithromycin!
" Day!1$5:!PPI!+!amoxicillin!
" Day!6$10:!PPI!+!clarithromycin!+!tinidazole!!
$ Second!line!!
o PPI!+!amoxycillin!+!metronidazole!x!7$14!days!!
o Quadruple!therapy!!
$ Third!line!!
o No!standard!third!line!agents!
!

GI!$!15!
 o Need!culture!&!sensitivity!to!guide!regime!(usually!levofloxacin/!rifabutin!containing)!!
!
Management!of!persistent!symptoms!!
$ Confirmation!of!eradication!!
o Urea!breath!test!/!fecal!antigen!test!!
" Done!after!4!weeks!to!avoid!false!negative!from!bacterial!suppression!!
o Repeated!endoscopy!if!otherwise!indicated!!
o *!Not!serology:!remained!positive!for!at!least!6$12months!
o *!HP!eradication!will!heal!the!ulcer!except!Aspirin/NSAID$induced!ulcer,!with!
complication!&!large!ulcer!(one!more!factor!but!I!forget!)!!!need!8!wks!PPI!!
$ Re$treatment!
o For!patients!have!confirmed!ulcers,!MALTomas!/!resected!CA!!
" Go!for!2nd!line!treatment!
o For!patients!from!test!and!treat!approach!!
" Look!for!other!possible!explanation!for!symptoms!!
" No!current!evidence!on!what!to!do,!may!try:!!
• Symptomatic!acid!suppression!!
• Repeat!test!and!treat!
• Endoscopy!for!other!pathologies!!
Acid3suppression3therapy3
Long$term!acid!suppression:!S/E!include!
$ Acid!help!absorption!of!B12!!!risk!of!anemia!
$ Acid!kill!bacteria!!!↑!risk!of!infection,!including!TB!
$ So!should!stop!acid!suppression!if!not!indicated,!e.g.!when!patient!no!longer!on!aspirin!/!
NSAIDs!
Middle3GIB3
Investigation!
$ Capsule!endoscopy,!RBC!scan,!CT!angiogram!
!
Treatment!!
$ Misoprostol:!prostaglandin!E1!(PGE1)!analogue!!
o For!small!bowel!bleeding!!!improve!healing!&!↓!risk!of!rebleeding!
" Aspirin$related!ulcer!is!due!to!↓!prostaglandin!level!
• Submucosal!hemorrhage!@!stomach!(seen!by!OGD!as!red!dots)!
o S/E:!abdominal!cramp,!diarrhea!
" Many!patients!cannot!tolerate!full!dose!∴!start!with!low!dose!then!titrate!up!
Obscure3bleeding3
$ Bleeding!from!unknown!origin!that!persist!/!recur!after!an!initial!–ve!endoscopic!evaluation,!
including!OGD!&!colonoscopy!
$ Occult!(Fe!deficiency!anemia)!vs!overt!(hematochezia!/!melena)!
$ Majority!lesions!in!SB!
o SB!angiodysplasia!(70$80%),!SN!neoplasm!(5$10%),!NSAID!enteropathy,!Meckel’s,!
IBD!
$ Investigations!
o Meckel’s!scan:!for!young!patients!
o Small!bowel!enema!(enteroclysis):!good!for!SM!neoplasm,!bad!for!angiodysplasia!
o Wireless!capsule!endoscopy!
o Balloon!enteroscopy:!push!&!pull!enteroscopy!
" Double!balloon!enteroscopy!/!single!balloon!enteroscopy!

GI!$!16!
Deranged3liver3function3
DDx!
$ Hepatitis!
$ Fatty!liver!disease!
$ Drug$induced!
$ Alcohol!
$ Autoimmune!hepatitis,!PBC,!PSC!
$ Obstruction!
$ Venous!obstruction!
$ Shock!liver!(hypotension)!
$ Metabolic:!Wilson,!primary!hemochromatosis!
!
History!taking!
$ Sx!of!hepatitis!/!obstruction:!RUQ!pain!
$ TOCC:!Hep!A,!E!
$ Risk!factors!of!Hep!B:!tattoo,!ear$piercing…!
$ Drug!use:!drugs,!OTC!drugs,!TCM,!health!supplements!
$ Alcohol!use,!e.g.!chronic!alcoholics!
$ PMH!of!metabolic!syndrome:!fatty!liver!disease!
!
Investigations!
$ Serology!for!Hep!A,!B,!C,!D,!E,!EBV,!CMV!
$ ANA,!anti$smooth!muscle!Ab!(autoimmune!hepatitis)!
$ ANCA!(PSC),!antimitochondrial!Ab!(PBC)!
$ AST:!release!from!mitochondria,!release!in!shock!liver!&!alcoholic!liver!disease!(both!toxic!to!
mitochondria)!!!AST:ALT!>!1:1!
Cholestasis3
Bedside!by!Prof!B!Ma!
$ Case:!TB!171,!ALP!1106,!ALT!257,!GGT!2775!!!cholestatic!picture!
$ 1st!thing!to!do:!differentiate!acute!vs!chronic!(look!at!previous!results)![This!case:!acute]!
$ Check!clotting!to!exclude!liver!decompensation!
$ Do!USG!to!exclude!extrahepatic!&!large!intra$hepatic!obstruction!
$ If!normal!USG!!!likely!intrahepatic!cholestasis!
o Commonest!cause:!drugs!
" Antibiotics:!erythromycin,!azoles,!sometimes!Augmentin,!amphotericin!
" Anti$thyroid!drugs!
" Anti$epileptics!
" NSAIDs!
" Chemo:!methotrexate!
" Anabolic!steroids!
" Illicit!drugs:!mushrooms!(but!tends!to!cause!fulminant!hepatitis!instead)!
o Other!causes:!fatty!liver!in!pregnancy!!
Acute3hepatitis3
History!taking!
$ Malaise,!↓!appetite,!tea!color!urine,!vomiting,!RUQ!discomfort/pain!
$ Unclean!food!/!sexual!activity,!travel!history!
$ TCM,!medication!(e.g.!paracetamol)!use!
$ Past!blood!transfusion,!Hep!B!status!of!spouse!
$ FHx!of!HCC!
!
Physical!examination!
!

GI!$!17!
$ RUQ!pain!
$ Hepatomegaly:!may!be!present!in!acute!hepatitis!
!
Investigation!
$ CBC!(Hb:!macrocytic!anemia:!chronic!liver!disease,!alcoholism,!WCC,!plt)!
$ INR!
$ R/LFT:!may!have!cholestatic!phase!leading!to!obstructive!pattern!
$ HBsAg,!anti$HBc!IgM,!anti$HCV,!anti$HAV,!anti$HEV!
o If!anti$HBc!IgM!–ve!!!unlikely!acute!hepatitis,!likely!chronic!
o Need!to!check!anti$HBc!IgM!in!additional!to!HBsAg!due!to!the!possibility!of!core!
window!
$ Bone!profile!/!amylase!
$ USG!abd:!r/o!obstruction!
!
Approach!
$ Supportive!treatment!
$ Check!HBsAg!6!months!later!to!see!whether!there’s!chronic!Hep!B!
!
Management!
$ DAT,!obs!Q4H!
$ H’stix!BD!(liver!failure!may!cause!hypoglycemia)!
$ Blood!x!CBC,!LRFT,!INR,!NH3!daily!
Hepatitis3A3
Introduction!!
$ RNA!picornaviridae!
$ One!serotype,!human!as!only!natural!host!!
$ Fecal!oral!transmission!
$ Incubation!2$6!weeks!!
$ Infection!with!HAV!induces!lifelong!immunity!

Clinical!presentation!!
$ Asymptomatic!esp!if!acquired!in!childhood!
$ Prodromal!symptoms-
o Fever,!profound!malaise,!anorexia,!myalgia,!arthralgia,!rash,!mild!diarrhea!-
$ RUQ!pain,!jaundice-
$ Fulminant!hepatitis!0.1%!-
$ Unusual!variants!
o Relapsing#hepatitis:!occur!in!a!small!proportion!of!patients!weeks!to!months!after!a!
full!recovery!to!HAV!infection,!but!this!is!again!usually!self$limiting!
o Cholestatic#hepatitis#!
!
Investigation!!
$ Anti$HAV!IgM!!
!
Prevention!!
$ Avoid!undercooked!seafood!
$ Active!immunization!(2!doses,!last!for!10!years)!!
$ Passive!immunization!(last!for!6!months)!!
o Primary!prevention!before!exposure!
o Used!in!early!incubation!period!as!secondary!prevention!!

GI!$!18!
Hepatitis3B3
Introduction!!
$ 8!Genotypes!
$ Hep!B!carrier:!~10%!in!HK!!
$ In!adults,!high!chance!of!clearance!after!acute!infection!(<5%!become!chronic)!
!
Serology!
HBsAg! $ Marker!of!infection!
Anti$HBs! $ Marker!of!protection!
$ Pre/post$vaccination!screening!
$ Indicate!recovery!&!immunity!from!Hep!B!infection!/!successfully!vaccinated!
o –ve!in!acutely!/!chronically!infected!
$ Acute!window!period:!HBsAg!disappears!but!anti$HBs!not!yet!developed!
Anti$HBc!IgM!! $ Marker!of!acute-infection-(+ve!in!recent!infection!≤6m)!
! $ If!–ve!during!hepatitis!!!likely!chronic!infection!/!reactivation!
$ Core!window!(~3$6!months!after!exposure):!HBsAg!became!–ve!but!anti$HBs!
not!yet!developed,!while!anti$HBc!IgM!is!usually!+ve!(remains!infected!but!is!
successfully!clearing!the!virus)!
$ Reappear!in!chronic!active!hepatitis!
Anti$HBc!IgG!! $ Marker!of!natural-infection!(past!/!chronic)!
! $ –ve!after!vaccination!
$ Screening!for!Tx!&!IC!patients!(Hep!B!may!reactivate)!
HBeAg! $ Marker!of!active-proliferation-of-virus!(infectiveness)!
! $ Presence!of!HBeAg!!!much!higher!rates!of!viral!replication!&!enhanced!
infectivity!
$ Only!for!patient!with!+ve!HBsAg!/!known!carrier!
Anti$HBe! $ Only!for!patient!with!–ve!HBeAg!
! $ Benign!outcome!in!e$seroconversion!(from!HBeAg+ve!!!$ve)!
HBV!DNA! $ Marker!of!active-proliferation-of-virus!(infectiveness)!
! $ More!accurate!than!HBeAg!(mutation!of!eAg)!
$ For!monitoring!response!to!treatment!(look!at!the!log!value)!
$ Sequence!of!events!
o HBsAg!!!Anti$HBc!IgM!!!Clinical!Sx!+!deranged!LFT!!!Anti$HBs!
$ Sequence!of!testing!
o Test!HBsAg!for!any!active!infection!
" If!–ve!!!maybe!occult!infection!(HBsAg!lower!than!detection!threshold)!!!if!
highly!suspicious!of!Hep!B!infection!!!
o Test!for!HBV!DNA!(more!sensitive!than!HBsAg)!
" If!–ve!but!still!very!suspicious!of!Hep!B!infection!!!
o Test!for!anti$HBc!IgG!!
" If!+ve!!!must!have!previous!infection!!!go!for!liver!biopsy!to!test!HBV!DVA!
(?)!
" Occult!infection:!HBsAg!–ve,!anti$HBs!–ve,!anti$HBc!IgG!+ve!
!
Implication!of!serological!markers!
$ Monitoring!of!active!disease:!by!HBV!DNA!&!ALT,!not!HBeAg!
o Traditionally!believe!that!HBeAg+ve!is!related!to!active!proliferation!of!virus!!!↑!
cirrhosis!&!HCC!
o So!earlier!seroconversion!/!shorter!HBeAg!+ve!phase!!!↑!chance!of!sustained!
remission!
" But!may!still!be!re$convert!to!HBeAg+ve!during!flare!up!
!

GI!$!19!
 o But!study!find!that!10$20%!patients!with!HBeAg$ve!patient!still!have!active!disease!
(high!HBV!DNA!&!cirrhosis)!
o So!use!HBV!DNA!to!monitor!is!better!
o Now!can!also!monitor!by!quantitative!HBsAg!(new)!
" When!virus!are!concentrated!in!liver!!!blood!level!of!HBV!DNA!may!be!low,!
but!HBsAg!remain!high,!∴!can!use!it!to!guide!Rx!
$ But!HBeAg!still!have!certain!implication!!
o HBeAg+ve!!!give!antiviral,!if!turn!into!HBeAg$ve!after!Rx!!!more!likely!have!
sustained!viral!response!!!can!stop!Rx!after!6$12m!
o If!HBeAg!–ve!but!still!active!disease!(immune!control!is!imperfect)!!!need!to!
continue!antiviral!for!long!term,!due!to!higher!chance!of!relapse!(80$90%)!
!
Prevention!
$ Active!vaccination!
o Recombinant!
o Universal!vaccination!in!newborn!at!0,1,6!months!!
o NOT!contraindicated!in!pregnant!women!
$ Passive!immunization!
o HBV!immunoglobulin!
o Given!to!babies!born!after!a!positive!mother!

Chronic3Hepatitis3B3infection3
$ *!Not!use!the!term!‘Hep!B!carrier’!now,!use!‘chronic!Hep!B!infection’!instead!
o Even!ALT!is!normal,!may!still!have!some!inflammation!going!on!
$ Prevalence:!7%!now!(vs!past!~10%)!in!HK!due!to!vaccination!
!
Natural!history!of!chronic!hepatitis!B!!
$ Replicative!phase:!Immune!tolerance!(NOT!in!
adult!acquired!HBV)!
o Immune!response!not!active!towards!
virus,!it!can!freely!replicates,!minimal!
disease!progression!!
o HBV!DNA!↑,!HBeAg!+ve,!liver!enzyme!
normal!!
$ Replicative!phase:!Immune!clearance!!
o Immune!response!active!towards!virus!
" But!sometimes!it!is!ineffective!
and!prolonged,!fail!to!clear!the!
virus!but!induce!continuous!heavy!damage!to!liver!
o HBV!DNA!↑!(decreasing),!enzyme!↑!
o 2$15%!annual!spontaneous!HBeAg!seroconversion!rate!
o 1%!annual!spontaneous!HBsAg!seroconversion!rate!in!anti$HBe!patients!(but!risk!of!
HCC!persists)!
$ Residual!/!Inactive!phase!!
o Successful!immune!clearance,!however!active!hepatitis!may!relapse!due!to!!
" HBeAg!seroreversion!!
" Occurrence!of!HBeAg$negative!hepatitis!!
o HBeAg!–ve,!HBV!DNA!low!
$ Reactivation!!
o In!residue!/!inactive!phase:!2$3%!annual!incidence!of!relapse!!
" More!in!M,!genotype!C,!those!who!seroconvert!after!40!
o HBV!DNA!↑!log!4$5,!ALT!↑!2$3x!ULN!
!

GI!$!20!
!
Investigation!
$ LFT!
o Monitor!A/G!ratio,!ALT,!ALP,!bilirubin,!albumin!
$ HBV!DNA!
$ (AFP)!
o Not!recommend!using!AFP!as!screening!for!HCC!
" Non$specific!nor!sensitive:!only!~40%!HCC!have!↑!AFP!
o But!due!to!limited!resources,!can’t!do!USG!too!often,!so!use!AFP!
$ USG!every!6!months!
$ Fibroscan!(elastogram)!
o Give!out!shock!wave!&!detect!rebound!of!wave!
o Detect!degree!of!fibrosis!in!liver!
o Highly!sensitive!&!specific!
" Vs!USG:!operator!dependent,!also!not!sensitive!&!specific!enough!for!detection!
of!degree!of!fibrosis!
o **!Not!done!in!acute!hepatitis:!overestimate!the!degree!of!fibrosis!in!acute!hepatitis!
o If!results!in!doubt!!!do!liver!biopsy!(gold!standard)!
$ OGD!
o All!cirrhotic!patients!have!to!do!OGD!to!r/o!eso!varices!
" 1/3!of!the!patients!having!their!1st!bleeding!varices!die!
!
Complications!
$ Cirrhosis!!
o Annual!incidence!of!2%!among!chronic!HBV!infection!
$ HCC!!
o Annual!incidence!of!5%!in!patients!with!HBV$related!cirrhosis!
o Incidence!is!related!to!HBV!DNA!load:!if!HBV!DNA!>4log!!!significantly!↑!risk!
o e$antigenemic!!!higher!risk!of!HCC!than!normal,!s$antigenemic:!50x!higher!risk!!
o Risk!factors!
! Modifiable! Non$modifiable!
Host! Cirrhosis,!DM,!obesity,! Older!age,!male,!genetics,!immunological!
smoking,!alcohol! status!
Virus! HBV!DNA,!HBeAg!status! Viral!genotype,!precore!&!core!promoter!
mutations,!co$infection!with!HCV!&!HIV!
$ Kidney!problem!
o Membranous!GN,!IgA!nephropathy!
!
Treatment!
$ Objective!!
o Sustained!viral!suppression!!!reduced!necroinflammation!of!liver!!!ultimate!↓!risk!
in!cirrhosis!/!HCC!development!
o Two!aspects!!
" Viral!suppression!therapy!
" HCC!surveillance!(AFP!and!USG!every!6!months)!!
• Study!showed!that!3!monthly!USG!have!no!additional!survival!benefit!
as!sensitivity!of!USG!is!limited!
• Frequency!not!depend!on!risk!factors!of!HCC!(e.g.!FHx)!as!growth!rate!
of!HCC!not!affected!by!risk!factors!
• PWH!still!use!AFP!as!HCC!screening!although!AASLD!guideline!remove!
this!from!the!recommendation!
$ Indication!of!starting!treatment!(international!guideline)!
!

GI!$!21!
 o Persistent!(>6months)!↑!in!ALT!(>2x!ULN)!&!
" HBeAg!+ve!&!HBV!DNA!>20,000!
" HBeAg!–ve!&!HBV!DNA!>2,000!
o Cirrhosis/fibrosis!with!detectable!HBV!DNA!
o On!immunosuppressant,!biologics,!chemo!
" But!in!HK:!azathioprine!is!weak!IS,!so!may!not!take!anti$viral!(need!money)!
$ Regime!
o Antiviral!
" In!non$cirrhotic!patient:!may!stop!antiviral!&!observe,!unless!persistently!
active!disease!(high!ALT/HBV!DNA/significant!fibrosis)!
" In!cirrhotic!patient:!must!continue!Rx!lifelong!
• If!stop!!!90%!will!flare!up!(cirrhosis!↑!risk!of!fulminant!hepatitis)!
• Consider!stepping!up!antiviral!in!case!of!incomplete!viral!suppression!
o Interferon:!a!finite!duration!of!treatment! (SC!injection)!
" Treatment!duration:!1!year!!!trigger!immune!system!to!control!HBV!
• ~30%!success!
" But!many!S/E,!e.g.!fever,!flu$like!symptom,!BM!suppression,!depression,!liver!
failure!if!already!decompensated!
" Used!in!young!F!patients!with!HBeAg!+ve!!!may!give!patient!to!have!drug!free!
period!for!few!years!!!can!get!pregnant!
o Combination!therapy!is!not!recommended!by!current!guidelines!
o *!Always!start!with!3rd!generation!/!pegylated!interferon!
o *!In!drug!resistance!case!(e.g.!resistance!to!entecavir)!!!ADD!another!antiviral!(e.g.!
Tenofovir)!instead!of!replace,!if!resistance!to!lamivudine!!!add!adefovir!
" Some!part!of!virus!may!be!sensitive!to!entecavir!but!resistance!to!tenofovir!
$ Drug!class!
o Nucleoside!analogue!!
" 1st!gen:!Lamivudine!!
• High!resistance!rate:!70%!in!5!years!(ymdd!mutant)!
• Effect!(reduction!in!disease!progression!rate)!is!more!significant!in!
wild$type!(without!drug!resistance)!
" 2nd!gen:!Telbivudine!!
" 3rd!gen:!Entecavir!(ETV)!
• Much!lower!resistance!rate:!1.2!%!in!6!years!
• Can!result!in!cirrhosis!regression!
o Nucleotide!analogue!!
" 1st!gen:!Adefovir!(resistance!rate!29%!in!5!years)!
" 2nd!gen:!tenofovir!(TDF)!(resistance!rate!0%!in!5!years)!
• Newest!anti$HBV!agent!
• Effective!in!lamivudine!resistant!patients!
• Much!lower!renal!toxicity!then!adefovir!!
• Can!also!result!in!cirrhosis!regression!
• Potential!1st!line!drug!in!treatment$naive!chronic!HBV!patient,!due!to!
its!ability!in!early!suppression!(at!wk!24)!of!HBV!DNA!(HbeAg!+ve:!
86%,!HbeAg!–ve:!50%)!
o Immune!!
" Conventional!interferons!
" Pegylated!interferons!(PEG$IFN)!!
• +!polyethylene!glycol!to!enhance!t½!
$ Goal!
o Seroconversion!to!HbsAg!–ve!(more!in!IFN!than!antivirals,!~1%/year!chance)!!
o Seroconverison!to!HbeAg!–ve!!
!

GI!$!22!
 o Prolonged!effective!suppression!of!HBV!DNA!(<300!copies/ml)!
" Virologic!response!=!HBV!DNA!become!$ve!
o ALT!less!than!1/2!the!upper!limit!!
$ Therapeutic!endpoints!over!time!
o HBV!DNA!suppression!!!ALT!normalization!!!HBeAg!seroconversion!!!improved!
histology!!!loss!of!HBsAg!!!↓!HCC!&!cirrhosis!!!improved!survival!
!
Anti$viral!prophylaxis!in!patients!on!strong!immunosuppressant/!steroid/!chemotherapy!
$ *!For!aza!/!MTX:!reactivation!rate!lower,!so!may!not!necessarily!give!anti$viral!(but!
rheumatology!guideline!still!recommend!it)!
$ Testing!before!starting!
o Test!for!HBsAg!
o If!HBsAg!–ve:!check!anti$HBc!total!to!look!for!occult!Hep!B!infection!(occult!=!HBsAg$
ve)!
o If!anti$HBc!(total)!+ve!!!check!HBV!DNA!
" If!+ve!!!anti$viral!prophylaxis!until!cessation!of!IS!for!6!months!
" If!–ve!!!check!DNA!regularly!to!monitor!any!flare!
$ Start!Lamivudine!2!wks$1!month!before!the!Rx!(can!give!IS!at!the!same!time!as!anti$viral!–!
Siew!Ng)!
o Consider!Entacavir!if!requiring!long!term!immunosuppressant!such!as!renal!
transplant!cases!
o Prefer!entecavir!/!tenofovir!than!lamivudine!as!long!term!medication!because!
resistant!rate!of!lamivudine!is!higher!
$ Then!maintain!antiviral!agent!for!6!months!after!completion!of!the!course!!
o *!Except!in!rituximab!(anti$CD!20!inhibitor):!need!to!take!longer!(12m!after!stopping!
the!drug)!due!to!delay!recovery!in!immunity!
$ Closely!monitor!the!LFT!!
$ The!period!of!the!most!easily!flare!up!=!tapering!of!steroid!/!withdrawal!!
o HBV!replicate!in!large!amount!during!the!immunosuppressant!therapy,!then!
resumption!of!immune!response!(immuno$reconstruction)!during!the!withdrawal!!
!
FU!in!OPD!
$ Symptoms!
o Screen!for!acute!flare!up!
" Usually!asymptomatic!in!chronic!Hep!B,!but!can!have!vague!general!malaise!&!
RUQ!pain!
" Hepatitis!symptoms! !
" Abdominal!distension ,!ankle!swelling!
" Hematemesis,!tarry!stool!
" Poor!sleep !!encephalopathy:!1st!sign!is!sleep$wake!cycle!
disturbance!
o Constitutional!Sx!(r/o!HCC):! !
$ Drug!history!
o How!long!the!patient!has!taking!the!anti$Hep!B!drug!
" The!longer!the!Rx!period!!!the!higher!risk!of!having!drug!resistant!mutant!&!
poor!compliance!
o Drug!compliance,!S/E!
o OTC!/!TCM:!may!affect!liver!function!
" Some!TCM!may!contain!heavy!metals!
$ Surveillance!
o Last!OGD,!USG,!AFP!
!

GI!$!23!
$ P/E!
o Ankle!edema!
Case:!Hep!B!&!DM!patient!!!HBV!DNA,!ALT!&!ALP!↑!
$ DDx:!!
o Drug!resistance!mutant!
o Early!stage!of!HCC:!ALP!also!↑!due!to!SOL!
o Poor!DM!control!leading!to!non$alcoholic!steatohepatitis!
$ Management!!
o USG:!r/o!HCC!
o Test!for!drug!resistant!mutant!(drug!resistant!test)!
o Tighten!DM!control!
!
Management!of!acute!flare!up!
$ Start!antiviral!drugs!straight!away!once!HBsAg!+ve,!not!wait!for!HBV!DNA!results!
o Give!lamivudine!in!acute!stage!
" One!small!observational!study!show!that!entacavir!may!worsen!outcome!in!
acute!hepatitis!when!ALT!is!very!high!(but!controversial)!!
$ Close!monitoring!of!LFT!&!clotting!to!look!for!deterioration!
o Look!for!decompensation:!bilirubin,!ALT,!INR,!albumin,!NH3!
o The!most!important!test!is!clotting:!synthetic!function!affected!&!effects!most!rapidly!
seen!
o If!keep!on!deteriorating!!!refer!patient!for!liver!transplant!
$ Check!HBV!DNA!again!only!after!6m!!
o Not!repeat!over!short!period!of!time,!as!there’s!no!implication!on!Rx!
o Target:!HBV!DNA!become!–ve!!
" Usually!become!–ve!after!1$1.5!years!
$ **!Acute!flare!up!Vs!acute!infection!
o By!history:!any!infection!before!
o HBeAg!status:!if!–ve!!!more!likely!chronic!as!already!seroconvertion!
Hepatitis3C3
$ RNA!virus,!flaviviridae!!
$ 6!genotypes,!commonest:!genotype!1b,!6a!
o In!Egypt:!commonest!is!genotype!4!due!to!Schistosomiasis!
$ Transmission!!
o Parenteral:!IVDA,!transfusion,!hemodialysis,!tattooing,!body!piercing,!dental!
procedures!in!unhygienic!place!
" In!HK:!mostly!get!from!IVDA!&!blood!transfusion!
o Rarely,!sexual!and!vertical!
$ Have!to!go!through!cirrhotic!stage!to!cause!HCC!(repeated!inflammation!and!repair)!!
o 1$2%!per!year!in!cirrhotic!patients!!
o Develop!cirrhosis!after!~10!years!of!infection!
!
Presentation!!
$ Acute!hepatitis:!nausea,!malaise,!anorexia,!jaundice,!RUQ!pain,!fulminant!failure!!
$ Chronic!hepatitis:!fatigue!as!major!symptom!
$ Cirrhosis:!present!with!complications!!
!
Association!!
$ Cryoglobulinemia#(Type#II/III,#also#called#mixed)#!
o 10$25%!of!HCV!
o Single!/!mixed!immunoglobulin!that!undergo!reversible!precipitation!at!low!temp!!
!

GI!$!24!
 o Vasculitic!skin!rash!
o Joint!and!muscle!ache!
o Neuropathy!
o Kidney!disease!
o Serum!cryoglobulins,!low!C3C4,!RF+!!
$ Mesangiocapillary!GN!Type!1!
$ Porphyria!cutanea!tarda!
$ Lichen!planus!(pruritic-polygonal-planar-purple-papules,-most-on-flexor-surfaces-and-mucosa)-!
$ Lymphoma!!
!
Investigations!(before!start!of!Rx)!
$ Anti$HCV!(may!be!undetectable!for!first!8!weeks)!
$ HCV!RNA!titer!(may!be!undetectable!for!first!2!weeks),!HCV!genotype!
$ Clotting!(INR),!CCB!(plt),!LFT!(bilirubin/albumin,!ALP,!ALT),!glucose!
$ USG!abdomen!
$ Anti$HIV!
$ TSH,!ANA,!ATG!(anti$thyroglobulin)!
o Treatment!of!Hep!C!may!induce!autoimmune!disease!
$ Fibroscan!
$ OGD!for!eso!varice!screening!
$ AFP!
$ ±!Liver!biopsy:!for!grading#(inflammation)!&!staging#(fibrosis)!!
o *!Not!everyone!require!a!liver!biopsy!before!treatment!
" Major!use!of!liver!biopsy!is!to!help!in!the!decision!of!whether!to!initiate!
treatment!or!to!delay!until!there!are!further!advances!in!the!field!
" Genotype!2!or!3:!high!response!rate!∴may!offer!Rx!regardless!of!the!severity!
of!hepatitis!shown!by!liver!biopsy!!!no!need!liver!biopsy!
" Genotype!1!with!laboratory!/!clinical!evidence!of!advanced!fibrosis:!can!be!
assumed!to!have!progressive!liver!disease,!∴!should!start!Rx!without!biopsy!!
" Some!patients!wish!to!be!treated!regardless!of!severity!of!the!underlying!
hepatitis!!!no!need!liver!biopsy!!
!
Treatment!!
$ Who!to!treat:!the!NDDIC!recommendation!!
o Detectable!HCV!RNA!(with!/!without!elevated!ALT)!
o Biopsy!showing!moderate!/!severe!necroinflammation,!or!fibrosis!!
o Liver#enzyme#!
" Elevated!enzyme!level!correlates!poorly!with!liver!injury!!
" Mild!disease!that!is!unlikely!to!progress!!!can!choose!treat!or!not!treat!!
o Biopsy#!
" Fibrosis/!severe!or!moderate!inflammation!and!necrosis!!!treat!!
" Mild!inflammation!and!necrosis!!!can!choose!treat!or!not!treat!!
$ Contraindications!!
o Allergy!
o Severe!psychiatric!disorder/!suicidal!ideation!!
o Autoimmune!diseases!!
o Decompensated!cirrhosis!(ascites,!persistent!jaundice,!wasting,!variceal!hemorrhage,!
or!hepatic!encephalopathy)!
o Severe!cardiopulmonary!diseases!!
" Anemia!(S/E!of!ribavirin)!may!further!compromise!patient’s!condition,!even!
MI!
o Renal!failure/!hemoglobinopathies!(for!ribavirin)!!
!

GI!$!25!
 o Pregnancy/lactation!!
$ Less!effective!in!!
o Elderly,!male,!Blacks!
o Advance!fibrosis!
o High!viral!load!(>800,000IU/mm3)!!
$ Pegylated#inteferon#α2a#or#α2b#(sc!weekly)!+!ribavirin#(PO!BD)!!
o Pegylated!inteferon!vs!standard!inteferon!!
" Longer!t½:!avoid!intermittent!&!fluctuating!levels!
" More!effective!in!viral!suppression!&!more!likely!to!achieve!sustained!immune!
responses!!
" Similar!side!effect!profiles!!
o Ribavirin!!
" Not!effective!as!monotherapy!
" But!when!added!to!peg$interferon,!↑!2$3!fold!of!sustained!viral!response!!!
$ Side!effects!!
o Peg$IFN!!
" Malaise,!fatigue,!fever,!polyarthralgia,!polymyalgia!
" Plt!↓,!WCC!↓!(esp.!PMN)!
" Psychological:!depression,!anxiety,!sleep!disturbance!!
• Try!antidepressants!or!anxiolytics!
" Induce!autoantibodies,!or!to!exacerbate!existing!autoimmune!disease!!
o Ribavirin!!
" Hemolytic!anemia,!in!almost!everyone!!
" Teratogenic!(both!M!&!F)!!
$ Time!and!Dose!!
o Genotype!1,4,5,6!!!48!weeks!(ribavirin!1000/1200mg!daily!depends!on!BW)!!
o Genotype!2,3!!!24!weeks!(ribavirin!800mg!daily)!!
$ Success!rate!
o 60%!in!non$cirrhotic!patients,!50%!in!cirrhotic!patient!
!
Monitoring!of!response!
$ Check!HCV!RNA!for!response!!
o At!week!4!of!Rx!
" If!–ve!test!(rapid#response)!!!predictive!of!sustained!viral!response!!!can!
consider!shorten!Rx!duration!to!6m!
• Not!applicable!to!cirrhotic!patients:!need!to!continue!to!48!weeks!
o At!week!12!of!Rx!
" If!level!↓!significantly!(i.e.!early#virologic#repsonse)!!!continue!Rx!
" If!failure!to!achieve!100$fold!reduction!(i.e.!not!effective)!!!stop!Rx!
• Even!continue!!!only!10$20%!will!response:!not!cost$effective!
o 6!months!after!Rx!
" If!–ve!!!sustained!virological!response!(SVR):!good!
" Not!test!immediately!after!Rx:!~10%!of!patients!with!HCV!RNA!–ve!at!the!end!
of!Rx!will!relapse!
$ 3!types!of!response!!
o Sustained!virologic!response!=!undetectable!for!>6!months!after!treatment!cessation!!
" 80%!for!genotype!2/3!!
" 50%!for!genotype!1/4/5/6!!
o Transient!virologic!response!!
" 10%!reappearance!of!RNA!during-treatment-(breakthrough)-!
" 20%!reappearacne!of!RNA!after-treatment-(relapse)-!
o Non$response!!
!

GI!$!26!
!
Management!for!non$responders!
$ If!peg$IFN!!!try!combination!treatment!
$ If!improved!liver!enzyme!/!histology!during!treatment!!!consider!maintenance#interferon#!
Hepatitis3D3
Introduction!
$ The!delta!agent!
$ Defective!RNA!virion,!require!HBV!surface!antigen!to!replicate!!
$ Usually!transmitted!by!IVDA!!
!
Clinical!presentations!!
$ Superinfection:!on!top!of!chronic!HBV!
o Severe!relapses!&!more!rapidly!progressive!disease!course!!
$ Coinfection:!infect!together!
o Fulminant!hepatitis!(clinically!indistinguishable!with!acute!Hep!B,!look!for!biphasic!
ALT!rise)!!
!
Investigation!!
$ Anti$HDV!IgM,!IgG!(*occur!in!both!acute!/!chronic!infection)!
Hepatitis3E3
Introduction!
$ RNA!caliciviridae!
$ Transmit!via!faecal!oral!route,!in!contaminated!water!!
!
Clinical!presentation!!
$ Asymptomatic!
$ Prodromal!symptoms:!fever,!profound!malaise,!anorexia,!myalgia,!arthralgia,!rashs,!mild!
diarrhea!!
$ RUQ!pain,!jaundice!
$ Fulminant!hepatitis!(exceedingly!high!mortality!in!pregnant!women!25%)!!
!
Investigations!!
$ Anti$HEV!IgM!
$ ALT:!usually!sky$high,!up!to!>1000!
Alcoholic3liver3disease3
Risk!factors!for!alcoholic!liver!diseases!!
$ Degree!of!consumption:!>8!unit!alcohol!per!day!for!>5!years!!
$ Women!!
o Affected!at!a!lower!alcohol!consumption!threshold!!
o More!prone!to!progression!from!alcoholic!hepatitis!to!cirrhosis!even!if!stopped!
drinking!!
$ Malnutrition!(esp.!protein,!may!potentiate!toxic!effects!of!alcohol)!!
$ Coexisting!liver!disease!!
!
Pathology!!
$ Alcoholic!fatty!liver!!
o Can!occur!within!days!of!heavy!alcohol!intake!!
o Subclinical!
o Reversible!with!abstinence!!
$ Alcoholic!hepatitis!(carries!a!VERY!high!mortality)!!
o Intermediate!stage!between!fatty!liver!and!cirrhosis!(though-some-MAY-skip-it)-!
!

GI!$!27!
 o Spectrum!of!clinical!picture:!non$specific!symptoms!to!fulminant!liver!failure!!
o Fever,!anorexia,!edema,!RUQ!pain,!jaundice,!encephalopathy!!
$ Alcoholic!cirrhosis!!
o An!irreversible!stage!with!micronodular!fibrosis!!
!
Investigation!!
$ CBC:!macrocytosis,!↑!WCC!
$ LFT!
o GGT!↑!
o AST!&!ALT!↑!
" <300IU/dL!!
" AST:ALT!>2:1!
$ RFT,!clotting,!glucose!!
$ AFP!
$ Liver!USG!!
!
Management!of!alcoholic!hepatitis!!
$ Total!abstinence!!
o With!chlordiazapoxide#if!severe!withdrawal!symptoms!!
$ Nutritional!support!!
o 35kcal/kg/day!non!protein!energy!!
o 1.5g/kg/day!protein!(less!if!encephalopathy)!!
o High!dose!vitamin!B!complex!!
$ Detect!and!treat!cirrhotic!complications!!
$ Specific!management!!
o Prednisolone#!
" 40mg/day!for!5!days,!taper!off!over!3!weeks!
" Need!to!exclude!bleeding,!systemic!infection!&!renal!failure!!
" Indications!!
• Maddrey'Discriminant'Factor'(DF)'=-(4.6-x-PT)-+-bilirubin->32'!
• Patients!with!encephalopathy!!
o Pentoxifylline:!for!decompensated!alcoholic!hepatitis!(↑!INR!&!bilirubin)!
" A!phosphodiesterase!inhibitor!with!weak!anti$TNF!effect!!!control!inflam!
reaction!!!improve!prognosis!of!decompensated!alcoholic!hepatitis!
" May!mediate!its!effect!in!reducing!death!hepatorenal!syndrome!
" *!Don’t!use!potent!anti$TNF!(e.g.!Infliximab):!it!↑!mortality!in!alcoholic!
hepatitis!due!to!sepsis!(liver!disease!already!↓!in!immunity)!
o ?!Infliximab/etanercept!!
" Aborting!the!TNF!!
" Result!not!promising!in!small!trials,!↑!infection!risk!!

Alcoholic3complication33
$ Alcoholic!dementia!
o Malnutrition!all!along!in!alcoholic!!!micronutrient!deficiency!!!thiamine!(Vitamin!
B1)!deficiency!!
$ Wernicke!Encephalopathy!(confusion,!ataxia,!ophthalmoplegia,!impaired!short!term!
memory)!!
$ Korsakoff!psychosis!(amnesia!and!confabulation)!if!WE!not!treated!
$ Cardiomyopathy!
$ Cirrhosis!
$ Myopathy!
$ Polyneuropathy!
!

GI!$!28!
$ SDH!+!ICH!(fall)!
$ Delirium!tremens!
o Typically!72!hours!after!withdrawal!
o Prevented!by!chlordiazepoxide,!diazepam,!clomethiazole!(Heminevrin)!
NonQalcoholic3Fatty3liver3Disease33
Pathophysiology!!
$ By!definition!daily!alcohol!consumption!<20g!!
$ Can!be!considered!as!hepatic#manifestation#of#metabolic#syndrome#(hypertension,!
diabetes,!hyperlipidemia,!obesity)!
$ Pathologically!very!similar!to!alcoholic!liver!disease!!
$ A!spectrum!of!manifestation:!simple!hepatic!steatosis!!!NASH!!!fibrosis!&!cirrhosis!
$ Accounts!for!quite!a!number!of!cirrhotic!patients!previously!labeled!"cryptogenic"!!
$ Leading!cause!of!death!is!from!cardiovascular!risks,!not!liver!disease!per!se!!
!
Clinical!presentation!!
$ Asymptomatic,!often-a-silent-disease-
$ Incidental!finding!of!deranged!LFT!
$ Fatigue!/!vague!RUQ!discomfort!±!50%!hepatomegaly!!
!
Investigation!!
$ LFT!
$ USG!for!fatty!changes!!
o Bright!liver!
o Stronger!echoes!in!the!hepatic!parenchyma!than!in!the!renal!parenchyma!vessel!
o Blurring!&!narrowing!of!hepatic!veins!lumen!!
$ Liver!biopsy:!macrovesicular!steatosis!!
o NOT!a!must!for!diagnosis,!as!the!result!seldom!alters!management!
$ Metabolic!work!up!!
o Fasting!glucose!!
o Fasting!lipids!!
o CXR,!ECG!
o RFT!!
!
Management!!
$ Control!the!metabolic!risk!factors!!
o Weight!loss!(rapid!weight!loss!may!exacerbate!steatohepatitis),!exercise!!
o Treat!HT,!DM,!lipids!
$ Look!for!and!detect!cirrhosis!complications!!
Cirrhosis3
Definition!!
$ Decompensated!cirrhosis!(>50%!mortality!in!2!years)!
o Cirrhosis!+!ascites/!persistent!jaundice/!variceal!hemorrhage/!hepatic!
encephalopathy!
!
Diagnosis!!
$ (Gold!standard:!examination#of#an#explanted#liver#at#autopsy/following#liver#
transplantation#during#which#the#architecture#of#the#entire#liver#can#be#appreciated)!
$ Liver!biopsy!
o C/I:!bleeding!tendency,!ascites!
o 0.3%!complication!rate,!e.g.!bleeding,!injury!to!surrounding!organs…!!

GI!$!29!
 o Not!necessary!if!clinical,#laboratory#and#radiological#findings#strongly!suggestive!
of!cirrhosis!(e.g.!ascites,!severe!coagulopathy!&!nodular!shrunken!liver!on!USG)!
$ Routine!scan!(USG)!
o Small!nodular!shrunken!liver,!splenomegaly,!varices,!ascites!
o *!Insensitive!for!fibrosis!&!early!cirrhosis!
$ Serum!test!
o May!involve!uncommon!parameters,!e.g.!apolipoprotien!A,!alpha2$macroglobulin!!!
may!not!be!widely!available!
o Also!may!not!be!accurate!
$ Fibroscan!(transient!elastography)!
o A!mechanical!impulse!generated!&!use!USG!to!detect!the!velocity!of!wave!
propagation,!a!faster!transmission!=!higher!degree!of!cirrhosis!
o Parameter:!liver!stiffness!measurement!!
o Can!decrease!need!for!liver!biopsy!
o Used!for!monitoring!the!degree!of!fibrosis!in!liver,!can!also!visualize!liver!(!!identify!
HCC)!
o Measure!liver!tissue!volume!100!times!of!liver!biopsy!(↓!sampling!error)!
o But!invalid!results!in!context!of!present!ascites!&!in!acute!hepatitis!(overestimate)!
!
Etiology!!
$ Chronic!hepatitis!B!
$ Chronic!hepatitis!C:!needle!injection!sites!
$ Alcoholic!liver!disease:!dupytrens!contracture,!parotid!enlargement!!
$ Non$alcoholic!fatty!liver!disease!
$ Autoimmune!!
o Autoimmune!hepatitis!
o Primary!biliary!cirrhosis!(PBC):!xanthelasma,!xanthomata,!(osteoporosis)!!
o Primary!sclerosing!cholangitis!(PSC)!
$ Genetic!!
o Wilson's!disease:!extrapyramidal!movement!disorders,!affective!features,!KF!rings!!
o Hemochromatosis:!clay!grey!complexity,!arthritis,!dilated!cardiomyopathy,!
hypogonadism!(osteoporosis)!
o Alpha$1$antitrypsin!deficiency:!emphysema-!
$ Drugs:!amiodarone,!methotrexate,!methyldopa!!
$ Budd$Chiari!syndrome!
$ Cryptogenic!!

Physical!examination!
$ Ascites!!
$ May!have!skin!hyperpigmentation!over!LL!
o DDx:!venous!insufficiency!
!
Investigation!for!cirrhosis!
$ Blood!taking!
o CBC:!pancytopenia!due!to!hypersplenism!
" Macrocytic!anemia!due!to!chronic!liver!disease!
" Thrombocytopenia!&!mild!neutropenic!due!to!hypersplenism!
o LFT:!assess!severity!
" If!patient!have!nephrotic!syndrome!!!albumin!level!is!not!reliable!to!assess!
severity!
" Reversed!A/G!ratio:!↑!in!IgA!production!in!cirrhosis!due!to!↑!in!immunogenic!
stimulation!!
!

GI!$!30!
 • Gut!antigens!shunt!direatly!to!systemic!circulation!through!porto$
systemic!shunts!
• Production!of!abnormal!Ag!by!cirrhotic!liver!
• Liver!is!responsible!to!remove!immunogen!
o RFT:!electrolyte!disturbance!
o CaPO4:!primary!biliary!cirrhosis!may!affect!absorption!of!fat!soluble!vit!!!affect!Ca!
absorption!
o HBV,!HCV,!HAV!
o AutoAb:!anti$nuclear!Ab,!anti$smooth!muscle!Ab,!anti$liver!kidney!microsomal!Ab,!RF,!
anti$mitochondrial!Ab!
o Copper,!ceruloplasmin:!Wilson’s!disease!
o Fe!profile:!hemochromatosis!
o Alpha$1$antitrypsin!
o Cholesterol,!fasting!lipid!level:!non$alcoholic!steatohepatitis!(NASH)!
$ USG!abdomen!
o Portal!tract!
o Hypersplenism!
o Gallstone!
o Intrahepatic!stone:!RPC!
o Ascites!!
$ OGD:!esophageal!varices!
!
Complication!
$ Portal!hypertension!
o Esophageal!variceal!bleeding!!
" Junction!between!portal!&!systemic!venous!systems:!gastroesophageal!
junction,!retroperitoneal,!umbilical,!rectal!plexus!
o Portohypertensive!gastropathy!
o Ascites!&!spontaneous!bacterial!peritonitis!
o Hypersplenism!!
$ Liver!failure!
o Hypoglycemia!
" In!patient!presenting!with!confusion!!!r/o!hypoglycemia!before!considering!
encephalopathy!!
o Hepatic!encephalopathy!
o Hepatorenal!syndrome!
$ Hepatocellular!carcinoma!
!
Child$Pugh!grading!of!cirrhosis!
$ Albumin,!Bilirubin,!Clotting!(PT),!Distention!(ascites),!Encephalopathy!
! 1!! 2!! 3!! Clinically!how!to!assess?!
Bilirubin!(umol/l)!! <34!! 34$51!! >51!! Jaundice!!
Albumin!(g/L)!! >35!! 28$35!! <28!! Leukonychia!
Prothrombin!time!(sec)!!1$3!! 4$6!! >6!! Bruising!
Ascites!! $!! Slight!! Moderate!! Ascites!
Encephalopathy!! $!! Grade!I/II!! Grade!III/IV!! Flapping!tremor!
$ Grade!A!=!5$6!*!Grade!B!=!7$9!*!Grade!C!=!≥10!
$ All!cirrhotic!patients!need!to!calculate!the!Child’s!score!
o If!Child!C!&!patient!<60!years!!!refer!to!liver!Tx!
$ Alternative:!MELD!(Model!for!End$Stage!Liver!Disease)!score!
o Use!bilirubin,!creatinine!&!INR,!assess!whether!suitable!for!Tx!
!

GI!$!31!
!
Management!!
$ Treat!the!underlying!cause!
$ Early!detection,!prevent!&!treat!cirrhotic!complications!
$ Propranolol!
o Used!in!portal!HT:!lower!portal!BP!!!prevent!esophageal!bleeding!
" Adequate!dose!when!HR!↓!for!20%!from!baseline!or!to!50$60/min!
$ Liver!transplantation!
Ascites3
Pathogenesis!!
$ Systemic#arterial#vasodilation#!!RAS/sym/ADH!fluid!retention!!
$ Increased!hydrostatic!pressure!due!to!portal!hypertension!!
$ Reduced!oncotic!pressure!due!to!hypoalbuminemia!!!transudation!
$ Peritoneal!irritation/metastasis!!
!
Clinical!implications!!
$ No!ascites!≥!6!years!survival!!
$ Mild!ascites!=!5!years!survival!!
$ Refractory!ascites!=!1!years!survival!!
o Defined!as!ascites!persist!despite!maximal!salt!restriction!&!diuretic!therapy!
!
DDx!of!acute!exacerbation!of!ascites!in!cirrhosis!
$ Non$compliance!of!treatment!!
o Salt!and!fluid!restriction!
o Drug!treatment!compliance!
o Need!to!ask!direct!history!of!drug!and!FU!compliance!!
$ Drug!!
o TCM!!
$ Infection!!
o Flare!up!of!hepatitis!B!
o HAV!unlikely!~!all!infected!after!40!years!old!!
o HEV:!Ask!for!any!high!risk!dietary!restaurant!!
$ SBP!(spontaneous!bacterial!peritonitis)!
o No!prominent!symptoms,!may!even!not!have!abdominal!pain!at!all!
" Since!the!marker!is!diluted!by!ascetic!fluid!!
o ∴!Need!to!rule!out!SBP!even!without!symptoms:!need!to!send!aspirate!for!cytology!
with!differential!(polymorph!>250!cells/µL!diagnostic)!
$ HCC!±!portal!vein!thrombosis!
o CLD!+!Unexplained!sudden!deterioration!of!LFT!!!think!of!HCC!!!!
o Sudden!surge!of!Portal!HT!
" Portal!HT!Vs!nephrotic!syndrome!flare!up:!nephrotic!syndrome!also!have!
ankle!edema!(anasarca)!&!morning!facial!puffiness!
o OV!!!think!of!HCC!!!!
$ Alcohol!
$ Malaria!EXPOSURE!!
o Although!RARE,!still!need!to!r/o:!be!open$minded!!!
!
Investigation!of!the!patient!(according!to!DDx)!!
$ Functional!status!of!Liver!!
o ALT!(Alkaline!transaminase)!
o Childs!grading:!PT,!Bilirubin,!Albumin!
!

GI!$!32!
$ Flare!up!of!hepatitis!B!!
o ALT:!Normal!against!flare!up!of!Hep!B!
o IgM!anti!core!(HBcAg)!antibody!
o HBV!DNA!(viral!load):!Likely!viremia!in!flare!up!
o X!HbeAg:!even!e!–ve!hepatitis!may!still!have!flare!up!!!
$ Abdominal!diagnostic!tap!!
o Unlimited!drainage,!but!if!>5L!drained,!need!5^10g#IV#albumin#for!each!liter!drained!
!!prevent!severe!recollection!hypovolemia!due!to!reaccumulation!of!ascitic!fluid!
o Tap!on!left!lower!quadrant!as!sigmoid!colon!is!more!mobile!!
o Peritoneal!fluid!analysis!!
" Serum^ascites#albumin#gradient#(SAAG):#portal#HT#Vs#non^portal#HT!
• High!gradient!(>11!g/L)!!!ascites!is!due!to!portal!HT!
o High!protein!(>2.5):!heart!failure,!Budd!Chiari!syndrome!
o Low!protein!(<2.5):!cirrhosis!of!the!liver!
o Also:!portal!vein!thrombosis,-venoocclusive!disease!
• Low!gradient!(<11!g/L)!!!non$portal!HT!causes!
o Nephrotic!syndrome,!TB,!malignancy,!pancreatitis,!connective!
tissue!disease!
" Cell!count!with!differentials:!look!for!neutrophil!>250!(SBP)!
" Gram$smear,!TB!smear,!bacterial!culture,!TB!culture!!
• C/ST:!10!ml!of!ascetic!fluid!in!blood!C/ST!bottle!(increased!diagnostic!
yield)!since!sensitivity!is!only!70%!
" Amylase!for!pancreatic!cause!
" Low!glucose!level!suggests!TB!/!malignancy!!
" Cytology!!
$ USG!(guide!drainage,!look!for!peritoneal!nodules)!!
!
Why!treating!ascites?!!
$ Reduce!diaphragmatic!splintage!!!less!SOB!!
$ Reduce!incidence!of!SBP!!
$ Reduce!energy!consumption!in!heating!up!fluid!!
!
Managements!!
$ Sodium!&!water!restriction!!
o Sodium!<2g/day!(~87mmol/day):!no!added!salt!diet!
" If!tap!10L!ascites!fluid!!!remove!~1400mmol!Na!!!need!~2!weeks!to!
reaccumulate!ascites!even!no!Na!is!loss!through!urine!(complete!refractory!to!
diuretics),!∴!if!reaccumulate!within!2!weeks!!!indicate!poor!salt!compliance!!
o Water!restriction!of!0.5$1L/day!ONLY!when!sodium!<120mmol/l!!
o Avoid!drugs!that!!
" Promote!water!retention!(steroids,!NSAIDs,!thiazolidenediones)!!
" Have!high!sodium!content!(iv#antibiotics#like!cephalosporins,!aspirin,!
phenytoin,!panadol)!!
• *!Cefotaxime!Sodium!in!PWH!=!48mg!Na!in!1!g!!
$ Diuretics!!
o Spironolactone#(100^400mg/day)#!
" Use!spironolactone!(aldosterone!antagonist)!rather!than!lasix!in!ascites!due!to!
cirrhosis!
• Because!in!cirrhosis:!fluid!is!trapped!to!extravascular!space!!!↓!
intravascular!volume!!!trigger!RAAS!!!use!aldactone!to!counteract!it!
" Switch!to!eplerenone#/!amiloride#if!S/E!develops!(e.g.!painful!gynaecomastia!
–!liver!failure!itself!can!already!cause!gynaecomastia)!
!

GI!$!33!
 o +#Frusemide#if!refractory!/!hyperK!
o **!Monitor!body!weight!to!guide!diuresis,!aim!reduction!~0.5kg/day#!
" Only!~700$900ml!of!peritopeal!fluid!can!travel!back!into!intravascular!spaces!
daily,!∴!daily!loss!of!!>1kg!weight!may!indicate!overdiuresis!
$ Large!volume!(>5L)!therapeutic!paracentesis!!
o Indication!
" Refractory!to!medical!treatment!(max!diuretic!/!renal!failure!when!using!
diuretics,!water!&!Na!restriction)!
o Provide!immediate!relief!of!cardiorespiratory!distress,!for!refractory!ascites!
o Before!doing!it,!should!
" Stop!diuretics!1$2!days!before:!diuretics!cause!substantial!impact!to!renal!Fx!&!
precipitate!HRS!
" Rule!out!dehydration!
" Check!BP/P!to!ensure!hemodynamically!stable!
" Check!RFT:!rule!out!deterioration!of!renal!function!
" Otherwise,!may!precipitate!hepatorenal!syndrome!
o Add!5$10g!IV!albumin!cover!for!each!liter!drained!!
" ↓!risk!of!SBP,!replace!intravascular!volume,!prevent!recollection!hypovolemia!
" Alternative:!colloid!infusion!(cheaper!but!less!effective)!
o Contraindications!!
" Acute!/!chronic!kidney!injury!
• Large!volume!paracentesis!cause!sudden!pressure!difference!!!water!
draw!out!to!3rd!space!!!↓!intravascular!volume!!!pre$renal!failure!
• Prevented!by!IV!albumin,!withhold!diuretics!/!nephrotoxic!drugs!(e.g.!
NSAIDs)!
" Hypotension!
" Sepsis,!SBP!
• Already!vasodilatation,!↓!in!intravascular!volume!may!trigger!
circulatory!collapse!
" Recent!variceal!bleeding!
• Further!↓!in!intravascular!volume!!!↓!perfusion!!!renal!failure!
" Hepatic!encephalopathy!!
• ↓!autoregulation!to!brain,!if!↓!perfusion!!!worsen!encephalopathy!
• ↓!risk!by!giving!lactulose!!
" !!do!controlled!volume!paracentesis!(e.g.!2$4L/day)!instead!(still!give!
albumin!cover)!
o S/E!
" Recollection!hypovolemia!(cover!with!IV!albumin)!!
• Rapid!reaccumulation!of!ascites!due!to!activation!of!renin!
" Hyponatremia!!
" Protein!loss!aggravating!malnutrition!!
o Monitor!BW,!RFT!
$ LeVeen!shunt!(not!useful,!even!↑!mortality!due!to!infection)!
o Long!tube!with!one$way!valve!running!subcutaneously!connecting!the!peritoneal!
cavity!with!the!IJV!
o Complications:!infection,!SVC!thrombosis,!acute!pulmonary!edema!!
$ TIPS!(transjugular!intrahepatic!portosystemic!shunt)!
o For!refractory!ascites,!but!does!not!prolong!life!!
o Contraindications!!
" General!surgical!C/I:!bleeding!tendency!
" Severe!hepatic!encephalopathy!!
!

GI!$!34!
 " Severe!right!heart!failure:!shunt!↑!right!heart!load!
" Polycystic!liver!disease!
" Shrunken!liver!vasculatures:!difficult!to!do!!
" Child's!C!cirrhosis!
" Patients!allergic!to!IV!contrast!!
" Relative!contraindications!
• Portal!and!hepatic!vein!thrombosis!
• Pulmonary!hypertension!
• Hepatopulmonary!syndrome!
• Active!infection!
• Tumor!within!expected!path!of!shunt!
$ Liver!transplantation!!
Spontaneous3bacterial3peritonitis3(SBP)33
Introduction!!
$ Bacterial!peritonitis!in!patients!with!ascites!in!the!absence!of!recognized!secondary!causes,!
e.g.!bowel!perforation!
$ Usually!Gram$ve!(>70%)/!Streptococcus!(enterococcus)!
$ Almost!always!in!context!of!clinically!detectable!ascites!!
$ 25%!of!cirrhotic!with!ascites!develop!SBP!
$ High!short!term!mortality:!20$30%!in$hospital!mortality!(renal!/!liver!/!multi$organ!failure)!
$ 32%!mortality!at!1!months,!78%!mortality!at!1!year!
!
Pathogenesis!
$ Increased!bacterial!gut!translocation!!
o Slow!gut!transit!with!bacterial!overgrowth!!
o Gut!edema!(due!to!hypoalbuminemia)!
o Reduced!mucosal!IgA!(due!to!↓!protein)!
$ Reduced!peritoneal!defense!!
!
Presentations!!
$ Fever!(usually!mildly!hypothermic)!!
$ Altered!mental!state!
$ Abdomen!tenderness!!
$ *!50%!may!be!asymptomatic!
!
Diagnosis!(diagnostic!small!volume!paracentesis)!
$ Absolute!polymorph!count!>250!cells/µL!or!TWCC!>!500!!!most!important!Ix!=!cell#count!!!
$ Gram!smear!&!culture!expected!to!be!low$yielding,!since!SBP!usually!has!a!low!bacterial!load!!
!
DDx:!secondary!bacterial!peritonitis!
$ GI!perforation!/!abscess!
$ Ascitic!fluid:!multiple!organisms!in!Gram!stain,!high!protein,!low!glucose,!high!LDH!
$ Mx:!urgent!imaging!&!surgical!consultation!
!
Treatment!!
$ IV!Cefotaxime#(or!quinolone:!norfloxacin!/!ciprofloxacin)!
o Cover!G$ve!&!streptococcus!(translocation!of!GI!bacteria)!
$ Volume!expansion!(high!dose!albumin!1.5g/kg!at!1st!day!then!1g/kg!at!3rd!day)!!
o Maintain!intravascular!volume!!!↓!risk!of!renal!failure!
$ Start!life$long!A/B!prophylaxis!(secondary!prevention):!ciprofloxacin!/!norfloxacin!

GI!$!35!
 o Without!prophylaxis:!recurrence!rate!is!>50%!in!the!following!year!&!mortality!of!2nd!
SBP!is!higher!
!
Prevention!
$ Primary!prevention!
o Active!upper!GIB:!3rd!GC!
o Child's!B$C!cirrhosis!with!ascitic!fluid!total!protein!<15g/l!(high!risk!due!to!low!Ig)!!!
quinolone!
$ Secondary!prevention:!after!1!episode!of!SBP!(68%!recurrence!rate!in!1!year)!!!quinolone!
Esophageal3variceal3bleeding33
Background!!
$ Varices!occur!in!50%!of!patients!with!cirrhosis!at!time!of!diagnosis!usually!!
$ Develop!when!hepatic#venous#pressure#gradient#>12mmHg#!
$ Development!rate!of!varices:!7%!per!year!
$ Growth!rate!of!varices:!7%!per!year!
$ High!risk!of!bleeding!!
o Large!size!
o Red!wale!marks!
o Advanced!liver!disease!(Child's!class!B/C)!!
o High!HVPG!!
!
Pathogenesis!!
$ Cirrhosis!!
$ Increased!resistance!to!portal!flow!(anatomical!&!functional)!!
$ Increased!portal!pressure!!
o Increased!vasodilating!factors!(NO)!!!new!vessels!formation!!
o Splanchnic!vasodilation!!!increase!portal!blood!flow!!!(2)!!
$ Variceal!formation!!
!
Presentation!
$ Hematemesis,!tarry!stool,!features!of!chronic!liver!disease!(e.g.!thrombocytopenia!due!to!
hypersplenism),!hepatic!encephalopathy!(↑!ammonia!due!to!breakdown!of!RBC)!
!
How!to!predict!bleeding!risk!from!OV?!!
$ Child's!B$C!cirrhosis!
$ Platelet!count!(/mm3)!to!spleen!size!(maximum!bipolar!diameter!by!USG!in!mm)!!
$ Large!varices!
$ Red!wale!sign!(surface!of!varices!is!stretched)!!
!
Primary!prophylaxis!against!variceal!bleeding!!
$ Screen!all!cirrhotic!patients!for!varices!
$ Propranolol#/#nadolol#/#low!dose!Carvedilol#(more!potent!than!propranolol)!
o Start!at!20mg!(P)!/!40mg!(N),!go!to!maximal!tolerated!/!HR!<55,!continue!indefinitely!
$ Endoscopic#variceal#band#ligation#!
o Q2$4wk,!until!variceal!obliteration!achieved,!usually!in!2$4!sessions!
o Followed!by!surveillance!endoscopy!every!6$12!months!(no!need!BB!after!EBL)!
$ !(Other!potential!agents!include!ACEI,!nitrates,!simvastatin)!!
!
Prevention!of!varices!and!first!variceal!bleeding!!
$ Small#varices#+#no#red#wale#marks,#no#severe#liver#disease#!
o Optional!for!nonselective!beta$blockers!(aim!HR<60),!OR!!
!
o Periodic!screening!for!variceal!growth!!
GI!$!36!
$ Small#varices#+#red#wale#marks/#severe#liver#disease#!
o Non$selective!beta$blockers!!
$ Large#varices#!
o Nonselective!beta$blockers;!OR!!
" Low!cost!
" Can!prevent!portohypertensive!gastropathy,!hypersplenism,!ascites!&!SBP!!
" No!expertise!needed!
" No!procedural!side!effects!(lethal!hemorrhage!from!post$procedure!ulcers)!
" Contraindicated!in!bradycardia,!asthma,!COPD,!PVD!!
o Endoscopic!variceal!ligation!(in!HK,!second!line!only!if!intolerable!to!BB)-!!
" Can!be!performed!at!time!of!endoscopic!screening!!
" Need!surveillance!endoscopy!every!6$12!months!!
" No!drug!side!effects!(fatique,!SOB)!!
!
Treatment!of!acute!variceal!bleeding!!
$ Resuscitation!+!Assess!severity!(BP/P,!Hb,!Urea)!&!indication!for!urgent!OGD!!
$ Pre$endoscopy!management!!
o NPO,!IVF!
o Crossmatch,!CBC,!LFT,!RFT,!clotting!
o Transfuse!up!to!Hb!7,!correct!coagulopathy!with!FFP,#platelet,#Vit#K#!
" Don’t!over$transfuse!patient:!↑!intravascular!volume!↑!risk!of!bursting!varices!
o Close!monitor!of!vitals,!u/o,!CVP!(aim!6$12cmH2O)!
o Vasoactive#agents:!stop!bleeding!in!80%!!! Key!points:!
" 1st!line:!somatostatin/#octreotide/#vapreotide#! 1. Stop!bleeding!
" Alternative:!terlipressin#(analogue!of!vasopressin)!! 2. Prevent!SBP!
• But!serious!S/E:!acute!MI,!bradycardia,!colic,! 3. Prevent!HE!
concomitant!infusion!of!nitroglycerin!may!help!
" Given!at!time!of!admission,!for!2$5!days!!
" Use:!↓!portal!pressure!by!splanchnic!vasocontriction,!less!engorged!varices,!
enhance!endoscopic!Rx,!↓!bleeding!rate!
o Prophylactic!antibiotics:!↓!risk!of!SBP!
" Ciprofloxacin#!
" Ceftriaxone:!for!severe!liver!disease,!esp!when!already!put!on!a!quinolone!
o Lactulose:!↓!risk!of!hepatic!encephalopathy!
$ Early!(<12h)!endoscopic!therapy!!!
o Choice!!
" Variceal#band#ligation#(better!but!need!to!repeat!procedure,!5!sessions!to!
complete!obliteration)!
" Sclerotherapy!!
• Many!S/E:!sclerosed!veins,!esophageal!stricture,!dysphagia,!ulcer…!
• But!can!be!done!in!1!single!session!(one$off),!∴use!in!those!with!limited!
life!expectancy,!e.g.!terminal!malignancy!
" *!Combination!of!the!two!is!no!better!but!more!complications!(PE,!esophageal!
perforation,!ulcers)!!
" *!Use!histoacryl!glue!for!gastric!varices!
o Post$endoscopic!care!!
" Monitor!S/S!of!rebleeding!
" Monitor!vitals,!U/O,!alertness,!CBP!(Hb),!clotting,!RLFT!(urea)!
" Watch!out:!SBP,!encephalopthy,!renal!failure,!aspiration!pneumonia!
" Continue!vasoactive!drugs!&!antibiotics!for!5$7!days!
" Lactulose!(prevent!HE)!!
!
• Bleeding!↑!protein!load!in!gut!!!risk!of!encephalopathy!!
GI!$!37!
 • Aim!to!maintain!BO!2!times/day!
$ IF!FAILED:!balloon#tamponade#+#repeated#endoscopy#!
o Sengstaken$Blakemore!tube!!
" 3!lumens:!gastric!balloon!+!esophageal!balloon!+!stomach!suction!!
o Minnesota!tube!!
" Additional!lumen!above!esophageal!balloon!for!saliva!suction!!
o Linton!tube!!
" No!esophageal!balloon!with!larger!gastric!balloon!capacity!of!700ml!!
$ IF!FAILED:!placement!of!TIPSS!/!surgical!shunting!/!devascularization!!
!
Prevention!of!recurrent!variceal!bleeding!!
$ Treatment!options!!
o Nonselective#beteblocker#+#variceal#ligation#!
" In!a!RCT:!lower!rate!of!rebleeding!than!combined!pharmacotherapy!!
• But!bleeding!from!all!sources!similar!due!to!bleeding!from!post$
procedural!esophageal!ulcer!
" In!metaanalysis:!rate!of!rebleeding!from!all!source!is!lower!!
• But!no!improvement!in!survival!
o Nonselective#betablocker#+#nitrates#!
" Adopt!if!patient!cannot!tolerate!the!above!regime!!
$ Treatment!goal!!
o HVPG!decreased!to!<12mmHg,!or!HVPG!decreased!by!20%!!
$ *!If!the!variceal!bleeding!is!recurrent!&!refractory!!!think!about!portal#vein#thrombosis,!
which!may!require!anticoagulants,!thrombolysis!or!shunting!
Portal3hypertensive3gastropathy33
$ Result!from!portal!hypertension!!!increased!blood!flow!to!stomach!
!
Endoscopic!features!in!GASTRIC!FUNDUS!OR!BODY!!
$ Mosaic!/!reticular$like!pattern!/!"snake$skin"!appearance!of!mucosa!!
$ Ectatic!blood!vessels!
$ Redspot!(recent!hemorrhage)!!
!
Clinical!presentations!!
$ Iron$deficiency!anemia!(fresh!blood!/!melana!is!RARE!)!!
!
Management!!
$ Nonselective!betablocker!+!iron!supplementation!±!transfusion!
$ If!failed!!!shunting!
$ *!If!gastropathy!is!localized,!argon!plasma!coagulation!can!be!tried!!
Liver3failure3
Types!!
$ Acute!
$ Decompensated!cirrhosis!!
!
Etiology!
$ Infections!!
o HAV,#HBV,!HCV,!HDV,!HEV!!
o Yellow!fever,!leptospirosis!!
$ Drugs/toxins!!
o Paracetamol#overdose,!halothane,!anti$TB!!
o Amanita!palloides,!carbon!tetrachloride!!
!

GI!$!38!
$ Vascular!!
o Ischemic#shock#!
o Budd!chiari!syndrome!(occlusion!of!hepatic!veins)!
$ Autoimmune!and!metabolic!!
o Acute!fatty!liver!of!pregnancy,!Reye’s!syndrome!(a/w!aspirin!usage!in!children)!
!
Investigations!!
$ Baseline!blood!!
$ Liver!function!!
o LFT,!clotting,!glucose,!ammonia!!
" INR!is!very!sensitive,!∴!if!bilirubin!↑↑↑!but!INR!normal!!!consider!other!
cause!of!↑!bili!(e.g.!hemolysis!!!look!at!retic!count,!indirect!bili,!haptoglobin!
(but!↓!may!due!to!↓!synthetic!function!of!liver),!LDH,!blood!smear!x!
schizocyte,!direct!Coombs!test…)!
" ALT!slightly!↑!in!end$stage!liver!failure!(Vs!ALT!↑↑↑!in!acute!state)!
" Albumin!↓!
" Urea!↓!as!it’s!produced!by!liver!
$ Etiology!!
o Anti$HAV!IgM/IgG,!anti$HEV!IgM!
o HBsAg,!anti$HBc!IgM!!
o Anti$HCV!
o Paracetamol!level!!
!
Management!!
$ Treat!the!underlying!cause!!
$ General!!
o Head!up!30!degree!!
o Monitor!!
" Temp/BP/P!
" Chart!I/O,!body!weight!
" LFT,!clotting,!glucose!!
o Nutritional!supplement!+!thiamine!+!folate!!
$ Treat!complications!!
o Clotting!derangement!!!Vitamin!K1,!platelets,!FFP!!
o Hypoglycemia!!!50ml!of!D50!if!<2mmol/l!!
o Encephalopathy!
o Cerebral!edema!!!mannitol!infusion,!hyperventilation!!
o Renal!failure!!

Hepatorenal3syndrome3(HRS)3
Pathogenesis!!
$ Splanchnic!arterial!vasodilation!with!reduction!in!effective!circulatory!volume!!
$ Raised!neuropeptide-Y,-ADH,-RAS-system,-noradrenaline!
$ Leading!to!intense!renal!(glomerular!afferent)!vasoconstriction!!!kidney!hypoperfusion!!
$ *!No!structural!damage!of!kidney!
!
Precipitating!factors!!
$ Diuresis!
$ Large!volume!paracentesis!!
$ SBP!
$ GIB!!
!
!

GI!$!39!
Type!!
$ Type!1!
o Rapidly!progressive!oliguric!renal!failure!
o Severely!ill!patients,!Child!C,!ppt!by!diuresis/!large!volume!paracentesis/!GIB/!SBP!
o Median!survival!<2!weeks!
$ Type!2!
o Chornic!form,!steady!deterioration!
o Child!B!patients!with!relatively!preserved!liver!function!!
o Median!survival!<6!months!
!
Diagnostic!criteria!!
$ Cirrhosis!with!ascites!
$ Creatinine!>133umol/l!
$ No!improvement!of!serum!creatinine!after!at!least!2!days!of!diuretic!withdrawal!&!albumin!
volume!expansion!!
$ Absence!of!shock!!
$ Absence!of!nephrotoxic!agents!
$ Absence!of!parenchymal!kidney!diseases!!
o Proteinuira!>500mg/day!
o Microscopic!hematuria!(>50RBC!on!high!power!field)!!
o Abnormal!renal!ultrasound!!
!
Treatment!!
$ A!fluid#challenge#to!distinguish!from!pre$renal!failure!!
$ IV!albumin:!improve!renal!function!but!not!survival!for!volume!expansion!
$ Terlipressin:!divert!blood!to!kidney!!!improve!renal!function!(but!not!survival…)!
$ Octreotide#+#midodrine#(alpha!1!agonist)!!
$ TIPSS!
$ Liver!transplantation!!

Hepatic3encephalopathy3(HE)3
Pathogenesis!
$ Factors!
o Impaired!liver!function!
o Porto$systemic!shunt!
o Muscle!wasting!(muscle!is!a!major!extrahepatic!ammonia!metabolising!site)!
$ Three!hypotheses!
o Ammonia!cross!BBB!!!metabolized!by!astrocytes!&!turn!into!glutamine!!!↑!osmotic!
pressure!!!astrocytic!swelling,!cytotoxic!cerebral!edema!!
" Plasma!NH3!normally!<!35umol/L!
o Increased!activity!of!GABA!system!!!↓!energy!supply!to!other!brain!cells!!
o False!neurotransmitters:!octopamine,!amino!acids,!mercaptans,!fatty!acids!
!
Precipitating!factors!!
$ High!protein!diet!
$ Upper!GIB!
$ Constipation!
$ Electrolyte!disturbances!(hypoK!↓!renal!ammonia!excretion):!diuretic,!vomiting,!diarrhea!!
$ Sedative!drugs!!
$ Sepsis:!SBP,!urinary,!chest!
$ Large!volume!paracentesis!!
$ Operation:!portal!systemic!shunts,!blood!loss,!anaesthesia,!shock!etc!
!

GI!$!40!
!
Grading!
$ G1:!Reversed!sleep!wake!cycle,!altered!mood!&!behavior!!
$ G2:!Flapping#tremor,!drowsiness!&!inappropriate!behavior!!
$ G3:!Confusion!&!inarticulate!speech,!stuporous!but!speak!&!obey!simple!commands!
$ G4:!Coma!
!
Physical!examination!
$ Asking!patient!to!draw!a!STAR✩ (not!this!one!✡)!for!any!constructional!apraxia!
$ Buttoning!the!clothes!!
$ Light!a!match!
!
Treatments!(Current!Rx!mainly!based!on!the!Ammonia!hypothesis)!
$ Identify!precipitating!factors!
o Stop!diuretics!or!sedatives!!
o Check!&!correct!hypoK!
o Treat!existing!sepsis!
$ Rehydration!
$ Lactulose#
o A!non$absorbed!disaccharide!broken!down!by!bacteria!to!acetic!&!lactic!acid,!
trapping!the!ionic!form!of!ammonia!(NH4+)!inside!colon!
o ↓!colonic!transit!time,!↓!bacterial!fermentation!that!forms!ammonia!!
o 45$90g/day,!aim!2!loose!stool!per!day!with!pH<6!!
o S/E:!diarrhea,!abdominal!cramping,!flatulence!
$ Oral!antibiotics:!bowel!decontamination!
o Rifaximin!550mg!BD!PO!better!S/E!profile!(minimal!absorption),!getting!popular!!!
o Neomycin!(otorenotoxicity):!used!in!the!past!
o Metronidazole!(peripheral!neuropathy)!
$ Dietary!protein!restriction!(temporary)!
o <20g/day!with!glucose!supplement!
o If!well,!increase!10$20g!every!48!hours,!to!40$60g/day!which!is!usually!the!limit!of!
cirrhotic!patients!!
o *!When!no!HE!!!↑!protein!intake!as!protein!deficiency!in!cirrhosis!lead!to!
proteolysis,!which!↑!risk!of!encephalopathy!
$ Liver!transplantation!!
!
Other!potential!treatments!!
$ Ammonia!hypothesis!!
o Enema!!
o Ornithine$aspartate:!stimulate!ammonia!metabolism!in!liver!!
$ GABA!hypothesis!!
o Flumazenil:!transient!benefit!(1!day)!!
$ False!neurotransmitter!hypothesis!!
o Branch$chain!amino!acid!infusion!!

Hepatopulmonary3syndrome3
$ Resistance!hypoxemia!(increased!A$a!gradient)!!
$ Intrapulmonary!vascular!dilation!(left!to!right!shunt!in!contrast!enhanced!echocardiogram)!
$ Characteristic!reduction!in!arterial!oxygen!saturation!on!standing!!
$ Other!causes!of!hypoxemia!in!cirrhotic!patients!
o Pulmonary!hypertension!!
o Pleural!effusion!
!

GI!$!41!
Paracetamol3overdose3
Pathophysiology!!
$ Normally,!liver!metabolizes!majority!of!paracetamol!to!nontoxic!conjugates!!
$ ~10%!converted!by!P450!to!a!highly!reactive!electrophilic!toxic!intermediate!NAPQI,!which!
usually!neutralized!by!thiol!groups!of!hepatic#glutathione!
$ In!overdose,!these!glutathiones!are!depleted!!!oxidative!damage!to!hepatocytes!occur!!
$ Lead!to!hepatic!failure!!
$ Patients!usually!die!from!fatal#cerebral#hemorrhage#(coagulopathy,!encephalopathy,!
cerebral!edema)!!
!
Clinical!presentations!!
$ Initially:!asymptomatic,!nausea!
$ Hours:!vague!abdominal!pain!
$ 2$3!days:!hepatic!failure,!lactic!acidosis!!
!
Investigations!!
$ CBC,!LFT,!RFT,!clotting,!glucose!
o Monitor!bilirubin,!albumin,!PT:!markers!for!decompensation!
o Most!sensitive!=!PT:!t½!of!factor!7:!6$8!hour!
$ ABG!!
$ 4h!paracetamol!level!!
!
Management!!
$ Rationale!!
o To!support!patient,!make!him!survive!through!the!acute!episode,!whereafter!hepatic!
regeneration!is!excellent!!
$ N^acetylcysteine/#methionine#!
o Thiol!containing!amino!acids!
o Serve!as!hepatic!glutathione!precursors,!or!directly!reduce!NAPQI!
o Indicated!when!serum#paracetamol#level#post^4h#is!above!the!treatment#line'!
" High!risk!treatment!line:!alcoholic,!on!enzyme!inducers,!anorexic!!
" Normal!treatment!line!!
$ Supportive!measures!for!liver!failure!!
o Correct!clotting!derangement!!
o Correct!hypoglycemia!
o Prevent!hepatic!encephalopathy!!
o Prevent!cerebral!edema!!
$ Liver!transplantation!(King's#college#criteria)!!
o Arterial!pH!<7.2!24h!after!ingestion!!
o Or!ALL!OF!THE!FOLLOWING!!
" PT!>100sec!
" Creatinine!>300umol/l!!
" Grade!III/IV!encephalopathy!!
Vascular3problem3in3liver33
Ischemic3hepatitis33
$ Also!called!the!"shock!liver"!
$ An!acute!insult!to!liver!due!to!a!hypoperfusion!episode!!
$ Result!in!sky$high!liver!enzyme!release!!

Cardiac3cirrhosis33
$
!
Chronic!liver!congestion!from!right!heart!failure!!
GI!$!42!
$ Nutmeg!appearance!&!centrolobular!fibrosis!!
$ Treatment:!control!the!heart!failure!!

Budd3Chiari3syndrome33
$ An!occlusion!of!hepatic!vein!
$ Pathology!similar!to!cardiac!cirrhosis,!but!clinically!lacks!features!of!heart!failure!!
$ Etiology!!
o Thrombosis!75%!!
o External!compression!25%!(e.g.!tumors)!!
$ Diagnosis!!
o Liver!Doppler!USG!!
o CT!scan!
$ Treatment:!anticoagulation!if!thrombosis,!resection/stenting!in!compression,!TIPSS!!

Venoocclusive3disease3(Hepatic3sinusoidal3obstruction3syndrome)33
$ Occlusion!of!small!veins!in!liver!
$ Usually!as!a!result!of!chemotherapy!before!bone!marrow!transplantation!!
$ Diagnosis!!
o Liver!Doppler!USG!!
o Liver!biopsy!!
Autoimmune3hepatitis3
Introduction!!
$ Exact!cause!unknown,!proposed!to!be!from!hepatotropic!viral!infection!(measles,!herpes)!
$ Leads!to!suppressor!T$cell!defects,!hence!autoantibody!against!hepatocytes!surface!antigen!
$ Young!&!middle!aged!female!!

Type!!
$ Adults!of!children;!SMA!80%,!ANA!10%!!
$ Children;!LKM1;!more!commonly!progress!to!cirrhosis!!
!
Presentations!!
$ Acute!hepatitis!+!autoimmune!features!
o Fever,!malaise,!urticaria!!
o Polyarthritis!
o Pleurisy!!
o Glomerulonephritis!!
$ Liver!failure,!Cirrhosis!!
$ Amenorrhea#!
!
Investigations!!
$ General!!
o CBC!
o LFT,!RFT,!clotting,!glucose!
o AFP!
o Liver!ultrasound!!
o Biopsy!!
" Mononuclear!infiltrate!of!portal!and!periportal!areas!!
" Piecemeal!necrosis!!
$ Specific!
o ANA#(Anti$nuclear!antibody)!
o SMA#(Smooth!muscle!antibody)!
o LKM1#(anti$liver/kidney!microsomal!antibody!type!1)!!
!

GI!$!43!
 o Anti#soluble^liver^antigen#antibody!
o Anti^measles#antibody!
o High!IgG#!
!
Management!
$ 30mg/day!Prednisolone#for!1!months,!maintain!at!5mg/day!for!2!years!!
$ Azathioprine!
$ Other!immunosuppressants!
$ Liver!transplantation!!
!
Associated!conditions!!
$ Pernicious!anemia!!
$ Autoimmune!hemolysis!!
$ Autoimmune!thyroiditis!!
$ Diabetes!mellitus!!
$ Glomerulonephritis!
$ Ulcerative!colitis!
$ Primary!sclerosing!cholangitis!(PSC)!
Primary3biliary3cirrhosis3(PBC)3
Introduction!!
$ Chronic!granulomatous!inflammation!of!interlobular!bile!ducts,!leading!to!intrahepatic!
cholestasis!!
$ ~50!years!onset,!M:F!=!1:9!
$ x20!chance!of!HCC!!!
!
Clinical!features!!
$ Pruritis,#Lethargy#!
$ Jaundice!!
$ Steatorrhea!+!malabsorption!of!fat!&!fat$soluble!vitamins!!
o Osteoporosis#(Ca,!PO4)!!
o Osteomalacia#(Vit!D)!!
$ Xanthelasma,!xanthoma!(bililary!obstruction!!!cannot!excrete!cholesterol)!
$ Non$jaundice!hyperpigmentation!(?increased-aMSH)!
$ Peripheral!neuropathy!(?Vit-E-deficiency,-?xanthomatous-peripheral-neuropathy)-!
$ Liver!failure,!Cirrhosis!!
!
Physical!examination!!
$ Scratch!marks!
$ Jaundice,!hyperpigmentation!
$ Xanthoma,!xanthelesma!
$ Hepatosplenomegaly#±!stigmata!of!chronic!liver!disease!!
$ Proximal!myopathy!
$ Peripheral!sensory!/!autonomic!neuropathy!!
!
Disease!phases!!
$ Asymptomatic!with!normal!LFT!+!positive!AMA!!
$ Asymptomatic!with!deranged!LFT!+!positive!AMA!!
$ Symptomatic!(from!when!on!the!mean!time!of!death!is!5$10!years...)!!
$ Decompensated!PBC!!
!
DDx!
$ Autoimmune#cholangitis#!
!

GI!$!44!
 o Histological!features!of!PBC!!
o Negative!AMA!
o Positive!ANA,!SMA!!
$ Periampullary!CA,!PSC!
o Painless!obstructive!jaundice!
!
Investigations!!
$ Blood!x!CBC!d/c,!RFT,!LFT,!clotting!
$ *USG#and!MRCP#to!exclude!extrahepatic!cholestasis!!!!
o Need!to!do!even!if!diagnosis!is!so!sure,!because!PAINLESS!JAUNDICE!is!always!
malignancy!until!proven!otherwise!!!
$ Specific!!
o Anti^mitochondrial#antibody#(E2#subtype)#!
" Targeted!to!mitochondrial!pyruvate!dehydrogenase!complex!
o Increased!IgM#!
o Increased!TSH!
o Increased!cholesterol!
o DEXA!for!osteoporosis!
o Liver!biopsy!(if!clinical!&!serological!diagnosis!is!equivocal)!!
" Portal!hepatitis!with!necrotic!duct!lesions,!lymphocytic!infiltrates!and!granuloma!!
" Periportal!hepatitis,!scanty!bile!ducts!with!proliferation!of!biliary!ductures!!
" Dense!fibrosis!with!scarring!of!portal!tract!!
" Established!cirrhosis!!
!
Management!!
$ Diet!!
o Low!fat!diet!!
o Fat!soluble!vitamin/Ca!supplements!!
$ Specific!!
o High!dose!Ursodeoxycholic#acid#!
" A!secondary!bile!salt,!non$toxic!to!liver!
" When!given!in!high!dose,!↓endogenous!production!of!TOXIC!bile!salts!
" Improve!LFT,!cholesterol,!??survival??!!
o Pruritis!!
" Cholestyramine#(bile!salt!binder!in!GIT,!and!remove!them)!improve!cholesterol!!
" Naloxone,#Neltrexone!
" Rifampicin#!
$ Detect!and!treat!cirrhotic!complications!!
$ Liver!transplantation!!
!
Prognosis!!
$ Once!jaundice!develops!survival!is!<2!years!!
!
Associated!conditions!!
$ Hashimoto!thyroiditis,!Type!I!DM,!Addison's!disease!
$ Sjogren's!syndrome,!RA,!systemic!sclerosis,!CREST!syndrome!!
$ Renal!tubular!acidosis,!Membranous!GN!!!
Primary3Sclerosing3Cholangitis3(PSC)3
Introduction!!
$ Rare!in!Asian!
$ Inflammation,!fibrosis!and!strictures!of!intra/extrahepatic!bile!ducts!!
$ ~40!years!old,!M:F!=!2:1!!
!

GI!$!45!
!
Clinical!features!!
$ Biliary!obstruction!(jaundice,!RUQ!pain,!pruritis,!tea!urine,!pale!stool)!!
$ Hepatomegaly,!signs!of!cirrhosis!!
!
Investigations!!
$ LFT:!ALP!rising!out!portion!to!bilirubin!
$ Clotting!profile!
$ Increased!IgM!
$ ANA,#SMA,#pANCA#!
$ MRCP:!multiple!biliary!strictures!in!a!bead!like!appearance!!
$ Liver#biopsy:!periductular!fibrosis!with!ductal!obliteration!!
!
Management!!
$ Pruritis!!
o Cholestyramine,#Neltrexone,#Rifampicin#!
$ Balloon#dilatation/#Endoscopic#stenting#!
$ Liver!transplantation!
o However,!recurrence!of!bile!duct!stricture!is!found!in!a!significantly!higher!%!of!pt!than!
other!liver!recipients!
!
Complications!!
$ Recurrent!bacterial!cholangitis!!
$ Cholangiocarcinoma!(7%!of!PSC)!∴!yearly!USG!!
$ Colorectal!carcinoma!∴!yearly!colonoscopy!!
!
Associated!condition!!
$ HLA!A1,!B8,!DR3!!
$ Ulcerative!colitis!!
$ HIV!infection!!
Wilson's3disease3(hepatolenticular3degeneration)33
Introduction!
$ Autosomal!recessive!!!ask!for!FHx!&!marriage!in!Hx!taking!
$ Chromosome!13,!code!for!a!copper!transporting!ATPase!(ATP7B)!
$ Failure!of!biliary!copper!excretion!!!toxic!accumulation!of!copper!in!liver!&!CNS!
!
Presentations!!
$ Younger!age!!!Hepatitis,!hepatic!failure,!cirrhosis!
$ Older!age!!!Neuropsychiatric!(basal!ganglia!&!cerebellar!tract)!
o Tremor,!dystonia,!dyskinesia,!parkinsonism,!stereotypes,!ataxia!
o Dysarthria,!dysphagia!
o Depression,!mania,!psychosis!
o Cognitive!/!behavioral!problem!
o *!Neuropsychiatric!symptoms!may!not!be!resolved!by!chelating!agents!
$ Kayser$Fleischer!rings!(slit!lamp)!!
o Bluish!discoloration!around!iris!
$ Sunflower!cataract!
o Radiating!orange$tinted!anterior!capsular!&!subcapsular!opacities!in!the!lens!due!to!
copper!deposition!
o Vision!unaffected!
$ Hemolytic!anemia!(10$15%)!
!

GI!$!46!
 o Coomb’s!–ve:!oxidative!damage!to!RBC!by!high!Cu!conc!
$ Renal:!urolithiasis,!Fanconi!syndrome!
$ Arthropathy:!degenration!(like!OA)!
$ Cardiomyopathy!(rare)!
!
Diagnosis!
$ Low!serum!ceruloplasmin!+!Kaiser!Fleischer!ring!
o No!need!liver!biopsy!if!have!KF!ring!
o Serum!ceruloplasmin!↓!because!without!Cu!binding,!they!are!rapidly!degraded!in!
bloodstream!
$ Low!serum!ceruloplasmin!+!raised!hepatic!copper!concentration!
!
Investigation!
$ General!
o CBC,!LFT,!RFT,!clotting,!glucose!
$ Specific!
o Serum!copper!(ceruloplasmin$bound!+!free!copper)!
" Usually!LOW!because!of!the!low!ceruloplasmin!
o Serum!ceruloplasmin:!low!
" Defective!copper!incorporation!into!ceruloplasmin,!lead!to!excess!catabolism!
o 24!urine!copper:!↑!free!form!of!serum!copper!
o Liver!biopsy!
o MRI:!basal!ganglia!degeneration!
!
Management!
$ Stage!1:!remove!the!accumulated!copper!
o Penicillamine!!
" S/E:!lupus!nephropathy!(∴!need!to!check!proteinuria),!GI!S/E,!
hypersensitivity!rash,!pancytopenia!(BM!suppression),!Goodpasture,!
nephrotic!syndrome!
o Trientine!!
" 2nd!line!if!penicillamine!not!tolerable!
" Less!S/E:!rash,!sideroblastic!anemia!(less!than!penicillamine)!
" May!exacerbate!neuropsychiatric!symptoms!
$ Stage!2:!prevent!reaccumulation!of!copper!
o Low!copper!diet!e.g.!Shellfish,!nuts,!chocolates,!organ!meats!
o Zinc$supplemented!diet!
" Inhibit!absorption!of!Cu!
" For!long!term!use!as!it!has!less!S/E!
" DON’T!give!together!with!penicillamine!or!trientine!as!they!chelate!zinc!as!
well!!
o Low!dose!chelating!agents!
$ Definitive:!Liver!transplantation!
!
Monitoring!treatment!response!
$ 24!hour!urine!for!copper:!should!be!<1.0!like!normal!
Primary3hemochromatosis33
Introduction!!
$ Autosomal!recessive!
$ HFE#gene,!chromosome!6,!point!mutation!(cysteine!>!tyrosine)!!
$ Resulted!in!increased!intestinal!absorption!of!iron!!
!

GI!$!47!
!
Presentations!!
$ Liver!failure!and!cirrhosis!
$ Bronze!skin!depigmentation!(90%)!
$ Diabetes!mellitus!(65%),!chronic!pancreatitis!
$ Pituitary!failure!
$ Hypogonadism!(from!both!cirrhosis!per!se!and!pituitary)!!
$ Dilated!cardiomyopathy!
$ Arthritis,!chondrocalcinosis,!CPPD!!
$ **!Female!present!later!due!to!regular!blood!loss!through!menstruation!
!
Investigations!!
$ Iron!profile!
o Serum!iron,!ferritin,!TIBC,!transferrin!saturation!!
$ LFT!
$ Fasting!glucose!
$ ECG,!echocardiogram!!
$ HFE!genetic!testing!!
$ Liver!biopsy!!
o Perl's!stain!positive!
o Hepatic!iron!index!>1.9!
o Mean!hepatic!iron!concentration!>80umol/g!!
!
Management!!
$ Venesection#!
o Regime!!
" 1!unit!per!week,!until!mildly!iron!deficient!!
" 1!unit!per!3!months!thereafter!Goal!!
o Goal!
" Hematocrit!<0.5!
" Ferritin!<100mcg/L!
" TIBC!>50umol/L!
" Transferrin!saturation!<40%!!
$ If!patient!is!anemic!!!subcutaneous!desferrioxamine#!
$ Dietary!advice!!
o Avoid!iron!rich!food!(red!meat,!liver,!seafoods,!enriched!cereal)!/!iron!supplement!!
o Avoid!vitamin!C!
o Avoid!white!wine!
o Take!coffee,!tea!or!red!wine!with!food!can!reduce!absorption!!
AlphaQ13antitrypsin3deficiency33
Introduction!!
$ Autosomal!recessive,!chromosome!14,!point!mutation!
$ Genetic!variant!typed!by!electrophoretic!mobility:!medium!(M),!Slow!(S),!Very!slow!(Z)!!
$ PiZZ!=!severe!disease!!
!
Presentations!!
$ Emphysema!
$ Liver!failure!and!cirrhosis!!
!
Investigation!!
$ Serum!alpha!1!antitrypsin!level!
$ Serum!electrophoryesis!(A1AT!making!up!90%!of!a1$globulin!)!!
!

GI!$!48!
$ Liver!biopsy!(Periodic!acid!Schiff+;!Diastase$resistant!granules)!!
!
Treatment!!
$ Quit!smoking!
$ Alpha#1#antitrypsin#pooled!from!human!plasma!(to-achieve-a-plasma-level-of->0.7g/L)-!
o If!FEVI!<80%!predicted!!
Liver3transplantation33
King's!college!criteria!for!Non$paracetamol!overdose!!
$ PT!>100sec!!
$ Or!3/5!OF!THE!FOLLOWING!!
o Drug!induced!liver!failure!
o Age<10!or!>40!
o >1week!between!onset!of!jaundice!and!encephalopathy!!
o PT!>50sec!
o Bilirubin!>300umol/l!!
!
King's!college!criteria!for!paracetamol!overdose!!
$ Arterial!pH!<7.2!24h!after!ingestion!!
$ Or!ALL!OF!THE!FOLLOWING!!
o PT!>100sec!
o Creatinine!>300umol/l!!
o Grade!III/IV!encephalopathy!!
!
Model!for!End!Stage!liver!Disease!score!(MELD!score)!!
$ MELD!=!3.78[Ln!serum!bilirubin!(mg/dL)]!+!11.2[Ln!INR]!+!9.57[Ln!serum!creatinine!
(mg/dL)]!+!6.43!!
$ For!prioritizing!patients!for!liver!transplantation!
$ It!improves!by!cancelling!the!"ceiling!effect"!of!Child!Pugh's!score!!
!
Milan's!criteria!for!liver!tumor!
$ 1!nodule!>5cm!!
$ 3!nodule!>3cm!!
!
Liver!donor!
$ Mortality!risk:!0.5%!(donate!R!liver)!/!0.1%!(L!liver)!
Porcelain3gallbladder3
Extensive!calcification!encrustation!of!GB!wall!
$ Originally!emphasized!blue!discoloration!&!brittle!consistency!of!GB!wall!at!surgery!
$ Now!some!doctors!use!this!to!describe!all!calcified!GB!
!
Investigation!!
$ AXR:!opaque!mass!at!RUQ!
$ CT:!curvilinear!/!rim!calcification,!usually!associated!with!calculi!in!anatomic!location!of!GB!
o If!have!adenoCA!!!pericholecystic!mass,!may!have!intrahepatic!met!&!hilar!
lymphadenopathy!
!
Complication!!
$ High!frequency!of!adenocarcinoma!in!porcelain!GB!!
o ∴!Should!surgically!remove!porcelain!GB!even!asymptomatic!
IgG4Qrelated3systemic3disease3
$ Disease!in!which!inflammatory!cells!cause!fibrosis,!the!deposition!of!connective!tissue!
!

GI!$!49!
$ Antibody!subtype!IgG4!can!be!detected!on!tissue!samples!&!often!↑!in!bloodstream!
$ Autoimmune!pancreatitis,!retroperitoneal!fibrosis,!mediastinal!fibrosis,!Riedel's!thyroiditis,!
Mikulicz's!syndrome,!Kuttner's!tumor,!inflammatory!pseudotumor!!

Autoimmune3pancreatitis3(AIP)3
Introduction!
$ Hyper$IgG4!disease!!!also!called!IgG4!pancreatitis!
$ A!type!of!chronic!pancreatitis!with!systemic!involvement,!e.g.!kidney!
$ Can!present!as!pseudotumor!!!mimic!pancreatic!CA!
!
Treatment!
$ Immunosuppressant:!azathioprine,!steroid!!
Constipation3
$ Check!thyroid!function!&!bone!profile!
o Hypercalcemia!&!hypothyroidism!!!constipation!
$ Treatment:!laxative!
o Bulk!forming:!Metamucil!
o Osmotic:!Lactulose!
o Stimulatory:!Senna/Senokot,!Dulcolax!(bisacodyl:!cause!abdominal!pain)!
Diarrhea3
Etiology!!
$ Infection#
o Food!poisoning:!bacillus!cereus,!salmonella,!staph!aureus!
o Viral!gastroenteritis:!adenovirus,!rotavirus,!norovirus!
o Bacterial!gastroenteritis:!campylobacter,!shigella,!salmonella,!E!coli!
" Campylobacter,!shigella,!salmonella!!!usually!affect!LB!
" Yersinia!!!usually!affect!SB!
" TB!!!can!affect!any!part!of!bowel!
o Parasite:!Entamoeba!histolytica,!giardia!lamblia!
o Pseudomembranous!colitis!!
$ Inflammatory!
o Inflammatory#bowel#disease#
o Ischemic!colitis!
" Fever,!severe!abd!pain,!metabolic!acidosis!
" A/w!alosetron!usage!(5$HT3!antagonist!for!Rx!of!IBS,!now!withdrawn)!
o Radiation!colitis!
o Behcet's!disease!
o Collagenous!colitis!
" 50!years!women,!watery!diarrhea,!normal!endoscopy!
" Biopsy!with!increased!subepithelial!collagen!deposition+!intraepithelial!
lymphocytes!!
" Rx:!5$ASA,!steroids!
o Lymphocytic!colitis!!
" 50!years,!watery!diarrhea,!normal!endoscopy!
" Biopsy!with!heavy!intraepithelial!lymphocytes!
" Rx:!5$ASA,!steroids!!
$ Secretary!
o Villious!adenoma!
o Carcinoid#tumor,!VIPoma,!gastrinoma!
o Ingestion!of!poorly!absorbed!sugars:!lactose!intolerance/sorbitol!
o Laxative#overuse##
!

GI!$!50!
$ Malabsorption!
o Intestinal!resection!
o Chronic#pancreatitis,#lactose#intolerance##
$ Coeliac!disease!!
$ Whipple's!disease!!
o Weight!loss,!steatorreha,!migratory!joint!pain,!dementia!
o Tropheryma!whippelii!
o Rx:!1yr!Septrin!(co$trimoxazole)!
$ Fecal!impaction!with!overflow!diarrhea!!
$ Hyperthyroidism,!Addison’s#disease,!DM#autonomic#neuropathy!!
$ Irritable#bowel#syndrome#(IBS)#
$ Bacterial#overgrowth#
$ Drugs:!antibiotics,!PPI,!cimetidine,!propranolol,!alcohol#
#
DDx!of!bloody!diarrhea!in!IC!patients!
$ Dysentery:!need!isolation!
$ CMV!ulcers!
$ GIB!(ulcers)!
$ B!cell!lymphoma!
!
History!taking!
$ Onset,!duration!
$ Frequency,!volume,!content!(blood,!mucus,!fat)!
$ Relation!with!meals!!
$ Tenemus,!urgency,!fecal!incontinence!
$ Fever,!abdominal!pain!
$ Weight!loss!
$ Diet,!drug!
$ Family/!Cluster/!Travel!history!!
!
Complications!
$ Metabolic!acidosis!in!severe!cases!!!respiratory!compensation!
o Acidotic!breathing!(Air!hunger):!very!deep!but!not!fast!
Constipations33
Causes!
$ Intestinal!obstruction!(IO)!
$ Constipation$predominant!irritable!bowel!syndrome!(IBS)!
$ Drugs:!CCB,!anti$cholinergics!!
$ Hypothyroidism,!hyperCa!
$ Spinal!cord!injury,!multiple!sclerosis!
$ Parkinsonism!!
$ Depression!!
Inflammatory3Bowel3Disease3(IBD)3
$ A!systemic!inflammatory!disease!with!predominant!manifestation!in!GTI!!
!
Etiology!!
$ Genetic#predisposition!!
o First!degree!relatives!3$20!times!likely!!
o Specific!HLA!linkages!!
" Non$HLA!genes:!NOD2/CARD15#in!Crohn's;!mutated!IL^23R#in!both!
$ Immunologic!factors!!
!

GI!$!51!
 o CD4+!T$cells!causing!mucosal!hyperesponsiveness!against!self$antigens!/!bacterial!
antigens!(?!mycobacterium!paratuberculosis,!Yersinia)!
o TNF!involved,!∴!anti$TNF!treatments!is!useful!
$ Environmental#factors!(perhaps!more!important!in!UC!than!CD)!!
o Microbial!trigger!!
" Provide!an!immune!trigger!to!a!dysregulated!immune!system!!
" Evidenced!by!the!high!incidence!in!bacteria!rich!ileum!&!colon,!&!absence!of!
IBD!in!flora$depleted!mice!
o Smoking:!↑!incidence!of!Crohn's!!
o Smoking!and!appendicectomy!are!PROTECTIVE!for!ulcerative!colitis!!
!
Types!!
$ Typical!IBD!
o Ulcerative!colitis!
o Crohn's!disease!!
o Colitis!of!undetermined!type!(indeterminate!colitis)!
$ Other!forms!of!IBD!(not!always!consider!as!typical!IBD)!
o Ischemic!colitis!
o Diversion!colitis!
o Behçet's!disease!
o Collagenous!colitis,!lymphocytic!colitis!!
$ DDx!
o Radiation!colitis!!
o Bacterial!dysentery,!Amoebic!dysentery,!Pseudomembranous!colitis!!
o CMV!colitis!
!
! Crohn's## UC##
Etiology!! Smoking!increases!risk!! Smoking!protective!!
Distribution!! From!oral!to!anal!! Large!bowel!(rectum!invariable),!
! Perianal!disease! sometimes!backwash!ileitis!!
Endoscopic!findings!! Patchy!! Continuous!!
! Cobblestone!appearance! Loss!of!vascular!pattern!
Pathology!! Transmural!ulcer!! Mucosal!ulcer!!
! Lymphocytic!infiltration!! Neutrophilic!infiltration!!
! Granuloma!! !
Complication!! Fissure,!fistula,!strictures!common! Dilatation!!
! Lower!CRC!risk! Higher!CRC!risk!
!
Extra$intestinal!manifestations!(*more!in!colonic!Crohn's)!
$ Conjunctivitis,!uveitis,!sacroiliitis,!migratory!polyarthritis!
$ Erythema!nodosum,!pyoderma!gangrenosum!
$ PSC,!cholangiocarcinoma!(both!rarer!in!Crohn's!)!!
o If!have!IBD!!!5$10%!have!PSC;!if!have!PSC!!!50%!have!IBD.!∴!if!have!PSC!!!should!to!
colonoscopy!to!r/o!IBD!
$ Renal!stones!(increased!free!oxalate!absorbed)!!
$ Amyloidosis!!
$ *!Conditions!that!run!independently!with!bowel!symptoms:!pyoderma!gangrenosum!
$ *!Conditions!that!usually!go!together!with!flare!up!of!bowel!symptoms:!arthalgia,!PSC,!uveitis!
$ *!Conditions!that!may!improve!after!bowel!resection:!monoarthropathy,!pyoderma!
grangrenosum,!uveitis!
!

GI!$!52!
Ulcerative3colitis3(UC)3
Types!
$ Proctitis!50%!
$ Left!sided!colitis!30%!
$ Pancolitis!20%!(±!backwash!ileitis:!contiguous!mucosal!involvement!of!terminal!ileum!as!a!
'spillover'!phenomenon)!!
!
Clinical!presentations!
$ Gastrointestinal:!diarrhea,!proximal!constipation,!rectal!bleeding,!cramps!!
o Nearly!all!UC!present!with!chronic!&!bloody!diarrhea!
o Nearly!all!have!rectal!involvement!
$ Systemic!
o Constitutional:!fever,!weight!loss,!anorexia!!
o Malnutrition!
o Anemia!!
$ Complications!!
o CA!!
o Perforation!!
$ Extra$intestinal!manifestations!!
!
DDx!of!flare!
$ Acute!bacterial!dysentery!!
!
Complications!!
$ Massive!GIB!!
$ Toxic!megacolon!!
$ Perforation!!
$ Colorectal!CA!!
!
Investigations!!
$ Blood!tests!!
o CBC!(anemia,!high!WCC)!
o Clotting!
o ESR,!CRP!
o LFT!(albumin,!PSC)!!
o RFT!(electrolytes,!amyloidosis)!!
o Iron,!folate,!B12!
o pANCA!!
" 11%!in!Crohn's!!
" 75%!in!UC!
$ Stool!!
o C/ST!and!microscopy!(to!exclude!bacterial!GE),!viral!/!parasites!/!spores!
o Stool!clostridium!toxin!!
$ Colonoscopy!!
o Hyperemia!with!edema!!
o Granular!mucosa!
o Deep!ulcers!
o Mucopus!and!contact!bleeding!!
$ Multiple!biopsies!!
o Crypt!atrophy,!destruction!of!crypt!architecture,!cryptitis!
o Dysplasia!associated!lesion/mass!
!

GI!$!53!
 o Chronicity#=#basal!neutrophils,!plasma!cells,!multiple!basal!lymphoid!infiltrates,!
crypt!abscess!
o Disease#distribution#=#limit!to!rectum,!continuous,!superficial!!
$ Imaging!!
o CXR,!AXR:!toxic!megacolon,!thumbprinting!signs,!obstruction!(more!in!Crohn's),!
perforation!!
o Barium!enema:!ulcerations,!loss!of!haustration!to!become!tubular!
o Radionuclide!scans!!
" Indium/!technetium!labeled!white!cell!scanning!!
" To!evaluate!areas!of!active!inflammation!esp!in!critically!ill!patients!!
o MRI:!for!pelvic!or!anal!involvement!of!diseases!(more!in!Crohn's)!!
!
Assessment:!with!prognostic!implications,!need!for!surgery!in!future!!
$ Disease#extent#(colonoscopy)!!
$ Disease#severity#(Truelove!and!Witts!Criteria),!severe!if:!!
o Bowel!motion!>6/24!hours!!
o Large!amount!rectal!bleeding!
o Fever!>37.8°!
o Tachycardia!>90bpm!
o Hb!<10.5g/dL!
o ESR!>30mm/h!!
!
Managements!!
$ Fluid!and!electrolytes!resuscitation!!
$ Transfuse!as!needed!
$ Nutritional!support!!
o NPO!+!IVF!in!active!attacks!under!treatment!
o If!in!remission!state!normal!diet!is!recommended!
o In!ileal!Crohn's,!avoid!high!fiber!diets!of!nuts!and!raw!fruits!to!prevent!obstruction!!
$ Monitor!BP/P/temp!!
$ Inducing!remission!!
o Mild!!!5$ASA!(suppository/enema)!OR!steroid!enema!
o Moderate!!!oral!5$ASA!OR!oral!steroid!
o Severe!!!IV!hydrocortisone!+!rectal!steroids!
o **!Route!of!administration!
" Proctitis:!suppository!
" L!sided$disease:!enema!!
" Pancolitis:!oral!tablet!±!enema!
o *!If!day!3!CRP!>45!or!stool!frequency!>6,!consider!cyclosporin/!infliximab/!surgery!!
$ Maintenance!!
o 5$ASA!(1st!line)!
o Azathioprine/6$MP!(if!steroid!dependent,!relapse!while!on!5$ASA,!severe!colitis!
requiring!cyclosporin!/!tacrolimus)!
o Infliximab!!
$ Regular!colonoscopy!for!CRC!screening!if!
o Total!colitis!>8!years,!L$sided!disease!>15!years!
o PCS:!CRC!risk!>50%,!need!colonoscopy!annually!!
o Chronic!inflammation!with!frequent!flare!up!
!
Management!of!mild!flare:!can!be!managed!as!out$patient!
$ Steroid,!stool!microscopy!&!culture!
$ Arrange!earlier!FU!
!

GI!$!54!
$ Colonoscopy!if!not!improved!!!look!for!ulcers,!CMV!
!
Medications!!
$ 5^aminosalicyclate#(5ASA)#compounds#!
o Useful!in!colonic!diseases,!either!as!remission!induction!/!for!maintenance!!
o Sulfasalazine#!(5ASA!+!a!sulfapyridine!moiety)!
" S/E!(mainly!from!the!sulfapyridine):!N&V,!hypersensitivity!(skin!rashes,!
fever,!hemolysis),!reversible!oligospermia,!hepatitis,!pancreatitis,!
paradoxical!worsening!of!colitis!
o Mesalazine#=!5ASA,!better!tolerated!!
o Olsalazine#=#5ASA!dimer,!better!tolerated!!
$ Glucocorticoids#!
o Used!only!in!remission!induction!
o NOT!FOR!MAINTENANCE,!owing!to!S/E!profile!!
o Enema,!oral!or!IV!form,!depending!on!the!severity!
o Need!to!rule!out!INFECTIVE!causes!before!prescription!
o Budesonide!has!a!high!first$pass!effect,!may!minimize!systemic!S/E!!
o Look!for!any!cushingoid!features!during!physical!exam!
o *!Taking!Steroid!for!1!month!already!can!cause!adrenal!insufficiency!!
$ Cyclosporin#!
o Calcineurin!inhibitor,!inhibit!T$cell!function!
o As!2nd!line!agent!after!steroid,!induces!remission!in!70%!of!patients!with!severe!
active!UC!!
o S/E:!tremor,!gum!hypertrophy,!hypertrichosis,!nephrotoxicity,!serious!opportunistic!
infections!!
$ Infliximab#!
o S/E:!serious!infusion!reactions,!reactivation!of!TB!or!histoplasmosis!!
o Not!used!in!active!sepsis!!
o Consider!to!add!azathoprine/methotrexate!to!↓!the!auto$immunity!of!infliximab:!↓!
antibody!formation!!!↑!efficacy!!
$ Azathioprine/#6^mercaptopurine#!
o Suppression!of!T$cell!activation!&!antigen!recognition!
o Takes!6$10!weeks!to!work,!∴not!for!induction!
o Steroid!sparing!agent!for!those!with!steroid!dependency!after!acute!colitis!!
o S/E:!nausea,!myalgia,!reversible!myelosupression!(check!CBC),!lymphoma,!
pancreatitis,!allergy!
$ (?Humanized!Antibody!to!the!α4β7!Integrin)!!
!
FU!in!clinic!
$ Disease!extent:!pan!/!L/!R!
$ Monitor!symptoms:!BO!__!times!/!day,!bleeding!
$ Measure!body!weight!every!visit!
$ Drugs!S/E!
o Sulfasalazine:!N&V!
o Azathioprine:!leucopenia!
o Biologics:!TB,!Hep!B!flare!up,!infection!
o Steroid:!Cushing!
$ Disease!activity!
o Acute!phase!reactant:!ESR,!CRP!
o Long$term!activity:!anemia,!albumin!

GI!$!55!
Crohn’s3disease3(CD)3
$ Rising!trend!in!all!over!the!world!(?!genetic!change,!diet,!change!in!microflora)!!
$ HK:!more!stricturing!disease,!more!upper!GI!involvement!
$ At!least!70$80%!patients!need!operation!in!lifetime!(↓!disease!free!survival!over!time)!
!
Types!
$ Ileocolic!/!ileal!/!colic!±!perianal!±!upper!GI!involvement!
o Ileocolonic!=!most!frequent!
!
Phenotypes!!
$ Inflammatory!(early)!
$ Stricturing!(late!–!typically!5!years!after!onset)!
$ Penetrating!(late!–!typically!10!years!after!onset)!
$ *!Perianal:!in!around!30%!of!patients,!70%!require!surgery,!rarely!heal!by!itself!!
!
Clinical!presentations!!
$ Gastrointestinal!!
o Inflammatory:!bloody!diarrhea,!cramps,!ulcers!
o Penetrating:!skin!discharge,!recurrent!UTI,!feculent!urethral!discharge,!
malabsorption!
o Stricturing:!constipation,!vomiting,!post$prandial!abd!distention!&!pain!(seldom!
present!as!IO)!
o Perianal:!fistula!and!abscess!!
$ Systemic!!
o Constitutional:!fever!(even!no!infection),!weight!loss,!anorexia!!
o Malnutrition!
o Anemic!symptom!
" Bleeding!due!to!active!disease!
" Also!anemia!due!to!absorption!problem!leading!to!Fe,!B12!deficiency!
• Need!to!replace!Fe!&!B12!aggressively!
• **!Need!to!consider!time!of!blood!taking!when!check!B12!level:!may!be!
falsely!normal!right!after!blood!transfusion!
" Chronic!sepsis!may!also!cause!anemia!
" Azathioprine!&!splenomegaly!also!cause!pancytopenia!
o Osteoporosis:!very!common!
" ↓!Ca!&!vit!D!absorption,!chronic!steroid!use,!high!metabolism!due!to!
inflammation…!
$ Complications!
o CA!!
o Perforation!
$ Extraintestinal!(*more!in!colonic!Crohn's)-!
!
Diagnosis!
$ Typical!history!
$ Colonoscopy!to!get!biopsy!for!histology:!non$caseating!granuloma!in!colon!(gold!standard!
for!CD,!but!only!present!in!5$10%!of!patients)!
o Not!do!in!acute!flare!up!!!able!to!get!biopsy!after!resolve!of!acute!stage!
" Need!bowel!prep!for!colonoscopy,!which!is!C/I!in!bowel!obstruction!/!
perforation!(which!are!DDx!of!acute!flare!of!CD)!
o Need!to!exclude!TB!colitis!(scattered!ulcers!rather!than!severe!colitis)!
" Hard!to!differentiate!from!TB!enterocolitis!(both!involve!ileocaecal!region)!
" But!treatment!is!very!different!
!

GI!$!56!
 • If!give!Crohn’s!Rx!to!TB!!!worsen!TB!enterocolitis!
• If!give!anti$TB!to!Crohn’s!!!may!induce!resistance!to!TB!
" Gold!standard!for!Dx!of!TB:!biopsy!for!AFB!smear!/!PCR!/!culture!!!but!
usually!negative,!∴!can!give!an!anti$TB!trial,!if!not!response!!!change!to!
immunosuppressant!
$ Therapeutic!response!to!steroid!
o Sometimes!difficult!to!differentiate!Crohn’s!Vs!TB!colitis!!!give!a!short!course!of!
steroid!then!do!FU!colonoscopy!
" If!improve!!!likely!Crohn’s!
" If!not!improved!!!may!be!TB!
!
DDx!of!ulcers!@!terminal!ileum!
$ TB!colitis:!colonoscopy!x!biopsy!!!caseating!granuloma,!AFB!stain,!culture!(need!8!weeks),!
TB!PCR!
$ CMV!ulcer:!cause!very!deep!ulcers;!colonoscopy!x!biopsy!!!inclusion!body!
$ GI!lymphoma!
$ Drug!cause:!NSAID,!aspirin!
$ Behçet's!disease:!ileal!&!caecal!region!affected!
!
DDx!of!acute!flare!up!!
$ Infective!causes:!gastroenteritis!
o Flare!up!!
" More!septic!looking,!abdominal!pain!(swelling!of!mucosa!!!partial!
obstruction),!bloody!diarrhea!but!sometimes!constipation,!less!acute!onset!
" Do!stool!culture!to!look!for!any!abnormal!growth!
o Bacterial!dysentery!(e.g.!Salmonella):!usually!no!need!A/B,!but!in!IBD!patients,!need!
A/B!due!to!abnormal!mucosa!
o TB:!mostly!at!R!side,!more!isolated!ulcer!than!Crohn’s!(multiple!ulcers!less!common)!
" ZN!stain,!PCR!
o CMV:!take!biopsy!via!colonoscopy!!!histology!for!owl!eye!appearance!(inclusion!
body)!
$ Intra$abdominal!abscess!
o In!CD!patient!with!fever!&!↑!CRP!!!need!to!r/o!intraperitoneal!abscess,!although!it!
can!be!solely!due!to!active!disease!
$ Obstruction!
$ Perforation:!may!not!have!severe!pain!due!to!heavy!immunosuppression!
!
Causes!of!flare!up!
$ Poor!drug!compliance,!infection,!NSAID!(paracetamol!is!ok)!
!
Assessment!!
$ Disease!extent!!
o Colonoscopy,!barium!studies,!CT,!CT!enteroclysis,!capsule!endoscopy,!perianal!/pelvic!
MRI,!double!balloon!enterscopy!(big!&!invasive!procedure,!so!not!commonly!done)!
" Capsule!endoscopy:!risk!of!causing!IO!if!have!stricture!
• Can!use!a!test!capsule:!same!size!as!the!pill!camera,!will!dissolve!if!
cannot!pass!through,!so!if!patient’s!didn’t!pass!the!test!capsule!out!!!
indicate!the!real!camera!cannot!pass!
$ Disease!phenotype:!inflammatory,!stricturing,!penetrating,!perianal!
$ Disease!activity!!
o Crohn's#disease#Activity#Index!
" CRP,!Hb,!platelet!(↑:!active!inflammatory!marker),!albumin!
!

GI!$!57!
 " Stool!frequency,!rectal!bleeding,!abdominal!pain,!weight!loss!
!
Investigations!!
$ Blood!tests!!
o CBC!(anemia,!high!WCC,!thrombocytosis)!!
o Crossmatch!
o Clotting!
o ESR,!CRP!!
o LFT!(albumin,!PSC)!
o RFT!(electrolytes,!amyloidosis)!!
o Iron,!folate,!B12!
o pANCA:!11%!in!Crohn's!(75%!in!UC)!!
$ Stool!!
o C/ST!and!microscopy!(to!exclude!bacterial!GE)!!
o Stool!clostridium!toxin!!
$ Ileo^colonoscopy:!gold!standard!
o Hyperemia!+!edema!!
o Creeping!fat!on!bowel!surface!!
o Linear!skipped!ulcers!!
o Cobblestone!appearance!!
o **!Not!done!in!obstructive!S/S!(abdominal!pain,!vomiting,!had!strictures!previously,!
AXR!show!dilated!bowel)!!!do!CTE!instead!
$ Multiple!biopsies!!
o Granulomas!
o Transmural!fissures!
o Neutrophilic!infiltration!with!crypt!abscesses!(less!than!UC)!!
o Paneth!cell!metaplasia!
o Hypertrophy!of!muscle!layer!thus!mural!thickening!!
$ Imaging!!
o CXR/AXR:!thumbprinting!signs,!stricture!/!obstruction,!perforation!!
o Barium!follow$through:!ulcerations,!string$sign!as!stricture!formation!!
o Radionuclide!scans!!
" Indium!/!technetium!labelled!white!cell!scanning!!
" To!evaluate!areas!of!active!inflammation!esp!in!critically!ill!patients!!
o CT/MRI!enteroclysis!!
" Enterocutaneous!fistula!
" Ileal!thickening!
" Peritoneal!&!omental!thickening!(DDx:!TB!affecting!omentum)!
o Capsule!endoscopy!
" Superior!to!Barium!follow$through,!CTE,!MRE!in!Dx!small!bowel!CD!
o MRI!pelvis:!for!perianal!diseases!!
" Fistula:!high!signal!track!indicating!active!inflammation!
!
Prognostic!factor:!poor!prognosis!if!
$ Perianal!!
$ Penetrating!disease!!
$ Young!patient!<40!!
$ Smoker!!
$ Steroid!requirement!!
!
Complications!!
$ Malabsorption!&!malnutrition!(folate,!B12,!major!nutrients)!!
!

GI!$!58!
$ Osteoporosis!(poor!Ca!absorption,!steroid!usage)!
$ Fistula#formations:!to!gut,!bladder,!vagina,!skin!!
o Enteroenteric!!!malabsorption!and!diarrhea!!
o Enterovesicle!!!pneumaturia!and!recurrent!UTI!!
o Enterovaginal!!!faecel!discharge!per!vagina!!
$ Stricture#thus!intestinal!obstruction!!
$ Intraabdominal!abscess!
$ Perianal#diseases!
$ Perforation!!
$ Malignancy!
$ Recurrent!infection!(e.g.!chest!infection)!due!to!use!of!steroid!/!IS!
o Steroid!is!2$3x!higher!risk!of!infection!than!other!IS,!∴!prefer!using!IS!in!pt!with!
recurrent!infection!
!
Outline!of!management!
$ Step!up!management!
o 5$ASA!(mild)!!!steroid!(moderate)!!!aza,!6$MP,!MTX!!!anti$TNF!!!surgery!
$ Mild!disease!!!use!mesalazine!!
$ Severe!disease!(e.g.!stricture,!ileocecal!involvement)!!!use!steroid!/!IS!directly!
$ Failed!medical!treatment!/!perforation!!!surgery!
o Risk!of!short!gut!syndrome,!so!surgery!not!1st!line!
!
Management!!
$ Aim!to!heal!the!mucosa,!prevent!Cx,!↑!QOL!
o Always!try!to!normalized!the!CRP!(↓inflam)!instead!of!just!↓!frequency!of!diarrhea!
$ Remission!induction!(steroid!/!anti$TNF;!No!role!for!cyclosporin)!!
o NPO!+!IVF!±!TPN!!
" TPN:!↓!inflammation!(rest!the!bowel)!&!improve!nutrition!
" But!generally!enteric!feeding!is!preferred,!except!in!severe!flare!up!e.g.!
having!perforation!
o Transfuse!as!needed!!
o 5$ASA,!e.g.!mesalazine:!for!mild!CD!
" Less!useful!compared!to!UC,!need!stronger!IS!in!CD!
o Steroid:!For!moderate!to!severe!flare!!
" Prednisolone!!
" Budesonide!
• High!1st!pass!effect!to!limit!systemic!toxicity!!!less!W/E!than!
prednisolone!
• Mainly!absorbed!in!SB,!so!less!effective!for!colon!disease!
" *!Most!Crohn’s!respond!well!to!steroid!
" *!But!if!tail!down!too!rapidly!!!may!relapse!
o Biologics!(Infliximab,!adalimumab,!certolizumab)!(Natalizumab:!anti$alpha4!
integrin)!!
" C/I!in!fistulizing!disease!with!IO,!toxic!megacolon!requiring!surgery,!active!
infection!
" Also!need!to!be!certain!of!Dx,!if!give!biologics!to!TB!colitis!!!high!risk!of!
perforation!as!TB!colitis!would!become!very!severe!rapidly!
" Patient!may!develop!Ab!making!biologic!not!effective,!if!so!!!give!more!
frequently!(6$weekly!instead!of!8$weekly)!/!change!to!another!biologic!
" S/E!
• Sepsis:!bacterial,!mycoses!
• TB:!CXR,!Tuberculin!test,!interferon$gamma!assay!
!

GI!$!59!
 • Infusion!reaction!and!↓!duration!of!response!
• Serum!sickness!
• Drug$induced!lupus!
• Mortality!in!patients!with!severe!heart!failure!
o Surgery!!
o Antibiotics:!metronidazole/!ciprofloxacin!!
" For!fistulizing!/!Perianal!CD!!
o Localized!perforation!(abdominal!pain!+!fever!+!peritoneal!signs,!mesenteric!gas!in!
CT!but!no!free!gas)!
" Can!manage!conservatively:!A/B,!NPO+TPN!
$ Maintenance!(No!role!for!cyclosporin,!5ASA,!steroid)!!
o Non$pharmacological!
" Quit!smoking!
" Low!bulk!diet!if!strictures!present:!avoid!high!fiber!diets!of!nuts!&!raw!fruits!
" Dietary!supplement:!B12,!folate,!Ca,!iron,!Vit!D!!
o Pharmacological!
" Azathioprine/6^MP#
• Azathioprine!takes!3$6!weeks!(even!6!months)!to!work,!so!only!for!
maintenance!not!induction#
" S/E:!hepatotoxicity,!neutropenia!(BM!suppression)#
" Methotrexate#
" Biologics##
$ **!If!on!≥3!immunosuppressant!!!need!cotrimoxazole!for!PCP!prophylaxis!
$ Ultimate!treatment:!stool!transplantation!!!restore!normal!flora!
o Still!not!proven!useful!in!CD!(Vs!recurrent!C.!difficile!infection:!>90%!cure!rate)!
o Infuse!the!stool!fluid!via!duodenal!tube,!need!repeated!times!
!
**!Caution!for!re$feeding!syndrome!after!effective!treatment!
$ Pathophysiology!
o Metabolism!shift!from!fat!to!carbohydrate!!!insulin!↑!&!metabolic!rate!↑!!!excessive!
cellular!uptake!of!electrolyte!!!shifting!of!electrolytes!&!fluid!balance!!!↑!cardiac!
workload!&!HR!
o ∴!Need!to!monitor!peripheral!&!pulmonary!edema!
o Also!need!to!monitor!ECG!&!electrolyte!(especially!K,!Mg!&!PO4)!
o Usually!PO4!is!the!first!to!↓!in!refeeding:!PO4!used!to!produce!energy!(ATP)!
!
CD!and!pregnancy!
$ Disease!usually!remain!quiescent!during!pregnancy!due!to!hormonal!change!causing!
immunosuppression!!
$ But!still!very!important!to!control!disease!NOT!stopping!the!drugs!!
o If!flare!up!!!risk!of!pre$term!labour!/!miscarriage!!
o If!have!fistulizing!disease!requiring!CT!scan!!!a/w!
" Damage!in!fetal!neural!tissue!!!↓!IQ!
" Childhood!malignancy:!thyroid!
" Miscarriage!(lower!risk)!
$ Medications!
o Steroid!&!azathioprine!are!safe!in!pregnancy!
o Biologics!C/I!in!3rd!trimester!as!it!crosses!placenta!!!BB!will!be!IC!at!birth!
$ Risk!of!flare!up!after!labour!due!to!immune!rebound!
!
FU!in!clinic!
$ Duration,!phenotype!(inflammatory!/!structuring!/!fistulating),!extend!!
!

GI!$!60!
$ Symptoms!
o Stricture:!post$prandial!abdominal!pain,!vomiting!
o Fistulizing:!perianal!fistula!(ask!&!inspect)!
o Extraintestinal!manifestation!
$ Body!weight!(trend),!albumin!level!
$ Drugs:!compliance,!S/E!
Splenic3abscess3
Causes!
$ IE,!typhoid,!paratyphoid,!malaria!
$ UTI,!pneumonia,!osteomyelitis,!otitis,!mastoiditis,!pelvic!infection!
$ Contiguous!infection!(pancreas,!retraperitoneal,!subphrenic!abscess)!
$ Trauma!!
Splenic3infarct3
Causes!
$ Hemoglobinopathy:!e.g.!sickle!cell!disease!
$ Leukemia,!polycythemia!
$ Vasculitis!
!
Complication!
$ Can!be!infected!&!evolve!into!splenic!abscess!
Esophagogastroduodenoscopy3(OGD)3
Consent!!
$ Diagnosis!&!reason!for!the!exam!
$ Name,!aim,!nature,!indication!of!procedure!
$ Details!of!procedure!
o Give!LA!into!throat!to!decrease!discomfort!
o The!endoscope!is!around!the!size!of!the!thumb!
o Look!at!esophagus,!stomach!&!duodenum!
o If!see!any!abnormality,!can!take!biopsy!
o Can!test!for!Hp!
o Have!do!hemostasis!if!have!bleeding!
$ Risk!&!possible!intervention!needed!if!complication!occur!
o Bleeding,!perforation,!aspiration,!unsuccessful!hemostasis!that!may!need!laparotomy,!
arrhythmia!
$ Possible!consequences!of!refusing!the!procedure!
$ Alternative!procedure!&!its!pros!and!cons!
!
Indications!
$ Diagnostic!
o Esophagus!
" Dysphagia,!odynophagia,!Barrett’s!eso,!abnormal!Ba!swallow!
• Barrett’s!vs!sliding!hernia:!look!for!any!rugae!in!the!part!which!has!gastric!
mucosa!
" GERD!symptoms!(heartburn/retrosternal!pain)!failed!PPI!
o Stomach!&!duodenum!
" Epigastric!pain,!RUQ!pain,!dyspepsia!
" Suspicious!for!CA!stomach:!epigastic!mass,!abnormal!Ba!meal,!anemia,!weight!loss!/!
anorexia!
" GI!bleed:!coffee!ground!vomiting,!hematamesis,!tarry!stool,!hematochezia!
$ Surveillance!
o Esophagus:!Barrett’s!eso,!esophageal!varices!
!

GI!$!61!
 o Stomach!&!duodenum:!GU,!DU!
$ Therapeutic!
o Upper!GIB:!hematemesis,!coffee!ground!vomiting,!malena!
o Removal!of!foreign!body!
o PEG!/!feeding!tube!insertion!
o Endoscopic!CA!resection!for!early!esophageal!/!gastric!cancer!
o Stricture:!dilatation!/!stent!insertion!
$ **!What-is-the-2-indications-for-emergent-OGD?!
o Fresh-hematemesis!
o Hemodynamic-instability-despite-resuscitation!
!
Contraindications!
$ Absolute!
o Perforated!viscus:!excruciating!pain!+!peritoneal!sign!±!free!gas!under!diaphragm!(SN!
only!70%)!!
" Pump!air!into!lumen!during!OGD!!!pump!the!content!out!!!peritonitis!
o Intestinal!/!gastric!outlet!obstruction!
$ Relative!
o Hemodynamically!unstable:!stabilize!patient!first!
" Stress!of!OGD!may!lead!to!on$table!arrest!!
o Severe!anemia!(similar!to!hypoxia):!correct!anemia!1st!if!possible!(elective!OGD)!
" OGD!!!stress!!!risk!of!MI/stroke!
" In!emergency!setting,!may!transfuse!at!the!same!time!of!OGD!
o Recent!MI!/!stroke!(3m?)!
o Uncontrolled!severe!HT!
" May!give!sedation!during!OGD!to!↓!risk!
o Unconscious!/!uncooperative!patients!
o Patient!with!high!risk!of!aspiration!
" Respiratory!failure,!e.g.!requiring!high!flow!O2!!!high!risk!of!aspiration!
• ∴!Need!ventilator!instead!
o Uncorrected!coagulopathy!/!on!anticoagulant:!correct!INR!1st!if!possible!(e.g.!by!Vit!K!/!
FFP),!avoid!biopsy!
o Inadequately!fasted!patients!!
o Oropharyngeal!dysphagia!(suspect!pharyngeal!pouch!!!may!perforate)!
!
Preparation!
$ Fast!for!≥6!hours!+!IVF!
o Gastric!emptying!need!~!6!hours!
o DDx!of!food!debris!present!inside!stomach!even!adequately!fast!
" GOO,!IO,!gastroparesis!(e.g.!DM!causing!autonomic!dysfunction)!
$ Crossmatch,!CBC,!clotting,!RFT,!LFT!
$ Consent!
!
Procedure!
$ Medications!
o Topical!oropharynx!anaesthetic:!lignocaine!spray!to!palate!&!ask!patient!to!swallow!!!↓!
gag!reflux!
" Cons:!↑!risk!of!aspiration!(∴need!NPO!for!30min!–!1hr!after!procedure),!bad!taste!
o Sedation:!IV!midazolam!/!diazemul#(an-injectable-emulsion-of-diazepam)!
" Indications!
• Expect!to!have!prolonged!exam!(e.g.!active!GIB,!variceal!ligation)!
!
• Recent!MI/stroke,!uncontrolled!HT!!!↓!stress!
GI!$!62!
 " Risk:!respiratory!depression,!aspiration,!shock!(in!patient!already!impending!shock,!
e.g.!severe!GIB:!benzo!↓!symp!drive!leading!to!shock)!
• Need!close!monitoring!of!SaO2!&!BP!during!&!after!procedure,!may!need!O2!
supplement!
" Antidote:!flumazenil!
o Analgesia:!IV!pethidine!
" Alternative!to!sedation!
" Risk:!respiratory!&!circulatory!depression,!bradycardia!
" Antidote:!Naloxone!
o Mouth$guard:!protect!the!teeth!(NOT!protect!the!airway,!which!need!intubation)!
$ Left!lateral!position!
o ↓!risk!of!aspiration,!prevent!tongue!falling!backward!
" R!main!bronchus!is!shorter!and!straighter!!!higher!risk!of!aspiration!
$ Continuous!monitoring!of!BP!&!SaO2!
o If!BP!too!high,!may!give!sedation!
o Aspiration!will!lead!to!desaturation!
$ Mouth#guard#to!prevent!patients!biting!on!endoscope#
$ Advance!through!esophagus,!stomach,!pylorus!to!D2!
$ J$maneuver!for!fundus!
$ Hemostasis!
o PU:!adrenaline!injection!+!heat!probe!
o Gastric!varices:!inject!sclerosant!!
" Histoacryl!glue:!once!contact!to!moisture!/!water!!!polymerization!!!clot!vessel!
• Radioactive!substance:!seen!as!patchy!thing!in!AXR!
o Esophageal!varices:!endoscopic!band!ligation!
$ Biopsy!/!brush!cytology:!needed!in!every!gastric!ulcer!due!to!risk!of!malignancy!
o At!edge!of!ulcer,!not!base!
" Base!only!have!granulation!tissue!
" After!heat!probe!!!cell!will!become!atypical!!!false!+ve!
o Test!biopsy!from!antrum!for!Hp!
" Rapid!urease!test:!NH4!produced!turn!phenol!red!from!yellow!to!red!
" Send!to!pathology!and!look!under!microscope,!not!culture!(difficult!to!grow)!
$ Remove!foreign!body,!e.g.!fish!bone:!use!grapser!
$ After!OGD!!!give!IV!PPI!infusion!for!clot!stabilization!(high!dose:!80mg!loading!+!8mg/hr!
for!72hr)!
!
Findings!
$ Identify!the!site!
o Stomach:!rugae!
o Duodenum:!villi!
$ Erosion:!lesion!confined!to!mucosa!(Vs!ulcer:!beyond)!
o Itself!cannot!account!for!iron!deficiency!anemia,!∴!may!need!to!do!colonoscopy!as!well!
to!find!for!site!of!GIB!
!
Complication:!overall!Cx!rate!~1/1000!for!diagnostic!OGD!
$ Aspiration!
$ Perforation!
o ↑!risk!in!patient!with!Zenker’s!diverticulum!
$ Bleeding!
$ Cardiorespiratory!compromise!
o Hypoventilation!!
o Cardiac:!arrhythmias,!MI!
!

GI!$!63!
$ Suboptimal!study!requiring!further!investigation!
$ Emergency!surgery!needed!if!perforation!/!tear!occur!
!
**!OGD!cannot!be!sterilized!(only!disinfect)!
$ Need!special!processing!in!highly!infectious!disease,!e.g.!TB,!prion!disease!
o In!prion!disease,!even!need!to!condemn!the!scope!!
Physical3examination3(Abdominal3exam)3
# OSCE!
o ‘Examine!abdomen’!!!examine!abdomen!1st!then!peripheral!(Prof!B!Ma)!
o ‘Examine!abdominal!system’!!!examine!general!1st!then!abdomen!
# Bedside!sign!with!‘no!BP!taking!on!L/R!arm’!
o DDx:!AVF!in!CKD,!post$mastectomy!(risk!of!lymphedema),!intervention!(e.g.!cardiac!
cath)!
# Use!‘not!dehydrated’!instead!of!‘hydration!normal’!
# Stigmata!of!chronic!liver!disease!
o Portal!HT:!esophageal!varices,!ascites,!splenomegaly,!caput!medusae!
o ↑!Estrogen:!gynaecomastia,!loss!of!axillary!hair,!spider!naevi,!testicular!atrophy!
" Feel!directly!on!nipple!for!any!soft!tissue!beneath!(normally!no)!
o ↓!Synthesis:!bruise,!leukonychia,!ascites,!ankle!edema,!jaundice!
o ↓!Detoxification:!liver!encephalopathy!(hepatic!flap,!talk!with!patient,!draw!star)!
# Hepatic!flap!
o Stretch!flexor!tendon!at!the!wrist!!!look!for!flap!on!contralateral!side!(hyper$reflexia)!
# Spider!naevi!!
o Failure!of!the!sphincteric!muscle!surrounding!a!cutaneous!arteriole!
o Due!to!↑!estrogen!level!
# Caput!medusae:!flow!away!from!umbilicus!(VS!IVCO:!upward)!
o Use!part!below!umbilicus!to!determine!direction!of!blood!flow!
o Abdominal!/!pelvic!malignancy!block!IVC!!!superficial!veins!on!abdominal!wall!&!flow!
upward!to!SVC∴!may!confuse!with!this!as!both!travel!upward!above!umbilicus!
# Alcoholic!liver!cirrhosis!characteristic!signs!
o Dupuytren’s!contracture!&!parotid!enlargement!
# Bruising!
o Bleeding!tendency!including!liver!cirrhosis!(not!only!indicate!liver!cirrhosis!!)!
o Subcutaneous!injection!(e.g.!insulin):!also!look!for!lipohypertrophy!
# Uremic!looking!in!kidney!disease!
# When!palpate!for!organomegaly!!
o Sit!down!to!palpate!until!examination!of!spleen!over!left!costal!margin!
o Tell!patient!to!breath!deeply!&!slowly!
" If!patient!breath!too!enthusiastically!!!may!tense!up!abdominal!muscle!
# Palpate!hepatomegaly!!!surface,!edge,!size!(normal:!10$12cm),!bruit!
# If!patient!have!gross!ascites,!may!do!percussion!of!spleen!in!R!lateral!position!so!that!fluid!
won’t!affect!it!
o Normal:!hyperresonance!at!Traube’s!space!(between!6th!rib!&!costal!margin!at!anterior!
axillary!line)!due!to!gastric!bubble!/!resonance!over!Castell’s!Point!(lowest!ICS!at!
anterior!axillary!line)!
# When!turn!patient!laterally!(shifting!dullness!+!spleen!hock)!!!feel!for!sacral!edema!&!look!
for!scar!at!the!back!(nephrectomy)!
# Spleen!hock:!tell!patient!to!bend!the!knee!!!relax!abdominal!muscles!
# Ascites!Vs!fat:!fat!will!fall!by!gravity!&!‘stick’!to!bed;!ascites!like!a!balloon!
# Do!fluid!thrill!if!abdomen!all!filled!with!fluid!(no!resonance)!!
# Bowel!sound:!sluggish!/!normal!/!hyperactive!
!

GI!$!64!
Extra!things!to!do!if!have!following!findings!
# Hepatomegaly!!!!
o Find!tattoo!(HBV,!HCV,!HDV,!HIV)!
o Testicular!atrophy!
o PR:!piles!(portal!HT),!CRC!(liver!secondary!to!CRC)!
o Caput!medusae!
o Urine:!ketone,!bilirubin!
o USG!
o Blood:!LFT,!clotting,!Hep!B!serology,!AFP!
# Ballotable!kidney!!!kidney!disease/!renal!cell!carcinoma!(RCC)!
o Eye:!pallor:!hemolysis!&!erythropoietin!
o Neck:!scar!for!temporal!HD,!thyroidectomy!scar!(3°!hyperPTH)!
o Forearm!/!elbow:!AV!(arteriovenous)!fistula!(for!hemodialysis)!
" Feel!for!thrill!&!auscultate!
o Abdomen!
" Hepatomegaly:!polycystic!liver!
" Scar!of!Tenckhoff!catheter!(for!peritoneal!dialysis)!
• Midline!scar!below!umbilicus,!catheter!come!out!few!cm!lateral!to!the!scar!
" Transplant!kidney!&!lower!quadrant!scar!(Gibson!incision)!
o Back:!nephrectomy!scar!
o Signs!of!fluid!overload!
o BP!!!(**!Make!sure!not!measure!on!the!arm!with!AV!fistula)!
o If!suspect!polycystic!kidney!!!
" Ask!for!FHx!of!polycystic!disease!
" Neurological!exam:!commonly!associated!with!Berry!aneurysm!!!look!for!
previous!stroke!(ruptured!aneurysm)!&!3rd!nerve!palsy!
" Cardiovascular!exam:!mitral!valve!prolapse!(connective!tissue!disease)!
o Ask!for!
" Urine!multistix:!hematuria!is!common!presentation!of!polycystic!kidney!
" USG!abdomen!/!IV!pyelogram!/!CT!(?!with!contrast!!!contrast!may!worsen!renal!
function)!
" Renal!function!test!
# Transplanted!kidney!
o Uremic!looking:!functional!status!of!the!Tx!kidney!
o Comment!on!the!renal!function!
" E.g.!fair!control!if!see!uremic!looking!but!no!AV!fistula!/!Tenckkhoff!catheter!(i.e.!
not!on!dialysis)!
o Comment!on!possible!etiology!of!disease!
" DM:!usually!so!poor!that!require!insulin!!!look!for!needle!marks!on!abdomen!
" Polycystic!kidney:!ballotable!kidneys!
o Cushing’s!feature:!due!to!long$term!steroid!
" Palpate!for!buffalo!hump!when!palpate!cervical!LN!
" Purple!striate!on!abdomen,!hirsutism!etc.!
o Side!effect!of!commonly!used!immunosuppressant!
" E.g.!cyclosporin!!!gum!hypertrophy,!hand!tremor,!hypertrichosis!
o Tenderness!&!bruit!over!the!transplanted!kidney!
" Stenosis!of!the!vessels!connected!to!it!!!bruit!
o Would!like!to!measure!BP,!do!urine!multistix!(RBB,!WCC,!albumin,!glucose…)!
o Check!for!any!uremic!symptoms!!
# Splenomegaly!
o Temp!chart:!infection!(TB,!malaria,!infective!endocarditis)!
o LN!(neck,!groin,!axilla,!i.e.!whole!body!LN):!lymphoproliferative!disease!
!

GI!$!65!
 o Pallor!&!bleeding!tendency:!marrow!involvement!of!lymphoproliferative!disease!
o Jaundice:!hemolysis!(e.g.!thalassemia)!may!lead!to!splenomegaly!
o Joint!deformity:!RA!
o Bone!marrow!examination!scar:!leukemia!
# Stomach!mass!
o Splashing!sign!
o Anemic!symptoms:!ulceration!of!tumor!
o (Upper!GI!symptoms,!e.g.!vomiting)!
# Ascites!
o Do!paracentesis!to!differentiate!transudate!vs!exudate!
o Transudate!!!check!BP,!urine!protein,!H’stix!(if!look!like!DM!nephropathy),!CVS!exam!
o Exudate!!!palpate!LN,!PR!(rectal!CA!with!peritoneal!met),!USG/CT!abdomen!
Presentation!–!4$tier!diagnosis!
$ Anatomical!/!pathological!Dx!
o E.g.!hepatomegaly!
$ Clinical!/!etiological!Dx!
o E.g.!HCC!
$ Functional!diagnosis!
o E.g.!Child’s!grading!
$ Complications!
o E.g.!portal!HT!as!evidence!by!caput!medusae,!ascites,!splenomegaly!
o E.g.!pancytopenia!as!evidence!by!pallor,!extensive!bruising!and!on!antibiotics!infusion!
DDx!
# Shifting!dullness!(ascites)!
o Transudative!
" Portal!HT!(cirrhosis),!nephritic,!heart!failure!
o Exudative!!
" TB!ascites,!metastatic!deposit!into!peritoneum!(e.g.!primary!GI!/!gynae!tumor),!
infection!(SBP),!inflammation!
# Hepatomegaly!
o Liver!cirrhosis!
" Fatty!liver!(alcoholic!/!NASH):!common!
" Wilson’s,!hemochromatosis!
" Autoimmune!hepatitis,!PBC,!PSC!!
o HCC!±!cirrhosis!!!patient!cachexic!or!not!
o Secondary!liver!cancer!
o Cardiac!cause:!pulsatile,!↑JVP!
o Acute!hepatitis:!tender!
o Lymphoma:!LN,!splenomegaly!
o Polycystic!liver:!can!be!very!massive!hepatomegaly!!
# Splenomegaly!!
o Spleen!tip:!just!palpable!with!spleen!hock!
" Hematological!malignancy:!lymphoma,!CML,!CLL!
" Thalassemia!
" Hemolysis!
" Autoimmune!gastritis,!atrophic!gastritis!
o Mild!splenomegaly:!palpable!<2cm!
" Thalessemia!intermedia!
" IE,!viral!infection!(EMV)!
" RA!
" Portal!HT!(cirrhosis)!
" Malaria!!
!

GI!$!66!
 o Moderate!splenomegaly:!palpable!between!2$10cm!
" Portal!HT!
" CML!
" AML!
" Malaria!!
o Massive!splenomegaly:!palpable!>!10cm,!around!umbilicus!
" Chronic!myeloid!leukemia:!usu!middle!age!M!
• Lymphoproliferative!disease!not!so!massive!
" Myelofibrosis:!little!bit!older,!e.g.!50s!
" Chronic!malaria!
" Parasites:!Kala!azar!(Leishmania-donovani)!
" Gaucher's!disease:!autosomal!recessive!lysosomal!storage!disease!
(glucosylceramide!accumulation)!
o Splenomegaly!but!no!lymphadenopathy!!!more!likely!meloid!than!lymphoproliferative!
disease!
o Splenomegaly!+!jaundice!
" Chronic!liver!disease!!!look!for!clubbing!&!ascites!
" Hemolytic!anemia,!e.g.!thalassemia,!hereditary!spherocytosis!
• Growth!retardation,!hyperpigmentation!
• **!Thalasemmia!unlikely!appear!in!exam!as!they’re!not!cared!by!adult!
department!!(If!yes,!most!of!them!is!thalassemia!intermediate)!!
# Hepatosplenomegaly!with!massive!spleen!
o Myeloproliferative!disease!(LN°):!CML!(have!Rx),!myelofibrosis!(no!Rx)!
o Lymphoproliferative!disease!(LN+):!lymphoma!(e.g.!splenic!lymphoma),!ALL,!late!stage!
of!
o Glycogen!storage!disease,!amyloidosis!
o Infection:!Kala!azar,!malaria,!!
o *!Unlikely!portal!HT!causing!massive!splenomegaly:!will!have!massive!ascites!
o *!Unlikely!infectious!mononucleosis:!not!massive!spleen!/!liver!
o *!Unlikely!thalassemia!
" Major!!!splenectomy!should!be!done!in!paedi!
" Intermediate!!!at!most!moderate!splenomegaly!
" Trait!!!should!not!have!palpable!splenomegaly!
# Ballotable!kidney!
o Unilateral:!unilateral!hydronephrosis,!tumor!
o Bilateral:!bilateral!hydronephrosis,!polycystic!kidney!
# Mass!in!LUQ!
o Spleen,!kidney,!colonic!mass!
" Colonic!mass!usu!quite!mobile!!!seldom!cannot!get!above!
o Rarer:!soft!tissue!sarcoma,!lipoma!(can!invade!into!kidney!leading!to!hematuria),!
lymphoma!(can!give!odd!shape,!big!&!grow!very!fast)!
# Cervical!lymphadenopathy!
o Benign!conditions!
" CMV,!EBV,!TB!
" Drugs!hypersensitivity!!!pseudolymphoma$like!
o Malignancy!
" Primary:!lymphoma,!leukemia!
" Secondary:!from!solid!organs!
!

GI!$!67!
Drugs3
Proton3pump3inhibitor3(PPI)3
Choices!
$ Pantoprozole!(Pantoloc)!
$ Esomeprazole!(Nexium)!
$ Lansoprazole!
o Have!suspension!form!in!PWH!!!can!give!via!Ryle’s!tube!
!
S/E!
$ Dry!mouth,!headache!
$ Infection:!C.!diff,!SBP!if!ascites!(↑!bacterial!translocation),!chest,!non$clostridial!enteric!
infections!
$ Osteoporosis:!if!long$term!(>10!years)!
$ Interstitial!nephritis!(rare)!
$ Interaction!with!clopidogrel!(except!lansoprazole,!pantoprozole),!↓!thyroxine!absorption!
$ Hypomagnesemia!!

Biologics3(E.g.3Infliximab3for3IBD)3
Need!to!test!for!TB!&!Hep!B!before!starting!
$ For!TB!
o Tuberculin!test:!patient!may!be!false!–ve!as!this!test!need!immune!response!
o Interferon!gamma:!more!sensitive!
o CXR:!check!for!upper!zone!changes!&!old!TB!
$ For!Hep!B!
o HBsAg!
o Anti$HBc!Ab:!detect!occult!Hep!B!in!HBsAg!–ve!!
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GI!$!68!
Hematology!
Pancytopenia ..................................................................................................................................2!
Anemia ...........................................................................................................................................2!
Fe!deficiency!anemia............................................................................................................................................................................4!
Thalassemia .............................................................................................................................................................................................4!
Megaloblastic!anemia ..........................................................................................................................................................................5!
B12!deficiency ........................................................................................................................................................................................6!
Pernicious*anemia .................................................................................................................................................................................7!
Folate!deficiency....................................................................................................................................................................................7!
Aplastic!anemia!(Empty!marrow!syndrome)............................................................................................................................8!
Hemolytic!Anemia.................................................................................................................................................................................9!
Immune*hemolytic*anemia..............................................................................................................................................................10!
Autoimmune*hemolytic*anemia....................................................................................................................................................10!
Paroxysmal*nocturnal*hemoglobinuria*(PNH) ......................................................................................................................11!
Paroxysmal*cold*hemoglobinuria ................................................................................................................................................11!
Isolated5neutropenia.....................................................................................................................11!
Platelet .........................................................................................................................................12!
Isolated!Thrombocytopenia ..........................................................................................................................................................12!
Dysfunction!platelet ..........................................................................................................................................................................12!
Clotting .........................................................................................................................................13!
Prolonged!APTT..................................................................................................................................................................................13!
Prolonged!PT!&!APTT.......................................................................................................................................................................13!
Hemophilia ...................................................................................................................................14!
Hemophilia!B!(Christmas!Disease) .............................................................................................................................................14!
Disseminated5intravascular5coagulation5(DIC) ...............................................................................14!
Immune5thrombocytopenia5/5idiopathic5thrombocytopenic5purpura5(ITP).....................................14!
Thrombotic5thrombocytopenia5purpura5(TTP) ...............................................................................16!
Hemolytic5uremic5syndrome5(HUS)................................................................................................17!
Eosinophilia ..................................................................................................................................17!
Hematological5malignancy ............................................................................................................17!
Myelodysplastic5Syndrome5(MDS).................................................................................................18!
Acute5leukemia .............................................................................................................................18!
Acute!Myeloid!Leukemia!(AML) ..................................................................................................................................................19!
Acute*promyelocytic*leukemia*(APL):*AML*M3......................................................................................................................20!
Acute!lymphoblastic!leukemia!(ALL) ........................................................................................................................................21!
Myeloproliferative5Disease5(MPD).................................................................................................23!
Chronic!Myeloid!Leukemia!(CML) ..............................................................................................................................................24!
Acute*blast*transformation.............................................................................................................................................................26!
Ph+ve!myeloproliferative!neoplasms.........................................................................................................................................26!
Polycythemia*vera*(PV) ....................................................................................................................................................................26!
Essential*thrombocythemia*(ET) .................................................................................................................................................27!
Primary*Myelofibrosis*(PMF).........................................................................................................................................................27!
Chronic5lymphocytic5leukemia5(CLL) ..............................................................................................28!
Plasma5cell5malignancy .................................................................................................................29!
Multiple!Myeloma!(MM)..................................................................................................................................................................29!
Smoldering!myeloma........................................................................................................................................................................32!
!

Hematology!+!1!
Monoclonal!gammopathy!of!undetermined!significance!(MGUS) ................................................................................32!
Plasmacytoma......................................................................................................................................................................................32!
Amyloidosis ..........................................................................................................................................................................................33!
Lymphoma ....................................................................................................................................33!
Hodgkins!lymphoma .........................................................................................................................................................................34!
Non+Hodgkin’s!Lymphoma ............................................................................................................................................................35!
Hyperviscosity5/5hyperleukostasis .................................................................................................38!
Tumor5lysis5syndrome ...................................................................................................................38!
Blood5smear..................................................................................................................................39!
Bone5marrow5aspiration5&5biopsy .................................................................................................39!
Transfusion ...................................................................................................................................40!
Acute!hemolytic!transfusion!reaction .......................................................................................................................................41!
Delayed!hemolytic!transfusion!reaction ..................................................................................................................................42!
Febrile!non+hemolytic!transfusion!reaction...........................................................................................................................42!
Allergic!reaction..................................................................................................................................................................................43!
Septic!reaction .....................................................................................................................................................................................43!
!
Pancytopenia5
Causes!
+ Production!
o Aplastic!anemia!
o B12,!folate!deficiency!
o Myelodyplastic!syndrome!(MDS)!
o Infiltration:!myelophthisis!(displacement!of!hemopoietic!BM!tissue!into!peripheral!
blood)!
! Hematological!cancers,!metastasis!of!solid!tumor,!myelofibrosis,!TB,!fungal!
infection!
+ Destruction!
o Hypersplenism!
o Autoimmune!disorder:!lupus,!Evans!syndrome!(Ab!attacking!own!RBC!&!platelets)!
o Paroxysmal!nocturnal!hemoglobinuria!(PNH)!
!
Investigations!
+ Blood!film,!B12,%folate!deficiency!
+ Bone!marrow!examination!
o Hypocellular!marrow:!aplastic!anemia!
! Congenital!
! Acquired:!PNH,!HBV,!HIV,!chemo,!metal,!toxins,!idiopathic…!
o Hypercellular!marrow!
! Primary!BM!diagnosis:!leukemia,!MDS!
! Secondary!
• Myelophthisis!(displacement!of!hemopoietic!BM!tissue!into!peripheral!
blood):!TB,!tumor,!fibrosis!
• B12/folate!deficiency!"!something!like!MDS!"!hypercellular!
• Spleen/immune:!peripheral!destruction!
Anemia5
Anemia!is!common!in!elderly!!
+ Loss!of!teeth!"!eat!less!vegetables!"!B12!/!folate!deficiency!
o ∴!Check!B12!&!folate!if!anemia!
!

Hematology!+!2!
+ Metformin!impair!B12!absorption!
+ H2!blocker!/!PPI!"!↓!gastric!acid!production!"!↓!B12!&!iron!absorption!
!
Causes!
+ Hypochromic!microcytic!
o Thalassaemia!
o Fe!deficiency:!commonest!cause!of!anemia!in!the!world!
o Anemia!of!chronic!illness:!chronic!infection!/!inflammation:!e.g.!TB,!RA!
! Usually!only!microcytic!but!not!hypochromic!
! Low!iron!&!low!TIBC!
! Transferrin!=!protein!produced!by!liver,!in!chronic!infection!&!inflam!"!↓!
protein!production!
o Sideroblastic!anemia!
! In!sideroblastic!anemia!due!to!MDS!"!affect!other!cell!lines!as!well!
o Lead!poisoning!(rare)!
+ Normochromic!normocytic!
o Hemolytic!anemia!
! Congenital!RBC!enzyme!deficiency,!e.g.!G6PD!
! Membrane!defect,!e.g.!hereditary!spherocytosis!
! Autoimmune,!ABO!/!Rh!incompatibility!
o Acute!blood!loss!
o Mixed!microcytic!+!macrocytic!
+ Macrocytic!
o Megaloblastic:!Folate!/B12!deficiency!
! Folate:!rich!in!citrous!fruit,!green+leaf!vegetables!
! B12:!rich!in!egg!yolk,!red!meat!
! B12!deficiency!not!symptomatic!within!1!year!(accumulate!in!liver)!
o Non+megaloblastic:!chronic!liver!disease,!hypothyroid,!alcohol,!hemolytic!anemia,!
myelodysplastic!syndrome!
+ **!Anemia!in!elderly!=!malignancy!until!proven!otherwise!
!
Physical!examination!
+ Fundi!exam!
o Severe!anemia!can!lead!to!retinal!hemorrhage!
!
Investigations!of!anemia!
+ Retic!count!
o Retic!count!↓!"!↓!production!
! Fe,!B12,!folate!deficiency!
! Aplastic!anemia,!congenital!
! Metastatic!lesion!of!BM!
o Retic!count!↑!"!↑!destruction!
! Hemolytic!anemia!
+ Blood!smear!
o Microcytic:!smaller!than!small!lymphocyte!(MCV!<!78)!
o Hypochromic:!central!pallor!>1/3!of!diameter!(MCH!<26.5)!
o Leukoerythroblastic!blood!picture!
! Nucleated!RBC,!tear!drop!cells,!polychromacia,!↓!platelets,!left!shift!of!WBC!(↑!
metamyelocytes,!↑!blasts)!
! If!see!this!"!refer!to!hematologist!!!(Myelofibrosis:!mostly!due!to!malignancy)!
• BM!infiltrated!&!irritated!"!everything!come!out!even!not!ready!
+ RDW!=!red!cell!distribution!width!
!

Hematology!+!3!
 o Fe!deficiency!"!RDW!↑!(RBC!normal!distribution!↑!"!dimorphic!RBC!size)!
o Thalassemia!"!RDW!↓!(all!small)!
o B12!/!folate!deficiency!"!RDW!↓!(all!large)!
+ Iron!profile!
o Don’t!check!ferritin!during!sepsis!as!it’s!acute!phase!reactant,!↑!during!sepsis!

Fe5deficiency5anemia5
Investigation!!
+ Gold!standard:!BM!biopsy!"!pearl!stain!to!stain!Fe!"!absence!of!staining!
o Too!invasive!"!not!done!!!
!
Treatment!!
+ Fe!supplement!!
o Similar!to!B12:!Hb:!not!↑!in!1st!week,!↑!1g/dL/week!2nd!week!onward!
+ Transfusion:!1!pack!"!~!↑!1!unit!of!Hb!
o Acute!blood!loss:!!
! No!need!to!give!back!to!normal,!most!important!control!symptoms!&!stop!
bleeding!
! No!need!to!give!Lasix:!risk!of!dehydration!
! *!Active!blood!loss:!actual!Hb!lower!than!measured!due!to:!
• Ongoing!loss!
• Loss!of!volume!
• Hemoconcentration!
o Chronic!anemia:!give!blood!&!give!Lasix!to!avoid!fluid!overload!

Thalassemia5
Types!of!thalassemia!
+ Alpha!!
o αα/αα:!normal!
o α+/αα:!silent,!mild!microcytosis,!no!anemia!
o αα/++!or!α+/α+:!trait,!mild!microcytosis,!mild!anemia,!no!therapy!required!
o α+/++:!intermediate,!HbH!disease,!sometimes!require!transfusion!
o ++/++:!!major,!Hb!Barts!–!hydrops!fetalis!unless!transfused!in!utero!
+ Beta!
o β/β:!normal!
o β/β0!or!β/β+:!minor,!mild!/!no!anemia!
o β+/β+:!intermediate,!symptomatic!with!moderate!anemia!(Hb7+10g/dL),!no!need!
regular!transfusion!
o β0/β0!or!β0/β+:!major!(Cooley’s!anemia),!severe!anemia,!transfusion!dependent!
o *!β0!=!no!β!chain!produced;!β+!=!small!amount!β!chain!produced!
!
Clinical!features!
+ Anemia,!depends!on!severity!of!disease!
+ Hepatosplenomegaly!!
+ Iron!overload:!↑!GI!absorption!±!transfusion!
o Body!cannot!differentiate!whether!the!anemia!is!due!to!iron!deficiency!or!not!"!
absorb!more!
o Cx:!cardiac!failure,!endocrine!problem,!liver!cirrhosis!
o Bronze!skin!color!
+ Cooley’s!anemia!(β!major):!expanded!BM!"!skeletal!changes!(hair!stand!on!end!appearance!
on!skull!XR)!
!

Hematology!+!4!
!
Thalassemia!intermediate!
+ Hepatosplenomegaly:!usually!no!massive!
+ May!also!have!mild!jaundice!
o Have!hemolysis!inside!BM:!due!to!defective!Hb!"!cannot!go!through!quality!control!
"!hemolysis!
!
Diagnosis!!
+ Hemoglobin!pattern!!
+ Iron!profile!
o Rule!out!Fe!deficiency!anemia!
o Ferritin:!show!iron!overload!status!
+ Genetic!tests!
!
Management!
+ Depends!on!severity!
+ Blood!transfusion!if!patient!has!symptomatic!anemia!
+ Iron!chelator!for!pts!with!Fe!overload!
+ Folic!acid!supplement!
+ Splenectomy:!in!severe!splenomegaly!
+ Bone!marrow!transplantation!(for!paedi!patients!with!β+thalassemia!major)!

Megaloblastic5anemia5
Introduction!
+ B12!and!folate!are!required!for!DNA!synthesis!(deficiency!"!cells!cannot!divide!"!big!cells)!
+ B12!is!also!required!for!neurological!functioning!(subacute!combined!degeneration!of!cord)!
+ B12!!
o Meats,!fish,!eggs,!dairy!product!
o Body!store!usually!sufficient!for!3!years!
+ Folate!
o Liver,!leafy!green!vegetables,!nuts,!yeast,!egg!yolk,!fortified!grain!products!(pasta,!
cereal,!bread)!
o Readily!destroyed!by!cooking,!especially!in!large!amount!of!water!
o Absorbed!throughout!the!small!bowel!
o Body!store!usually!sufficient!for!3+4!months!
+ **!Folate!deplete!1st,!so!usually!give!folic!acid!for!patient!with!↑!RBC!turnover!(e.g.!hemolytic!
anemia),!not!giving!B12!
!
Investigation!
+ The!larger!than!MCV,!the!more!likely!it!is!megaloblastic!anemia.!If!MCV!=130!"!almost!
diagnostic!
+ Blood!film:!oval!macrocytes,!hypersegmented!neutrophils!(>5%!neutrophils!with!>5!lobes)!
+ May!have!↑!in!bilirubin!due!to!hemolytic!anemia!due!to!ineffective!erythropoiesis!"!check!
LDH!&!haptoglobin!
+ Serum!B12!
+ Fasting!serum!folate!/!RBC!folate!(serum!folate!level!affected!by!recent!diet)!
+ LFT,!TFT:!chronic!liver!disease,!hypothyroidism!&!alcohol!lead!to!macrocytic!anemia!
+ Thyroid!autoAb:!pernicious!anemia!may!be!related!to!other!autoimmune!disease,!e.g.!thyroid!
+ OGD:!atrophic!gastritis!leading!to!B12!deficiency!
+ Drug!history:!high!dose!long!term!metformin!

Hematology!+!5!
B125deficiency5
Causes!
+ Inadequate!intake!
o Alcoholism!"!not!eat!meat!
o Strict%vegetarian%%
o Elderly!with!no!teeth!
+ ↓!Absorption!
o Ask!history!of!diarrhea!!!(malabsorption!"!diarrhea)!
o Post5total%gastrectomy%
o Pernicious%anemia%
o Terminal!ileum!pathology!(Crohn’s,!TB,!terminal!ileal!ulcer)!/!resection!
o Metformin!affect!absorption!
o Malabsorption:!tropical!sprue,!coeliac!disease!
o Intestinal!bacterial!overgrowth:!e.g.!blind+loop!syndrome!(bacteria!compete!for!
available!B12,!but!folate!↑!as!bacteria!produce!folic!acid)!
o Parasite:!Diphyllobothrium!latam!(fish!tape!worm)!"!see!eosinophil!count!in!CBC!!!
o Transcobalamin!II!deficiency!
!
Presentation!
+ Megalobastic!anemia!
+ Atrophic!mucositis!
+ Subacute!combined!degeneration!
o Posterior!cord!syndrome!
! Dorsal!column!=!loss!of!proprioception!and!vibration!
! Corticospinal!tract!=!UMN!weakness,!upgoing!plantar!
o Peripheral!neuropathy!=!Distal!areflexia!+!sensory!impairment!
+ Dementia!
!!
Diagnosis!
+ Pancytopenia,!high!MCV!
+ Hypersegmented!neutrophils!(more!active)!
+ Serum!B12!level!
+ Methylmanolic!acid/!homocysteine!(elevated)!=!a!more!sensitive!test!
+ Anti+parietal!cell!/!anti+intrinsic!factor!antibody!
o If!+ve!"!no!need!to!do!Schilling!test!
+ Schilling!test!(not!commonly!available!in!hospitals,!due!to!need!of!radioactive!isotope)!
o Saturate!body!store!with!1000ug!of!IM!B12!
! Need!to!detect!the!excretion!of!radioactive!B12!in!urine,!so!need!to!saturate!the!
body!store!1st!!
! Monitor!K!meanwhile:!↑!cell!production!may!cause!hypoK!
o Part!I:!oral!1ug!radioactive!B12!"!test!ability!of!gastric!mucosa!to!secrete!IF!
o Part!II:!oral!1ug!radioactive!B12!+!IF!"!test!the!ability!of!terminal!ileum!to!absorb!B12!
o Part!III:!oral!1ug!radioactive!B12!+!antibiotics!"!exclude!bacterial!overgrowth!
o **!Not!accurate!with!inadequate!renal!function!
+ OGD:!anti+parietal!cell!Ab!in!pernicious!anemia!may!lead!to!pan+gastritis!
+ BM!biopsy:!malignancy!infiltrate!into!BM!!
!
Treatment!
+ B12!supplement!by!IM!injection!(1mg!monthly)!or!oral!
+ Depend!on!symptoms!"!transfusion!

Hematology!+!6!
Pernicious5anemia5
+ Autoimmune!atrophic!gastritis!"!Achlorhydria!+!IF!deficiency!
!
Treatment!
+ IM!B12!(hydroxocobalamin)!alternate!days!for!2!weeks!(usually!6!injections!in!total!is!
adequate,!more*in*subacute*combined*degeneration)!
o Caution!in!patient!taking!warfarin:!avoid!IMI,!use!SC!&!press!longer!after!injection!OR!
give!large!dose!oral!(1mg)!
o May!lead!to!sudden!hypoK!after!giving!B12!supplement!due!to!↑!in!cell!production!in!BM!
! ∴Should!monitor!RFT!&!give!K!supp!
o 3+4!days:!BM!start!to!react!"!synthesis!
! Plt,!WBC!~!2!weeks!back!to!normal!
! Hb:!not!↑!in!1st!week,!↑ 1g/dL/week!2nd!week!onward!
+ IM!B12!every!3!months!thereafter!
+ *!Avoid!red!cell!transfusion!before!B12!replacement,!it!may!potentially!worsen!the!current!
neurological!signs,!making!it!irreversible!
!
Association!
+ Autoimmune!thyroid!disorders!
+ Addison's!disease!
+ Type!I!DM!
+ Hypogonadism!
+ Vitiligo!
+ Myasthenia!gravis!
!
Prognosis!
+ Peripheral!neuropathy!>!Myelopathy!(Sensory!>!motor)!

Folate5deficiency5
Causes!
+ Reduced!intake!
o Poor!nutrition,!e.g.!poverty!/!old!age!
+ Poor!gastrointestinal!absorption!
o Diffuse!inflammatory!/!degenerative!diseases!of!small!intestine:!Crohn’s,!chronic!
enteritis,!entero+enteric!fistulae!
o Resection!of!small!bowel!
+ Increased!requirement!/!losses!
o Pregnancy,!lactation,!↑ turnover!e.g.!hemolysis,!malignancy,!exfoliative!dermatitis,!renal!
dialysis!
+ Drugs!
o Induce!malabsorption:!phenytoin,!barbiturates,!valproate,!contraceptive!
o Anti+folate!drugs:!methotrexate!(inhibit!dihydrofolate!reductase),!trimethoprim,!
pentamidine!
+ Alcohol:!poor!nutrition!+!direct!depressant!effect!on!folate!level!
+ Dihydrofolate!reductase!deficiency!
!
Association!!
+ Glossitis,!diarrhea!
+ Depression,!confusion!
+ Fetal!neural!tube!defects!!
!
!
!

Hematology!+!7!
Investigation!
+ Erythrocyte!folate:!reflect!body!store!
o Vs!serum!folate:!may!be!affected!by!recent!intake!
!
Treatment!
+ Folate!replacement!(5mg!daily!PO!x4!months)!only!after!B12!deficiency!ruled!out!!
o B12!deficiency!can!cause!neurological!deficit!(impair!myelination!of!NS),!folate!may!
aggravate!neurological!symptoms!

Aplastic5anemia5(Empty5marrow5syndrome)5
+ A!severely!depressed!marrow!cellularity!(usually!<!25%)!accompanied!by!a!decrease!in!2!
out!of!3!blood!lineages!
!
Etiology!
+ Fanconi's!anemia:!congenital!disease,!in!paedi,!a/w!BM!failure!&!AML!
+ Idiopathic:!not!uncommon!!
o Need!to!think!of!autoimmune!disease!!!
+ Post+viral!infection!(Hepatitis!A)!
+ Drugs!(sulfonamides,!chloramphenicol,!gold,!phenylbutazone)!
+ Chemotherapy,!radiation!
+ Chemicals!(benzene,!pesticides)!
+ Radiation!
+ Immune!diseases!
+ Paroxysmal!nocturnal!hemoglobinuria!(PNH)!
+ Pregnancy!
!
Investigations!
+ Pancytopenia!
+ High!MCV!
+ Hypocellularity!in!bone!marrow!biopsy!
!
Classification!
+ Severe:!2!of!the!following!3!criteria!
! Absolute!neutrophil!count!<500/mL!
! Platelets!<20,000/mL!
! Absolute!reticulocytes!count!<40,000/mL!
+ Very!severe:!neutrophils!<200/mL!
+ Non+severe!(moderate!AA):!AA!not!fulfilling!severity!criteria!
+ Chronic!MAA:!persistent!moderately!depressed!counts!>!3!months!
!
Treatment!
+ Immunosuppression!
o Anti+thymocyte!globulin!(horse!/!rabbit)!
! T+cell!mediated!
! Cx:!anaphylaxis,!serum!sickness!due!to!animal!protein!
• So!need!to!combine!with!cyclosporin!
o Cyclosporine!(for!6!months)!
o Cyclophosphamide!(high!dose)!
+ BMT:!for!young!patient!with!severe!AA!with!HLA!matched!sibling!
+ Stem!cell!transplant!
+ Transfusion!support!
+ Others:!androgens,!G+CSF,!Daclizumab!
!

Hematology!+!8!
Hemolytic5Anemia55
Approach!!
+ Increased!Red!cell!breakdown?!CBC!(Hb),!LDH,!unconjugated!bilirubin,!urobilinogen!
+ Increased!Red!cell!production?!!CBC!(MCV),%retic%count,!Blood%film!(macrocytosis,!
polychromasia)!
+ Intra!or!Extravascular?!!Haptoglobin,!Hemogloblinemia,!Hemoglobinuria,!
Hemosiderinuria,!Methaemoalbuminemia!
+ Immune!or!non+immune?!!Coomb's%test!
+ Finally...What!is!the!root!cause?!
!!
Etiology!!
+ Intracorpuscular!hemolysis!
o Membrane!abnormalities!
! Hereditary!spherocytosis,!elliptocytosis,!South!east!asia!ovalocytosis!
! Paroxysmal*nocturnal*hemoglobinuria*(PNH)!
o Metabolic!abnormalities!
! G6PD*deficiency,*pyruvate*kinase*deficiency*
o Hemoglobinopathies!
! Sickle*cell*anemia,!thalassemia!
+ Extracorpuscular!hemolysis!
o Non+immune!
! Mechanical*valve,*Microangiopathic*(DIC,*TTP,*HUS,*eclampsia,*IE)*
o Immune!
! Acute*hemolytic*transfusion*reaction*
! Paroxysmal*cold*hemoglobinuria*
! Autoimmune*hemolytic*anemia*(cold)*
! Autoimmune!hemolytic!anemia!(warm)!
+ *!Italic*=*intravascular;!underline!=!extravascular!
!
! Intravascular! Extravascular!
Splenomegaly! (Malaria)! +++!
Urine!Hb/!hemosiderin! +++! !
Smear! Heinz,!bite,!blister!cells! Microcytic!hypochromic!thalassemia!
Schistocyte!(fragmented!RBC)! Spherocytosis,!elliptocytosis!
Plasmodium!parasites!
Haptoglobin! DECREASED! !
Free!plasma!Hemoglobin! ++! !
Methaemalbuminemia! ++! !
(heme!+!albumin)!
!!
Investigations!
+ CBC!(anemia,!high!MCV,!??thrombocytopenia)!
+ Blood!film!
o Hemolysis:!macrocytosis,!polychromasia,!reticulocytes!
+ Reticulocyte!count!
+ Bilirubin!
+ Haptoglobin!(bind!free!Hb!to!liver),!hemopexin!(bind!heme)!>>!methemalbumin!(heme!+!
albumin,!brown)!>>!hemogloblinemia/!hemoglobinuria!
+ LDH,!AST!
!

Hematology!+!9!
+ Urine!dipstix!(urobilinogen,!hemogloblin,!hemosiderin)!
+ Coomb's!test!
+ Clotting!profile!

Immune5hemolytic5anemia5
+ All!require!antigen+antibody!reactions!
+ Antibodies!combine!with!RBC!&!either!
o Activate!complement!cascade!→!intravascular!haemolysis!
o Opsonize!RBC!for!immune!system!→!extravascular!haemolysis!
!
Causes!
+ Drug+related!hemolysis!
o Methyldopa,!L+DOPA,!ibuprofen,!quinidine,!quinine,!isoniazid,!penicillins,!
cephalosporins!
+ Alloimmune!hemolysis!
o Hemolytic!Transfusion!Reaction!!
o Hemolytic!Disease!of!the!Newborn!
+ Autoimmune!hemolysis!
o Warm!autoimmune!hemolysis!
o Cold!autoimmune!hemolysis!
!
Investigation!!
+ Direct!antiglobulin!(Coombs’)!test:!looks!for!Ig!&/or!C’!of!surface!of!RBC!
+ Indirect!antiglobulin!test:!looks!for!anti+RBC!Ab!in!patient’s!serum!
!
Treatment!
+ Steroid,!IVIg,!immunosuppressant!
+ Plasma!exchange!NOT!1st!line!
o In!such!severe!anemia,!doing!plasma!exchange!may!kill!patient!(need!to!draw!blood!
outside!body)!

Autoimmune5hemolytic5anemia5
Warm!(Ab!binds!RBC!best!at!37°C)!
+ Mediated!by!IgG!
+ Extravascular!hemolysis!
+ Causes*(most*are*idiopathic)!
o Lymphoproliferative*diseases!
o Malignancy!
o Connective*tissue*diseases!
o Drugs*(methyldopa,*penicillin,*quinine)!
!!
Cold!(Ab!binds!RBC!best!at!4+18°C),!also!called!cold%agglutinins!
+ Mediated!by!IgM!
+ Intravascular!hemolysis!
+ Causes!
o Infection:*Mycoplasma,*EBV*!
o BVcell*neoplasm!
!!
Management!(**response*usually*unsatisfactory*for*COLD*type)!
+ Find!the!underlying!cause,!treat!if!treatable!
+ Asymptomatic!=!no!treatment!
+ Symptomatic!
!

Hematology!+!10!
 o Prednisolone,!tapered!over!3!months!to!maintain!effect!
o If!no!response!in!3!weeks!"!splenectomy!
o If!failed!too!"!consider!danazol,%cyclophosphamide,%azathioprine,%IVIg!
+ Life!threatening!
o Transfusion!
! If*patient*is*IndirectVAntiglobulinVTest*positive,*almost*all*blood*units*will*be*
incompatible.*Still,*it*does*not*preclude*transfusion*simply*because*of*this.*
Transfusion*of*100V150mL*of*incompatible*blood*may*be*life*saving!

Paroxysmal5nocturnal5hemoglobinuria5(PNH)5
Introduction!!
+ The!only!ACCQUIRED!RBC!membrane!defect!!
+ May!arise!as!primary!disease!or!together!with!aplastic!anemia!
!!
Pathogenesis!
+ Lack!of!glyceryl%phosphatidyl%inositol%(GPI)!
+ Decreased!anchoring!of!CD55%and!CD59!
+ Loss!of!protection!from!complement!lysis!"!leading!to!intravascular%hemolysis!
!!
Clinical!presentation!
+ Nocturnal!hemoglobinuria!
o 2!proposed!mechanisms!
! At!night,!blood!turns!more!acidic!&!RBC!become!highly!sensitive!to!
complement!lysis!
! At!night,!urine!become!concentrated!where!the!red!color!become!apparent!
+ Pancytopenia!
+ Thombotic!tendency:!DVT,!PE,!Budd+Chiari!syndrome!(hepatic!v),!portal!vein!thrombosis,!
mesenteric!ischemia!(IMA,!SMA)!
o Platelets!hypersensitive!to!complements!become!dysfunction!!
o Free!Hb!in!blood!scavenge!free!NO!which!is!potent!anti+thrombotic!
o Associated!aplastic!anemia!may!lead!to!thrombocytopenia!
o *!Mesenteric!ischemia!may!lead!to!GI!bleed!"!difficult!to!manage!as!there’s!
thrombosis!&!bleeding!at!the!same!time!
+ Dysphagia,!odynophagia,!abdominal!pain,!erectile!dysfunction!
o Free!Hb!binds!with!circulating!NO,!which!is!potent!smooth!muscle!relaxant!
!!
Investigation!!
+ DAT!–ve!!
+ Ham's!acid!hemolysis!test:!place!RBC!in!mild!acid;!a!positive!result!(increased!RBC!fragility!
+ Neutrophil!alkaline!phosphatase!(NAP):!low!
+ Flow!cytometry!for!CD55!&!CD59!on!WBC!&!RBC:!normal!/!reduced!/!absent!levels!of!CD55!
&!CD59!
+ Check!bone!marrow!for!aplastic!anemia!

Paroxysmal5cold5hemoglobinuria5
+ After!infection!e.g.*syphilis,*measles,*mumps,*adenovirus,*EBV!
+ Autoantibody!(Donath+Landsteiner!antibody)!binds!on!RBC!when!cold!
+ Complement+induced!lysis!when!re+warmed!
Isolated5neutropenia5
Causes!
+ Production!
o Agranulocytosis:!Drugs!(antithyroid!drugs,!anticonvulsants,!gold)!
!

Hematology!+!11!
 o Kostmann's!syndrome!
+ Destruction!
o Autoimmune!diseases!
!
Management!
+ If!neutropenia!<0.5!broad%spectrum%antibiotics!
+ G5CSF,%GM5CSF!
Platelet5
Isolated5Thrombocytopenia5
**!Make!sure!no!platelet!clumping!(pseudothrombocytopenia)!by!checking!blood%film!
!
DDx!
+ ↓!production:!aplastic!anemia,!thrombocytopenia!with!absent!radii,!MDS%/%AML,!
megaloblastic!anemia,!chronic!liver!disease!(e.g.!secondary!to!HCV),!alcoholism!
o Not!likely!if!RBC!&!WBC!normal,!as!there’s!not!much!disease!entity!causing!isolated!
platelet!production!problem!
o WBC!has!short!lifespan,!so!WCC!likely!to!come!down!first!when!production!is!
affected,!e.g.!radiation!of!BM!
+ ↑!destruction/consumption:!ITP,!HUS,!TTP,!HIT,!DIC,!SLE!
+ Sequestration:!hypersplenism!(chronic!liver!disease,!myelofibrosis,!Gaucher’s!disease,!ITP)!
o Usually!platelet!comedown!first!before!WCC!decrease,!then!Hb!also!come!down!!
+ Drug:!aspirin,!NSAID,!heparin,!digoxin,!amiodarone,!quinidine!
!
Consideration!
+ Absolute!platelet!count!
+ Rate!of!decrease!in!platelet!count!
+ Platelet!function!
o E.g.!on!aspirin!/!NSAID,!septic,!uremia,!paraproteinemia!(spontaneous!bleeding!
happen!if!platelet!<20!in!septic!patients!(vs!<10!in!normal!people))!
o ∴!Consider!treat!even!platelet!count!not!lower!than!threshold!of!treatment!
!
Management!!
+ Look!for!mucosal!bleeding!(not!skin!bruising!–!common!to!have!easy!bruising!in!elderly)!
+ Do!crossmatch,!order!platelet!
+ No!IM!injection!(put!the!sign!on!bedside)!
+ Indication!for!treatment!!
o Active!bleeding!
o <100!who!under!eye/brain!surgery!
o <50!who!under!surgery!except!eye/brain!surgery!
o <30!who!are!asymptomatic!!
o <10!who!are!on!chemo!(give!platelet!transfusion)!
+ Options!
o Platelet!transfusion!
o DDAVP!(Desmopressin):!↑!factor!VIII!&!von!Willebrand!factor!"!help!platelet!
aggregation!
! For!platelet!dysfunction,!e.g.!uremia,!chronic!liver!disease!
! Also!for!hemophilia!A!&!vWF!deficiency!

Dysfunction5platelet5
DDx!
+ Congenital!
!

Hematology!+!12!
 o GP!Ib+XI!(adhesion)!
o GP!IIb/IIIa!!!!
+ Acquired!
o Renal!/!liver!failure!
o Myeloproliferative!disease!
o Drug:!aspirin,!NSAID!
o Alcohol!!
Clotting55
Clotting!cascade!
+ Intrinsic!pathway!(pre+kalikrein)!
o Factor!12,!11,!9,!8!
+ Extrinsic!pathway!(tissue!factor)!
o Factor!7!
+ Common!pathway!
o Factor!10,!5,!pro+thrombin,!fibrinogen!

Prolonged5APTT55
Mixing!study!(1:1!mixing!with!normal!plasma)!
+ No!change:!inhibitor!
o Lupus!anticoagulant!(e.g.!antiphospholipid!syndrome),!heparin!
o Acquired!inhibitor:!autoimmune!disease,!metastatic!disease!
+ Improved:!factor!deficiency!
o Hemophilia!A!(factor!8),!B!(factor!9)!
o Factor!11!deficiency!(autosomal)!
o Factor!12!deficiency!(no!bleeding!tendency!although!↑!APTT)!
o Von+Willibrand!disease!
! Heterogenous!hemorrhagic!disorder!caused!by!deficiency/dysfunction!of!vWF!
! Impaired!primary!hemostasis!due!to!defective!interaction!between!platelet!&!
vascular!wall!!
! Female!bleeding!disorder!
! Sx:!easy!bruising,!menorrhagia,!bleeding!aggravated!by!aspirin,!better!by!OCP!
! Ix:!vWF!assay,!Ristocetin!(A/B!that!cause!plt!aggregation!in!presence!of!vWF)!
! Rx:!FFP,!Factor!8,!vWF!concentrate!
+ If!APTT!prolonged!after!2!hour!incubation!"!TIME%DEPENDENT%INHIBITOR!
!
Management!
+ Transamin!(Tranexamic!acid)!
o Anti+fibrinolytic!agent!

Prolonged5PT5&5APTT5
DDx!
+ DIC:!↓!platelet,!↑!D+dimer!&!FDP!
+ Liver!disease:!↓!all!clotting!factors!except!factor!8!(produced!by!endothelia)!
+ Vit!K!deficiency:!↓!factor!2,!7,!9,!10!
!
Management!
+ FFP:!200+250ml!
o *Also!contain!protein!C!&!S,!anti+thrombin!(but!short!t½,!so!transient!effect!only)!
+ Prothrombin!complex!concentrate!(PCC)!
o Vit!K!dependent!factors!with!small!volume!
+ Cryoprecipitate!!
o More!concentrated:!prevent!fluid!overload!even!need!to!replace!many!clotting!factors!
!

Hematology!+!13!
 o Poor!source!of!vit!K!dependent!clotting!factor,!so!not!used!in!warfarin!overdose!
+ Platelet,!pack!cell!
+ Vit!K!
o Onset:!6+12!hours,!PT!corrected!after!24!hours!
Hemophilia5
Hemophilia5B5(Christmas5Disease)5
+ Originally!named!“Christmas!disease”!for!the!1st!person!diagnosed!with!disorder!in!1952!
+ Inhibitors!may!develop!after!repeated!clotting!factor!transfusion!
+ Physical!exam!
o Extensive!bruising!/!ecchymosis!at!venipuncture!site!
Disseminated5intravascular5coagulation5(DIC)5
+ Excessive!thrombosis!with!consumptive!coagulopathy!
!
Causes!
+ Severe!sepsis,!pancreatitis!
+ Malignancy!(M3,!prostate)!
+ Obstetric!causes:!abruptio,!amniotic!fluid!emboli,!eclampsia,!HELLP!syndrome!
+ Severe!transfusion!reaction,!trauma,!e.g.!neurotrauma!
+ Large!vessel!aneurysm,!Kasabach+Merritt!syndrome!
!
Investigations!
+ Clotting!profile!
+ Platelet!count!
+ Blood!film!(schizocytes)!
+ Fibrinogens!
+ FDP/!D+dimers!
!
Management!
+ Identify!and!treat!the!underlying!etiology.!
+ Platelets!if!<50,!FFP!+!cryoprecipitate!
+ Activated%pro5C!in!DIC!with!severe!sepsis!or!MOD!(anti+thrombotic)!
+ Transamin*(antiVfibrinolytic)*is*relatively*contraindicated,*because*it*potentially*worsen*the*
ongoing*thrombosis!!
Immune5thrombocytopenia5/5idiopathic5thrombocytopenic5purpura5(ITP)5
+ Autoimmune!disorder!causing!immunologic!destruction!of!normal!platelets!in!response!to!
an!unknown!stimulus!
+ The!most!common!cause!of!isolated!thrombocytopenia!
!
Pathogenesis!
+ Platelet!destruction!
o Ig!autoreactive!Ab!coat!plt!"!macrophage!bind!to!platelet!"!plt!destroyed!through!
phagocytosis!in!spleen!
+ Inadequate!Platelet!Production!
o Auto+Ab!bind!to!megakaryocytes!in!bone!marrow!"!megakaryocytes!destroyed!
prevented!from!maturation!" plt!turnover!↓!despite!normal!TPO!levels!!!
!
Classification!!
+ Acute!=!2!weeks!after!viral!infection!
+ Chronic!=!lasting!more!than!3!months!
+ Primary:!isolated!
!

Hematology!+!14!
+ Secondary:!a/w!other!disorders!
o Anti+phospholipid!syndrome,!SLE!
o Infection:!CMV,!Hp,!Hep!C,!HIV,!VZV!
o Lymphoproliferative!disorders!
o Vaccine!/!drugs!S/E!
!
Diagnosis!
+ By!exclusion!of!secondary!causes!of!thrombocytopenia!
o No!diagnostic!tests!to!confirm!ITP,!can’t!use!the!Ab!
!
History!taking!
+ Focus!on!!
o Identifying!evidence!of!bleeding!AND!
o Excluding!other!causes!of!thrombocytopenia!/!secondary!ITP!
! Fever,!weight!loss,!hepatomegaly,!lymphadenopathy!"!HIV,!SLE,!lymphoma!
!
Physical!exam!
+ Mild!splenomegaly!may!be!found!in!younger!patients,!but!moderate!/!massive!splenomegaly!
suggests!an!alternative!cause!!
!
Investigations!
+ CBC:!should!be!isolated!thrombocytopenia!only!
o *!May!have!anemia!from!blood!loss,!if!so!"!look!at!reticulocyte!count!to!differentiate!
poor!production!vs!increased!destruction!of!RBC!
+ Film%comment:!rule!out!pseudothrombocytopenia!(clumping)!/!other!DDx!(e.g.!schistocytes!
in!TTP)!
+ HIV,%HCV!(secondary!ITP,!control!of!these!infections!may!result!in!complete!hematologic!
remission)!
o Routine!screening!for!HIV!&!HCV!in!adult!patients!with!suspected!ITP!is!
recommended!by!the!latest!ASH!guidelines!
+ Coomb's!test,!ANA!usually!not!needed,!only!if!clinical!feature!is!suggestive!
+ ±!BM!examination!
o Only!do!in!patient!with!abnormalities!in!CBC!&!peripheral!blood!smear!other!than!
thrombocytopenia!(i.e.!if!suspecting!other!diseases,!e.g.!leukemia)!
o ASH!guideline!2011:!no!longer!routinely!indicated!in!patients!>60!
!
Treatment!
+ Indications!!
o Treat!when!patient!is!symptomatic!(bleeding!tendency!/!when!platelet!count!<30!
even!asymtopmatic)!
! Platelet!count!>100!"!consider!normal!
! Platelet!count!50+100!"!in!general!patient!won’t!bleed,!except!in!e.g.!brain!
surgery!
• Treat!if!symptomatic,!or!in!asymptomatic!pt!undergo!major!surgery!
! Platelet!<30!"!bleeding!risk!is!increased!
! Platelet!<10!"!give!platelet!transfusion!for!patient!on!chemo!
o Once!start!treatment,!treat!until!platelet!count!>50,!then!taper!off!Rx!
o **!Don’t!want!to!over+treat!the!patient!
! Immunosuppress!"!↑!risk!of!infection!
+ 1 !line!Rx!
st

o Steroids%(dexamethasone/!methylprednisolone!/!prednisolone)!
! Effective,!but!most!of!patient!will!relapse!
!

Hematology!+!15!
 ! Need!days!to!weeks!to!start!response!
o IV%anti5D!
o IVIg!
! Used!in!emergency!setting,!e.g.!active!bleeding!!
! Respond!quickly:!many!within!24!hours,!typically!2+4d!
! Risk!of!thrombosis,!expensive!
2nd!line!Rx!
o Give!once!to!induce!remission!/!chronic!administration!to!maintain!remission!
o Splenectomy%
! Decision!should!be!deferred!for!≥6!months!
• Spontaneous!improvement!/!late!remission!may!occur!in!6+12!months!
! 1/3!of!patient!may!still!relapse!in!5!years!
! Surgical!Cx:!bleeding,!infection,!prolonged!hospitalization,!etc!
! Long!term:!infectious!complications,!esp!to!encapsulated!bacteria!
• Vaccine!against!Streptococcus*pneumoniae,!Neisseria*meningitidis,!and!
Haemophilus*influenzae*at!least!2!weeks!before!
o Danazol%(not!in!reproductive!age!female:!androgenic!effect)!
o Dapsone!!
o Immunosuppressant:!azathioprine,!cyclophosphamide,!cyclosporin!A,!MMF,!
rituximab,!Vinca!alkaloids!
o Stem!cell!transplant!
o Thrombopoietin%receptor%(TPOr)%agonists%targeted%therapy:%Eltrombopag,!
romiplostim!
! Platelet!production!may!be!decreased!in!a!substantial!fraction!of!patients!with!
ITP,!esp!those!with!refractory!disease!
! Well!tolerated,!but!may!be!lifelong!treatment,!very!costly!
!
Thrombotic5thrombocytopenia5purpura5(TTP)5
Pathology!
+ Lack!of!metalloproteinase!ADAMTS513,!which!breaks!down!the!circulating!large!multimers!
of!vWF!"!thrombi!formation,!particularly!at!sites!of!high!shear!stress!
!!
Causes!
+ Idiopathic!
+ Drugs!(clopidogrel,!ticlopidine,!quinine,!cyclosporin,!tacrolimus)!
+ HIV!
+ Pregnancy!
+ Bone!marrow!transplant!
+ Cancer!
!
Classical!pentad!
+ Fever!
+ Neurological!symptoms!(fluctuating):!hallucinations,!bizarre!behavior,!altered!mental!status,!
stroke,!or!headaches!
+ Renal!impairment!
+ Microangiopathic!hemolytic!anemia:!anemia,!jaundice,!fragmented!RBC!
+ Thrombocytopenia:!bruising!/!purpura!
!!
Treatment!
+ Plasmapheresis!
+ FFP!infusion!(which!contains!ADAMTS+13)!
+ Immunosuppressants!if!refractory!
!

Hematology!+!16!
!!
Monitoring!
+ Platelet!count!
+ LDH!
+ Renal!function!
Hemolytic5uremic5syndrome5(HUS)5
Pathogenesis!
+ Infection!by!E.!coli!O157,!produce!verotoxin!that!damage!endothelial!cells!
+ Platelet!aggregation!predominantly!in!renal!vasculature!
+ Fibrin!strand!lyse!red!cells!
!
Enterohemorrhagic!E.!coli!infection!(O157:H7)!
+ Produce!a!verotoxin!(shiga+like)!
o Locally!cytotoxic!and!produce!ulcers!
o Attach!the!ENDOTHELIAL!CELLS!in!renal!vessels!
! "!Trigger!platelet!aggregation!locally!in!renal!vessels!
• Causing!the!microangiopathic!hemolytic!anemia!&!acute!renal!failure!
!!
Shiga%toxin:!Subunit!A!+!subunit!B!(pentamer)!
+ Subunit!B!binds!to!GM1%ganglioside%receptors,!particularly!the!Gb3!
o Gb3!is!present!in!greater!amount!in!renal!capillaries!"!giving!pathogenesis!of!HUS!
+ Subunit!A!enters!the!enterocytes,!binds!to!ribosomes,!disrupting!protein!synthesis!"!
cytotoxic!
!
Presentation!
+ Microangiopathic!anemia!
+ Thrombocytopenia!!
!
Treatment!
+ NO!ANTIBIOTICS!!
+ Emergent!dialysis!
+ Plasma!exchange!
Eosinophilia5
Causes!
+ Allergic!reaction:!look!for!drug!allergy!!
+ Parasite!
+ Systemic!autoimmune!disease,!e.g.!SLE!
+ Hodgkin's!lymphoma,!leukemia!
+ Addison’s!disease!
Hematological5malignancy5
Multi+potential!hematopoietic!stem!cells!
+ Common!myeloid!progenitor!
o Erythrocyte!
o Myeloblast!"!promyelocyst!"!myelocyte!"!metamyelocyte!"!band!cells!"!
basophils,!eosinophils,!neutrophils,!monocytes!("!macrophage)!
o Megakaryocyte!"!thrombocytes!
+ Common!lymphoid!progenitor!
o Natural!killer!cell!(large!granular!lymphocyte)!
o Small!lymphocyte!"!T!cell!lymphocyte,!B!cell!lymphocyte!("!plasma!cell)!!
!
Hematological!malignancy!
!

Hematology!+!17!
+ Lymphoid!neoplasms!
o Leukemia:!from!lymphoblast!(more!immature!cells,!arrest!in!maturation,!excessive!
proliferation!of!blasts)!
o Lymphoma:!from!more!mature!cells!(have!maturation)!
+ Myeloid!neoplasms!
o Myeloid!leukemia!
o Myelodysplasia:!maturation,!but!dysplastic!(cells!are!abnormal)!
o Myeloproliferative!syndromes:!problem!in!all!stage!of!maturation!
!
Diagnosis!
+ ALL!"!BM;!lymphoma!"!incisional!/!excisional!biopsy!of!LN;!CLL!"!peripheral!blood!
Myelodysplastic5Syndrome5(MDS)5
Introduction!!
+ Clonal!disorder!of!hemopoietic!stem!cells,!leading!to!ineffective!hematopoiesis!
+ Marrow!partly!/!wholly!replaced!by!a!clone!of!mutant!multi+potent!stem!cells,!that!retains!
the!capacity!to!differentiate,!but!in!a!manner!that!is!both!ineffective!&!disordered!
+ Usually!in!age!>70!
+ Pre+leukemic!state!/!smoldering!leukemias!
o May!undergo!transformation!to!AML,%esp.!secondary!type!
+ NO!hepatosplenomegaly!(Vs!myelofibrosis)!
!!
Two!forms!
+ Idiopathic!/!primary!
+ Secondary!to!chemo/radiation!
!!
Investigations!
+ Any%cytopenias!with!elevated!MCV!
+ Low!retic!count!
+ Bone!marrow!aspirate!
o Multinucleated!RBC!precursors/!Ringed!sideroblasts!
o Hyposegmented!and!hypogranulated!WBC!precursors!
o Hypolobulated!megakaryocytes!
o Blast!cells!<20%!
+ Trephine!biopsy!
o Hypercellularity!(with!peripheral!pancytopenia!!)!
!!
Treatments!
+ Curative!(usually!for!young!fit!patients)!
o Stem!cell!transplantation!
o Intensive!combination!chemotherapy!
+ Palliative!
o Chemotherapy,!immunosuppressive!agents!(cyclosporin,!antithymocytes!globulins)!
o Blood!product!transfusion!
o Growth!factors:!erythropoietin!/!G+CSF!
Acute5leukemia5
+ Children:!ALL!>!AML,!adult!AML!>!ALL!
!
Management!
+ Treatment/!prevention!of!complications!
o Aggressive!fluid!therapy!and!allopurinol!to!prevent!tumor!lysis!syndrome!
o Leucophoresis!to!treat!leukostasis!if!WBC!count!very!high!&!symptomatic!
!

Hematology!+!18!
 ! But!not!commonly!do,!as!RCC!low!"!draw!blood!out!may!lead!to!cardiac!arrest!
o Transfusion!of!blood!products!
o Protective!isolation!and!anti+microbials!for!infection!
+ Confirm!the!diagnosis!(*!can’t!differentiate!AML!vs!ALL!on!CBC!alone)!
o Bone!marrow!study,!immunophenytoping,!!
o Cytogenetic!study!(prognostic!information)!

Acute5Myeloid5Leukemia5(AML)5
Introduction!!
+ Clonal!proliferation!of!myeloid!progenitor!cells,!with!differentiation!arrest!
+ Associated!with!MDS/myeloproliferative!disorder,!Fanconi's!anemia,!CML,!down's!(M7),!
ionising!radiation,!alkalyting!chemotherapy!
!
WHO%classification!
+ AML!with!recurrent!genetic!abnormalities!
+ AML!multi+lineage!dysplasia!(secondary!to!MDS)!"!very!poor!prognosis!
+ AML,!therapy!related!(alkylating!chemotherapy)!"!very!poor!prognosis!
+ AML!NOS!
!!
French5American5British%(FAB)%classification!
+ M0+!undifferentiated!
+ M1+!without!maturation!
+ M2+!with!granulocytic!maturation!
+ M3+!acute!promyelocytic!
+ M4+!acute!myelomonocytic!
o M4Eo:!myelomonocytic!with!BM!eosinophilia!
+ M5+!acute!monoblastic!(M5a)!/!acute!monocytic!(M5b)!
+ M6+!acute!erythroleukemic!
+ M7+!acute!megakaryoblastic!(down's!related)!
!!
Clinical!presentations!
+ Pancytopenia!
+ Bone!pain!
+ Infiltrative!symptoms:!(less!striking!than!that!in!ALL)!
o Hepatosplenomegaly!(mild/moderate!splenomegaly),!lymphadenopathy!!
! Esp!in!AML+M4!(usually!myeloid!seldom!cause!hepatosplenomegaly)!
o Gum!hypertrophy,!skin!involvements,!CNS!involvements!in!AML5M4/M5!
o DIC!in!AML5M3!
+ Leukostasis!(symptomatic!hyperleukocytosis):!abnormal!intravascular!leukocyte!
aggregation!&!clumping!
!!
Investigations!
+ CBC,!crossmatch,!LRFT,!Ca,!PO4,!clotting,!glucose,!LDH,!urate!
o Can’t!differentiate!AML!vs!ALL!in!CBC!d/c!alone,!need!to!confirmed!by!
immunophenotyping,!BM!exam,!genetic!expressed!by!the!blast!&!cytoflowmetry…!
+ HBsAg,!anti+HBc,!antiHBs,!Anti+HCV,!anti+HIV!
+ Serum!lysozyme!for!M4/M5/chronic!myelomonocytic!leukemia!
o Lysozyme!is!in!granulocytes!&!monocysts!but!not!lymphocytes!
o ↑!level!in!monocytic!leukemia!(M5b),!but!↓!in!lymphocytic!leukemia!
+ Tartrate!resistant!acid!phosphatase!(TRAP)!for!hairy!cell!leukemia:!↑!in!expression!
+ Peripheral!blood!film!!
o Presence!of!blast!cells!(>20%)!
!

Hematology!+!19!
 ! Present!of!nucleoli!(white!dots!inside!nucleus)!with!large!nuclear+cytoplasmic!
ratio!"!blast!cells!
o Auer!rods!(M3):!elongated!needles!formed!by!clumps!of!
azurophilic!granular!material!
+ Bone!marrow!aspirate:!blast!cells!(≥30%)!
+ Trephine!biopsy:!hypercellularity!
+ High!LDH!and!high!urate!
!!
Management!
+ Supportive!
o Blood!product!support!
o Allopurinol!and!adequate!hydration!
o Prophylactic!antibiotics!for!fever!/!neutropenia!
o Leukophoresis!for!leukostasis!
+ Chemotherapy!
o Induction!(achieve!a!complete!remission!by!reducing!leukemic!cells!into!undetectable!
levels)!!
! Remission!=!no!evidence!of!leukemia!in!blood!+!normal!blood!count!+!<5%!
blast!in!bone!marrow!
o Consolidation!(eliminate!any!residual!undetectable!disease)!
+ Induction:!Cytarabine%(cytosine%arabinoside)%+%an%anthracycline%(daunorubicin)!
o 7%+%3%regime!=!7!days!continuous!infusion!of!cytarabine!+!3!days!anthracycline!
o Cytarabine!
! Damage!DNA!and!hold!cell!cycle!at!S+phase!
! 100!mg/m2/d,!continuous!IV!infusion!(it!rapidly!metabolized!into!an!inactive!
compound),!D1+7!
! S/E!=!myelosuppression,!GI!toxicity,!conjunctivitis!in!high!dose!(use!dexa!eye!
drops)!
o Anthracycline!
! 45!mg/m2/d,!IV!push,!D1+3!
! S/E!=!cardiotoxicity!(arrhythmia,!cardiomyopathy,!heart!failure)!consider!+!
dexrazoxane!(cardioprotective!agent),!mucositis,!myelosuppression,!red!
urine!
+ Consolidation!
o High!dose!cytarabine!intensification!
o Comparable!to!allo+BMT!or!ABMT,!with!comparable!OVERALL!SURVIVAL,!but!worse!
in!DISEASE!FREE!SURVIVAL!
+ Allogeneic!stem!cell!transplantation!(bone!marrow!transplantation)!is!an!option!for!relapse!
or!high!risk!cases!
!
Prognosis!
+ Depends!on!age,!genetic!abnormalities!and!initial!response!to!chemotherapy!
+ Chemotherapy!leads!to!a!initial!complete!remission!rate!of!70+80%!in!younger!patients!but!
about!half!of!them!will!relapse!
+ Older!patients!>!60!years!have!a!much!lower!cure!rate,!usu!<!10%!

Acute5promyelocytic5leukemia5(APL):5AML5M355
Characteristics!
+ Faggots!cells!with!multiple!Auer!rods!forming!bundles!
+ Hypergranular!cells!
+ Fusion!of!PML5RARA!gene:!t(15;17)(q22;q12)!

Hematology!+!20!
 o Chimeric!gene!product!that!binds!with!retinoic!acid,!thus!block!terminal!
differentiation!and!promote!cell!growth!
+ Good!prognosis,!very!responsive!to!anthracycline+based!chemotherapy!&!ATRA,!with!clinical!
remission!in!60+80%!
+ High!incidence!of!early!death,!due!to!DIC%(release!of!thromboplastin)!
!
Management!!
+ Blood!test!
o INR,!fibrinogen,!D+dimer,!CBC,!LRFT,!Ca,!PO4,!urate,!LDH,!T&S,!Hepatitis!marker!
+ All5trans5retinoic%acid!(ATRA)!(*same!drug!used!in!acne!vulgaris)!
o When!used!in!high!dose,!it!acts!as!a!differentiating!agent!
o Combined!with!induction!chemotherapy!
! Clinical!remission!in!80%!if!alone,!but!all!relapse!if!stopped!
! Improve!complete!remission!rate!!
o Can!improve!coagulopathy,!↓!complication!a/w!DIC!
o Differentiation!/!retinoic!acid!/!ATRA%syndrome!(50%)!
! Fever,!peripheral!edema,!pulmonary!opacities,!hypoxemia,!respiratory!
distress,!hypotension,!renal!&!hepatic!dysfunction,!rash!&!serositis!(pleural!&!
pericardial!effusions)!
! Due!to!release!of!inflammatory!cytokines!from!malignant!promyelocytes!
during!induction!therapy!leading!to!capillary!leak!syndrome!
! Rx:!dexamethasone!
o Hyperleukocytosis!
+ Arsenic!trioxide:!for!relapsed!patients!
+ Anthracycline!based!chemo!
o Clinical!remission!in!80%!if!alone!
o Risk!of!DIC!and!major!bleeding!
o SO!NOW:!combined%treatment!(ATRA!+!chemo)!with!clinical!remission!90%!
+ Transfuse!platelet!if!platelet!<50!
+ Transfuse!FFP!if!INR!≥!1.3!
+ No!IMI!/!arterial!puncture!

Acute5lymphoblastic5leukemia5(ALL)5
Introduction!!
+ Commonest!cancer!in!childhood!(3+5years),!rare!in!adults,!but!bimodal!peak!at!50!
+ Malignancy!arises!from!differentiation!arrest!and!clonal!proliferation!of!lymphoid%
precursors%(lymphoblasts)%+!either!B+cell!and!T+cell!
!
Classification!
+ French5American5British%(FAB)%system%(morphological)!
o L1:!uniform,!small!blast!cells!with!scanty!cytoplasm!
o L2:!larger!blast!cells!with!more!cytoplasm,!more!heterogeneity;!nuclei!often!indented!
(*adult!ALL!more!often!presents!as!L2)!
o L3:!large!prominent!nucleoli,!strongly!basophilic!cytoplasm,!cytoplasmic!vacuoles!
o **!This!system!cannot!distinguish!between!B+!or!T+!lineage!
+ Immunological!markers!
o B5lineage!(85%!)!
! Early!precursor!B!(Pro+B)!
! Common!(calla/CD10+;%hyperdiploidy!"!better!prognosis!)!
! Pre+B!(cytoplasmic%IgM+)!
! Mature!B!(t(8,14)=Burkitt's)!
o T5lineage!(15%)!
!

Hematology!+!21!
 ! T+lymphoblastic!
+ Prognosis!prediction!
o ALL!in!adult!indicates!POOR!PROGNOSIS!
! The!incidence!of!poor!prognostic!abnormalities!is!greater!in!adults!than!
children!an!may!account!for!the!poor!outcome!for!adults!with!ALL!
o t(4,11)!"!POOR!prognosis!!
o t(9,22)=Philadelphia!–!commonest!in!adults!"!POOR!prognosis!
o t(8,14)=Burkitt's!"!POOR!prognosis!
o TEL+AML1!t(12;21)!–!commonest!abnormality!in!children!(22%)!"!GOOD!prognosis!
o Hyperdiploidy!"!GOOD!prognosis!
o *!Chromosomal!abnormalities!present!in!60+85%!
!!
Clinical!presentation!
+ Marrow!failure!symptoms!!(almost!ALWAYS!associated!with!anemia)!
+ Bone!pain!
+ Infiltration!symptoms!
o Hepatosplenomegaly!
o Lymphadenopathy!
o Orchidomegaly!
o CNS!involvement!(more!common!in!ALL!then!AML)!
o Mediastinal!compression!(*!in!T5lymphoblastic%ALL,!enlargement!of!thymus!and!
mediastinal!lymph!nodes!are!common)!
!!
Investigations!
+ Complete!blood!count!
+ Peripheral!blood!film!
o >20%!blasts!is!diagnostic!
o Look!for!the!characteristic!morphologies!described!above!
+ Bone%marrow!aspirate:!blast!cells!(>30%)!
+ Trephine!biopsy:!hypercellularity!
+ Biochemical:!high!LDH,%high!urate!
+ Lumbar!puncture:!to!look!for!CNS!involvement!
+ CXR!
o Widen!mediastinum!(in!T+cell!ALL)!
o Look!for!lytic!bone!lesions!
!!
Treatments!
+ Supportive!
o Blood!product!support!
o Allopurinol!and!adequate!hydration!
o Prophylactic!antibiotics!for!fever!or!neutropenia!(PCP%prophylaxis%by%septrin)!
o Leukophoresis!for!leukostasis!
+ Remission!Induction!
o Vincristine:!inhibit!tubulin!assembly!hence!no!mitotic!spindle!formation!
! S/E:!dose+limiting!peripheral!neuropathy!(paresthesia,!areflexia),!SIADH,!
Raynaud's!phenomenon!
o Prednisolone!
o Daunorubicin%5%an!anthralcycline!
! S/E!=!cardiomyopathy,!bone!marrow!suppression,!mucositis,!red!urine!
o L5asparaginase!!
! ALL!cells!cannot!produce!its!own!aspargine!while!normal!cells!can,!this!drug!
converts!asparagine!into!aspartate!&!ammonia!"!prevent!tumor!growth!!
!

Hematology!+!22!
 ! S/E!=!allergy,!anaphylaxis,!hemorrhagic!pancreatitis!
o Cyclophosphamide!
+ Consolidation!
o High!or!medium!dose!multi+drug!regimen!given!in!blocks!
+ CNS!prophylaxis!
o Intrathecal!methotrexate/!cytosine!arabinoside!
o Cranial!irradiation!
+ Maintenance!
o Daily!PO!mercaptopurine!
o Weekly!PO!methotrexate!
o Monthly!PO!prednisolone%and!IV!vincristine!for!5!days!
o 2!years!for!girls!and!adults;!3!years!for!boys!
+ Bone!marrow!transplant!
o The!only!cure!for!Philadelphia!chromosomes!!
Myeloproliferative5Disease5(MPD)5
Definition!
+ Clonal!stem!cell!disorder!(cytogenetic!study),!leading!to!overproduction!of!mature!cells!
+ Hypercellular!marrow!
+ Increase!in!peripheral!counts!of!at!least!one!MYELOID!lineage!
+ JAK2!mutation!"!confirm!Dx!(not!reactive)!
o +ve!in!90%!of!PV,!50%!of!ET!/!MF!
+ Proliferation!of!myeloid!cells!
o Chronic!myeloid!leukemia!(CML)!
! Philadelphia)chromosome*+ve!!
o Polycynthemia!rubra!vera!(PRV!/!PV)!
o Essential!thrombocynthemia!(ET)!
o Myelofibrosis!
o Unclassified*(no*"Philadelphia*Vve*CML")*Chronic*basophic/neutrophilic/eosinophilic*
leukemia!
!!
Cynthemia%(primary%marrow%disorder)%Vs%cytosis%(reactive)!
Erythrocytosis!(Hypoxia!>>!erythropoietin!>!Hb)!
+ Hypoxia!!
o System!hypoxia:!chronic!lung!diseases!(COPD),!cyanotic!heart!diseases,!high!altitude,!
CO!poisoning,!OSA,!smoking,!pulmonary!HT!
o Renal!hypoxia:!renal!vascular!disease!(RAS),!renal!perfusion!problem,!polycystic!
kidney!
+ Ectopic!/↑!erythropoietin!
o Paraneoplastic!syndrome:!RCC,!Wilm’s!tumor,!HCC,!pheochromocytoma,!massive!
uterine!fibroma,!cerebellar!hemangioblastoma!
o Rebound!erythrocytosis!(very!rare:!only!8%/day!max!+!daily!turnover!~1%,!
accelerated)!
o Von!Hippel–Lindau!(VHL)!disease!
o Reactive!to!sepsis!
+ Ix:!CBC,!ABG!for!hypoxia,!USG!kidney!and!vessels,!liver,!uterus,!BM!biopsy!
!!
Thrombocytosis!(Bleeding!>>!thrombopoietin!>>!platelet)!
+ Bleeding!
o Active!bleeding!from!whatever!source!
o Post+op,!post+trauma,!post+splenectomy,!hemolytic!anemia,!Fe!deficiency!anemia!
+ Ectopic!thrombopoietin!
!

Hematology!+!23!
 o Rebound!thrombocytosis!(recovery!from!myelosuppressive!therapy!(e.g.!post+
chemo),!B12,!folate!replacement)!
o Paraneoplastic!syndrome:!solid!tumors!
+ Infection,!inflammation!(e.g.!RA)!
!!
Leukocytosis!(infection!>>!growth!factors!>>!WBC)!
+ Infection/Inflammatory!conditions!
+ Ectopic!growth!factors!
o Rebound!leukocytosis!
o Paraneoplastic!syndrome!
!
S/S!of!MPD!
+ Hyperviscosity!
o Stroke,!TIA,!confusion,!reduced!mentality,!blindness,!hearing!
o Angina,!arrhythmia,!poor!exercise!tolerance!
o Pleuritis,!chest!pain,!pulmonary!infarct!
o Pallor,!claudication,!gangrene,!ulcers!
o Oliguria,!ARF!
+ Hypermetabolism!
o Weight!loss,!sweating,!fever,!malaise!
o Hyperuricemia!(gouty!attacks,!renal!stones)!
+ Qualitative!defect!despite!cytosis!
o Paradoxical!infection!
o Paradoxical!bleeding!
!!
Progression!
+ ET!&!PV!will!slowly!progress!to!MF,!then!will!progress!to!CML!(?)!
!
Management!of!MPD!
+ Curative!
o Bone!marrow!transplantation!
+ Palliative!
o Cytotoxic!drugs,!chemotherapy!
o Venesection/leukophersis/thrombopheresis!in!Blood!cell!separator!by!centrifugation!
! For!severe!/!life!threatening!/!very!very!high!cell!counts!esp!monocytes!

Chronic5Myeloid5Leukemia5(CML)5
Introduction!
+ Uncontrolled!clonal!proliferation!of!myeloid!cells!
+ Part!of!the!myeloproliferative%disorder!
o Similar!with!AML!in!that!malignant!cells!will!flood!both!marrow!and!peripheral!blood!
o Different!with!AML!in!that!TERMINAL!DIFFERENTIAION!is!initially!unaffected,!thus!it!
can!give!rise!to!mature!cells!in!blood!
+ CML!is!defined!by!Philadelphia%chromosome,%t(9,22)%[chimeric%bcr5abl%gene]%
o Whenever!Ph!chromosome!/!BCR+ABL!fusion!protein!is!present!"!CML!no!matter!
which!cells!it!produce!more!
+ Adult!male!
!
Clinical!presentations!
+ Symptoms!of!marrow!failure!
+ Bone!pain!
+ Hypermetabolism!symptoms:!weight!loss,!fever,!fatigue,!sweating!
!

Hematology!+!24!
+ Hyperviscosity!from!leukostasis:!hearing/!visual!disturbance,!angina,!stroke,!claudication,!
priapism,!confusion,!fever,!chest!pain,!SOB!
+ Massive!splenomegaly!
o Infiltrative!disease!"!normal!architecture!of!spleen!may!be!distorted!at!advanced!
stage!"!may!not!have!notch!
o Vs!portal!HT,!CHF!"!back!pressure!"!normal!architecture!"!splenomegaly!with!
notch!
!
Investigations!
+ CBC:!whole!spectrum!of!myeloid!cells!
+ Peripheral!blood!film:!whole!spectrum!of!immature!white!cells!present!
+ Neutrophil%alkaline%phosphatase%score:!low!
o Used!to!differentiate!it!from!reactive!leukocytosis,!where!the!score!is!high!!
+ BM!trephine!biopsy!
o Hypercellularity!
o Cytogenetic!study:%Philadelphia%chromosome%(BCR:%ABL)%t(9;22)%present!95%!
! This!need!BM!exam,!because!need!to!arrest!the!dividing!cells!to!look!at!
chromosomes!
! Can!also!look!for!other!chromosomal!abnormalities,!which!may!affect!Rx!
+ Peripheral!blood!
o PCR!/!FISH!for!BCR5ABL%fusion%gene!(tyrosine!kinase!activity),!faster!results,!but!can!
only!look!at!specific!abnormality!
!!
Natural!history!
+ Chronic!(<5%!blast):!lasting!months!or!years,!with!minimal!symptoms!(indolent)!
+ Accelerated!(5+20%!blast):!increasing!symptoms!and!spleen!size!despite!therapy!
+ Acute!leukemic!phase!(>20%!blast):!blast!transformation!(blast!crises):!AML>ALL!
+ **50%*of*patients*will*progress*into*acute*blastic*phase*without*passing*through*the*stage*
accelerated*phase!
!
Treatments!
+ Aim!
o Avoid!disease!progression!
o Complete!cytogenetic!response!=!eliminate!Ph!chromosome!(an!early!response!can!be!
translated!to!cure)!
o Molecular!response!=!reduced!BCR+ABL!transcript!
+ Chronic!phase!
o Imatinib!mesylate!(Gleevec,!a!tyrosine5kinase%inhibitor)!OR!nilotinib/dasatinib!
(better!early!cytogenetic!response,!as!2nd!line!for!those!with!imatinib!resistance)!
o Alpha5IFN%±%cytarabine:!prolong!survival!by!1+2!years,!but!toxicity!and!$$!
o Hydroxyurea!+!busulfan:!good!clinical!and!hematological!response,!but!no!impact!
on!cytogenetic!abnormality,!disease!progression!and!survival!
o Allogenic%BMT!
! BM!transplant!only!if!tyrosine!kinase!inhibitor!fails!
• BMT!may!cause!graft!vs!host!disease!"!another!chronic!disease!
• BMT!is!a!high!risk!procedure!
! Unless!in!very!young!patient,!as!drug!may!fail!in!the!future!&!BMT!have!lower!
risk!in!younger!patient!
+ Blastic!phase!
o Treat!as!de!novo!acute!leukemia,!but!response!is!dismal!
o Imatinib!offers!a!better!response!

Hematology!+!25!
Acute5blast5transformation5
Presentation!&!management!
+ Anemia!
o HF,!MI!
o Rx:!transfusion!
+ Thrombocytopenia!
o Petechiae,!ecchymosis,!overt!bleeding!
+ Neutropenia!
o Neutropenic!fever!
o Mx:!septic!workup,!broad!spectrum!antibiotics!(Tazocin:!piperacillin!+!tazobactum)!
+ Leukocytosis!(hyperviscosity)!
o Presentation!
! Brain:!stroke,!psychosis,!headache!
! Eye:!ground+glass!blurred!vision!
! Heart:!MI,!HF!
! Limb:!claudication!
o Rx:!leukophoresis!(not!G+CSF!in!acute!phase)!
+ Tumor!lysis!syndrome!
o Presentation:!gouty!attack,!renal!failure,!hyperK!
o Ix:!LDH,!urate,!RFT!
o Rx:!alloperinol,!good!hydration!
+ Extramedullary!infiltration,!e.g.!spine!infiltration!
o Can!be!treated!by!RT!as!palliation!when!failed!pain!control,!but!expect!to!recur!as!
leukemia!is!a!systemic!disease!
+ Other!management:!
o Check!blood!film!&!look!for!any!Auer!rods!indicating!AML!M3!
! If!yes!"!give!all+trans+retinoic!acid!(ATRA)!
+ **!Very!difficult!to!treat!secondary!acute!myeloid!leukemia!compared!with!primary!

PhWve5myeloproliferative5neoplasms5
Clinical!presentation!
+ Short!term:!vascular!events!
o Thrombosis!"!stroke,!MI,!venous!thromboemolism!
+ Long!term!(3+5!years)!
o Marrow!failure!
o Progressive!organomegaly!/!extra+medullary!hematopoiesis!
o Progress!to!leukemic!transformation!
!
JAK2!V617F!gene!mutation!
+ Janus!kinases!(Just!Another!Kinase)!
+ JAK2!is!non+receptor!tyrosine!kinase!that!is!essential!for!growth!factor!signaling!
o Important!for!cell!survival,!proliferation,!differentiation!
+ JAK2!mutation!"!keep!sending!signal!despite!no!messenger!binding!to!it!
+ Mutation!+ve!in!97%!of!PV,!60%!of!ET!&!60%!of!PMF!
+ JAK2!mutation!=!1!of!the!major!criteria!in!the!WHO!Diagnostic!criteria!of!PV,!ET!&!PMF!
Polycythemia5vera5(PV)55
+ Mutation!in!JAK+2!V617!(downstream!of!EPO+R)!
o Even!no!stimulus!"!keep!multiplying!RBC!
+ Hb>16.5!female/!18.5g/dl!male!
+ May!also!have!mild!↑!in!WCC!&!platelet!
!
!

Hematology!+!26!
DDx!of!polycythemia!
+ Primary!!
+ Secondary:!reactive!erythrocytosis!!
+ Relative:!dehydration,!burns,!stress!polycythemia!
!
Treatment!
+ Low!dose!aspirin:!↓!thrombotic!complication!
+ Venesection!if!Hct!>0.55+0.6!due!to!risk!of!thrombotic!stroke!
Essential5thrombocythemia5(ET)5
+ Plt!>!450x109/L,!in!the!absence!of!thrombopoietin!
+ 60%!JAK!mutation!!
+ Progression:!myelofibrosis!/!leukemic!transformation!
!
Complications!
+ Bleeding:!platelet!quality!is!not!good,!also!not!enough!vWF!to!anchor!into!bleeding!site!!
+ Thrombosis:!risk!↑!in!elderly!(more!problem!in!vessel!"!↑!risk)!&!have!previous!thrombosis!
!
Management!
+ Risk!stratification!
Low%risk! Patients%aged%<40%years%with:!
+ No!prior!thrombosis!
+ Platelet!count!<1500!x!109/L!
Intermediate%risk! Patients%aged%40–60%years%with:!
+ Cardiac!risk!factors!or!familial!thrombophilia!
+ Platelet!count!<1500!x!109/L!
High%risk! Patients%either%aged%>60%years%OR%with%any%one%of%the%following:!
+ Prior!thrombosis!or!major!hemorrhage!OR!
+ Platelet!count!>1500!x!109/L!
+ All!patients!
o Manage!reversible!CV!risk!factors!aggressively!(e.g.!smoking,!HT,!
hypercholesterolemia,!obesity)!
+ High+risk!patients!!
o Hydroxyurea!(anagrelide!/!interferon+a!2nd!line)!AND!
o Low!dose!aspirin!(except!if!platelet!>!1,500!x!109/L)!
+ Intermediate+risk!patients!
o Low!dose!aspirin!except!in!patient!with!bleeding!phenotype!!
o Consider!cytoreduction!if!other!CV!risk!factors!present!
+ Low+risk!patients!!
o Low!dose!aspirin!except!in!patient!with!bleeding!phenotype!

Primary5Myelofibrosis5(PMF)5
+ Peripheral!blood!smear!
o Leukoerythroblastosis:!nucleated!red!cells,!immature!white!cells!(myelocytes,!
promyelocytes)!
! DDx:!leukemia,!solid!tumor!metastasis!
o Tear!drop!cell!
+ BM!biopsy:!r/o!benign!causes!of!BM!infiltration,!e.g.!TB,!fungal!infection!
o Very!difficult!to!get!BM!aspirate!
o BM!biopsy!show!fibrosis!
!
Treatment!
!

Hematology!+!27!
+ <65!years!old:!BM!transplant!
+ >65!years!old:!palliative!
o Blood!products!!
o RT:!last!resort!
! ↓!spleen!size!"!symptomatic!relieve!
Chronic5lymphocytic5leukemia5(CLL)5
Introduction!!
+ Monoclonal!proliferation!of!non+functional!mature%B5cell!(T+cell!very!rare)!in!BM!
o A!disorder!more!similar!to!lymphoma!than!ALL!
+ Commonest!form!of!leukemia!in!the!Western!world!
+ Usually!in!elderly!
!
Stages!!
+ Binet!staging!system!
o Stage!A:!<3!regions!of!lymphadenopathy!/!organ!enlargement,!no!anemia!/!
thrombocytopenia!
o Stage!B:!≥3!nodal!/!organ!enlargement!
o Stage!C:!presence!of!anemia!(Hb!<10g/dL)!&/or!thrombocytopenia!(plt!<100!x!
109/L),!irrespective!of!lymphadenopathy!&!organomegaly!
+ RAI!staging!system!
o Stage!0:!lymphocytosis!alone![median!survival!=!14.5!years]!
! DDx:!acute!viral!infection,!TB,!fungal!infection,!autoimmune!disease!
o Stage!I:!lymphocytosis!+!lymphadenopathy![median!survival!=!8!years]!
o Stage!II:!lymphocytosis!+!spleno/hepatomegaly![median!survival!=!6!years]!
o Stage!III:!lymphocytosis!+!anemia!(Hb!<11!g/dL)![median!survival!=!2!years]!
o Stage!IV:!lymphocytosis!+!thrombocytopenia!(<100x109/L)![median!survival!=!2!yrs]!
!
Clinical!presentations!
+ Asymptomatic!(70%):!present!as!incidental!finding!of!lymphocytosis!
+ Anemia,!recurrent!infection,!weight!loss!!
o Susceptibility!to!infection!from!hypogammaglobulinemia!(no!diverse!antigen!
specificity)"!herpes!zoster!
o Autoimmune!hemolytic!anemia/!thrombocytopenia!(auto+Ab!produced!by!B!cells)!
+ Bone!marrow!failure!(late!stage)!
+ Lymphadenopathy,!hepatosplenomegaly!
!!
Clinical!course!
+ Clinical!course!is!often!indolent!but!can!be!more!aggressive!in!advanced!stages!
+ Some!transform!to!aggressive!lymphoma!(Richter's%syndrome)!
!!
Investigations!
+ Peripheral!blood!film:!smear/smudge%cells,!AHIA!(autoimmune!hemolytic!anemia)!
o Smudge!cells:!artifacts!produced!by!lymphocytes!damaged!during!slide!preparation!
! Fragile!WCC!partially!rupture!during!preparation!of!smear!
o Peripheral!blood!film!is!diagnostic,!no!need!BM!to!make!Dx,!but!need!BM!before!&!
after!Rx!to!quantify!the!response!(see!the!%↓!in!lymphocytes!in!BM)!
o Vs!lymphoma!with!lymphocytosis!(stage!4):!abnormal!looking!cells!seen!in!blood!film!
(CLL:!look!like!normal!lymphocytes!/!smudge!cells)!
+ Flow!cytometry:!↑!in!CD!5!lymphocytes!
+ Bone!marrow!aspiration:!mature!lymphocytes!
+ Trephine!biopsy:!hypercellularity!
!

Hematology!+!28!
+ *!Diagnosis!is!established!by!blood!count,!blood!smear!&!immunophenotyping!of!peripheral!
blood!(no!need!BM!exam)!
+ *!FISH!is!to!look!for!chromosomal!abnormalities!which!can!guide!prognosis!&!Rx!strategy!
!
Treatment!
+ Supportive!
o Blood!product!support!
o Allopurinol!and!adequate!hydration!
o Prophylactic!antibiotics!for!fever!or!neutropenia!(IVIg!if%recurrent%infections)!
o Leukophoresis!for!leukostasis!
o Steroids%for!AHIA!
+ Chemotherapy:!usually!not!needed!in!early!stage!(stage!I/II!or!stage!A)!
o Survival!high!in!early!stage!"!patient!usually!die!with!disease!not!die!of!disease!
o Indication!for!treatment!
! Advanced!stage:!stage!B/C,!stage!III/IV!
! B!symptoms,!severe!fatigue!
! Progressive!anemia/thrombocytopenia!!
! Massive!/!rapid!progressive!splenomegaly!/!lymphadenopathy!
! Lymphocyte!doubling!time!<!6!months!
! Refractory!AIHA!/!ITP!
! *!Absolute*lymphocyte*count*is*not*specifically*a*criterion*
o Standard!Rx!‘go!go’:!for!<65!AND!physically!fit!
! FCR:!Fludarabine!(oral)!+!cyclophosphamide!(oral)!+!rituximab!(IV)!
o ‘Slow!go’:!>65!or!have!co+morbidities!"!rituximab!+!chlorambucil!
o Frail!‘no+go’!"!chlorambucil!for!palliation!(not!very!effective!but!minimal!S/E)!
o Others:!fludarabine!
o Consider!allogenic!stem!cell!transplant!for!patients!with!early!relapse!or!17p!deletion!
Plasma5cell5malignancy5
Multiple5Myeloma5(MM)5
Introduction!!
+ Clonal!proliferation!of!plasma!cells!in!BM!(malignant!clone!in!BM!"!plasma!cells!mature!at!
BM)!
+ Single!clone!of!plasma!cells!producing!identical!immunoglobulin!!
o Subtypes!
! Heavy!chain!myeloma!
! Light!chain!myeloma:!all!IgG,!A,!M,!D,!E!↓!in!serum!
• If!not!see!spikes!in!serum!electrophoresis!(no!heavy!chain!spike!&!spike!
of!light!chain!not!prominent)!but!suspect!light!chain!myeloma!"!still!
do!IF!for!light!chain!
! Combination!(complete!immunoglobulin)!myeloma!
o IgG!(~2/3)!>!IgA!(~1/3)!>!light!chain!myeloma!(IgM!is!uncommon)!
+ Peak!age!70!years!old!
+ Very!slow!growing!disease!"!not!every!patient!diagnosed!in!symptomatic!state!
o Symptomatic:!related!tissue!damage!
o Smoldering:!no!end!organ!damage!(asymptomatic)!"!no!need!to!treat!
!
Clinical!presentations!
+ Osteolytic!bone!lesion!+!hypercalcemia!
o MM!secrete!cytokines!"!osteoclasts!very!active!
o ALP!don’t!↑!despite!bone!lesion,!as!it’s!osteoclastic,!ALP!is!a/w!osteoblastic!activity!
!
o Bone!lesions!"!pain,!fractures,!cord%compression%(important!complication!)!
Hematology!+!29!
 ! Skull!XR:!punch!out!lesions!(pepper!pot!skull)!
+ Anemia,!bleeding!tendency:!BM!infiltration!by!tumor!cells!
+ Recurrent!infections!(immunoparesis!+!neutropenia)!!
+ Proteinuria!!
o Presence!of!large!amount!of!protein!"!very!frothy!urine,!difficult!to!flush!away!
o *!Only!light!chain!can!enter!urine,!∴!macroglobulin!won’t!enter!urine!
! But!heavy!chain!can!deposit!in!glomeruli!causing!damage!&!cause!nephrotic!
syndrome!(may!still!have!proteinuria)!
+ Renal!impairment!
o Cast!nephropathy!
! A!distal*tubular*lesion!
! The!intraluminal!light!chains!pass!through!kidney!tubules!(not!nephrotic!
syndrome!as!light!chain!is!much!smaller!that!albumin!"!not!detected!by!
urinestix)!&!aggregates!with!Tamm+Horsfall!proteins,!and!form!obstructive!
casts!which!occlude!tubules!
! Volume!depletion!and!hypercalcemia!would!promote!this!process!
o Hypercalcemia!&!hyperuricemia!(high!cell!turnover)!
! Induce!nephrogenic!DI!+!sodium!wasting!"!promote*volume*depletion*which*
further*aggravates*the*calcium*level*increase!
! Potentiate!cast!nephropathy!!
o Amyloidosis!"!damage!glomerulus!"leaky!"!nephrotic!syndrome!
o Recurrent!infections!(pyelonephritis,!UTI)!
o Local!infiltration!of!tumor!cells!(myeloma!kidney)!
o Renal!vein!thrombosis!
o Hyerpviscosity!syndrome!
o Drugs:!NSAIDs!(due!to!bone!pain!"!analgesic!nephropathy),!contrasts!("!contrast!
nephropathy)!
o Fanconi!syndrome!
+ Systemic!AL+amyloidosis!!
+ Hyperviscosity!syndrome:!rare,!involve!heavy!chain!
o Vs!Waldenström's!macroglobulinemia!(tumor!producing!IgM):!common!(85%)!
!
Physical!exam!
+ Neurological!exam!for!LL:!cord!compression!!
+ Look!for!hepatosplenomegaly:!MM!itself!won’t!cause!hepatosplenomegaly,!but!can!do!to!r/o!
amyloidosis!&!lymphoproliferative!disease!
!
Investigations!
+ Blood!!
o CBC!d/c:!usually!no!lymphocytosis!as!plasma!cells!stay!in!BM!(but!rarely!may!have!
plasma!cell!leukemia!–!very!aggressive!disease)!
o Blood!film:!rouleaux!–!paraprotein!makes!RBC!become!sticky!
o ESR:!↑↑!due!to!↑!in!Ig!(DDx!of!very!high!(>120)!ESR:!TB,!giant!cell!arteritis,!MM)!
o RFT,!Ca:!hyperCa!
o LFT:!reversed!A/G!ratio!(DDx:!cirrhosis,!renal!disease,!CHF,!AIDS,!?SLE)!
o Serum%protein%electrophoresis,%immunofixation%%
! Electrophoresis:!narrow!band!/!M+spike,!see!how!much!paraprotein!present!
o Quantification!of!immunoglobulins!
o β2!microglobulin,!CRP,!LDH!!
o Measurement!of!free!monoclonal!light!chains!if!available!
+ Urine!
o Routine!urinalysis,!24!h!urine!protein!(r/o!glucosuria!/!albuminuria)!!
!

Hematology!+!30!
 o Urine%protein%electrophoresis%&%immunofixation:!look!for!Bence+Jones!protein!!
! Urine!protein!electrophoresis:!screening,!if!–ve!"!no!need!to!test!IF!
• Look!at!the!distribution!of!light!chain!"!narrow!band!
! IF:!more!sensitive!&!specific,!confirm!type!of!light!chain!present!
+ BM!aspirate!&!trephine!biopsy!(cytogenetics,!immunophenotyping):!%!of!plasma!cells!
+ Skeletal%survey!(use!plane!XR)/MRI!spine,!pelvis,!skull,!humeri!&!femurs:!osteolytic!lesions!
o Skull!XR:!multiple!punch!out!lytic!lesions!
o MRI!spine:!very!sensitive!
o *Not!bone!scan:!bone!scan!is!nuclear!imaging!"!see!metabolism!"!not!sensitive!as!
osteoclastic!>!osteoblastic!activity!in!MM!
+ Renal!biopsy!if!nephrotic!range:!differentiate!MM!(light!chain!deposit)!from!amyloidosis!
Paraprotein!Vs!Bence+Jones!protein!
+ Paraprotein:!monoclonal!Ig!/!light!chain!produced!by!
malignant!clonal!plasma!cell! Ig!=!heavy!x!2!+!light!chain!x!2!
o Vs!infection:!polyclonal!(all!GAMDEλκ)! 5!heavy!chains:!IgG>!A>M>D>E!
o Seen!as!a!‘M+spike’!(monoclonal!protein)!in! 2!light!chains:!λ,!κ!
serum/urine!protein!electrophoresis!
o Seen!in!myeloma!(plasma!cell!disorder)!/!mature!B!lymphocyte!disorder!(not!much!
paraprotein!as!plasma!cells!are!the!one!who!produce!most!Ig)!
+ Bence+Jones!proteins:!monoclonal!light!chains/incomplete!Ig!
o Secreted!in!urine!(only!light!chains!can!pass!through!kidney!tubules)!
o Detected!by!immunofixation!!
o Not!detected!by!urinestix!(only!detect!large!proteins)!
o DDx!of!↑!light!chain:!AL!amyloidosis,!MGUS,!Waldenström's!macroglobulinemia!
!
Diagnostic!criteria!for!symptomatic!myeloma!!
+ Monoclonal!plasma!cells!≥10%!on!BM!biopsy!&/or!presence!of!biopsy+proven!plasmacytoma!
o Normally!plasma!cells!should!be!<5%!in!BM!
+ A!monoclonal!protein!(paraprotein)!in!serum!/!urine!electrophoresis!(Radha:!>3g/dL)!
+ Evidence!of!myeloma+related!organ!dysfunction!"CRAB"!(1!or!more)!
o HyperCalcemia!(corrected!calcium!>2.75!mmol/L!OR!>!0.25!mmol/L!above!ULN)!
o Renal!insufficiency!attributable!to!myeloma!(Cr!>173!mmol/L)!
o Anemia!(Hb!<10!g/dL!OR!2g/dl!below!lower!limit!of!normal)!
o Bone!lesions!(lytic!lesions!/!osteoporosis!with!compression!fractures)!
!
Management!
+ General!
o Rehydration!(forced!diuresis)!"!↓concentration!of!light!chain!
o Chemotherapy:!systemic!control!
o Radiotherapy:!local!control!
+ Hypercalcemia!and!bone!pain!
o Analgesic!(cautious!use!of!NSAIDs)!!
o Hydration!(>3L/day)!
o Bisphosphonate!
! Suppress!osteoclasts!"!↓risk!of!Cx!(fracture,!cord!compression)!
o Local!radiotherapy!±!dexamethasone!!
o Orthopaedic!procedure!
+ Marrow!failure!
o Transfusion!or!erythropoietin!
o Broad!spectrum!antibiotics!for!acute!infection!!
o IVIg!for!recurrent!infection!
+ Renal!impairment!
!

Hematology!+!31!
 o Adequate!hydration!
o Avoid!NSAIDs!
o Good!control!of!hypercalcemia!!
o Dialysis!
+ Chemotherapy!
o No!good!targeted!therapy!against!MM!(incurable)!
o Only!indicated!when!symptomatic!/!have!complication!(palliative)!
o Elderly!=!malphalan/cyclophosphamide!+!prednisolone!!
o Young!=!vincristine!+!adriamycin!+!dexamethasone!!
o +!thalidomide!&!bortezomib!in!relapsing!cases!!
! S/E!of!thalidomide!
• Neurotoxicity!(polyneuropathy):!can!do!baseline!nerve!conduction!test!
before!starting,!monitor!symptoms!(e.g.!numbness)!
• Venous!thromboembolism!"!stroke!/!MI!
o ∴!Need!thromboembolic!prophylaxis!/!aspirin!
• Sedation:!∴!give!in!night!time!
• Embryotoxicity!(teratogenicity):!class!X!drug,!causing!amelia!(no!limbs)!
• Neutropenia!
+ Autologous!stem!cell!transplant:!symptom!control,!prolong!disease!course!
+ Allogenic!stem!cell!transplant:!curative,!but!high!mortality,!for!young!patients!

Smoldering5myeloma5
+ Asymptomatic:!very!early!state!of!MM!"!small!amount!of!paraprotein!
+ Diagnosis!
o Clonal!plasma!cells!in!BM!≥10%!
o Presence!of!monoclonal!protein!(paraprotein)!in!serum!/!urine!electrophoresis!
(≥3g/dL)!
o No!organ!/!tissue!damage!!
+ No!need!to!treat!if!no!symptoms,!but!may!progress!in!time!

Monoclonal5gammopathy5of5undetermined5significance5(MGUS)5
+ Common,!age+related!!
+ Accumulation!of!BM!plasma!cells!derived!from!a!single!abnormal!clone!
+ Resemble!multiple!myeloma!!
o Level!of!Ab!are!lower!
o Number!of!plasma!cells!in!BM!lower!
o No!symptoms!!
+ 3!criteria:!
o A!monoclonal!paraprotein!<!30!g/L!(<!3g/dL)!
o Plasma!cells!<!10%!on!BM!exam!(Vs!>10%!in!smouldering!myeloma)!
o No!evidence!of!end!organ!damage:!bone!lesions,!anemia,!hypercalcemia,!or!renal!
insufficiency!related!to!paraprotein!!
+ No!treatment!is!indicated!
+ However,!MM!develops!at!the!rate!of!about!1+2%!a!year,!∴!recommend!monitoring!yearly!
+ Rarely,!may!a/w!slowly!progressive!symmetric!distal!sensorimotor!neuropathy!!

Plasmacytoma5
+ Malignant!plasma!cell!tumor!growing!within!soft!tissue!(extra+medullary)/!skeleton!
(medullary)!!
o Abnormal!collection!of!plasma!cell!outside!BM!(normally!plasma!cells!stay!inside!BM)!
+ Monoclonal!paraprotein!<3g/dL,!plasma!cells!<10%!in!BM,!no!end!organ!damage!
o Same!as!MGUS,!but!MGUS!have!no!focal!lesion!
!

Hematology!+!32!
+ Management!
o RT!to!treat!the!localized!disease!(not!use!systemic!chemo)!
o Closely!FU!to!look!for!development!of!MM!(high!risk!of!dissemination!to!become!MM)!!

Amyloidosis5
+ Accumulation!of!abnormal!protein!with!change!in!protein's!secondary!structure!into!beta+
pleated!sheet!(insoluble)!
+ Causes!
o Amyloid!light!chain!(MM)!"!AL!type!
o Serum!amyloid!A!protein,!SAA!(RA,!AS,!IBD,!TB)!"!AA!type!
o β2!microglobulin!(hemodialysis)!"!Aβ2M!type!
o β!amyloid/APP!(Alzheimer!disease)!"!Aβ!type!
o Others!
+ Diagnosis!
o Biopsy!@!abdominal!wall!fat!/!rectum!/!salivary!gland!
o Congo!red!stain!+!polarized!light!"!apple!green!birefringence!
o Immunofixation!to!identify!type!of!protein!involved!!
+ Manifestations!
o Nephrotic!syndrome!(mimic!MM),!macroglossia,!heart!failure,!splenomegaly!(even!
rupture),!hemoptysis,!GIB,!polyneuropathy!
Lymphoma5
+ Tumors!originating!from%lymphoid%tissues,!mainly!of!lymph!nodes!(normally!lymphocytes!
mature!in!LN,!spleen)!
!
Clinical!presentation!
+ Lower!limb!swelling!
o Enlarged!LN!obstructing!venous!return!"!pitting!edema,!DVT,!superficial!venous!
distension,!overlying!erythema,!hemosiderin!pigmentation!
o Enlarged!LN!obstructing!lymphatic!drainage!"!non+pitting!edema!(lymphedema)!
+ Tachycardia!
o Think!of!pericardial!effusion!!!!
!
Investigation!
+ CBC,!blood!film!
+ ESR,!LRFT,!Ca,!PO4,!LDH,!urate!
o LDH:!a!progostic!factor!for!lymphoma!(Vs!leukemia:!a!marker!of!cell!death!&!tumor!
lysis!syndrome)!
+ Excisional%/%core%needle%biopsy!
o Need!look!at!nodal!architecture!&!lymphomatous!infiltrates!for!Dx!(e.g.!nodular!
sclerosing!type)!
+ Bilateral%iliac%crest%BMA%and%biopsy!
o Bilateral!because!NHL!has!non+contagious!spread!&!BM!involvement!is!usually!patchy!
"!↓!sampling!error!
! Vs!Hodgkin!lymphoma:!spread!along!a!tract!from!neck!to!mediastinum!down!
! Vs!leukemiaL!whole!body!disease!"!unilateral!BM!biopsy!is!enough!
+ HIV!serology!in!NHL!
+ CXR!
+ CT!abdomen!&!pelvis!±!thorax!
+ LP!in!lymphoblastic,!Burkitts,!diffuse!large!B!cell!lymphoma!with!+ve!BM!biopsy!
+ Gallium!scan!(SPECT)!/!PET!in!large!cell!lymphoma!

Hematology!+!33!
Hodgkins5lymphoma5
Introduction!!
+ 20%!of!lymphomas!
+ 2!peaks!of!incidence:!30s!and!elderly!
+ 50%!associated!with!EBV!infection!
+ Presence!of!Reed5Sternberg%(RS)%cells!
o Owl!eye!nucleus!with!prominent!nucleoli!
o Background!reactive!eosinophils,!lymphocytes,!plasma!cells,!histiocytes!
o Express!CD30%and!CD15!!!
+ Prognosis!better!than!NHL!
!!
Types!
+ Classical!Hodgkins!
o Nodular!sclerosing!70%!
! Mostly!young!women!
! Thick!bands!of!collagens,!lacunar!cells!often!numerous!
! Mediastinal!presentation!common!"!SVCO,!pleural!effusion!
o Mixed!cellularity!20%!
! Plasma!cells!and!eosinophils!present!
o Lymphocyte!depleted!
! Mononuclear!Hodgkin's!cell!with!diffuse!fibrosis!
! Poor!prognosis!
o Lymphocytes!rich!
! Good!prognosis!
+ Nodular%Lymphocyte%predominant%6%!
o Young!males!
o Popcorn%cells!
o With!B+lymphocyte!marker,!no%CD530!!
o Most!favorable!prognosis!
!!
Clinical!presentations!
+ Painless!enlargement!of!lymph!nodes!
o Asymmetrical,!rubbery,!multiple!
o 70%!cervical!nodes!
+ B+symptoms!
o Unexplained!fever,!night!sweats,!weight!loss!
o Itchiness!
o Alcohol!induced!lymph!nodes!pain!
+ Symptoms!of!infiltration!
o Pancytopenic!symptoms!in!bone!marrow!infiltration!
o Mediatstinal!involvement!in!60%,!may!cause!SOB!and!SVCO!
o Spinal!cord!compression!
+ Splenomegaly!in!50%:!reactive,!not!involvement!
!!
Staging!(Ann5Arbor%system)!
+ Stage!I:!single!lymph!node!region,!or!single!extralymphatic!organ!(IE)!
+ Stage!II:!>1!lymph!node!region!on!the!same!side!of!diaphragm,!or!single!extralymphatic!
organ!plus!its!regional!nodes!(IIE)!
+ Stage!III:!lymph!node!region!on!both!sides!of!diaphragm,!with!single!extralymphatic!organ!
(IIIE)!or!spleen!(IIIS)!or!both!(III!E+S)!
+ Stage!IV:!>1!extralymphatic!organs,!including!liver,!BM!or!nodular!involvement!of!lungs!
+ *!Suffix!(E)!for!localized!extranodal!extension!
!

Hematology!+!34!
+ *!Suffix!(A)!for!absence!of!constitutional!symptoms!
+ *!Suffix!(B)!for!presence!of!constitutional!symptoms:!fever,!night!sweats,!weight!loss!<10%!
in!6!months!
+ *!Suffix!(S)!for!splenic!involvement!
!!!!
Management!
+ Risk!stratification!(so!as!to!choose!appropriate!modality,!dosage!and!treatment!duration)!
+ Early%stage!disease!=!IA/IIA!"!RT%(more%localized)%/%chemo/!combination!
+ Advanced!stage!disease!"!Chemo!±!RT!
o Stage!III/IV!
o B+symptoms!
o Bulky!stage!II>10cm!
o Mediastinal!disease!>33%!transthoracic!diameter!
o ?!High!ESR!
+ Radiation:!IFRT%=%involved%field%radiotherapy!
o S/E!
! Second%cancer!
! Ischemic!heart!disease!
! Hypothyroidism!
! Lung!fibrosis!according!to!field!(esp!with!bleomycin)!
+ Chemotherapy!
o *ABVD!!=!adriamycin!(doxorubicin),!bleomycin,!vinblastine,!dacarbazine!
o MOPP%=!Mechlorethamine,!Oncovin!(vincristine),!Prednisolone,!Procarbazine!
o ABVD/MOPP%hybrid!
o BEACOPP%=!Bleomycin,!Etoposide,!Adriamycin!(doxorubicin),!Cyclophosphamide,!
Oncovin!(vincristine),!!Procarbazine,!Prednisolone!
! As!effective!as!ABVD!
! But!$$,!more!secondary!cancers,!require!G+CSF!support!
o Side!effects!
! Second)cancer!
! Infertility!(MOPP!+!with!mechlorethamine,!an!alkylating!agent)!
! Pulmonary!fibrotic!pneumonitis!(Blepmycin!±!mantle!field!irradiation)!
! Avascular!necrosis!(Prednisolone)!
! Fatigue!
! Sepsis!(from!staging!splenectomy)!
+ Second!cancer!development!
o AML%due!to!the!use!of!alkalyting!agents!(dacarbazine!and!mechlorethamine)!
o Solid%tumors!(lung,!breast,!thyroid,!bone/soft!tissue,!esophagus,!stomach,!uterine,!
cervix):!due!to!RT!±!Chemo!
o *!Advise!quit!smoking!!

NonWHodgkin’s5Lymphoma5
Follicular%lymphoma!
+ Commonest!B+cell!NHL,!22%!
+ Benign!and!low+grade!
+ Microscopy:!neoplastic!follicles!=!malignant!equivalent!of!normal!geminal!centres!
+ Cytogenetics!
o Express!BCL52,%anti+apoptotic!gene!
o t(14,18)!translocation!
+ Sometimes!transform!into!a!diffuse!large!B!cell!lymphoma!
!!

Hematology!+!35!
Extra5nodal%marginal%zone%B5cell%lymphoma%of%mucosal%associated%lymphoid%tissue%
(MALT%lymphoma)!
+ Most!common!in!stomach,!other!sites:!GIT,!lung,!H&N,!ocular!adnexae,!skin,!thyroid,!breast!
+ Associated!with!
o H.!pylori!induced!chronic!gastritis!
o Hashiomoto's!thyroiditis!
o Sjogren's!syndrome!
+ Indolent!!
+ May!respond!to!triple!therapy!in!HP!eradication!
!!
Burkitt's%lymphoma!
+ High!grade!
+ Three!types!
o Endemic!in!Africa%(typically!destroy!the!jaw/!other!facial!bones)!
o Sporadic!
o Immunodeficiency+related!
+ Associated!with!EBV!infection!
+ Cytogenetics!
o t(8,14)!translocation!
o Activate!c5myc!oncogene!
+ Microscopy:!diffuse!proliferation!of!B+cells!
o Scattering!of!macrophages!containing!debris!from!very!rapid!cell!turnover!(starry%
sky%appearance)!
o Cells!with!uniform!size!&!shape,!with!scanty!cytoplasm!&!round!nucleus!with!slightly!
coarse!chromatin!&!several!nucleoli!
!!
Diffuse%large%B5cell%lymphoma!
+ Common:!31%!
+ High!grade!
+ Large!malignant!B+cells!growing!in!diffuse!pattern!rather!than!in!follicles!
+ Special!subtypes!
o Mediastinal!large!B+cell!lymphoma!
o Intravascular!large!B+cell!lymphoma!(poor!prognosis)!
o DLBCL!transformed!from!low!grade!lymphoma!(poor!prognosis)!
!!
Extranodal%NK/T5cell%lymphoma%
+ Site:!nasal,!base!of!skull!involvement,!GI!
+ May!have!generalized!edema!due!to!cytokine!release!syndrome!(extravasation!due!to!
hypercytokemic!state)!
+ P/E:!check!for!CN!palsy!if!lymphoma!is!in!nasopharynx!(base!of!skull!involvement)!
+ Cx:!hemophagocytic!syndrome:!fever,!hepatosplenomegaly,!pancytopenia!
o Macrophages!eating!RBC!&!platelet!
o Can!be!life+threatening!!Due!to!severe!coagulopathy!&!bleeding!tendency!
o Mx:!treat!the!underlying!lymphoma!
!
Etiology!
+ Immunodeficiency!(HIV,!drugs)!
+ Infection!(EBV,!HTLV+1,!H.!pylori,!HIV,!HCV,!HHV+8)!
+ Gluten!enteropathy!
!
Clinical!presentation!
+ Lymphadenopathy!
!

Hematology!+!36!
+ Infiltrative!symptoms!
o Marrow!infiltration!
o Spinal!cord!compression!
o Mediastinal!disease!with!SVCO!
+ Local!symptoms!of!extranodal!disease:!oropharynx,!skin!(T+cell),!bone,!gut,!CNS,!lung!
+ Constitutional:!fever,!night!sweat,!malaise,!weight!loss!
!!
Staging!&!Classification!
+ The%WHO%classification!
o Classified!into!B+cell,!T+cell!or!NK!cell!lymphoma!according!to!pathological!
characteristic!
+ Ann%Arbor%Scheme!
+ A!practical!approach!
o Limited!stage!=!Ann!Arbor!I/II!+!no!B+symptoms!+!mass<10cm!"!brief!chemo!+!local!
RT!
! Stage!I/II:!cure!rate!~80+90%!
o Advanced!stage!=!Ann!Arbor!III/IV!or!B+symptoms!or!mass!>10cm!"!extended!
chemo!±!RT!
! Stage!III:!cure!rate!~50+60%!
+ General!class!
o Indolent%(low!grade)!=%follicular!"!palliative!Rx!
o Aggressive%(high!grade=!diffuse!large!B+cell,!Burkitts,!lymphoblastic!"!curative!Rx!
(CHOP)!
!!
International%prognostic%index%(IPI)!**for*aggressive*NHL,*predict*prognosis*&*guide*treatment!
+ Age!>60!
+ Performance!status!2/3/4!
+ Stage!III/IV!
+ Extranodal!sites!>1!
+ High!LDH!
!!
Follicular%lymphoma%International%prognostic%index%(IPI)!**for*follicular*NHL,*predict*
prognosis*and*guide*treatment!
+ Age!>60!
+ Hb!level!<12.0g/dL!
+ Stage!III/IV!
+ Extranodal!sites!>1!
+ High!LDH!
!!
Management!
+ Supportive!
o Blood!product!support!
o Allopurinol!and!adequate!hydration!
o Prophylactic!antibiotics!for!fever!or!neutropenia!
+ Indolent!NHL!
o Generally!good!prognosis!but!incurable!"!palliative!Rx!
o Choices!
! Defer!treatment!with!careful!monitoring!
! Treat!by!RT!alone/!CT!alone/!combination!
+ Aggressive!NHL!(more!common!)!
o *%R5CHOP!!
o CHOP%=%Cyclophosphamide,%Doxorubicin,%Oncovin%(vincristine),%Prednisolone!
!

Hematology!+!37!
 ! CHOP!21!+!every!21!day!cycle!
! CHOP!14!+!G+CSF!support!
o Rituximab!(chimeric!anti+CD20!human!monoclonal!antibody)!
o *!+!radiotherapy!
o *!CNS!prophylaxis!in!high!risk!patients:!intrathecal%methotrexate%or%cytarabine!
Hyperviscosity5/5hyperleukostasis5
Causes!!
+ Leukemia,!polycythemia!vera!
+ IgM!myeloma,!MM,!typically!IgM+producing!myeloma!
+ Lymphoma!(Waldenström's!macroglobulinemia)!
!
Presentation!!
+ Headache!(frontal),!stroke,!TIA,!confusion,!reduced!mentality![↓!cerebral!perfusion]!
+ Hearing!/!visual!disturbance,!even!blindness![retinal!vessel]!
+ Angina,!arrhythmia,!poor!exercise!tolerance!!
+ Pleuritis,!chest!pain,!SOB,!pulmonary!infarct!
+ Pallor,!claudication,!gangrene,!ulcers!
+ Priapism,!oliguria,!ARF!
!
Diagnosis!!
+ Serum!viscosity!disc:!but!not!very!useful!clinically!(need!long!time,!not!very!sensitive!test)!!
+ So!mostly!base!on!clinical!features,!e.g.!blast!count!>100!&!symptomatic!
+ If!in!doubt!"!treat!!
!
Management!of!hyperleukostasis!
+ TLS!prophylaxis!
+ Hydroxyurea/!Cytarabine!(chemo!drug):!need!tumor!lysis!prophylaxis,!need!6+8!hours!to!
work!
+ Leukapheresis!
o Used!in!patients!who!need!immediate!lowing!of!WCC,!e.g.!ICH!
+ Chemotherapy!
o Should!be!on!tumor!lysis!prophylaxis!(IVF,!allopurinol,!monitor!closely,!electrolyte!
every!8+12!hours)!
+ Cautious!transfusion!
o Don’t!transfuse!patients!until!try!to!bring!blast!count!down,!can!ppt!further!
hyperleukostasis!
Tumor5lysis5syndrome5
+ Occur!when!large!tumor!load!&!after!chemo!(cytocidal!phase)!
o Highest!risk!period:!3!days!before!&!7!days!after!chemo!
!
Presentation!
+ Gouty!attack,!renal!failure,!hyperK!
!
Investigation!
+ Blood!
o RFT,!LDH,!urate!
o *!Everything!↑!except!Ca!(as!PO4!released!from!cells!bind!Ca)!
!
Prevention!&!treatment!!
+ Maintain!hydration!by!NS!/!½!½!solution!at!3L/m2/day!
+ Alkalinized!urine!&!keep!urine!pH!at!≥7.0!by!sodium!bicarbonate!
!

Hematology!+!38!
 o Increase!excretion!of!uric!acid!
o Not!do!if!phosphate!is!very!high!(cause!precipitation!in!renal!tubules!&!risk!of!renal!
failure)!
+ Allopurinol:!300mg/m2/day!
+ Monitor!serum!chemistry!
+ Rasburicase!0.2mg/kg!daily!if!uric!acid!&!serum!Cr!remain!high!after!24+48!hours!
+ Hemodialysos!if!
o Serum!K!>6,!uric!acur!>10,!phosphate!>10/increasing,!symptomatic!hypoCa!!
Blood5smear5
RBC!morphology!
+ Poikilocyte:!abnormally!shaped!RBC!
+ Target!cells:!Fe!deficiency,!thalassemia,!liver!disease,!asplenia!
+ Tear!drop!cells:!leukoerythroblastic!picture!(myelofibrosis)!
Bone5marrow5aspiration5&5biopsy5
Use!
+ Bone!marrow!aspirate!!
o Immunophenotyping:!flow!cytometry!(specify!cell!lineage)!
o Cytochemistry:!chemical!expression!of!cell!(specify!cell!lineage)!
o Immunohistochemistry:!detect!antigen!on!cell!surface!(specify!cell!lineage)!
o Cytogenetics:!cells!are!cultures!&!look!for!chromosomal!abnormalities!during!
metaphase!(slow)!
! Diagnostic!&!prognostic:!gene!translocation!
! Therapeutic:!gene!targeted!therapy,!monitor!treatment!
o Molecular!study:!gene!rearrangement!(can!see!all!23!pairs!of!Ch,!rapid)!
+ BM!biopsy!
o Can!see!the!architecture!of!the!BM!
!
Procedure!!
+ Before!procedure!
o Even!platelet!=1!can!do!(Vs!e.g.!procedure!done!on!abdomen)!
! Because!the!puncture!site!is!easily!compressible!
! And!sometimes!some!immune+mediated!thrombocytopenia,!even!you!give!
platelet!transfusion,!still!not!useful!
o If!INR!is!low,!can!give!FFP!
+ Instrument:!Jamshidi!needle!(a!trephine!needle!for!performing!bone!marrow!biopsy)!
+ Patient!in!prone!/!lateral!position!
+ LA!@!skin!&!periostium!
+ Incise!skin:!at!the!outer!upper!quadrant!of!the!buttock!(lowest!risk!area)!
o NOT!inner!upper:!both!vessels!&!sciatic!nerve!exit!there!!
o Small!wound!(~2mm)!needed!only!to!avoid!excessive!bleeding!
+ Insert!Jamshidi!needle,!enter!needle!vertically!
+ Aspirate!BM!blood!&!put!on!EDTA!tube,!roll!the!tubes!horizontally!so!that!blood!can!get!
contact!with!EDTA!evenly!
+ Ensure!there’s!yellow!dots!on!EDTA!tube!before!taking!out!the!needle!(they’re!the!thing!we!
need!to!send!for!in!BM!aspirate,!if!not!present,!need!to!aspirate!again)!!
+ Insert!needle!again,!then!rock!the!needle!with!circular!motion!
+ Take!out!the!needle!&!take!the!trephine!biopsy!into!specimen!bottle!
o Take!it!out!in!revered!direction!(not!via!the!needle!tip)!in!order!not!to!crush!the!
trephine!
!
Risk!
!

Hematology!+!39!
+ Bleeding!
+ Infection!
+ Injury!to!surrounding!tissues/organ!&!related!surgery!
o Damage!sciatic!nerve!
o Puncture!lumbar!artery!"!may!bleed!into!retroperitoneum!
+ Cardiopulmonary!compromise!
Transfusion5
Consent!
+ Indication!
+ Risk!
o Fever,!rash,!acute!hemolytic!reaction!
!
Tests!for!donated!blood!
+ ABO,!Rh!
+ HIV,!HBV,!HCV,!HTLV!
+ Syphilis,!CMV!
+ Bacterial!surveillance!
!!
Compatibility!testing!
+ Blood!typing!
o RBC!with!anti+A,!anti+B,!anti+D!antibodies!
o Serum!with!A+RBC!and!B+RBC!
+ Antibody!screen!
o Recipient's!serum!+!Commercially!supplied!RBCs!(with!all!antigens!on!it)!![needs!
5min]!
o Followed!by!Indirect*antiglobulin*test*+!adding!Coomb's!reagent!(anti+human!
globulin),!thus!agglutinates!RBC!if!there!is!any!antibody!binding!
+ Crossmatch!
o To*be*performed*only*when*ANTIBODY*SCREEN*is*positive!!
o Recipient's!serum!+!Donor's!RBC!![needs!30min,!and!crossmatched!one!by!one]!
!!
Packed!cells!
+ Contain!citrate!to!chelate!Ca,!prevent!clotting!
+ 300cc/pack!
+ 4+5cc/kg!to!raise!Hb!for!1g/dl!(~1!pack!for!1)!
+ Complete!transfusion!in!4!hours!to!avoid!infection!sets!in!
+ 7!weeks!shelf+life!in!2+6!degree!
+ NOT!given!with!D5!/!½!½:!RBC!will!use!up!the!dextrose!turning!it!hypotonic!solution!"!
hemolysis!inside!the!transfusion!tubing!
!!
Adverse!Transfusion!Reaction!
+ Acute!
o Hemolytic!transfusion!reaction!!
! RBC;!1!in!million!!
o Febrile!non+haemolytic!transfusion!reaction!!
! Plt/leukocyte;!1!in!100!
o Allergic!reaction!!
! WBC;!1!in!100+300!!
o Septic!reaction!
o Circulatory!overload!
o Transfusion!related!acute!lung!injury!(TRALI)!
+ Delayed!
!

Hematology!+!40!
 o Delayed!haemolytic!reaction!(1!in!1000)!
o Transfusion!associated!graft+versus+host!disease!
o Post+transfusion!purpura!
o Transmission!of!infectious!diseases!
o Iron!overload!
!
Suspected%Transfusion%Reaction%%
“Possible”%Etiology% Timing%of%Symptoms%
Signs%&%Symptoms%
Fever!(≥! 38°C!to!<!39°C!and!no! Febrile!non+hemolytic! During!or!up!to!4!hours!
38°C!and!↑! other!symptoms! transfusion!reaction! post+transfusion!
at!least!1°C! <!39°C!and!other!
Bacterial!contamination!
from! symptoms!(i.e.!rigors,!
OR! Usually!within!first!15!
baseline)!! hypotension)!!
Acute!hemolytic! minutes!but!may!be!later!
and/or! OR!
transfusion!reaction!
Chills/rigor! ≥!39°C!
During!transfusion,!up!to!3!
No!other!symptoms! Allergic!reaction!
Urticaria!or! hours!from!start!
rash! With!other!symptoms!
Usually!early!in!
! (i.e.!dyspnea,! Anaphylaxis!
transfusion!
hypotension)!!
During!or!up!to!4!hours!
Circulatory!overload!
post+transfusion!
Dyspnea,!↓SaO2! Transfusion!related!acute! Within!6!hours!of!
OR! lung!injury!(TRALI)! transfusion!
Hypotension! Acute!hemolytic!
Usually!within!15!minutes!
transfusion!reaction!
but!may!be!later!
Bacterial!contamination!

Acute5hemolytic5transfusion5reaction5
+ Estimated!risk!1:250,000!to!1:1,000,000!units!transfused!
+ 74%!of!all!fatalities!due!to!ABO!incompatibility!
+ Rapid!destruction!of!red!cells!immediately%/%within%24%hours!of!transfusion!
!
Causes!!
+ Infusion!of!incompatible!blood!components!!
o Clerical!error:!misidentification!of!the!patient!(most!common)!
! Venipuncture!of!the!wrong!patient!
! Failure!to!identify!patient!correctly!
! Wrong!name!placed!on!sample!
! Blood!taken!to!the!wrong!patient!
! Failure!to!properly!identify!the!patient!prior!to!transfusion!
o Others:!blood!bank!error!in!blood!group!typing,!mixing!of!results,!dispensing!of!blood!
units,!etc!
!
Presentation!
+ Fever,!chills!&!rigors!
+ Pain!at!the!infusion!site!/!localized!to!loins,!abdomen,!chest!or!head!!
+ Hypotension,!tachycardia!
+ Agitation,!distress!and!confusion;!particularly!in!the!elderly!
+ Nausea!or!vomiting!
+ Dyspnoea!
+ Flushing!
!

Hematology!+!41!
+ Hemoglobinuria!(due!to!hemolysis)!
!
Management!
+ Stop!transfusion!immediately!and!spigot!off!the!unit!
+ Treat!shock!if!present,!maintain!BP!with!IV!colloid!solutions!
+ Use!a!new!giving!set!&!keep!vein!open!with!normal!saline!
o Y!set:!one!end!connected!to!blood!product,!one!to!NS!
! Need!to!stop!infusion,!take!off!the!set!&!set!up!new!set!for!IVF!(otherwise!will!
give!another!5+10ml!of!blood!to!patient!and!cause!further!hemolysis)!
+ Insert!indwelling!catheter!to!monitor!hourly!urine!output!
o Patient!need!to!excrete!all!hemolysed!RBC!through!urine,!then!recover!
o Diuretics!(mannitol!/!frusemide)!may!be!used!to!maintain!adequate!urine!output!!
o If!patient!develop!renal!failure!"!dialysis!!
+ Save!the!blood!units!&!blood!giving!set!for!investigation!
+ Check!ABO!blood!group!of!donor!bag!is!compatible!with!patient’s!ABO!blood!group!in!
record/CMS!
+ Send!to!blood!bank!all!DONOR%BAGS%of!the!same!transfusion!episode!
+ Send!6%ml%EDTA%&!10%ml%clotted%blood%(post+transfusion!specimen!from!patient)!to!blood!
bank!for!serological!investigation!together!with!a!printout!of!the!AIRS!reporting!form!
+ Check!CBC,!coagulation!profile,!RLFT!for!patient!

Delayed5hemolytic5transfusion5reaction5
+ Estimated!risk:!1!in!1000!
+ Destruction!of!transfused!red!cells!by!antibody!not!detectable!during!the!pre+transfusion!
compatibility!testing!
o Pre+transfusion!testing!is!only!valid!for!3!days,!need!to!repeat!testing!
! New!antibodies!are!developing!
+ Rapid!secondary!boost!in!antibody!level!after!transfusion:!anamnestic!response!
!
Presentation!!
+ Most!are!asymptomatic!&!found!to!have!a!failure!to!have!a!predicted!response!from!blood!
transfusion!(Hb!not!increase!/!even!drop!after!transfusion!&!blood!loss!is!excluded)!
+ Typically!cause!jaundice!at!day!5!onwards!
+ Fever,!hemoglobinuria!
+ Renal!failure!very!rare!
!
Management!!
+ Supportive!!
+ Hemolysis!may!be!severe!in!some!enough!to!require!active!treatment!
+ Investigate!for!the!Ab!involved!&!reason!for!failure!of!detection!in!pre+transfusion!testing!

Febrile5nonWhemolytic5transfusion5reaction5
+ Frequent!1:100!with!non+leukoreduced!blood!products!
+ Mainly!occur!with!red!cells!&!platelets!transfusion!
+ Alloimmunization!to!antigens!on!donor!leukocytes!/!platelets!
+ Transfusion!of!cytokines!released!from!donor!leukocytes!during!storage!
!
Presentation!
+ Onset:!usually!~30min+2hr!after!starting!RBC!transfusion,!earlier!for!platelet!transfusion!
+ Flushing,!fever,!tachycardia,!sometimes!rigors!
o DDx:!septic!reaction!–!infection!from!contaminated!blood!product!
!
!

Hematology!+!42!
Management!
+ Stop!transfusion!immediately,!keep!vein!open!
+ Clerical!check!for!compatibility!between!recipient!and!blood!unit(s)!given!
+ Antipyretic!e.g.!paracetamol!can!be!given!
+ For!mild!febrile!reaction!&!rapidly!resolving!symptoms,!transfusion!may!be!resumed!slowly!
+ For!severe!febrile!reaction!(e.g.!rise!in!temperature!>!1.5°C),!the!same!unit!should!not!be!
restarted!
+ Hemolytic%transfusion%reaction!&!septic%reaction!should!always!be!suspected!&!
investigated!&!managed!accordingly!

Allergic5reaction5
+ Frequent,!1:100!to!1:300!
+ Usually!mild,!self+limiting!
+ Recipient!is!allergic!to!something!in!the!donor!(foodstuff,!medication,!protein)!
+ Rash,!urticaria!
+ Pre+medication!with!antihistamine!(piriton)!can!prevents!allergic!reaction!
+ May!need!to!use!washed!products!
!
Anaphylactic!reaction!
+ Dyspnoea,!wheezing!
+ Laryngeal!edema,!bronchospasm,!shock!
+ Frequency!1:20,000!to!1:50,000!
+ Usually!seen!in!IgA!deficient!subjects,!form!antibodies!to!donor!IgA!
+ Need!to!use!saline+washed!red!cells!/!IgA!deficient!products!
!
Management!of!allergic!reaction!
+ Stop!transfusion!immediately!and!keep!vein!open!
+ Give!antihistamine!as!directed!
+ Observe!for!anaphylaxis!
+ For!anaphylaxis,!adrenaline!injection!may!be!required!!
+ If!urticaria!are!the!only!sign,!the!transfusion!may!sometimes!continue!at!a!slower!rate!

Septic5reaction5
+ Transfusion!of!bacterial!contaminated!blood!/!blood!components!"!immediately!develop!
septicemia!
+ Red!cell!1:500,000,!Platelet!1:10,000!
!
Presentation!!
+ Rapid!onset!of!chills!and!rigors!
+ High!fever!usually!>!2°C!
+ Nausea,!vomiting,!diarrhea!
+ Hypotension,!DIC,!intravascular!hemolysis,!renal!failure!!
!
Management!
+ Stop!transfusion!immediately,!keep!vein!open!
+ Monitor!patient!closely!for!septicemic!shock!
+ Clerical!check!for!compatibility!between!recipient!&!blood!unit!given!and!exclude!hemolytic!
transfusion!reaction!accordingly!
+ Take!blood!culture!from!patient!&!blood!culture!(+Gram!stain)!from!implicated!blood!unit!!
+ IV!broad!spectrum!antibiotics!with!adequate!anti+pseudomonas!coverage,!e.g.!ceftazidime!
+ Report!through!hospital!blood!bank!to!HKRCBTS!for!further!investigation!

Hematology!+!43!
Infectious+Disease!
Positive+blood+culture .....................................................................................................................1!
General+management+of+infection...................................................................................................2!
Septic+shock ....................................................................................................................................2!
Staphylococcus+aureus+spondylitis ..................................................................................................3!
Staphylococcal+scalded+skin+syndrome+(SSSS)..................................................................................3!
Skin+&+soft+tissue+infection..............................................................................................................3!
Clostridium+difficile .........................................................................................................................3!
Pneumococcal+infection ..................................................................................................................4!
Meningococcal+infection .................................................................................................................4!
Mycobacterium...............................................................................................................................4!
Tuberculosis!(TB)!–!notifiable!disease ........................................................................................................................................4!
Non.tuberculous!mycobacterium!(NTM) ...................................................................................................................................7!
PCP+(Pneumocystis+jiroveci+pneumonia)..........................................................................................8!
H7N9...............................................................................................................................................8!
Middle+East+Respiratory+Syndrome+(MERS) .....................................................................................8!
Aspergillosis....................................................................................................................................8!
HIV+(Human+Immunodeficiency+Virus)+/+AIDS ..................................................................................9!
Immune!reconstitution!inflammatory!syndrome!(IRIS)...................................................................................................14!
Syphilis .........................................................................................................................................14!
Malaria .........................................................................................................................................15!
Zoonoses.......................................................................................................................................15!
Blood+test .....................................................................................................................................15!
Influenza+accination ......................................................................................................................15!
Antibiotics.....................................................................................................................................16!
Augmentin!(amoxicillin!+!clavulanate).....................................................................................................................................16!
Sulperazon:!Cefoperazone!+!sulbactum ...................................................................................................................................16!
Vancomycin...........................................................................................................................................................................................16!
Linezolid.................................................................................................................................................................................................17!
Gentamicin ............................................................................................................................................................................................17!
Anti.pseudomonas.............................................................................................................................................................................17!
!
Positive+blood+culture+
G+ve!cocci!in!clusters!(Staph)!
. Do!P/E!to!search!for!primary!sites!
o Skin!&!soft!tissue!infection,!infected!drip!site,!blood!taking!site!
! Don’t!forget!to!look!at!LL:!common!site!of!cellulitis!
o Joints!
o Heart!murmur:!acute!IE!
o Resp!system!
. Repeat!blood!culture!to!r/o!contamination!
. Staph!aureus!bacteremia!"!cloxacillin!(don’t!assume!contamination!every!time)!
!

Infectious!Disease!.!1!
. MRSA!septicemia!"!vacomycin!x!21!days!
. Coagulase!staph!bacteremia:!esp!in!patients!with!catheters/!long!lines!
o Need!to!search!carefully!for!signs!of!sepsis!
!
G+ve!cocci!in!chains!(Strep)!
. Strep!pyogenes!(group!A)!
o Necrotizing!fasciitis,!strep!throat,!scarlet!fever!
. Group!B!Strep!
o IE,!bacteremia,!meningitis!
. Enterococcus!
. Strep!viridans!(mouth!flora)!!
o Subacute!infective!endocarditis!
. Strep!suis!
o Bacteremia,!meningitis!
. Strep!bovis!(group!D)!
o Endocarditis,!CRC!/!polyps!(∴!need!colonoscopy!to!screen)!
!
G+ve!cocci!in!pairs!!
. Strep!pneumonia!!
o Sinusitis,!pneumonia,!otitis!media,!bacteremia,!meningitis!
!
G+ve!bacilli!
. Diphtheroids!
o Skin!contaminant,!non.pathogenic!
o Vs!diphtheriae:!cause!diphtheria!
. Anthrax!
. Listeria!
. Clostridium!(anaerobe)!
!
G.ve!bacilli!
. Enterobacteriaceae:!E.!coli,!Klebsiella,!Proteus,!Salmonella,!Shigella…!
o UTI,!intra.abdominal!infections,!e.g.!cholangitis,!pyelonephritis…!
o Bacteremia:!very!sick,!may!develop!septic!shock!
o Pneumonia,!meningitis!
o Cannot!be!contaminant!
. Pseudomonas!aeruginosa!
. Hemophilus!influenzae!(coccobacilli)!
. Bacteroides!fragilis!(anaerobe)!
o Intra.abdominal!infections!
!
G.ve!cocci!
. Neisseria!gonorrheae!
o Septic!arthritis,!STD!
. Nesseria!meningitidis!
o Skin!rash,!meningitis!
General+management+of+infection+
.!Source!control:!drain!pus!
Septic+shock+
Management!outline!
. Resuscitation!
. Investigation!of!the!cause!of!sepsis!
!

Infectious!Disease!.!2!
. Definitive!therapy!
. Adjunctive!therapy!
Staphylococcus+aureus+spondylitis+
Clinical!presentation!
. Non.specific!symptoms,!e.g.!low!back!pain!
. May!have!isolated!spondylitis,!even!may!not!have!fever!
!
Investigations!
. Blood!culture:!usually!+ve!
o +ve!culture:!need!to!treat!as!infection!(instead!of!contamination)!until!proven!
otherwise!
o +ve!culture!"!think!of!spondylitis!&!IE!
! "!Arrange!Echo!(a!must!!Even!Dx!spondylitis,!still!need!echo!since!they!can!
co.exist)!&!ask!for!low!back!pain!±!imaging!of!spine!(MRI!/!CT)!
o But!need!to!repeat!blood!culture!x!2!times!to!r/o!skin!contamination!
. *!Primary!source!usually!not!known!
!
Treatment!
. High!dose!treatment!
. Duration:!depends!on!duration!of!disease!
o If!acute!"!weeks;!if!chronic!"!months!
. MSSA:!cloxacillin!
o If!penicillin!allergy!"!clindamycin!
. MRSA:!
o Vancomycin!
! S/E:!ototoxic,!nephrotoxic!
! Red!man!syndrome:!mast!cell!degranulation!"!facial!rash,!flushing!(prevented!
by!↑!infusion!time)!
! TDM:!trough!level!(before!next!dose)!after!reaching!steady!state!(after!3.4!
dose)!
o +!cotrimoxazole/!fusidic!acid/!rifampicin!if!deep.seated!infections!
o Linezolid!/!daptomycin!if!vancomycin!allergy!/!vancomycin.resistant!
Staphylococcal+scalded+skin+syndrome+(SSSS)+
. Epidermolytic!exotoxins!A!&!B!"!detachment!within!epidermal!layer!
Presentation!!
. Widespread!thin!walled!blisters!that!are!easily!ruptured!!
. Widespread!painful!erythroderma!!
o Usually!involve!face,!diaper,!intertriginous!areas!
. Nikolsky's!sign!+ve!
o Slight!rubbing!of!skin!results!in!exfoliation!of!outermost!layer,!forming!a!blister!
within!minutes!
o DDx:!TENS,!pemphigus!vulgaris!
Skin+&+soft+tissue+infection+
Drip.site!infection!
. Empirical!treatment!
o Augmentin!or!amoxicillin+cloxacillin!
Clostridium+difficile+
Presentation!
. Typically!watery!diarrhea!+!leukocytosis!+!low!grade!/!no!fever!+!abd!cramps!
o Diarrhea!onset!>3!days!after!hospitalization!(3!days!rule)!
!

Infectious!Disease!.!3!
 o 5%!population!has!C.!difficile!as!colonization!without!infection!∴look!for!symptoms!
not!only!lab!results!!
!
Investigation!!
. PCR!for!gene!toxin!(sensitive)!
. EIA!for!toxins!(fair!sensitivity!but!good!specificity)!
. Endoscopy!&!biopsy:!pseudomembranes!
o Specific!but!non.sensitive!
o Reserve!for!toxin!–ve!cases!/!prompt!Dx!is!needed!
!
Prevention!
. Alcohol!swap!is!useless!because!it!cannot!kill!spores!
. Stool!isolation,!droplet!precaution!
!
Treatment!!
. Metronidazole!(oral!/!IV)!/!vancomycin!(oral!only,!as!IV!cannot!enter!gut)!
Pneumococcal+infection+
Treatment!!
. CNS!infection!
o If!resistance!"!use!other!drug!
! As!higher!dose!can’t!enter!brain!due!to!penetration!problem!
. Extra.CNS!infection!
o If!resistance!"!can!use!higher!dose!of!penicillin!
Meningococcal+infection+
Prevention!
. Droplet!transmission!
. If!contact!patient!unprotectly!"!need!prophylaxis:!rifampicin!/!fluoroquinolone!
Mycobacterium+
Terminology!!
. Non.tuberculous!mycobacterium!(NTM)!
. Mycobacteria!Other!Than!Tuberculosis!(MOTT)!
. Atypical!mycobacterium!(e.g.!M!avium)!!
. Rapid!growing!mycobacterium!(growth!within!2!weeks!instead!of!6.8!weeks)!

Tuberculosis+(TB)+–+notifiable+disease+
. Primary!TB:!within!5!years!after!infection!
o If!involve!LNs!"!Ghon’s!complex!
. Post.primary!TB:!reactivation!occur!≥5!years!after!primary!infection!
o 10%!lifetime!risk!of!reactivation,!higher!in!HIV.infected!pt!(10%!per!year)!
!
2!types!of!pulmonary!TB:!
. Miliary!TB:!hematogenous!spread!(usually!secondary),!no!sputum!"!less!infectious!
. Bronchopulmonary!TB:!spread!by!airway!"!sputum!+ve!"!highly!infectious!!
!
Presentation!!
. Cough!with!sputum!
o In!bronchopulmonary!TB!
o Not!in!miliary!TB!(it’s!in!vessel!which!is!outside!alveoli!),!but!when!miliary!TB!
rupture!into!airway!then!have!mixed!pattern!
. Enlarged!LNs!!
o Cervical!(most!common),!mediastinal!(2nd!commonest)!
!

Infectious!Disease!.!4!
. Cavitation!in!CXR!
o Young!&!immunocompetent:!apicoposteral!region!of!lower!lobe!(upper!part!of!middle!
zone!on!CXR)!
o Elderly:!apical!region!
o More!immunocompromised!patients:!miliary!pattern!
o Uncommon!in!perihilar!region!
!
Investigation!available!!
. Microscopy!(Ziehl!Neelsen!stain)!
o 5000.10000bacilli/ml!
o 40%!are!sputum!smear!+ve!(need!isolation),!very!low!yield!for!pleural!fluid!or!CSF!!
o Detect!acid%fast)bacilli,!not!necessarily!MTB!!
. Culture!(highly!SN!&!SP)!
o 10.100bacilli/ml!
o For!species!identification!and!sensitivity!testing!!
o LJ!medium!~6.8weeks!!
o Broth!medium!~!3.4weeks!!
. PCR!(highly!SP!but!low!SN)!
o Good!for!confirming!species!in!smear)positive)cases,!also!good!for!BAL/CSF)!
o Bad!(50%!sen)!for!smear!negative!cases!!
. ESR!↑↑↑!
. Adenosine!deaminase!
o An!enzyme!abundant!in!lymphocytes,!used!in!pleural)fluid,!cutoff!at!40!!
o Non.specific,!also!found!in!lymphoma,!malignancy!or!RA!SLE!
. Histology!!
o For!caseating!granulomas,!Langerhan's!giant!cells,!aggregates!of!epitheloid!cells!!
o Enlarged)nodes,)pleural)biopsy)!
. CXR/CT!!
o Upper!lobe!fibrosis,!calcification,!hilar!lymphadenopathy!!
o Tree!in!bud!appearance!(signify!peribronchovascular!infection:!affect!distal!airway)!
! DDx:!NTM!(non.tuberculous!mycobacterium),!fungal!infection!(rare)!
!
Diagnosis!
. Sputum!AFB:!most!common!
o Smear!+ve,!PCR!+ve!"!TB!
o Smear!–ve,!PCR!+ve!"!TB!with!low!bacterial!load!
o Smear!+ve,!PCR!–ve!"!not!TB!(e.g.!non.tuberculous!mycobacterium)!
o Smear!–ve,!PCR!–ve!"!can’t!r/o!TB!as!sensitivity!not!very!high!
. If!dry!cough!(no!sputum)!"!bronchoscopy!x!BAL!±!transbronchial!biopsy!/!CT!
!
Baseline!investigation!before!starting!Rx!
. LFT,!HBsAg:!anti.TB!drug!is!hepatotoxic,!and!need!to!differentiate!hepatotoxicity!Vs!acute!
flare!of!Hep!B!if!deranged!liver!Fx!after!treatment!
. HIV!status!
. Eye!examination:!before!using!Ethambutol!
!
Management!
. Admit!to!negative!pressure!isolation!room!
o For!open!TB!(sputum!smear!+ve),!release!if!smear!–ve!
! Smear!+ve/.ve:!depend!on!bacterial!load!
• Smear!–ve!still!infectious,!but!lower!risk!
!

Infectious!Disease!.!5!
 ! Isolate!until!smear!conversion!(3!consecutive!smear!–ve!sputum)/!≥2!weeks!
after!effective!TB!Rx!if!no!more!sputum!can!be!coughed!out!
o Need!isolation!in!laryngeal!TB!too:!can!be!spread!by!talking!!(Airborne!)!
. Airborne!precaution!
. DAT!
. O2!supplement!if!needed!
. Monitor!BP/P/SaO2/RR/Temp!
. Sputum!x!C/ST,!gram!smear,!TB!smear,!TB!culture,!PCR!±!cytology!!
. Blood!x!CBC,!RFT,!LFT!±!blood!culture!
. CXR!
. Empirical!Anti.TB!drugs!
o Direct!observed!treatment!short!course!!
o Warn!about!side!effects!
o Alert!for!drug.drug!interactions!!
o Regime!
! Normal!=!2HRZ!+!(E/S)!/!4HR!
! HIV/DM/silicosis!=!2HRZ!+!(E/S)!/!7HR!
! TB!meningitis/!Miliary!TB!=!3HRZE±S!/!9HR±E!
o Treatment!resistant!TB!(5!for!3!months,!first!3!for!18!months)!!
! Ethambutol!!
! Ethionamide!!
! Pyrazinamide!!
! Aminoglycoside!!
! Fluoroquinolones!
o Alternatives!
! Fluoroquinolones!
! Streptomycin!/!clarithromycin!
. Oral!pyridoxine!
. Contact!tracing!
. Inform!Department!of!Health!
!
Drugs!!
. Side!effects!!
o Isoniazid!(H)!
! B6!deficient!neuropathy,!hepatotoxicity!
o Rifampicin!(R)!
! Orange!color!secretions,!hepatotoxicity,!fever!&!vasculitis,!N&V!
• Another!drug!that!also!causes!orange!urine:!phenazopyridine!(for!UTI)!
! Enzyme!inducers,!e.g.↓!effectiveness!of!OCP!!
! Thrombocytopenia,!hemolytic!uremic!syndrome!
o Pyrazinamide!(Z)!
! Arthralgia,!gout,!hepatotoxicity!
o Ethambutol!(E)!
! Retrobulbar!neuritis!(blue.green!color!halo!in!peripheral!vision!initially,!↑!risk!
in!renal!impairment,!elderly)!
! Peripheral!neuropathy,!gout!!
o Streptomycin!(S):!rash,!nephrotoxic,!ototoxic!(cross!placenta)!
. *!Never!use!monotherapy!
o Resistance!depend!on!viral!load!
o Spontaneous!mutation!rate!to!anti.TB!agent:!1!in!106!
o Viral!load!in!cavitating!TB!(the!type!with!highest!viral!load):!109!
!

Infectious!Disease!.!6!
 o If!use!2!anti.TB!agents!"!need!1012!virus!to!produce!spontaneous!mutation!leading!
to!resistance!"!very!low!risk!even!in!cavitating!TB!
. *!Should!take!all!the!drugs!all!together!at!same!time!once!a!day!!
o Need!to!achieve!very!high!blood!level!(transient),!which!is!useful!to!kill!TB!
o Should!take!it!before!bedtime!"!↓!S/E,!e.g.!nausea!
!
Adverse!reaction!to!anti.TB!agents!
. Liver!derangement!(hepatotoxicity)!
o Definition!!
! ALT!level!>3!times!ULN!!
! Bilirubin!>2!times!ULN!!
! **!Need!to!differentiate!hepatotoxicity!of!drug!&!acute)flare)of)Hep)B!
o Stop!all!agents!together!
o Start!an!intrim!regime!(Streptomycin!+!Ethambutol!+!Levofloxacin)!
o Reintroduce!after!ALT!normalized!(in!sequential!manner):!rifampicin!"!isoniazid!!
! Never!re.add!pyrazinamide!as!rechallange!may!result!in!stronger!reaction!
(permanently!discontinued!pyrazinamide!,!with!Rx!extended!to!9!months)!
. Paradoxical!LN!enlargement,!even!rupture!
o Sometimes!the!body!produce!too!strong!immune!response!after!Rx!
!
Detecting!latent!TB!
. Indication!
o High!risk!for!new!infection!(close!contact!to!open!TB)!!
o High!risk!for!reactivation!(HIV,!silicosis,!immunosuppressants,!anti.TNF)!
. Methods!
o Tuberculin!skin!test!(Mantoux!test)!
! Inject!2unit!of!Purified!protein!derivative!PPD.RT23!intradermally,!observe!
for!induration!in!48.72h!!
! ≥5mm:!immunocompetent!household!contact!<!1!year,!HIV!+ve!pts!
! ≥10mm:!pt!with!silicosis!&!pt!receiving!anti.TNF!therapy,!DM!
! ≥15mm:!immuno.competent!household!contact!≥!1!year!
o Blood!interferon.gamma!release!assay!(for!TB!exposure)!
! Can!look!for!latent!TB!but!cannot!used!to!diagnose!active!TB!infection!
! Not!affected!by!BCG!vaccination!!Good!!
! In!vitro!blood!tests!of!cell.mediated!immune!response;!they!measure!T!cell!
release!of!interferon.gamma!(IFN.gamma)!following!stimulation!by!antigens!
unique!to!M.!tuberculosis!
. Treatment!
o *!Consider!treatment!of!latent!TB!infection!in!high!risk!patients!by!9!months!
Isoniazid,!after!ruling!out!active!TB!infection!(clinical,!radiological!and!smear)!
!
Prevention!
. BCG:!Bacillus!Calmette!Guerin!
o Live!attenuated!vaccine!"!C/I!in!AIDS!&!pregnancy!
o Risk:!BCG!sepsis!(rare)!"!liver!derangement,!reactive!arthritis,!↑!in!WCC,!ESR,!CRP!

NonXtuberculous+mycobacterium+(NTM)+
. !All!the!other!mycobacteria!except!Mycobacterium!tuberculosis!complex!which!can!cause!
tuberculosis!(M.!tuberculosis,!M.!bovis,!M.!africanum,!M.!microti!and!M.!canetti)!&!M.!leprae!
and!M.!lepromatosis!
. Common!environmental!organism!"!no!need!isolation!
. May!cause!abscess!by!rapid.growing!mycobacterium!
!

Infectious!Disease!.!7!
. Risk!factors:!underlying!lung!disease!(bronchiectasis,!COPD,!destroyed!lung…)!
. Ix:!AFB!+ve!but!culture!show!not!TB!
. Rx:!macrolide.based!Rx!(but!don’t!just!randomly!give!macrolide,!have!to!follow!clinical!
guideline!"!refer!to!ID!if!not!know!how!to!treat)!
PCP+(Pneumocystis+jiroveci+pneumonia)+
Presentation!!
. Gradual!onset!fever,!dry!cough,!progressive!dyspnea,!may!have!hemoptysis!
. Hb!desaturation!on!minimal!exertion!
!
CXR!!
. Bilateral!peri.hilar!infiltrate!without!signs!of!HF!(e.g.!cardiomegaly)!
. Cysts!in!mid!&!lower!zones!±!PTX!(as!the!cyst!rupture,!in!up!to!10%)!
. *!Comparatively!lack!of!clinical!features!despite!very!extensive!consolidation!
!
Diagnosis!
. Bronchio.alveolar!lavage!(BAL)!/!sputum!"!
o Toluidine!blue!o!stain!/!silver!stain!/!IF)assay!for!cysts!/!PCR!
. *!Prone!to!pneumothorax,!esp.!after!bronchoscopy!with!BAL!done!
!
Treatment!!
. Systemic!
o Cotrimoxazole!(trimethoprim.sulfamethoxazole)!x!21!days!
! Contain!sulphur!group!"!caution!in!G6PD!(need!to!check!G6PD!beforehand)!
! S/E:!skin!reaction!(higher!risk!in!HIV!patient,!may!↓!risk!by!giving!vit!C)!
o Clindamycin!+!primaquine!(oral!drugs)!
o Pentamidine:!IV!drugs,!S/E:!hyper/hypoglycemia,!arrhythmia!"!not!preferred!
o Dapsone!
o Add!prednisolone!in!severe!cases!(PO2!<9.5kPa)!
. Local!Rx:!Pentamidine!(inhalation,!for!patient!with!poorer!condition)!
H7N9+
. No!specific!radiographic!features!
. !!70%!had!contact!with!poultry!/!contaminated!environment!!
. Limited!human.human!transmission!
. Oseltamivir!effective!if!given!early!
Middle+East+Respiratory+Syndrome+(MERS)+
. No!specific!radiological!features!
. Epidemiology!data!important!!
. Median!age!58!years!in!KSA!&!majority!have!comorbidities,!DM,!CRF,!male!75%!
. About!20%!of!patients!had!animal!contact!history!
. Bats!likely!the!source!but!intermediary!animals!uncertain!
. Limited!human.human!transmission!
. No!known!effective!anti.viral!therapy!at!present!
Aspergillosis+
Introduction!!
. ~35!pathogenic!species,!most!common!one!is!Aspergillus*fumigatus!
. A!hyaline!branching!mold!growing!in!decomposing!plant!materials!
. IMMUNOCOMPETENT!=!only!intense!exposures!are!sufficient!to!cause!disease!
. IMMUNOCOMPROMISED!(profound!neutopenia/!steroid!usage)!
!!
Clinical!manifestation!
!

Infectious!Disease!.!8!
. Invasive!aspergillosis!
o Damage!lung!tissue,!spread!to!brain,!bone,!skin!and!other!organs!
o Only!in!very!immunocompromised!patients!
. Chronic!pulmonary!aspergillosis!
o Cavities!expanding!over!a!period!of!months!/!years!±!fungal!ball!±!pleural!thickening!
o Systemic!symptoms!(weight!loss!and!fatigue)!
o Pulmonary!symptoms!(dry!cough,!wheezing,!SOB,!mild!hemoptysis)!
o Can!progress!to!upper!zone!fibrosis!
. Allergic!bronchopulmonary!aspergillosis!(ABPA)!
o A!hypersensitivity!reaction,!in!1%!of!asthma!
o Cough!up!thick!sputum!casts!brown!in!color!
o Hemoptysis!
o Investigations!!
! Eosinophilia!
! Positive!skin!prick!test!
! Elevated!total!IgE!
! Aspergillus.specific!IgE!and!IgG!
!!
Treatment!
. Invasive!=!Voriconazole!(posaconazole,!caspofungin,!liposomal!amphotericin!B)!
. Others!=!Itrazonazole!
HIV+(Human+Immunodeficiency+Virus)+/+AIDS++
. HIV.1:!enveloped!retrovirus!with!a!plus.stranded!RNA!genome!
. Cause!immune!destruction!(CD4!T!helper!cell!depletion)!"!↑!infection!&!malignancy!
o Normal!CD4!count!~400.500!
o ↑!risk!of!infection!when!CD4!count!<!200!
o Mean!decline!in!CD4!in!HIV!patient:!~50/year!
. AIDS!=!acquired!immunodeficiency!syndrome!
!
Transmission!
. Sexual!
o Risk!↑!with!higher!viremia,!receptive!anal!intercourse,!presence!of!other!STD!(esp!
genital!ulcers)!
o Prevention:!safe!sex!(condom,!limit!no!of!concurrent!partners),!treat!other!STDs,!male!
circumcision!(↓!heterosexual!transmission),!ART!for!discordant!partners!(1!+ve!1.ve)!
. Injection!drug!use!
o Associations:!poor!socioeconomic!conditions,!homeless,!unsafe!sexual!practice!
o Prevention:!drug!abuse!Rx,!methadone!clinics,!needle!&!syringe!exchange!program,!
HIV!counseling!&!testing!programmes!
. Mother.to.child!transmission!
o Without!intervention:!risk!15.40%!(in!utero,!intrapartum,)postpartum)!
o Prevention:!universal!antenatal!HIV!testing,!effective!antenatal!/!intrapartum!/!
postpartum!ART,!C/S,!avoid!breastfeeding!
. Nosocomial!/!occupational!
o Transfusion!of!contaminated!blood!products,!organ!transplantation,!healthcare!
workers!(as!source!/!victim)!
o Prevention:!screening!of!blood!products!&!organ!donors,!post.exposure!prophylaxis!
!
Investigation!
. Indications!for!HIV!testing!
o At.risk!individuals:!STD,!commercial!sex!workers!
!

Infectious!Disease!.!9!
 o Non.AIDS!defining!illnesses!
! Unexplained!generalized!lymphadenopathy,!unexplained!weight!loss!
! Idiopathic!thrombocytopenia!
! Oral!candidiasis,!Herpes!zoster,!severe!bacterial!infections!(e.g.!pneumococcal)!
o AIDS.defining!diseases!
o Unexplained!symptoms:!weight!loss,!chronic!diarrhea!
o Pregnancy:!universal!antenatal!HIV!screening!
. Window!period:!interval!between!infection!&!production!of!measurable!antibodies,!usually!3!
weeks!.!6!months!
. Screening!test!(sensitive)!
o Anti.Env!antibody!detection!test:!
window!period!~3!weeks!
o Nucleic!acid!test!(NAT:!detect!HIV!
RNA):!shortest!window!period!
! For!blood!donor!screening!&!
neonates!if!mother!is!+ve!
o ELISA!(combo!assay:!test!for!both!
Ab!&!p24!Ag):!window!period!~2!
weeks!
o *!If!–ve!"!repeat!6!weeks!after!due!
to!window!period!
. Confirmatory!test!(specific)!
o Western!blot:!antibody!detection!
test!
. Other!tests!after!confirmation!
o CD!4!count,!HIV!RNA!(viral!load)!
o Anti.HAV!IgG,!HBsAg,!anti.HCV!
o Tuberculin!skin!test,!CXR!
o Toxoplasma!IgG!
o Syphilis!serology,!tests!for!
gonorrhea!&!Chlamydia!trachomatis!
o PAP!smear!for!F!(cervical!cancer)!
o G6PD!assay!(cotrimoxazole!prophylaxis!may!be!needed)!
!
Clinical!course!
. Acute!retroviral!syndrome!
o Onset!of!illness!1.6!weeks!after!exposure!
o Mononucleosis.like!illness!in!50.60%!(some!are!asymptomatic)!
! Fever,!pharyngitis,!lymphadenopathy,!rash!
! Last!10.15!days!
o Need!to!repeat!HIV!Ab!test!if!test!–ve!(window!period)!
o Initiation!of!anti.retroviral!therapy!recommended!
. Clinical!latency!
o Diagnosis!of!HIV!=!incidental!finding:!STD!clinics,!MSM,!antenatal!testing,!body!check!
o Latent!HIV!reservoirs:!ongoing!HIV!replications!despite!effective!antiretroviral!Rx!
. Opportunistic!diseases!
!
AIDS!defining!illnesses!
. Multiple!/!recurrent!bacterial!infections!(in!age!<13)!
. Candidiasis!of!bronchi,!trachea,!lungs,!esophagus!
. Invasive!cervical!cancer!
. Disseminated!/!extrapulmonary!Coccidioidomycosis!!
!

Infectious!Disease!.!10!
. Extrapulmonary!Cryptococcosis!!
. Chronic!intestinal!Cryptosporidiosis!(>1!month)!
. Cytomegalovirus!(CMV)!
o Disease!other!than!liver,!spleen,!or!nodes,!onset!at!age!>1!month!
o Cytomegalovirus!retinitis!(with!loss!of!vision)!
. HIV!related!encephalopathy!
. Herpes!simplex!(HSV)!
o Chronic!ulcers!(>1!month)!!
o Bronchitis,!pneumonitis,!or!esophagitis!(onset!at!age!>1!month)!
. Disseminated!or!extrapulmonary!Histoplasmosis!
. Chronic!intestinal!Isosporiasis,!(>1!month)!
. Kaposi!sarcoma!
. Lymphoid!interstitial!pneumonia!/!pulmonary!lymphoid!hyperplasia!complex!
. Burkitt!lymphoma,!immunoblastic!lymphoma,!primary!brain!lymphoma!
. Disseminated!or!extrapulmonary!Mycobacterium*avium!complex!/!Mycobacterium*kansasii!
. Pulmonary/)disseminated/)extrapulmonary)Mycobacterium-tuberculosis-(MTB))
. Disseminated!/!extrapulmonary!Mycobacterium!of!other!/!unidentified!species!
. Pneumocystis)jirovecii)pneumonia)(PCP))
. Recurrent!pneumonia!
. Progressive!multifocal!leukoencephalopathy!
. Recurrent!Salmonella!septicemia!
. Toxoplasmosis!of!brain!(onset!at!age!>1!month)!
. Wasting!syndrome!attributed!to!HIV!
!
Opportunistic!infection!/!malignancy!
. PCP!(Pneumocystis!jirovecii!pneumonia):!commonest!
o When!CD4!count!<200!
o Gradual!onset!fever,!dry!cough,!progressive!dyspnea!
o Prone!to!pneumothorax,!esp.!after!bronchoscopy!with!biopsy!done!
. Candida:!2nd!most!common!
o Oral!thrush!
o Esophagitis!
! OGD:!white!spots!in!esophagus!
! Rx:!azole,!nystatin!
• Fluconazole:!most!commonly!used,!useful!for!albicans!
• Voriconazole,!itraconazole,!posaconazole:!stronger,!for!non.albicans!/!
empirical!Rx!for!transplant!patient!having!neutropenic!fever!
o Itraconazole:!poor!oral!absorption!in!tablet!form,!better!with!
liquid!form!
• **!NOT!oral!ketoconazole:!not!used!anymore!due!to!liver!toxicity,!only!
used!in!shampoo!for! !
. Penicillosis:!3rd!most!common!
o Constitutional!Sx:!weight!loss,!fever!
o Rash:!popular!rash!with!central!unbilication!
o Pancytopenia!!
o Ix:!blood!culture!(fungemia)!&!BM!aspirate!for!culture!
. Toxoplasma!(a!parasite)!
o Cat!is!the!carrier,!toxoplasma!found!in!cat!faeces!
! Pregnant!ladies!&!IC!patients!can!still!have!cats,!but!should!avoid!cleaning!
their!faeces!
o Brain!abscess!
! Investigation!
!

Infectious!Disease!.!11!
 • Cannot!do!LP!(SOL!in!brain)!
• Blood!serology!
• MRI!/!CT!finding!!
o Usu!multiple!lesions,!with!a!predilection!for!basal!ganglia!&!
corticomedullary!junction!
• ±!brain!biopsy!
• Blood!culture!to!r/o!bacterial!causes!
. CMV!
o When!CD4<100!
o Retinitis!
! Peripheral!lesion∴need!to!dilate!pupil!in!order!to!be!seen!lesion!by!
fundoscopy!"!tomato!&!cheese!pizza!appearance!
o Colitis:!chronic!diarrhea,!even!bloody!(dysentery!due!to!deep!ulcer!in!colon)!
! Do!colonoscopy!to!look!for!ulcer!&!take!biopsy!(at!ulcer!base):!CMV!
intracellular!inclusion!body!(owl!eye!appearance)!
! Or!do!serology!!
o Esophagitis!/!gastritis!/!pneumonitis!/!encephalitis!(less!common)!
o Dx:!serology!!
! CMV!pp65!antigenemia!test:!IF.based!assay!
• Identify!the!pp65!protein!of!CMV!in!leukocytes!
• Can!determine!viral!load!"!used!to!monitor!Rx!response!
! ELISA!to!measure!Ab!to!CMV!
o Rx:!ganciclovir!(IV)!/!valganciclovir!(oral)!
! S/E!of!ganciclovir!
• Granulocytopenia,!neutropenia,!anemia,!thrombocytopenia!
• N&V,!dyspepsia,!diarrhea,!abdominal!pain,!flatulence,!anorexia!
• Liver!&!renal!derangement!!
• Fever,!headache,!confusion,!hallucination,!seizures!!
. TB!
o Features!
! Minimal!inflammation:!normal!CXR,!relatively!normal!CSF!WCC/protein!!
! Unusual!manifestations:!extra.pulmonary!TB!
o Mx:!should!start!anti.TB!treatment!immediately!
! Replace!rifampicin!by!rifabutin!(less!drug!interaction!with!protease!inhibitor!
(PI).based!ART)!
o Problem!for!TB!+!HIV!co.infection!
! Immune!reconstitution!inflammatory!syndrome!(IRIS)!!
• Higher!risk!if!start!HAART!early!after!initiation!of!TB!Rx!
o But!overall!survival!of!early!start!can!be!improved!although!
higher!risk!of!reconstitution!syndrome,!so!now!tends!to!start!
HAART!early,!except!in!!
! CNS!infection,!e.g.!TB,!cryptococcal!
! Retinitis!!
! "!delay!start!of!HAART,!e.g.!3.4!weeks!later!due!to!
severe!consequence!if!IRIS!occur!
• Mx:!both!ART!&!TB!Rx!should!be!continued!while!managing!IRIS!
o Can!give!steroid!/!NSAID!to!suppress!inflammatory!response!
o May!stop!HAART!if!very!severe!(e.g.!CNS!infection,!retinitis)!
! Drug!interaction!
• Less!interaction!for!rifabutin!than!rifampicin!
• Need!to!reduce!dose!
. Cryptococcal!meningitis!
!

Infectious!Disease!.!12!
 o Basal!meningitis:!enhancement!of!basal!meninges!in!CT!
o India!ink:!thick!capsule!
. Penicilliosis!
o Fever,!skin!lesions,!anemia,!hepatosplenomegaly,!septic!shock,!liver!failure!
o Dimorphic!fungi:!yeast!&!mold!
o Rx:!2!weeks!of!amphotericin!B,!then!10!weeks!of!oral!itraconazole!
. Lymphoma!
. Kaposi!sarcoma!
o Purplish!lesion!on!skin,!also!in!GI!tract,!airway,!by!human!herpesvirus!8!(HHV8)!
o Very!vascular!lesion!
o Rx:!!
! HAART!to!boost!up!CD4!count!"!eventually!subside!
! Chemo!if!severe!GI!involvement!but!uncommonly!used!as!immune!status!is!
already!very!poor!
!
DDx!of!upper!GI!bleed!in!IC!patients!
. Candida!esophagitis!
. CMV!esophagitis!
. Herpes!simplex!ulceration!
. Ix:!OGD!for!white!patches,!biopsy!for!inclusion!body!
!
Treatment!!
. Treat!the!opportunistic!infections!
. HAART!(highly!active!anti.retroviral!therapy)!/!cART!(combination!anti.retroviral!therapy)!
o Indication:!for!ALL!HIV.infected!people!(DHHS!guideline!2013)!
! Priorities!in!resource.limited!settings!
• Pregnancy,!CD4!<200,!Hx!of!AIDS.defining!illness,!HIV.associated!
dementia,!HIV.associated!nephropathy,!HBV!co.infection!(anti.Hep!B!
can!also!treat!HIV,!if!only!give!anti.hep!B!=!single!drug!Rx!for!HIV!"!↑!
risk!of!resistance),!acute!HIV!infection!
o Drugs!!
! Nucleoside!/!nucleotide!analogs!(NRTIs):!zidovudine,!lamivudine,!tenofovir!
! Non.nucleosides!(NNRTIs)!
! Protease!inhibitor!(PIs):!ritonavir,!atazanavir!
• Drug.drug!interactions!
o Statin:!simvastatin!C/I.!Use!low!dose!atorvastatin!/!rosuvastatin!
o Rifamycin:!rifampicin!C/I.!use!rifabutin!
o PPI!not!recommended!if!used!atazanavir!
! Entry!inhibitor,!fusion!inhibitor!
! Integrase!inhibitor!
o Regime:!2!NRTIs!+!PI!/!nNRTI!/!integrase!inhibitor!
o Benefits!
! ↓!Mortality!&!AIDS!
! ↓!End!organ!damage:!direct!effect!of!HIV!&!HIV.associated!inflammation!
! ↓!Liver!complications!(HBV!/!HCV),!cardiovascular!disease!
! ↓!Malignancy!(AIDS!&!non.AIDS)!
! ↓!Neurocognitive!decline!
! ↓!Transmission!(perinatal!&!sexual)!
o Toxicities!
! Metabolic:!↑!TC,!TG!&!LDL!
! CVD:!MI!
!

Infectious!Disease!.!13!
 ! Lipodystrophy:!lipoatrophy!in!face,!limb!(veins!become!very!obvious)!+!
lipohypertrophy!at!back,!visceral!organs!(buffalo!hump,!central!obesity)!
. Prevention!of!opportunistic!infection!
o Antibiotics!
! CD4!<200:!cotrimoxazole!(PCP!&!toxoplasma)!
! CD4!<50:!azithromycin!/!clarithromycin!(MAC)!
o Vaccination:!pneumococcal,!influenza,!HAV,!HBV!
o Tuberculin!test!/!IGRA!&!treat!latent!TB!

Immune+reconstitution+inflammatory+syndrome+(IRIS)++
. Worsening!of!a!recognized!(paradoxical!IRIS)!/!unrecognized!(unmasking!IRIS)!pre.existing!
infection!in!improved!immunologic!Fx!
. CD4!count!increase!after!start!of!ART!"!↑!inflammatory!response!"!worsening!of!TB!
meningitis!Sx!
. Diagnosis!by!exclusion!
o Drug.resistance!/!non.drug!compliance!"!progression!of!primary!disease!
o Other!new!infections!
o Drug!toxicity!
. Common!infections!a/w!IRIS!
o TB,!Mycobacterium!avium!complex!(MAC),!Cryptococcus!neoformans,!CMV!
. Risk!factors!
o Low!nadir!CD4!
o Rapid!rise!in!CD4!after!HAART!
o Early!initiation!of!HAART:!but!still!preferred!as!can!↓!risk!of!opportunistic!infection!
Syphilis+
Screening!(non.treponemal!tests)!
. EIA!(enzyme!immunoassay)!
o More!sensitive,!now!use!this!as!screening,!if!+ve!"!test!for!VDRL!&!TPHA!
. VDRL!(venereal!disease!research!laboratory)!
o Not!sensitive,!but!quantitative!∴!can!be!used!to!monitor!Rx!response!
!
Diagnosis!
. Microbiological!
o Dark!ground!microscopy!of!serous!fluid!from!a!chancre!&!look!for!spirochete!
! Another!spirochete:!Leptospira!(in!fresh!water,!from!rat!urine)!
. Serology!(treponemal!test)!
o Treponemal!pallidum!particle!agglutination!(TPHA)!!
o Fluorescent!treponemal!antibody!absorption!test!(FTA.Abs)!
!
Types!
. Primary!
. Secondary!
o Cutaneous!papular!lesion!in!palm!&!sole!(DDx:!HFMD)!
. Latent!
o Early!/!late!latent:!cutoff!=!2!years!
! If!no!recent!symptoms!&!no!Hx!of!Rx!"!treat!as!late!latent!
o Do!LP!to!r/o!neurosyphilis!"!if!normal!"!treat!as!latent!
o Rx:!IM!penicillin!G!weekly!x!3!
. Tertiary!
o Neurosyphilis!
! Memory!loss,!personality!change,!dementia!
!

Infectious!Disease!.!14!
 ! LP:!normal!opening!pressure,!normal!WCC,!↑!protein!(pleocytosis),!normal!
glucose,!CSF!VDRL!(>1:1!"!+ve!"!Dx)!
! Rx:!high!dose!penicillin!G!/!ceftriaxone!(high!CSF!penetration)!x!14.21!days!
• Alternative:!doxycycline!
• Need!to!give!high!dose!IV!prednisolone!24!hour!before!starting!A/B!for!
3!days!
o Prevent!Jarisch.Herxheimer!reaction:!endotoxins!release!from!
the!death!if!spirochete!"!fever,!rash,!tachycardia!&!hypotension!
! Monitor!serial!serum!VDRL!after!½!year!
Malaria+
. Cerebral!malaria:!diffuse!encephalopathy!
. Presentation!/!complications!
o Fever!!
o Hemolytic!anemia!(hemolysis!of!parasitized!cells),!severe!anemia,!hemoglobinuria!!
o Jaundice!
o Convulsion!
o Acute!renal!failure:!acute!tubular!necrosis!
o APO!
o Hypoglycemia!
o Metabolic!acidosis!
o Septicemia:!compromise!of!gut!barrier!
. Treatment:!quinine!
Zoonoses++
Cat!scratch!disease!
. Organism:!Bartonelloses,!Rabies!
. Treatment:!azithromycin!
Cat!bite!
. Augmentin,!tetanus!vaccine!±!rabies!vaccine!(in!endemic!area)!
Blood+test+
. Widal!test:!typhoid!fever!(Salmonella!enterica!serotype!typhi)!
. Weil.felix!test:!typhus!(Rickettsia)!
Influenza+accination+
Indications!!
. Pregnant!women!
. Elderly!persons!living!in!residential!care!homes!
. Long.stay!residents!of!institutions!for!the!disabled!
. Persons!aged!≥50!years!!
. Persons!with!chronic!medical!problems!including!obese!individuals!with!BMI!≥30!!
. Children!aged!6!months!.!6!years!
. Health!care!workers!!
. Poultry!workers!
. Pig!farmers!and!pig.slaughtering!industry!personnel!

General!information!
. Take!~2!weeks!for!antibodies!to!develop!&!provide!protection!
. ↓!risk!of!infection!&!↓!complications!even!if!infected!
!
Contraindication!
. Allergic!to!a!previous!dose!of!inactivated!influenza!vaccine!or!other!vaccine!components!(e.g.!
neomycin!or!polymyxin)! !
!

Infectious!Disease!.!15!
. Egg!allergy:!mild!not!C/I!! !
. Bleeding!disorders!/!on!warfarin:!may!receive!the!vaccine!by!deep!subcutaneous!injection!
. Fever:!should!be!deferred!till!recovery! !
. History!of!GBS!developed!within!6!weeks!after!receiving!influenza!vaccine!!
!
Side!effects!(usually!well!tolerated)!
. Occasional!soreness,!redness!or!swelling!at!injection!site!
. Flu.like! symptoms:! fever,! muscle! /! joint! pain! &! tiredness! beginning! 6–12! hours! after!
vaccination!and!lasting!up!to!2!days !
o If!fever!or!discomforts!persist,!please!consult!your!doctor!
. Rare!but!severe!adverse!reactions!
o GBS!(rare:!1.2!in!1!million)! !
o Inflammation!of!brain!membranes!or!brain!disease!(1!in!3!million)!!
o Severe!allergic!reaction!(9!in!10!million):!e.g.!hives,!swelling!of!the!lips!/!tongue,!and!
difficulties!in!breathing!!
o Rare!and!require!emergency!medical!attention!
Antibiotics+
Augmentin+(amoxicillin+++clavulanate)+
. Excreted!by!renal!route!"!concentrate!in!urine!"!lower!dose!for!UTI!than!other!infections!
!
Route!&!dosage!(bioavailability!similar!in!oral!&!IV!"!same!efficacy)!
. Oral:!1g!
. IV:!1.2g!
. Syrup:!914mg!(formula!of!457mg/5ml)!!

Sulperazon:+Cefoperazone+++sulbactum+
. 3rd!generation!Cephalosporins!+!β.lactamase!
. Cover!Pseudomonas!
. Has!side!chain!similar!to!warfarin!"!inhibit!vit!K!epoxide!reductase!"!hypothrombinemia!
(↑!INR)!in!~10%!patients!
o Give!Vit!K1!with!it!in!the!beginning!(1!dose)/!close!monitoring!of!INR!

Vancomycin+
Route!&!rate!
. Cannot!be!absorbed!nor!released!in!gut!
o For!C.!difficile!"!give!oral!(125mg!QID)!
o For!MRSA!"!give!IV!(systemic)!
. IV:!slow!infusion!over!60min,!because!
o High!incidence!of!pain!&!thrombophlebitis!
o Avoid!infusion!reaction:!red!man!syndrome!
! Flushing!&!erythematous!rash!affecting!face,!neck!&!upper!torso!
! Due!to!non.specific!mast!cell!degranulation!but!not!IgE.mediated!allergic!
reaction!
! May!also!have!hypotension!and!angioedema!!
! Rx!/!prevention:!antihistamines!(e.g.!diphenhydramine)!
!
Side!effects!
. General:!hypersensitivity,!GI!upset!
. Specific:!red!man!syndrome!
o Mx:!stop!infusion!(as!DDx!=!hypersensitivity),!then!resume!in!slower!infusion!rate!
!
!

Infectious!Disease!.!16!
TDM!
. AUC/MIC!correlate!best!with!clinical!efficacy:!target!≥400!
. Trough!level!(pre.dose):!surrogate!marker!for!AUC!
o Obtained!just!before!next!dose!at!steady!state!(4th!dose!if!normal!RFT)!
o Should!always!>10mg/L!to!avoid!development!of!resistance!
o Also!used!to!monitor!S/E!(nephrotoxicity)!
! If!level!high!"!stop!it!"!
• Check!RFT,!rehydrate!the!patient!!
• Recheck!the!level,!restart!when!fall!back!to!therapeutic!range!"!
lengthened!by!spacing!out!dose!/!↓!dose!

Linezolid+
. Against!G+ve!bacteria,!including!VRE,!MRSA!
. For!skin!&!soft!tissue!infection,!also!pneumonia!(e.g.!HAP)!

Gentamicin+
. Aminoglycosides!
. t½:!2.3!hours!if!normal!RFT,!prolonged!(up!to!100h)!in!renal!impairment!
. Cause!nephrotoxicity!!!Monitor!RFT!
!
TDM!
. Cmax/MIC!correlate!best!with!clinical!efficacy!
. Multiple.daily!dosing!
o Peak!(30min!after!end!of!infusion)!+!trough!(within!30min!before!next!dose)!
o Or!trough!level!only!
! Most!achieve!therapeutic!target,!except!in!obese,!burns!&!critically!ill!patients!
. Once.daily!dosing!
o Random!but!timed!sample!collected!6.14h!after!infusion!"!use!nomogram!to!
determine!subsequent!dosing!interval!

AntiXpseudomonas+
Broad.spectrum!anti.pseudomonal!
. Penicillin:!Piperacillin/tazobactam!(Tazocin)!
. Cefphalosporon!(cross!reaction!with!penicillin!<8%)!
o 3rd!generation!
! Ceftazidine!(Fortum)!
! Cefoperazone/sulbactum!(Sulperazone):!only!available!in!Asia!!
o 4th!generation:!cefepime!(IV)!
. Carbapenem!(may!still!cross.react!with!penicillin!allergy):!meropenem!!
!
Other!anti.Pseudomonals!
. Fluoroquinolone!
o Ciprofloxacin:!not!cover!anaerobes!
o Levofloxacin:!weaker!action!against!pseudomonal,!have!moderate!anaerobic!
coverage,!but!not!used!as!monotherapy!as!treatment!
. Aminoglycoside!(e.g.!gentamycin):!no!anaerobic!coverage!
Tutorial:+case+study!by!Dr!Grace!Lui!6/12/2013!
Case!1!
58/M!
Presented!with!oral!lesions!&!discomfort!
. Onset!2!weeks!ago!
. Multiple!lesions!over!whole!upper!roof!of!mouth!
!

Infectious!Disease!.!17!
. Not!painful,!no!dysphagia!
. No!fever!
P/E:!white!streaks!&!patches!over!on!hard!&!soft!palate!&!throat!
Dx:!candidiasis!
!
Hx!
. Any!DM!
. PMH!!
o Immunocompromised,!e.g.!risk!factors!of!HIV!infection!
. Drug!Hx!!
o Steroid!use,!esp!inhaled!steroid!
! E.g.!OTC!drugs!for!bone!pain,!joint!pain!
o Immunosuppressant,!chemo!
o TCM!
o Recent!use!of!antibiotics!
!
Investigation!
. Swab!of!lesion:!candida!albicans!
. Urine!for!glucose!
. (Test!for!HIV)!
!
Treatment!
. Oral!fluconazole!
. Nystatin!(drops)!
!
1!month!later!
. Generalized!weakness!&!weight!loss!
. Desaturation!requiring!1L!O2!supplement!
. CXR:!peri.hilar!infiltrate!
!
Investigation!
. CBC:!mildly!anemic!(NcNc),!WCC!&!platelet!normal!
. L/RFT!normal!
. Sputum!culture:!oral!commensals!
. HIV:!+ve!
. CD4!count:!7!
!
DDx!
. Pneumocystis!jirovecii!pneumonia!(PCP)!
o Toluidine!Blue!O!staining!!
o Pneumocystis!carinii!stain!(silver!stain)!
o *Used!induced!sputum!/!bronchoalveolar!lavage!
! Nebulized!hypertonic!saline!(5.85%!NS)!to!induce!sputum!
• Yield!in!expectorated!sputum!is!too!low!
! Send!for!both!stain!to!increase!sensitivity!
o ±!PCR:!but!sometimes!over.sensitive!
!
While!waiting!for!the!results,!patient!develop!further!desaturation!&!respiratory!failure!
. DDx!
o Progressive!pneumonia!without!treatment!
o PCP!may!cause!cysts!"!pneumothorax!(esp!if!done!bronchoscopy!for!transbronchial!
biopsy)!
!

Infectious!Disease!.!18!
 ! Cysts!may!be!seen!in!CXR/CT!as!ground.glass!appearance!
o Transient!inflammatory!response!induced!by!bronchoscopy!
!
Treatment!for!PCP!
. Steroid!before!1st!dose!of!co.trimoxazole!(septrin),!cover!whole!septrin!course!but!with!
tappered!dose!
o Co.trimoxazole!cause!lysis!of!PCP!"!more!severe!inflammatory!response!in!lung!
(paradoxical!respiratory!failure)!
. Co.trimoxazole!(trimethroprim.sulphamethoxazole)!
o R/o!G6PD!deficiency,!sulpho.group!allergy!
o If!resp!failure!"!don’t!wait!for!G6PD!result!to!come!back,!monitor!Hb!level!for!
hemolysis!closely!
!
G6PH!deficiency!
. Quinolone!
. Dapsone:!used!for!leprosy,!PCP!prophylaxis!
. Primaquine:!anti.malarial!
!
Treated!PCP!&!started!HAART!&!PCP!prophylaxis!
Persistent!low!grade!fever!after!discharge!
. Multiple!bilateral!nodules!at!bilateral!lung!in!CT!thorax!
. Enlarged!LN!in!mediastinum!
!
DDx!of!lung!nodules!in!IC!patients!!
. Residual!disease!of!PCP!
. TB!
. MAC:!mycobacterium!avium!complex!
o Can!cause!disseminated!disease!including!pulmonary!nodules!
. Fungal!infection:!aspergillosis,!cryptococcus,!penicilliosis!(dimorphic!fungus,!mainly!in!
Asian)!
. Malignancy!
o Kaposi!sarcoma:!HHV.8!
! Purplish!vascular!type!of!skin!lesions!
! Can!also!cause!LN,!pulmonary,!gastric!lesions!
o Lymphoma!
! Non.Hodgkins!lymphoma,!Burkitt’s!lymphoma,!other!lymphoma!(e.g.!CNS)!
Ix!
. Bronchoscopy!for!biopsy!x!LN,!histology!&!culture!
. EUS!
!
Case!2!
45/M!presented!with!fever!&!confusion!for!few!days!
. Fever!with!2.3!weeks!with!flu!symptoms!
o Intermittent!fever,!don’t!know!exact!temperature!
o No!cough!
o No!dizziness!/!weakness!
o Visited!GP!2.3!times!for!flu.like!symptoms,!given!medications!without!improvement!
. Confusion!for!3.4!days!
. Good!past!health!
!
Physical!exam!
. GCS!14,!mainly!disoriented!
!

Infectious!Disease!.!19!
. No!focal!neurological!signs!
. No!meningism!
. No!skin!rash!
o Look!for!generalized!non.blanchable!purplish!MP!rash,!typically!start!from!lower!
limbs:!meningococcus!
. No!murmur!(IE!can!cause!septic!emboli!to!brain)!
!
Investigation!
. CBC,!L/RFT!normal!
. Blood!culture!
. CT!brain!/!MRI:!patient!has!confusion,!also!r/o!C/I!for!LP!
. LP!
o Clear!appearance!
o Cell!count:!WCC!400!(polymorph!60%,!lymphocytes!40%),!RCC!10!
! Polymorph:!lymphocytes!is!~50:50!"!not!very!accurate!
o CSF!glucose:!0.4!
o CSF!TP!3.4!
o Gram!stain!–ve!
o AFB!stain!–ve!!
!
Bacterial!vs!TB!meningitis!
. Onset!
o Subacute!onset!"!more!likely!TB!
! But!can!also!be!partially!treated,!need!to!ask!whether!the!GP!gave!A/B!to!pt!
. Contact!Hx!of!TB,!past!Hx!of!TB!
o If!patient!has!past!Hx!of!TM!"!may!be!TB!reactivation!
o But!if!patient!has!beed!adequately!treated!"!seldom!reactivation!
o FHx!of!TB!(genetic!factor:!polymorphism)!
. Constitutional!symptoms!of!TB!
o Nigh!sweat,!weight!loss!
. CXR!
o Bilateral!upper!lobe!patchy!&!nodular!lesions,!homogenous!
. Can!do!TB!PCR!on!CSF!
!
DDx:!fungal!meningitis!(cryptococcal)!
. India!stain!
. Latex!agglutination!on!Cryptococcus!antigen!on!blood!&!CSF:!very!sensitive!
. Clinical!picture!similar!to!TB!
. CXR:!more!discrete!lung!nodules!than!TB!
!
Think!about!encephalitis!(HSV,!japanese!encephalitis)!due!to!confusion!!
. Although!late!meningitis!can!also!cause!confusion!
. Viral!cause!usually!won’t!cause!such!abnormality!in!CSF!protein!&!glucose!"!less!likely!to!be!
viral!causes!
. "!!
o Japanese!encephalitis!(typically!thalamic!encephalitic!change):!need!paired!serology!/!
CSF!serology!
o Enterovirus,!HSV1,!HSV2,!VZV!
!
Dx:!TB!meningitis!confirmed!by!TB!PCR!
Treatment!
. Watch!out!for!increased!ICP!
!

Infectious!Disease!.!20!
. Steroid!cover:!to!decrease!inflammatory!response!
o Dexamethasone!for!1st!few!weeks,!tapering!dose!
o ↓!risk!of!hearing!deficit!(TB!usually!basal!meningitis)!
o ↓!mortality!of!TB!meningitis!
o (For!bacterial!meningitis:!given!dexa!before!/!with!1st!dose!of!A/B,!for!4!days,!only!for!
pneumococcal!meningitis!because!↓!in!mortality!is!only!evidence!based!for!
pneumococcal)!
o (Also!need!steroid!for!TB!pericarditis,!to!↓!risk!of!constricting!pericarditis)!
. Anti.TB!x!9.12!months!
o Not!common!to!use!streptomycin!now!
! Highest!resistance!rate!(~10%)!
• Vs!rifampicin:!~2.3%!
! Need!IMI!
. Vit!B6!
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Infectious!Disease!.!21!