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Course Instructors: Dr. Francis, Dr. Wolf and Dr.

Bautista
Hemostasis
Lymphoma & Leukemia
251
Amino Acids
Biochemistry
Endocrinology
Neurophysiology
Hematology
Vitamins, Minerals, Trace Elements
Cellular Physiology
Membrane Physiology
244
Low Energy State
Inflamation
Nephritic-Nephrotic
254
248
218
Reproductive Endocrinology
Renal Physiology
76
159
171
192
220
Gastrointestinal Physiology (GI) 135
5
45
53
55
80
87
64
71
105
116
125
Electrolyte Physiology
Pulmonary Physiology
Neuromuscular Physiology
Vascular Physiology
Cardiac Physiology
Page Lecture
Note Pages
Welcome to the Program
Rheumatology
238
PASS PROGRAM
USMLE REVIEW STEPS 1, 2 AND 3
Course Instructors: Dr. Francis, Dr. Wolfe & Dr. Bautista
184
1
Anabolic Pathways
Cancers
Immunodeficiencies
Lymphocytes
Leukocytes
Immunology
Catabolic Pathways
Protein Structure and Function
Enzymes
Microbiology
Antibiotics
Granulocytes
Biochemistry, Glycolysis,
Gluconeogenesis & TCA
Viruses
497
515
Antibiotics (Dr. Cordova)
Surgery & Trauma (Dr. Cordova)
413
453
477
408
292
303
329
335
344
371
262
277
282
351
358
369
Obstectrics and Gynecology
Note Pages
The Four Hypersensitivities 366
2
PASS PROGRAM
USMLE REVIEW STEPS 1, 2 and 3
Week 1 Monday Tuesday Wednesday Thursday Friday
Introduction Behavioral science Test taking/Time mgt. Membrane Phys Cardio Pathology
7:15-9:00 am Low Energy State EKG Phys Cardiac Phys

7:15 9:00 am Low Energy State EKG Phys Cardiac Phys
1 hr break Vitamins Psychiatry Arrhythmias Murmurs
10:00-12:00 Minerals Endocrine Phys
Trace elements Endo Path
LUNCH
1:30-4:00pm Cellular Phys Psych Endo Neuromuscular Cardio
Vascular Phys
Week 2 Monday Tuesday Wednesday Thursday Friday
Gastrointestinal Surgery Principals Pulmonary phys Renal Phys Neuro Phys
7:15-9:00 Physiology
1 hr break Trauma Pulm Path Renal Path Neuro Path
10:00-12:00 GI Path
LUNCH LUNCH
1:30-4:00pm
GI Ansthesia Pulm Renal Neurology
Week 3 Monday Tuesday Wednesday Thursday Friday
Amino Acids OB Glycolysis Ketogenesis Nucleotides
7:15-9:00 Protein structure Gluconeogenesis Glycogen 7:15 9:00 Protein structure Gluconeogenesis Glycogen
1 hr break Protein function GYN Fructose/Galactose Pentose Pathway
10:00-12:00 OB/GYN Pharm Pyruvate metab.
LUNCH
1:30-4:00 pm Quaternary protein Reproductive TCA cycle Amino acids DNA
Repro Pharm Lipolysis Fatty acid synth.
Week 4 Monday Tuesday Wednesday Thursday Friday
Oncology Pediatricts Leukocytosis Rheumatology Myobacteria, Spiro.
7:15-9:00 Development Leukemia's Rickettsia
1 hr break Myelodysplasia Normal Flora Virus
10:00-12:00 Pediatricts Pharm Gram+/-
LUNCH
O l I l G l t F Oncology Immunology Granulocytes Fungus
1:30-4:00pm Imm. Deficiency Hypersensitivities Parasites Closing remarks!!!
Transplantation Protozoa
Dr. Francis
Cellular physiology
Dr. Wolf
Time management
Teaching Associates
Antibiotics- Dr Cordova (date TBA)
Cellular physiology
Behavioral
Cardiology
Pulmonary
Biochemistry
Reproductive
Immunology
Pediatricts
Oncology
Time management
Endocrine
Rheumatology
Gastrointestinal
Renal
Neurology
Microbiology/Antibiotics
OB/GYN
Antibiotics Dr Cordova (date TBA)
Surgery/Ansthesia- Dr Cordova
Hematology- Dr Qi (date TBA)
Statistics- Dr Qi (date TBA)
DNA/RNA- Dr Bautista
Biochem pathways- Dr Lee

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44 44
4/30/2008
1
Making the most
out of your time
here at the PASS
program !!!
Making the most
out of your time
here at the PASS
program !!!
Study smart
not hard
Study smart
not hard
Power is in
knowledge !
Power is in
knowledge ! gg
NBME- National Board
of Medical Examiners
NBME- National Board
of Medical Examiners
For For
profit
company
NBME- National Board
of Medical Examiners
NBME- National Board
of Medical Examiners
Shortage of family
doctors throughout
US
Shortage of OB/GYN
physicians in Fl,
Shortage of family
doctors throughout
US
Shortage of OB/GYN
physicians in Fl, p y
Texas, California, and
Michigan
Cutoff for USMLE
Steps were raised
from 182 to 185?
p y
Texas, California, and
Michigan
Cutoff for USMLE
Steps were raised
from 182 to 185?
Youre the next cutting edge
physician
20,000 new residents
Your pay?
Youre the next cutting edge
physician
20,000 new residents
Your pay?
What do you want to do when
you finish medical school?
What do you want to do when
you finish medical school?
p y
Radiology, Dermatology,
Ortho.
Those making decisions,
control how many come
across the bridge
p y
Radiology, Dermatology,
Ortho.
Those making decisions,
control how many come
across the bridge
45
4/30/2008
2
Why do so many fail the
test?
Why do so many fail the
test?
ZOO
THEORY THEORY
A physician sits and writes a question based
off of the discipline they want to test you on
A h l i t d th ti th
A physician sits and writes a question based
off of the discipline they want to test you on
A h l i t d th ti th
How do they comprise a test
that is written for you to fail?
How do they comprise a test
that is written for you to fail?
A psychologists rewords the question the way
your mind thinks
This is why the wrong answers always look
good
A psychologists rewords the question the way
your mind thinks
This is why the wrong answers always look
good
5 PASS rules in answering
question
5 PASS rules in answering
question
1. Cover the answers
2. Read the last sentence and decide if
it is a clue or concept
1. Cover the answers
2. Read the last sentence and decide if
it is a clue or concept
5 PASS rules in answering
question
5 PASS rules in answering
question
1. Cover the answers
2. Read the last sentence and decide if it is
a clue or concept question
1. Cover the answers
2. Read the last sentence and decide if it is
a clue or concept question
it is a clue or concept
question
3. Read the vignette, and isolate the
facts of the vignette
4. Comprise a thought process
5. Look down, click and move !!!!!!!
it is a clue or concept
question
3. Read the vignette, and isolate the
facts of the vignette
4. Comprise a thought process
5. Look down, click and move !!!!!!!
3. Read the vignette, and isolate the facts
of the vignette
4. Comprise a thought process
5. Look down, click and move !!!!!!!
3. Read the vignette, and isolate the facts
of the vignette
4. Comprise a thought process
5. Look down, click and move !!!!!!!
A 38 y/o woman has congestive heart failure,
premature ventricular contractions and
repeated episodes of ventricular tachycardia.
Her blood pressure is normal and there are no
murmurs. Her heart is markedly enlarged.
A 38 y/o woman has congestive heart failure,
premature ventricular contractions and
repeated episodes of ventricular tachycardia.
Her blood pressure is normal and there are no
murmurs. Her heart is markedly enlarged.
Coronary angiography shows no abnormalities.
Which of the following is the
most likely diagnosis ?
Coronary angiography shows no abnormalities.
Which of the following is the
most likely diagnosis ?
A.Acute rheumatic fever
B.Congenital fibroelastosis
C.Constrictive pericarditis
D.Myocardial infarction
A.Acute rheumatic fever
B.Congenital fibroelastosis
C.Constrictive pericarditis
D.Myocardial infarction
E.Primary cardiomyopathy E.Primary cardiomyopathy
A.Acute rheumatic fever
B.Congenital fibroelastosis
C.Constrictive pericarditis
D.Myocardial infarction
A.Acute rheumatic fever
B.Congenital fibroelastosis
C.Constrictive pericarditis
D.Myocardial infarction
E.Primary cardiomyopathy E.Primary cardiomyopathy
46
4/30/2008
3
USMLE Step 2 and Step 3 approach USMLE Step 2 and Step 3 approach
What is the next best step in management?
Is the patient stable? (based on hemodynamics)
- Unstable: ABCs
- Stable: read the vignette
What is the next best step in management?
Is the patient stable? (based on hemodynamics)
- Unstable: ABCs
- Stable: read the vignette
Do you have enough information to make a
definitive diagnosis?
- Yes- treat
- No- order a test (BLIS)
blood/labs/image/surgery
Do you have enough information to make a
definitive diagnosis?
- Yes- treat
- No- order a test (BLIS)
blood/labs/image/surgery
A 23 y/o man who is HIV positive has a 2 week
history of midsternal chest pain that is aggravated
by eating spicy foods; the pain is unrelated to
exertion or position and he reports no dysphagia.
Treatment with H2 receptor blocking agents has
provided no relief. He takes clotrimazole for
thrush and zidovudine (AZT). He has a CD4+ T
A 23 y/o man who is HIV positive has a 2 week
history of midsternal chest pain that is aggravated
by eating spicy foods; the pain is unrelated to
exertion or position and he reports no dysphagia.
Treatment with H2 receptor blocking agents has
provided no relief. He takes clotrimazole for
thrush and zidovudine (AZT). He has a CD4+ T ( )
lymphocyte count of 220/mm3 (N>500).
Which of the following is the most
appropriate next step in
management?
( )
lymphocyte count of 220/mm3 (N>500).
Which of the following is the most
appropriate next step in
management?
A.Therapeutic trial of acyclovir
B.24 Hour pH probe
C.Acid perfusion test
D.Esophageal manometry
A.Therapeutic trial of acyclovir
B.24 Hour pH probe
C.Acid perfusion test
D.Esophageal manometry
E.Esophagoscopy E.Esophagoscopy
A.Therapeutic trial of acyclovir
B.24 Hour pH probe
C.Acid perfusion test
D.Esophageal manometry
A.Therapeutic trial of acyclovir
B.24 Hour pH probe
C.Acid perfusion test
D.Esophageal manometry
E.Esophagoscopy E.Esophagoscopy
Procrastination in doing
questions
Procrastination in doing
questions
How many read before doing
questions?
Wh t t ti ?
How many read before doing
questions?
Wh t t ti ? What are you testing ?
2 weeks later, what
happens?
What are you testing ?
2 weeks later, what
happens?
Procrastination in doing questions Procrastination in doing questions
How many read all the choices
in the explanation?
f
How many read all the choices
in the explanation?
f Prior exposure to future
questions
I have a lot of
details in my head
Prior exposure to future
questions
I have a lot of
details in my head
47
4/30/2008
4
Procrastination in doing
questions
Procrastination in doing
questions
How many do the questions
in tutor mode?
How many do the questions
in tutor mode?
Driving a car
and lost
Driving a car
and lost
Its ok to be wrong !!!! Its ok to be wrong !!!!
Block of 50 question and get
45/50 correct, are you any more
prepared for the boards from the
moment you started that test?
Block of 50 question and get
45/50 correct, are you any more
prepared for the boards from the
moment you started that test?
If you get 30 /50 wrong, you will
not be very happy
Found a hole, that can be fixed
Remember every time you fall
If you get 30 /50 wrong, you will
not be very happy
Found a hole, that can be fixed
Remember every time you fall
Why do we not listen to our first
thought?
Why do we not listen to our first
thought?
We are scared of being wrong We are scared of being wrong
We do not want our over all
average to be lower than the mean
We do not want our over all
average to be lower than the mean
My friends told me to do as
many questions as I can
before I take the test
My friends told me to do as
many questions as I can
before I take the test
6000 questions
Multiple banks
You are doing questions to learn
from them
Do we order test to learn about a
pathology
(i.e. Hypothyroidism TSH panel)
6000 questions
Multiple banks
You are doing questions to learn
from them
Do we order test to learn about a
pathology
(i.e. Hypothyroidism TSH panel)
3 steps to studying:
1. Obtain the information
2. Questions
3. Results of the bank
3 steps to studying:
1. Obtain the information
2. Questions
3. Results of the bank
Questions: Organ system based
50 question
Questions: Organ system based
50 question
Do they ask you 50 new things?
Pathological presentation does not
change, just the story line (clues are
so important)
Will you see the pattern in mixed
blocks?
Do they ask you 50 new things?
Pathological presentation does not
change, just the story line (clues are
so important)
Will you see the pattern in mixed
blocks?
What bank to use? What bank to use?
Q-Bank USMLE Rx. USMLEworld Q-Bank USMLE Rx. USMLEworld
Do you see a pattern?
At the end of your first week,
you will be evaluated by several
tutors to determine which is the
best test bank for you to use.
Do you see a pattern?
At the end of your first week,
you will be evaluated by several
tutors to determine which is the
best test bank for you to use.
48
4/30/2008
5
What should I do, with the
results of my question bank?
What should I do, with the
results of my question bank?
50 questions completed
(what is right or wrong)
Example: Polyhydramnios: Down syndrome
50 questions completed
(what is right or wrong)
Example: Polyhydramnios: Down syndrome Example: Polyhydramnios: Down syndrome
What is the most common cardiac
abnormality?
Write the subject matter
Look for patterns in the question
This is what you will read about
Example: Polyhydramnios: Down syndrome
What is the most common cardiac
abnormality?
Write the subject matter
Look for patterns in the question
This is what you will read about
What do most students do What do most students do
Vignette.. Downs syndrome
Answer: Endocardial cushion defect
Read about it from the author
Transcribe to note cards on ECD
Vignette.. Downs syndrome
Answer: Endocardial cushion defect
Read about it from the author
Transcribe to note cards on ECD Transcribe to note cards on ECD
Read the notes about ECD
Read the CMDT about ECD
Harrisons and read about ECD
Are you any more prepared for
Downs syndrome on the boards?
Transcribe to note cards on ECD
Read the notes about ECD
Read the CMDT about ECD
Harrisons and read about ECD
Are you any more prepared for
Downs syndrome on the boards?
NBME practice exam NBME practice exam
On line at http://www.NBME.org
Step 1 5 forms (do not take form 3)
Step 2 3 forms
On line at http://www.NBME.org
Step 1 5 forms (do not take form 3)
Step 2 3 forms
Step 3 1 form
When should I take
may NBME ?
Step 3 1 form
When should I take
may NBME ?
Not enough time in the day !!!!!!!
- Exercise
- 210 score
- Proper sleep hygiene - Proper sleep hygiene
-Take time out to
reward yourself
PASS program clues vs. class notes PASS program clues vs. class notes
You should drill the PP-clues with a
partner for at least 1 hour a night.
( hour new, hour random review)
You should drill the PP-clues with a
partner for at least 1 hour a night.
( hour new, hour random review)
Caution in drilling class notes:
Teacher vs. Student
Caution in drilling class notes:
Teacher vs. Student
Tutoring: Tutoring:
This is your time to ask questions that
you may have with the material
Do questions with your tutor (remember
This is your time to ask questions that
you may have with the material
Do questions with your tutor (remember Do questions with your tutor (remember
its ok to be wrong)
Your tutor is there to help
you find and fix your weakness
Do questions with your tutor (remember
its ok to be wrong)
Your tutor is there to help
you find and fix your weakness
49
4/30/2008
6
Tutoring cont. Tutoring cont.
Try several tutors to find the chemistry that
works for you
If you can not make it to your secession, please
inform your tutor, so they can fill the spot with
another student
Try several tutors to find the chemistry that
works for you
If you can not make it to your secession, please
inform your tutor, so they can fill the spot with
another student
Once you are comfortable with a
couple of tutors, there is a request
book in the back.
(The key word, just a request book)
Once you are comfortable with a
couple of tutors, there is a request
book in the back.
(The key word, just a request book)
50







Physiology:
Weeks One & Two
51 51
52 52
1
INTRODUCTION: THE MOST
POWERFUL CONCEPT IN
MEDICINE
THE LOW ENERGY STATE
WHO USES ENERGY?
BRAIN
MUSCLES
PRIMARY ACTIVE TRANSPORT
HEART
MEMBRANE MOVEMENT
RAPIDLY DIVIDING CELLS
SKIN
HAIR
GI
RESPIRATORY
RENAL(PCT)
BLADDER
ENDOMETRIUM
ENDOTHELIUM
BREASTS
SPERM
GERM CELLS
CUTICLES
BONE MARROW
RED BLOOD CELLS
WHITE BLOOD CELLS
PLATELETS
PRESENTATION OF A DISEASE
When it bothers the patient enough, he or
she will see the doctor as soon as possible
Weakness so that the patient can not go to
work
Shortness of breath scares people; they think
they might die
SIGNS OF DISEASE: WHAT YOU
CAN SEE
TACHYPNEA and DYSPNEA
SYMPTOMS: THE PATIENTS
COMPLAINTS
WEAKNESS
SHORTNESS OF BREATH
MOST COMMON INFECTIONS
PULMONARY INFECTIONS
URINARY TRACT INFECTIONS
53 53
2
OTHER COMPLICATIONS
Dry skin
Hair dry and brittle
Nails brittle
Bone marrow suppressed
Anemia
Leukopenia
Thrombocytopenia
COMPLICATIONS, cont
Endothelium atrophic
Endometrium
atrophic
Breasts atrophic
Sperm count low
GI nausea, vomiting
and diarrhea
Renal- PCT shuts
down
Bladder atrophic;
leads to UTIs
Respiratory weak
cough > infections
Germ cells unable to
replicate > leads to
skin and GI cancers
CNS: MR (children)
and dementia (adults)
CV heart failure
MOST COMMON CAUSE OF DEATH?
HEART FAILURE!!!
ANYTIME YOU CAN CONNECT TO THE LOW
ENERGY STATE
APPLY THE ENTIRE CONCEPT
THIS ACCOUNTS FOR
APPROXIMATELY 98% OF ILLNESSES
WHENEVER IN DOUBT > ASSUME IT IS
A LOW ENERGY STATE
STOP GUESSING!!!
54 54
VITAMINS, MINERALS and
TRACE ELEMENTS
THE BEGINNING
Vitamin A
A cofactor for PTH
Necessary for CSF production
Used for epithelial maturation, especially
hair, skin, and eyes
Most unique function is night vision
A mild antioxidant
Vitamin A deficiency
Poor night vision
Decreased CSF production: asymptomatic
Hypoparathyroidism
Epithelial cells fail to mature
Vitamin A excess
Pseudotumor cerebri: excess CSF
production
Hyperparathyroidism: moans, groans,bones
and stones
Pseudotumor Cerebri
Sign: papilledema
Symptom: headache
Evaluation: CT scan ( shows enlarged
ventricles)
Treatment: d/c vitamin A; serial LPs (30cc at a
time)
Main complication: blindness
This is the only cause of increased ICP where
you dont have to worry about herniation
Vitamin B1: Thiamine
Necessary for four important enzymes:
Pyruvate dehydrogenase
Alpha-ketogluterate dehydrogenase
Branched chain amino acid dehydrogenase
Transketolase
55 55
Thiamine Deficiency
Beriberi
Dry beriberi
Wet beriberi
Wernickes Encephalopathy
Receptive aphasia
Wernicke-Korsakoff syndrome
Mamillary bodies now also involved
Confabulation
Inability to move short-term memory to long-term
memory
Vitamin B2: Riboflavin
Used in cofactors ( FAD)
Best source is milk
Sunlight breaks riboflavin down
Riboflavin deficiency
Angular Cheilosis
Vitamin B3: Niacin
Necessary for cofactors ( NAD, NADH,
NADP, NADPH)
Needed by pyruvate dehydrogenase,
alpha-ketogluterate dehydrogenase, and
branched chain amino acid
dehydrogenase
Niacin deficiency
Pallegra : 4 Ds diarrhea, dermatitis,
dimentia and death
Hatnups disease: presents just like pallegra
Defective renal transport of tryptophan
Vitamin B4: Lipoic acid
Needed by pyruvate dehydrogenase,
alpha-ketogluterate dehydrogenase, and
branched chain amino acid
dehydrogenase
No deficiency state
56 56
Vitamin B5: Panthotenic Acid
Needed by pyruvate dehydrogenase,
dehydrogenase, alpha-ketogluterate
dehydrogenase, and branched chain
amino acid dehydrogenase
No deficiency state
Vitamin B6: Pyridoxine
Needed by all transaminases
INH pulls pyridoxine out of the body
Forms the cofactor pyridoxalphosphate
Pyridoxine deficiency
neuropathy
Vitamin B9: Folate
The first vitamin to run out whenever you
have rapidly dividing cells
Used to make tetrahydrofolate (THF) from
which you make nucleotides
Folate deficiency
Megaloblastic anemia
Hypersegmented neutrophils
Neural tube defects in fetuses
Mcc: overcooked vegetables
Vitamin B12: Cyanocobalamin
Needed by two enzymes:
Homocysteine methyltransferase
Methylmalonyl-CoA mutase
Used to make tetrahydrofolate
Used to recycle odd-numbered carbon
fatty acids
57 57
Vitamin B12 deficiency
Megaloblastic anemia
Hypersegmented neutrophils
Neuropathy, especially involving the dorsal
column pathways and corticospinal tracts
Mcc: pernicious anemia (type A gastritis)
Vitamin C
Used for hydroxylation
Hydroxylates proline and lysine in collagen
and elastin
Main antioxidant in the GI system
Vitamin C deficiency
Scurvy
Bleeding from hair follicles and gums
Vitamin D
Necessary for bone and teeth formation
Stimulates osteoblastic activity
Stimulates calcium AND phosphorous
absorption and reabsorption
Mineralizes bones and teeth
Vitamin D deficiency
Rickets: in children
Lateral bowing of the legs
Osteomalacia: in adults
Vitamin D resistant rickets
Defective renal reabsorption of phosphorous
As phosphorous leaks out, it pulls calcium
with it
Vitamin E
The main antioxidant in your blood
Absorbs free radicals
58 58
Diseases involving oxidation
Cancer
Alzheimers disease
Coronary artery disease
Hemolytic anemia ( esp. G6PD)
Antioxidants
Vitamin E: in blood
Vitamin C: in GI tract
Vitamin A
Beta-Carotene
Biotin
Necessary for carboxylation
Biotin deficiency
Many carboxylases would lose their
function
Vitamin K
Needed for gamma-carboxylation
Adds a third (gamma) carboxyl group to
the vitamin k dependent clotting factors
Clotting factors II, VII, IX, X, Protein C &
Protein S
Protein C has shortest half life, followed by
factor VII
Warfarin
Competitive inhibitor of vitamin K
Given orally
Always give heparin first
Crosses the placenta
Teratogenic
Follow PT ( prothrombin time )
INR 2 to 3x normal
59 59
Heparin
Acts as a cofactor for antithrombin III
Blocks thrombin, as well as clotting factors
IX, X, XI, and XII
Follow by measuring PTT ( INR 2 3X NL)
To reverse the action: protamine sulphate
If patient acutely bleeding: give FFP to
reverse immediately
What are germs good for?
Vitamins related to gut flora
They make: 90% of vitamin K
Biotin
Folate
Panthotenic acid
They help absorb
Vitamin B12
MINERALS
Minerals
Calcium
Magnesium
Zinc
Copper
Iron
Calcium
Intracellular calcium needed for all muscle
contraction
Smooth muscle uses extracellular calcium
for second messenger systems
Atrium is ONLY membrane that uses
calcium to depolarize
Cardiac ventricle depends on extracellular
calcium to trigger off its intracellular
calcium release
60 60
Calcium, cont
Used for axonal transport
Presynaptic influx of calcium necessary for
release of ALL neurotransmitters
Needed for normal bone and teeth
development
Magnesium
A cofactor for ALL kinases
A cofactor for PTH
Interacts with potassium as well, but
location currently unknown
Zinc
Needed by hair, skin, sperm and taste
buds
Zinc deficiency: dysguisia
Copper
Needed by lysine hydroxylase in the
formation of collagen
Also needed by complex IV of electron
transport system
Copper excess
Wilsons disease
Autosomal recessive
Ceruloplasmin deficiency
Copper deposition in lenticular nucleus (basal
ganglia), iris (Kayser-Fleischer rings) and in
the liver (causing cirrhosis)
Tx: penicillamine
Movement disorder in a middle-
aged person
HUNTINGTONS
DISEASE (90%)
Autosomal dominant
Trinucleotide repeats
Involves caudate
nucleus
Has anticipation
Treat with
antipsychotics
Mcc of death: suicide
WILSONS DISEASE
Autosomal recessive
Ceruloplasmin def
Copper deposition in
lenticular nucleus, liver
and iris
Treat: penicillamine
61 61
Trinucleotide repeats
Huntingtons disease
Fragile X
Fredriecks ataxia
Prader Willi syndrome
Myotonic dystrophy
Iron
Needed for formation of heme and
hemoglobin
Ferrous iron binds oxygen
Needed by complex III and IV of electron
transport system
And finallythe trace elements Trace Elements
Chromium
Selenium
Molebdenum
Manganese
Tin
Flouride
Chromium
Enhances insulin action
Def: causes diabetes
Selenium
Needed primarily by the heart
Excess: breath smells like garlic ( arsenic
as well)
Def: dilated cardiomyopathy
62 62
Molebdenum and Manganese
Needed by many enzymes in glycolysis
Xanthine oxidase: needs both elements
Tin
Needed for hair growth
Flouride
Needed for teeth and bone growth
Excess: blocks enolase of glycolysis
THE END
BUT, it is really the beginning
63 63
CELLULAR PHYSIOLOGY
CELL ORGANELLS
IRREVERSIBLE CELLULAR INJURY
APOPTOSIS
CELL MEMBRANE
DISSOLVES FIRST
PROGRAMMED CELL
DEATH
NONINFLAMMATORY
PYKNOSIS
KARYORHEXXIS
KARYOLYSIS
NECROSIS
NUCLEUS
DISSOLVES FIRST
UNEXPECTED
INVOLVES
INFLAMMATION
PYKNOSIS
KARYORHEXXIS
KARYOLYSIS
NECROSIS
ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE
NECROSIS
ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE
NECROSIS
ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE
64 64
NECROSIS
ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE
NECROSIS
ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE
NECROSIS
ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE
NECROSIS
ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE
NECROSIS
ISCHEMIC(COAGULATIVE)
PURULENT
GRANULOMATOUS
FIBRINOUS
CASEOUS
FAT
HEMORRHAGIC
LIQUEFACTIVE
MESS WITH THE
CHROMOSOMES
MONOSOMIES: DIE! DIE! DIE!
MCC: NONDISJUNCTION
90% IN DAD, USUALLY IN MEIOSIS 1; BUT
SPERM DIE ON A DAILY BASIS
FEWER OCCUR IN MOM; BUT MOM KEEPS
HER EGGS FOR LIFE AND IS THEREFORE
MORE LIKELY TO TRANSMIT HERS
IF ONE WERE TO SURVIVE TO BE BORN, IN
THE LEAST, THINGS WILL NOT GROW
65 65
TURNER SYNDROME
WEBBED NECK
CYSTIC HYGROMA
GONADAL STREAKS
SHIELD-SHAPED CHEST
COARCTATION OF AORTA
TRISOMIES
DIE! DIE!
FEW LIVE
TRISOMIE 13: PATAU SYNDROME
POLYDACTYLY
PALATE IS HIGH-ARCHED
PEE-ING SYSTEM ABNORMALITY
TRISOMIES
TRISOMIE 18: EDWARDS SYNDROME
ROCKERBOTTOM FEET (IN 95%)
TRISOMIES
TRISOMIE 21: DOWNS SYNDROME
MCC: NONDISJUNCTION
ROBERTSONIAN TRANSLOCATION:
HIGHEST INCIDENCE (33% OF
OFFSPRING)
HAS MANY THINGS TO CONSIDER
DOWNS SYNDROME
MENTAL RETARDATION 100%
IQ: AVERAGE IS 85 TO 100 WITH A STANDARD
DEVIATION OF 15
SUPERIOR INTELLIGENCE: IQ > 130
MILD MR: IQ < 70
MODERATE MR: IQ < 55
SEVERE MR: IQ < 40
PROFOUND MR: IQ < 25 NEEDS 24HR CARE
MILD TO MODERATE MR CAN BE TAUGHT BASIC
ADLS
66 66
DOWNS SYNDROME
EARLY-ONSET ALZHEIMER DISEASE
HIGHER FREQUENCY OF AML;BUTALL IS THE
MOST COMMON LEUKEMIA
20 TO 40% HAVE congenital heart
DISEASE
-ENDOCARDIAL CUSHION DEFECTS
VSD and ASD
VSD
ASD
DOWNS SYNDROME
CYANOTIC CONGENITAL HEART
DISEASE
TRANSPOSITION OF GREAT ARTERIES
TETROLOGY OF FALOT
DOWNS SYNDROME
50% HAVE HYPOTHYROIDISM
WIDELY-PACED CRANIAL SUTURES
MACROGLOSSIA
DUODENAL ATRESIA
HIRSCHSPRUNGS DISEASE
CLUES:
MONGLIAN SLANT TO EYES
WIDELY SPACED FIRST AND SECOND TOES
SIMIAN CREASE
TRISOMIES
XXX: Normal female; has two barr bodies
XXY: Klinefelters syndrome. Tall male
with gynecomastia, small penis and
testicles
X- Fragile X syndrome
Mcc of chromosomal induced MR
Short stature; macrochordism
Collagen disorder (increased risk of MVP)
Isolated using the drug METHOTREXATE
Chemotherapy
67 67
CHEMOTHERAPY
Stops rapidly dividing cells
Attacks the nucleus in some way
Causes irreversible cellular death
WILL kill some patients
No such thing as safe chemo
ANTIMETABOLITES
ARA-A
ARA-C
5-FU: blocks thymidylate synthetase
6-MERCAPTOPURINE: promotes gout; recognized by
xanthine oxidase
THIOGUANINE
METHOTREXATE: inhibits dihydrofolate reductase(as
does TRIMETHOPRIM and PYREMETHAMINE)
Most commonly used antimetabolite
Used to treat molar pregnancies
Used to treat STEROID RESISTANT disease( followed by
AZOTHIOPRINE and CYCLOSPORINE)
ANTIMETABOLITES
METHOTREXATE
Causes folate deficiency and megaloblastic
anemia
Give LEUCOVORIN > FOLINIC ACID to
prevent the anemia
ANTIMETABOLITES
AZOTHIOPRINE
Used for steroid resistant diseases( behind
METHOTREXATE and before
CYCLOSPORINE)
ALKYLATING AGENTS
Bind to double stranded DNA
Used primarily for slow growing cancers
Cause the most nausea and vomiting
ONDANSETRON: serotonin blocker used to treat
nausea and vomiting in chemotherapy
ALKYLATING AGENTS
Bleomycin
Busulphan
Adriamycin
Cisplatnin
Cyclophosphamide
Isophosphamide
Mitomycin
Antimycin
Acridine dyes
Hydroxyurea
Melphalan
Mechlorethamine
Procarbazine
Dacarbazine
Chlorambucil
FOR RESCUES
Desroxzasane
Mesna
68 68
MICROTUBULE INHIBITORS
Vinblastine
Vincristine
Paclitaxel
NUTRIENT DEPLETION
L-ASPARAGINASE
IMMUNEMODULATORS
LEVAMISOLE
IRREVERSIBLE CELLULAR
DEATH
NUCLEAR DAMAGE
LYSOSOMAL DAMAGE
MITOCHONDRIAL DAMAGE
OCCURS IN 6 HOURS in all tissues
69 69
IRREVERSIBLE CELLULAR
DEATH
NUCLEAR DAMAGE
LYSOSOMAL DAMAGE
MITOCHONDRIAL DAMAGE
OCCURS IN 6 HOURS in all tissues
except the brain
IRREVERSIBLE CELLULAR
DEATH
OCCURS IN 20 MINUTES IN THE BRAIN
The End?
To Be Continued
70 70
MEMBRANE PHYSIOLOGY
A MEMBRANES JOB IS NEVER
DONE
WHAT A MEMBRANE DOES
PROVIDE SHAPE
AMPHIPATHIC
HYDROPHILIC and HYDROPHOBIC
WATER SOLUBLE and FAT SOLUBLE
HYDROPHOBIC wants to be INSIDE away from
water
HYDROPHILIC wants to be OUTSIDE in contact
with water
FAT SOLUBLE COMPOUNDS
DO NOT interact with the outer cell
membrane. They go right through and
head for the nucleus
HAVE NUCLEAR MEMBRANE
RECEPTORS
Concentration gradient is only limiting
factor
STEROID HORMONES
MADE FROM CHOLESTEROL
FAT SOLUBLE( hydrophobic)
Do NOT interact with cell membrane
ALL have a nuclear membrane receptor
except CORTISOL
CORTISOL has a cytoplasmic receptor;
but it still translocates to the nuclear
membrane
71 71
WATER SOLUBLE HORMONES
HYDROPHILIC
CAN NOT simply go through a fat soluble
membrane
Must bind to the outside membrane to a
receptor
Requires a SECOND MESSENGER
But first, what about ANY water soluble
compound?
WATER SOLUBLE COMPOUNDS
Factors affecting diffusion
CONCENTRATION GRADIENT
SIZE of molecule
Net charge on molecule
pH (affects the net charge of a molecule)
THICKNESS of membrane
SURFACE AREA of membrane
FLUX (dx/dt)
REFLECTION COEFFICIENT
NUMBER OF PARTICLES RETURNED / NUMBER
OF PARTICLES SENT TO MEMBRANE
FICKS EQUATION
Factors that FAVOR diffusion go in the
NUMERATOR
Factors that NEGATIVELY affect diffusion
go in the DENOMINATOR
OTHER FUNCTIONS OF A
MEMBRANE
CREATE and MAINTAIN concentration
gradients
SELECTIVE permeability
Has SATURATED fats( no double bonds)
Has UNSATURATED fats( double bonds)
Easier to break down
Better temperature regulation
More fluidity of movement, especially lateral
ESSENTIAL FATS
Can get them ONLY through the diet
LINOLENIC
LINOLEIC
Used to make ARACHADONIC ACID
Arachadonic acid becomes essential if linoleic
acid is missing from the diet
OTHER MEMBRANE FUNCTIONS
PHAGOCYTOSIS: requires energy
ENDOCYTOSIS: primarily for nutrition
EXOCYTOSIS: primarily for getting rid of
waste products ( i.e. lipofuscin )
PINOCYTOSIS: for movement of fluids and
electrolytes
SKIN is only organ that does this process
72 72
OTHER MEMBRANE FUNCTIONS
TEMPERATURE REGULATION
RADIATION > concentration gradient
CONDUCTION > requires contact
CONVECTION > movement of environment
drags heat out of the body
OTHER MEMBRANE FUNCTIONS
ALL membranes can depolarize
Resting membrane potentials
ELECTROLYTE MOVEMENT
CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY
CHANNELS: small ions
PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS
TRANSPORT PROTEINS
PRIMARY ACTIVE TRANSPORT
>requires an ATPase. Going against a
gradient
SECONDARY ACTIVE TRANSPORT
Requires sodiums gradient
SYNPORT or COTRANSPORT >moving in
the same direction as sodium
ANTIPORT > movement in opposite direction
as sodium
SECOND MESSENGERS
C-amp > most common second messenger
73 73
PHOSPHODIESTERASE INHIBITORS
CAFFIENE
THEOPHYLLINE
SILDENAFIL
VARDENAFIL
TADALAFIL
SECOND MESSENGERS, cont
IP3 -DAG
IP3-DAG SYSTEM
All HYPOTHALAMIC HORMONES, except
CRH
All SMOOOTH MUSCLE CONTRACTION
by hormone or neurotransmitter
CALCIUM CALMODULIN SYSTEM
4 calcium molecules: 1 calmodulin
All SMOOTH MUSCLE CONTRACTION
by DISTENTION
CALCIUM
Used as a second messenger by
GASTRIN only
TYROSINE KINASE
INSULIN and all GROWTH FACTORS
74 74
NITRIC OXIDE
NITRIC OXIDE > GUANYLATE CYCLASE
> elevates c-GMP
NITRATES
ENDOTOXIN
ANP
NITRATES
VASODILATORS
TACHYPHYLAXIS; rapid tolerance
Nitroglycerin
Dinilatrate
Sodium Nitroprusside
The End
Insane in the membrane
75 75
INFLAMMATION
SHUTTING DOWN THE Na-K ATPase
Potassium still leaks out
Cell becomes more negative > less likely
to depolarize
SHUTTING DOWN THE Na-K ATPase, cont
With Na trapped within the cell, calcium
also gets trapped within the cell
This increases contractility
DIGITALIS
DIGITOXIN
OUBAIN
EKG CHANGES
Na-K ATPase shuts down when a vessel
is 70% stenosed
Potassium leaks out, making cells more
negative
This is why you get ST-wave
DEPRESSION
ST-WAVE DEPRESSION
Early ischemia
70% stenosis
SYMPTOMS BEGIN
Subendocardial ischemia
STABLE ANGINA
Comes on with exertion; goes away with rest
30% flow is enough at rest, but not on exertion
TX: VASODILATORS > increase radius increases
flow
FOLLOW-UP FOR ANGINA
PAIN GOES AWAY
Hospitalize for 24hours
Do serial EKGs and CIEs (Q6h x 24h)
If negative workup, then discharge home
Do a regular STRESS TEST in 6 weeks
Do STRESS THALLIUM test in 6 weeks
Thallium flows through the coronary arteries
Look for COLD AREAS: NO FLOW( ISCHEMIC)
76 76
FOLLOW-UP FOR ANGINA, cont
If you think they might have had an MI,
then do a Ca-PYROPHOSPHATE scan
Cells that die calcify
Dead cells will take up the Ca-
PYROPHOSPHATE
Look for a HOT SPOT
FOLLOW-UP FOR ANGINA, cont
IF PATIENT UNABLE TO PERFORM THE
STRESS TEST:
DOBUTAMINE STRESS TEST
DIPYRIDAMOLE STRESS TEST
EKG CHANGES
Na gets trapped within a cell when there is
at least 90% stenosis
Cells become more POSITIVE
UNSTABLE ANGINA
90% stenosis
EVENTS OCCUR
PLAQUE RUPTURED, and platelets are
closing off the rest of the lumen
TX: Aspirin > Nitrates> Oxygen > Heparin
> tPa > Morphine > B-blockers > Take to
CATH LAB for angiogram
ANGIOGRAM FINDINGS
LEFT MAIN CORONARY ARTERY
OCCLUSION ( 70% stenosis or more)
THREE OR MORE VESSELL DISEASE
TX: GO STRAIGHT TO SURGERY
ANGIOGRAM FINDINGS, cont
ANY SINGLE OR DOUBLE VESSELL
DISEASE
TX: PTCA with STENT placement coated
with CLOPIDOGREL
77 77
CELLS ARE MORE LIKELY TO
DEPOLARIZE WHEN ISCHEMIC
After a stroke: SEIZURES
After an MI: ARRYTHMIAS
After ischemic bowel: BLOODY DIARREA
After a DVT: CRAMPS
WITH Na and Ca trapped within the
cell
Since atria use Ca to depolarize, the
trapped Ca may cause atrial arrythmias
Contractility of muscles increases
WITH CELL DYING,
Sodium continues to accumulate inside
cell
Chloride will follow
WATER will follow next
SWELLING is therefore the FIRST visible
change of cellular injury
SWELLING
Cerebral edema
Papilledema
Hydropic changes
Dilated lymphatics
Third spacing
INFLAMMATION TIME LINE
< 24 hours: SWELLING
AT 24 hours: NEUTROPHILS show up
and peak at 3 days
T-cells and MACROPHAGES: show up at
day 4 and peak at day 7
FIBROBLASTS: show up at day 7, peak at
day 30, and take 3 to 6 months to
complete their work ( chronic
inflammation)
WHEN TOO MUCH SODIUM
INSIDE CELL.
Sodium begins to leak OUT of the cell now
that concentration gradient is reversed
The only way for sodium to get out is to
use the Na-Ca exchange protein which is
concentration driven
78 78
IF BLOOD SUPPLY NEVER
RETURNS TO THE CELL
The sodium can pull ALL the calcium into
the cell
WHILE calcium is moving into cell, more
atrial arrythmias may develop
WHEN ALL CALCIUM NOW
TRAPPED WITHIN THE CELL
Cells that depend on EXTRACELLULAR
calcium will lose function
SMOOTH MUSCLE
ATRIUM
VENTRICLE
SIGN OF CHRONIC DISEASE
ON BIOPSY: you see evidence of fibrosis
ON X-RAY: you see calcifications
ALL inflammatory processes
DONE!!!
79 79
Electrolyte Physiology
Something in the way she moves
me
Electrolyte Movement
CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY
CHANNELS: small ions
PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS
Electrolyte Movement
CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY
CHANNELS: small ions
PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS
Electrolyte Movement
CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY
CHANNELS: small ions
PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS
Electrolyte Movement
CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY
CHANNELS: small ions
PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS
Electrolyte Movement
CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY
CHANNELS: small ions
PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS
80 80
Electrolyte Movement
CONCENTRATION GRADIENT
ELECTRICAL GRADIENT
DRIVING FORCE
NERNST NUMBER (E-ion)
CONDUCTANCE (G-ion)
PERMEABILITY
CHANNELS: small ions
PORES: medium-sized molecules (sweat)
TRANSPORT PROTEINS
Electrolyte Movement
Depolarize: to become positive from
baseline
Overshoot: more positive than the
threshold potential
Repolarization: to become negative from a
positive potential
Hyperpolarization ( or undershoot): to
become more negative than baseline
potential
Sodium Channels
81 81
HEART BLOCKS
NORMAL PR-interval : <0.2sec
FIRST DEGREE HEART BLOCK: fixed
and prolonged PR-interval
Problem is AT the SA node or BETWEEN the
SA node and the AV node
NO treatment necessary
Speeding up the heart rate( exercise) will
make the block disappear
HEART BLOCKS, cont
SECOND DEGREE HEART BLOCK
MOBITZ 1: progressive lengthening of PR-
interval until QRS is dropped
Early ischemia at the AV node
Also called WENCKEBACKS
Put in pacemaker if symptomatic; do nothing if
asymptomatic
HEART BLOCKS, cont
MOBITZ II: PR-interval is normal; QRS
complexes are dropped erratically
Late ischemia at the AV node
Some cells are negative; some cells are
positive
ALL must have a pacemaker
82 82
HEART BLOCKS, cont
THIRD DEGREE HEART BLOCK
COMPLETE AV DISSOCIATION
AV-node has INFARCTED
P-waves and QRS complexes have NO
relationship
ALL must have a pacemaker
QRS COMPLEXES
Premature ventricular complex (PVC)
No P- wave; wide QRS complex; a pause
following the QRS complex
BIGEMINY: A PVC every other beat
TRIGEMINY: A PVC every third beat
VENTRICULAR TACHYCARDIA: three or
more consecutive PVCs with a minimum heart
rate of 150
VENTRICULAR FIBRILLATION: NO
recognizable QRS complexes
VENTRICULAR TACHYCARDIA
IF PATIENT STABLE: treat with
medication
IF PATIENT UNSTABLE:
SHOCK with 200joules
SHOCK with 300joules
SHOCK with 360(max)joules
LIDOCAINE
SHOCK
BRETYLIUM or AMIODORONE
VENTRICULAR FIBRILLATION
EPINEPHRINE
TREAT LIKE VENTRICULAR
TACHYCARDIA
ATRIAL ARRHYTHMIAS
Premature atrial contraction (PAC)
Multifocal atrial tachycardia
Paroxysmal supraventricular tachcardia
Atrial flutter
Atrial fibrillation
If ACUTE and STABLE: treat with medication
If ACUTE and UNSTABLE: DEFIBRILLATE
If CHRONIC: treat medically; put on coumadin
May defibrillate after minimum 2 weeks on coumadin
TX: use synchronized button
ELECTROLYTES AFFECT
DEPOLARIZATIONS
FOUR SPECIALIZED MEMBRANES
NEURONS
SKELETAL MUSCLES
SMOOTH MUSCLES
CARDIAC MUSCLE
ATRIUM: uses calcium to depolarize
VENTRICLE: uses sodium to depolarize; uses
intracellular calcium to contract; depends on
extracellular calcium to trigger off intracellular
calcium release
83 83
HYPERMAGNESEMIA
LESS LIKELY TO DEPOLARIZE
AFFECTS CALCIUM AND POTASSIUM
GETS IN THE WAY OF SODIUM
TX: IV normal saline; loop diuretic
HYPOMAGNESEMIA
MORE LIKELY TO DEPOLARIZE
AFFECTS CALCIUM and POTASSIUM
AFFECTS all KINASES
TX: magnesium sulphate
HYPERCALCEMIA
LESS LIKELY TO DEPOLARIZE
everywhere except the atrium( more likely)
SMOOTH MUSCLE: initially less likely
(blocks nerve) to depolarize, then more
likely to CONTRACT (due to second
messenger systems)
TX: IV normal saline; loop diuretics
HYPOCALCEMIA
MORE LIKELY TO DEPOLARIZE
everywhere except the atrium( less likely)
WILL AFFECT SECOND MESSENGER
SYSTEMS
SMOOTH MUSCLE: initially more likely to
depolarize( nerve fires more) followed by
less likely to CONTRACT (affects second
messenger systems)
HYPERKALEMIA
Initially MORE LIKELY TO DEPOLARIZE
Potassium will flow into the cell, taking the
membrane potential closer to threshold
Potassium gets trapped INSIDE the cell during
repolarization; repolarization therefore takes
longer > LESS LIKELY TO DEPOLARIZE
Peaked T waves
Widened T waves
Prolonged QT interval
Predisposes to arrythmias
HYPOKALEMIA
LESS LIKELY TO DEPOLARIZE
Potassium will rush out of the cells,
making them more negative
Cells repolarize even faster
Cells repolarize too much
Narrow T waves
Flat T waves
Flipped and inverted T wave
The U wave( exaggerated flipped T wave)
84 84
HYPERNATREMIA
MORE LIKELY TO DEPOLARIZE
SODIUM rushes into the cells, making
them more positive
After sometime, the NA-K ATP-ase kicks
Into high gear, making the cells more
negative( less likely to depolarize)
TX: IV normal saline; correct slowly
HYPONATREMIA
MORE LIKELY TO DEPOLARIZE
SODIUM will now leak out of a cell by Na-K
exchange
When calcium leaks INTO cell in exchange for
sodium leaking OUT, cells become more
positive
TX: IV normal saline; correct slowly
Use 3% saline if sodium under 120 with symptoms
Use fluid restriction if hyponatremia due to SIADH
Hyponatremia The End: Turn off the lytes
Antiarrhythmics
Class 1: Na channel blockers
1a
Quinidine
Procainamide
Disepyramide
1b
Lidocaine
Tocainide
Mixelitine
Phenytoin
1c
Encainide
Flecainide
propofenone
85 85
Class II: Beta Blockers
All end in lol
Specific beta 1: begins with A thru M, but
NOT L or C
Nonspecific: begins with N thru Z,
including L and C
Class II: Beta Blockers
Propanolol Acebutalol
Esmalol Atenalol
Sotalol Pindalol
Timalol
Butexalol
Labetalol
Carvedilol
Class III: K Channel blockers
Napa ( from procainamide)
Sotalol
Bretylium
Amiodorone
Class IV: Ca Channel blocker
Verapamil Quinidine
Diltiazem Procainamide
Nifedipine Phenytoin
Nicardipine
Nimodipine
Femlodipine
Amlodipine
IF YOU PLAY WITH LYTES You may go down IN FLAMES
86 86
PULMONARY PHYSIOLOGY
TAKING A DEEP BREATH
PULMONARY PHYSIOLOGY
Foregut Endoderm
Respiratory Tract
GI Tract > from the mouth to the second
part of the duodenum
Neural Crest
Tracheal cartilage
Laryngeal cartilage
Embryogenesis
Develops in the first trimester like every
other organ
Surfactant production is NOT complete
until approximately 32 to 34 weeks
Brain develops first in embryo: notochord
visible by 3 weeks; brain formed by 8
weeks
Surfactant
Decreases atmospheric pressures effect
on the alveoli > PREVENTS
ATELECTASIS
Increases compliance of alveoli
Compliance = change in volume / change
in pressure
87 87
4:23
You know surfactant production is
complete when
Lecithin / sphyngomyelin ratio is 2:1 or
greater or
You detect phosphatidylglycerol, a
breakdown product of surfactant
If mom comes in with preterm labor
Check L / S ratio
Check for phosphatidylglycerol
If both of the above are negative
Beclamethasone
Betamethasone
If baby still born early, then there is synthetic
surfactant that can be applied
When there was NO surfactant
Alveoli would collapse: Atelectasis
> leads to very poor compliance
> increases work of breathing
> weakness and shortness of breath
> oxygen is given
> oxygen has difficult time diffusing across
> oxygen builds up, causing free radical
formation > alveoli develop hyaline membrane in
order to protect themselves
Restrictive Lung Disease
Have poor
compliance
Have trouble
breathing in
Have poor diffusion
Have increased A-a
gradient
pO2 =low pCO2 =low
pH =high
Develop a secondary
perfusion problem
LOW ENERGY state
LOW VOLUME state
ALL die from heart
failure known as COR
PULMONALE = right
sided heart failure
due to pulmonary
HTN (severe RVH)
Hyaline Membrane Disease
THE FIRST RESTRICTIVE LUNG
DISEASE
88 88
COMPLICATIONS of HMD ( or RLD)
As compliance drops, the need for
pressure support increases
As diffusion decreases, the need for
oxygen increases
More oxygen means more free radicals,
which means more hyaline membrane
Bring in the JET VENTILATOR
Complications, cont
More pressure support can lead to a
PNEUMOTHORAX
Kussmaul sign: increased JVD on inspiration
Pulsus paradoxicus: exaggerated drop in BP
( more than 10mm) or in pulse rate ( more
than 10 bpm)
Loss of pulse and BP
Cyanosis
Hammans sign: subcutaneous emphysema
Pneumothorax
Spontaneous
Traumatic
Asymptomatic
symptomatic
As free radicals traumatize the
AIRWAY
Airway produces mucus to protect itself
Airway thickens
Goblet cell hyperplasia
Airway lumen narrows
Increased REID index
BRONCHOPULMONARY DYSPLASIA
The first obstructive lung disease
Obstructive Lung Disease
Difficulty breathing OUT
Problem with VENTILATION
ABG: pO2 = nl or low pCO2 = high pH=low
Too much airway mucus
Airway thickening
Goblet cell hyperplasia
Increased Reid Index
Mcc of death is BRONCHIECTASIS
EVERY lung disease presents with
the SAME signs and symptoms!!!
89 89
Can it really be this easy???
Amniotic Fluid Production
80% is a filtrate of moms plasma
To SUBTRACT:
Swallow ( a reflex)
Digest ( need patent UGI)
20% comes directly from the fetus
To ADD:
Process the swallowed fluid, then add 20%
more than was swallowed, then URINATE
Role of Amniotic Fluid
Main function is shock absorption
Secondary action is to prevent
atmospheric pressure from affecting the
fetus, especially the lungs
Problem with amniotic fluid
POLYHYRAMNIOS
Autonomic dysfunction
( Riley-Day syndrome)
Neuromuscular
disease ( Werdnig-
Hoffman syndrome)
UGI atresia
Esophageal atresia
Duodenal atresia
OLIGOHYDRAMNIOS
RENAL agenesis or
obstruction
Potters Syndrome
When OLIGOHYDRAMNIOS leads to
pressure effects on the fetus ( everything
is flattened)
Will lead to pulmonary aplasia or
hypoplasia due to the positive pressure
90 90
Prune Belly Syndrome
Absence of abdominal wall musculature
Fetus is unable to urinate in utero
Fetus is unable to bear down and raise
abdominal pressure for urination
OLIGOHYDRAMNIOS
Unable to urinate due to neuromuscular
weakness?
Teach to (self) catheterize
It is important to have negative
pressure in the thoracic cavity!
Diaphragmatic Hernias
The diaphragm forms from Ventral to
Dorsal
Bochtalek defect: rear defect
Morgagni defect: anterior, midline defect
Visible by sonography in utero
Bowel sounds in chest exam
Must repair surgically immediately after birth
Extrathoracic Airway
From the lips to the glottis
Narrows on inspiration; expands on
expiration
NOT protected by the thoracic cage
Intrathoracic Airway
From the glottis to the alveoli
Expands on inspiration; narrows on
expiration
Protected by the thoracic cage
Has a vacuum surrounding it
91 91
15.PUL2
Trachea
Has 16 to 20 C-shaped cartilage rings,
with the opening to the C facing posteriorly
This allows partial collapse of the airway
during swallowing to prevent aspiration
Has three anatomic narrowings
The glottis
Midway: due to anterior compression by aorta
Carina: located at T4 (level of nipple)
Aspiration
If patient is unable to speak, then the
object is lodged in the trachea
LARGE OBJECTS tend to lodge at the
glottis 90% of time
Perform the Heimlick Maneuver
Perform Back Thrusts if less than 2 y/o
If still unable to dislodge the object
Perform emergency cricothyroidotomy
Aspiration, cont
Small objects tend to lodge in the right
lower lobe
Recurrent RLL pneumonia: R/O FB aspiration
Do inspiratory-expiratory films
Right mainstem bronchus is larger and
straighter than the left
If person is sitting or standing UP, the object will
lodge in the superior segment
If patient is lying DOWN, the object will lodge in the
posterior segment
Evaluation for aspiration
Inspiratory film: all lobes are inflated
Expiratory film: the lobe with the aspirated
object does NOT collapse
Tx: bronchoscopy
Airway Anatomical Divisions
Dead space
Respiratory unit
Dead space ventilation
Alveolar ventilation
Total ventilation
92 92
Histology
Pneumocytes
Type 1: macrophages
Type 2: produce surfactant
Goblet cells: produce mucus to trap debris
Mucus moves 1 inch per cough
Smooth muscle
Clara dust cells
cartilage
Epithelium
Upper 1/3 of trachea has squamous cells
Mid 1/3 of trachea is a combination
Main respiratory epithelium is tall columnar
ciliated epithelium
The more you smoke, the longer the zone
of squamous cells
Cilia
Line the entire airway
Beat in one direction > orad
Has the 9 + 2 configuration (9
microtubules surrounding 2 actin proteins)
Need a Dynein arm to have flexibility
Kartageners Syndrome
Dynein arm is defective
An obstructive lung disease
Bronchiectasis
Infertility
Situs Inversus
Lung Sounds
Stridor: narrowing in extrathoracic airway
Wheeze: narrowing in intrathoracic airway
Rhonchi: air moving over mucus
Crackles: collapsed airways popping
open
Surfactant is missing
Alveoli have been scarred down
93 93
Lung Sounds, cont
Decreased breath sounds: space between
alveolus and chest wall is occupied
Dullness to percussion: as above
Increased fremitus: consolidation on same
side or atelectasis on opposite side
Bronchophony, egophony, or e to a
changes: as above
Lung Sounds, cont
Tracheal deviation: towards atelectasis
and away from a pneumothorax
Hyperresonance: pneumothorax on same
side or atelectasis on opposite side
Lung Infections
Croup
Bronchiolitis
Bronchitis
Acute
chronic
Pneumonia
Airway
interstitial
tracheitis
Airway Infections
Epiglotitis: H. Influenza B
Tracheitis: C. Diptheria
Pneumonia
Rusty colored sputum: Strep Pneumonia
Curant jelly sputum: Klebsiella Pneumonia
Sulphur granules: Actinomyces Israelii
Frequent after the flu: Staph Aureus
Malodorous smell or gas formation:
Anaerobes
Interstitial Pneumonias
Atypicals
Chlamydia: from 0 to 2 mo
Mycoplasma: from 10 to 30 y/o
Legionella: over 40 y/o
Fungus
Histoplasmosis: midwest
Blastomycosis: northeast
Coccidiomycosis: southwest
Interstitial pneumonias
Fungus, cont
Paracoccidiomycosis: South America
Aspergillus: moldy hay or moldy basement
Sporothrix: rose thorn
Pneumoconioses
Asbestosis
Silicosis
Bissinosis
berrylliosis
94 94
Interstitial pneumonias, cont
Nocardia: the only G+ that is partially acid
fast
Sarcoidosis: noncaseating granulomas;
large hilar adenopathy; high ACE levels
Lung Masses
Most common MASS in children:
hamartoma
Most common MASS in adults:
granulomas
Most common TUMOR: adenoma
Central Cancers
Squamous Cell Carcinoma: produces PTH
Small Cell Carcinoma
Anaplastic
Located at the carina
Produces 4 hormones:
ACTH: 90%
ADH: 5%
PTH: 3%
TSH: 2%
Peripheral Cancers
Bronchogenic adenocarcinoma
Bronchioalveolar adenocarcinoma
Carcinoid syndrome
flushing, wheezing and diarrhea
Too much serotonin
Measure 5-HIAA in the urine
Large cell adenocarcinoma
Risk factors for lung cancer
Primary smoking
Risk increases with amount AND duration
If you STOP smoking: 5 yrs > reversal of
damage visible; 15 yrs > risk back to baseline
Radon
Second hand smoke
(1) sidestream smoke (2) mainstream smoke
Pneumoconioses
Time for the PHYSIOLOGY of the lung!!
95 95
Three PHYSIOLOGIC parts to the lung
Intrathoracic space
Chest wall
Pleural space
Pulmonary vasculature
Pulmonary airway
Lung Volumes
RV: the amount of air left in the lungs AFTER
forced expiration
Can not be physiologically forced out
Maintains some compliance in the airway
ERV: the amount of air that can still be FORCED
out AFTER a normal exhalation
Fills up the dead space; decreases the tidal volume
that you would have to take in
FRC: a combination of RV and ERV
Lung Volumes, cont
TV: the amount of air you take IN during a
NORMAL inhalation effort
IRV: the amount of air you can FORCE
INSPIRE after a normal inhalation effort
TLC: ALL the air in your lungs at the END of a
deep breath ( RV + ERV +TV + IRV)
VC: all the air you can breathe in AFTER forced
exhalation ( ERV + TV + IRV)
96 96
15 PUL3 27:30
IMPORTANT: recap 37:40 run thru
Compliance and Air Flow Inspiration
Beginning: expansile forces of the CHEST
WALL is greater ( 0 to 49%)
Middle: expansile forces of the LUNG is
greater ( 50 to 99%)
End: recoil force of the chest wall
EQUALS the expansile force of the lung
Expiration
Beginning: recoil forces of the CHEST
WALL are greater ( 0 to 49%)
Middle: recoil forces of the LUNG are
greater ( 50 to 99%)
End: the recoil force of the lung EQUALS
the expansile force of the chest wall
Breathing in
FRC: baseline > intrathoraxic pressure is
negative ( - 3 to 5)
TV: intrathoraxic pressure gets more
negative ( -10 to -12)
TLC: intrathoraxic pressure most negative
(-20 to -25)
Intrathoraxic Pressure should always be
NEGATIVE
Intrathoracic Pressure Intrathoraxic Pressure
Should ALWAYS remain negative
Should decrease with inspiration
If it gets positive, then it will resist any
blood or air from entering the thorax
If you do not breathe in, there will be NO
pressure gradient for blood to enter the
thorax
97 97
Positive Intrathoracic Pressure
Kussmaul sign: increased JVD with
inspiration
Pulsus paradoxicus: exaggerated drop in
BP( more than 10mmHg) or pulse ( more
than 10bpm) on inspiration
Mcc: pericardial tamponade or
pneumothorax
Pericardial Tamponade
Mcc: trauma or cancer
CXR: enlarged cardiac shadow
ECHO: compressed small heart
Tx: pericardiocentesis
If recurrent: put in a pericardial window
Pneumothorax
Traumatic
Spontaneous
Associated with estrogen use or collagen
disease
Less than 25% occupation & asymptomatic
More than 25% occupation or symptomatic
Tx: chest tube placement
Pulmonary Vasculature Flow( Q )
As you breathe in, the lung Inflates, pulling
on traction fibers attached to vessels
As vessels DILATE, flow increases
As flow increases, oxygen dilates the
vessels, significantly increasing Q
The increased Q keeps the pulmonary
valve open longer, INCREASING S-2
splitting
98 98
Flow ( Q ) is greater to the bottom of
the lungs because
(1) gravity
(2) less resistance
(3) more oxygen goes to the bottom of the
lungs with each breath
Normal RR = 12 to 16 breaths/min
Q increases on inspiration and decreases
on expiration.
S-2 Splitting
Increases on inspiration due to Increased
pulmonary blood flow
Decreases on expiration due to decreased
pulmonary blood flow
This is why RIGHT sided heart sounds
increase on INSPIRATION
This is why LEFT sided heart sounds
increase on EXPIRATION
Oxygenation
Directly related to DIFFUSION and
PERFUSION
More oxygenation is accomplished at the
bottom of the lungs only on inspiration
Most of oxygenation is accomplished at
the top of the lungs > ALWAYS OPEN!
Ventilation (V)
Inversely related to pCO-2
Definition: patent airway
Measurement: pCO-2 ( on ABGs)
More V to the bottom of the lungs only on
inspiration
Most V at the top of the lungs because it is
ALWAYS PATENT
The Law of V / Q
V /Q is greatest at the top of the lungs,
equally matched in the middle, least at the
bottom
If you change one, you MUST change the
other in the SAME direction
ANY V / Q mismatch will lead to hypoxia
Pulmonary Airway
99 99
Pulmonary Airway Pressure
The Only Pressure That Gets
Positive With Each Breath
How The Brain Monitors Pulmonary
Physiology
Signals from the lungs and chest wall
J-receptors: found in the interstitium of
lungs
Senses interstitial particles
Increases respiratory rate
Slow adapting receptors: found in the ribs,
especially the sternocostal junctions
Senses stretch and inflation
Causes exhalation
100 100
SINUSES
Maxillary
Ethmoid
Sphenoidal
Frontal
BODIES
AORTIC BODY: found in the arch of the
aorta
Measures pCO-2, pH, and H+ ions
CAROTID BODY: located at the
bifurcation of the internal and external
carotids
Measures PO2, PCO2, pH, and H+ ions
BRAIN
More sensitive to elevated pCO-2
Hypoxia and Hypercarbia are synergistic
Forms of pCO-2:
90% in the form of HCO-3
7% as carbaminohemoglobin and
carboxyhemoglobin
3% is dissolved ( .03pCO2 )
Medulla
Responsible for BASIC functions; has a
RR of 8 to 10
BRAIN DEAD: no function above the
medulla
COMATOSE: cerebral cortex is still alive,
but patient unable to respond
101 101
Pons
RESPONDS to the environment
Locked-In syndrome: damage to pons; patient
only able to blink as response
Most sensitive to osmotic shifts > Central Pontine
Demylinolysis
Apneustic center: senses hypoxia; causes
inspiration
Pneumotactic center: senses hypercarbia;
causes exhalation
Kussmaul Breathing
RAPID, DEEP breathing
Means METABOLIC ACIDOSIS
Apneustic Breathing
Pneumotactic center is desensitized, as in
COPD
A lesion below the pneumotactic center
but above the apneustic center
102 102
Apnea
Central Apnea: NO inspiratory effort, with or
without bradycardia, in 20 seconds or more
Apnea monitor
Tx: Caffiene; theophylline
Obstructive Apnea: occlusion of airway during
sleep, usually caused by obesity
Weight loss
Progesterone
CPAP
Surgery: Uvulopalatoplasty
Lesions to MEDULLA
Lesions to MEDULLA
Hypoglycemia
Ischemia
Thoracic outlet syndrome
Subclavian steal syndrome
THE END
103 103
And now for a few good CLUES Obstructive Lung Diseases
Bronchitis
Acute
chronic
Bronchiolitis
Asthma
Intrinsic
extrinsic
Cystic fibrosis
Bronchiectasis
Emphysema
Panacinar
Centroacinar
Distoacinar
Bullous
Staph aureus
Pseudomonas
Really! The End!!
104 104
NEUROMUSCULAR
PHYSIOLOGY
I WANT A CONTRACT
NEUROLOGICAL CONTROL
Central Nervous System
Involves the BRAIN and SPINAL CORD
PARASYMPATHETIC system
Controls the craniosacral divisions
SYMPATHETIC system
Controls the thoracolumbar divisions
Inhibitory Neurotransmitters
GABA: brain; causes an influx of chloride
GLYCINE: spinal cord; causes an influx of
chloride
PARASYMPATHETIC SYSTEM
Uses acetylcholine for preganglionic fibers
and postganglionic fibers
DEPOLARIZES the head and neck as well
as below the belt
HYPERPOLARIZES the thoracolumbar
areas
Has long preganglionic fibers, short
postganglionic fibers
SYMPATHETIC SYSTEM
Uses acetylcholine for preganglionic
fibers; uses primarily NE for postganglionic
fibers
Some pathways use DA or SEROTONIN
DEPOLARIZES the brain and the
thoracolumbar areas
HYPERPOLARIZES the sacral area
Has short preganglionic fibers, long
postganglionic fibers
105 105
Second Messengers
PARASYMPATHETIC: c-GMP
SYMPATHETIC: c-AMP
Smooth muscle contraction by
neurotransmitter or hormone: IP3/DAG
Smooth muscle contraction by distention:
calcium-calmodulin
Parasympathetic Receptors
Most are MUSCARINIC except at ganglia
or neuromuscular junctions which are
NICOTINIC
Sympathetic Receptors
Many are NICOTINIC, except for sweat
glands which are muscarinic or
Alpha 1 Receptors
Arteries: vasoconstriction
Sphincters: tighten
Radial muscles of the eyes: mydriasis w/o
cycloplegia
Alpha 2 Receptors
All presynaptic sympathetic fibers: inhibit
NE release
Islet cells of pancreas: inhibit insulin
secretion
106 106
Beta 1 Receptors
CNS: increased activity
SA NODE: increase heart rate and
contractility
JG Apparatus: increased renin release
Alpha cells of pancreas: increased
glucagon release
Beta 2 Receptors
CNS: increased activity
Ventricles: increased contractility but NOT
rate
Lungs: bronchodilation
Arterioles: vasodilation
Islet cells of pancreas: increased insulin
Uterus and Bladder: relaxation
If you want to stimulate
You want to depolarize
Make the cell more positive
Make Na move INTO the cell
Make Ca move into SA node
If you want to inhibit
CNS: make CL move into cell
PNS: make K move out of cells
In either case, cells become more
NEGATIVE and are less likely to
depolarize
NOW FOR THE MUSCLES! TYPES of MUSCLES
CARDIAC muscle
SKELETAL muscle
SMOOTH muscle
107 107
STRIATED MUSCLES
Cardiac muscle
Skeletal muscle
Striations due to sarcomeres
Smooth Muscle
Appear smooth due to lack of striations
Skeletal Muscle
Use intracellular calcium for contraction
100% electrochemically coupled
Function as motor units( one nerve fiber
and all the muscle fibers it innervates
Demonstrate RECRUITMENT
NO AUTONOMICS
NO SYNCYTIAL activity
Cardiac Muscle
Uses intracellular calcium for contraction
Needs extracellular calcium to trigger off
intracellular calcium release
Complete SYNCYTIAL activity
The most gap junctions
Complete AUTONOMICS
Can function without innervation,
neurotransmitters or hormones
Smooth Muscle
Uses intracellular calcium for contraction
Needs extracellular calcium for its second
messenger system ( when it flows inside
the cell)
Has AUTONOMICS
Has partial SYNCYTIAL activity
Can function without innervation,
neurotransmitters or hormones
NEUROMUSCULAR TRANSMISSION
108 108
MUSCLE CONTRACTION
Calcium binds trop-C
Trop-C releases trop-I
Trop-I releases
tropomyosin
Tropomyosin releases
actin binding sites
Myosin heads bind actin
CONTRACTION occurs
Myosin heads release
ADP from previous rd
Myosin heads bind
new ATP
Myosin heads
hydrolyze ATP
RELEASE occurs
Myosin heads return
to start position
MUSCLE CONTRACTION, cont
Tropomyosin binds actin
Trop-I binds tropomyosin
Trop-C binds trop-I
Ca-ATPase pumps Ca back into SR
Phospholambin inhibits Ca-ATPase when
it is done pumping
Clinical Application
Diagnosis of a Myocardial
Infarction
EKG: Na-K pump stops > peaked T-wave > ST-
wave depression > ST-wave elevation > T-wave
depression, then inversion > Q-wave
Troponin I: rises at 2 hours > peaks in 2days >
positive up to 7 days
CK-mb: rises in 6 hours > peaks in 12 hours >
gone in 24 to 36 hours
LDH 1: rises in 24 hours > peaks in 48hours >
gone in 72 hours
Management of an MI
24 hour hospitalization
Check EKG Q6
Check CIEs Q6
Monitor for arrythmias
Discharge after 24 hours IF asymptomatic
Re-evaluate in 6 weeks
109 109
In 6 Weeks
Exercise stress test
Positive IF: chest pain is reproduced; ST-wave
changes; drop in BP
Stress Thallium test
A perfusion test; looking for a COLD spot
Dobutamine or Dipyridamole stress test
Use when patient unable to exercise
Calcium Pyrophosphate scan
Taken up by DEAD tissue; looking for HOT spot
2-D echo
Evaluates anatomy of heart; measures SV and CO
The Functional Unit of Muscles
THE SARCOMERE
MUSCLE DIFFERENCES
CARDIAC MUSCLE
In addition to wave of depolarization,
calcium MUST flow into the T-tubules
during phase 2 for contraction to occur
Ventricle depends on EXTRACELLULAR
calcium to trigger its contraction
Smooth Muscle
Has NO sarcomeres
Contains NO troponin > actin and myosin
are always bound ( LATCHING)
Contains BASAL BODIES
Has NO myosin ATPase activity
Has MLCK and MLCP working together
110 110
As Muscle Contracts
LENGTH decreases
FORCE and TENSION increase
A band stays the same
Amount of OVERLAP increases
The H band and I band therefore shrink
Length/Tension Curve
Golgi Tendon Organs
Located at muscle insertions
Monitor the force of muscle contractions
Allows muscle to hold MAXIMUM muscle
contraction force for only one second
Once it fires, muscle fibers MUST relax
Prevents destruction of sarcomeres
Muscle Strain
Overstretching or tearing a muscle
When a muscle is torn, it goes into spasm
to keep the fibers together for proper
healing
Tx: rest it > apply heat > NSAIDS > muscle
relaxants
JOINT SPRAIN
TORN tendon or ligament
Tx: Rest it > Ice Compression > Elevate
the extremity
Frank-Starling Curve
111 111
Congestive Heart Failure
Over 50% mortality in 5 years
Most common medicare diagnosis
Muscle fibers are overstretched
Dilated ventricle
Increased EDV and ESV
Decreased contractility > decreased CO
and EF
Congestive Heart Failure after a
myocardial infarction
AT LEAST 40% of myocardium lost
EJECTION FRACTION is less than 45%
Due to left coronary artery infarcts 90% of
time
Treating CHF: Applying
Frank-Starling Curve
Decrease volume
Restrict sodium intake
Restrict volume intake
Increase contractility
Digitalis
Dobutamine
Dopamine
Decrease TPR
Ace inhibitors
NEUROMUSCULAR PROFILE
ALL YOU NEED NOW IS THE
CLUE
Inflammatory Myopathies
Myositis
Polymyositis
Dermatomyositis
Fibrositis
Fibromyalgia
Polymyalgia
rheumatica
Temporal Arteritis
ALL HAVE:
High ESR
High WBC count
Myoglobinemia
High AST, ALT and
Aldolase
112 112
Muscular Dystrophies
Duchennes
Gowers sign
Waddling gait
Pseudohypertrophy of the calf
Dystrophin protein
X-linked recessive; onset BEFORE age 5
Beckers
Onset AFTER age 5
Myotonic
Neuropathies
Guillian Barre
Diabetes mellitus
Syphilis
Myesthenia Gravis / Myesthenic or Eaton
Lambert syndrome
Acetylcholinesterase inhibitors:
reversible
Edrephonium
Neostigmine
Pyridostigmine
Physostigmine
Acetylcholinesterase inhibitors:
irreversible
AKA Organophosphates
End in .phate ( diflorophate; echothiophate)
End in .thion ( malathion; nalathion;
parathion)
If they come back complaining
about more weakness
Myesthenia Gravis has gotten worse or
Cholinergic crisis
REPEAT EDREPHONIUM TEST!!
IF patient gets better > disease is worse
Increase neostigmine
IF patient gets worse > cholinergic crisis
Hold neostigmine > give atropine > decrease
neostigmine
Anticholinergic Drugs
Side effects are sympathetic except for
HOT, DRY SKIN!
Atropine
Glycopyrollate
Pilocarpine
Benztropine
Trihexyphenidyl
ipratropium
113 113
Neoplastic Associations
Myesthenia Gravis: THYMOMA
Myesthenic syndrome: SMALL CELL
CARCINOMA; a paraneoplastic syndrome
Sarcoplasmic reticulum is slow to sequester
calcium; cancer blocks some calcium
channels
Neuropathies, cont
Multiple sclerosis
Metachromatic leukodystrophy
Treatment of MS
STEROIDS
IV GAMMGLOBULINS
PLASMAPHARESIS
Lower Motor Neuron Disease
Amyotrophic lateral sclerosis
Werdnig-Hoffman Disease
Polio
Cerebellar Disease in 5 to 10 Y/O
children
Ataxia Telangiectasia
Fredricks Ataxia
Adrenoleukodystrophy
Cerebral Palsy
Any permanent neurological damage suffered
PRIOR to age 21 years
Spastic Diplegia
Midline cortical problem
Spastic Hemiplegia
Cortical problem on ONE SIDE of the brain
Choreoathetosis
BASAL GANGLIA is involved: kernicterus
Atonic
FRONTAL CORTEX: involves the CST
114 114
THE END
115 115
VASCULAR PHYSIOLOGY
YOU GOTTA HAVE SOME FLOW
Im Talking About
SMOOTH
SMOOTH MUSCLE, that is
Smooth Muscle
THICKEST layer of smooth muscle is
found in the aorta
MOST smooth muscle by surface area
found in the arterioles
LEAST smooth muscle found In the veins
and veinules
Arterioles
Considered the STOPCOCKS of the
vascular tree
MOST smooth muscle by surface area
allows most vasodilatation and
vasoconstriction
Maintain AUTOREGULATION
Do the MOST to regulate BP, up or down
AUTOREGULATION
Between BP 60 to 160 systolic : cerebral,
coronary, and renal perfusion remains
constant
ISCHEMIC infarct: BP went below 60
systolic
HEMORRHAGIC infarct: BP went above
160 systolic
Veins and Veinules
Have the most CAPACITANCE
Have the least smooth muscle
60% of blood ( the most) is pooled here
Depend on skeletal muscle contractions to
squeeze blood upward
Have one-way valves which move blood
from superficial to deep veins
116 116
9:30
Vasc.1
Gotta Talk it OUT!!! otherwise you won't remember
**22:30 pt1
CONTROL of vessels
VEINS: under parasympathetic control
This is why veins are usually dilated
Blood flow rate is quite slow
example: subdural hematomas
If Hypovolemia Develops
VENOCONSTRICTION is first response to
loss of volume > gets volume back into
circulation
Venoconstriction is most significant in skin
and GI
Poor skin turgor
Loss of bowel sounds and ileus
A-V Anastamoses
Shunt blood away from nonessential
organs
More concentrated in fingertips, tips of
toes, tip of nose, lips and earlobes
Severe vasoconstriction
hypothermia
CONTROL of vessels, cont
ARTERIES: under sympathetic control
This is why arteries are usually constricted
Reactive hyperemia: cutting an artery or
the nerve to that artery causes immediate
vasodilatation
i.e. epidural hematoma
Receptors
ARTERIES: alpha one ( IP3/DAG)
vasoconstriction
ARTERIOLES: beta 2 ( c-AMP)
vasodilatation
VEINS: alpha 1 ( IP3/DAG)
venoconstriction
Capillaries
Have the thinnest membranes
Made for diffusion
Have the greatest surface area
117 117
29:30
watch 33:15, scenarios
38:10 Scenarios see the physio
Filtration Fraction
As Blood Flows Through the
Capillaries
Fluid diffuses out; large proteins (albumin)
stay in
Osmotic pressure rises in the capillaries
Concentration gradient pushes particles
out of capillaries
In the Veins and Venules
Osmotic pressure is now high enough to
PULL waste products into vessels
Blood PULLS waste products back into
circulation
Total Pressure in a vessel As a Vessel Narrows
Velocity increases
Flow decreases
Resistance increases
Blood Pressure rises
Resistance in Series
118 118
51:20 pt.1
54:10
Big Small
Portal V. empties into Hepatic
We dont want this
Resistance in Parallel During Diastole
Ventricles are relaxing
Very LOW RESISTANCE in coronaries
Aortic valve is closed
Aorta has MORE TRANSMURAL
PRESSURE
MORE CORONARY BLOOD FLOW
During Systole
Ventricles are CONTRACTING
There is HIGH RESISTANCE in coronary
vessels
Velocity in aorta is too high
Aortic valve is open
LOW TRANSMURAL PRESSURE
LESS CORONARY BLOOD FLOW
In Summary
LESS blood flow through coronary arteries
during SYSTOLE
MORE blood flow through coronary
arteries during DIASTOLE
Most work is done in systole!
A-V O2 difference created during systole
Therefore: MOST O2 EXTRACTION
occurs in systole
A-V O2 Difference
At REST: the heart extracts 97% of O2
With EXERCISE: skeletal muscle
After EATING: GI system
During INTENSE CONCENTRATION: the
brain
LOWEST A-V O2 difference: the kidneys,
at all times
Lets Look at FLOW
119 119
*1:12:30
Breakdown!
:00:00 pt. 2
1:00 pt. 2
get compressed
no touch
walls
14:40 patho
POISSOILE LAW
Regulation of Radius
CNS: pCO2 pO2
LUNGS: pO2
MUSCLES: pCO2 pH
CV: adenosine
SKIN: temp pCO2
GI: food, especially fats
RENAL: PGE2; dopamine; ANP
NEUROLOGICAL control of blood
pressure
Carotid Sinus
Located at the bifurcation of the common
carotid
Responds to FLOW or STROKE VOLUME
Increased STRETCH means increased
FLOW
Sensory nerve : CN IX
Efferent nerve : CN X
REMEMBER!
Stroke volume, carotid sinus stretch, CN
IX firing and CN X firing ALWAYS go in
the same direction
CN IX and CN X are ALWAYS firing
Amount of firing varies always in SAME
DIRECTION as the stroke volume
120 120
8:
Autonomic Dysfunction
Mcc: DIABETES MELLITUS
In Newborns: Riley-Day syndrome
In Parkinsonism: Shy-Dragger syndrome
In elderly: Sick Sinus syndrome
Low Volume State
Low stroke volume >
low carotid stretch >
low CN IX firing >
decreased CN X firing
>increased heart rate
> increased NE from
NTS in medulla >
increased TPR >
decreased RBF >
decreased GFR >
> increased renin,
angiotensinogen,
aldosterone secretion
> increased Na
reabsorption >
increased total body
Na > decreased
urinary Na >
decreased FENa >
increased urinary K >
> > >
Low Volume State
Decreased serum Na( dilutional)
Decreased serum Cl ( dilutional)
Decreased serum K (real and dilutional)
Decreased urine pH ( aldosterone
excretes H)
Increased serum Ph (metabolic alkalosis)
Increased TPR
Most common cause of
hyponatremia?
LOW VOLUME STATE
Most common cause of
hypokalemia?
LOW VOLUME STATE
121 121
Most common cause of
hypochloremia?
LOW VOLUME STATE
Most common cause of high TPR ?
LOW VOLUME STATE
Most common cause of metabolic
alkalosis?
LOW VOLUME STATE
ALKALOSIS favors calcium precipitation
with phosphate
KIDNEY STONES !!!!
Ace Inhibitors
Stop conversion of AT-1 to AT-II
Increased bradykinin
VASODILATION and VENODILATION
Decreased preload and afterload
BALANCED dilation
Contain sulphur
Decrease mortality in CHF; decreases
proteinuria in diabetic nephropathy
Ace Inhibitors
Captopril
Lisenopril
Enalopril
rinilopril
Angiotensin Receptor Blockers
Losartan
Vosartan
Do not contain sulphur
NO elevation in bradykinin
122 122
What is a VASCULITIS? Vasculitis
Schistocytes ( Burr cells; helmet cells)
Petechiae, purpura and ecchymoses
LOW ENERGY STATE
LOW VOLUME STATE
Restrictive lung disease profile
CELL MEDIATED inflammation
All You Need Now is the Clue!!!
Ig-A nephropathies
Bergers
Henoch-Schonlein Purpura
Alports
More vasculitides
Buergers
DIC
HUS
TTP
DM
Syphilis
Takayasu
kawasaki
More vasculitides
Temporal arteritis
Ankylosing Spondylitis
PAN
Wegeners
Goodpastures
Leukocytoclastic
Churg-Strauss
123 123
Collagen Vascular Diseases
CREST syndrome
Scleroderma
Progresive Systemic Sclerosis
MCTD
RA / JRA (Stills disease)
Feltys: RA & leukopenia and splenomegaly
Becets : RA & GI ulcerations
Sjogrens : RA & xeropthalmia, xerostomia
Collagen Vascular Diseases with
LOW COMPLEMENT
PSGN
Serum Sickness
SBE
SLE
MPGN : type l, ll
Cryoglobulinemia
THIS IS THE END
124 124
CARDIAC PHYSIOLOGY
THE HEART OF THE MATTER
PRESSURE is the GRADIENT of the
organs!
OPENING SNAP
A valve is popping open during diastole
TRICUSPID STENOSIS
MITRAL STENOSIS
EJECTION CLICK
A valve is popping open during systole
AORTIC STENOSIS
PULMONARY STENOSIS
MIDSYSTOLIC CLICK
Blood is coming at high velocity, slapping
the mitral valve on the way out
Occurs closer to S-1 with standing and
closer to S-2 with lying down
MITRAL VALVE PROLAPSE
Occurs in 7% of normal women (estrogen
connection)
125 125
SOFT S-1
One of the two valves that contribute to
this sound is NOT closing
TRICUSPID REGURGITATION
MITRAL REGURGITATION
VALVE IS NOT THERE!
Tricuspid atresia
Mitral atresia
BOTH ARE CYANOTIC
LOUD S-1
Either you have a stiff valve that bangs
shut: TRICUSPID or MITRAL STENOSIS
Or the ventricle is contracting harder
SOFT S-2
One of the two valves that contribute to
this sound is NOT closing
AORTIC REGUGITATION
PULMONARY REGURGITATION
OR the valve is not present
AORTIC ATRESIA
PULMONARY ATRESIA
BOTH ARE CYANOTIC
LOUD S-2
Either one of the valves is stiff and
BANGS shut when it tries to open
AORTIC STENOSIS
PULMONARY STENOSIS
Or there is HIGH pressure in front of the
valves (systemic or pulmonary
hypertension)
S-3
Sound made by a noncompliant ventricle
????????????????
S-3
VOLUME overload
DILATED ventricle
DECOMPENSATION
S-3 said to be normal ONLY in an
adolescent female
126 126
baby born blue
Do Cardiac phys1. 27:40
baby born blue
34:45
47:30
51:45
56:30
(Stretch mus. fibers)
59:30
ESTROGEN CONNECTION
Estrogen is a muscle relaxant
Causes liver to produce many proteins
High ESR or CRP
Lipoproteins
TBG
Angiotensinogen
Clotting factors
Especially fibrinogen, but not factor 11
S-4
Sound made by an atrial kick
PRESSURE overload
HYPERTROPHY
COMPENSATION
Most common gallop (atherosclerosis)
MURMURS! MURMURS! MURMURS!
MURMURS CAUSED BY
TERBULENCE
Reynolds number > 2500
Murmur: if it is in the heart
Bruit: if it is in a vessel
Occurs when you have 70% stenosis
127 127
Breakdown: 1:03:30
Rewatch
1:25:00
1:26:50 rewatch!
MURMUR GRADES
Grade 1: barely audible
Grade 2: easily audible
Grade 3: pretty loud
Grade 4: palpable thrill
Grade 5: able to hear with stethoscope off
the chest
Grade 6: able to hear across the room
without stethoscope
A SYSTOLIC MURMUR
Valves that are supposed to be open are
stenotic ( PULMONARY or AORTIC
STENOSIS)
OR valves that should be closed are not
closing ( MITRAL REGURGITATION or
TRICUSPID REGURGITATION)
SYSTOLIC MURMURS
Aortic stenosis
Pulmonary stenosis
Mitral regurgitation
Tricuspid regurgitation
Ventricular septal defect
HOLOSYSTOLIC ( PANSYSTOLIC)
MURMURS
Tricuspid regurgitation
Mitral regurgitation
VSD
PANSYSTOLIC increases on
INSPIRATION
Tricuspid regurgitation
PANSYSTOLIC increases on
EXPIRATION
Mitral regurgitation
VSD
Radiates into the axilla: MITRAL
128 128
SYSTOLIC EJECTION MURMURS
Aortic stenosis
Pulmonary stenosis
AORTIC STENOSIS
Radiates to the carotids( neck)
LOUDER with leaning forward, making a
fist, blowing up a blood pressure cuff, or
squatting
Crescendo decrescendo or diamond
shaped murmur
PULSUS TARDUS
DELAYED CAROTID UPSTROKE
IHSS
Autosomal dominant
Muscle fibers are hypertrophied but
disorganized
Any young athlete who dies suddenly,
especially during peak exercise
Septum is asymmetrically thick, especially
the top > causes SUBAORTIC stenosis
IHSS, cont
Excessive hypertrophy compresses the
coronary arteries
Excessive hypertrophy obliterates the
ventricular space
Murmur is LOUDER with standing or with
Valsalva; decreased with increased TPR
PULSUS BISFERIENS
IHSS, cont
Tx: need to decrease contractility; allow
time for adequate ventricular filling
Beta blockers
Adequate fluid intake
Bar from organized sports
Do an ECHO on entire family
DIASTOLIC MURMURS
Either the valves that should be open are
stenotic (MITRAL STENOSIS or
TRICUSPID STENOSIS)
Or the valves that should be closed are
regurgitant ( AORTIC REGURGITATION
or PULMONARY REGURGITATION)
129 129
DIASTOLIC BLOWINNG or
DECRESCENDO MURMUR
AORTIC REGURGITATION
PULMONARY REGURGITATION
Increases on inspiration: Pulmonary
regurgitation
Increases on expiration: Aortic
regurgitation
Aortic Regurgitation
Radiates to carotids; LOUDER with leaning
forward, making a fist, blowing up a blood
pressure cuff, or squatting
Austin-Flint murmur: mitral regurgitation
Widens the pulse pressure
bounding pulses
waterhammer pulse
head-bobbing
Quinckes pulses
Pulmonary Regurgitation
Radiates to the back
Louder on inspiration
Graham-Steele murmur: tricuspid
regurgitation
Diastolic Rumbles
TRICUSPID STENOSIS
MITRAL STENOSIS
Increases on inspiration: tricuspid
regurgitation
Increases on expiration: mitral
regurgitation
CARDIAC PATHOLOGY
CARDIOMYOPATHIES
DILATED
HYPERTROPHIC
RESTRICTIVE
CVD
Amyloidosis
Hemochromatosis
CONSTRICTIVE
Tamponade ( Kussmaul sign; Pulsus Parodoxicus)
Trauma
cancer
130 130
EFFUSIONS
Transudate: mostly water
Exudate: mostly protein
Transudate: sp. G < 1.012
Protein < 2grams
Exudate: sp. G > 1.012
Protein > 2grams
Congenital Heart Diseases
VSD
ASD
PDA
Coarctation
Cyanotic Congenital Heart Disease
Transposition of Great Arteries
Tetrology of Falot
Tricuspid Atresia
Total Anomalous Pulmonary Venous Return
Truncus arteriosus
Pulmonary Atresia
Aortic Atresia
Hypoplastic Left Heart
Ebstiens Anomaly
VALVULAR DISEASES: most common
causes
Aortic stenosis: aging
Aortic regurgitation: aging
Mitral stenosis: Rheumatic fever
Mitral regurgitation: MVP, SBE, collagen
diseases
Tricuspid stenosis: Rheumatic fever,
carcinoid syndrome
Tricuspid regurgitation: acute endocarditis
Pulmonary Disease
Most common cause is ALWAYS
congenital
Pulmonary valve is protected on BOTH
sides
131 131
Flow Volume Loops
Antiarrhythmics
132 132
Na Channel Blockers
Class Ia
Quinidine
Procainamide
Disepyramide
Class Ib
Lidocaine
Tocainide
Mixeletine
Phenytoin
Class Ic
Encainide
Flecainide
Propofenone
Wolf-Parkinson-White Syndrome
Class IV Ca Channel Blockers
Verapamil
Diltiazem
Nefedipine
Nicardipine
Nimodipine
Amlodipine
Femlodipine
Class II Beta Blockers
End in lol
Specific B-1: begin with A thru M (not L,C)
Specific B-2: begin with N thru Z (incl L,C)
133 133
Class II Beta Blockers
Propanolol Acebutalol
Esmalol Atenalol
Timolol Pindalol
Butexalol
Sotalol
Labetalol
Carvidalol
Class III: K channel Blockers
Napa
Sotalol
Bretylium
Amiodorone
THE END
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PHYSIOLOGY
Midgut (rotation 270)
Foregut (rotation 90)
Celiac artery
Parasympathetic:
Vagus
Sympathetic:splanchnic
nerves T5-T9
Hindgut ( Septation)
Inferior mesenteric
Parasympathetic: pelvic
splanchnic nerves
Sympathetic: lumbar
splanchnic nerves: L1-L2
Superior mesenteric
Parasympathetic:
Vagus
Sympathetic: splanchnic
nerves T9-T12
Gives rise to the GI, from mouth to second
part of duodenum, including the respiratory
tract
Lungs and upper GI have many congenital
connections
Extends from the second part of duodenum
to the spleenic flexure
Develops in the YOLK SAC
Must go through a 270 degree rotation as it
migrates from yolk sac into abdominal cavity
MIDGUT ROTATION requires ciliary action
KARTAGENERS: SITUS INVERSUS
FROM splenic flexure to the anus
WATERSHED AREA: the spleenic flexure
H th l t bl d l Has the least blood supply
Most susceptible to ischemic infarcts
CNS
ORAL
PHARYNGEAL PHARYNGEAL
ESOPHAGEAL
UGI
LGI
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SENSORY INFORMATION
THINKING about food
HEARING about food
SMELLING food
TOUCHING food
TASTING food TASTING food
ALL sensory information must reach the cortex;
Response is via the CORTOCOBULBAR pathway via the vagus
No longer do a vagotomy for peptic ulcer disease (cant enjoy
food)
Highly selective parietal cell vagotomy now
Cortex can over ride any basic urge:
(outer layer of the cerebrum-forgut)
LIMBIC SYSTEM- responsible for basic urges
Hippocampus long term memory
Amygdala- reward and fear, mating
Responsible for setting time: Circadian rhythms
Neurotransmitter: melatonin
Light outside- melatonin low- DAYTIME
Dark outside melatonin high NIGHT Dark outside- melatonin high- NIGHT
Morning- catabolic processes are in their highest
function- working out in the morning is the best
Melatonin from tryptophan- milk and turkey
- Bright lights in companies, casinos
- 1
st
, 2
nd
, 3
rd
shift workers/ workers comp
Feeding Center
(HUNGER)
Location:
Lateral hypothalamus
Satiety Center
Location:
Vento-medial nucleus of
the hypothalamus
Destruction: Anorexia
Destruction:
Hypothalamic obesity syndrome
Lateral hypothalamus
Stimulus:
Feeding (hunger) Glucose
If sugar remains normal the
center will not fire
Stimulus:
Stop feeding: Glucose
Stomach stretch will
stimulate satiety center
Can override- Cortex
ANOREXIA NERVOSA
Starvation
Desentasize your
hunger center
Body dysmorphic
Bulimia
Enjoys eating
Chunky female
Trying to please her
b f i d
ody dys o p c
disorder
Small body frame and
thinks they are over
weight
Young female trying to
please her mother
BMI < 17
boyfriend
Purging
Abrasion on knuckles
Tooth enamel erosion
Laxative abuse
BMI > 25
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Lesion of the satiety center (Ventormedial)
Uniparental disomy- one parent carrying lesion
Paternal in origin
T i l id Trinucletide repeats
Chromosome 15
Very aggressive appetite
Die due to over eating
Men: 5 feet = 106 lbs
Women: 5 feet= 100 lbs
Add 5 lbs for each inch past that
Small frame: add 15 lbs
Large frame: add 30 lbs
(i.e. male 510: 106 + 50 +30 = 186 lbs)
Norepinephrine or Serotonin (more important),
so many people use Amphetamines for weight
loss
80% of time > stimulates satiety center 80% of time > stimulates satiety center
20% of time > stimulates hunger center
They are taken up presynaptically, causing release
of all catecholamines
Increase DA, NE and Serotonin
Nausea/ vomiting -(DA) stimulates Nausea/ vomiting (DA) stimulates
Neuromuscular- basal ganglia- tics (DA)
Amphetamine tox. clue vertical nystagmus
Methylphenidate- ritilan (1
st
line) [drug dependence]
Narcolepsey (hipnogogic)hallucinations as you fall asleep
Pemoline-
hepatic necrosis (hepatitis)- off the market 2005
D d i d t i i ht l OTC Dexadrine- dexatrim - weight loss OTC
LSD- hallucinations from Seratonin (slow, lazy)
PCP- hallucinations from Seratonin (violent, aggressive)
ECSTACY- hallucinations from Seratonin (stimulate thirst)
Controls MENSES- progesterone stimulates
hunger system
Pregnancy- due to corpus luetum
FOOD craving.
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Controls TEMPERATURE:
ANTERIOR Hypothalamus: cools (inhibits NE)
Lesion anterior- die from: hyperthermia
POSTERIOR Hypothalamus: warms
Lesion posterior- die from hypothermia
Acetametaphen: for use with fever
(stimulate anterior hypothalamus- cools), then it
blocks posterior so you do not go back up again
Toxicity- microsteatosis, Reye syndrome in children
Tx: N-acetylcystine-reducing agent
- 4 hour level will determine if you use it
STRESS RESPONSE:
Parasympathetic first (HR dec.) increased
gastric motility, increase acid production
Sympathetic second (B/P inc) constipation,
pulls blood from GI, so you can not buffer acid
Stress from burn- Curlings ulcer
ICP- Cushing's ulcer
Seizure- foam at the mouth, defecate, urinate
(all parasympathetic)
Hollywood and sphincter control
Put food into mouth- salivary glands respond
SALIVARY GLANDS
Parotid [ in front of ear ](serous)-water - CN 9
Lingual [ on tongue ] (most serous) CN 7 Lingual [ on tongue ] (most serous) CN 7
Sublingual [under tongue] (most mucus) CN 7
Submandibular [jaw] (mucus) CN 7
Saliva in your mouth has to be HYPOTONIC (cracker)
Food on your cheek- food will get stuck (gummy bear)
Acetylcholine- CNS: excitatory, PNS: activates
muscles
Methacholine- dx asthma (old), beta 2 agonist to
bring you out
Pilocarpine- sweat test ( > 60), open angle
glaucoma (chronic)
Carbachol- post op urinary retention (stimulate
bladder emptying)
Bethanecol- post op urinary retention
Norepinephrine- and 1
Epinephrine- has methyl group (hormone)
Ephedrine- OTC med
Pseudoephedrine stress incont.
Phenylephrine- neurogenic shock Tx (constrict) Phenylephrine- neurogenic shock Tx (constrict)
RESULT: remove the blood supply to the GI causing
a decreased saliva that has increased osmolarity
(less saliva- more salt)
Exercise- mouth dry, white film in corner
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MCC: of malabsorption in children
CFTR gene on chromosome 7
Defective CHLORIDE transport Defective CHLORIDE transport
Chloride traps sodium, increasing the salt
content and thickness of secretions
Affects GI tract, lungs, pancreatic duct, sweat
glands and epididymus
Meconium ileus: first presentation in neonate
Malabsorption develops as pancreatic ducts
become clogged
Infertility in men develops as epididymus is
clogged (unable to ejaculate)
Obstructive lung disease develops over the
years (unable to cough up thick mucus)
Worst bacterial enemies:
Staph Aureus and Pseudomonas Auregenosa
MUST cover Staph Aureus with one
antibiotic and Pseudomonas Auregenosa
with two antibiotics
Dx: Pilocarpine: Cl sweat test
< 40 Normal
40 60 Heterozygous
> 60 CF
IgA
Lipase- little fat break down
Amylase: breaks alpha 1,4 bonds
Lysozyme: a detergent
HCO3 h f id HCO3: three sources of acid
From food- drinks
Produced by bacteria ( strep mutans)
Reflux
A normal phenomenon: GERD
ESOPHAGITIS- tissue inflammation (T-cell/Mac)
BARRETTS ESOPHAGUS- short to long
columnar
MALORY WEIS SYNDROME- tears in submucosa
(ETOH, vomiting)
BOORHAAVES SYNDROME- Rupture of
esophagus
INCISORS: cut 10 15 months
BICUSPIDS: chop 15- 18 months
MOLARS: grind 18 24 months
P i h f ll b 8 d Primary teeth fall out by age 8 and are
replaced by permanent teeth
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Masseter- closes
Temporalis- (closes) moves jaw forward and back
Medial Pterygoids (closes)
Lateral Pterygoids- (opens) lowers jaw
Innervated by cranial nerve 5 (Trigeminal)-
mandibular V3
Develop from first branchial arch
Tip of tongue rises >
Sides of tongue rise and fold medially >
Tip of tongue rises to hard palate >
Gravity begins bolus rolling >
When bolus approaches trachea epiglottis When bolus approaches trachea, epiglottis
Closes off glottis >
Bolus rolls over epiglottis/touches the pharynx>
CN 9, 10 sense the bolus >
UES opens relaxes >
Bolus drops into esophagus
UPPER ESOPHAGEAL SPHINCTER
Voluntary
Skeletal muscle in upper 1/3 of esophagus
Constrictors of the pharynx
Stylopharyngeus y p y g
Develops from 4
th
pharyngeal arch
Innervated by
CN 9(stylopharyngeus)
CN10(all others)
Nucleus Ambiguus: innervates the UES-
efferent vagus (motor CN 10)
Dorsal motor nucleus: innervates the rest
of GI efferent vagus (motor CN 10)
Primary peristalsis: requires vagus nerve
and Auerbachs plexus; begins just distal
to the UES only
Secondary peristalsis: intrinsic to smooth
muscle; can begin anywhere in GI
UES
1 Peristalsis
- Vagus CN 10
- Auerbauch (VIP)
Nucleus
Ambiguous
2 Peristalsis
- Stretch from food
Dorsal motor nucleus
of CN 10 (Vagus)
LES
Receptive
relaxation
No receptive
relaxation:
Achalasia
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7
Esophageal Pathology
Choanal atresia: lack apoptosis /blue-
feeding
Esophageal atresia w/ distal TE fistula
Vomit on first feeding
Plummer
Vinson
UES
Syndrome
Iron deficiency
Strips of mucosal tissue- lack apoptosis
Risk of esophageal cancer
Young woman
Microcytic anemia
Schatzki rings:
-Intermittent
dysphagia
- Around LES
LES
Zenckers: congenital
Traction diverticula: occurs due to large bolus
Zenckers
Diverticulium -
C it l
UES
LES
Congenital
Traction
Diverticulium
Patients with a history of GERD > 5 years
(Screening for Barrettes esoph.-sq. to columnar)
Tx: PPIs, upper endoscopy every 2-3 years
Patients with long standing cirrhosis: screening for
varices
Tx: Propranolol- decreases risk of bleeding
Abnormal esophageal acid exposure
> 4 week trial of PPIs still having symptoms
E l d GERD i i i h l i d Exclude GERD in patients with unexplained
chest pain
GERD symptoms with a negative upper
endoscopy
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8
Best initial test for dysphagia
Not the best test if the problem is due to an
obvious obstruction, then the best test is
upper endoscopy upper endoscopy
Achalasia- bird beak
Diffuse esophageal spasm- cork screw
Diagnosis:
Dysphagia
Unexplained chest pain w/o mechanical obst.
T d l d i h d Transducer placed in esophagous to record
pressure
Most accurate test for Achalasia, Esophageal spasm
Diagnosis: GERD
NGT placed at the esophageal junction
Dil h d hl i id i i j d h h Dilute hydrochloric acid is injected through
the NGT to reproduce the symptoms of GERD
OLD TEST..PPIs and 24 hour pH monitor
ALWAYS THE WRONG ANSWER !!!!!!!!!
Cardia
Fundus
FOOD
LES
Caudad
Region
Orad
Region
Body
Antrum
G cells
Pyloris
Duod
Orad region- fundus and proximal portion of
the body
Thin muscle wall
Caudad region distal portion of the body Caudad region - distal portion of the body
and the antrum
Thicker muscle wall
Region responsible for mixing the food
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Receptive relaxation: relaxation of the lower
esophagous sphinctor and the orad region to
accept food into the stomach.
Vagovagal reflex both afferent and efferent Vagovagal reflex- both afferent and efferent
limbs of the reflex are carried in the vagus
nerve
Vagus
Afferent
Efferent
Mechanoreceptors detect distension of
the stomach and relay this information
to the CNS via sensory neurons
CNS then sends efferent information to
the smooth muscle wall of the orad
stomach, causing it to relax
f Neurotransmitter released from the
postganglionic vagal nerve fibers is VIP
Vagotomy eliminates receptive
relaxation
VIP
During fasting- periodic gastric contrations
occur MMC
migrating myoelectric complexes
d d l Mediated my Motilin
Occur ever 90 minutes
Function to clear the stomach of any
residue remaining from a previous meal
Takes approximately 3 hours to empty
Rate must be regulated to provide adequate time to Rate must be regulated to provide adequate time to
neutralize the gastric H+ in the duodenum
adequate time for absorption of nutrients
Two factors slow or inhibit gastric emptying:
Fat and H+ in the duodenum
Fat- mediated by CCK (secreted by duodenum)
H+- mediated by reflexes of the enteric nerves (myenteric
plexus) ensures content is delivered to the duodenum
slowly
Four major components:
Hydrochloric acid (HCL)- function is to reduce pH for
the conversion of pepsinogen to pepsin
Pepsinogen (inactive) Low pH converts it to the active Pepsinogen (inactive) Low pH converts it to the active
form- pepsin for protein digestion
Intrinsic factor-for the absorption of Vit. B12 in the
ileum (essential)
Mucus- protects the gastric mucosa from HCL
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Glands of the Body of the Stomach
Empty their secretory products via ducts
Opening of the glands are called pits
Lined with epithelial cells
Gastric
Lumen
Epithelial cells
Mucous cells
Parietal cells
Chief cells
HCL & Intrinsic factor
Pepsinogen
Glands of the Antrum of the Stomach
Contain 2 cell type:
Mucus cells- mucus and HCO3 are
protective
G-cells (secrete gastrin into circulation)
Gastric
Lumen
Epithelial cells
Mucous cells
G - cell Gastrin
Mucus, Pepsinogen, and HCO3-
Mucus from goblet cells
Prostaglandins (PGE2)
HCO3: alkaline tide
A i i i ibl bl k C 1 & 2 Aspirin- irreversible block Cox 1 & 2
NSAIDs - reversible inhibit COX
Steroids
COX 1 GI COX 2- Joints
Misoprostyl- replace PGE
(Vasocon/Vasodilation- alprostadil)
Cox 2 inhibitors Cox 2 inhibitors
Celecoxib- only one left
Rofecoxib- off the market
Valdecoxib off the market
(problem if on > 18 mo)- block
prostacyclins- inhibit platelet agg.
Gastric ulcers due to lack of blood supply;
sympathetic output causes vasoconstriction
CUSHINGS ULCER
CURLINGS ULCER
STRESS ULCER
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Regulation of H+ Secretion
Is the most common cause of upper GI
bleeding in older children and adults
Superficial erosions
Type A Gastritis (located in body)
Autoimmune etiology
Antiparietal cell antibody
Atrophic gastritis
Adenocarcinoma risk
Body
Type B gastritis (located in antrum)
Due to a breakdown in barrier protection
NOT TOO MUCH ACID!
Associated with Helicobacter Pylori
Gastric Ulcer
Pain is worse during the meal
Located in the antrum Located in the antrum
Associated with H. Pylori 70% of time
Associated with CANCER 20% of time
Endoscopy on ALL patients
Duodenal Ulcers
Pain is worse 30 to 40 minutes after a meal and
also at night
Located in the second part of the duodenum
Associated with H. Pylori 95% of time
Cancer risk < 1%
Treat empirically with medication
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Surgical indications:
Intractable pain- meds fail
Hemorrhage- massive UGB Hemorrhage massive UGB
Obstruction- Scarring
Perforation- Retroperitoneal
R/O- CT
Definition: a mass made of
undigestible materials
Most common type: Hair yp
Causes a gastric outlet obstruction
TX: endoscopy and removal
SLIDING TYPE: 90%
Involve sliding of the fundus into the esophageal
hiatus
MCC: obesity; restrictive lung disease
TX: conservative measures; medications;
surgery( Nissan fundoplication)- no belch
High incidence of GERD
ROLLING TYPE:
Due to a defect in the diaphragm
Requires surgery q g y
Risk of strangulation and infarction
Rare
Large RUGAL FOLDS on biopsy
H l i f bl ll Hyperplasia of goblet cells
Cells ooze out proteins
Like nephrotic syndrome
Low albumin
Hypertrophy of the pyloric muscle
Presents at 3 to 4 weeks of life
PROJECTILE vomiting J g
Olive sign; string sign on Barrium;
DX: ultrasound
TX: correct fluids and electrolytes
pyloromyotomy
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PROTEIN: no protein digestion in the mouth;
significant digestion in the stomach;
completed in the small bowel
SUGARS: significant digestion in the mouth; it g g ;
stalls in the stomach; completed in the small
bowel
FATS: negligible digestion in the mouth; it
stalls in the stomach; completes in the small
bowel
Now we call it CHYME
Secretin
CCK
Motilin
GIP GIP
VIP
Somatostatin
Enterokinase
Zymogens: inactive enzymes
First trypsin activated by
enterokinase enterokinase
Trypsin then activates all other
enzymes
Breaks alpha 1,4 glycosidic bonds
Lactose
Sucrose
Maltose
Alpha-dextrins p
Fructose is only sugar with its own transport system
Lactase
Sucrase
Maltase
Alpha-dextrinase
Sucrase def is most common primary Sucrase def is most common primary
disacharidase deficiency
Lactase def is most common secondary
disacharidase deficiency
First enzyme to disappear in gastroenteritis; last
one to return( in about 48 hours)
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The most common severe abdominal pain
Pain is mid-epigastric, boring through to the
back
Children: MCC is (1)abdominal trauma
(2) infections
Cocksackie B, Mumps virus
Adults: MCC is (1) alcohol
(2) gallstones
Phlegmon: inflamed pancreas with the
intestines wrapped around it
Causes a severe ileus
Severe dehydration Severe dehydration
Ransons criteria:
Age > 55 years
Blood sugar rises above 200
WBC > 16,000
LDH > 350
AST > 250
Poor prognosis in first 24 hours if
Patient needs more than 6 liters of fluid
pO2 < 55 (ARDS)
Hemoglobin drops by 2 or more grams
Calcium drops to below 8
MANAGEMENT: (for ANY abdominal pain)
NPO
NG tube
IV normal saline IV normal saline
Meperidine
Abdominal x-ray
Hemorrhagic pancreatitis:
Bleeding into the retroperitoneal
Grey-Turner sign
Cullen sign Cullen sign
TX: subtotal pancreatectomy
Pseudocyst: has no epithelial lining
Can become infected ( abscess)
Tx: connect it to skin or small bowel
Characterized by persistent high amylase
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Virchows triangle
Bile
Lecithin
Salts
Cholesterol
RUQ colic (stone): pain comes in waves
Murphys sign: cessation of inspiratory
effort with RUQ palpation
80% are made of cholesterol (not seen on x-ray) 80% are made of cholesterol (not seen on x-ray)
20% are made of calcium bilirubinate (hemolytic
anemia) excess biliruben
90% get lodged in cystic duct (Alk phos normal)
10% get lodged in the common bile duct
(Inc. Alk phos)
3 clues for common bile duct stone:
Pancreatitis
High alkaline phosphatase- common bile duct High alkaline phosphatase common bile duct
High WBC count and fever- pus backs up
Dx: Ultrasound;
HIDA scan (most specific)- injectable radioactive
- if an obstruction- non visualization of gall bladder
Management: like ALL abdominal pains Management: like ALL abdominal pains
NPO
NGT
IV
Opiates- meperadine (always start with)
ABD xray
Stone in common bile duct
Surgery: ERCP (endoscopic retrograde
choleangopancreotophagraphy-pull it out by mouth;
Laporoscopic cholecystectomy- 90% of cases
Asymptomatic gallstones-ursodeoxycolic acid
(DM, OCP, pregnancy) and schedule for surgery (60 % will
progress)
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Helps EMULSIFY fats
Comes from Phosphatidylcholine
Modified to make surfactant
Bile acids:
Cholesterol go to the liver and forms
Cholic and Chenodeoxycholic acids Cholic and Chenodeoxycholic acids
which are conjugated to Glycine and
Taurine to form bile salts
Help EMULSIFY fats
Cholestyramine
Colestipol
Side effects: need cholesterol to make
EEstrogen
Steroids
Malabsorption (diarrhea)
Fat for energy
Fat soluble vitamins
Cause gall stone
Micelle
Short chain fatty acids
Medium chain fatty acids
Long chain fatty acids
Chil i Chilomicrons
VLDL
IDL
LDL
HDL
LDL and B100
FOAM CELL
Atherosclerosis
Clathrin Pits
Symptoms:
70% Stenosis
FOAM CELL
Cholesterol Atheroma
Events:
90% Stenosis
Metabolism of the lipoprotein is
defective
Triglycerides, cholesterol or both can
be elevated
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Predisposes to xanthelesma and
pancreatitis
Defective metabolism of VLDL, IDL
or Chilomicrons
Predisposes to early coronary artery
disease and xanthomas
Defective metabolism of LDL
TYPE 1: elevated chilomicrons
TYPE 2A: elevated LDL
TYPE 2B: elevated LDL & VLDL
TYPE 3: elevated IDL
TYPE 4: elevated VLDL
TYPE 5: elevated VLDL & CHILOMICRONS
STATINS: block HMG-CoA reductase
Main side effects: myositis; hepatitis
Lovastatin
Provostatin Provostatin
Simvastatin Works best after 8pm
Atorvastatin
Cirivastatin
Valdestatin
Reduvastatin
Cholestyramine- binds bile and blocks
reabsorption
Colestipol
Niacin : (-) VLDL
Probucol
Gemfibrozil : increases LPL
Clofibrate
Niacin
Probucol
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Intravascular hemolysis
Vasculitis
Schistocytes
Low haptoglobin
Fibrin deposition in vessels
Extravascular hemolysis
Splenomegaly
Something is wrong
with RBC membrane
Mcc: autoimmune
Fibrin deposition in vessels
tear RBCs and platelets
hemolytic anemia
Direct hyperbilirubinemia: conjugated
Indirect hyperbilirubinemia: unconjugated
INDIRECT INDIRECT
Low albumin
Gilbert syndrome
Criggler-Najjar syndrome
Type 1
DIRECT
Criggler-Najjar syndrome, type 2
Rotors syndrome
Dubin-Johnson syndrome Dubin Johnson syndrome
Newborns: choledochal cyst; biliary atresia
Children and adults: pancreatitis; gallstones;
sclerosing cholangitis; primary biliary
cirrhosis cirrhosis
After age 40: pancreatic cancer
The Ileum: in children
The Sigmoid: in adults
Diverticulosis Diverticulosis
Diverticulitis
Volvulus
Intussusception
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The last part of the small bowel
An organ with NO known function
Begins with pain around umbilicus
(visceral pain)
Pain settles into RLQ ( McBurneys point)
somatic pain somatic pain
Caused by a fecolith
Management: like ALL abdominal pains
30% perforate in 24 hours
Incidental appendectomies can be done
The first part of the colon
The largest part of the colon
Cecal cancer has poor prognosis
LAST chance to REABSORB fluids and
electrolytes
Many Na-K pumps controlled by
aldosterone
Haustration
Mass movement Mass movement
Watershed area: spleenic flexure
Haustration
Mass movement
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Sits at a 90 degree angle with the
descending colon AND rectum
Pubococcygeus muscle forms the
sling that holds the rectum at 90
degree angle
Relax pubococcygeus muscle
Rectum falls in line with sigmoid colon
Gravity and distention start moving stool
down
Once stool touches internal anal sphincter,
f d f first urge to defecate occurs
Once stool touches external anal sphincter,
last urge to defecate occurs
Relaxation of pelvic floor muscles relaxes
both sphincters
NO sympathetic input to defecation
Duodenum Jejunum Ileum
Amino
Acids
FATS
Sugars
80
90
90
Iron
A,D,E,K,
B12
All else
90
90
100
Ca-carbonate
Aluminum hydroxide
Mg-hydroxide
Gaviscon
Sucralfate
h
PPI
Omeprazole
Esomeprazole
Pantaprazole
Robeprazole
lomeprazole
Bismuth
H-2 Blockers
Cimetidine
Ranitidine
Famotidine
Nizatidine
Simethicone
Loperamide
Diphenoxylate
Mineral oil
Cisapride
Metachlopramide
Psillium
Sorbitol
Mg-citrate
Phenophthalien
Docussate sodium
Sulfasalazine
Sulfapyrazone
Abetalipoproteinemia
Ataxia telangiectasia
Selective Ig-A def
H h i di Heavy chain disease
Celiac Sprue
Tropical Sprue
Necrotizing enterocolitis
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Irritable bowel syndrome
Spastic colon
Whipples disease
Toxic megacolon
Ischemic bowel
Crohns disease
Women
Transmural
Melena
Granulomatous
Creeping fat
Ulcerative Colitis
Men
Hematochezia
Mucosal
Starts in rectum > prox
Pseudopolyps Creeping fat
Cobblestoning
Skip lesions
From mouth to anus
Starts in ileum
Fistulas
Pseudopolyps
Continuous
HLA B-27
Sclerosing choolangitis
Toxic megacolon
Lead pipe colon
Colon cancer risk: 10%
at 10 years
Begin annual colonoscopy
at 7 years
Newborns: swallowed maternal blood
Children: epistaxis
Ad l i i Adults: gastritis
Massive UGI bleeding
Children: meckels diverticulum
Adults: Peptic ulcer disease
Newborns: swallowed maternal blood
Infants: anal fissure
Child l Children: polyps
Adults: IBD
Elderly: Angiodysplasia
Diverticulosis
Cancer
Newborns:
Choanal atresia
C-type esophageal atresia
Duodenal atresia
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3 to 4 weeks old
Pyloric stenosis y
4 to 6 months old
achalasia achalasia
6 months to 2 years of age
intussusception
2 years to 40 years
Adhesions Adhesions
Internal hernias
FIRST year of life
Hirschsprungs disease Hirschsprung s disease
1 year to 40 years
Adhesions Adhesions
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After age 40
Adhesions
Obstipation Obstipation
Diverticulitis
Cancer
GI
Management Management
Measurement of radiolabeled carbon dioxide after
the oral ingestion of labeled urea
H. pylori splits urea with urease
Confirm eradication of H pylori Confirm eradication of H. pylori
If ulcer is found on endoscopy, the test of choice
will be biopsy, not urea breath test
Detect steatorrhea as a sign of fat
malabsorption
Pick Sudan black stain when you see a patient
with chronic pale greasy malodorous with chronic pale, greasy, malodorous
diarrhea and no evidence of infection
Suspect chronic pancreatitis in pts w/steatorrhea
Trypsinogen levels are low from a burned out
pancreas
Pick trypsinogen level only after Sudan black stain has Pick trypsinogen level only after Sudan black stain has
confirmed a fat malabsorption
Wheat or gluten (gliadin) antigens
DX of celiac disease
Small bowel biopsy is the most accurate test for
celiac disease
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Differentiate between intestinal malabsorption and
chronic pancreatitis
D-xylose is a sugar that should be absorbed if the small
bowel is intact
Low urine levels of D-xylose- defective intestinal mucosa
( Celiac, tropical sprue and Whipples disease)
Best initial test for Wilsons disease
Unexplained hepatic and psychiatric abnormalities
with movement disorder
Low ceruloplasmin levels = Wilsons disease
Most accurate test is a liver biopsy
Best initial test in the diagnosis of acute pancreatitis
Lipase is more specific to the pancreas
Amylase can be elevated from damage to the salivary y g y
glands, esophagus or small bowel
Most accurate test for acute pancreatitis is abdominal
CT- indicator of the need for a pancreatic biopsy
Best initial test for autoimmune hepatitis
Young female with liver disease
Liver biopsy most accurate test
Best initital test for primary biliary cirrhosis
(PBC)
Middle aged female with itching (pruritus) and
an elevated alkaline phosphatase with normal
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ENDOCRINOLOGY
Endocrinology, cont
Exocrine: secreted into a cavity (pancreas)
Paracrine: secreted, then works only in the vicinity
(somatostatin)
Autocrine: secreted by the cell it works on
(granulosa cells)
Apocrine ( merocrine) tip of cell is secreted with the
substance (sweat glands)
Holocrine: entire cell is secreted with the substance
(sweat glands of the arm pit and groin)
HORMONE
Name and where it comes from
Main stimulus
Main inhibitor
Where does it go? g
What is the main action?
What is second messenger?
Miscellaneous syndromes
HORMONES
STEROID HORMONES
Fat soluble
Nuclear membrane
receptor
PROTEIN HORMONES
Water soluble
Cell membrane
receptors
receptor
Affect DNA replication,
transcription and
translation
Work via proteins
NO second messengers
receptors
Work via second
messengers
ERYTHROPOETIN
Made by: renal parenchymal cells
Signal: hypoxia ( NOT anemia)
Inhibitor: increased oxygen Inhibitor: increased oxygen
Where it goes: bone marrow
What it does: erythropoiesis
Second messenger: tyrosine kinase
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POLYCYTHEMIA
First.check erythropoietin
Normal erythropoietin:
Gaisbock syndrome;
Stress polycythemia;
Spurious (not real) ;
Due to loss of plasma volume
POLYCYTHEMIA
Increased erythropoietin: due to hypoxia
Acute hypoxia: tachypnea and dyspnea
Chronic hypoxia: clubbing
(angiogenen newvessels) (angiogenen-new vessels)
Restrictive LD; COPD;
RENAL CELL CARCINOMA- adults
Wilms tumor- children
POLYCYTHEMIA
Decreased erythropoietin:
You have a cancer !!!!!!!!
Bone marrow is acting on its own g
POLYCYTHEMIA RUBRA VERA
Essential thrombocythemia
(platelets>600000)
Angiotensin II
ACTH
ACTH
ADRENAL CORTEX
Zona Glomerulosa: ALDOSTERONE
Stimulus: hypovolemia; hyponatremia; hyperkalemia
Inhibition: hypervolemia
Where it goes: late DCT
What it does: stimulate synthesis of Na-K pumps
Second messenger: none
ALDOSTERONE, cont
Miscellaneous syndromes: (tumor)
Too much: CONNS SYNDROME
Hypernatremia
Hypokalemia (K freely filters out)
Alkalosis (K/H exchange)
Hypertension (3 H2O for every Na+)
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ALDOSTERONE, cont
Too little: ADRENAL INSUFFICIENCY
21 hydroxylase def
11 hydroxylase def
In adults:
Abrupt withdrawal of steroids
Autoimmune adrenalitis
21 Hydroxylase deficiency:
Decreased Aldosterone [mineral corticoid]
(Na+ wasting)- hypotension
Lo co tisol [Gl coco ticoid] Low cortisol [Glucocorticoid]
no feedback by ACTH
Increased Androgens-
virilization
11 Hydroxylase deficiency:
Excess 11-Deoxycorticosterone-
retain salt HTN
Aldosterone decreased desmolase rate limiting
t i th th ll t i ti t AT II step in the pathway- allosteric activator- AT-II
(down regulated due to the HTN)
Low cortisol- no ACTH feedback
Increased Androgen production- virilization
Zona Fasciculata
CORTISOL
Stimulus: stress; hypoglycemia
Inhibitor: hyperglycemia
Where it goes: everywhere >PERMISSIVE
What it does: up regulates ALL receptors during stress
Second messenger: none
CORTISOL
Physiologic affects
Proteolysis
Gluconeogenesis
(break down protein
Anti-inflammatory
Kills T-cells and
eosinophil
Inhibit macrophage (break down protein
to make glucose)
Inhibit macrophage
migration
Stabilizes endothelium
Stabilizes mast cells
Inhibits phospholipase-A
Cortisol, cont
Too little: Adrenal insufficiency ( Addisons )
Too much: CUSHINGS SYNDROME
Pituitary adenoma: Cushings disease (to much ACTH)
Small cell carcinoma: Cushings disease
Adrenal adenoma: Cushings syndrome
Disease affects one organ
Syndrome affects many organs
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Dexamethasone suppression test
Lo-dose: 0.5mg IV Q6 x 4
If suppression occurs
Obesity Obesity
Depression
Normal variant
Dexamethasone suppression test
Hi dose: 1 mg IV Q6 x 4
If suppression occurs
Pituitary adenoma
If suppression does NOT occur
Check ACTH levels:
High ACTH: SMALL CELL CARCINOMA
Low ACTH: ADRENAL ADENOMA
ZONA RETICULARIS
Testosterone
Stimulus:
Controls male external genitalia in utero
Increase in appetite Increase in appetite
Aggression and violence
Increases libido and RBC count
Stimulated by ACTH
Second messenger: none
TESTOSTERONE
DHT: made in testes by 5 alpha reductase
Leads to secondary male characteristics at
puberty.
Responsible for hair growth Responsible for hair growth
Too much leads to hair loss, especially in the
middle and front of scalp
Male patterned baldness
FENESTERIDE blocks 5 alpha reductase
FLUTAMIDE blocks DHT receptors
ADRENAL MEDULLA
Epinephrine:
Stimulus: stress/hypoglycemia
Inhibition: hyperglycemia
Where it goes: liver and adrenal cortex
What it does: gluconeogenesis;
glycogenolysis
Second messenger: c-AMP
Misc. syndromes
Pheochromocytoma or Neuroblastoma
An excess of NE and Epi
Intermittent palpitations, HTN, diaphoresis and headache
Neuroblastoma:
hypsarrythmia (dancing eyes) hypsarrythmia (dancing eyes)
opsoclonus (dancing feet)
Dx: measure urinary VMA and metanephrines
( dopamine > HVA)
Phentolamine- short acting alpha blocker for diagnosis
Tx: phenoxybenzamine (longer acting, not specific)
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Pheochromocytoma or Neuroblastoma
Difficult to differentiate benign from malignant
on biopsy; they look alike
Neuroblastoma is MOST common abdominal
mass in children
Pheochromocytoma
10% are malignant
10% are bilateral
10% are in children
10% are familial
10% are metastatic at diagnosis
Pheochromocytoma
24 hr urine collection
Metanephrine
Vanillyl mandelic Acid (VMA)
Catecholamines Catecholamines
If elevated CT or MRI
If CT or MRI find nothing:
meta-iodo-benzyl-guanidine (MIBG) scinigraphy
(NE analogue that concentrates in the adrenals)
Stress Hormones
Epinephrine:
immediately
Glucagon: within 20
minutes
Cortisol: within 2 to 4
Insulin: within 30 min
ADH: within 30 min
Insulin pushes the
i t ll d
Cortisol: within 2 to 4
hours
GH: after 24 hours
THESE PRODUCE THE
SUGAR
sugar into cells and
ADH normalizes the
osmolarity
Pancreatic Hormones
Glucagon: from ALPHA cells
Insulin: from BETA cells
Somatostatin: from DELTA cells
Pancreatic Polypeptide: from F cells
Glucagon
From: pancreatic alpha cells (1 receptors)
Stimulus: hypoglycemia and stress
Inhibition: hyperglycemia
Where it goes: adrenal cortex, liver, and
di ti adipose tissue
What it does: gluconeogenesis (raises
sugar), glycogenolysis (glycogen), lipolysis
(fat), and ketogenesis
Second messenger: c-AMP
Misc. syndromes
Glucagonoma
Pancreatic tumor
High glucose; high lipids; and high
ketones
Related to MEN I ( Wermers)
Hormone responsible for KETOACIDOSIS
in type 1 diabetes
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cells of the pancreas lnsulin
From: pancreatic islet cells cells
(2 and 2 receptors)
Stimulus: hyperglycemia
Inhibition: hypoglycemia
Wh it h t BRICKLE Where it goes: everywhere except BRICKLE
What it does: increase all anabolic
processes
Second messenger: tyrosine kinase
Misc syndromes
Insulinoma vs Nessidioblastosis
INSULINOMA
Seen primarily in
adults
Causes hypoglycemia
M hi h i li
NESSIDIOBLASTOSIS
seen primarily in
infants
causes
hypoglycemia
Measure high insulin
and high C-peptide
Dx: cat scan
Tx: remove surgically
hypoglycemia
measure high insulin
and high C-peptide
Tx: subtotal
pancreatectomy
Somatostatin
From: pancreatic DELTA cells
Stimulus: insulin and glucagon
Inhibition: low insulin and glucagon
Wh Where it goes: paracrine
What it does: inhibits insulin and glucagon
Second messenger: c-AMP
Misc. syndromes
Somatostatinoma
Usually a pancreatic tumor
Severe constipation
Dx: cat scan
Tx: surgery
Pancreatic Polypeptide
NO KNOWN FUNCTION!
Wh t i th l k ith What is the only know organ with no
known function?
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GI
HORMONES
GI Hormones
Stomach
Gastrin
Duodenum
Secretin
CCK
Motilin Motilin
GIP
VIP
Somatostatin
Secretin
From: duodenum
Stimulus: low pH
Inhibition: high pH
Where it goes: paracrine (pancreas &
gallbladder) gallbladder)
What it does: stimulates production and
secretion of bicarbonate ions from pancreas
& GB
Second messenger: c-AMP
Misc. syndromes: none
CCK
From: duodenum
Stimulus: food, especially fats
Inhibition: high pH
Where it goes: pancreas (digestive enzymes)
and gallbladder (bile)
What it does: primarily fat and protein
digestion
Second messenger: IP3/DAG
Misc. syndromes: none
GIP
From: duodenum
Stimulus: glucose
Inhibition: high pH
Wh it ti i l t ll Where it goes: pancreatic islet cells
What it does: enhances insulin secretion
Second messenger: c-GMP
Misc. syndromes
GIP Syndromes
Dumping Syndrome: seen after Bilroth ll
procedure
Increased osmotic load dumped Into duodenum
Causes osmotic diarrhea
Can also cause postprandial (reactive) Can also cause postprandial (reactive)
hypoglycemia
Causes insulin resistance over time (type 2
diabetes)
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Somatostatin
From: duodenum
Stimulus: duodenal hormones
Inhibition: high pH
Where it goes: paracrine
What it does: purely inhibitory
Second messenger: c-AMP
Misc. syndromes: somatostatinoma
VIP
From: duodenum (from Auerbachs
plexus)
Stimulus: duodenal hormones
Inhibition: high pH
Where it goes: paracrine
What it does: purely Inhibitory to all
duodenal hormones
Second messenger: c-AMP
Misc. syndromes
Vipoma
Usually a pancreatic tumor
WATERY or secretory diarrhea
Dx: cat scan Dx: cat scan
Tx: surgery
Gastrin
From: antrum of stomach
Stimulus: high pH
Inhibition: low pH
Where it goes: parietal cells of the Where it goes: parietal cells of the
stomach (mostly in the body of stomach)
What it does: production of HCL and
intrinsic factor (for absorbing VIT B12)
Second messenger: calcium
Misc. syndromes
Gastrinoma
Usually a pancreatic tumor
Zollinger-Ellison syndrome
Gastrin levels are high all the time Gastrin levels are high all the time
Can be part of MEN-1 syndrome
ANP ( B-type natriuretic peptide )
From: right atrium
Stimulus: high volume (stretch of right Atrium)
Inhibition: low volume
Where it goes: kidney
What it does: dilates the afferent renal artery;
inhibits aldosterone
Second messenger: nitric oxide
Misc. syndromeleads to polyuria, nocturia and
hyponatremia in right atrial distention
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PTH
VITAMIN D
CALCITONIN
CALCIUM
METABOLISM
PTH
Superior parathyroids: 4
th
pharyngeal pouch
Inferior parathyroids: 3
rd
pharyngeal arch
Stimulus: low calcium; high phosphorus
Inhibition: high calcium; low phosphorus
Where it goes: (1) osteoclasts of bone (2)late Where it goes: (1) osteoclasts of bone (2)late
DCT
What it does:
(1) stimulate osteoclastic activity
(2) increases secretion of phosphorus
(3) activates 1-alpha hydroxylase
PTH, cont
Second messenger: c-AMP
Misc. syndromes
PTH Syndromes
HYPO-PARATHYROIDISM
Primary: due to thyroidectomy
P d t t ki h t 3
rd
Pseudo: receptor not working; short 3
rd
and 5
th
digit
Pseudopseudo
HYPOPARATHYROIDISM : only
difference is that calcium is normal
PTH Syndromes
HYPER-PARATHYROIDISM
Primary: due to parathyroid adenoma;
MCC of isolated hypercalcemia in adults
Secondary: due to renal failure
Renal Osteodystrophy
Osteitis Fibrosa Cystica- fibrous tissue
Osteopenia- low density
Osteomalacia- nutrition
Osteosclerosis- trauma
Vitamin D
From: skin > liver > renal
Stimulus: low calcium; low phosphorus
Inhibition: high calcium; high phosphorus
Where it goes: (1) kidney and (2) GI
What it does: (1) production of Ca-ATPase and
(2) production of CBP ;(3) stimulates
osteoblastic activity
Second messenger: none
Misc. syndromes
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Vitamin D syndromes
Deficiency: Osteomalacia in adults; Rickets in
children
Excess: high calcium; high phosphorus g g p p
Calcitonin
From: parafollicular cells
Stimulus: high calcium
Inhibition: low calcium
Where it goes: bone
What it does: inhibit osteoclastic activity
Second messenger: c-AMP
Misc. syndromes
MEN Syndromes
MEN 1: pituitary adenomas, parathyroid
adenomas, and pancreatic adenomas
(Wermer syndrome)
MEN 2: medullary carcinoma of thyroid (high MEN 2: medullary carcinoma of thyroid (high
calcitonin), pheochromocytoma, plus or minus
parathyroid adenoma( Sipple syndrome)
MEN 3: men 2 with neuroma/ganglioneuroma but
minus parathyroid adenoma
Bisphosphonates
Inhibit osteoclastic activity like calcitonin
Second line drugs for osteoporosis
Very corrosive in the GI Very corrosive in the GI
Causes osteonecrosis (if received via IV)
Stored in bone for up to 20 years
i.e. etidranate; elandronate; ibondranate,
residronate
Hypothalamic Hormones
Pituitary Hormones
Prolactin:
Stimulate PRL release- nipple
stimulation
Inhibit PRL release- DA
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Dopamine Agonists
L-Dopa/Carbidopa
Bromocriptine- old (stop lactation)
Selegyline- MAO type B, increases extracellular
dopamine
Amantadine- antiviral (influenza A)
(-) prolactin- cant lactate
N/V CTZ
Movement disorders- gross motor
Dopamine Blockers (D-2)
Phenothiazines
Chlorpromazine
Prochlorperazine (Compazine): anti-N/V
Promethazine
Fluphenazine Fluphenazine
Thioridazine- pigment retinopathy
Thioxanthenes
Thiothixene- long acting (>30 days)
Dopamine Blockers (D-2)
Butyrephenones
Haloperidol- antipsychotic- schizophrenia, psychosis
Droperidol - antimetic
At i l bl k D 4 t Atypicals: block D-4 receptors
Used for negative symptoms
Used when pt has had extrapyramidal side effects
Clozapine- agranulocytosis
Onlazapine- wt. gain
Resperidone- neuroleptic anesth.
(fever, muscle stiffness)
Pituitary Tumors
Nonfunctional (chromophobic) adenomas: most
common pituitary tumor
Prolactinoma: most common functional pituitary
ttumor
ALL pituitary tumors associated with high prolactin
levels
High PRL > galactorrhea and amenorrhea
Hypothyroidism
Cretinism- Mom and fetus- hypo
Iodine deficiency
Hashimotos disease
DeQuarvains disease- Virus (painful)-self limiting
Lymphocytic thyroiditis (postpartum )
Riedels Struma- capsule cancer (woody)
Tx: Thyroxine(T-4) or L-Thyronine (T-3)
Hypothyroidism:
3 T4 TSH TRH
2 T4 TSH TRH
1 T4 TSH TRH
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Hyperthyroidism
Graves Disease ( autoimmune) < 50 y/o TSH
antibody
Plummers Syndrome: toxic multinodular goiter
> 50 y/o one area hot (iodine takeup)
Tx: propanolol
Propylthiouracil- blocks peroxidation
Methimazole- block peroxidation
I-131- destroy the tissue
Thyroxine- replacement
THE
END
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Rheumatology gy
Steps to evaluate a patient
First Step: Distribution
Polyarticular symmetric-
Monoarticular arthritis
Oligoarticular asymmetric-
Migratory arthropathy-
Polyarticular symmetric
Rheumatoid arthritis (RA)
SLE (spares joint destruction)
Viral (Hep B EBV CMV B19) Viral (Hep. B, EBV, CMV, B19)
First Step: Distribution
Polyarticular symmetric:
Monoarticular arthritis
Oligoarticular asymmetric
Migratory arthropathy
Monoarticular arthritis
OA
Gout
Septic arthritis
First Step: Distribution
Polyarticular symmetric:
Monoarticular arthritis:
Oligoarticular asymmetric:
Migratory arthropathy:
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2
Oligoarticular asymmetric joint
Spondyloarthropathies
First Step: Distribution
Polyarticular symmetric:
Monoarticular arthritis:
Oligoarticular asymmetric:
Migratory arthropathy:
Migratory arthropathy
Rheumatic fever
Gonococcal arthritis (disseminated)
Lyme disease
Pain move around the body
Second step:
Acute or Chronic
Osteoarthritis
Septic arthritis
Crystal induced
Third step:
Is there any evidence of systemic
symptoms?
LLungs:
Kidney:
CNS:
Skin:
Hemotologic:
Fourth step:
Any evidence of inflammation?
OA:
RA:
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3
Inflammation association
Morning stiffness > 1hr
Red, warm, tender , ,
Erythematous joint
Increased ESR and CRP
CASE 1
72 y/o woman
presents with left presents with left
knee pain.
Monoarticular
OA (chronic)
Septic (acute)
Crystal induced (acute)
CASE 2
30 y/o female
presents with wrist presents with wrist,
MCP and PIP
swelling and pain.
Polyarticular
SLE
Viral
RA
CASE 3
32 y/o male presents with
knee swelling after you had
seen him for left wrist pain
the day before which has
now resolved.
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4
Migratory arthropathy
GC GC
Rheumatic fever
Lyme disease
Case 4
25 y/o female presents
complaining of right
knee pain and swelling
and left hip pain.
Oligo-arthropathy
Spondyloarthropathy (Reiters)
Test in
Rheumatologic Rheumatologic
diseases
Test:
Joint Aspiration: whenever there
is fluid in a joint, you need to
aspirate it aspirate it
Exception: Contraindication
Test:
Joint Aspiration: whenever there is fluid
in a joint, you need to aspirate it
Exception: Contraindication
Bleeding disorders
Anticoagulants with bleeding diathasis
Cellulitis overlying
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5
Test:
Always order the 3 Cs and a
gram stain
1.
2.
3.
WBC ranges
OA / Traumatic arthritis
Inflammatory (RA, Gout)
Septic arthritis
Crystals:
OA / Traumatic arthritis
RA
SLE SLE
Gout
Pseudo gout
Septic
Anti-Nuclear Antibodies (ANA)
Antibodies against part of the
nucleus
10% of normal people have + ANA
High AB titer
Anti-Nuclear Antibodies (ANA)
97% of SLE patients have a + ANA
S if h l b k So if the test results come back
negative, assume they dont have
SLE
If you think the patient may have
SLE, what is your first step in
management?
If positive, order
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6
Ab association
SLE (60%), lupus nephritis
SLE (30%)
Drug induced lupus
Neonatal lupus, Sjogrens
Sjogrens
CREST
Mixed connective tissue dz.
Rheumatoid Factor (RF)
Antibodies against antibodies
Fc portion of IgG
Increase with age
Anti-Neutrophilic Cytoplasmic
Antibodies (ANCA)
Antibodies against certain
proteins in the cytoplasm of
neutrophils.
(c) ANCA:
(p) ANCA:
Diseases:
Rheumatoid Arthritis
Systemic Lupus Erythematosus
Scleroderma (SSc)
Sjogren Syndrome
Rheumatoid Arthritis
Chronic inflammatory disease
Target- Synovium
Symmetric distribution
Potential to destroy cartilage and bone
erosion
Rules of 6:
Morning stiffness > 1 hr - for at least 6 weeks
Swelling of wrist, MCP, PIP 6 weeks
Swelling of at least 3 joints- 6 weeks
Symmetric joint swelling 6 weeks
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Extra-articular manifestations
Damage to tendon and ligaments
Boutinniere deformity- PIP flexion, DIP extension
Swan neck deformity- PIP extension, DIP flexion
Rheumatoid nodules- vasculitis
Caplan syndrome- rheumatoid nodules in lungs
Labs for RA
RF
Anemia
ESR
X-ray:
Synovial fluid analysis
Mgt. for RA
Old Tx:
NSAIDS > Steroids > Methotrexate (2yrs later)
NEWTX: Start with MTX NEW TX: Start with MTX
after 1 week add prednisone for 1 week
only use for flare-ups
Antimalarial- hydroxychloroquine- MTX backup
CASE 5
Patient with RA presents
with a swollen painful calf.
Diagnosis?
Alentoaxial Subluxation in RA
C1, C2
Dx: X ray / CT Dx: X-ray / CT
Must rule out before surgery
Systemic Lupus Erythematosus (SLE)
Systemic disease
Tissue and multiple organ damage by
antibodies and immune complexes
Remember: you can have all the criteria for
SLE, but if the ANA is negative, the patient
does not have lupus
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Organs involved with SLE
CNS: confusion, personality change
Skin:
Kidney:
Lungs:
Hematologic:
Immune:
Bone:
Diagnosis of SLE
Best screening test ANA
Specific Abs associated
Complement levels (C3,C4,CH50)
Active lupus
Lupus nephritis
Case 6
26 y/o female, admitted for
confusion. Hx. SLE and was recently
tappered off prednisone (10 pp p (
mg/day). Pt was fine a couple of days
ago. PE- no focal deficits.
DDx?
Pregnancy and SLE
Fertility rates:
Spontaneous abortions and still births
DOC Mgt.:
Exacerbation (flare up) DOC:
All pregnant women with SLE need to be
screened:
Mgt. SLE
NSAIDs for arthritis
Antimalarials: Chloroquine
Steroids: for major organ involvement
Cytotoxins: Azathioprine
Cyclophosphamide
Drug induced lupus
Limited form of lupus due to a drug
No major organ involvement
Dx: rash + anti-histone antibodies
(complement normal)
Mgt: Discontinue offending drug
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Scleroderma (SSc)
Chronic multisystem disease
Thickening of the skin
Raunaud phenomenon
Visceral organ involvement g
GI: esophageal dysmotility, hypomotility of small
intestine
Pulmonary
Renal
CREST syndrome
Limited form of scleroderma
Symmetrical skin thickening
C
RR
E
S
T
Anti-centromere antibodies
Sjogren Syndrome
Chronic auto-immune disease
Xerostomia and dry eyes
Lymphoproliferative disease- Malignant lymphoma
Bilateral parotid enlargement
Itchy eyes, sand under their eyes
Keratoconjunctivitis sicca
Spondyloarthropathies
Ankylosisng spondylitis
Reactive Arthritis
Psoriatic Arthritis
Enteropathic arthropathy
Ankylosing spondylitis
Inflammatory disorder of axial skeleton and peripheral
joints
Rare after age 40
90% of patients + HLA-B27
Young male 20s, chronic lower back pain, morning
stiffness > 1hr, get better with exercise
Cervical spine involvement- late stage of the disease
Extra-articular manifestations AS
Cardiac:
Spine:
Eyes:
Skin:
Mgt: NSAIDs, Physical therapy, Exercise
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Reactive Arthritis:
Complication of an infection somewhere in
the body.
Non-Gonococcal urethritis:
1. 1.
2.
Infectious diarrhea:
1.
2.
3.
Reactive Arthritis Mgt.
NSAIDs
Antibiotics (prompt) Antibiotics (prompt)
Psoriatic Arthritis
DIP joint
Nail pitting
Sausage shaped digits
Enteropathic Arthropathy
Ulcerative colitis
Crohns disease
Skin lesions:
Pyoderma gangrenosium
Erythema Nodosum
Osteoarthritis (OA)
Target- articular cartilage
Hypertrophy of bone
NOT an inflammatory disease
MC joint affected?
2
nd
most common joint affected?
Joint involved with the greatest disability?
Osteoarthritis (OA)
Target- articular cartilage
Hypertrophy of bone
NOT an inflammatory disease
MC joint affected? Knee
2
nd
most common joint affected?
Joint involved with the greatest disability?
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Two forms of OA:
Idiopathic
Secondary (cause)
Arthropathies - gout
Endocrine dz
Desosition dz
Mechanical factors
Association with OA
Joint pain with exercise
Relieved by rest
Morning stiffness (< 20- 30 min)
Slow, progressive, irreversible
NO systemic manifestations
Labs with OA
CRP and ESR : Normal
X-ray: Osteophytes
Unequal joint space
Bouchards nodules (PIP)
Heberdens nodules (DIP)
Mgt. with OA
Non- pharmacological
Correct poor posture
Weight reduction
Physical therapy Physical therapy
Drug therapy
First drug- Acetaminophen (contra: use ibuprofen)
Add Capsaicin
Orthopedic surgery and joint
arthroplasty
Unsatisfactory medical Tx
Quality of life decreased Quality of life decreased
Crystal Induced Arthropathies
Monosodium urate (MSU)
Calcium phrophosphate (CPPD)
Calcium oxylate (CaOx)
Calcium hydroxyapatite (CaHA)
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Gout:
Acute Monoarthritis
Tophi:
Metaatarsophalangeal joint (first toe):
First episode:
Red, tender, warm
Predispose to Gout:
Excess ETOH
Trauma
Infection
Diuretics: Hydrochlorthiazide, Furosemide
Anti-TB meds: Pyrazinamide
Ethambutol
Diagnosis of Gout:
It is made with fluid analysis of synovial fluid
MSU crystals
N i Bi f i Negative Birefringent
Needle shape crystals
WBC 5,000-50,000
Mgt. Acute Gouty Arthritis
NSAIDs
Indomethacin 50 mg 3 x day
Colchicine: 0.6 mg every hr until symptoms
resolve
Steroids: intraarticular or oral (elderly)
Chronic Hypouricemic Therapy
Low urine levels of uric acid
Usually life long therapy
Follow uric acid levels here !!!
Probenecid- under secretors
Allopurinol- over producers
Pseuod-gout:
CPPD crystal formation
Elderly and pre-existing joint damage
May present acute like gout
Knee most common joint affected
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13
Diagnosis of pseudo-gout
Arthrocentesis:
Rhomboid crystals
+ Birefrengent
X-ray: linear radiodense deposits in joint
menisci Condro- calcinosis
Mgt: same as acute gout
Septic Arthritis
MCC gonorrhea
70% of cases > age 40
Elderly- Staph aureus (pre-existing joint
destruction)
Mgt. Septic Arthritis
Non-GC: (older) Staph aureus
GC (younger) sexually active
Both WBC > 50,000 and negative crystals
Staph aureus- IV Vancomycin
GC- IV Ceftriaxone
Therapeudic arthrocentesis
THE END THE END
183
1
REPRODUCTIVE
ENDOCRINOLOGY
Menstrual irregularities
The number one reason an adult woman
goes to see a doctor
The number one reason a teenage female
misses work or school (dysmenorrhea)
Dr. Naegle Naegles Rule
Assumed that a womans menstrual cycle
lasts 28 days long
Allows us to calculate the EDC
Begin with the last first day of menses, go
forward 9 months or go backward 3 months,
then add one week
If the womans menstrual cycle varies from 28
days, then you add/subtract the difference at
the end
Some Rules
Term pregnancy: 37 to 42 weeks
Average birth weight: 2500gms to
3500gms (5 to 7 pounds)
Preterm: birth prior to 37 weeks
Postterm: birth after 42 weeks
SGA: small for gestational age
LGA: large for gestational age
Naegles rule also allows us to
185 184
2
Oogenesis
Begins in-utero at about 5mo gestation
At birth, a female ovary contains about
400k eggs
Beginning at puberty, 8 to 10 follicles
begin development; but, only ONE egg will
ovulate
The eggs that do not finish development will
turn into small white nodules (corpus
albicans)
Oogenesis: The Steps
One round of mitosis first: 2n to 4n (occurs in
utero)
Primary oocyte
Enters meiosis 1 and arrests in Prophase (cells
still at 4n)
Eggs remain arrested in meiosis 1 in prophase
until ovulation occurs
If egg ovulates, it will complete meiosis 1, give
off first Polar Body, and enter meiosis 2,
arresting again in Metaphase(4n to 2n)
Secondary oocyte
Oogenesis: The Steps
If fertilization occurs, egg will complete
meiosis 2, give off the second Polar Body,
and form a zygote (2n to 1n)
Tertiary oocyte
Because moms eggs remain
arrested for SO long
You can trace 80% of
chromosomal mutations to MOM
186 185
3
OCPs
Norethindrone
Mestranol
Depo-provera
Estrone
Estradiol
Estriol
HRT
Decreases symptoms
Decreases osteoporosis ( decreases
osteoclastic activity)
Decreases risk of CAD ( increase HDL;
vasodilator)
Controversy!!
Other Hormonal Drugs
Clomiphene
Leuprolide
RU-486 (mifeprostone)
Now, introducingTYRONE!
Spermatogenesis
Begins at puberty
First sign of puberty in a male is testicular
enlargement
Controlled by testosterone
LH > testosterone > spermatogenesis
FSH > Sertoli cells > produce inhibin
Sertoli Cells
Produce inhibin
Maintain the blood-testes barrier
Protect and nourish the sperm to maturity
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4
Spermatogenesis
One round of mitosis: 2n to 4n
Primary spermatogonium
Meiosis 1: 4n to 2n
Secondary spermatocyte
Meiosis 2: 2n to 1n
Tertiary spermatid
One spermatogonium gives rise to 64 spermatids
As spermatogonia mature, they move from the basal
layer into the epididymus to finish maturing
Spermatogenesis, cont
Each day 20 to 40 million sperm mature
Complete spermatogenesis takes 41 to 72
days
Sperm can live for 5 days in fallopian tube
while an egg can live for only 3 days
Virility
20 to 40 million sperm per cc of semen
4 to 5cc of semen per ejaculate
No more than 40% abnormal forms
30 to 60% of sperm must still be motile
after 5 minutes on a glass slide
The pH is basic
Infertility
50% male factor
Always do sperm analysis first
30% female factor
Mcc is PID
20% miscellaneous
Before Sperm Can Leave
Seminal vesicles: semen; fructose
Bulbourethral ( Cowpers ) gland: HCO3
Prostate: Zn ; acid phosphatase;
hyaluronidase
188 187
5
Sexual Response
Sexual Dysfunction
In young men: premature ejaculation
In older men: stress induced impotence
In the elderly: vascular impotence
Atherosclerosis decreases blood flow
Takes longer to establish an erection
Harder to maintain an erection
Need for more direct stimulation
Longer refractory phase
The Difference Between the Sexes
Men have a longer refractory phase; short
excitement phase
Women have a longer excitement phase;
short refractory phase
To Address Premature
Ejaculation
Apply the SQUEEZE TECHNIQUE
Gently squeeze the head of the penis; it starts
retrograde peristalsis in the ejaculatory duct
and epididymus
189 188
6
Once the sperm are deposited in
the vagina
Sperm hide under the semen
HCO3 is released to neutralize lactic acid
Zn is used for the Capacitation Reaction
Fructose is used for energy
70% of sperm are dead before reaching
the cervix
Acid phosphatase is used to eat through
cervical mucus
Once the sperm are deposited in
the vagina
Sperm enter the uterus
They swim through the fallopian tubes
By the time the sperm approach the egg,
only a few thousand sperm remain
Sperm surround the egg
They dart in and out, opening their heads
to release enzymes ( Acrosomal Reaction)
Once the sperm are deposited in
the vagina
Once one sperm head fuses with egg, a
wall forms behind the sperm (
Crystallization Reaction)
This prevents Polyspermy
A ZYGOTE is formed when egg (1n) and the
sperm head (1n) fuse
Stages to Know
Zygote: 2 cell stage
90% fertilizations occur in the ampulla
It must now migrate into the fallopian tubes
Ectopic pregnancy: mcc is PID (forms scars)
Morula: 16 cell stage
This stage enters the uterus
Blastula: 256 to 512 cell stage
This is the stage that implants
Formation of the Placenta Placental Hormones
HCG
PROGESTERONE
ESTRIOL
HUMAN PLACENTAL LACTOGEN
INHIBIN
RELAXIN
190 189
7
HCG
Detectable in BLOOD one week after
fertilization; in the URINE two weeks after
Has the same alpha subunit as FSH. LH,
and TSH ( check the beta-HCG)
Maintains the corpus luteum
Increases GI motility and absorption
Sensitizes the TSH receptor
HCG, cont
Maintains corpus luteum production of
progesterone
Can lead to Hyperemesis Gravidarum
DES
Cervical incompetence
Adenomyosis
Clear cell carcinoma of the vagina
Increases BMR
HCG, cont
Doubles every 2 days until week 12
HCG of 600: viable fetus
HCG of 2000: fetus visible on abdominal
ultrasound
How to Follow the First Trimester
Fundal height rises 1cm per week
Pubic symphasis = 12 weeks
Umbilicus = 20 weeks
HCG doubles every 2days
Estriol level rises linearly
If fetus dies: estriol level falls first
Think of Molar Pregnancy if
Fundus growing higher than predicted
HCG rising faster than predicted
HTN in first trimester
Complete mole
Incomplete mole
Progesterone
Increase RR from pons
Increase appetite
Pica
Increase RBC mass by 30%
Causes acne
Hyperpigmentation
Cloasma or malasma
Helps increase plasma volume by 50%
191 190
8
Estrogen
Smooth muscle relaxation
Stimulates protein synthesis in the liver
High ESR
Hyperlipidemia
Increased TBG
Increased angiotensinogen
Increased clotting factors
Inhibin
Inhibits FSH
Prevents another menstrual cycle from
beginning
Human Placental Lactogen
BLOCKS moms Insulin receptors
Creates insulin resistance
Gestational diabetes
Relaxin
Relaxes tendons and ligaments
Stretches the pelvis
The END
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4/29/2008
1
At different points of gestation, various
organs are embryologically developed.
For example:
- Notochord at 2 wks
Renal Embryology:
Notochord at 2 wks
- Brain at 4 wks
- Renal system is formed at 12 wks
METANEPHROS - give rise to the kidney
URETERIC BUD i i t th ti URETERIC BUD - gives rise to the entire
collecting system
Collecting duct, major and minor calices, papillae,
hilum and ureters
Ureteric bud must make contact with the
metanephros or kidney will NOT develop
Renal
Pelvis
Metanephros
URETERIC BUD
Calyx
Gives rise to the GENITALIA in MALES
H kid
Develops into the testes, seminal vesicles, vas
deferens and epididymus
To develop, you need a Y chromosome and MIF
Has kidney
function prior
to kidney
formation
Gives rise to female genitalia
Paramesonephros
(never functional) (never functional)
as a kidney
Develops into the ovaries, fallopian tubes, uterus and
upper vagina
A female can develop either by DESIGNor by DEFAULT
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2
Vitelline Duct: Allantois:
Omphalomesenteric duct
IN MALES: prostate, prostatic urethra and
bulbourethral ( Cowpers) glands
IN FEMALES: lower vagina, and labia minora
Urogenital Sinus
IN MALES: becomes the PENIS
IN FEMALES: becomes the CLITORIS
Urogenital
Tubercle
L1 and L2 levels:
right kidney is positioned
li htl l th th l ft slightly lower than the left
kidney
Why?
Cortex: outermost layer of the kidney.
It contains the nephrons, PCT, and DCT
Cortical nephrons are shorter in length
compared to the medullary nephrons
Functions to maintain an isotonic urine
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3
Medulla: deeper layer of the kidney
Pyramids collect urine from the collecting
ducts that drain into each renal papilla p p
From the papilla > calyces > ureters
Responsible for hypertonic urine
Why do we sweat in different regions?
In hot places, we sweat and lose water.
I cold d t t d th d In coldareas, we do not sweat and thus do
not need to preserve this water.
The nephrons elongate after 3-4 days
Allows for more water conservation
(hypertonic urine) and fluid replacement lost
Renal Blood Supply
Right renal artery
Right renal vein
Renal Blood Supply
Right gonadal vein
directly drains into the y
IVC. Right sided
infection or cancer has
a worse prognosis
Left gonadal vein
drains into the left
renal vein
Healthy
Kidney
Sodium and
water
removal
Unhealthy
Kidney
Fluid
overload
Waste
removal
Hormone
production
Renin
Erythropoietin's
Prostaglandins
Elevated
waste- Urea,
Creatinine,
Potassium
Changes in
hormone levels
Blood pressure
Making red blood
cells
Uptake of calcium
194
Medulla = Concentrates Urine
IF anything messes with Blood flow... what affected 1st? MEDULLA
4/29/2008
4
Divide the kidney into 4 regions.
When one of the 4 are affected, ultimately it will affect the others
Tubules Glomeruli
Blood
vessels
Interstitium
20% f bl d f th CO i i t th kid
Blood
Vessels
20% of blood from the CO is going to the kidneys
90% of it, supplys the cortex
Only blood supply for the medulla - vasa recta
Medulla- first place to infarct in a low volume
state leading to medullary necrosis
Consist of visceral epithelial cells
(foot processes-podocytes)
Glomeruli
Glomular basement membrane
(electron dense-type 4 collagen)
Parietal epithelium lines bowman's space
Fenestrae (in the endothelium)
Most glomerular diseases are immunologically
mediated.
Proximal convoluted tubule (80% of reabsorption)
Tubules
Loop of Henely (triple transport)
Distal convoluted tubule
Collecting tubule (for concentrating the urine).
Most tubular diseases are frequently
caused by toxic or infectious agents
In the cortex, comprising mostly of fenestrating
Interstitium
capillaries (so any change in space, i.e. edema is
abnormal).
Most interstitial disorders are
frequently caused by toxic or infectious
agents.
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Patient presents with polyuria and
polydyspia
You rule out diabetes based on glucose
What next?
Diagnosis Cause Labs
Psychogenic DI
Excessive fluid intake
i.e. As much as 10-12 gallons
of H2O a day
Uosm/Posm > 0.7
Restrict H2O for 24 hours
Urine will concentrate
Central DI
Posterior pituitary does not
release the stored ADH
Uosm/Posm < 0.7
ADH i t t b t
Central DI
i.e. Infarction of the pituitary
gland
ADH is not present, but
when you give it, expect
the urine to concentrate
Nephrogenic DI
Renal kidneys are
unresponsive to ADH
i.e. Renal failure, lithium,
low volume state infracting
the medulla of the kidney
Uosm/Posm < 0.7
ADH is present and wants
to work, but its a receptor
problem
Urine will not concentrate
For burn patients: Parkland formula
( to calculate fluid deficit only)
4cc x Wt (Kg) x % burned areas
Never calculate more than 50% of burned
body area
Replace fluids:
within the first 8 hrs ( from time of trauma)
Remainder over the next 16 hrs
Head and neck: 9%
Each arm: 9%
Front of torso: 18%
Back of torso: 18% Back of torso: 18%
Each lower extremity: 18%
Genitalia: 1%
For newborns: subtract 9% from each lower
extremity and add it to the head and neck
Head 27%, legs 9%
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6
A 36 y/o fire fighter (70 kg),was trapped in a
burning building and suffered 2
nd
and 3
rd
degree
burns to over 65% of his body. What will be the
fluid replacement management?
Urine output : 1cc/kg/hr
70 kg x 50 %= 3500 x 4cc = 14,000 ml (14L)
7 L first 8 hrs : 7 L remaining 16 hrs
2
nd
day that, 3
rd
day nothing
Urine Output: 1cc/kg/hr (70 kg male)
A. 15, 20, 15 ml/hr
B. 300, 250, 270 ml/hr
C. Over 48 hrs, urine output has been
between 50-100 ml/hr. Now on day 3,
urine output 250, 300. Next step in mgt.?
Never give a hypertonic solution this will pull fluids out of the
extracellular fluid to help fill the vascular space, which will be
replaced by the intracellular fluid.
H
2
O
Ok great job on getting patient Xs blood pressure back to the normal range, but
at what cost. the tissue (oops!!!)
Cell
H
2
O
H
2
O
Intracellular
Extracellular
Exception to the rule:
Hyponatremic patient ( Na <120) patients:
Use 3% (hypertonic) saline to get sodium
above 120
Body water is broken down into fluid compartments:
Intracellular fluid (2/3 of Body Water)
Extracellular fluid (1/3 of Body Water)
Interstitial fluid (ISF) 2/3 ECF
Vascular fluid (VF) 1/3 ECF
ICF ECF
ISF VF
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7
Loss of isotonic fluid:
Hemorrhage, Diarrhea, Vomiting
Osm
ICF ECF
Loss of hypotonic fluid:
Dehydration, Diabetes Insipidus, Alcoholism
ICF ECF
Gain of isotonic fluid:
Isotonic saline
ICF ECF
Gain of hypotonic fluid:
Hypotonic saline, Water intoxication
ICF ECF
Gain of Hypertonic fluid:
Hypertonic saline, Mannitol
ICF ECF
Renin
Angiotensinogen Angiotensinogen
Pathway
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8
Renin
(JG cells-afferent)
Liver
AT-II (stimulates)
alpha 1 vasoconstriction
Ad l (Z Gl l )
(Angiotensinogen)-
release AT-I
Lungs
(AT-I is converted
to AT-II via ACE)
Adrenals (Z. Glomerlus)-
Aldosterone release
Posterior pituitary- ADH release
CNS- thirst center
Bartter's syndrome:
JG cell hyperplasia with renin excess
No increase in blood pressure due to insensitivity
of the presser effects of AT-II
Defect in the kidney's ability to reabsorb
potassium p
Excessive amount of potassium is excreted from
the body. This is also known as potassium wasting
DKA metabolic acidosis, which causes a
switch in H+/K+ pumps leading to K+
leaving the cells and intering the serum.
Not a true hyperkalemia, just ions shifted in
the wrong place.
Kid ill i th hi h K+ d t t Kidneys will recognize the high K+ and start
to secrete it in the urine.
(Hyperkalemia to Hypokalemia)
Hypomagnesemia due to decreased
gastrointestinal (GI) absorption
(Diarrhea, malabsorption, diet)
or increased renal loss(diuresis due to
alcohol, thiazides and loop diuretics)
Always look a pH first, then HCO3-
You should be able to differentiate
based off of these two
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For example
If the patients pH is acidic, you should
expect that patients HCO
3
- to be low
(buffering)
If not, then the problem has to be
respiratory
A id i
Respiratory
PaCO2
HCO
3
-
(compensations)
HCO
3
- normal
(non-compensation)
ACID / BASE Disorders:
Acidosis
Metabolic
HCO3-
PaCO
2

(compensation)
PaCO
2
normal
(non-compensation)
Alk l i
Respiratory
PaCO
2

HCO
3
-
(compensating)
HCO
3
- normal
(non-compensation)
ACID / BASE Disorders:
Alkalosis
Metabolic
HCO
3
-

PaCO
2

(compensating)
PaCO
2
normal
(non-compensation)
Arterial pH 7.3
pCO2 30 mm Hg
pO2 95 mmHg pO2 95 mm Hg
Serum HCO3- 14 mEq/L
What is the diagnosis?
Arterial pH 7.3 (ACID)
pCO2 30 mm Hg
pO2 95 mm Hg
Serum HCO3- 14 mEq/L (low) Serum HCO3- 14 mEq/L (low)
What is the diagnosis?
Metabolic Acidosis
w/respiratory compensation
Metabolic acidosis
Check anion gap... Na
+
- (Cl
-
+ HCO
3
-)
(N: 8-12 mEq/L)
Increased anion gap
Normal anion gap
Increased anion gap
MUD PILES
M- methanol
U- uremia
D- DKA
P- paraldehyde or phenformin
I- iron tablets or INH
L- lactic acidosis
E- ethylene glycol
S- salicylates
Normal anion gap
Diarrhea
Renal tubular acidosis
Hyperchloremia
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Diuretics
PCT
Acetazolamide, Dorzolamide:
Mannitol:
Ethacrynic Acid (no sulfa)
Furosemide (sulfa)
Hydrochlorothiazide (sulfa)
Indapamine (no hyperlipidemia)
Spironolactone:
Amiloride:
Triamterene: (no anti-androgenic effects)
Intra- Renal
Pre- Renal
Post-Renal
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Kidneys stop functioning properly: increase in
Creatinine
BUN and/ or
Decreased urine output
Oli i d i i ( 400 /d ) Oliguria : decrease in urine output ( < 400 cc/day)
Anuria ( < 100 cc/day)
Volume depletion
Dehydration (nausea, vomiting)
Burns ( massive)
Third spacing (i.e. liver chirossis)
Diarrhea
Decrease in Aldosterone (Addisons)
Cardiovascular
Hypotension (CHF)
Coarctation / tamponade
Pre-
Renal
Decrease in Oncotic pressure
Low Albumin
Nephrotic syndrome
Edematous states ( Cirrhosis)
Renal Artery Vasoconstriction
Medications ( NSAID's- block PG's, ACE-I)
Anatomical Renal Artery Stenosis
Decreased Vascular Resistance
Shock
(inflow to
the
kidneys)
Pre-Renal
BUN/Cr > 20/1
Urine Na
+
< 10 Urine Na < 10
FeNa
+
< 1%
UOsm > 500
Intra-renal problems
Drugs ( Gentamicin,
Amphoteracin B, Cisplatin) -
takes 5 to 7 days to damage
Crystals-
Uric acid tumor lysis
Renal
Uric acid - tumor lysis
Oxilate stones- antifreeze
or malabsorption
Crushing injuries-cell lysis
dipstick positive (NO RBC's)
Thromboembolism, ATN
(Kidneys)
Renal
BUN/Cr < 20/1
Urine Na
+
> 20 Urine Na > 20
FeNa
+
> 2%
Low specific gravity
(can not concentrate urine)
Bladder obstruction
Prostate enlargement
Pelvic tumors
Urethral strictures
(foley,retroperitoneal
Post-
Renal
( out flowobstruction)
fibrosis)
Urethral obstruction
Tumor
Stones
( out flow obstruction)
Both kindeys need
to be affected to
see any deficit
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Post- Renal
Obstruction
(hydronephrosis)
Increased post void
residual volume
If you suspect a pre-renal problem-
the patients usually have
positive orthostatics
d b dry mucous membranes
increase for thirst
rapid heart rate
skin tenting (turgor)
Consider (co-morbid) conditions that could
lead to their pre-renal problem
For a renal problem (intra-renal)-
consider drug history
Knowing the patients drugs could prevent Knowing the patients drugs could prevent
unnecessary test for the patient and time
wasted in determining the cause.
Any recent history of exposure to possible
toxins that could be nephro-toxic.
Myoglobin is a normal intracellular proteins:
- toxic to the kidneys
- intra-renal damage
If you suspect arteroemboli, look for If you suspect arteroemboli, look for
subcutaneous nodules
digital ischemia or immobility
With Glomerulonephritis:
red cast
edema (protein loss)
hypertension (renin pathway)
If you suspect a post-renal problem,
check for
prostate disease (Prostitis, BPH, Prostatic CA)
all can lead to an enlarged bladder with pain
radiating to the flanks
Check the urine (RBC's, WBC's, cast,
eosinophils), Electrolytes
FeNa+ can destinguish between pre-
renal and renal problems renal and renal problems
DRE, urinary cath as well as ultrsound
can rule out an obstruction
Renal biopsy only when the cause of
intra-renal can not be determined
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Dialysis if necessary Hyperkalemia
Attempt to balance fluids and
electrolytes
Discontinue medications if they are the cause of the
renal disease
Dialysis if necessary- Hyperkalemia,
Metabolic acidosis, Fluid overload, Pericarditis,
Encephalopathy
Urinalysis CLUES
Eosinophils
(Most common cause-
Cephlosporins)
Drug induced
hypersensitivity
RBC cast
Glomular
RBC cast
nephritis
WBC's
Bacteria Infection
Crystals
Uric Acid (Gout)
Urinalysis CLUES
Proteinuria (bence
jones)
Multiple
myeloma
Blood dipstick +, but
no red blood cells Myoglobinuria
Proteinuria >
3.5gm/d
Fat cast
Nephrotic
syndrome
Glomerular Disease:
Have you ever noticed, that when you
wake up in the morning and urinate,
there is a soapy appearance to your
urine in the toilet bowl?
Why is it, that when a nurse is going to
do a morning U/A on a patient, you ask
her to get a mid-steam catch?
When we look at nephritic or nephrotic
syndromes, we need to decide what sets
them apart from each other.
Aside from a few details, it just comes down
to protein loss and the magical number is
3 5g/day 3.5g/day.
If less than 3.5 g/day then we name that
Nephritic and if greater than 3.5 g/day, we
call that Nephrotic.
Why 3.5 g/day?
Hypertension
Macroscopic /
Microscopic
hematuria
(smokey brown
urine)
Oliguria Edema
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24 hour U/A ( best initial test) - look
for hematuria, proteinuria
If GFR is decreasethink auto-immune If GFR is decreasethink auto immune
check complement, ANCA and anti-GBM
Renal biopsy (most definitive) - LM, IF, or
EM to help in the diagnosis
Treat any hypertension, fluid overload and
uremia with
Salt and water restrictions, diuretics and if
needed, dialysis
If the underlying cause is inflammation of the
glouerular, the give corticosteroids
1. Post Strep GN
2. Good Pasture GN
3. RPGN
4. IgA Nephropathy
5. Membranoproliferative GN
(can be both)
Proteinuria (> 3.5 g/day)
Generalized edema
Hypoalbuminemia Hypoalbuminemia
Hyperlipidemia.
Approximately one-third of all cases are
the result of systemic diseases such as
DM, SLE, or amyloidosis.
Generalized
Edema
Foamy urine
Ascites
Hypercoagulable
state
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U/A - proteinuria (>3.5 g/day),
lipiduria
Blood chemistry- decreased albumin
(<3g/dL), hyperlipidemia
Always look for secondary causes
Renal biopsy (definitive): LM, IF, EM
Diuretics and antihyperlipidemics
Diet restrictions of salt and protein
Vaccinate (PPV 23)- patients at risk of Streptococcus
pneumoniae infections
If the patient is a diabetic- put them on an ACE-I for it
decreases the prograssion of the disease
Diuretics and antihyperlipidemics
Nephrotic Syndrome
Mcc in children: minimal change disease
Mcc in adults: membraneous nephropathy Mcc in adults: membraneous nephropathy
Mcc in Blacks and Hispanics: FSGN
Fat cast
1.Membranous GN
2.Minimal change disease
3.Focal Segmental GN
4. Amyloidosis
5.Nodular Glomular Sclerosis
Block aldosterone
Have sulfur in them- anaphylaxis, hapton to RBCs
Angioedema- block C1 esterase inhibitor
S i ( ) Serum Na- dec. , K -inc., pH dec (hangs onto H+)
Captopril
Lisenopril
Enalopril
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Acute Renal Failure
Renal Plasma flow
BUN
(lab) use PAH
GFR- look at Cr clearance:
Renal Blood Flow- assocated with Cr
clearance
(Lab) use inulin
Pa Pb
FLOW
X
If you increase resistance at X
Pa pressure will increase
Pb pressure will decrease
Flow will decrease throughout
GC
Glomerular
cap pressure
Peritubular
cap pressure
Renal
plasma flow
1. Constrict efferent
GFR
Post- efferent Efferent
2. Dilate efferent
3. Constrict afferent
4. Dilate afferent
E
A
GC
E
A
GC
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E A
GC
E A
GC
Rate at which plasma is filtered into
bowmans capsule.
Units of filtration:
(Volume filtered per unit of time)
e.g. ml/min, L/day
Glomerula Filtration Rate (GFR)
= Oncotic
y
Decreased in
pregnancy, liver
failure, over
hydration
GFR = Kf [ (P
GC
-P
BC
)-(
GC
-
BC
)]
P= Hydrstatic
Inreased in
kidney stone,
obstruction
Breakdown of
bowmans
capsule
P
GC

GC
P
GC
is the main
factor that
determines GFR
(promotes filtration)
P
BC

BC
P
BC
opposes filtration
Does not affect the
rate of filtration,
except in obstruction
Should not be a factor
The negative charge of the filtering
membrane inhibits the filtering of
proteins [anions (-)] proteins [anions ( )]
If the negative charge is not
present, significant protein
filtration takes place
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Filtration fraction (FF) fraction of material that
enters the kidney, that is filtered normally (.20 or 20%)
GFR 140 ml/min
RPF 400 ml/min
.35 or 35% FF
Constrict Efferents
Carriers are easily saturated
Carriers have high affinity for the substrate
Low back leak
The entire filtered load is reabsorbed until the
carriers are saturated, then the excess is excreted.
Morning glucose is 600 mg/100ml,
how much will leave the kidneys?
120 (GFR) x 6 = 720mg
will be filtered
How much will leave
in the urine?
(normal carrier Tm 375 mg/min)
So urine dipstick will measure
345 mg/min
Tubular Secretion (PAH):
(para-amino-hippurate)
Secreted from the peritubular
capillaries into the PCT.
There are enough carrier to
secrete 4 times the amount
filtered.
If you inject 100 mg of PAH into
a patient, how much will be
excreted?
100 mg
(20% filtered and 80% secreted)
Protein
Lipid soluble
Inulin
Manitol
(filtered, not
secreted or
reabsorbed)
Glucose
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Theoretical volume of plasma from which a substance is removed over a
period of time
Calculate the clearance ?
V = 2ml/min
Px = 2mg/ ml
Ux = 2mg / ml
2 x 2 = 2 ml/ min
2
Each kidney measures about 3 to 7 inches
If kidneys too small
Renal Artery Stenosis
Kidney Pathology Kidney Pathology
Renal Artery Stenosis
If kidneys too large
Polycystic kidney disease
Medullary sponge kidneys
Medullary cystic kidneys
Renal Artery Stenosis
atherosclerosis
fibromuscular dysplasia
Unilateral
If the kidneys are too small If the kidneys are too small
Unilateral
Abdominal bruit
Low volume state
Dx: ultrasound; renal vein renin elevated
( higher renin output indicates stenosis)
Goldblat Kidney
Treatment
h
Avoid ACE-inhibitors once HTN is severe
(AT-II Dependent)
RAS: most common cause of secondary
hypertention
Ipsilateral atherectomy (or stent if not a surgical
candidate) and contralateral nephrectomy
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If you have large kidneys
Polycystic kidney disease
Medullary sponge kidneys Medullary sponge kidneys
Medullary cystic kidneys
Polycystic Kidney Disease
ADULT TYPE
AD
Bilateral, HTN, RF
SAH - berry aneurysms
INFANTILE TYPE
AR
Unilateral
NO HTN
In posterior
communicating artery
CN 3- blown pupil
Worst headache
Tx: Transplant
NO HTN
NO RF
Medullary Cystic Kidneys
Multiple cysts destroy the medulla
Polyuria
Polydypsia Polydypsia
Low volume state
Occasional kidney stone
Dx: Sonogram (bubbles)
Medullary Sponge Kidneys
Many holes develop in the medulla
Polyuria
Polydypsia Polydypsia
Low volume state
Multiple kidney stones
Dx: Sonogram (holes)
Ureters: 3 anatomical narrowings
Hilum
Mid ureter: caused by going
over the iliac bones over the iliac bones
Ureteropelvic junction
( where it enters the bladder)
Kidney stones
Most common type: calcium
MCC: hypercalciuria
Tx: Normal saline
Opiates for pain
Thiazides decrease hypercalciuria
by forcing the PCT and Loop to
increase Ca2+ absorption
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Kidney stones
Struvite stones (Staghorn calculus)
Triple phosphate stones
C M NH4 Ph h t Ca-Mg-NH4-Phosphate
MCC: urease positive UTIs
Tx: normal saline; opiates for pain
Urease Positive Bugs
Proteus
Pseudomonas
Ureoplasma
N di Nocardia
Cryptococcus
Helicobacter Pylori
Staph Saprophyticus
Brucellosis
Kidney stones
Uric acid stones
The only stone NOT visible on xray
(radiolucent) (radiolucent)
Associated with rapid cellular death
(burn pt, CA, massive trauma)
Tx: normal saline
opiates for pain
Kidney stones
Cystine stones
CYSTINURIA
Cysteine
Ornithine
Lysine
Arginine
AD
Coffin lid, enveloped
Defective renal transport of amino acids
Tx: normal saline; opiates for pain
Kidney stones
Oxalate stones
Due to malabsorption in GI tract
When you have malabsorption, calcium gets
trapped in the malabsorbed fat (saponification) and
do not therefore bind oxalates from proteins
breakdown. Oxalate get absorbed in the GI
Can be hexagonal
Kidney Stones: management
IV normal saline
Opiates for pain
< 5mm ( cm)
Let it pass Let it pass
5mm to 1cm
Lithotripsy (whorl pool)
> 1cm
Open laparotomy (i.e. struvate)
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-Street- Heroin (short acting)
-For withdraws- Methadone (long acting)
-Kidney stones- Morphine Kidney stones Morphine
-Abdominal pain- Meperadine
(no contraction of sphincter of odi)
Kidney Stones: management
If pyelonephritis develops:
percutaneous nephrostomy stent placement
to drain the pus
Dx: KUB; spiral CT; IVP;
Sonogram (if with hydronephrosis)
Ureteroscopy- if stone is in the middle or
lower 1/3 of ureter
HYDRONEPHROSIS
Newborns:
(1)malimplantation of the ureters (lack 2 90)
(2) posterior urethral valves
Children: UTIs
Adolescents: urethral strictures ( from STDs)
Adult men: BPH
Adult women: uterine prolapse and cystocele
BPH
Most common cause of urinary obstruction in
adult men
Obstruction is periurethral (central) : Dx DRE Obstruction is periurethral (central) : Dx DRE
Tx: terazosin or doxazosin
(alpha 1 blockers) loosen sphinctor
Tamsulosin (Flomax)- least side effects
2
nd
line - Fenesteride (block 5 alpha recductase)
Sx TURP (transurethral resection of prostate)
HYDRONEPHROSIS
UNILATERAL
Kidney stones
BILATERAL
Retroperitoneal
fibrosis
Methysergide Methysergide
(seretonin Rx for
migranes)
Nitrofurantoins
Bladder
Allantois develops into
Urachus develops in the
abdomen and descends into the
pelvis
forming the Bladder
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Urachal Cyst
Urachus retains attachment to the
umbilicus
Clue: urine drains fromthe umbilicus Clue: urine drains from the umbilicus
Tx: surgery
Exotrophy of the Bladder
Bladder was caught outside the abdominal
cavity
Predisposes to bladder cancer (MC
complication)
Risk for bladder cancer persists even after
surgery (UA and CT every year)
Tx: surgery
MCC: Atherosclerosis
Location: 90% occur below the renal arteries
Presentation:
1. Ripping, tearing pain down the lower back
2. Pulsating abdominal mass
(can only feel if they are thin)
Dx: Sono, CT scan
< 4 cm diameter
- control HTN
- follow
> 6 cm in diameter
- control HTN
- surgery
4 6 cm (surgery is the doctors call)
MCC: 1# Trauma , 2# Collagen disease
Presentation:
1. Ripping, tearing pain between the shoulder blades
Diagnosis: Spiral CT
Treatment: Type A control HTN, surgery
Type B- control HTN, pray
(not much connective tissue)
Incontinence
The involuntary loss of urine
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Urge Incontinence
Detrusser muscle activity is increased.
A spastic bladder ( UMN lesion)
Bladder capacity is low due to repetitive
bladder emptying
Sphincter pressure is normal
Gotta gogotta gogotta go
Tx:
Imipramine (in children) TCA
Oxybutynin (in adults) Blocks Ach (M)
(to decrease bladder contractions)
Urge Incontinence, cont
Tx: have patient urinate around the
clock beginning with
- hourly for 2 to 3 days - hourly for 2 to 3 days,
- then every 2 hours for 2 to 3 days,
- then every 3 hours for 2 to 3 days,
- then every four hours (normal)
Stress Incontinence
Due to weak pelvic floor muscles
Estrogen connection
Any increase in abdominal pressure
( like from sitting down, laughing, coughing,
sneezing, etc) causes a sudden loss of urine
Detrussor muscle function is normal
Bladder capacity is normal
Sphincter pressure is decreased
Stress Incontinence, cont
MCC: obesity; estrogen connection
Tx: weight loss; Kegle exercises to
tighten up pelvic floor muscles tighten up pelvic floor muscles
Use pseudoephedrine to tighten up the
sphincter (alpha adrenergic)
Suggest diapers or panty liners in the
meantime
Overflow Incontinence
Due to an anatomical obstruction
Detrussor muscle activity is decreased due to
stretching
Bl dd it i i d Bladder capacity is increased
Sphincter pressure is increased
Sx: a weak urine stream; dribbling after urination;
urgency; frequency
Tx: surgically remove the obstruction
Overflow Incontinence, cont
Causes:
In newborns: posterior urethral valves
In children: strictures In children: strictures
In adult men: BPH
In adult women: uterine prolapse and
cystoceles
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Urethra: Penis
Develops dorsal (top) to ventral
(bottom)
Fuses fromthe tip to the base of penis or Fuses from the tip to the base of penis or
clitoris
Hypospadia yp p
The most common congenital genitourinary abnormality!
Hypospadia ( still zipping)
Located at the base of the penis just next
to the anus
Predisposes to UTIs Predisposes to UTIs
Tx: surgical correction immediately to
prevent UTIs
Circumcision
Done primarily for cosmetic reasons
UTI argument
Penile cancer argument
Should be done in first 48 hours
Clean by pulling the foreskin up, then
clean; pull the foreskin back, then clean
Inflammatory Problems
Phimosis: foreskin is scarred and
adherent to the head of the penis
Paraphimosis: foreskin is scarred and Paraphimosis: foreskin is scarred and
adherent to the base of the penis
Tx: urology consult
Infections
Ballanitis ( head of the penis )
Staph Aureus
Urethritis ( dysuria) infection of urethra Urethritis ( dysuria)- infection of urethra
Chlamydia Trachomatis # 1 (90% asymp.)
Nisseria Gonorrhea # 2 (90% symp. Men)
(50% symp. Women)
Actinomyces Israelii
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Azythromycin 1gm or 2gm (Chlam + GC)
Ceftriaxone (250 IM)
Cefixeme ( 400 PO) Cefixeme ( 400 PO)
Cefoxitin (250 IM)
Quinolones (400 PO)
Ciprofloxacin
Ofloxacin
Gatifloxacin
Infections, cont
Cystitis: ( urgency and frequency)
Pyelonephritis: ( WBC Casts)- only nephron
can formcast can form cast
Causes:
E. Coli
Proteus
Klebsiella
Enterococcus: nitrite negative
Nephritis
Pyelonephritis: WBC Casts; sepsis
Interstitial nephritis: drug allergy;
collagen vascular disease collagen vascular disease
Glomerulonephritis: RBC Casts; hematuria
Casts
WBC casts: nephritis
RBC casts: glomerulonephritis
Eosinophil casts: interstitial nephritis
Fat casts: nephrotic syndrome
Waxy casts: chronic renal failure
Hyaline and epithelial casts: normal findings;
represent sloughed off cells, most from the PCT
Crescents: RPGN. Goodpastures or Wegeners
RTAs
Type I: distal H/K exchange is defective
Urine pH is very high; renal stones; UTIs
Type II: proximal CA does not work
Urine pH is very high ( distal H/K exchange still
works)
Can not reabsorb HCO3-
TYPE III: combines the above two
Urine pH is normal
Type IV: hyporenin-hypoaldosterone syndrome
Seen in diabetics; JG apparatus is infarcted
THE END ! THE END !
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218

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M ki Th C i Making The Connections
Embryology of the Brain
Primitive Streak
Spinal cord
Notochord
In the first trimester
Notochord: visible by 3 weeks
Brain: fully formed by 8 weeks
Brain is active early with movements,
especially reflexes
Brain is active in formation of amniotic fluid
Amniotic Fluid
80% of amniotic fluid is filtrate from moms
plasma
Fetus SUBTRACTS by swallowing the Fetus SUBTRACTS by swallowing the
fluid
Fetus must absorb and digest the fluid
20% is addedby the fetus
Fetus then urinates the additional fluid into
the sac
Polyhydramnios
AFI
N l di Neuromuscular disease
Autonomic dysfunction: dry eyes- Riely Day syndrome
Muscle disease: in a newborn fasciculation- Wernig
Hoffman syndrome
GI obstruction
Oligohydramnios
Renal agenesis
Urinary outlet obstruction
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Spinal Cord
Develops from the notochord
Goes down as far as L-1 or L-2
End : Conus Medullaris
Nerves: Cauda equina
Filum terminalis: anchors
Vertebral Arches
Fuse ventral to dorsal
Begins at the cervical level g
Proceeds bi-directionally
If child born prematurely, a hole can
be still present at either end
Upper- vertebral arch defects
Anencephaly no contact to the brain
Only has the medulla
Breath 8-10 ipm Breath 8-10 ipm
Encephalocele
Encephalo-meningocele
Encephalo-meningo-myelocele
Lower vertebral arch defects
Spina Bifida Occulta
Spina Bifida Aperta
1. Meningocele
2. Meningomyelocele
Arnold Chiari Malformation (Type I and II)
Syringomyelia
AFP
A filtrate of plasma
Made by the Choroid Plexus in each ventricle
Now you need some CSF
y
Requires Vitamin A
Requires Carbonic Anhydrase
How CSF differs from plasma
Less HCO3
-
More CL
-
Lower pH 7.34 (acidic)
Up to 25 WBCs normal in first month of life normal
>1 month, only up to 3 WBCs normal
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Lateral ventricles >
foramen of Munro >
3
rd
ventricle >
aqueduct of Sylvius >
4
th
ventricle >
foramina of Lushka & Magendie
subarachnoid layer >
spinal canal >
dural sinuses >
back into plasma
CSF Flow
Vomiting Centers
Chemotactic Trigger Zone: located on
the floor of the 4
th
ventricle
Responds to any increase in ICP
Stimulated by dopamine
Vomiting Centers
Area Postrema: located on the blood
side of the blood brain barrier (BBB)
Responds to offensive smells or
taste
Stimulated by dopamine
Hydrocephalus
Non-communicating:
due to an obstruction
Communicating:
overproduction of CSF
Communicating Hydrocephalus
Newborns: mainly premature newborns
Intraventricular hemorrhage
Children: due to inflammation
Meningitis (posterior fossa) CN 3,
9,10,11,12
Adults: over ingestion of vitamin A
Pseudotumor Cerebri
Communicating Hydrocephalus
Elderly: due to brain atrophy
Normal Pressure Hydrocephalus
Ventricles enlarge
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Normal Pressure Hydrocephalus
Ventricles expands as the brain atrophies
Enlarged ventricles then compress the long midline
fibers that go to the bladder and legs fibers that go to the bladder and legs
Triad:
Dementia
Incontinence
Ataxia
Tx: VP shunt
Noncommunicating Hydrocephalus
Due to some form of obstruction
In newborns:
MCC: Aqueductal stenosis MCC: Aqueductal stenosis
2
nd
Dandy-Walker cyst
In children: meningitis, especially TB
In adults: cancer
In elderly: cancer
The role of CSF
To add cushion for the brain
Shock absorption
Head Injury
Coup lesions
Contracoup lesions worst than the
coup (brain makes CSF for repair)
Neurocutaneous Syndromes
Sturge Weber Syndrome:
Benign port wine stain- capillaries
Opthalmic branch of CN V
Mental retardation
Seizure
Neurocutaneous Syndromes
Osler-Weber Rendu Syndrome
Small aneurysmal telangiectasia on
h k d b the skin and mucus membrane
Causes GI bleeding
Pulmonary AV fistula
Neurocutaneous Syndromes
Tuberous sclerosis: benign tumors
AD
M l d i Mental retardation
Seizure
Retinal angiomyolipoma
Cardiac rhabdomyoma
Pancreatic cyst / Coloboma
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Neurocutaneous Syndromes
Von-Hippel Lindau
Cerebellar hemangioma g
Retinal hemangioma
Renal cell carcinoma
(increased EPOs)
Embryology of the Brain
Prosencephalon Telencephalon cerebrum
Diencephalon thalami and BG
Mesencephalon Mesencephalon midbrain
Rhombencephalon Metencephalon pons & cerebellum
Myelencephalon medulla
Visual Cortex
Light must hit the retina by 3 months of age
or the child is blind for life
You must verify that a child has a RED reflex
on eye exam at birth (retinal arteries, and if
you can see them- nothing is in the way)
Abnormalities of the Eyes
Anisocoria: unequal pupil size
MCC: Congenital (AD) check parents
If it occurs in childhood- inc. ICP until proven
h i D CT LP otherwise Dx: CT, LP
Amblyopia: difference in visual acuity
Lazy eye
Tx: Patch the eye up to age 5
Weak muscles- CN: 3,4,6
Abnormalities of the Eyes
Strabismus: misalignment of the eyes
Isotropia
Exotropia Exotropia
Weak muscles of the eye.. Tx. Patch good eye
Stigmatism: corneal defect
Straight line card (pt will see a blip in the line)
Convex or a concave defect in the cornea
Laser keratotomy
Vision Correction:
20/20 20/100 (5 times the difference)
20 ft. 4ft
20/200 legally blind (no drivers license)
can not see details
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Abnormalities of the Eyes
My-opia: near sightedness (can not see far)
Focus of light is before the retina
Tx: Concave lens- disperses light
Hyperopia: far sightedness
Focus of light is behind the retina
Tx: Convex lens- focuses light earlier
Presbyopia: loss of accommodation seen with aging
Due to muscles weakening with age
Ability to focus on objects coming close
Myopia- can not see far away
White Reflex
Cataracts: opacification of the lens
Does not allow light to hit the retina
Must be removed
d d h h h l Increased incidence with high glucose or
galactose ( sorbitol or galactitol accumulates)
Idiopathic: 90%
Diabetes or galactosemia
Rubella
White Reflex
Retinoblastoma (rare)
Rb gene Rb gene
Cancer
High association with Ewings
sarcoma
Visual field deficits Visual field deficits
Optic Nerve
Optic Tract
Optic Chiasm
Meyers
Optic Radiation
Calcarine
Fissure
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Optic Radiation
Meyers Loop
Monocular Visual Loss
Optic Nerve
L
L
R
R
Monocular blindness
Monocular blindness
Newborns: cataracts or retinoblastoma
Children: optic nerve gliomas
Neurofibromatosis
MEN III
Adults: embolic phenomena
TIA (Amaurosis Fugax)
Acute retinal artery occlusion
(white retina, macula has its own blood supply)
Acute retinal vein occlusion (bluish retina)
Elderly: macular degeneration
Receives the smallest arteries of the retina - atherosclerosis
Bitemporal Hemanopsia
L
L
R
R
Optic Chiasm Lesions
Optic Chiasm Lesions
Pituitary tumors: 90%
Pituitary sits just beneath the chiasm
Pineal tumors
Pineal gland sits just lateral to the
chiasm
Circadian rhythm - Responds to light
Contralateral
Homonymous
Hemianopia
L
L
R
R
Optic Tract Lesions
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Optic Tract Lesions
M Mcc:
cancers or tumors
Contralateral Superior
Quadrantanopia
L
L
R
R
Contralateral Inferior
Quadrantanopia
L
L
R
R
Contralateral
Homonymous
Hemianopia with
Macula Sparing
L
L
R
R
Quadranopsia
Can get such a lesion in
the Optic radiation or
Meyers loop Meyer s loop
Pie in the sky
Frontal Lobe ( Precentral Gyri)
CST (corticospinal tract) motor fibers
originates from here
Unique information:
Personality is stored in the frontal lobe
Abstract reasoning
(dont cry over spilled milk)
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Frontal Lobe Lesions
Atonic seizures- generalized (knock out CST)
Dementias
Al h i ' Alzheimer's
Picks disease
Schizophrenia: loss of asymmetry
Frontal lobotomies
Temporal Lobe
Hearing
Balance
Hallucinations ( released by serotonin) Hallucinations ( released by serotonin)
PCP
LSD
Posterior temporal lobe: Wernickes area
Amphetamines
Taken up presynaptically; cause release
of catecholamines
Clue: vertical nystagmus
Amphetamines
Used in ADD
Methylphenidate (use in Narcolepsy)
Pemoline -
Adderal
Dexadrine
OTC for weight loss
Dexatrim
Cause hallucinations
LSD
PCP
ECSTACY
SSRIs
Fluoxetine
Paroxetine
Luvoxetine Depression, eating disorders
Sertraline (MAOI- wait a month)
Nefazadone
Trazadone
Parietal Lobes
Dominant lobe: long term memory; all the
things you learned since kindergarten
left side is dominant in 90%of right- left side is dominant in 90% of right
handed and left-handed people
Nondominant lobe: apraxia and hemineglect
Right side is nondominant in 90% of right-
handed and left-handed people
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Anterior Cerebral
Anterior
Communicating
Posterior Cerebral
Superior Cerebellar
Anterior Inferior Cerebellar
Posterior Inferior Cerebellar
Vertebrals
Lateral Pontine Syndrome
Occlusion AICA (anterior
inferior cerebellar artery) inferior cerebellar artery)
CN 7- ipsilateral facial
paralysis
CN 8- hearing loss
Lateral Medullary Syndrome
( Wallenberg)
Occlusion of PICA (posterior inferior
cerebellar artery )
Cerebellar peduncle- ipsilateral limb
ataxia
Descending hypothalamics-
ipsilateral horners
Nucleus ambiguus- dysphagia
Medial Medullary
Syndrome
Occlusion of vertebral artery
Pyramid- contralateral spastic
hemiparesis
CN 12- tongue deviates
toward the lesion
Median Midbrain Syndrome
(Weber)
Occlusion of posterior cerebral
artery
CST- contralateral spastic
hemiparesis (upper limb)
Corticobulbar tract- lower face
(contra)
CN3- eye (down and out)
Epidural Hematoma
Middle meningeal
artery
Fracture of
temporal bone
Lucid interval
Lenticular shape
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Subdural Hematoma
Bridging vein
Venous bleed
Delayed onset
Shaken baby
Elderly
Crescent shape
Subarachnoid Hemorrhage
Aneurysm rupture
Worst headache of Worst headache of
their life
Bloody spinal tap
THALAMI- SENSORY
Epithalamus
Thalamus Thalamus
Hypothalamus
Subthalamic Nucleus
Epithalamus
The ONLY nucleus with NOknown
function
Thalamus
ALL SENSORY information in and out of
the brain MUST stop here
ALL information about the ARMS stay
LATERAL
ALL information about the LEGS stay
MEDIAL
Hypothalamus
Controls hunger
Hunger center: lateral
Satiety center: medial- 80% NE and 5HT (+)
You can override via cortex stimulus FOOD
Controls menstrual cycle
Controls temperature
Anterior: cools
Posterior: warms
Controls stress response (NE release)
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Stress Response
Parasympathetic discharge always first
Sympathetic discharge always second
Stress ulcers
Curlings ulcers
Cushings ulcers (triad: bradycardia, HTN, Inc. ICP)
IBS
Acetomenophen
Works at the level of the hypothalamus
First, it cools the body (+ anterior hypothalamus)
2
nd
it resists fever (blocks posterior h pothalamus) 2
nd
it resists fever (blocks posterior hypothalamus)
Oxidizes the liver (toxicity) by destroying bisulfur
groups
Treat with n-acetylcystiene ( reducing agent);
the four hour level is the most important factor
Subthalamic Nucleus
Final relay station for coordinating
fine motor movements fine motor movements
Lesion: Ballismus and Hemiballismus
Substantia Nigra
Responsible for INITIATING movements
Uses DOPAMINE for neurotransmitter
Receives inhibitory signals from basal ganglia via ACH
or GABA
Parkinsons Disease
Loss of DOPAMINE fibers from substantia nigra
to striatum (caudate and putamen)
Unable to initiate activities Unable to initiate activities
Mask like facies
Bradykinesia
Shuffling gait
Pill rolling tremor
Autonomic dysfunction: Shy Dragger syndrome
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Parkinsons Disease, cont
Treatment: L-dopa/ carbidopa
2
nd
line: Bromocryptine (dopamine agonist)
Amantadine (Tx influenza A)- increase DA
release from nerve terminal
Selegyline (MAO-B inhibitor)- prevent DA
breakdown
Movement disorder in middle-aged people
Huntingtons disease
90%
AD
Trinucleotide repeats
Wilsons disease
< 10%
AR
Ceruloplasmin def Trinucleotide repeats
Caudate nucleus involved
Anticipation
Decreased GABA fibers
Treat with DA blockers
(they have too much DA)
Ceruloplasmin def
Copper excess
Lenticular nucleus
involved
Kayser-Fleischer rings
Liver involvement
Treat with penicillamine
Internal Capsule
ALL MOTOR fibers going in and out of the brain goes
through here
Bl d l f h l i l i i Blood supply comes from the lenticulostriate arteries
( smallest arteries in the brain)
Lacunar hemorrhages: due to HTN
Causes significant MOTOR deficits
Reticular Activating System (RAS)
Maintain FOCUS on one item at a time
Requires NE and Serotonin Requires NE and Serotonin
cAMP second messenger (sympathetic)
Has a refractory period first thing in the
morning
Sleep cycles
BAT D
Beta waves wide awake (eyes open)
Alpha waves - Eyes close - awake not asleep
Theta waves
light waves stage 1 and 2. (Stage 2: K complex and sleep spindles)
Delta waves Deep sleep big stage 4 all motor activities (teeth
griding, sleepwalking, enuresis).
Night terrors occur
Benzos, imipramine inhibts this fase
Beta waves - Rem sleep. Every 90 min. (REM latency) 5-7 x night
Parasympathetic. Most of the rest.
Dreams, penile/clitoral erection
NE, EtOH, Barbs, Age inhibts this
5-HT, Ach increase
Attention Deficit Disorder
ADD or ADHD (Not focus).
RAS not working
Poor attention and focus Poor attention and focus
Restlessness
Unable to sit long enough to complete a task
Tx: methylphenidate (1
st
in children);
pemoline; dexadrine; adderal
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Mid brain Mid-brain
Corticospinal Tract
Responsible for fine motor activity
Has to inhibit extension so that smooth flexion can
occur
Spasticity- can not flex
Babinski extension of toes
Hyperreflexia
Clonus
Corticospinal Tract, cont
Fibers originate from the frontal lobes,
the precentral gyri
Fibers descend through the internal
capsule and CROSS at the medullary
pyramids
CST Pathology
Atonic seizures: depolarization
goes across the frontal cortex
B-12 deficiency
ALS
Increased Intracranial Pressure
First sign: papilledema (optic nerve)
First symptom: headache
Second sign: esotropia (CN VI paralysis)
abdusence
Second symptom: diplopia or blurred vision
Third sign: Sluggish pupils
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Decorticate Posturing
If Herniation Continues
Second sign of herniation:
DECORTICATE posturing
Compression has occurred below CN Compression has occurred below CN
III but above the red nucleus
Red nucleus still makes the upper
extremities flex while the legs extend
UNTIL
The Final Push
Herniation goes beyond the red nucleus
CST and Corticorubral and rubrospinal
tracts are all lost tracts are all lost
All extremities will extend by default
Medulla is pushed through the foramen
magnum.
DECEREBRATE posturing
DECEREBRATE posturing
Dorsal Columns
Vibratory sensation
Two-point discrimination
Positionsense Position sense
(toe m0vement)
Conscious proprioception
(eyes closed knowing what he is doing)
The only sensory pathway with four
synapses
Dorsal Columns, cont
Gracilis: carries leg fibers; located
MEDIALLY MEDIALLY
Cuneatus: carries arm fibers; located
LATTERLY
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Dorsal Columns, cont
FIRST SYNAPSE: dorsal root ganglion
Fasciculus gracilis: ( lower extremities)
Fasciculus cuneatus: ( upper extremities)
SECOND SYNAPSE: MEDULLA
THIRD SYNAPSE: THALAMUS
FOURTH SYNAPSE: parietal lobes
( postcentral gyri)- ALL SENSORY
Dorsal Column Pathology
Syphilis
Vitamin B-12 Def
Brown-Sequard
Spinothalamic Tract
Pain and Temperature
(opposite all other lesions)
The only pathway that CROSSES in the
spinal cord (only one)
Fibers enter the spinal cord, ascend two
levels, then cross to opposite side via the
anterior white commisure
Spinothalamic Tract
FIRST SYNAPSE: dorsal root ganglion
SECONDSYNAPSE: thalamus SECOND SYNAPSE: thalamus
THIRD SYNAPSE: parietal lobes
( postcentral gyri)- Sensory
Spinothalamic Tract Pathology
Syringomyelia
P
Spinocerebellar Pathway
The only pathway in the spinal cord that crosses
twice ( equivalent to ipsilateral)
Responsible for depth perception
Signs of damage:
INTENTION TREMOR (during reach)
DYSMETRIA (heal to shin) or PRONATOR DRIFT
DYSDIODOKINESIS (rapid movement)
ROMBERG SIGN (loss of unconscious proprioception)
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Spinocerebellar Pathway, cont
This pathway does NOTreach the cortex
Unconscious proprioception
(dont have to think about it) (dont have to think about it)
FIRST SYNAPSE: dorsal root ganglion
SECOND SYNAPSE: thalamus
THIRD SYNAPSE: cerebellum
Spinocerebellar Pathway Pathology
Alcohol attacks the vermis (midline) of the cerebellum
while other diseases attack the hemispheres
Fredriecks Ataxia-retinitis pigmentosa
Ataxia Telangiectasia- spider vein all over your body
Adrenoleukodystrophy- defective long chain FA
PONS
Responsible for responding to the environment
Contains the
PNEUMOTACTIC (superior)inhibitory to the APNEUSTIC
(bottom) responds to pO2 dec., pCO2 inc.
CNS area most sensitive to osmotic shifts
Pons Pathology
Locked-in Syndrome
Central Pontine Demyelinolysis Central Pontine Demyelinolysis
Medulla
Controls ALL basic functions
Respiration of 8-10 ipm
Make sure you know the cranial nerves !
Midbrain 3,4
Medulla 9,10,11,12
Pons 5,6,7,8
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How Do I Figure
Out Any Lesion? Out Any Lesion?
You know its a spinal cord
lesion when
Pain and temperature loss is opposite to
all other deficits
Level of the lesion is two dermatomes above
where pain and temperature loss begins and on the
opposite side (Lesion L2- loss at L4)
You know its a CNS lesion
when
UMN signs on one side of the body
( upper and lower extremities)
Then the lesion is on the opposite side of the brain
Use the cranial nerves to locate the level of the
lesion
THE END !
Too slow grasshopper !!!!
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Hematology
Hasenchecheg Qi MD Ph D Hasenchecheg Qi MD., Ph.D.
Red Blood Cell
Hemoglobin
1. A Hb is composed of:
1). four globins, proteins
pair of alpha (a2): located on chromosome 16
pair of beta (b2): located on chromosome 11.
2). four heme groups, with the iron compound which binds with the O2
2. Hb has 2 forms:
T (taut) low affinity for O2
R (relaxed) high affinity for O2
3. Function
1). In the lungs, each iron on Hb combines O2 reversibly.
2). Each Hb also has attached a single cysteine, which attracts nitric oxide (NO).
3). The enriched Hb circulates to the tissues, where the NO dilates the small capillaries,
allowing to deliver O2 to the tissues.
4). Then the O2- and NOfree Hb picks up CO2 and free NO and transports both back to
the lungs, where they are exhaled as waste.
5). When RBC are destroyed
the hema (iron) is stored in the liver for the manufacture of new red blood cells.
Globins is converted into bile and stored in the gall bladder
Hemoglobin
1. Hb A 22 m.c.
2. Hb A2 22 2.5% chain synthesis begins late in the
third trimester and in adults
3. Hb F 22 m.c. in the
fetus
small amounts in an adult, may be
abnormally elevated in certain forms
of anemia of anemia
4. Hb S sickle-cell
hemoglobin
5. Hb H 4 An abnormal Hb is not effectively
transport O2, it is usually associated
with a -thalassemia syndrome.
6. Barts 4 An abnormal Hb that is not effective in
O2 transport, found in -thalassemia.
Hb <11 mg/dl
MCV (80100) MCV < 80 MCV > 100
1. Thalassemia
2. AOC
3. Iron deficiency
i
1. B12 deficiency
2. Folate Deficiency
3. Alcoholic Liver
Reticulocyte
< 2.0 %Low > 2.0% high
Anemia
anemia
4. Lead Poisoning
5. Sideroblastic
anemia
disease
4. Drug induce
1. Marrow failure
2. Aplastic
Anemia
3. Myelofibrosis
4. Ca matastasis
5. AOC
6. Renal failure
2. All the
autoimmune
anemia
1. All the
hemolytic
anemia
Intra-
vascular
Extra-
vascular
1. Sickle Cell Disease
2. Hemaglubin C
Disease
3. G-6-P-D deficiency
4. Thelassemia Major
5. PNH
Hereditary
Spherocytosis
Heme Synthesis (mitochondria)
Glycine + Succiny CoA
-Aminolevulic acid
Prophobilinogen
ALA dehydrase
Lead (Pb)
ALA Synthase
Rate limited
B6 +
Sideroblastic
Anemia
Uroporphyrinogen-III
Protoporphyrin IX (protoheme)
Heme
Uroporphyrinogen-I
synthase
Ferrochelatase Fe2+ Lead (Pb)
Acute Intermittent
Porphyria
Iron Deficiency
Anemia
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Sideroblastic Anemia Lead Poisoning
cause Symptoms
1. decrease Vit B6 (m.c.) 1. Lead Line: in gums
2. isoniazid therapy 2. CNS : Encephapathy,
3. Abdominal pain (lead colic)
4. PNS: wrist and foot Drop
Diagnosis: Diagnosis:
Microcytic Anemia
Diagnosis: Diagnosis:
1. BM: ring sideroblast
(most specific test)
An erythroblast containing
granules of ferritin
1. blood lead level > 10 g/dl
2. increase free erythrocyte
protoporhyrin
2. Lab 3. basophilic stippling (remnants of
RNA) :
Treatment Treatment
Pyridoxine succimer (PO), EDTA
Acute Intermittent Porphyria Porphyria Cutanea Tarda
Uroprophyrinogen-1 Synthase
deficiency
Uroprophyrinogen
decarboxylase deficiency
Clinical Feature Clinical Feature
1. AD, variable expression 1. Photosensitivity
2. acute abdominal pain 2. blistering of skin
Microcytic Anemia
p
multiple laparoscopies (scars on
abdomen)
g
3.psychotic changes
4. increase ALA and PBG
(prophobilinogen)
5. no photosensitivity
6. Contraindicate: barbiturate
Anemia of Chronic Disease (AOCD)
Definition Lab Treatment
1. Iron being trapped in
bone marrow
macrophages, causes
inability to use of iron in
stores.
1. serum ferritin
elevated
2. serum iron low
3. reticulocyte count
lo low
2. long term chronic
disease cause decreased
liver functions,
1. decrease protein
synthesis
2. Transferrin low =
TIBC low
3. It can be microcytic or
normocytic
reticuloendothelial
system
Anemia of Chronic Disease (AOCD)
Iron deficiency Anemia Iron deficiency Anemia
Cause 1. decrease intake or
Increase demand
elderly, children, pregnant women
2. decrease absorption:
(malabsorption)
1) decrease acid (Vc)
2) Dumping Syndrome: decrease
small intestine transit time
3) after gastrectomy
3. chronic blood loss
(m.c.)
1) GI Ca (m.c. in USA)
2) GYN bleeding
( )
2) GYN bleeding
3) Hookworm (m.c. rest of the world)
Sequence
event due
to iron
deficiency:
1. decrease storage iron in
intestinal mucosa, spleen,
and liver
Decrease ferritin
2. decrease circulating iron Decrease serum iron
Increase TIBC
3. formation of
microcytic/hypochromic
anemia
Decrease RBC size
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Iron deficiency Anemia
Symptoms 1. General Low energy state, pallor of skin and nails,
2. others 1. Koilonychia: spooning of the fingernails
2. Pica
Lab Hb, MCV, Ht Decrease
RDW decrease
Serum iron decrease
Transferrin (TIBC) increase
ferritin decrease ferritin decrease
microscope microcyte
anisocytosis abnormal size
poikilocytosis abnormal shape
Diagnosis 1. depend on lab
2. definitive Dx: bone marrow
Treatment 1. diet
2. ferrous sulfate tablets
3. parenteral iron
4. blood transfusion: most effective
Terminology
1. Hb Hemoglobin F12-15 g/dl,
M 13-16g/dl
2. Ht (Hct) Hematocrit % of RBC in the blood 40 --50%
3. MCV mean cell (corpuscular) volume 80100
4. MCH mean cell hemoglobin 25.435 pg/cell
5. MCHC mean cell hemoglobin concentration 3136 g/dl
6. RDW red cell distribution width (A measure
of the variation in size of red blood
cells)
612%)
7. Reticulocyte immature RBC (1 day, normal 1.5%)
< 1%, poor bone marrow response
> 1%, good bone marrow response
Bluish color (polychromasia) due to
free ribosome RNA
Terminology
serum iron 100mg/dl
Ferritin 1. physiological storage iron form
2. intestinal mucosa, spleen, and liver
Hemosiderin 1. degraded ferritin + lysosomal debris
2. Prussian blue positive
Transferrin A beta globulin in blood serum that combines with and
transports iron.
Total iron-binding
capacity (TIBC):
1. means transferrin level
2. Transferrin = TIBC = 300 mg/dl
% saturation of
transferrin
serum iron/TIBC = 1/3
Microcytic Anemia
Iron
deficiency
AOCD Thalassemia
minor
Sideroblastic
anemia
serum
Iron
decrease decrease normal increase
serum decrease increase normal increase
Go Back
serum
ferritin
decrease increase normal increase
TIBC increase decrease normal decrease
%
saturation
decrease decrease normal increase
B12 Deficiency Anemia
Causes
1. Dietary
deficiency
1. B12 in red meat and fished
2. B12 stores at body for more than 1 year supply.
3. strict vegetarians, alcoholism
2. Decrease
absorption
1. decrease IF, gastrectomy or pernicious anemia
2. Pancreatic insufficiency
3. intestinal malabsorption
a. parasites: fish tapeworm diphyllobothrium latum p p p y
b. bacteria: blind-loop syndrome
c. Crohns disease
Sign and symptom
1. beefy tongue due to generalized epithelial atrophy
2. peripheral neuropathy
3. SCDSD: (Subacute combined degeneration of the spinal cord)
ii. demyelination of the posterior columns and lateral corticospinal tracts and
spinocerebellar tracts
iii. Urinary and fecal incontinence, impotence
iv. Dementia
B12 Deficiency Anemia
Diagnosis
1. peripheral smear Macroblastic anemia, hypersegmented
neutrophils
2. anti-IF: initial test sensitivity 50-80% , specificity 100%
3. serum homocysteine
increase
Due to folate or B12 deficiency
4. increase
methylmalonic acid
only due to B12 deficient
methylmalonic acid
5. Schilling test: over the 24 hours, a normal result shows at least
10% of the oral intake radioactive vitamin B12 will
be in the urine.
i. B12 injection + radiolabelled B12 orally
ii. B12 injection + radiolabelled B12 orally + IF
Treatment Treatment
B12 oral
Or parenteral
After give B12, may develop hypokalemia in 48
hrs, because potassium rapidly go into cells
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Folate Deficiency
Folate Deficiency
1. contain in green leaves vegetable
2. 3 month supply
Cause by
1. cause by tea and toast life-style
2. Methotrexate
3 Ph t i
Go Back
3. Phenytoin
4. Pregnancy
Lab
1. serum homocysteine increase: due to both folate and B12 deficiency
Treatment
Folic acid
Autoimmune Hemolytic Anemia (AIHA)
Warm AIHA Cold AIHA
Mechanism The IgG attach to a RBC,
leaving their F
C
portion
sticking out. The F
C
is
recognized and grabbed onto
by monocytes and
macrophages in the spleen.
antibodies initiate
complement lysis of
red blood cells
Antibody 1. IgG to Rh type 1. IgM
2. IgA
Cause 1. Methyldopa
2. Penicillin
1. Quinidine
coombs test + IgG, or IgG + C3 C3
Cold agglutinin negative positive
Treatment 1. steroid
2. splenectomy
3. treat causes
4. Cyclophosphamide
1. Cyclophosphamide
2. Chlorambucil
Normocytic Anemia
Intravascular (SH GTP) Extravascular Microangiopathic
Hemolytic Anemia
increase methemoglobin
(oxidized hemoglubin)
Rx; methylene blue
no methemoglobin 1. increase shictocytes
(fragmented RBC)
2. Helmet cell
markedly decrease decrease
haptoglobin heptoglobin
1. Sickle Cell Disease
2. Hemaglubin C Disease
3. G-6-P-D deficiency
4. Thelassemia Major
5. PNH
Hereditary
spherocytosis
1. DIC
2. TTP
3. HUS
4. Prosthetic Heart Valve
5. HELLP
Hereditary Spherocytosis
Definition 1. AD,
2. defect spectrin in RBC membrane
Clinical
feature
1. splenomegaly
2. increase risk for acute aplastic crisis with Parovirus
B19 infection
Lab 1. increase spherocytes
2. normocytic hyperchronic
3. increase MCHC
4. increase osmotic fragility
Rx
Sickle Cell Diasese Hemoglobin C Disease
single nucleotide change in codon casues
valine (neutral) to replace normal glutamic
acid (acidic) at 6 position of the -globin
chain
single nucleotide change in
codon causes lysine (basic) to
replace normal glutamic acid
(acidic) at 6 position of the -
globin chain
Hemoglobin S Sign:
1. become less soluble under decreasing
oxygen concentrations
1. splenomegaly
Sickle Cell Disease
oxygen concentrations
2. The deoxygenated molecules form rigid
rods called polymers into crystals that distort
the red blood cells into a sickle shape.
2. target cell
3. These abnormally sickle-shaped cells are
both rigid and sticky.
3. rod-shaped crystals in RBCs
Genitic types
1. heterozygous (AS): trait
blood urine and resistance to malaria
2. Homozygous (SS):Sickle cell disease
Sickle Cell Disease
Affecting factors 1. increase concentration (dehydration), make it
worse
decrease concentration make it better
2. Decrease pH decrease oxygen affinity: worse
3. increase HbF: better
Increase RBC 1 Erythroid hyperplasia Increase RBC
destruction cause
1. Erythroid hyperplasia
2. increase bilirubin
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Vaso-occlusion
1. Hand-foot syndrome (dactylitis) 1st sign of SD, in children
2. Vaso-occusive (painful) crisis Rx: 1. Self limiting, last 2-7 days
2. hydration: NS
3. Morphine for pain
4. keep warm
5. Oxygen
3. Autosplenoectomy 1. Howell-Jolly bodies in peripheral blood:
t f l h ti
Sickle Cell Disease
remnant of nuclear chromatin
2. increase infection of encapsulated
organisms, Rx: vaccinations
4. Leg ulcers increase Salmonella osteomyelitis (leg pain)
5. Avascular necrosis of the joints M.c. hip, 2nd shoulder
6. Priapism Emergencies, Rx: transfusion
7. Acute chest syndrome Emergencies, Rx: transfusion
8. Aplastic crisis with infection of B19, Rx: folic acid
Treatment 1. Hydroxyurea; increase HbF
2. BM transplantation
G-6 PD Deficiency
G-6 PD Deficiency
G-6 PD deficiency causes decrease glutathione peroxidase
(antioxidant)
Clinical Feature
1. X-link R
i. African American type:
ii. Mediterranean type
2 H i b di id ti f h l bi 2. Heinz bodies: oxidation of hemoglobin
3. Bite cell: to eat heinz bodies by splenic macrophages
Treatment
Thalassemia Syndrome
Definition: quantitative, not qualitative, abnormalities of hemoglobin
1. -thalassemia 2. -thalassemia
1. decrease -globin chains ,
excess -chains
1. decrease -globin chains,
excess -chains
2. most commen in Asian population 2. most common in Mediterranean
3. expression in prenatally and
postnatally
expressed postnatally only
postnatally
-Thalassemia
Genetic
Normal
4 -chain (/)
Silent carrier 1. deletion 1-chain
2. (-/),
-Thal trait
(minor)
deletion 2 -chain 1. Genotype: cis (--/) type
in Asian
2 G t t ( / ) 2. Genotype: trans (-/-)
type in African-American
Hb H disease
(major)
1. deletion 3 -chain
2. (--/-)
1. increase Hb H,
2. forms Heinz bodies
Hydrops fetalis 1. deletion 4 -chain,
2. lethal in utero (--/--)
increase barts Hb
-Thalassemia
Genetic 1. normal: 2 chains,
2. point mutations,
1. -Thal minor asymptomatic, increased HbA2 or HbF
2. -Thal intermedia a severe anemia, but no transfusions needed
3. -Thal major
(Cooley Syndrome)
1). normal at brith
2). develop at about 6 month as HbF decrease
3). severe hemolytic anemia
a. increase bilirubin, gallstones
b. Congestion heart failure is most common cause of
death
4). Erythroid hyperplasia in BM: x-ray: crewcut skull ,
chipmunk face
5). Peripheral in the blood: Numerous target cells
Treatment 1. do not require specific treatment
2. -major: blood transfusions 1 or 2 / month:
SE: Hemochromatosis, treat with deferoxamine
3. splenectomy eliminates severe hemolytic anemia:
4. Bone marrow transplantation
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6
PNH
Paroxysmal Nocturnal Hemoglubinuria
decreased glycosyl phosphatidyl inositol (GPI) linked proteins, especially
decay accelerating factor (DAF)
Function of DAF:
1. inhibit the activation of the complement cascade by breaking down C3
convertase
2. decrease O2, trigger complement pathway
Symptoms and Complication Symptoms and Complication
aplastic anemia, leukemia, venous thrombosis
Diagnosis
1. Hams test (Acidosis in vitro)
2. sucrose lysis test (sugar water test)
3. flow cytometry: CD55, CD59, much more sensitive and specific
Treatment
1. Glucocorticoids
2. BM transplantation
Summery
RBC shapes Diseases
Anisocytosis Iron deficiency anemia
Poikilocytosis Iron deficiency anemia
Shperocytes 1. hereditary spherocytosis
Target cells Thalassemia, Hb C disease, Liver Disease
Bite cell G6PD deficiency
Teardrop cells Myelofibrosis
Elliptocytes Hereditary elliptocytosis
Acanthocytes abetalipoproteinemia
Echinocytes (burr cells) uremia
Schistocytes (Helmet cells) HUS, DIC, TTP
Rouleaux Multiple myeloma
Summery
RBC
inclusions
Diseases
Basophilic
stipling
Cytoplasmic remnant
RNA
Lead poisoning
Ho ell Joll Remnants of n clear Iron deficienc anemia Howell-Jolly
bodies
Remnants of nuclear
chromatin
Iron deficiency anemia
Ring
sideroblasts
Iron trapped
abnormally in
mitrochondria forming
a ring around nucleus
Sideroblastic anemia
Heinz-bodies G6PD
Other types Anemia
1. Diamond-Blackfan Syndrome:
congenital pure RBCs anemia
2. Fanconi anemia (Constitutional)
pencytopenia with abnormal structures
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Hemostasis
Bleeding Disorder g
Hasenchecheg Qi MD., Ph.D.
3:1 = M:E (myeloid to erythroid) ratio.
Bleeding
Hemostasis
Hemostasis
1. vascular wall
injury
1. bleed
2. transient
vasoconstriction
changes blood flow cause
turbulence and stasis
Reynolds number = (diameter)
(velocity) (density)/viscosity
> 2000 = turbulent flow
< 2000 = laminar flow
3. thrombogenic factors 1. release tissue factor, activate
VII ( t i i ) VII (extrinsic)
2. active factor XII (intrinsic)
due to expose subendothelial
collagen
3. release vWF
2. transient clotting platelet clotting bleeding time 27 min
3. Secondary
clotting
Extrinsic Coagulation
factor
PT: Prothrombin Time 12sec
Intrinsic Coagulation
factor
PTT: Partical Throboplastin
Time 30sec
Adhesion
Aggregation
1. platelets
adhesion
1. vWF adheres
to subendothelial
collagen
2. Platelets
adhere to vWF
by glycoprotein Ib
2. platelets
activation
1. platelets
changes shape
and
degranulation
Platelets
Aggregation
2. synthesis of
TXA2
3. platelets
aggregation
1. ADP
clopidogrel,
Ticlopidine
2. TXA2
3. GpIIb/IIIa
Abciximab,
Eptifibatide,
Tirofiban
ADP
Coagulation Factors
Vitamin K
Glutamyl Carboxylase
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2
Thrombomodulin (transmembrane protein)
Thrombin
(60 hrs)
Protein C
(Half life 14 hrs)
C-activated protein
+
(Half life 14 hrs)
Protein S
Inactivates
Factors Va and VIIIa
+
Factor V leiden:
variant of factor V
Wafarin:
Transient deficiency
of protein C
Bleeding Disorder
Platelet 150,000450,000/mm
3
bleeding time: 27 min
1. Decrease Platelet
account
2. Abnormal Platelet
function
3. Von Willebrand
Disease (vWD)
AD/AR, vWF 1. bleeding time prolong
2. ristocetin
attributed to Factor 8
deficiency
3. PTT prolong
Rx: Desmopressin
acetate (DDAVP)
4. Bernard-Soulier
Syndrome
Gp Ib deficient Rx: Platelet
5.Glanzmann
Thrombasthenia
Gp IIb/IIIa deficient Rx:
Immune
Thrombocytopenia
Purpura
Thrombotic
Thrombosytopenia
Purpura
Hemolytic
Uremic
Syndrome
Disseminated
Intravascular
Coagulation
1. anti-platelet Fever
Anemia
Thromcytopenia
Diarrhea
Renal failure
1. D-dimers
2. Increase BM
megakaryocyte
2. Platelet count
decrease
3. acute form: child
after viral infection
Renal failure 3. Bleeding time increase
4 chronic: adult Neuropathy 4 PT and PTT increase
Thrombocytopenia
4. chronic: adult
women 20-40 yo
Neuropathy 4. PT and PTT increase
Treatment Treatment Treatment Treatment
1. child self limited in
6mo, or prednisone
plasmapheresis 1. adult:
plasmapheresis
1. supportive
2. adult
a. prednisone
b. IVIG, anti Rh (D): fast
c. splenoectomy,
Vaccine
d. platelet transfusion
2. child:
self limited
2. FFP
3. Cryoprecipitate
4. treat causes
Thrombocytosis (reactive) Essential Thrombocythemia (ET)
Cause Clinical Features
1. Bleeding, hemolysis 1. Increased platelet count
2. Inflammation 2. increased BT
3. Iron deficiency, Stress 3. increased BM megakaryocytes
4 t l t
Thrombocytosis
4. postsplenectomy
5. Malignancy
Disorder of Coagulation
von Willebrands Disease Hemophillia A Hemophillia B
vWF deficiency, VIII deficiency, IX deficiency,
AD/AR, XR, XR,
May have VIII deficiency vWF normal
Clinical Feature Clinical Feature
1. Cutaneous and mucosal bleeding 1. joint and soft tissue bleeding
2. Menorrhagia, 2. Hemarthrosis: m.c.
3. GI bleeding 3. Intracranial bleeding: 2nd m.c.
Di i Di i Di i Diagnosis Diagnosis Diagnosis
1. BT increase, may with increase PTT 1. PTT increase 1. PTT increase
Treatment Treatment Treatment
Do not give Aspirin/NSAIDs
1. DDAVP (desmopressin) 1. factor VIII 1. factor IX
2. Factor VIII concentrations,
give all Pt with vWD after major trauma
or during surgery
(reduced ristocetin-induced platelet
aggregation)
2. FPP not recommended because virus infections
Treatment of Acute hemarthrosis
1. Analgesia, (Codeine)
2. Immobilization
3. Synovectomy (arthroscopic) or radiosynovectomy
for severe and recurrent hemarthrosis
Hypercoagulation
1. XII deficiency
Thrombosis, no bleeding PTT prolong,
2. XIII deficiency
Rare,
newborn bleeding from cut
umbilical cord
Normal PT and PTT
Dx. Clot solubility test in 5M
urea, positive
3. Antithrombin (AT)
III deficiency
Thrombosis PTT prolong
4. Antiphospholipid
antibody Syndrome
Thrombosis
Recurrent abortion
PTT prolong
antibody Syndrome
5. Factor V leiden
Leiden variant of factor V,
(Activated protein C
resistance)
recurrent DVT
Rx: life-along anticoagulation
(Warfarin)
6. Protein C
Deficiency
Active Factors Va and VIIIa 1. dermal vascular thrombosis
2. skin necrosis
7. Protein S
Deficiency
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3
Plasma: no cells from blood
Serum: no coagulation factor from plasma.
include all the ion and antibodies, immunoglobulin.
Streptokinase
Urokinase
+
Alteplase (tPA)
Reteplase (rPA)
Anistreplase
Thrombolytics
Anticoagulation Medications
Heparin LMWH Warfarin
Low-Molecular Weight Heparin VIt K antagonist
Inhibit IIa and Xa Mostly inhibit Xa Inhibit II, VII, IX, X, and protein C and S
Half-lift time Half-lift time Half-lift time
1 hour 3-24 hours 4 days
Administration Administration Administration
1. therapeutic dose:
IV heparin, monitor PTT
1. subcutaneously
PTT monitor not necessary
1. orally: monitor PTT, Monitor INR (2-3)
2. prophylactic dose:
SC low dose heparin SC low-dose heparin,
PTT monitor not necessary
SE and Advantage SE and Advantage SE and Advantage
1. Bleeding 1. easer use out Pt 1. Hemorrhage
2. Heparin-induced
thrombocytopenia (HIT)
2. no HIT or osteoporosis 2. skin necrosis ( decrease protein C)
3. Osteoporosis 4. no osteoporosis 3. Teratogenic during pregnacy
4. Transient alopecia 5. more expensive
5. rebound hypercoagulability
d/t depression of ATIII
SE Treatment SE Treatment
1. stop medication, 2. Give PPF, 3. Warferin over dose may also give Vit K
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4
247
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1
Lymphoma
&
L k i Leukemia
Hasenchecheg Qi M.D.; PH.D.
3:1 = M:E (myeloid to erythroid) ratio.
Lymphoma
Precursor
B-Cell
Mature
B cell
ALL T-ALL
Precursor
T-Cell
Mature
T cell
Plasma Cell
Neoplasma
1. Multiple myeloma
2 MGUS (Monoclonal Gammopathy
Non-Hodgkin Disease HD
1. not infections
Not B-cell
Not T-cell
< 15 year old
Positive TdT
Thymoma
< 25 years old
2. MGUS (Monoclonal Gammopathy
undetermined significance)
3. Waldenstrom macroglobulinemia
2. owl-eye
3. R-S cell
1. NS: m.c. Lacunar cell
2. LP: popcorn cell
3. LD: most RS cell
4. Mixed: eosinophils, IL-5
1. L1
2. L2
3. L3
Acute Lymphoblastic Leukemia
1. ATLL
2. MF and Sezary S.
Terminal Deoxynucleotide
transferase
Lymphoma
Mature B cell
Non-Hodgkin Disease HD
If > 65 years old
1. CLL: m.c.
chronic lymphocytic leukemia, or
small lymphocytic lymphoma
1. Follicular 1. m.c. non-HD 18: bcl-2: inhibits
2. Hairy cell leukkemia
Dx: TRAP +
Rx: 2CDA
1. Follicular
Lymphoma
1. m.c. non HD
2. t (14, 18)
18: bcl 2: inhibits
apoptosis by blocking the
bax channel
2. Diffuse large B-
cell lymphoma
1. EBV
2. HHV-8
3. Samll noncleaved
lymphoma (Burkitt
lymphoma)
1. starry-sky
2. t (8, 14)
8: c-myc
4. Mantle Cell
Lymphoma
T (11, 14) 11: bcl-1 (cyclin D)
5. MALToma
(Marginal zone
Lymphoma)
Treat as H.pylori
2-
chlorodeoxyadenosine
Tartrate-resistant acid
phosphatase
Leukemia
AML
CML
1. M0M4: myelo-, WBC
2 M3 t (15 17)
BM blast <30%
MDS
ET P. vera
Myeloproliferative Syndrome
MF
BM blast > 30%
1 t (9 22) 2. M3: t (15, 17)
15: PML
17: retinoic acid receptor -gene
(RAR-)
3. M5: monoblasts
4. M6: erythroblasts
5. M7: megakaryocytes
1. Dry tap
2. Teardrop RBC
1. t (9, 22)
9: c-abl
22: bcr
2. LAP low
248







Biochemistry:
Week Three
261 249
262 250
1
BIOCHEMISTRY
AMINO ACIDS
Three sources of energy
Proteins
Fats
Sugars
Proteins
The main intracellular buffers
AMINO ACIDS
An Acid
Pka is less than 7
A Base
Pka is greater than 7
263 251
2
An Acid
Dissociates early
Likes to give up hydrogen ions (protons)
Pka is less than 7
Strong acid: Pka 1 to 3
Weak acid: Pka 4 to 7
A Base
Dissociates later
Likes to accept hydrogen ions (protons)
Pka greater than 7
Weak base: Pka 7 to 9
Strong base: Pka greater than 9
Pka 4 to 9
Can be a weak acid or a weak
base
Three Easy Words That are Hard
To Understand
Dissociate: to lose a hydrogen (proton)
Soluble: charged or polar
Bioavailable: neutral
Dissociation
Dissociation
To Lose A Hydrogen
264 252
3
Soluble Soluble
Charged Or Polar
Soluble
Water Soluble
Bioavailable
Bioavailable
Neutral
Bioavailable
Fat Soluble
265 253
4
AMINO ACIDS As an acid dissociates
It gains a negative charge
It gains solubility
It loses bioavailability
As a base dissociates
It loses its positive charge
It loses solubility
It gains bioavailability
Henderson-Hasselback Equation
Henderson-Hasselback Equation
ACIDS
IF you want to absorb more
Add more Acid
IF you dont want to absorb it
Add base
266 254
5
Base
IF you want to absorb more
Add more base
IF you dont want to absorb it
Add acid
Acids you need to know
Aspirin
Barbiturates
Myoglobin
TCAs
Bases you need to know
Amphetamines
The main acid used in
medicine
NH4CL
The main base used in
medicine
HCO3
Now we look at the ISOELECTRIC
POINT
267 255
6
Isoelectric Point
NO NET charge on the molecule
Also called a zwitterion
Will NOT migrate towards anode or
cathode
Cathode
Where CATIONS go: the
negative electrode
Anode
Where ANIONS go: the positive
electrode
268 256
7
To further categorize the
amino acids
Glycine
Smallest amino acid
NO chiral carbon
Inhibitory neurotransmitter for the spinal
cord
PHE, TRP, TYR
Aromatic amino acids
Recognized by chymotrypsin
LYS, ARG
Basic amino acids
Have a positive charge
Recognized by trypsin
Asp, Glu
Acidic amino acids
269 257
8
Asp
The only excitatory amino acid in the brain
( NMDA pathway)
Cys, Met
Contain sulphur
Make disulphide bonds
Asparagine, Glutamine
Involved in N- bonds
Serine, Threonine, Tyrosine
Involved in O- bonds
Leu, Iso, Val
Branched chain amino acids
Tyr
Used to make catecholamines
Used to make melanin
270 258
9
Trp
Used to make serotonin
Ketogenic Amino Acids
Lysine
Arginine
Both glucogenic and ketogenic
PHE
ISO
THR
TRP
Glucogenic Amino Acids
ALL OTHERS
Essential Amino Acids
You get them ONLY from the diet
NO cycle in YOUR body can make these
A deficiency will ALWAYS lead to a
disease
Deficiencies put the body into a starvation
state
Essential Amino Acids
271 259
10
How does the body utilize energy
during starvation?
Energy Utilization
(1) plasma glucose: lasts 2 to 4 hours
(2) liver glycogen: lasts 24 to 28 hours
(3) proteolysis for gluconeogenesis
(4) lipolysis
(5) ketogenesis
Notables
PHE used to make TYR
TYR becomes essential if PHE is deficient
MET used to make CYS
CYS becomes essential if MET is deficient
Phenylketonuria
Phenylalanine hydroxylase is deficient
Unable to make tyrosine
Unable to make DA and NE and EPI
Unable to make melanin without tyrosine
Blonde hair; blue eyes; fair skin
Phenylacetate and phenylpyruvate build
up
Musty odor
PKU
Must screen all newborns at 48 hours
Must avoid aspartame (nutrisweet)
Pregnant mother must be on restricted diet
especially during first 8 weeks while brain
is developing
Rainbow colored wheel on food products
would warn these patients against
aspartame
Newborn Screening
PKU ( Guthrie test)
Hypothyroidism (TSH)
CAH
Biotinidase def
Galactosemia
272 260
11
Albinism
Tyrosinase deficiency
Predisposed to skin cancer
Vitiligo
Autoimmune antibodies against
melanocytes
Loss of pigmentation
Predisposed to skin cancer
Alcaptonuria (ochronosis)
Homogentisic acid oxidase deficiency
Tyrosine builds up
Urine turns black when exposed to air
Maple Syrup Urine Disease
Involves branched chain amino acids
Defective renal transport of these amino
acids
LEUCINE
ISOLEUCINE
VALINE
Cystinuria
Defective renal transport of amino acids
Hexagonal, envelope shaped, or coffin lid
shaped crystals in the urine
CYSTIENE
ORNITHINE
LYSINE
ARGININE
THE END
TO BE CONTINUED
273 261
1
Protein Structure
and Function
Putting the Amino Acids
Together
Protein Structure
Primary
Secondary
Tertiary
Quarternary
Protein Structure
Primary
Secondary
Tertiary
Quarternary
Primary Structure
The amino acid sequence
Involves peptide bonds
Restriction enzymes are used to sequence
proteins
Peptide Bond Peptide Bond
Planar
Restricted mobility
R-groups are in trans-configuration
274 262
2
Sequencing
Before we understand the
present
We need first visit the past!
The history of sequencing
Acid hydrolysis
Gel electrophoresis
Ninhydrin reaction
Edmans degredation
Restriction peptidases
Acid Hydrolysis
Denatures the protein
Does NOT actually sequence the protein
Turns asparagine into aspartate (acidic
form) and glutamine into glutamate (acidic
form)
Gel electrophoresis
Uses agarose gel to separate proteins by
size first, charge second
Smaller proteins migrate further
Larger proteins stay closer to the start site
Does NOT sequence the proteins
Gel Electrophoresis
275 263
3
Ninhydrin Reaction
Reacts with all amino acids creating a
purple color
Proline reaction creates a yellow color
Good ONLY for counting prolines
Edmans degredation
Uses phenylIsoThioCyanate (PITC)
Reacts with ANY amino acid starting on
the amino terminal
Amino acids are identified by
spectrophotometry (light transmission)
Procedure is accurate ONLY up to 100
amino acids
Restriction Peptidases
Restricted by what amino acids they can
recognize
Used to actually sequence proteins
Restriction Peptidases
Trypsin: cuts to the right of LYS and ARG
Chymotrypsin: cuts to the right of the
aromatic amino acids, PHE, TRP, TYR
Elastase: cuts to the right of GLY, ALA,
SER
CNBr: cuts to the right of MET
Aminopeptidase: cuts to the right of the
amino terminal amino acid
Restriction Peptidases, cont
Carboxypeptidase: cuts to the left of any
amino acid on the carboxyl terminal
Mercaptoethanol: breaks up disulfide bonds
An Example
276 264
4
Secondary structure
Alpha helix
Beta pleated sheet
Alpha helix
Beta pleated sheet Serum proteins
Functional
Acute phase reactants
Too many proteins in your plasma
Elevated ESR or CRP
Indicates nonspecific inflammation
Falsely high ESR: anemia
Falsely low ESR: sickle cell anemia;
polycythemia
Acute phase reactants caused by IL-6
TOO many acute phase
proteins
Leads to AMYLOIDOSIS
277 265
5
AMYLOIDOSIS
Primary: autosomal dominant
Massive intracerebral hemorrhage in a young
person with no prior h/o HTN
Secondary: due to any chronic
inflammatory disease
Congo red stain
Apple green birefringence
Secondary Amyloidosis
AA: chronic inflammatory disease
AB: Alzhiemers disease
AB-2: Chronic renal failure
AE and AF: MEN-II
AL: Multiple myeloma
Tertiary Structure
3-D structure
Most important factor is hydrophobic and
hydrophilic interactions
Covalent bonds now form
Quarternary Structure
Two or more proteins are interacting
Cooperativity
Allosterism: refers to enzymes
Allosteric enzyme means the slowest enzyme;
means rate-limiting enzyme; means the
kinetic curve is sigmoidally shaped
Hemoglobin
The first quarternary protein
discovered
Hemoglobin
Type A: 2 alpha 2 beta chains
Type A-2: 2 alpha 2 delta chains
Type F: 2 alpha 2 gamma chains
278 266
6
Hemoglobin F
Found in the fetus
Disappears by 6 months of age
Has a low affinity for 2,3, DPG
Has a high affinity for oxygen
Hemoglobin F
Erythropoiesis
Begins: in yolk sac at 4 months gestation
6 mo gestation: moves into the liver,
spleen, and flat bones
8 mo gestation: moves into the long bones
1 year of age: liver, spleen, and flat bones
close
If you lose the long bones after 1 year, the
spleen can reopen causing massive
splenomegaly
Heme Synthesis
Iron deficiency anemia
Most common cause of microcytic
hypochromic anemia
In children: Mcc is inadequate intake
In young adults: Mcc is still inadequate
intake
20 to 40: IBD
> age 40: mucasal bleeding
Tx: ferrous sulphate
Lead Poisoning
Lead inhibits delta ALA dehydratase as
well as ferrochetolase
Mcc: eating peeling paint from old
buildings
Classic clue: basophilic stippling; elevated
FEP (free erythrocyte protoporphrins)
279 267
7
Heme Synthesis Lead levels to know
Normal: < 10
If above 10: notify PHD; treat with succimer
If above 30: notify PHD; hospitalize; do a
Ca-EDTA challenge; treat with
penicillamine and dimercaprol (BAL) if
urinary lead is high
If above 50: do as above; skip EDTA
challenge
Drug induced lupus
Antihistone antibodies
Hydralazine
INH
Procainamide
Penicillamine
Phenytoin
Ethusuximide
Lead used to be the most
common cause of mental
retardation
But NOT ANY MORE!
Mental retardation
Fetal alcohol syndrome
Fragile X syndrome
Downs syndrome
Porphyrias
A group of enzyme deficiencies
Synthesize too many porphyrin rings or
inadequate metabolism are the problems
Porphyrin rings in the urine make it red
Two types are most important
280 268
8
Acute Intermittent Porphyria
Enzyme dificiency
A build up of porhyrin rings
Porphyrin rings are deposited in visceral
organs and around nerves
Recurrent severe abdominal pain and
neuropathy
Tx:
Erythrocytic Protoporphyria and
Porphyria Cutanea Tarda
Enzyme dificiency
Porphyrin rings are deposited underneath
the skin
Light reacts with the rings causing a
release of heat which leads to burns
Mcc of death: skin infections
Tx: protect them from light
Opiates
CNS depressants
Muscle relaxants
Analgesics
Receptors:
Mu ( CNS)
Kappa: Spinal cord
Opiates
Heroin
Methadone
Morphine
Meperidine
Codone
Oxycodone
Codiene
Dextromethorphan
Loperimide
Diphenoxylate
Fentanyl
Pentazocine
Hemoglobinopathies
Hemoglobin S disease
Hemoglobin C disease
Hemoglobin S disease
Autosomal recessive
High prevalence in Africa ( natural
selection)
Substitution of valine for glutamate at
position 6 of beta chain
Hypoxia causes cells to sickle leading to
vaso-occlusion
281 269
9
Vaso-occlusive crises
CVA
PULMONARY INFARCTION
SPLENIC SEQUESTRATION
PRIAPISM
Tx: exchange transfusion; oxygen
Aplastic crisis
Complete bone marrow suppression
Always check the reticulocyte count
Mcc: parvovirus B-19
A Few Points to Remember
Functional asplenia by age 6 due to
infarcts
Susceptible to encapsulated organisms
Give pneumovax anytime after age 2
Infections are mcc reason for crises
Hydroxyurea increases HgF, decreasing
chance for hypoxia
Use opiates for pain
Transfuse when anemic and symptomatic
Hemoglobin C disease
Autosomal recessive
Substitution of LYS for GLU at position 6
of beta chain
NO sickling occurs since both amino acids
are hydrophilic
Thallesemias
Represent gene deletions
Autosomal recessive
Common in Mediterainian people
Minor: at least one gene remaining
Major: no genes remaining
Hemoglobins
282 270
10
Alpha Thalessemia Baseline labs
RBC Mass: 3.5 to 4.5 million
Hemoglobin/Hematocrit: 15/45%
Alpha Minor
One gene missing
Asymptomatic ( HG 12) 75%
Two genes missing
IF sedentary: asymptomatic
IF active: symptomatic (HG 7.5) 50%
Three genes missing
Symptomatic in ALL (HG 4 to 5)
Alpha Thalessemia Major
NO genes remaining
Unable to make any hemoglobin at all
Hydrops Fetalis
Hemoglobin Bart ( 4 gamma chains)
Hemoglobin H ( 4 beta chains)
Beta Thalessemia: 2 genes
Beta minor (Hg 7.5)
One gene missing
If sedentary:
asymptomatic
If active: symptomatic
Increased Hg A-2 and
Hg F
Ineffective
erythropoiesis
Beta major
Both genes missing
Able to make only Hg
A-2 and Hg F
Asymptomatic until 6
months of age
Transfusion dependent
Blood Transfusions
Done ONLY when patient is symptomatic
One unit of PRBCs
Raises Hg by 1 to 2 grams ( 3 to 6 HCT)
Delivers 3.4 grams of iron
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11
Iron Overload
Hemosiderosis: bone marrow is
overwhelmed by iron
Hemochromatosis: iron overload has
involved other organs
Skin: bronze pigmentation
Liver: bronze cirrhosis
Pancreas: bronze diabetes
Heart: restrictive cardiomyopathy
Hemochromatosis
Primary
Autosomal recessive
Too much iron
absorption from
duodenum
HLA A3 on
chromosome 6
Secondary
Too many transfusions
Mcc of death in first 10
years: transfusion
related infections
Mcc of death after 10
years: CHF
Transfusion Related INFECTIONS Transfusion related infections
HIV Bacterial infections
Hepatitis B Malaria
Hepaitis C Babesiosis
Hepatitis D Syphilis
EBV
CMV
Hemorrhagic viruses
Hemoglobin Saturation Curve
COLLAGEN
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12
More than a quarternary
structure
Its a TRIPLE HELIX
4 Types of collagen
Type 1: Skin
Type 2: Connective tissue
Type 3: Arteries
Type 4: Basement membrane
To synthesize collagen
Glycine: every third amino acid
Lysine
Proline
OH-Proline
OH-Lysine
Protein synthesis for packaging
Protein synthesis for packaging Protein synthesis for packaging
285 273
13
Protein synthesis for packaging
Who makes collagen?
Fibroblasts: simple scarring
Myofibroblasts: if you need wound
contraction
When collagen synthesis goes
wrong
DESMOPLASIA
COLLAGENOUS REACTION
SURROUNDING A TUMOR
KELOID
TOO MUCH COLLAGEN
DEPOSITION
COLLAGEN PROFILE
286 274
14
ALL YOU NEED NOW IS A CLUE
Collagen diseases
Ehlers Danlos
Marfans
homocystienuria
Scurvy
Osteogenesis imperfecta
Minkys kinky hair syndrome
Secondary collagen diseases
Ankylosing spondylitis
Fragile X syndrome
Syphilis
Takayasus disease
Collagen Vascular Diseases
CREST
Scleroderma
Progressive systemic
sclerosis
Rheumatoid arthritis
Feltys syndrome
Becets syndrome
Sjogrens syndrome
SLE
MCTD
ELASTIN
Elastin
Has many GLYCINES
Has PROLINES
Has LYSINES
Has OH-PROLINES
NO hydroxylysines
287 275
15
Elastin
Provides COMPLIANCE
Provides ELASTICITY
Has DESMOSINE
Elastase
Destroys elastin
Cuts to the right of GLY, ALA, and SER
Alpha-one antitrypsin inhibits elastase
Found in neutrophils and bacteria
Smoke inhibits alpha-one antitrypsin
Decreased alpha-one antitrypsin with
aging
Emphysema
Destruction of elastin
Loss of recoil
Panacinar: alpha-one antitrypsin deficiency
Centroacinar: smoking
Disto-acinar: aging
Bullous: staph aureus and pseudomonas
Whos afraid of staph aureus and
pseudomonas?
Neutropenic
Burn patients
Cystic fibrosis
Diabetics
If any fever, cover staph aureus with one
antibiotic and cover pseudomonas with
two antibiotics
Keratin
Made for tensile strength
Contains a lot of CYSTEINES
THE END
ONLY FOR NOW
288 276
1
ENZYMES
THE MOST IMPORTANT
PROTEINS IN YOUR BODY
IF asked whether a reaction is
possible
THE answer is always YES!
ANYTHING, as we know
IS POSSIBLE!!
A Reaction
An Enzyme
Brings substrates together in space and
time
Lowers the free Energy of activation
Stabilizes the hi energy intermediate
Is not consumed in the reaction
An ENZYME has
289 277
2
Competitive inhibition
Inhibitor is similar to the substrate
The inhibitor is competing for the active
site
Affinity I decreased
Km increases
Vmax remains the same ( just add more
substrate)
reversible
Noncompetitive inhibition
NOT similar to the substrate
Does NOT bind active site
Binds to regulatory site
Turns off the enzyme
Km remains the same
Vmax decreases
irreversible
What makes a reaction favorable
and spontaneous
Effects of temperature on a
reaction
E
REDOX POTENTIAL
E
You want it to be negative
When negative: has electrons
to give
When positive: wants to accept
electrons
290 278
3
Reducing agent
Has a negative delta E
Wants to give away electrons
Gets oxidized after the reaction
Oxidizing agent
Has a positive delta E
Wants to accept electrons
Gets reduced after the reaction
Electron Transport System
Inhibitors and Uncouplers
291 279
4
Inhibitors Uncouplers
DNP
ASPIRIN
FREE FATTY ACIDS
How to name enzymes
FIRST NAME of an enzyme
IS the name of the SUBSTRATE
LAST NAME of an enzyme
Is what you did to the substrate
LAST NAMES of enzymes
Kinase
Phosphorylase
Isomerase
Epimerase
Mutase
Transferase
Lyase
Carboxylase
Synthase
Synthetase
Dehydrogenase
Hydrolase
292 280
5
Coming to a screen near
you
THE PATHWAYS
293 281
Anabolic Pathways:
Putting it all back together
As soon as you eat
You replenish your plasma glucose
After glucose returns to
the liver
You turn off gluconeogenesis
After you turn off
gluconeogenesis
You turn on glycogen synthesis
Glycogen Synthesis
294 282
Pentose Pathway
NADPH is used for
Fatty acid synthesis
DNA synthesis
RBC repair ( used by glutathione)
X-linked Recessive Enzymes
G6PD
Fabrys ( alpha galactosidase)
Hunters ( Iduronidase)
CGD ( NADPH Oxidase)
Lesch-Nyhan ( HGPRT)
Pyruvate Dehydrogenase
Adrenoleukodystrophy ( CAT-1)
G6PD
More common in Meditteranians ( protects
them from malaria)
Mcc of hemolytic crisis: ( 1) infection (2)
drugs
Drugs that oxidize RBCs: sulfa drugs;
antimalarials; metronidazole; INH
295 283
Amino Acid Synthesis Fatty Acid Synthesis
Palmitic Acid
The main fatty acid that we make every
day
Saturated FA: NO double bonds
Unsaturated FA: has double bonds
Omega FA: counting carbons from the right
side
Omega 3 FA: Lowers serum cholesterol
Pocosanol
Rules for Fatty Acids
We do NOT go beyond C-16
Double bonds have to be at least 3
carbons apart
NO double bonds after C-10
Essential Fatty Acids
Linolinic
Linoleic ( used to make arachadonic acid)
Come ONLY from the diet
Your body can not make these
296 284
Arachadonic Acid
Irreversible Cyclo-Oxygenase
Inhibitor
Aspirin
Reversible Cyclo-Oxygenase
inhibitors
NSAIDs
Indomethacin
Phenylbutazone
Ibuprofen
Naproxen
Baclofen
Ketorelac
cyclobenzaprine
Steroids
Antiinflammatory
actions
Inhibit PLP-A
Kills T-cells and
eosinophils
Inhibits macrophage
migration
Stabilizes mast cells
Stabilizes endothelium
Physiologic actions
Proteolysis
gluconeogenesis
Steroids
Prednisone
Methylprednisalone
Triamcinalone
Beclamethasone
Betamethasone
Hydrocortisone
Dexamethasone
fludrocortisone
Cypropterone
Megestrol
Fluticasone
Mometasone
Danazol
Mast Cell Stabilizers
Cromolyn
Nedacromyl
297 285
LRBs
Zifurlekast
Montelekast
Zileutin
Triglyceride Synthesis
Triglyceride Transport
Chilomicrons
VLDL
IDL
Signs:
Xanthelesma
Pancreatitis
Sphyngolipids
Lysosomal Storage Diseases
Gaucher: glucocerebrosidase
Fabrys: alpha galactosidase
Krabbes: beta galactocerebrosidase
Tay Sacks: hexoseaminidase A
Sandhoffs: hexoseaminidase A & B
Nieman Pick: sphyngomylinase
Metachromatic leukodystrophy: arylsulphatase
Hurlers: iduronidase
Hunters: iduronidase sulphatase
And Now
The final anabolic
process
298 286
Cholesterol Synthesis NUCLEOTIDES
NUCLEOTIDES
RNA
DNA
ENERGY
CARRIERS ( UDP & CDP)
METHYL GROUP CARRIER ( S-AM)
SECOND MESSENGERS
PURINES
Adenine
Guanine
PYRIMIDINES
Thymidine
Cytidine
Uracil
NUCLEOTIDES
299 287
THE BLOTS
Southern blot: DNA
Northern blot: RNA
Western blot: PROTEIN
PCR: amplifies DNA or RNA
ELIZA
EUCHROMATIN
Loose DNA; has more A and T
HETEROCHROMATIN
Tight DNA; has more G and C
PURINES
PYRIMIDINES
RIBONUCLEOTIDE REDUCTASE
300 288
SCID
Adenosine deaminase def
Unable to make DNA
Affects all rapidly dividing cells, especially
bone marrow
Bone marrow transplant is now current
therapy
The DNA Helix
HISTONES
Help bind DNA helix
H-1
H-2a
H-2b
H-3
H-4
Basic
Anti-Histone Antibody
Hydralazine
INH
Procainamide
Penicillamine
Phenytoin
Ethusuximide
CELLULAR CYCLE DNA REPLICATION
301 289
TRANSCRIPTION TRANSLATION
DIFFERENCES
DNA Replication
DNA POL alpha
DNA POL beta
DNA POL gamma
DNA POL delta
DNA POL epsilon
Replication forks
Transcription
Monocistronic
polycistronic
Translation
Fmet vs met
MUTATIONS
Frameshift mutations
Point mutations
Transition mutations
Transversion mutations
Silent mutations
Missence mutations
Nonsence mutations
CAN IT BE ?
YES, IT IS!!!
IT IS THE END
302 290
OR IS IT.
303 291
Catabolic Pathways
Breaking it all down
Sources of Energy
Glucose ( 40% of diet)
Proteins ( 30% of diet)
Fats ( 30% of diet)
Ketones ( last resort)
Breaking Down Sugars First
Breaking Down Sugars
Begins With Glycolysis
RBC Connection
RBCs use ONLY glucose for energy
Hypoglycemia will ALWAYS affect RBCs
first, causing a hemolytic anemia
The only other pathway RBCs have is the
pentose pathway for making NADPH to
maintain the membrane
304 292
Glycolysis
Glycolysis
The most active pathway in your body
CATABOLIC in all cells except the liver
where it is ANABOLIC
CATABOLIC STATE
Is controlled by the sympathetic system
Second messenger is C-amp
Is controlled hormonally by epinephrine
and glucagon
How to use energy
305 293
DHAP
Used in the glycerol 3 phosphate shuttle
Used in triglyceride synthesis
Glyceraldehyde 3 phosphate
dehydrogenase
Has sulphur in the active site
Is blocked by mercury poisoning
Mercury Toxicity
Mcc: (1) Tuna (2) a child biting into a
thermometer
Blocks glyceraldehyde 3 phosphate
dehydrogenase
LOW ENERGY STATE
RBCs affected first
Brain affected the most
Pallegra
Niacin deficiency
The 4 Ds
Dermatitis
Diarrhea
Dimentia
Death
Hartnups: presents just like pallegra.
Defective renal transport of tryptophan
306 294
Flouride Poisoning
Blocks the enzyme ENOLASE
Caused in the past by eating rocks of
flouride
Rare today since flouride added to water
and toothpaste
Clue: extra white teeth and bones
Gluconeogenesis
Gluconeogenesis
Controlled by epinephrine and glucagon
Second messenger is C-amp
Occurs only in the liver (90%) and the
adrenal cortex (10%)
Occurs while other tissues are running
glycolysis
Occurs in the mitochondria and cytoplasm
307 295
To reverse glycolysis
Pyruvate carboxylase ( rate limiting)
PEP Carboxykinase
F16DPase
G6Pase
Galactose Metabolism
Detecting Sugars
In the urine: CLINITEST
In the stool: positive REDUCING SUBSTANCES
Galactosuria
Galactokinase deficiency
Hexokinase fills in for galactokinase
Galactose in the urine ( clinitest positive)
Symptoms: polyuria; polydypsia; UTIs
308 296
Galactosemia
Galactose 1 phosphate uridyltransferase
deficiency
Galactose 1 phosphate builds up in the
cells
RBCs affected first
Brain affected the most
LOW ENERGY STATE
Fructose Metabolism
Fructosuria
Fructokinase is missing
Hexokinase fills in
Fructose in the urine ( clinitest positive)
Polyuria
Polydypsia
UTIs
Fructosemia
Aldolase B is missing
Fructose 1 phosphate is trapped within the
cells and can not leave
RBCs affected first
Brain affected the most
LOW ENERGY STATE
Before you enter the KREB CYCLE
YOU NEED TO
KNOW
309 297
THE FIVE FATES OF
PYRUVATE
5 FATES OF PYRUVATE
Pyruvate Dehydrogenase
KREB CYCLE
Malate-Aspartate Shuttle
Glycerol 3 Phosphate Shuttle
310 298
Amino Acid Catabolism Fatty Acid Catabolism
Palmitic acid: C-16 the main fatty acid we
make daily
Three formulas to know:
( C/2 1) : the number of rounds it takes to
break down a fatty acid chain or the number
of rounds it took to make a fatty acid chain
( C/2 1) 2 : the number of NADPHs it cost to
make a fatty acid chain
( C - 1): the number of ATPs it cost to make it
Fatty Acid Catabolism
Adrenoleukodystrophy
Defective carnitine shuttle
Long chain free fatty acids accumulate in
the cytoplasm, unable to enter
mitochondria
X-linked recessive
Adrenal gland failure
Early white matter involvement
X-linked Recessive Enzymes
G6PD
Pyruvate dehydrogenase
NADPH-Oxidase
HGPRT (Lesch-Nyhan)
Alpha-Galactosidase ( Fabrys)
Iduronidase ( Hunters)
CAT-1 (Adrenoleukodystrophy)
Beta - Oxidation
311 299
Odd numbered carbon fatty acid
metabolism
Ketogenesis
IDDM ( TYPE 1 DIABETES)
Autoimmune
2 weeks after a viral
(Cocksackie B) infection
Anti-islet cell antibody
Sx begin after 90% of
islet cells are destroyed
Remaining 10% will
undergo hyperplasia
( honeymoon period)
Signs and sx: LOW
ENERGY STATE
DKA
Hypovolemia
Lack of insulin
Low body potassium
Hyperkalemia
Hypophosphatemia
Pseudohyponatremia
Correcting sodium
Visceral pain
False high creatinine
Correcting glucose
Correcting acidosis
Reasons NEVER to give bicarbonate
in treatment of DKA
It merely corrects a number without
correcting the actual problem
Decreased cardiac output
Causes hypokalemia
Shifts hemoglobin dissociation curve to the
left
Bicarbonate ion does NOT cross the blood
brain barrier ( CSF pH falls paradoxically)
NIDDM ( Type II Diabetes)
Genetic
Connected to obesity
Downregulation of
insulin receptors
Hyperinsulinemia
Nonketotic
Hyperglycemic,
nonketotic coma
Complications
Vasculitis
Clots
Bleeds
Nephropathy
Neuropathy
IDM
Tx: weight loss
Meds
insulin
Sulfonylureas
Chlorpropamide
Tolbutamide
Tolezalide
Glipizide
Glyburide
312 300
Other Oral Hypoglycemics
Ascarbose
Miglitol
Metformin
Piaglitazone
Rotiglitazone
Repaglinide
Troglitazone
Insulins
Dawn effect
Increase in blood sugar each morning
caused by the normal increase in
epinephrine, glucagon and cortisol that
occurs each morning
Tx: increase morning regular insulin
Somoji effect
Actually caused by HYPOGLYCEMIA that
occurred in the early morning ( 2 to 3 am)
leading to reactive HYPERGLYCEMIA in
the late morning ( 6 to 7 am)
Tx: decrease evening NPH insulin
Glycogen: Synthesis / Catabolism Glycogen: Synthesis / Catabolism
313 301
Glycogen: Synthesis / Catabolism Glycogen: Synthesis / Catabolism
Glycogen: Synthesis / Catabolism
Glycogen Storage Diseases
Glycogen Storage Diseases
Von Gierkes: glucose 6 phosphatase
Andersons: branching enzyme
Corys: debranching enzyme
Hers: liver phosphorylase
Mcardles: muscle phosphorylase
Pompes: cardiac alpha 1,4 glucosidase
The End of CATABOLISM
The Beginning of ANABOLIC
PATHWAYS
314 302
1
Forgiveness
Through Gods love, you always have
infinite forgiveness
Unfortunately, you dont always have
infinite time
The Physiology of CANCERS
CELLS OUT OF CONTROL
Anaplasia
Cells revert back to their mesenchymal
origin
NO MATURATION TIME NEEDED
The most aggressive type of cancer
Divides rapidly
Metastasizes early and aggressively
SENSITIVE to radiation or chemo
Metaplasia
Replacement of one adult cell type for
another
The new cell can better handle the stress
315 303
2
Desmoplasia
A collagenous reaction surrounding a
tumor
Dysplasia
Loss of cell to cell contact inhibition
Cells begin to crawl on top of each other
This is the FIRST STAGE OF CANCER
Also known as carcinoma in situ ( CIN)
Any cancer that is caught at this stage has
a good prognosis if removed ( 90% 5 year
survival)
ALL screening is done to find cancer at
this stage
NEOPLASIA
BENIGN
Well circumscribed
Freely mobile
Encapsulated
Does not outgrow
capsule
Does not outgrow
blood supply
NO METS
Obeys physio
MALIGNANT
Not circumscribed
Adherent
Not encapsulated
Outgrows capsule
Outgrows blood supply
METS
Does NOT obey
physio
Malignant Neoplasia
Angiogenin
Endostatin
316 304
3
When you have one BILLION
cells
You can SEE the cancer with the naked
eyes
You can PALPATE it on exam
Chemo must kill at least one billion cells to
be considered effective
How long does it take for ONE
BILLION cells to reassemble?
If a cancer outgrows its blood
supply, go to the
BRAIN
LUNGS
BONE
LIVER
ADRENAL
PERICARDIUM
To Name a Tumor
First name: the most common cell type
Last name: add - oma at the end
To Name a Cancer
First name: most common cell type being
stressed
Prefix for every glandular tissue is ADENO
Last name: carcinoma if it originates from
epithelium
Sarcoma if it originates from connective tissue
TRICKY - OMAs
Hamartoma: abnormal growth of normal
tissue
Choristoma: abnormal location of normal
tissue
317 305
4
Cancers that lost their proper
endings
Hepatoma
Seminoma
Lymphoma
Teratoma
Mesothelioma
Retinoblastoma
Neuroblastoma
Nephroblastoma ( Wilms tumor)
Let us now beginone organ at a
time
BRAIN
Most common INTRACRANIAL tumor:
MENINGIOMA
Displaces the brain
Psammoma bodies ( calcifications)
Psammoma Bodies
Papillary carcinoma of thyroid
Serous
Adenocarcinoma of the ovaries
Meningioma
Mesothelioma
BRAIN, cont
Most common primary brain tumor:
ASTROCYTOMA
GLIOMA
OLIGODENDRIGLIOMA
EPENDYMOMA
Neurocutaneous Syndromes
ALL have mental retardation, seizures and
cerebral calcifications in common
All have tumors or cancers associated with
them
All have different cutaneous findings
318 306
5
Neurofibromatosis
Caf au lait spots ( hyperpigmented
macules)
Associated with chromosome 17/22
Neuromas
Peripheral neuromas: chromosome 17(type 1)
Central neuromas: chromosome 22(type 2)
fibromas
Sturge Weber syndrome
Port wine stain on forehead
Angiomas of retina and brain
BRAIN, cont
Most common primary brain cancer:
astrocytoma grade IV or GLIOBLASTOMA
MULTIFORME
Most common cancer: METASTASES
Usually found at the grey-white matter
junction
Pituitary
Most common tumor: pituitary ADENOMA
Cell types:
Chromophobes ( nonfunctional) 95%
Acidophils (produce PRL and GH)
Basophils ( produce ACTH, TSH, FSH and LH)
Most common FUNCTIONAL tumor:
PROLACTINOMA
Most common cancer:
ADENOCARCINOMA (rare)
Pineal
Most common tumor: pineal adenoma
( PINEALOMA)
CN VI palsy (esotropia)
Precocious puberty
Most common cancer:
ADENOCARCINOMA (rare)
Posterior Fossa Tumors
Present with early morning vomitting
Common in children
MEDULLOBLASTOMA
Cerebellar origin; it sits on top of the medulla
CRANIOPHARYNGIOMA
Develops from Rathkes pouch
Has a motor oil appearance
Has some calcifications
May damage anterior or posterior pituitary
319 307
6
Mediastinum
Anterior
Middle
Posterior
Posterior Mediastinum
Mostly ganglia located there
Most common tumor: NEUROMA
Most common cancer:
NEUROBLASTOMA
Neural Crest Cancers
NEUROBLASTOMA
Most common
abdominal mass in
children
Hypsarrythmia
Opsoclonus
Highest spontaneous
regression rate (2%)
PHEOchromocytoma
Located in adrenal
medulla
10% in children
10% bilateral
10% metastatic
10% familial
10% malignant
Neural Crest Cancers
Paroxysmal palpitations, HTN, headache
and diaphoresis
Unable to differentiate benign from
malignant histologically
Must remove ALL of them
Dx: check urinary VMA, metanephrines, or
HVA
Phentolamine
Phenoxybenzamine
Anterior Mediastinum
Thymus
Thyroid
T-cell leukemias/lymphomas
Teratomas
Thymus
Most common tumor: THYMOMA
Associated with ALL autoimmune diseases
except Graves disease
These cells are pleuripotent;
Thymus is immunopreviledged
Most common cancer:
ADENECARCINOMA (rare)
320 308
7
Thyroid
Most common mass: cyst( throglossal)
Most common tumor: follicular adenoma
Most common cancer: papillary
carcinoma
Local metastases only
Psammoma bodies
Risk factor: previous irradiation to the neck
Thyroid Masses
CYSTIC
Thyroglossal cyst is
most common
Do ultrasound to verify
Do FNA: diagnostic
and therapeutic
SOLID
First do a thyroid scan
cold nodule and h/o
previous irradiation to
the neck: lobectomy
If hot nodule: treat
hyperthyroidism
Cold nodule w/o h/o
previous irradiation:
biopsy
Do lobectomy only if
malignant
Parathyroid
Located behind the thyroid glands
Most common tumor: parathyroid adenoma
Most common cause of isolated
hypercalcemia in adults
Most common cancer:adenocarcinoma
Men Syndromes
MEN Syndromes
MEN I: pituitary, pancreatic, and
parathyroid tumors ( Wermer Syndrome)
MEN II: medullary carcinoma of thyroid,
pheochromocytoma, plus or minus
parathyroid adenomas ( Sipple
Syndrome)
MEN III: MEN II plus neuroma or
ganglioneuroma but w/o PTH adenomas
Parafollicular Gland
Also found behind the thyroid glands
Most common tumor: adenoma
Most common cancer: medullary
carcinoma of thyroid (produces calcitonin)
Middle Mediastinum
Contains the heart
Heart has three layers: endocardium,
myocardium, and epicardium. Pericardium
encases the heart
321 309
8
Endocardium
Most common tumor: myxoma
Usually seen in left atrium
Diastolic plop
Middle aged female who passes out, only to
recover a few seconds later
Estrogen connection
Most common cancer: angiosarcoma (rare)
Myocardium
Related to skeletal muscle
Most common tumor: rhabdomyoma
Most common cancer: rhabdomyosarcoma
Epicardium
Hardly ever involved in neoplasia
Pericardium
Most common tumor: fibroma
Most common cancer: metastases
Lungs
Most common mass in children:
hamartoma
Most common mass in adults: granulomas
Most common tumor: adenoma
Most common cancer: metastases
Most common intrathoracic cancer:
squamous cell carcinoma
Most common primary cancer:
bronchogenic adenocarcinoma
Lung Cancers
CENTRAL: squamous cell carcinoma
( produces PTH)
Small cell carcinoma ( produces ACTH, ADH,
PTH and TSH)
322 310
9
Lung Cancers, cont
Peripheral: bronchogenic adenocarcinoma
and bronchoalveolar adenocarcinoma
Bronchoalveolar adenocarcinoma is the
only primary lung cancer NOT related to
smoking
Lung Cancers, cont
RISK FACTORS: primary smoker risk
increases with amount and duration
Radon
Second hand smoke
Sidestream smoke
Mainstream smoke
Pneumoconioses: all of them increase risk of
cancer except anthracosis
Pneumoconioses
Anthracosis
Asbestosis
Silicosis
Bissinosis
berryliosis
Treatment of Lung Cancer
Poor prognosis
Surgery done only if lesion smaller than
2cm in size and localized, and if there is a
V/Q mismatch
Chemo or radiation is effective against
small cell carcinomas
Pleural Cavity
Most common tumor: mesothelioma
Most common cancer: mesothelioma
Ferrugenous bodies
Psammoma bodies
Pleural thickening
Nasopharynx
Most common mass: polyp
Aspirin sensitive asthma: avoid aspirin or
NSAIDS
Most common tumor: fibroma
most common cancer: nasopharyngeal
carcinoma
Commonly seen in Chinese women
EBV association
323 311
10
Oral Cavity
Most common tumor: fibroma
Most common cancer: squamous cell
carinoma
Floor of mouth
Lower lip
Tip of tongue
Esophagus
Most common tumor: leiomyoma
Most common cancer: squamous cell
carcinoma
Most common cancer in lower 1/3
rd
of
esophagus: adenocarcinoma
Risk factor: Barretts esophagus
Almost always ulcerates
Odynophagia
Poor prognosis ( < 5% 5 year survival)
Stomach
Most common tumor: leiomyoma
Most common cancer: adenocarcinoma
Virchows nodes
Leather water bottle appearance
Linnitis plastica
Signet ring cells
Kruckenberg tumor
Severe weight loss ( due to stomach
distention)
Risk Factors for UGI Cancers
Smoking
Alcohol
Nitrites
Japanese
Small Intestine
Most common tumor: leiomyoma
Most common cancer: adenocarcinoma
Most common cancer of the ileum:
lymphoma
Early UGI obstruction
Napkin ring lesion
70% of lymphoid tissue is located in the ileum
Appendix
Most common tumor: leiomyoma
Most common cancer: carcinoid
Does NOT metastasize
Carcinoid syndrome usually originates from
the (1) pancreas and (2) ileum
Puts out large amounts of serotonin (check urinary
5-HIAA
324 312
11
Colon
Most common tumor: leiomyoma
Most common cancer: adenocarcinoma
Napkin ring lesion
Eaten apple core lesion
Pencil thin stool
Melena
Third most common cancer, and most
common cause of cancer deaths in both
sexes
Colon cancer risk factors
Low fiber diet
High fat diet
Polyps
Ulcerative colitis
Polyps Liver
Most common mass: cyst
Most common tumor: adenoma and AVMs
Most common cancer: metastases
Most common primary cancer:
hepatocellular adenocarcinoma
Hepatic Adenoma
Associated with estrogen use or injected
steroids
Tends to rupture if abdominal pressure
rises significantly
Rupture can lead to acute life threatening
hemorrhage
AVMs
Connect arteries to veins
Increased venous oxygen
Decreased AVO2 difference
Risk:
Burst and bleed
Sequester platelets and cause bleeding
Sequester blood, leading to high output heart
failure
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AVM Syndromes
Osler Weber Rondu: multiple AVMs in
the pulmonary circulation
Von Hipple Landau: multiple AVMs in the
abdomen and brain
Has an increased incidence of renal cell
carcinoma
Associated with chromosome 3p
Risk Factors for Hepatocellular
Carcinoma
Smoking
Alcohol
Hepatitis B
Hepatitis C
Shistosomiasis
Analene dyes
Aflatoxin
Vinyl Chloride ( Angiosarcoma)
Benzene
Gallbladder
Most common tumor: leiomyoma
Most common cancer: adenocarcinoma
Poor prognosis because its hidden
beneath the liver
Thickened calcified gallbladder
Biliary Tract
Most common mass: choledochal cyst
Most common tumor: cholangioma
Most common cancer: cholangiosarcoma
Risk increase with chronic scarring
PRIMARY BILIARY CIRRHOSIS
Antimitochondrial antibodies
SCLEROSING CHOLANGITIS
Seen in ulcerative colitis
Pancreas
Most common mass: cyst
Most common tumor: adenoma
Most common cancer: Adenocarcinoma
Cholestatic jaundice: blocks biliary tract
High direct ( conjugated) bilirubin
Trousseau syndrome: migratory
thromphlebitis
Most common mucinous cancer
Pancreatic Adenomas
Glucagonoma: elevated glucose, lipids,
and ketones
Insulinoma (or nessidioblastosis): high
insulin and high C-peptide
Somatostatinoma: severe constipation
Vipoma: watery diarrhea
Gastrinoma (Z-E syndrome) elevated
gastrin levels all the time
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Ovary
Most common mass: follicular cyst
Most common tumor: serous cystadenoma
Most common cancer: serous
cystadenocarcinoma
Highly malignant
Most mucinous cancer in women
Other Ovarian Tumors
Fibroma: associated with pleural effusion or
ascites ( Meigs syndrome)
Granulosa cell tumor: high estrogen
Yolk sack cancer: high AFP
Choriocarcinoma: high HCG
Sertoli-Leydig cell tumor: masculinization
Mucinous cystadenocarcinoma: very mucinous
(pseudomyxoma peritonei)
Teratoma: struma ovarii
Uterus
Most common mass: polyp
Most common tumor: leiyomyoma
Most common concer: adenocarcinoma
Uterine Polyp
Presents with passing of blood clots
Tx: surgery
Fibroids
Submucosal (90%): presents with
menorhagia
Subserosal: presents with pelvic pain or
pressure
Dependent on estrogen
Focal thickening; firm mass
Tx: OCPs; Leuprolide; surgery
Endometrial adenocarcinoma
Dependent on estrogen
Presents with metrorrhagia
Metrorrhagia after age 35 requires
endometrial biopsy
Tx: surgery
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Cervix
Most common mass: warts
Most common tumor: fibromas
Most common cancer: squamous cell
carcinoma
Warts
Condyloma lata: secondary to syphilis
Fleshy appearance
Condyloma accuminatum: secondary to
HPV
Verrucous or mushroom like warts
Tx: podophyllin drops; cryosurgery
Cervical cancer
Squamous cell carcinoma
Risk factors: HPV; other STDs
Tx: hysterectomy
Vagina
Most common mass: warts; Bartholin cyst
Most common tumor: fibroma
Most common cancer:
Upper half: squamous cell carcinoma from the
cervix
Lower half: skeletal muscle
Tumor: rhabdomyoma
Cancer: rhabdomyosarcoma (sarcoma botyroides)
Warts
Condyloma lata: secondary to syphilis
Fleshy appearance
Condyloma accuminatum: secondary to
HPV
Verrucous or mushroom like warts
Tx: podophyllin drops; cryosurgery
Bartholin cyst
Congenital
Fluctuant mass behind the labia majora
Complication: infections/ abscess
formation
After first infection: treat with antibiotics
After second infection: surgery
(marsupialization)
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Rhabdomyoma/
Rhabdomyosarcoma
90% of rhabdomyosarcomas occur under
age 3 years
Increased incidence in Tuberous Sclerosis
Sarcoma botyroides: looks like a ball of
grapes when removed
Kidney
Most common mass: cyst
Most common tumor: adenoma
Most common cancer:
In children: Wilms tumor
In adults: renal cell adenocarcinoma
Wilms tumor
Renal cancer in children
Classic clues: aniridia and
hemihypertrophy
Renal Cancer
90% occur on superior pole of kidney
Presentation: painless hematuria; flank mass
Most vascular cancer
Produces erythropoietin
Metastasizes via retroperitoneum
Favorite metastatic site: lungs (cannon ball
metastases
20% contralateral recurrence
Renal Cancer, cont
Risk factors: smoking; Von Hippel Landau;
Tuberous Sclerosis
Evaluation: UA; sonogram;IVP; CT scan;
angiogram;
Tx: surgery
Annual CT scans after surgery to detect
contralateral recurrence
Adrenal Gland
Most common mass: cyst
Most common tumor: adenoma
Most common cancer: adenocarcinoma
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Adrenal adenomas
Glucagonoma
Insulinoma
Somatostatinoma
Pheochromocytoma
Bladder
Most common mass: diverticulum
Most common tumor: leiomyoma
Most common cancer (including ureters):
transitional cell adenocarcinoma
Bladder diverticulum
Complications: UTIs and kidney stones
Tx: surgery
Bladder Cancer
Transitional cell adenocarcinoma
Multiple primaries
Presents with painless hematuria
Tx: surgery; radiation
Risk factors: smoking; anilene dyes; benzene;
aflatoxin; cyclophosphamide
Squamous cell carcinoma
Schistosoma hematobium
Prostate
Most common tumor: BPH
Most common cancer: adenocarcinoma
BPH
Presentation: strains to urinate; weak
stream; dribbling after urination; frequency
and urgency
Tx: terazicin/doxazocin; tamsulocin;
fenesteride; TURP
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Prostate Cancer
Most common cancer in men
Second to lung cancer for cancer deaths
in men
Tx: surgery; hormonal therapy or radiation
after surgery
Prostate cancer screening
Age 35: baseline rectal/prostate exam
After age 40: annual rectal/prostate exams
Annual sigmoidoscopy begins after age 40
After 2 normal annual sigmoidoscopies,
repeat in 3 to 5 years
Colonoscopy every 3 to 5 years begin at
age 50
Full colonoscopy should follow any abnormal
sigmoidoscopy
Testicles
Most common mass:
In newborns: hydrocele
In children and adults: hematoma
In older adults: varicicele
Most common tumor: adenoma
Most common cancer:
In first year of life: yolk sak cancer
In teens to adults: seminoma
Testicular exams
Begin in adolescence
ANY firm testicular mass: perform an
orchiectomy
Skin
Most common mass:
Skin tag (acrochordon)
hemangioma
Most common tumor: fibroma
Most common cancer: basal cell
carcinoma
Most common malignancy: squamous cell
carcinoma
Skin Tags
Very common
Tx: shave it off
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Hemangiomas
Found anywhere on the body
An enlarged flat blood vessel
Tx: observation for 18 months; inject with
steroids; laser surgery
fibromas
Very common
Easy to remove if you need to do so
Many of them seen in neurofibromatosis
Neurocutaneous Diseases
Neurofibromatosis
Sturge Weber
Tuberous Sclerosis
All Neurocutaneous Diseases
have
Mental retardation
Cerebral calcifications
Seizures
Neurofibromatosis
Caf au lait spots (at least 3 with 1.5 cm
diameter minimum); hyperpigmented
macules
Neuromas
Fibromas
Chromosome 17/22 involved
Type 1: chromosome 17; peripheral
neuromas
Type 2: chromosome 22; central neuromas
Sturge - Weber syndrome
Port wine stain on face ( V-1)
Angiomas of retina and brain associated
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Tuberous Sclerosis
Ashen leaf spots (hypopigmented
macules)
Tubors: primary brain tumors
Rhabdomyomas and rhabdomyosarcomas
of the heart
Renal cell carcinoma
Basal cell carcinoma
Most common skin cancer; but, it does
NOT behave malignantly
Usually found on the face from sun
exposure
Wide resection is curative
Squamous cell carcinoma
Behaves malignantly
Ulcerates
Main risk factor: sun exposure (use SPF
15 )
Predisposing skin diseases: actinic
keratosis; Bowens disease
Diseases with increased risk: albinism;
vitiligo; porphyria cutanea tarda; PKU;
Wiscott-Aldridge; Jobs syndrome
melanoma
The MOST malignant skin cancer
Melanotic nevi are risk factors
Malignant risk:
Area
Borders
Color
Depth of invasion (worst prognostic factor)
Bone neoplasia Epiphysis
Made of cartilage
Most common tumor: chondroma
Most common cancer:chondrosarcoma
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Diaphysis
Made of osteocytes
Most common tumor: osteoma
Most common cancer: metastases
Most common primary cancer:
osteosarcoma
Metaphyseal osteosarcoma
Seen mainly in adults
Codmans triangle
Star burst effect on the cortex
Diaphysis
Made of osteocytes
Most common tumor: osteoma
Most common cancer: metastases
Most common primary cancer:
In children: Ewings osteosarcoma
In adults: plasmacytoma or multiple myeloma
Ewings osteosarcoma
Primary bone cancer in children
Onion skinning seen in bone
T(11/22)
Multiple myeloma
Plasmacytoma: when single lesion
Multiple myeloma: MULTIPLE osteolytic
lesions
IG-g: most common heavy chain
Kappa: most common light chain
Hypercalcemia
Ruleaux formation
Breasts
Most common mass: cyst
Most common tumor:
< 25y/o: fibroadenoma
>25y/o: fibrocystic disease
Most common cancer: intraductal
adenocarcinoma
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Fibroadenomas
Estrogen dependent
Enlarges in first two weeks of menstrual
cycle
Fibrocystic disease
Progesterone dependent
Enlarges in the two weeks preceeding
menses
Has greenish fluid on aspiration
Intraductal adenocarcinoma
Estrogen dependent
Top locations: upper outer quadrant;
nipple
Usually presents with a dimple
Metastases can be osteolytic or
osteoblastic
Other breast neoplasms
Intraductal papilloma: nipple bleeding
Lobular adenocarcinoma: contralateral primary;
cells lined up in single file
Comedocarcinoma: focal areas of necrosis
Inflammatory adenocarcinoma: peau dorange
(infiltrates lymphatics); the most malignant
cancer
Cystsarcoma phylloides: a sarcoma; explodes out
of the breast, then stops growing; wide resection
is adequate
Breast cancer screening
Baseline exam: age 35
Age 40 to 50: annual breast exam by
doctor; monthly SBE
Age 50 to 79: add annual mammogram
Family h/o breast cancer: begin
mammography 5 years before the age of
the index case
Cystic breast mass
History
Physical
Ultrasound
Fine needle aspiration: diagnostic and
therapeutic
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Firm breast mass
History
Physical
Mammogram
Lumpectomy
Send to pathologist for definitive
identificaton
Benign firm breast mass
After lumpectomy, we are done
Malignant firm breast mass
After lumpectomy, perform a modified
radical mastectomy
Nodal dissection
Check for estrogen and progesterone
receptor positivity
Tamoxifin or Roloxifene for estrogen
positive cases
Chemotherapy for premenopausal women
and radiation for postmenopausal cases
Tamoxifin / Roloxifene
Anti-estrogen at the breast and pituitary
Proestrogen at the bone, liver, and the
uterus (Tamoxifin only)
Cancer Profile
Signs and symptoms: low energy state
Cancer more common in males: under age
30 and after age 50
Cancer more common in women: age 30
to 50
Most common cause of death: infections,
except for uterine and cervical cancers
(renal failure)
Cancer Antigens
Prior to surgery: associated with
After surgery: if it rises again, there is a
95% chance you have recurrence or
metastases
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Cancer Antigens
PSA
CEA
S-100
AFP
HCG
C-MYC
L-MYC
N-MYC
Desmin
Vimentin
Ca-125
Ca-19
BCL-2
RET
RB
Cancer Markers
T(9/22)
T(8/14)
T(14/18)
T(11/22)
T(15/17)
ERB
HER 2 NEU
BRCA
P53
THE END
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Microbiology & Immunology:
Week Four
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Immunology
LISCENCED TO KILL
Immunology
Study of the immune system
Antigen
HAPTEN
Less than 6000D
Too small to set off the
immune system by
itself
IMMUNOGEN
Greater than 6000D
Large enough to set
off the immune system
by itself
The most important factor that
determines Immunogenicity is
Antigen
HAPTEN
Less than 6000D
Too small to set off the
immune system by
itself
IMMUNOGEN
Greater than 6000D
Large enough to set
off the immune system
by itself
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Carrier Effect
What macrophages do for a living
Ingest
Phagosome formation
Digest
Present
MHC II complex
V-beta region
Invariant chain is displaced
IL-1 is released
Making use of the carrier effect
IL-1
Fever
Nonspecific symptoms of illness
Recruits T-helper cells
Fever
Def: one degree above normal body temp
Raises heart rate 10bpm for each degree
rise above normal
Allows immune cells to come around
faster
Causes secretion of Ig-A
Infections that cause heart block
Legionella
Lyme disease
Chagas disease
Diptheria
Typhoid fever
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Fever
Means that IL-1 showed up
By itself can NOT tell you the cause
The pattern of fever can be diagnostic
Causes discomfort at about 101 degrees F
Antigen
HAPTEN
Less than 6000D
Too small to set off the
immune system by
itself
IMMUNOGEN
Greater than 6000D
Large enough to set
off the immune system
by itself
How do you make an Immunogen
less immunogenic?
Detergent
Disrupts the ADHESION of pathogens by
disrupting membrane forces
Antiseptic/Disinfectant
Phenol is most common
Iodine is most common in the hospital
These chemicals DESTROY the
membrane and INACTIVATE endotoxin
These chemicals actually KILL 99% of
germs
Sterilization
For spores
A dormant form of a bacteria
CAN NOT replicate in this form
CAN still release toxin, especially when
exposed to heat
Bacillus and Clostridium
Done at 121* C with VAPORIZED heat
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Most immunogenic bacteria
SHIGELLA
Only 8 to 10 microbes required to get a full
infection
The two arms of the Immune
system
HUMORAL
BLOOD
CELL MEDIATED
TISSUE
The two arms of the Immune
system
HUMORAL
BLOOD
B-CELLS
NEUTROPHILS
CELL MEDIATED
TISSUE
T-CELLS
MACROPHAGES
MACROPHAGES
Microglia: brain
Type-1 pneumocytes: lungs
Kuffler cells: liver
RES cells: spleen
Dendritic cells: lymph nodes
Osteoclasts: bone
Mesangial cells: kidneys
M cells: Peyers patches
Langerhans cells: skin
Monocytes: blood
Connective tissue: epitheloid cells; giant cells; histiocytes
The two arms of the Immune
system
HUMORAL
BLOOD
B-CELLS
NEUTROPHILS
BACTERIA
CELL MEDIATED
TISSUE
T-CELLS
MACROPHAGES
ALL ELSE!!!
All Else
Virus
Fungus
Mycobacteria
Protozoa
Parasite
Neoplasm
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Inflammation Acute Inflammation
Look for SWELLING or NEUTROPHILS
Chronic Inflammation
Cellular infiltrate: T-cells and macrophages
What you see on biopsy: fibrosis
What you see on x-ray: calcifications
Can it really be this easy?
Can it really be this easy?
YES!
THE END
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Or Maybe Not. Let The Leukocytes Loose!
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1
Immunodeficiencies
LACKING A LITTLE
Humoral Immune Sytem
Protect the blood
Humoral Immune Sytem
Protect the blood
B cells
Humoral Immune Sytem
Protect the blood
B cells
Neutrophils
Humoral Immune Sytem
Protect the blood
B cells
Neutrophils
Bacterial infections
Cell mediated Immune System
Protect the tissues
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Cell mediated Immune System
Protect the tissues
T-cells
Cell mediated Immune System
Protect the tissues
T-cells
Macrophages
Cell mediated Immune System
Protect the tissues
T-cells
Macrophages
Nonbacterial infections
Cell mediated Immune System
Protect the tissues
T-cells
Macrophages
Nonbacterial infections
Virus
Fungus
Mycobacterium
Protozoa
Parasite
neoplasm
T-cell immunedeficiencies
DiGeorge syndrome
Chronic mucocutaneous candidiasis
Steroids
Cyclosporine
Hairy cell leukemia
SCID
Wiscott-Aldridge syndrome
HIV
DiGeorge syndrome
Third pharyngeal pouch is missing
Inferior parathyroids glands are missing
The only immunodeficiency with
hypocalcemia
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Chronic Mucocutaneous
Candidiasis
A T-cell defect at a submolecular level
T-cells can fight everything else under all
else except candida
Candida infections on skin and mucous
membranes
Causes chronic fatigue syndrome
Steroids
Anti-inflammatory actions
Kills T-cells and eosinophils
Inhibits macrophage migration
Stabilizes mast cell membranes
Stabilizes endothelium
Inhibits phospholipase A
Physiologic actions (catabolic)
Proteolysis
Gluconeogenesis
Upregulates all receptors during stress ( permissive)
Steroids
Prednisone
Hydrocortisone
Methylprednisalone
Triamcinalone
Beclamethasone
Betamethasone
Fluticasone
Mometasone
Fludrocortisone
Danazole
Cypropterone
Megesterol
Dexamethasone
Cyclosporine
Revolutionized transplantations in America
Prolongs the longevity of transplanted
organs
Inhibits calcineurin which is needed to
produce the interleukins
Causes gingival hyperplasia and
hirsutism
Tacrilimus
Now used in place of cyclosporin due to
much fewer side effects
Hairy Cell Leukemia
Most commonly a B-cell leukemia (75%)
More frequently a T-cell leukemia (25%)
Has hairy cell membrane projections
Tartrate Resistant Acid Phosphatase (TRAP)
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T-cell Lymphomas
Mycosis Fungoides ( cutaneous)
Sezary syndrome ( present in the blood)
T-cells have characteristic indented cell
membrane
SCID
Involves adenosine deaminase deficiency
DNA synthesis is disrupted
Affects all rapidly dividing cells
Affects T and B-cells
Bone marrow transplant is now the
standard of care
Wiscott-Aldridge syndrome
Involves T-cell interaction with B-cells
X-linked recessive
Fair-skinned
Eczema
Thrombocytopenia
Normal Ig-A and Ig-E levels
Increased incidence of lymphoma
B-cell Immunodeficiencies
Brutons agammaglobulinemia
CVID
Leukemias
Lymphomas
Plasmacytoma
Multiple myeloma
Heavy Chain disease
Selective Ig-A def
Selective Ig-G2 def
Jobs syndrome
SCID
Wiscott-Aldridge syndrome
Brutons Agammaglobulinemia
X-linked recessive
Cell signalling is defective
B-cell count is normal; function is lacking
Early onset
CVID
Late onset Brutons ( after first year of life)
B-cell count is also normal; B-cell function
is lacking
Cell signalling is defective
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Leukemias
98 B-cells for every T-cell in periphery
Lymphomas
98 B-cells for every T-cell in periphery
Plasma Cell Cancer
Plasmacytoma: only ONE lesion
Multiple Myeloma: MULTIPLE osteolytic
lesions
Ruleaux formation
Hypercalcemia
Ig-G is most common M-spike
Kappa light chains are most common Bence
Jones protienuria
Heavy Chain Disease
Ig-A Multiple Myeloma of the bowel wall
Ig-A plasma cells visible on biopsy
Causes malabsorption
Selective Ig-A def
Many mucosal infections
Runs with selective Ig-G2 def 95% of time
Anaphylaxis during a transfusion
Must use a filter for all subsequent
transfusions or use blood from another Ig-A
def patient
Selective Ig-G2 def
Runs with selective Ig-A def
Ig-G is main opsin ( coats encapsulated
organisms)
Recurrent encapsulated organism
infections
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Encapsulated Organisms
Gram positive
Streptococcus
pneumonia
Gram negatives
Salmonella
Klebsiella
H. Influenza B
Pseudomonas
Nisseria
citrobacter
Jobs syndrome
Cell signalling defect
Increased Ig-E
Fair-skinned
Red-haired female
The Final Two
SCID
WISCOTT-ALDRIDGE
Neutrophil Defects
Myeloperoxidase def
NADPH-oxidase def (CGD)
Absolute neutropenia
Myeloperoxidase def
Recurrent gram positive infections
Chronic Granulomatous Disease
(CGD) NADPH-oxidase def
X-linked recessive
Negative NBT test ( detects nadph-oxidase)
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Absolute Neutropenia
ANC = ( % Neutrophils + % bands) WBC
< 2500
<1500
<1000
At risk for staph aureus and pseudomonas
infections
If any fever: cover staph aureus with one
antibiotic and pseudomonas with two
antibiotics
At Risk for Staph and Pseudomonas
Infections
Absolute neutropenia
Cystic Fibrosis
Burn patients
Diabetics
Macrophage Defects
NADPH-Oxidase def ( CGD)
Chediak-Higashi
Chediak-Higashi syndrome
Lysosomes are slow in fusing with
ingested pathogen
Lysosomal inclusions
Albinism
HIV
The two populations with the highest
incidence are heterosexual Black women
and the elderly
Lowest risk population: prepubertal female
HIV likes acidic medium, mucosae, and
CD-4 receptors
Where CD-4 receptors are found
Female cervix
Blood vessels
Macrophages
T-helper cells
CNS
Testes
HIV is only virus that does NOT penetrate
the cells; it injects its RNA into the cells
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Cancers Common in HIV
Cervical cancer
Kaposi sarcoma ( helped by Herpes 8)
CNS and testicular lymphomas
HIV Infection
Attaches to CD-4 receptor using GP120
GP 41 has no known function
Injects the RNA inside
POLymerase protein is used to integrate
the RNA into host genome
Reverse transcriptase is used for
transcription
P17 and P24 used for assembly
To Prevent Attachment of HIV
CCR5
CCR4
Screening for HIV
ELIZA ( Ig-G antibody test)
Western blot ( detects protein)
Northern blot ( detects RNA)
Southern blot ( detects DNA)
PCR ( amplifies RNA or DNA)
Screening for HIV, cont PCR
MORE sensitive than Southern blot or
Northern blot
Used for screening only in the first 18
months of life ( moms Ig-G interferes with
ELIZA)
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T-helper cell Counts
Normal: 800 to 1200
normal in newborns: 1500
Begin treatment: CD4 counts < 500
Pediatrics: < 50% ( 750)
Begin PCP prophylaxis
CD4 count < 200
Pediatrics: < 20%
Begin MAI prophylaxis
CD4 count < 100
Pediatrics: <10%
HIV Treatment
START with two nucleoside inhibitors and
one protease inhibitor
AZT
3TC
4DT
DDI or DDC
Rotenovir; Indinavir; Sequinavir
PCP Prophylaxis
Trimethoprim/Sulfamethoxazole
Pentamidine aerosole
Mycobacterium Avium
Intracellulare ( MAI)
Clarithromycin
Azithromycin
HIV: THE END
THE MOST COMMON CAUSE OF DEATH FROM AGE
19 TO 44 !!!
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1
LEUKOCYTES
Shoot when you see the WHITES of
their eyes
Leukocytes
NORMAL: 4 to 12K
Leukopenia: < 4K
Leukocytosis: > 12K
Your leukocyte count accounts for only
10% of total leukocytes
90% of leukocytes are marginated
When Leukocytes are needed
Demargination: caused by epinephrine and
cortisol
Pavementing:
Selectrins
Integrins
Margination
Diapedesis
Migration
Leukopenia
Most common causes: acute viral infection
and drugs
Viruses that commonly suppress
leukocytes
Any virus can do it; but, the most common
are
Parvovirus B19
Hepatitis E
Hepatitis C
Drugs that suppress the
bone marrow
Vinblastine
AZT
Chloramphenicol
benzene
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Drugs that cause agranulocytosis
Carbamezapine
Ticlopidine
Clozapine
Leukocytosis
Stress demargination
Infections
Leukemoid reaction
Leukemia
Myelodysplastic syndromes
Leukocytosis Leukemoid Reaction
Extreme demargination
Looks like leukemia because WBCs so
high
Increased leukocyte alkaline phosphatase
( LAP)
Extreme stress
Leukemia
Too many white cells in the periphery
A cancer
Acute: cancer began in the bone marrow
Chronic: cancer began in the periphery
Lymphomas
Cancer of the lymph nodes
Involves the lymphocytes
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Myelodysplastic syndromes
Cancer that involves the ENTIRE bone
marrow
All cell lines are involved
Leukemias
Lymphomas
Hodgkins lymphoma: 20 to 40 y/o
Characterized by the Reed-Sternberg cells
which have the CD 30 marker
Commonly begins as a swollen lymph node
Most malignant lymph nodes
Supraclavicular
Epitrochlear
inguinal
Lymphomas, cont
Nonhodgkins lymphoma
Usually occurs in immunocompromised
persons
Presents as an abdominal mass in America,
or a jaw mass in poor countries
Most common type: follicular lymphoma
BCL-2
T( 14/18)
Burkitts Lymphoma
BCL-2
C-myc
T( 8/14)
EBV
Starry sky appearance
Lymphomas
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4
Lymphomas Lymphoma: Staging
Stage 1: one group of lymph nodes involved
Stage 2: two groups of lymph nodes on
same side of diaphragm involved
Stage 3: two or more groups of lymph
nodes on both sides of diaphragm
involved
Stage 4: metastases
Lymphoma Treatment Lymphoma Treatment, cont
Nodular Sclerosis
More common in women
The fewest Reed-Sternberg cells
Intermediate prognosis
Lymphocyte Predominance
Best prognosis
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Lymphocyte Depleted
Worst prognosis
A paucity of lymphocytes
Mixed Lymphocytic/Histiocytic
Intermediate prognosis
Has the most Reed-Sternberg cells
(lacunar cells)
Myelodysplastic Syndromes Myelodysplastic syndromes
Hyperproliferative:
Polycythemia Rubra Vera
Essential thrombocythemia
Hypoproliferative:
Aplastic Anemia
Myelophistic Anemia ( myelifibrosis;
agnogenic myeloid dysplasia)
Polycythemia Rubra Vera
ALL cell lines are elevated; RBCs elevated
the most
HCT> 60%
Itching after a hot bath
Uric acid stones
Increased gout
Splenemegaly
Increased LAP
Essential Thrombocythemia
ALL cell lines are increased; platelets are
increased the most
Platelet count > 600K
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Aplastic Anemia
ALL cell lines are depleted
Bone marrow usually suppressed by virus
or drugs
Bone marrow usually replaced by fatty
infiltration
Low reticulocyte count
Aplastic Anemia: Viruses
Parvovirus B-19: 90%
Hepatitis E : pregnant women
Hepatitis C : occassional
Aplastic Anemia: Drugs
Chloramphenicol
AZT
Benzene
Vinblastine
Myelofibrosis
Bone marrow is destroyed by cancer and
replaced by scarring
Tear drop cells
Low reticulocyte count
The End
Or Is It??
361 349
7
Aint No Groove Like A Granulocyte
Groove
362 350
1
Lymphocytes
The ultimate control
B-Lymphocytes
Develop in the bone marrow
Mature : Bursa of Fabricus equivalent ??
Differentiate : germinal centers of lymphoid
tissue
B-Lymphocyte Differentiation
Macrophage ingests antigen
Macrophage forms a phagosome
Lysosome digests the antigen
Macrophage presents the antigen
Antigen binds to MHC-II complex
IL-1
IL2
IL-3
B-Lymphocyte Differentiation
IL-4
1L-5
IL-6
IL-10
IL-12
T cells talk to B cells via the CD-40 ligand
B cells display CD-19 and CD-20
Stages of B cell development
363 351
2
To stimulate B cells
Endotoxin
Pokeweed mitogen
Then add labelled thymidine
Primary Response
IG-M:
Arrives in 3 days
Peaks in 2 weeks
Lasts for 2 months
IG-G:
Arrives in 2 weeks
Peaks in 2 months
Lasts for 1 year
Vaccines Schedule Memory
Memory Response
(Anamnestic)
Develops beginning at 12 months; fully
developed by 15 months
Involves ONLY IG-G
IG-G has highest affinity
Arrives in 3 days
Peaks at 5 years
Lasts for 10 years
Memory Response
364 352
3
Antibody Structure/Function Live Vaccines
MMR
BCG
OPV ( Sabin)
Varicella
Rotavirus
Smallpox
Yellow fever
Vaccine changes at age 6
Pertussis no longer needed
HIB no longer needed
Only half dose diptheria needed (D
becomes d)
Isotype
Antibody Class: Gamma;
Alpha; Mu; Delta; Epsilon
Idiotype
The actual antigen binding
site
Allotype
Differences between two
members of same species
365 353
4
Xenotype or Heterotype
Differences between two
members of different
species
Applied to Transplants
Isograft or Syngraft
Twin to Twin transplants
Allografts
Transplants between
members of same species
Autografts
Self to Self transplants
Xenograft or Heterograft
Transplant between
members of different
species
366 354
5
T cell
maturation/differentiation
T cell differentiation
Macrophage ingests antigen
Macrophage forms a phagosome
Lysosome digests the antigen
Macrophage presents the antigen
Antigen binds to MHC-II complex
IL-1
IL2
IL-3
T cell differentiation
IL-4
1L-5
IL-6
IL-10
IL-12
T cells talk to B cells via the CD-40 ligand
T cells talk to macrophages via B-7 molecule (on
T cell) connecting with the CD-4 receptor
causing the formation of the CD-28 molecule
T Lymphocytes
Develop in the bone marrow
ALL T cells have CD3
ALL have CD4 and CD8 labels when they
leave the bone marrow
They have to go to the thymus to
differentiate
Express the MHC II complex
One T cell controls many B cells
At the thymus
T cells enter undifferentiated
They must go through NEGATIVE
selection followed by POSITIVE selection
Thymosin and Thymopoietin control clonal
deletion
Thymus is one of four immunopriviledged
sites in the body
Have no lymphatics; express NO antigens
367 355
6
Immunopriviledged sites
Brain
Thymus
Cornea
Testicle
CD 8 CELLS
First cells to make it through clonal
deletion
Express MHC I complex; respond to MHC I
antigens (self antigens)
T suppressors: keep infection from
spreading
T cytotoxic: destroy infected cells
CD 4 CELLS
The second set of lymphocytes to make it
through clonal deletion
Express MHC II complex; responds to
foreign antigens
Speaks to B cells via CD 40 ligand;
speaks to macrophages via B7 / CD28
molecule
T Helper cells
T Helper cells
T Helper 1: respond to cell mediated
T Helper 2: respond to humoral
Secrete every interleukin except IL-I
Produce interferon gamma and TNF
gamma
Control B cells and macrophages
NK Cells
Develop WITH the T cells in the thymus
Do NOT go through clonal deletion
Express MHC I complex and actually
COUNT MHC I antigens
Express CD 16 and CD 56
Responsible for immunosurveillance
Can detect cancer at the one cell stage
Levamisole
Enhances NK cells ability
368 356
7
Once a T cell processes
an antigen
It is considered differentiated
GREED
A MAN SPENDS HIS HEALTH CHASING
GREAT WEALTH
THEN HE SPENDS HIS WEALTH TRYING
TO GET BACK HIS HEALTH
THE ENDFOR NOW
369 357
1
Granulocytes
What do they do for a living?
Granulocytes
Granulocytes Granulocytes
Gram stain
Step 1: add crystal violet ( binds to
exposed peptidoglycan)
Step 2: add iodine ( seals blue color into
wall)
Step 3: wash with alcohol ( washes off
excess crystal violet)
Step 4: add saffrin ( colors outer
membranes)
370 358
2
Acid fast stain
Also called Ziel Neilson stain
The pathogen stains pink;ALL other cells
stain blue
Completely acid fast: mycobacterium
Partially acid fast: Nocardia ( gram
positive) and Cryptosporidium ( protozoa)
Neutrophils
The most abundant granulocytes
60% of WBCs
First line of defence
Show up at 24 hours; peak at day 3
10% are circulating; 90% are marginated
Contain myeloperoxidase and NADPH-
Oxidase
Catalase positive bacteria
Staph Aureus
Pseudomonas
Nisseria
371 359
3
Free Radicals
Begin coming into the area at 3 hours
Oxygen burst ( peak free radical formation)
occurs at day 7
Hi energy free radicals transfer their
energy to anything in the way
Area becomes anaerobic once oxygen
burst occurs
Now you have an abscess
Abscesses
Day 1 to 3: staph aureus
Day 3 to 7: strep pyogenes
After day 7: anaerobes
Abscesses are anaerobic by nature
Occurs most commonly in: the brain
( liquefactive necrosis)
Occurs least commonly in: the lungs (most
oxygen)
Clues to anaerobic infections
Malodorous smells
Gas formation
Absolute Neutropenia
ANC = (% neutrophils + % bands) WBC
< 2500
< 1500
< 1000
ANY FEVER: cover staph aureus w/ one
antibiotic and cover pseudomonas with
two antibiotics; and if fever persists after 48
hours, then cover for fungus
Neutropenia
Most common causes: viral infection and
drugs
372 360
4
Monocytes
A macrophage in circulation
They change names after they enter
tissues
Interferon mediates their transformations
after they enter different tissues
Contain ONLY nadph-oxidase for killing
since free radicals can kill anything
Macrophages in the
Brain
Lungs
Liver
Kidneys
Spleen
Lymph nodes
Skin
Bone
Peyers patches
Connective tissue
Monocytosis
Mcc: viral infection ( cell mediated)
Extreme monocytosis: monocytes > 15%
Salmonella typhi
Tuberculosis
EBV
Lysteria
Syphilis
Granulocytes
Understanding Allergies
MAST CELLS EOSINOPHILS
Primary response to allergens
First contact: asymptomatic
Allergen was ingested
Phagasome formed
Digested
Presented to T-lymphocytes
T-cells bind to B-cells by CD-40 ligand
T-cells produced IL-4
B-cells produced Ig-E
373 361
5
Secondary response to allergens
Symptomatic
When allergen re-enters the system, Ig-E
now binds the allergen
Ig-E buries the F-c portion into a mast cell
Mast cell degranulates
Understanding Allergies
MAST CELLS
Histamine (immediate)
SRS-A ( 4 to 8 hrs later)
ECF-A
EOSINOPHILS
Histaminase
Arylsulphatase
heparin
Histamine
Responsible for all of the acute symptoms
of allergies
Redness and flushing
Wheezing
Itching
Warmth
Swelling (nasal congestion; rhinitis;
conjunctivitis; wheal and flare; urticaria)
Slow Reacting Substance of
Anaphylaxis (SRS-A)
The most potent bronchoconstricter that
we know
This is responsible for late symptoms of
allergies
Produced 4 to 8 hours after initial
symptoms
Responsible for killing many asthmatics
before we understood it
Eosinophil Chemotactic Factor of
Anaphylaxis ( ECF-A)
Chemoattractant for eosinophils
Responsible for the eosinophilia seen in
allergic reactions
In other words
Eosinophils
Are counter-regulatory
Make sure mast cells do NOT get out of
hand
374 362
6
Eosinophils
Histaminase: breaks down histamine
Eosinophils
Histaminase: breaks down histamine
Arylsulphatase: breaks down SRS-A
Eosinophils
Histaminase: breaks down histamine
Arylsulphatase: breaks down SRS-A
Heparin : breaks down any clots that might
have formed
Heparin
Acts as a cofactor for antithrombin III
Blocks thrombin as well as clotting factors
IX,X,XI and XII ( the intrinsic clotting
cascade)
Follow the PTT
INR should be 2 to 3 times normal
If INR too high, reverse it with protamine
sulphate
Heparin, cont
If patient acutely bleeding then give FFP to
correct immediately
Side effects:
Bleeding
Hyperlipidemia ( activates hormone-sensitive
lipase)
Heparin induced thrombocytopenia ( acts as a
hapten, inducing autoimmune antibodies)
Low Molecular Weight Heparins
Well standardized to minimize physician
errors
BENEFITS:
NO need to do daily PTTs (saves on
nursing and hospital costs)
Fewer bleeding complications
Lower incidence of heparin induced
thrombocytopenia
375 363
7
Eosinophilia
N
A
A
C
P
Eosinophilia
Neoplasia, especially lymphomas
A
A
C
P
Eosinophilia
Neoplasia
Allergies and Addisons disease
Allergic rhinitis and conjunctivitis
A
C
P
Allergic Rashes: type 1
hypersensitivity
Urticaria
Erythema multiforme
Stevens-Johnson syndrome
Toxic Epidermal Necrolysis
Allergic Rashes: type IV
hypersensitivity
Atopic dermatitis
Contact dermatitis
Eczema
Spongiotic
nummular
Eosinophilia, cont
Neoplasia
Allergies and Addisons disease
Asthma
C
P
376 364
8
Asthma
Intrinsic asthma: you are born with it; colds
and cold air set it off
Extrinsic asthma: caused by environmental
factors
Dust mites
Roach droppings
Pet dander
Eosinophilia, cont
Neoplasia
Allergies and Addisons disease
Asthma
Collagen Vascular Disease
P
Eosinophilia, cont
Neoplasia
Allergies and Addisons disease
Asthma
Collagen Vascular disease
Parasites
Bands
Immature neutrophils with maximum germ
fighting ability
Have myeloperoxidase and NADPH-
Oxidase enzyme systems
Come straight out of the bone marrow
without margination
Increased numbers = a left shift
Basophils
Said to be precursors to mast cells
They have similar granules to mast cells
To Be Continued
377 365
THE FOUR HYPERSENSITIVITIES
PUTTING IT ALL
TOGETHER
TYPE I
Immediate hypersensitivity
Involves mast cells and eosinophils
NO COMPLEMENT involved
TYPE II
Cytotoxic
A deliberate attack on self
Complement comes in after the attack
TYPE III
Immune complex deposition
NOT a deliberate attack on the tissue
Tissue is damaged due to inflammation
So much COMPLEMENT used that it
measures LOW
TYPE IV
CELL MEDIATED
T cells
Macrophages
Complement System
378 366
Angioedema
Due to C-1 esterase inhibitor deficiency
Too much C5-A produced
Causes recurrent facial swelling and
abdominal pains
Mcc of death: suffocation due to airway
swelling
Caused by ACE inhibitors and ARBs
ACE Inhibitors and ARBs
Captopril
Enalopril
Lisenpril
Rinilopril
Losartan
Vosartan
ANTIBODIES
Antimicrosomal
Antithyroglobulin
Anti-TSH receptor
Anti-ACH receptor
Anti-myelin
Anti-parietal cell
Anti-mitochondrial
Anti-melanocyte
Anti-IgG
Anti-rho, La, SSA
Anti-SM
Anticardiolipin
Anti-DS DNA
Anticentromere
Anti-smooth muscle
Antihistone
Anti-Scl 70
Anti-RNP
Antibodies
Anti-topoisomerase
P-anca
C-anca
Anti-GBM
Anti-anchoring
proteins
Antiplatelet
Anti-RBC
TRANSPLANT IMMUNOLOGY ABO
379 367
CROSSMATCH
MIXED LYMPHOCYTE REACTION
HLA TYPING
Rejection
Hyperacute
Acute
Chronic
Graft vs host
Just when you thought it was over
Now it is time for the BUGS !!!
380 368
4/29/2008
1
Antibiotics
Gram + Cocci: Semisynthetic PCNs
Oxacillin
Cloxacillin
Dicloxacillin
Nafcillin
More efficacious than Vancomycin
Beta-lactamase resistant PCN
MRSA tx- Vancomycin (linezoid)
Streptococci: pyogenes
viridans
pneumonia
Penicillin G
P i illi VK Penicillin VK
Ampicillin
Amoxicillin
Ampicillin + Amoxicillin:
can be used for Strep infections
when combined with beta-lactamase
inhibitor:
- Sulbactam
A illi + l l t - Amoxacillin+clavulanate
Effective against: Enterococci
Listeria
Cephalosporins:
1
st
Generation: Cefazolin 2
nd
Generation: Cefoxitin
Cefadroxil Cefotetan
Cephalexin Cefuroxime
Cefprozil
Loracarbef
1
st
generation: Staph and Strep g p p
Some gram negatives (E. coli, Moraxella)
2nd generation: Moraxella, E. coli, Haemophilus,
Klebsiella, Citrobacter, Proteus Vulgaris
Cephalosporins:
3
rd
Generation:Ceftazidime 4
th
Generation: Cefepime
Cefotaxime
Ceftraxone
Cefotaxime
O l C ft idi & C f i P d Only Ceftazidime & Cefepime cover Pseudomonas
3
rd
Generation: not good for Staph (especially
Ceftazidine)
4
th
Generation: Cefipime (never pick Stap/Strep)
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2
Allergic cross reactivity with penicillins:
Genuine allergy to PCN has less than 5% cross
reactivity with Cephalosporins
Seldom anaphylactic reaction will occur
Patients usually just get a rash, so you can still use
cephalosporins
Allergic cross reactivity with penicillins:
If anaphylaxis to PCN, never pick a Cephalosporin as
an answer
Minor infection- Macrolide (Clarithromycin, Azithro) Minor infection Macrolide (Clarithromycin, Azithro)
New fluoroquinolones : (Levofloxacin, goti, moxi)
Serious infections: life threatening
- Vancomycin, Linezolid
Quinolones:
Ciprofloxacin
Levofloxacin
Gatifloxacin
Moxifloxacin
Ofloxacin
Good for. E. coli Moraxella
Proteus Citrobacter
Enterobacter Serratia
Haemophilius Kelbsiella
Ciprofloxacin is good for pseudomonas
New fluoroquinolones- first line in pneumonias
because it covers, Mycoplasma, Chlamydia,
Legionella
Aminoglycosides:
-Gentamicin
-Tobramycin
-Amikacin
Monobactams:
-Aztreonam
For the test, think of these as exclusively
Gram negative agents
Aminoglycosides have a synergistic effect
with PCN
Carbapenems:
- Imipenem
- Meropenem
Best use for Gram negative infections: g
- Pseudomonas
- Enterobacteraceas
Excellent staph and anarobic coverage
Anaerobes:
Metronidazole (Flagyl)- most active against
anaerobes
Clindamycin- less active against anaerobic
gram negative bacteria in the bowel gram negative bacteria in the bowel
(Bacteroides fragilis, Clostridium difficle)
Carbapenems have the same efficacy as
Metronidazole
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1
Microbiology:
Normal Flora
Microbiology:
Normal Flora
What is bugging you !!! What is bugging you !!!
If a bacteria normally lives on
a part of your body, normally
exposed to OXYGEN
If a bacteria normally lives on
a part of your body, normally
exposed to OXYGEN
Call it a GRAM POSITIVE Call it a GRAM POSITIVE
If a bacteria lives on a part
of your body NOT normally
exposed to oxygen.
If a bacteria lives on a part
of your body NOT normally
exposed to oxygen.
Call it a GRAM NEGATIVE Call it a GRAM NEGATIVE
Skin flora Skin flora
Staphylococcus aureus
Staphylococcus pyogenes
Staphylococcus epidermitis
Staphylococcus aureus
Staphylococcus pyogenes
Staphylococcus epidermitis Staphylococcus epidermitis
Staphylococcus saprophyticus
Propionobacterium acne
Staphylococcus epidermitis
Staphylococcus saprophyticus
Propionobacterium acne
Strep pyogenes is # 1 Strep pyogenes is # 1
Lymphangitis
Impetigo
Lymphangitis
Impetigo
Necrotizing fascitis
Erysipelas
Scarlet fever
Necrotizing fascitis
Erysipelas
Scarlet fever
Skin Infections Skin Infections
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Skin Infections Skin Infections
Cellulitis: flat, red, blanches Cellulitis: flat, red, blanches
Skin Infections Skin Infections
Mastitis: cellulitis around the breast Mastitis: cellulitis around the breast
Skin Infections Skin Infections
Balanitis: infection at the head of the penis Balanitis: infection at the head of the penis
Skin Infections Skin Infections
Panniculitis- cellulitis around abdomen Panniculitis- cellulitis around abdomen
Skin Infections Skin Infections
Periorbital cellulitis: infants, trauma
Staph aureus
Periorbital cellulitis: infants, trauma
Staph aureus
Skin Infections Skin Infections
Orbital cellulitis: proptosis, older patient
Strep pneumonia
Orbital cellulitis: proptosis, older patient
Strep pneumonia
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Skin Infections Skin Infections
Carbuncle: nodular induration w/ infection Carbuncle: nodular induration w/ infection
Skin Infection Skin Infection
Furuncle: hair follicle in middle of
carbuncle, No pus
Furuncle: hair follicle in middle of
carbuncle, No pus
Skin Infections Skin Infections
Carbunculosis: deep skin infection
Staph aureus
Carbunculosis: deep skin infection
Staph aureus
Skin Infection Skin Infection
Furunculosis: many infections of hair shafts Furunculosis: many infections of hair shafts
Skin Infection Skin Infection
Fasciitis: inflammation of fascia
Plantar or Necrotizing
Fasciitis: inflammation of fascia
Plantar or Necrotizing
Skin Infection Skin Infection
Folliculitis: infection of hair shaft Folliculitis: infection of hair shaft
373
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4
Skin Infection Skin Infection
Blepharitis: infection of eye lid Blepharitis: infection of eye lid
Mouth Flora Mouth Flora
Strep pyogenes
Strep pneumonia
H. Influenza
Strep pyogenes
Strep pneumonia
H. Influenza
Nisseria catarrhalis
N. gonorrhea
N. meningitidis
Nisseria catarrhalis
N. gonorrhea
N. meningitidis
Mouth Flora cont. Mouth Flora cont.
Peptococcus
Peptostreptococcus
Fusobacterium
Peptococcus
Peptostreptococcus
Fusobacterium
Actinomyces
Strep viridans
S. mutans
S. sanguis
S. salivarius
Actinomyces
Strep viridans
S. mutans
S. sanguis
S. salivarius
Stomach Flora Stomach Flora
Helicobacter pylori Helicobacter pylori
Urease Positive Bugs Urease Positive Bugs
Proteus
Pseudomonias
Ureoplasma
Proteus
Pseudomonias
Ureoplasma
Nocardia
Cryptococcus
H. Pylori
Staph. Saprophyticus
Brucellosis
Nocardia
Cryptococcus
H. Pylori
Staph. Saprophyticus
Brucellosis
Curved Rods Curved Rods
Vibrio
Camphlobacter
Vibrio
Camphlobacter
Lysteria
H. pylori
Lysteria
H. pylori
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5
Small Intestinal Flora Small Intestinal Flora
95% E. coli 95% E. coli
Small Intestinal Infections Small Intestinal Infections
Cholecystitis
Ascending cholangitis
Appendicitis
Cholecystitis
Ascending cholangitis
Appendicitis pp
Spontaneous bacterial peritonitis
Abdominal abscess
pp
Spontaneous bacterial peritonitis
Abdominal abscess
E. Coli makes E. Coli makes
90% of your vitamin K
Biotin
Folate
90% of your vitamin K
Biotin
Folate Folate
Panthotenic acid
Folate
Panthotenic acid
E. Coli helps you absorb.. E. Coli helps you absorb..
Vitamin B12 Vitamin B12
Distal ileum and colonic flora Distal ileum and colonic flora
Proteus
Klebsiella
Serratia marscencens
Proteus
Klebsiella
Serratia marscencens
Acenetobacter
Citrobacter
E. coli
Acenetobacter
Citrobacter
E. coli
Big MaMa anerobes Big MaMa anerobes
Bacteroides fragilis
Strep bovis
Clostridium melanogosepticus
Bacteroides fragilis
Strep bovis
Clostridium melanogosepticus Clostridium melanogosepticus
Clostridum difficile
Clostridium melanogosepticus
Clostridum difficile
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6
Rectal flora Rectal flora
Group B Strep
E. Coli
L t i t
Group B Strep
E. Coli
L t i t Lysteria monocytogenes Lysteria monocytogenes
GET READY FOR THE
RIDE..
It ll b d f
GET READY FOR THE
RIDE..
It ll b d f Its all buzz words from
here on !!!!
Its all buzz words from
here on !!!!
Gram Gram
Positives Positives
STAPHLOCOCCUS STAPHLOCOCCUS
GRAM POSITIVE
COCCI IN CLUSTERS
GRAM POSITIVE
COCCI IN CLUSTERS
Staphylococcus aureus enzymes:
Catalase + : breaks down H2O2
-lactamase : breaks through lactam
containing drugs containing drugs
Coagulase & Staphlokinase- eats
through clots
MCC of Acute Endocarditis- eats
through valves
MCC of death in burn patients in the first week
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7
Enzymes continued::
Lipase: breaks down fat
Panniculitis
Folliculitis
Mastitis
Elastase: breaks elastin
B ll E h (P t ll ) Bullous Emphysema (Pneumatocelle)
Collagenase: skin & bone (breaks peptide bonds)
MCC of osteomyolitis (2
nd
Salmonella)
Type IV (basement membrane)
Type III (endothelium- arteries affected)
Type II (connective tissue)
Staph Scalded Skin Syndrome:
Exfoliating (Nikolski sign)
Red rash all over the body
Palms and Soles
Staphylococcus aureus toxins:
Toxic Shock Syndrome:
Triad: high fever, hypotension (shock), rash (P & S)
Retained tampon
Erythrodermic Toxin:
Scarlet fever [Strep]
Sand paper rash, palms and soles, strawberry tongue
Staphylococcus aureus toxins:
Lecithinase: causes skin infections
subcutaneous fat
i f d Enterotoxin: causes food poisoning
dairy products- gastroenteritis
Fast 2-6 hours
Staph epidermidis:
Catalase +
White pigment
Resides under the skin
MCC of shunt infections and central line
infections
Tx: Vancomycin
Linezolid- for Vancomycin resistance
Keep patient is a negative pressure room
Staph saphrophyticus:
Catalase +
No Pigment
Frequent cause of UTIs:
Age 5-10- play with themselves
Age 18-24: post coital UTI,
no circumcision
(E. coli- MCC of UTIs)
STREPTOCOCCUS STREPTOCOCCUS
Gram positive
cocci in chains
Gram positive
cocci in chains
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Groups: A, B, C, D
Types of hemolysis:
hemolysis- partial (green zone)
Streptococcus
Streptococcus
hemolysis partial (green zone)
hemolysis- complete (clear zone)
hemolysis- no hemolysis (red zone)
Streptokinase- responsible for
hemolysis- clear zone
Breaks clots converts plasminogen to
plasmin
If recent Strep infection it will not If recent Strep infection- it will not
work, use tPA
- Converts plasminogen to plasmin-
breaks clots
- Binds fibrinogen- will not clot again
Thrombolytics
Urokinase- opens fistulas and grafts
Streptokinase- hemolytic- acute MI
Tissue plasminogen activator (tPA)-
acute MI, acute stroke (within 3 hrs)
Antidote: aminocaproic acid
(for all three)
Strep pneumoniae
(Pneumococcus)
Gram + diplococci
hemolysis (green zone)
80 strains 80 strains
Pneumococcal vaccine (pneumovax)
Covers 23 strains (98%) coverage
:
Who should be on it
> 65 y/0
> 2 y/o with Sickle cell (spleen- encapsulated
organisms)
End organ failure
PSGN (skin and throat can cause this)
strain 12
Group A: Strep pyogenes
-hemolytic (clear zone)
70 Strains
Most common cause for throat infections-
can lead to Rheumatic fever
2
nd
most common cause of skin
infections
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9
Group B: Strep agalactaciae
Most common cause of Neonatal Sepsis
- hemolytic (clear zone) hemolytic (clear zone)
Group D: Strep viridians
(mutans, saguis, salivarius)
hemolytic (green zone)
# 1 cause of Subacute Bacterial # 1 cause of Subacute Bacterial
Endocarditis
Previous damage to heart valve
predispose to SBE
Tx: Amoxicillin
Group D: Strep viridians
(mutans, saguis, salivarius)
# 1 cause of Subacute Bacterial Endocarditis
Septic emboli to brain
Roth spots- emboli to retina
Osler nodes- emboli to fingers (painful)
Splinter hemorrhages- emboli to nail beds
Janeway lesions- emboli to toes
Enterococcus
(Faecalis, Faeceum)
Anaerobic
hemolytic (red zone)
Likes immunocompromised patients Likes immunocompromised patients
Nitrite Negative UTI
Tx: Vancomycin
Vancomycin:
MOA: cell wall inhibitor
Inhibits phospholipid carrier (irreversible)
Tx for all gram +
Toxicity:
Red man syndrome
Intense histamine release (not allergic)
Ototoxicity
Nephrotoxicity
Vancomycin treatment:
1. MRSA
2 Staph epidermidis 2. Staph epidermidis
3. Enterococcus
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Meningitis
0 to 2 mo:
Group B strep: Strep agalactaciae
E. Coli
Lysteria
2 mo to 10 years:
Strep pneumonia
Nisseria M.
10 years to 21 years:
Nisseria M.
Strep pneumonia
> 21 years:
Strep pneumonia
Cornybacterium Diptheria
Chinese letters
Toxin that ADP-ribosylates EF-2
(affects translocation of protein synthesis)
Intracellular pathogen
Cells die, slough off, and mix with
mucus, forming a grey membrane in
posterior pharynx
Do NOT scrape: will hemorrhage profusely
Cornybacterium Diptheria,
cont.
Toxin may also cause heart block
DPT: 2m, 4m, 6m, 18m, 5-6y
Tx: antitoxin first; antibiotic (toxin is
hurting the patient, not the bug)
ADP-Ribosylators
G
s
: Vibrio cholera, ETEC
Gi: Bordatella pertussus p
EF2: C. diptheria, pseudomonas
Cause heart block
Lyme disease
Legionella
Typhoid fever yp
Diptheria
Chagas disease
:
SPORE FORMERS
BACILLUS &
CLOSTRIDIUM
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A SPORE
Made of Ca-dipocholinate
Dormant form of the bacteria
C NOT li t b t CAN l t i Can NOT replicate but CAN release toxin
especially when exposed to heat
(MAD!!!)
Is destroyed ONLY by sterilization process
121 degrees centigrade vaporized heat
Bacillus
Has poly D-Glutamate membrane
(we have L-amino acids)
B. Anthrax
Has a toxin: (1) lethal factor kills cell
(2) edema factor (2) edema factor
(3) protective factor- mediates entry
Cutaneous Anthrax: malignant pustule
(skin necroses)
Pulmonary Anthrax: wool sorters disease
(hot desert) mediastinal hemorrhagic
lymphadenitis
Bacillus
B. Cereus:
Fried / Reheated rice (hot wok)
Two toxins: Two toxins:
Emetic toxin- (from the rice) fast (1-6 hrs)
diarrhea, vomiting
Diarrheal toxin (meats, sauces):
18 hrs- increases cAMP- watery diarrhea
Clostridium
C. difficile: gastroenteritis associated with
antibiotic use
Antibiotics destroy E. coli
Pseudomembranous colitis- gray membrane Pseudomembranous colitis gray membrane
with yellow plaques on colon
Most effective drug - vancomycin;
Current treatment is metronidazole
(promotes production of free radical)
Side effect: dysguzia, disulfiram reaction
Clostridium
C. perfringens:
Gas gangrene
Known to attack extremities in diabetics
Dry gangrene- necrotic skin
Wet gangrene- blood to the area
(risk of gas emboli)
Tx: Immediate amputation
(hyperbaric chamber) ?????
Clostridium
C. perfringens: food poisoning
Gastroenteriti
associated with holiday ham or turkey associated with holiday ham or turkey
Enterotoxin
Immediate symptoms- diarrhea
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Clostridium
C. melanogosepticus
Associated with colon cancer
( along with strep bovis ) ( along with strep bovis )
Produces a black pigment
Clostridium
C. tetani
Associated with dirty wound
Give anti-immunoglobulin to bind toxin g
(into the wound)
Toxin:
inhibits release of glycine (inhibitory)
in the spinal cord- increasing contraction-
respiratory failure
Lock jaw
: Clostridium
C. botulinum: - botulism
Toxin- inhibits presynaptic release of
Ach- flaccid paralysis (floppy baby) p y ( ppy y)
Muscle wont work- die of respiratory
failure
C. botulinum: - botulism
:
Children- honey, molasses
Do not give children honey until 6 mo of age
(normal flora will appear)
Adults- ingest spores via canned foods
Tx: antitoxin first, antibiotic second
Propionobacterium Acne
Progesterone stimulates propionic acid or
sebum
Acne more severe in women and adolescent
boys boys
Refer to a dermatologist when its nodular
or nodulocystic
Gram positive anaerobe; hides in the
hair follicles
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Propionobacterium Acne,
cont.
White comedones: clear vesicles
Black comedones: sebum has been
oxidized; turns black
Tx: oxy-5 or oxy-10; benzoyl peroxide
or abrasive pads; antibiotics
( minocycline, clindamycin, or
erythromycin ); retinoic acid
Retinoic acid
Pre vitamin A
Cause proliferation of skin cells, pushing the
pathogen to the surface (hypersensitivity) pathogen to the surface (hypersensitivity)
Main side effects:
hyperlipidemia (fat soluble);
hyperparathyroidism;
pseudotumor cerebri;
teratogenic (must do pregnancy test)
Lysteria monocytogenes
The only gram positive with endotoxin
(kills quickly)
Causes monocytosis- granulomatous Causes monocytosis granulomatous
inflammation
Attack placentas, causing abortions
Requires iron to grow; high incidence in
patients with hemochromatosis
Monocytosis
Syphilis
Tuberculosis
EBV
Lysteria monocytogenes
Salmonella typhi
STELS
Lysteria monocytogenes
Causes neonatal sepsis
Causes gastroenteritis associated with
migrant workers, raw cabbage, spoiled
ilk h t d milk, hot dogs
Curved rod, tumbling motility
Intracellular, Cold growth
Tx: Ampicillin, Macrolide, Vancomycin
Curved rods
Vibrio
Campylobacter
Lysteria
H. Pylori
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Listeria cont.
Listeria meningitis:
Is the most common cause of Is the most common cause of
meningitis in
Renal transplant patients
Adults with cancer
Gram Negatives Gram Negatives
Hemophilus
Gram negative pleomorphic rod
Has IgA protease (cuts IgA)
Part of normal flora for the posterior
pharynx
Hemophilus
80% are not encapsulated and
therefore cause noninvasive
respiratory diseases
( bl ) (non-typeable)
20% are encapsulated
( poly D-glutamic acid) causes
the systemic form (H. inf. B)
Hemophilus
Influenza:
2
nd
MCC of sinusitis, otitis media, , ,
bronchitis and pneumonia
Strep pneumoniae # 1
Hemophilus
Influenza, type B: #1 ONLY for epiglottitis
thumb print sign
droolingg
fever
stridor
Tx: intubate immediately
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Thumb Print Sign
Hemophilus
Aegyptus: Pink eye (not viral conjunuctivitis)
A
B
Hemophilus
Ducreyi: MCC of chancroid, the most common
painful genital lesion (LN unilateral)
Painful genital lesions
Chancroid ( H. Ducreyi)- Most common ulceration
with central necrotic area. Tx: Ceftriaxone
Herpes ( Herpes Simplex II)- small vesicular rash
Acyclovir 5x day
Pancyclovir 3x day
Valcyclovir (Valtrex) 2x day- more compliant
Remember: does not cure- dec. symptomatic days
dec. viral shedding
dec. recurrence
Pregnancy- symptomatic within 2 weeks of
planned deliver- you must do a C-section
Painful genital lesions
Lymphogranuloma venereum (
Chlamydia trachomatis- ulcerative LN drain
(bilateral)
Tx: Doxycycline
Granuloma Inguinale
( Calymmatobacterium Donovini)
Donovini bodies macrophages with the
bug in it
HiB Vaccine
Has cut HiB infections down by 90%
Given at 2m, 4m, 6m, 18m;
Last dose (at 5y) no longer needed
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Nisseria
The only gram negative diplococci
Has IgA protease
Part of normal throat flora Part of normal throat flora
Encapsulated (Has the largest capsule)
The ONLY gram negative that releases
endotoxin during the log phase
Nisseria
Meningitidis: ferments maltose + glucose
Presents with DIC (uses up clotting factors)
D-dimer and Fibrin split products
Waterhouse-Fredrickson syndrome-hemorrage into
adrenal gland
MCC of meningitis from 10 to 21y/o
Give Dexamethasone BEFORE antibiotic
to prevent hearing loss from inflammatory
neurological damage
Give Rifampin to close contacts (>25 hrs wk)
Nisseria
Gonorrhea: ferments glucose
Has pili that naturally transform each year
( phase variation)
#1 for causes of purulent STDs
#2 for causes of STDs (1# Chylamidia)
In men: 90% of cases are symptomatic
In women: 50% are symptomatic
Uses the pili to walk up the uroepithelium
to gain access to the blood
Nisseria
Gonorrhea, cont
Fitz-Hugh-Curtis syndrome: purulent
abscess right underneath the liver
Gonococcal arthritis: it loves tendons and
ligaments (i.e. tenosynovitis)
When cultures positive, cover for
chlamydia as well ( but not vice-versa)
One dose therapy for GC
and Chlamydia
Azythromycin: 1gm or 2gm
Ceftriaxone: 250mg I.M.
Cefixime: 400mg po Cefixime: 400mg po
Cefoxitin: 250mg I.M.
Ciprofloxacin: 500mg po
Gatifloxacin: 400mg po
Ofloxacin: 400mg po
Nisseria
Catarrhalis : does not ferment sugar
Most common strain in the back of the throat
Loves mucus
#3 for respiratory tract infections
( sinusitis; otitis media; bronchitis;
pneumonia)
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Helicobacter Pylori
Curved rod, Urease positive
Silver stain GI tissue
CLO test
Associated: duodenal ulcers (95%) and
t i l (70%) gastric ulcers (70%)
Treat ALL positive gastric cultures
Hydrogen breath test is most
diagnostic if available for eradication
H. Pylori
Treatment: Amoxicillin, Bismuth, H-2
blocker or PPI
Bismuth- suffocates
3 drugs for 2 weeks (98%
eradication)
MCC- bad water (sewer system)
Urease positive bugs
Protease
Pseudomonas
Ureoplasma Urolyticum
Nocardia
Cryptococcus
H. Pylori
Staph Saprophyticus
Brucellosis
E. Coli
Makes up 95% of small intestinal normal flora
Small intestinal infections: Small intestinal infections:
Acute cholecystitis- + murphy sign, colic pain
Ascending cholangitis- inc. alk phos
Acute appendicitis
Abdominal abscess
Acute spontaneous bacterial peritonitis
E. Coli
Makes:
90% of vitamin K
Biotin
Folate
Panthotenic acid
Helps absorb:
Vitamin B-12
Dorsal column
Cortical spinal tract
USA- pernicious anemia
Antiparietal cell Ab
ETEC (Enterotoxogenic E. coli)
Major cause of diarrhea in
developing areas
Travelers diarrhea (rice water)
Severe watery diarrhea
( > 20 L day)
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EPEC (Enteropathognic E. coli)
Young children and infants
Causes loss of microvilli
Diarrhea from malabsorption
EIEC (Enteroinvasive E. coli)
Plasmid shared by Shigella
Invades intestinal mucosa
Produces shiga like toxin (verotoxin)
Bloody, purulent diarrhea
EHEC (Enterohemorrhagic E. coli)
O157:H7 (out break- epidemic)
Cattle, sheep, goats
I ti f t i t d f d Ingestion of contaminated food
Bloody diarrhea, endemic HUS
(renal failure)
Anemia, thrombocytopenia, renal failure
Proteus Mirabilis
#2 for UTIs (1# E. coli)
Urease positive
Associated with high urine pH,
struvite stones, staghorn calculus,
high ammonia in the urine
Tx: Quinolones
Klebsiella Pneumonia
#3 for UTIs
Likes to attack alcoholics and homeless
people
In lungs: curant ( blood mixed with
mucus) jelly sputum; likes to attack
fissures
Encapsulated
Like Immunocompromised
people
Serratia Marscesens
Citrobacter Citrobacter
Pseudomonas auregenosa
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Serratia Marscesens
Produces a red pigment
Citrobacter
Produces citric acid
Encapsulated
Likes to attack 0 to 2m/o (babies)
Causes multiple cerebral abscesses
Pseudomonas Auregenosa
Same enzymes as Staph aureus
Likes to attack diabetics, burn patients,
neutropenics, and cystic fibrosis
G ld i l k h Gold pigment like staph aureus
Also produces a green pigment
Has a fruity grape smell when plated
Likes plastic ( endotracheal tubes; bladder
catheters)
Pseudomonas Auregenosa
Causes: whirlpool folliculitis:
Tennis shoe folliculitis- nail through shoe
Malignant otitis externa- mastoid (coagulase)
Mcc of death in second week after a burn
Recurrent pulmonary infections in CF
ICHTHYMA GANGRENOSUM- blood form
(black bulla on the skin)
Shigella
Causes gastroenteritis associated with daycare
outbreaks
Most immunogenic bacteria
Has an exotoxin ( shigatoxin) which causes
seizures
S. Sonneii: common in the US
S. Dysentery: common outside the US
Salmonella
Encapsulated
Loves to attack people with sickle cell
anemia ( causes osteomyelitis)
Causes gastroenteritis associated with Causes gastroenteritis associated with
raw chicken or raw eggs
Runs and hides in the gallbladder if
you treat it with antibiotics
Can precipitate cholecystitis
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Salmonella, cont
Causes monocytosis
d S. Enteritidis: most common strain
in US
S. Dysentery: common outside the
US
Salmonella Typhi
The cause of typhoid fever
Triad: (1) Fever (2) Rose spots (3)
Intestinal fire
Causes heart block
Associated with contaminated water
Treat with ciprofloxacin
Bordatella Pertussis
Causes whooping cough
Prodromal stage- fever, runny nose
Catarrhal stage- increase mucus
Paroxysmal stage- cough
Has an exotoxin that ADP-ribosylates Gi
subunit of the G-protein
Exotoxin is intracellular; kills cells
High cAMP increases mucus in the lungs
Bordatella, cont
Causes extreme lymphocytosis (? PMNs)
Mcc of death was suffocation
Vaccination
Diagnosis: do ELIZA on nasopharyngeal
washings
Treatment: erythromycin; also treat
close contacts with erythromycin
Pasturella Multocida
Causes cellulitis associated with an
infected cat or dog bite.
Found in the saliva of cats and dogs
Tx: Amoxacillin
Brucella
Causes undulating fever (5 to 7 fever
spikes per day)
Seen primarily in vetrinarians and
farmers who deliver animals
Attaches to placenta
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Bartonella Henselae
Silver stains
Causes cat scratch disease
Carried by kittens
Francisella Tularensis
Causes tularemia or oculo-glandular
fever
Transmitted by rabbits (90%) and
deer (10%)
Treatment: Streptomycin
Miscellaneous
Gram Negatives
Miscellaneous
Gram Negatives
Vibrio
CHOLERA
Curved rod
Has an exotoxin that ADP ribosylates Gs and elevates
cAMP
Rice water diarrhea (also ETEC) Rice water diarrhea (also ETEC)
PARAHEMOLYTICUS
Diarrhea associated with raw fish
VULNIFICUS
Diarrhea associated with raw oysters
Campylobacter Jejunii
A curved rod
Attacks the jejunum, causing a
copious bloody diarrhea p y
Causes diarrhea associated with raw
chickens or raw eggs
Treat with erythromycin
Yersinia
Likes the Southwest
PESTIS
Bubonic plague Bubonic plague
Pneumonic plague
Enterocolitica
Likes to attack the ileum, causing ileitis
or mesenteric adenitis (mimic append)
Causes Reiters syndrome
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HLA-B27 DISEASES
Reiters Syndrome- any post infection
arthritis
Ankylosing Spondilytis- Shoeberg
test, bamboo spine
Psoriasis- silver plaque on extensor
surfaces
Psoriasis w/o arthritis- HLA B13
Atypicals Atypicals
Atypicals
Have NO cell wall
Granulomatous inflammation
Covered by Quinalones, Macrolides and
Tetracyclines
Causes interstitial pneumonia
Symptoms out of proportion to physical
findings
Chlamydia
Parasites: depend on host for ATP
Eosinophilia
Has two forms:
elementary body (infectious)
reticulate body ( dormant form)
Granulomatous inflammation
Chlamydia Trachomatis
Causes trachoma: Mcc of neonatal blindness
in the world
Trachoma: destruction of cornea from scarring
Prevention: apply erythromycin to eyes
Mcc of lymphogranuloma venereum
Mcc of STDs ( 90% are asymptomatic)
Mcc of infertility in WOMEN
Mcc of ectopic pregnancy ( from scarring)
Chlamydia Trachomatis
Do ELIZA with all pap smears
One-dose treatment: azithromycin
1gm 1gm
Old treatment: doxicycline
for 7 days
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Chlamydia Pneumonia
Mcc of atypical pneumonia (0 to 2 mo)
Eosinophilia
Interstitial pneumonia
Symptoms out of proportion to physical findings
Steccato coughing
Found to be connected to alzheimers
disease and coronary artery disease
Chlamydia Psitacii
Associated with parrots and
parakeets
Causes interstitial pneumonia or Causes interstitial pneumonia or
nonbacterial endocarditis
Mycoplasma
NO cell wall
NO epithelial lining
Look like jellyfish
Mycoplasma Pneumonia
Mcc of atypical pneumonia from age
10 to 30
Cold agglutinins (cryoglobulinemia) gg ( y g )
Causes walking pneumonia
Interstitial pneumonia with symptoms
out of proportion to physical findings
Mycoplasma Hominis
An occassional cause of vaginitis
Legionella Pneumophila
Mcc of atypical pneumonia age 40yr
Interstitial pneumonia
silver stains
Grows on CYAE
Likes standing water on heating and air
conditioning systems
Causes high rise building syndrome
or hotel/motel syndrome
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Legionella Pneumophila
Pontiac Fever: fever and nonspecific
symptoms
Legionnaires disease: full blown g
pneumonia
Granulomatous inflammation
Causes heart block
Heart Blocks
First degree: fixed prolonged PR
interval
Second degree:
Mobitz 1: progressively prolonged PR Mobitz 1: progressively prolonged PR
interval until a QRS complex is dropped
Mobitz 2: normal PR interval; erratic
dropping of QRS complexes
Third degree: NO relationship
between P waves and QRS complexes
Infections that cause heart
blocks
Legionella
Lyme
Diptheria
Chagas
Typhoid fever
Ureoplasma Urolyticum
An occasional cause of vaginitis
Has NO cell wall or epithelial lining
like mycoplasma like mycoplasma
Urease positive
Urease Positive
Proteus
Pseudomonas
Ureoplasma
Nocardia Nocardia
Cryptococcus
H. Pylori
Staph saprophyticus
Brucellosis
Fungi Fungi
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FUNGI
Like warmth and moisture
(skin folds, groin, axilla, vagina)
Like to eat sugar- in diabetics
To prevent fungal infections, keep cool
and dry
Have a unique lipid in their
membrane called ergesterol
Antifungals
Bind to ergestrol
Amphotericin B- IV for systemic fungal infections
Gets confused with cholesterol
Pokes holes in your cells- releasing K+
Nystatin
Mycostatin
Miconazole
Clotrimazole
Tolnaftate
Terbenafine
Flucytosine (5FC) inhibits mitosis
(acts like pyramadine)
Antifungals
Inhibits ergesterol synthesis
Fluconazole- best CNS penetration
Itraconazole
Ketoconazole- inhibits P450s, blocks 5
reductase
Inhibits microtubules
- Griseofulvin
Superficial Fungi
Piedre black balls on the hair
shaft
Tx: cut hair
Microsporum Beigeii- white
balls on hair shaft
Tx: cut hair
Cutaneous Fungi
General (4 classes):
Dermatophyton skin
Trichophyton- hair follicle
Epidermaphyton- epidermis
Microsporum- (Wood lamp +)
Cutaneous Fungi
Tinea
Capitus - scalp
Versicolor- v on back
Corporus- body ring worm
Manis between fingers Manis between fingers
Nigra palms life lines get dark
Intertrigo- skin to skin
Cruris- jock itch - groin
Pedis between the toes
Unguum under nail beds (one nail
affected)
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Deep Fungi
Onychomycosis- fungus of nails
Candidiasis most common Candidiasis most common
cause of vaginitis
Vaginitis
Candida: curdy white discharge; pruritic
Candida part of normal flora and lactobacili keep
it in check (antibiotics will destroy lactobacilli)
Tx: Fluconazle
G d ll fi h d l ll Gardnerella: fishy odor; clue cells
Tx: Metronidazole
Trichamonas : frothy green discharge
Protozoa: flagella
Tx: Metronidazole and remember to treat
partner (STD)
Systemic Fungi
Histoplasmosis (Midwest) pigions, bats
Blastomycosis (North east) pigon,
broad base budding
Coccidiomycosis ( South west) Broad
base budding
Paracoccidiomycosis (South America)
shipwheel
Systemic Fungi
Sporothrix- rose gardner, skin-potassium
iodine; Amph B and Fluconazole if systemic
Cryptococcus- AIDS patient with
meningitis indian ink stain meningitis, indian ink stain
Aspergillus-Moldy hay or moldy
basement (mimics asthma)
Rhizor/ Mucor nose of diabetic
patients
Symptoms from the
Southwest
Coccidiomycosis- fungus
H t i i (h h i ) Hantavirus- virus (hemorrhagic)
Yersinia Pestis- bacteria
Pulmonary Infiltrate with
Eosinophilia
Allergic Bronchopulmonary Dysplasia
Loefflers Syndrome
Necator Americanus
Anclystoma Duodenale
Strongyloides
Shistosomiasis
Ascaria Lumbricoides
Churg-Strauss
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PARASITES PARASITES
FARTENPOOPIN FARTENPOOPIN
PARASITES
Cause gastroenteritis
T-cells, Macrophages, Eosinophils
LOW VOLUME STATE
Chronic infections lead to iron
deficiency anemia
Liver Flukes
Schistosomiasis : walking barefoot thru a
swamp
S mansoni: liver cancer
S. hematobium: causes squamous cell carcinoma
of the bladder (chronic irritation)
Ecchnococcus : messing with sheep; raw
lamb; dog food
Causes solitary ( hydatid) cyst of the liver
Liver Flukes
Toxacara : cat or dog poop
Carti- cat larvae
Cani- dog larvae
Cutaneus larva migrans- burrowing under
skin
Liver Flukes
Clinorchis ( or opthorchis)
Sinensis: seen in Chinese; likes the
biliary tract (Alkaline Phosphatase) y ( p )
TX for all liver flukes:
Parziquantel
Hookworms
Hooks into the intestinal/bowel wall
Severe cramps and diarrhea
NEAT AS NEAT AS
Necator americanus
Enterobius Vermiculris- pin worm
Pruritis ani (eggs)
Scotch tape test- female comes out at night
Worm lives in the cecum
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Hookworms
NEAT AS
Anclystoma Duodenale
Duodenal obstruction
Trichuris Trichurium- Whip worm Trichuris Trichurium Whip worm
Anchors into rectum
Rectal prolapse
Ascaris lumbricoides
Strongyloides
Hookworms
Treatment:
Mobendazole- paralyzes microtubules
(cant hook on to tissue)
Pyrantel pamaoate- specific treatment
for pin worm
Thiobendazole- tx for Strongyloides
NASSA
NASSA- parasites associated with
loffler syndrome (endocarditis
and pneumonitis)
Necator americanus
Anclystoma duodenale
Schistosomiasis
Strongyloides
Ascaris lumbricoides
Flat Worms
Will curl around the intestine:
D. Latum- like to eat B12
Tanea Saginatum- raw beef
Tanea Solium- raw pork, swims in
aqueous humor of the eye q y
Trichinella Spiralis- raw bear meat,
tunnel under skin causing myoisitis
Tx: Hyclosamine
Niclosamine
Inhibit oxidative phosphorylation decreasing ATP
Protozoa Protozoa
Protozoa
Brain:
Naeglaria Fowleri
Swimming through swamp- cribiform plate
Fulminant meningo encephalitis
Toxoplasmosis Toxoplasmosis
Cat litter (feces)
Parietal lobe ring enhanced lesion
Tx: Pyremethamine/ Sulfadiazine
Trypanosoma Rhodienses
Carried by Tsetse fly
African sleeping disease
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Protozoa
Cornea:
Acanthomoeba
Contact lenses
Will eat through cornea
Protozoa
Erlichiosis
Dog licking face (in saliva)
Penetrates side of eye
Protozoa
Heart
Trypanasoma Cruzi
Chagas disease
Eats ganglia and causes heart block g g
South America
Reduuvid bug
Protozoa
Lung:
Pneumocystic Corinii
Silver stain (also Legionella)
CD4 count < 200
Tx: Bactrim (SMX-TMP)
Protozoa
GI
Giardia- gastroenteritis
Loves fresh water/well water
Hiking in the mountains
Tx: IV Metronidazole Tx: IV Metronidazole
E. histolyticum
Multiple liver abscesses
(never do surgery)
Tx: Metronidazole (8 weeks)
Protozoa
GI
Microsporidium
MCC of diarrhea in AIDS patients
Cryptosporidium
Watery diarrhea
Partially acid fast
Tx: Ciprofloxacin
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Protozoa
GU
Trichimonas
3
rd
MCC of Vaginitis
Tx: Metronidazole 2gm x 1 g
Also treat partner
Protozoa
Skin
Leschmaniasis (RASH)
Gulf War syndrome
Sand fly
Leschmania Donivini (face eaten away)
Attacks skin and nostrils
Leschmania Rhodiensis (organ)
Systemic (attacks organs)-Kala Azar
Tx: Stibogluconate
Protozoa
Lymphatics
Wucheria Bacrofti
Elephantitis
No treatment
Protozoa
Blood
Babesiosis
East coast East coast
Looks different on a smear
Tx: anti-malarial
Ixodes tick
(same for Lyme disease)
Protozoa
Blood
Plasmodium Malaria
- MC strain world wide (fever every 3
rd
day)
Falciparum- most fatal (hemolize Falciparum most fatal (hemolize
RBCs)
Black water fever- urine turn black
Vivax- go to the liver (chronic malaria)
Likes reticulocytes (young RBCs)
Ovale- go to the liver (chronic malaria)
Likes mature RBCs
Protozoa
Blood- Plasmodium
Symptoms
Malaria- fever every 3
rd
day
Falciparum, vivax, ovale- fever every 2
days
Treatment:
Quinine
Chloraquine- mostly RBCs
Mefloquine- good liver penetration
Primaquine- best liver penetration
(vivax and ovale)
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Mycobacterium,
Spirochetes ,
Rickettsia
Mycobacterium,
Spirochetes ,
Rickettsia
Mycobacterium
NOT a true bacterium
Has bacterium in its name because
it has a peptidoglycan wall
Atypical due to MYCOLIC ACID in Atypical due to MYCOLIC ACID in
its membrane
Cell mediated inflammation
If you destroy mycolic acid, you
destroy mycobacterium
Mycolic Acid
A special lipid found in the wall of
mycobacterium
INH works by inhibiting mycolic acid INH works by inhibiting mycolic acid
synthesis
Isoniazid ( INH)
Inhibits the synthesis of mycolic acid
Fat soluble
Pulls vitamin B6 out of the system
Must give vitamin B6 with this drug to Must give vitamin B6 with this drug to
prevent neuropathy
Side effects: myositis; hepatitis;
hepatic necrosis ( especially after
age 35 years); neuropathy;
oxidizes RBCs: blocks P450
Primary response to
Mycobacterium
Asymptomatic
Ghon focus: naked tubercle on
respiratory epithelium
Vi l f CHORD FACTOR Virulence factor: CHORD FACTOR
Ghon complex: tubercle ingested by
macrophages and taken to the
lymph nodes
Granuloma: macrophages now
surrounded by T cells
Primary Tuberculosis
Usually lands in the RLL in terminal
bronchioles
Once GRANULOMA is formed:
Interferon
Tumor Necrosis Factor
1 hydroxylase
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Infliximab
An antibody against TNF
Useful in patients with RA
Decreases joint destruction
As long as your T cells and
macrophages stay healthy
You have nothing to worry g y
about.
.
But if cell mediated immunity is
ever impaired
Mycobacterium is still alive within
macrophages
Mycobacterium explodes out of the
h d i t th i macrophages and into the airways
Hemoptisis occurs
Mycobacterium works its way to
the upper lobe and sets up a
cavitary lesion
Patient now very symptomatic
Secondary Tuberculosis
Fever, night sweats, weight loss,
and hemoptysis
RLD profile
Cavitary lesion visible in upper Cavitary lesion visible in upper
lobes on the Xray
Tx: first isolate patient when
TB is suspected; get sputum
sample for culture
After TB replicates inside of the cavity,
it then disseminates
Mycobacteriumnowhas full access Mycobacterium now has full access
to the entire body.
Disseminated Tuberculosis
In GI: causes ileum obstruction
Bone: Potts Disease
Lymph Nodes: diffuse lymphadenopathy
Skin: Erythema Nodosum
Along Psoas Muscle: cold abscess
CNS: posterior fossa
Neuropathies
Hydrocephalus
Meningitis
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Disseminated Tuberculosis
Renal: sterile pyuria
Adrenal gland: insufficiency
In pregnant woman: treat as in
anyone else anyone else
Most people dont know they
have ever come in contact
with TB unless
TB Treatment
Four drugs for 4 months for everyone
If strain of TB is sensitive to both INH
and RIFAMPIN, then finish 8 more
months with just these two drugs
If strain of TB is NOT sensitive to both
of these drugs, complete 8 more
months with four drugs
Substitute other drugs if any bad
side effects
TB Treatment
At the end of twelve months of treatment, then
culture the sputum again
Sputum cultures are repeated monthly
Stop treatment when there are three
consecutive negative sputum samples
Patient may take drugs every day; or he
may opt to take it every other day but
witnessed by a healthcare professional
TB Prophylaxis
INH plus vitamin B6 for 9 to 12
months
In pregnant women, you must still
i h l i give prophylaxis
In patients with history of BCG
vaccine, ignore the history, and
merely follow the algorhythm
Mycobacterium Family
M. TB
M. Leprae ( Hansons Disease)
M. Avium Intracellulare
f l M. Scrofulaceum
M. Marinum
M. Ulcerans
M. Kansasii
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Dapsone
Indicated for the treatment of dermatitis
herpetiformis, Pneumocystis carinii in HIV
patients, and for leprosy
For leprosy: use with clofazimine and
rifampin for 6 to 24 months p
Mimics PABA like sulfa drugs
Side effects: megaloblastic anemia;
oxidizes RBCs; coombs positive hemolytic
anemia; inhibits P450 system
Spirochetes
So named due to their spiral shape
Have axial filaments at their two
ends ends
Use a lateral tumbling motion
Cell mediated response
Treponema Pallidum
Causes syphilis
The most common cause of painless
genital ulcer
Primary syphilis- non tender chancre Primary syphilis- non tender chancre
( contagious )
Secondary syphilis- 1 to 3 mo
( rash P & S )
Tertiary syphilis *
Tertiary Syphilis
Tabes Dorsales
Shooting, lancinating, stabbing neuropathy
Syphilitic aortitis
Argyle Robertson pupil
Syphilis loves to attack bones
( saber shins)
TORCH infections
They attack in the first trimester
( except herpes)
They cause severe neurological
damage damage
All cause IUGR, microcephaly,
hypotonia and developmental
impairment
How do you separate them ?
Toxoplasmosis
Multiple ring enhancing lesions in the parietal
lobes
Caused by cat urine
Asymptomatic in healthy people (walled off
in a granuloma)
S t ti i t d t Symptomatic in pregnant women due to
suppressed immune system
Pregnant women should NOT change a litter
box
Treat with pyremethamine/sulfadiazine
combo
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Syphilis
Loves to attack bones
Flat forehead
Saddle nose
Sniffles
Micrognathia
Rhagades
Hutchinsons teeth
Sabre shins
Rubella
Blueberry muffin rash
Cataracts
PDA
l Hearing loss
Autism
Autism
Four features:
Inability to bond
Impaired language development
Automatism- no control of there actions
Overreacts to small disturbances
Brain is found on autopsy to be
arrested in development
MMR controversy
Autistic
AUTISM- below normal intelligence, difficulty
forming relationships
Asperger syndrome: milder form, normal
intelligence and lack social skills intelligence and lack social skills
Pervasive developmental disorder of childhood
Retts syndrome- girls only, starts by
age 4, hand wringing
Cytomegalovirus
Loves to attack the retina
Mcc of Congenital blindness
Causes central calcifications
Attacks the midline
Herpesvirus
Attacks newborn on the way through the
vagina
Loves to attack the temporal lobe, causing
temporal lobe hemorrhagic encephalitis
If pregnant mother has an outbreak of
lesions within two weeks of delivery, do a
C-section
Give pregnant mother acyclovir in last
month to prevent outbreaks
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Syphilis
Treatment:
Primary syphilis: 1.2 million units of long
acting penicillin (Procaine or Benzathine)
Secondary syphilis: 2.4 million units, half in
h b tt k each buttock
Tertiary syphilis: 2.4 million units once
weekly for 3 weeks
Neonatal syphilis: 50,000 units per
Kg per day in divided doses
Treponema Family
Treponema Pallidum
Treponema Pallidum variant: Bijel
Treponema Pertenue: Yaws-
tropical form
Treponema Carateum: Pinta
Borellia Borgdorferi
Lyme Disease
Primary stage- bulls eye rash (resolve
in 1 month)
Secondary stage- flu like symptoms , y g y p ,
organ involvement
Tertiary stage- arthritis
Dx: history of Erythema Chronicum
Migrans;
Do IgM and IgG titers
Borellia Borgdorferi
Treatment:
Penicillin
Doxycycline
If a pregnant woman is bitten by a tick,
treat with IV ceftriaxone
Any patient with heart block,
hospitalize and treat with
IV ceftriaxone
Borellia Recurrentis
Causes Relapsing Fever
Fever occurs once weekly
Organism hides in lymph nodes and
mutates slightly each week
Treat with penicillin or doxicycline
Leptospira Interrogans
Causes leptospirosis
Seen primarily in sewage workers
Transmitted by rat urine
Weils Disease: attacks the liver
(hepatitis) and the kidney (nephritis)
Causes Fort Braggs Fever
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Rickettsia
Rickettsia Rickettsia: RMSF: tick borne
Rickettsia Typhi: endemic typhus: flea borne
Rickettsia Prowzekii: epidemic typhus: louse
borne
Rickettsia Akari: rickettsial pox: mite borne
Rickettsia Tsutsugamushi- scrub typhus;
chiggers
Rickettsia
Treatment: Doxicycline or
Chloramphenicol
We both wish you the best
of luck on your exam !!!!
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And NOWThe final topic!
VIRUSES
What all viruses do
Invasion
Adhesion
Penetration
Uncoating
Replication
Assembly
Lysogeny
To prevent uncoating
Amantidine
Rimantidine
To prevent replication
Acyclovir
Pencyclovir
Demcyclovir
Valcyclovir
Famcyclovir
Gancyclovir
Ribavarin
Detectives
Southern blot
Northern blot
Western blot
Southwestern blot
ELIZA
PCR
The 90%
DNA Viruses
Double stranded ( ex
parvovirus and
hepadnovirus
Replicate in nucleus ( ex
RNA Viruses
Single stranded ( ex
orthomyxovirus and
renovirus
Replicate in cytoplasm p (
poxvirus)
Assemble on nuclear
membrane
Naked ( ex herpesvirus)
p y p
(ex retrovirus)
Assemble on cell
membrane
Enveloped (ex
cocksackievirus)
+-strand vs -strand
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Most Common causes of
viral infections viral infections
From head to toe
Encephalitis
Presents with headache and ataxia
Causes:
Arbovirus
Herpesvirus
Meningitis
AKA aseptic meningitis
Presentation: mild headache; photophobia;
Kernigs and Brudzinskis signs
CS l CSF results
Causes: enteroviruses
Common Cold
Rhinovirus
Coronavirus vs Adenovirus
Herpesvirus
Influenzavirus
Parainfluenzavirus
Common Childhood infections
Mumps
Rubeola
Rubella
Varicella
Hand-Foot-Mouth
disease
Kawasaki disease
Molluscum
i
Varicella-Zoster
Fifths disease
Roseola
Pityriasis Rosea
Rosacea
contagiosum
Childhood Rashes
Seborrheic dermatitis diaper dermatitis
Erythema toxicum Pediculosis pubis
Milia
Mongolian spots
Nevus Flemmeus
Caf au lait spots
Port wine stain
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The four itchiest rashes
Urticaria
Scabies
Dermatitis herpetiformis
Lichen planus
Croup
Stridor and barking cough
Steeple sign on neck film
Cause:
Parainfluenzavirus 80% mild
RSV 15% severe
Adenovirus
Influenzavirus
Bronchiolitis
All the signs and symptoms of asthma
Under 2 years of age
Caueses:
Parainfluenzavirus 80% mild
RSV 15% severe
Adenovirus
Influenzavirus
Myocarditis
Leads to loss of contractility
Diffuse ST wave depression on EKG
Cause:
Cocksackie B Virus
Pericarditis
Causes a friction or tri-phasic rub
May lead to tamponade
Diffuse ST wave elevation
Cause:
Cocksackie B Virus
Gastroenteritis
In adults: Adenovirus
In children: Rotavirus
Travel: Norwalk agent
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Cystitis
Urgency and frequency
Cause: Adenovirus
Hepatitis
Hepatitis
Chronic Active Hepatitis
Active inflammation on biopsy
Fibrosis present
May progress to liver cancer
Will lead to cirrhosis
Due to Hepatitis B: Tx with interferon and
lamuvidine
Due to hepatitis C: Tx with interferon and
ribavarin
Chronic Persistent Hepatitis
Elevated liver enzymes or persistent
symptoms after 6 months
No active inflammation or fibrosis on liver
biopsy biopsy
Chronic Carrier
Still has positive HbSag after 6 months
No active inflammation or fibrosis on biopsy
Still pose a threat to others
Can NOT be blood donors or organ donors
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THE END
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Obstetrics and
Gynecology
G5 P4 Ab1
G: Gravita: number of
pregnancies
P: Para: > 20 Weeks P: Para: > 20 Weeks
Ab: Abortive: abortions
G6 P0 Ab5
Prenatal
Diagnostic g
Testing
Ultrasound (Utz.)
Non-invasive imaging
No adverse effects on the fetus
18-20 weeks of gestational
anatomical anomalies
Accuracy for gestational age:
At 12 weeks +/- 5 days
At 18 weeks +/- 7 days
Nucal Translucency
10- 14 weeks via Utz.
Thick area you should think of
cystic hydroma Downs Syndrome
Chorionic Villous Sampling
(CVS)
Aspiration of placenta
tissue (9-12 wks)
Sono guided
Karyotyping
Pregnancy loss rate 0.7%
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Amniocentesis
Transabdominal needle to withdraw
amniotic fluid under sono (15-20 wks)
Looking at DNA from fetal cells
Not enough fluid prior to 15 weeks Not enough fluid prior to 15 weeks
Pregnancy loss rate (0.5%)
24 weeks- Rh isoimmunization
(bilirubin levels)
34 weeks- Lecithin-sphingomyelin
Percutaneous Umbilical Blood
Sampling (PUBS)
Fetal blood from umbilical vein
(> 20 weeks)
Fetal karyotyping
IgM antibody
Blood typing
Intrauterine Blood Transfusion
Pregnancy loss rate 1-2%
Fetoscopy
Experimental (18-20 weeks)
Fetal tissue biopsy
Ichthyosis y
Genetic skin condition
(fish scales)
Coagulation in twin-twin
transfusion
Fetal Development
1 week for Implantation
Folic acid
1mg
4mg
Week 2-3 post conception
Bilaminar germ disk:
- Epiblast
- Hypoblast
Cytotrophoblast
Synchotrophoblast
Primitive streak
Weeks 4-8 Post Conception
Major organs forming
Teratogenic risk
- Ectoderm
- Mesoderm
- Endoderm
Must have all 3 in order to a
teratogen to cause problems
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Female vs Male cells
Theca
Granulosa
L di Leydig
Sertoli
5 alpha reductase DHT (external
genitalia)
Teratogenesis Stages
Conception to end of first week
Weeks 3-8
Post week 9
Teratogens
Ionizing radiation
Chemotherapy
T b Tobacco
ETOH
Cocaine
Teratogenic Syndromes
Alcohol: fetal alcohol syndrome
Long philtrum
Midfacial hypoplasia
Short palpebral fissure
Teratogenic Syndromes
Diethylstilbestrol (DES)
T-shaped uterus
Vaginal adenosis clear cell Vaginal adenosis- clear cell
carcinoma
Incompetent cervix
Teratogenic Syndromes
Isotretinoin (Accutane)
Congenital deafness
Congenital heart defects
iPLEDGE
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Teratogenic Syndromes
Lithium:
Ebstein anomaly (R heart defect)
Tricuspid lower
Very large right atrium
Teratogenic Syndromes
Streptomycin
CN 8 damage- hearing
Teratogenic Syndromes
Tetracycline
Competes with Ca2+
Teeth discoloration after 4 months
Teratogenic Syndromes
Thalidomide: drug for N/V
Phocomelia (days 42-48)
Pyloric and duodenal stenosis
Teratogenic Syndromes
Valproic acid (Depakote)
Neural tube defect
Mgt: Migrans and Bipolar Mgt: Migrans and Bipolar
Teratogenic Syndromes
Warfarin (Coumadin)
Chondrodysplasia: stippled
epiphysis
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Pregnancy
Hormones Hormones
Human Chorionic Gonadotropin
Syncytrophoblast
In blood by day 10
Alpha subunit
Beta subunit (specific)
High levels of hCG
Twins
Hydatiform moles
Choriocarcinoma
LOW levels:
Ectopic
Threatened abortion
Missed abortion
Human Placental Lactogen
(HPL)
Increased through pregnancy
Antagonizes insulin tago es su
Organ
system
changes in changes in
pregnancy
Skin
Line nigra
Chloasma
Chadwick sign
Stria gravidarum
Spider angiomata/palmer erythema
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Heart
Blood pressure
Plasma volume
Femoral venous pressure
CO
Peripheral vascular resistance (PVR)
Murmurs
Systolic murmur:
Diastolic murmur:
Blood
RBCs
Plasma volume
WBCs
Platelets
Coagulation
GI
Stomach:
Large bowel Large bowel
Pulmonary
Tidal Volume
Minute volume
Respiratory volume
Blood gases
Renal
Increase in size:
Gl i Glucosuria:
Proteinuria:
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Endocrine
Pituitary
Thyroid
Fetal Circulation
3 in utero shunts:
Ductus venosus
Foramen ovale
Ductus arteriosus
Fetal
Testing Testing
Fetal Hart Tone (FHT)
Doppler stethoscope: 10-12 wks
Auscultation 18-20 wks
Quickening: 16-18 weeks
(primigravida 18-20)
Ultrasound Dating
1
st
trimester:
2
nd
trimester and 3
rd
Biparietal diameter
Head circumference
Abd. Circumference
Femur length
Pregnancy 1
st
trimester
< 13 weeks
N/V
S tti / bl di Spotting/ bleeding
Wt gain 5-8 lbs
Complication: spontaneous
abortion
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Pregnancy 2
nd
trimester
13 26 weeks
Round ligament pain
Braxton-Hicks contractions Braxton-Hicks contractions
Quickening
Wt gain 1 lb/wk
Complication: incompetent cervix
Pregnancy 3
rd
Trimester
Decreased libido, back pain, urinary
frequency
Lightening
Bloody show
Wt gain 1 lb/week
Complication: PROM
Prenatal
Lab Lab
Test
Mean Corpuscular Volume
Hb/Hct- low due to dilution
MCV most reliable MCV most reliable
< 80
> 100
Rubella IgG antibody
Antibodies present
Absence puts patient at risk
Immunization:
Hepatitis B Virus
HBV surface antibody: successful
vaccination
HBV surface antigen:
E antigen:
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STD screening
Cervical cultures:
Syphilis:
VDRL
RPR
MHA-TP
FTA
Mgt. Penicillin
Urine Screening
Urinalysis:
Proteinuria
Ketones
Glucose
Bacteria
Culture: asymptomatic bacteruria
(ASB)
Tuberculosis Screening
PPD or Tine test:
Positive skin test
CXR negative CXR negative
CXT positive
HIV screening
Recommended for all pregnant
women
Opt out: informed refusal
Opt in: informed consent
Elisa test
Detectable HIV antibodies
Babies born to an HIV + mothers
Western Blot
Zidovudine
Alpha Fetal Protein
True causes of increased AFP:
MCC d ti MCC- dating errors
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Triple Marker Screening
MS-AFP
hCG
Estriol
Accurate dating is important Accurate dating is important
Triple marker screening
Trisomy 21 Trisomy 18
Downs Edwards
MS-AFP MS-AFP
hCG
Estriol
Do karyotype for both
Third Trimester Lab Test
Diabetic Test:
1hr (50 gm) oral glucose
3hr (100 gm) oral glucose
Normal: FBS: < 95, 1hr <180, 2hr < 155,
3hr < 140
Antenatal
Fetal Fetal
Testing
Nonstress Test (NST)
Check frequency of fetal movement
External fetal HR monitor
Accelerations
< 32 wks: > 10 or more BPM, < 32 wks: > 10 or more BPM,
lasting >10 sec
> 32 wks: > 15 or more BPM,
lasting > 15 sec
Fetal Monitor Tracing
Base line FHR: 110-160
< 110 Bradycardia
Meds: beta adrenergic blockers, anesthetics
Fetal arrhythmia congenital heart block (lupus) Fetal arrhythmia- congenital heart block (lupus)
>160 Tachycardia
Meds: beat adrenergic agonist (terbutaline,
ritodrine)
Fever
Fetal repetive movements
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Early Deceleration:
head compression
Variable Deceleration-
cord compression
Late Decelerations- uteroplacental
insufficiency ( fetal acidosis)
Biophysical profile (BPP)
5 components of fetal well
being:
1. NST: scores 0-2 for each
2. Amniotic fluid volume
3. Fetal gross body movement g y
4. Fetal extremity tone
5. Fetal breathing movements
2-5 assessed through Utz.
BPP scoring
8-10 = reassuring (weekly BPP)
4-6 = worrisome
> 36 wks- deliver
< 36 k BPP 12 24 h < 36 wks- BPP every 12-24 hours
0-2 = fetal hypoxia (deliver ASAP)
Contraction stress test (CTS)
Testing fetus response to tolerate
transitory decreases in blood flow
Presence or absence of late
deceleration
Induce with IV oxytocin
Negative test is good- no late D-
cells
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Umbilical Artery Doppler
Measures ratio of Systolic and
Diastolic blood flow in umbilical
artery
Increased throughout pregnancy, g p g y,
since diastolic pressure falls more
Infections
Group B beta hemolytic Strep
Normal GI tract flora
30% of women are asymptomatic carriers
Vertical transmission
Early onset
Late onset
Mgt: IV penicillin: if allergic- Clindamycin
and Erythromycin
Treat for Group B Strep if
Positive urine culture GBBS
Previous baby had GBBS
Screening by vaginal cultures:
3
rd
trimester
If + then prophylaxis IV PCN
Preterm or Membrane rupture > 18hrs,
or maternal fever Mgt.
Prophylaxis IV PCN
Toxoplasma Gondii
Parasite associated with cat feces
Raw goat milk
Under cooked infected meat
Vertical transmission Vertical transmission
Lethal if first trimester
Third trimester- asymptomatic
Intracranial calcification
Mgt: Pyrimethamine Sulfadiazine
Varicella
Chicken Pox
Herpes Zoster
Spread via respiratory droplets
ZIG ZAG skin lesion
Maternal varicella pneumonia Maternal varicella pneumonia
Mgt: administer VZIG to suspected
gravid within 96 hrs of exposure
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Rubella
RNA virus spread through
respiratory droplets
Transmission only if primary
infection
Fetus= VSD
Neonate= congenital deafness Neonate= congenital deafness
Prevention: rubella IgG antibody
screening
Live attenuated virus- avoid
pregnancy for 1 month after
immunization
Cytomegalovirus (CMV)
Spread via body secretions
Life long latency, so fetus can get
it on reactivation
Periventricular calcification
MCC of congenital deafness
Mgt: Ganciclovir
Herpes Simplex Virus (HSV)
Multinucleated Giant Cells
Maternal genital lesion is MC route
for fetal infection
Dx: + culture from ruptured vesicle
Prevention: C section Prevention: C-section
If membrane already ruptured and it
has been >8-12 hours- too late to
do a C-section
Mgt: Acyclovir
Human Immunodeficiency Virus
HIV + mothers take zidovudine
starting at 14 wks until delivery
C-section for delivery
Breast feeding contraindicated
Neonate gets AZT for 6 wks, then
check again
Maternal Syphilis infection
Primary- painless ulcer with rolled up
edges (chancre)- gone in 2-3 wks
Secondary- 2-3 months after contact,
maculopapular skin rash and
condyloma lata condyloma lata
Tertiary- organs affected
Heart- aortitis
Dorsal column- tabes dorsalis
CSF +
Mgt: Vaginal delivery: Benzathine PCN and if allergic
desensitization to PCN
Bleeding
during late g
pregnancy
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Bleeding
Initial evaluation:
Maternal : check vitals
Fetus: FHT
Mgt: large bore IV NS
Foley- monitor output
If fetal jeopardy is present or +/- 36
wks- deliver
Abruptio Placenta
Painful bleeding
Overt (external) Concealed (internal)
Types of Abruption
Mild- no fetal abnormality
Moderate- 25 50% surface
separation
Monitor for late D-cells o to o ate ce s
Severe- abrupt, knife like uterine
pain
> 50% placental separation
DIC may occur
Severe late D-cells
Mgt. of Abruptio
Emergency Cesarean if mother or
fetal jeopardy
Vaginal delivery if bleeding is Vaginal delivery if bleeding is
controlled or > 36 wks
Conservative (in hospital)
Stable and remote from term
Confirm placental location on sono
Replace fluids
Placenta Previa
Painless bleeding
Placenta is implanted in lower
uterine segment
Common early in pregnancy
(migration)
3 types:
Total, complete or central- covers os
Partial- partial cover of os
Marginal, low lying- near os
Mgt. for Placenta Previa
Emergency Cesarean if mother or
fetal jeopardy
Vaginal delivery- lower placental
edge must be > 2cm of os
Scheduled C-section
Fetal lung maturity by amniocentesis
Conservative (in hospital)
Bed rest, preterm, confirm placental
location
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Complications of Placenta Previa
Villi may invade uterine tissue
Endometrium
Placenta Placenta
accreta 75%
Placenta Increta
20%
Placenta
percreta 5%
Bladder
Myometrium
Serosa
Vasa Previa
Fetal vessels transverse the internal OS
Bleeding from fetoplacental circulation
Rapid fetal exsanguination
Due to amniotomy (AROM)
Triad:
ROM
Painless vaginal bleeding
Fetal bradycardia
Mgt: immediate C-section
Uterine Rupture
Triad:
Painful bleed
Loss of FHT
Head floating
MCC- classical incision MCC classical incision
Myomectomy
Excessive oxytocin
Mgt: surgical
Obstetrical
Complications p
Abortion vs fetal demise
Fetal death prior to 20 weeks:
Abortion
- Missed
- Threatened
- Inevitable
- Incomplete
- Complete
After 20 weeks: fetal demise
Must report to the state
Fetal demise (>20 wks)
Most serious consequence
DIC (disseminated intravascular
coagulation)
Usually takes 3-4 wks to occur
Release of thromboplastin from
deteriorating fetal organs
Do not deliver until mom is ready as
long as there is no DIC
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Twin Delivery
Vaginal C-section ?
B
B
B
Both
Cephalic
A- breech
B- cephalic
A- cephalic
B- breech
A
B
A
A
B
Rho GAM
Pooled anti-D IgG
Passive antibodies (IM)
I G tib di tt h t th IgG antibodies attach to the
foreign RBC and lysis occurs
before mom can produce an
immune response
RhoGAM given at
Give to Rh(D) negative mothers at
28 weeks
Within 72 hours of
Chorionic villus sampling Chorionic villus sampling
Amniocentesis
Rh+ delivery
D & C
Give 300 micrograms (1 vial)
Kleihauer Betke Test
Quantitates fetal RBCs in moms
blood
Looks at a peripheral smear
Will access if more than one vial is
needed
Premature Rupture of Membrane
(PROM)
Risk of ascending infection
History of sudden gush of copious
vaginal fluids
Oligohydramnios on Utz.
Diagnosis PROM
Sterile speculum
Pooling clear fluid in posterior
vaginal fornix
Nitrazine positive (turns paper blue) p ( p p )
Fern test- on microslide
Chorioamnionitis:
Maternal fever
Uterine tenderness
Confirmed PROM
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Management PROM
Uterine contractions present
(dont use tocolysis)
Chorioamnionitis- IV antibiotics, Chorioamnionitis IV antibiotics,
delivery
No infection
< 24 wks- dismal outcome
>24- bed rest, IM betamethasone, 7 day
prophylaxis of ampicillin and
erythromycin
Preterm Labor
3 criteria:
Between 20 and 37 weeks
Uterine contractions (3 in 30 min.)
Cervical changes
(dilation changes > 2cm)
Tocolytic Agents
Prolong pregnancy for up to 72 hrs
IM betamethasone to work
Transport mother/fetus to neonatal Transport mother/fetus to neonatal
intensive care
Given parenteral
Types of Tocolytics
MgSO4- blocks Ca2+
Monitor: DTR
Antidote: IV calcium gluconate
Contraindications: renal insufficiency, MG
Beta adrenergic agonist- terbutaline,
ritodrine
Ca2+ blockers- Nifedipine, Procardia
PG inhibitors- Indomethacin
Post Date Pregnancy
Worried about placental breakdown
Fetus not getting the O2 it needs
Meconium risk
42 wks maximum time in uterus
Shoulder dystocia
HTN during
pregnancy p g y
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Preeclampsia:
Mild Severe
B/P
Proteinuria
Gestation
Mgt.
Eclampsia
Unexplained grand mal seizures
with
HTN
Proteinuria
> 20 wks gestation
Severe diffuse cerebral
vasospasms
Mgt. of Eclampsia
First protect the mothers airway
IV MgSO4, with IV bolus of 5g to stop
seizure seizure
Maintenance dose 2g/hr
Deliver at any gestational age
Lower diastolic B/P to 90-100mmHg
HELLP Syndrome
5-10% of preeclamptic patients
H- hemolysis
EL- elevated liver enzymes
LP- low platelets
Mgt. prompt delivery at any age
Fetal Presentation
Cephalic- head presents first
Breech- feet or buttock first
Frank (vaginal delivery)- sucking on
toes
Complete
Footling
Compound- more than one body part
present
Station in delivery
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Overview of Labor
Uterine changes:
Contraction of upper uterine segment
Exerting expelling forces
Cervical effacement:
Thinning due to oxytocin and PGE2
breaking disulfide bonds in collagen
fibers
Normal cervix: 2cm long/ 2cm wide
Cardinal Movement in Labor
Engagement
Descent
Flexion
Internal rotation
Extension
External rotation
Expulsion
Stages of Labor
Stage 1: onset of uterine contraction
and ends with complete dilation
Latent- cervical dilation up to 20 hrs (3-4 cm)
Active rapid cervical dilation (1.2 cm/hr)
Stage 2: complete cervical dilation to
delivery (2 hrs) delivery (2 hrs)
Stage 3: delivery to placental expulsion
(30 min)
Stage 4: observation of mother for
preeclampsia and post partum
hemorrhage
Abnormal
L b Labor
Prolonged Latent Phase
Cervical dilation <3cm for
> 20hrs primipara
> 14 hrs multipara
MCC i j di i l i MCC injudicious analgesia
Mgt. Therapeutic rest
Prolonged Active Phase or Arrest
Cervical dilation > 3cm
Prolonged dilation < 1.2 cm for > 2h
Passenger problem: size or
orientation
Power problem: inadequate uterine
contraction
Hypotonic muscle- IV oxytocin
Contraction normal- go to C-section
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Prolonged 3
rd
stage
Placenta has not delivered within 30
min
If it does not remove with IV
oxytocin, then think accreta (etc.) y , ( )
Mgt. manual removal or
Hysterectomy
Prolapsed Umbilical Cord
Obstetric emergency
Cord gets compressed affecting
fetal oxygenation
Occult- head and uterine wall
Partial- head and cervical os
Complete- protruding into vagina
Mgt. Knee-chest position
Elevate presenting part
Immediate C-section
Shoulder Dystocia
Delivery of fetal shoulder is
delayed after delivery of head
Impacted of pubic symphysis
Mgt. suprapubic pressure
McRoberts maneuver- thigh flexed
Woods corkscrew- internal rotation
Manual delivery of posterior arm
Cesarean Section
Maternal mortality and morbidity is
higher than vaginal delivery
Hemorrhage : > 1000 ml
Infection
Visceral injury: bowel, bladder
Thrombosis- DVT
Uterine Incisions
Lower segment transverse
(pull bladder down)
Fetus must be in longitudinal lie Fetus must be in longitudinal lie
Cut non-contractile portion of uterus
Can still have VBAC
(vaginal birth after c-section)
Cervical Ceretage
Pts with incompetent cervix
Shirodkar- beneath cervical
mucosa- left in place with deliver
of C-section
McDonald- removed by 36 wks for
vaginal delivery
Placed at 14 wks, before cervical
dilation and effacement occur
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Post Partum Fever
PP day 0: Atelectasis
PP day 1-2: UTI
PP day 2-3: Endometritis
PP day 4-5: Wound infection
(antibiotics and drain) (antibiotics and drain)
PP day 5-6: Septic thrombophlebitis
(IV heparin 7-10 days)
PP day 7-21: Infectious mastitis
(oral cloxacillin and continue
breast feeding)
Gynecologic
Neoplasia
and Cancer
Human Papilloma Virus (HPV)
16, 18, 31, 33 and 35
Premalignant
Cancerous
6 11 6,11
Benign condyloma acuminata
PAP test
Screening for premalignant lesions
Transformation zone (T-zone)
squamous/columnar
3 years after onset of sexual
activity or 21 y/o act ty o y/o
Discontinued >70 with 3 negative
paps
< 30 y/o annually (2 yrs liquid based)
> 30 every 2-3 yrs after 3 (-) paps
Bethesda System
Negative- no malignancy
ASC- atypical squamous cells
LSIL- low grade squamous intraepithelial LSIL low grade squamous intraepithelial
lesion (HPV or CIN I)
HSIL high grade squamous intraepithelial
lesion ( CIN 2,3, moderate dysplasia)
Cancer- invasive
Diagnostic Approach
Accelerated repeat PAP: ASC-US
HPV-DNA testing: ASC-US
Colposcopy- abnormal pap Colposcopy abnormal pap
(acetic acid)
Endocervical curettage (ECC)- r/o
endocervical lesion [not in pregnancy]
Cone biopsy- PAP worse than histological
473
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Mgt. according to histology
Observation: CIN I, repeat pap 6-12
months
Ablative: CIN 1, 2, 3: Cryotherapy
Excisional: CIN 1, 2, 3: LEEP (loop
electrosurgical excision), cold
knife
Hysterectomy- recurrent CIN 1,2,3
Invasive Cervical CA
Penetrated through basement
membrane
Postcoital vaginal bleeding
Dx. Cervical biopsy- sq. cell CA
Mgt. Hysterectomy
Cervical Neoplasia in
Pregnancy
Pregnancy does not change
progression
Test female same as non-pregnant p g
Skip ECC- cervix more vascular
Invasive CA:
<24 wks: hysterectomy
> 24 wks: wait until 32-33 wks, then
C-section and hysterectomy
Post Menopausal Bleeding
Menopause- after 3mo or cessation
of menses
Endometrial carcinoma (MCC)
Unopposed estrogen
Dx: Endometrial sampling
Mgt: Positive histology: TAH & BSO
Enlarged Uterus
Leiomyoma:
Benign smooth muscle of the
myometrium
More common in black females
Mgt. Observation
Presurgical shrinkage 3-6 mo GnRH analog
Myomectomy
Embolization
Hysterectomy
Enlarged Uterus
Adenomyosis:
Ectopic endometrial glands and stroma
located within the myometrium of the
uterine wall
Tender uterus in absence of pregnancy p g y
Dx. Utz or MRI
Mgt. Levonorgestrel intrauterine system
Definitive : Hysterectomy
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Ovarian
Neoplasia Neoplasia
Premenopausal Adnexal Mass
Simple Cyst- luteal or follicular
Complex cyst- dermoid (germ layers)
Dx. hCG levels to rule out pregnancy:
Sonogram
Mgt.
Simple cyst- observation, OCPs,
(>7cm laparoscopic)
Complex cyst- surgical removal
Adnexal Mass With Pain
Sudden onset of severe lower
abdominal pain in presence of
adnexal mass.Ovarian torsion
Mgt. untwist Mgt. untwist
Observation to assure revitalization
Routine exam annually
Prepubertal Adnexal Mass
Functional ovarian cyst not
possible because ovarian
follicles are not functioning
Suspicious of neoplasm p p
Dx. Tumor markers
LDH- dysgerminoma
Beta HCG- Choriocarcinoma
Alpha fetal protein- endodermal sinus
tumor
Postmenopausal Adnexal Mass
Ovaries should be atrophic
Any enlargement, should draw
suspicion of ovarian cancer
BRCA-1
Classifications
Epithelial tumor (80%)- post menopausal
MC serous
Germ Cell tumor (15%)- teenagers
MC dysgerminoma
Stromal tumor (5%)
Granulosa cell tumor- increased estrogen
Metastatic tumor- Krukenberg
stomach to ovary
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Vulvar Neoplasia
Vulvar lesion with pruritus
Vulvar itching
Squamous hyperplasia
(whitish focal area) ( )
Mgt. corticosteroids
Lichen Sclerosis
(bluish-white papule)
Parchment like
Mgt. testosterone cream
Vulvar Intraepithelial Neoplasia
(VIN)
Squamous dysplasia
Mgt. surgical excision
The
End
476
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1
Trauma" refers to a serious
or critical bodily injury,
wound, or shock, as from
violence or accident.
Immediately life-
threatening injuries
Potentially life-
threatening injuries
Airway obstruction
Simple
pneumo/haemothorax
Tension pneumothorax Aortic rupture
Open pneumothorax Blunt cardiac injury
Massive haemothorax Pulmonary contusion
Flail chest Tracheobronchial rupture
Cardiac tamponade Diaphragmatic rupture
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SIGNS & SYMPTOMS: (Your CLUES)
1. No, weak, noisy, labored or gurgled respiration
2. Pale, cool, clammy skin; delayed capillary refill
3. Irregular/unstable vital signs
4. Contusion, abrasion, laceration, hematoma
5. Pain, tenderness, guarding, numbness/tingling
6. Bruising, swelling, deformity, false/limited motion
7. Muscle weakness/paralysis, loss of sensation
8. Altered mental status
9. Asymmetric pupils, JVD, incontinence
OBTAIN HISTORY OF:
1. PMH/Meds/Allergies
2. Mechanism of injury/weapon description
3. Use of protective devices: helmets, seatbelts,
airbags, padding
4. Substance abuse
5. Estimated blood loss at scene
6. Time of injury
7. Loss of consciousness
STABLE or UNSTABLE
UNSTABLE
The Famous A B Cs
- Airway
- Breathing
- Circulation
The Famous A B Cs
In the vignette:
- GET RID OF DISTRACTORS!
- Look for Pt. Stability and
decide:
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The Famous A B Cs
In the vignette:
- GET RID OF DISTRACTORS!
- Look for Pt. Stability and
decide:
Case:
25 y/o man falls from a tree. At the moment
he is unconscious. His breathing is difficult
and his mouth is full of blood. His arm has an
unusual angle and theres laceration in his
forehead and chest. What is the best next
step?
Case:
25 y/o man falls from a tree. At the moment
he is unconscious. His breathing is difficult
and his mouth is full of blood. His arm has an
unusual angle and theres laceration in his
forehead and chest. What is the best next
step?
AIRWAY:
What to check?
-No, weak, noisy, labored or gurgled respiration
-Abnormal, silent or low voice or uncompleted
sentences while talking
- Unconsciousness
AIRWAY:
Then: Administer air ANYHOW!
- Mask w/ 100% O2
- Orotracheal intubation
- Cricothyroidotomy
AIRWAY:
Then: Administer air ANYHOW!
- Mask w/ 100% O2
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AIRWAY:
Then: Administer air ANYHOW!
- Orotracheal intubation
AIRWAY:
Then: Administer air ANYHOW!
- Cricothyroidotomy
AIRWAY:
Then: Administer air ANYHOW!
How to choose?
Rules:
1.-Use less invasive first
2.-Follow the order if the patient
has been started but
oxygenation didnt succeed
(Check PULSE OX. <90)
AIRWAY:
Possible causes: (If diagnose is asked)
- Foreign object
- Body fluids (blood, vomit)
- Swelling of trachea, epiglottis,
tongue, uvula, etc
- Disruption of airway (direct trauma)
- Anesthesia, drugs
- Head trauma
Case:
25 y/o man falls from a tree. At the moment
he is unconscious. His breathing is difficult
and his mouth is full of blood. His arm has an
unusual angle and theres laceration in his
forehead and chest. In the ambulance the
patient is intubated successfully. Physical
Examination: Loud blow sound in the left
when ambu is compressed. What is the best
next step?
Case:
25 y/o man falls from a tree. At the moment
he is unconscious. His breathing is difficult
and his mouth is full of blood. His arm has an
unusual angle and theres laceration in his
forehead and chest. In the ambulance the
patient is intubated successfully. Physical
Examination: Loud blow sound in the left
when ambu is compressed. What is the best
next step?
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BREATHING:
What to check?
-Symmetry of air flow
-Is air going to lungs actually?
-Breath automatism
-OVERVENTILATION
-Crepitus in peri respiratory system
BREATHING:
Then: CORRECT (Depends in vignette)
- One side airflow - Re-direct tube
- Crepitus peri resp. - Other way of ventilat.
- Pulse Ox. Low - Other way of ventilat.
- Air outside lungs - Re-diagnose
BREATHING:
Possible causes:
- Bad technique
- Flail chest
- Cardiac tamponade
- Rupture of airway, thorax,
diaphragm or arthery (hemo,
pneumo thorax)
- Under ventilation
Case:
19 y/o unmarried, at term pregnant woman
has a MVA 30 minutes ago. She is able to
answer the anamnesis and is lucid. At the
moment she is crying, and seeks for
companion, she is very worried about the
baby because she doesnt feel movements
anymore and ask for the mother to be called.
Temperature is 37C, Pulse 102m, BP 60 over
40. Fetal signs negative. What is the best next
step?
Case:
19 y/o unmarried, at term pregnant woman
has a MVA 30 minutes ago. She is able to
answer the anamnesis and is lucid. At the
moment she is crying, and seeks for
companion, she is very worried about the
baby because she doesnt feel movements
anymore and ask for the mother to be called.
Temperature is 37C, Pulse 102m, BP 60 over
40. Fetal signs negative. What is the best next
step?
CIRCULATION:
What to check?
-History of profuse bleeding
-Hypotension
-Pale, cool, clammy skin
-Delayed capillary refill
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CIRCULATION:
What to check?
-History of profuse bleeding
-Hypotension
-Pale, cool, clammy skin
- Dry mucosas (Tounge, no tears)
- Depresed fontanelles (children)
-Delayed capillary refill
CIRCULATION:
Then: Restore volume ASAP
1.Two IV lines (16-Gauge)
2. Plenty liquids:
Ringer lactate
Normal saline
Blood
3. If not enough, third line in
saphenous vein
4. Children <4y/o Intraosseus in tibia
or frontal
CIRCULATION:
Then: Control of hemorrhage
- Direct pressure
- Clamping artery
- Curettage if obstetric
CIRCULATION:
Possible causes:
- Trauma in abdomen or thorax (not in
cranium, not enough space to cause
shock)
- Bleeding (obstetric, big wounds)
- Dehydration (deprivation)
- Hyper urination (DI, diuretic overuse)
SHOCK
DUE TO SKIN
CO SVO2 SVR PCWP
SEPTIC BACT.
TOXIN
WARM HIGH HIGH LOW LOW
VOLUME BLEEDING
LIQ. DEP
PALE
COLD
LOW LOW HIGH LOW
CARDIO HYPO
MOTILITY
PALE
COLD
LOW LOW HIGH HIGH
NEURO VAGAL
REFLEX
WARM LOW LOW LOW LOW
CO: Cardiac Output
SVR: Sistemic Vascular Resistance
SVO2: Systemic Venous Oxigen
PCWP: Pulmonary Capilary Wedge Pressure
GENERAL:
1) All Trauma Patients: CS, Chest, Pelvic XR
2) If unstable, proceed to laparotomy
3) If abdomen cannot be examined: CT scan
of abdomen and pelvis w/ oral and IV
Contrast
4) Gunshot in abdomen: Laparotomy
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BEST WAY ORGANIZATION:
From HEAD TO TOES
EPIDURAL HEMATOMA:
- Bleeding between skull bone and
dura mater
- Rupture of Middle Meningeal Artery
- PROGRESSION:
- Unconciusness
- Lucid interval
- Coma
EPIDURAL HEMATOMA:
- Anisocoria
- Bi-concave hematoma
- Tx:
1. After trauma, only image
w/o symptoms at all: OBSERVATION
2. Symptoms & Immage:
EMERGENCY SURGERY
EPIDURAL HEMATOMA: SUBDURAL HEMATOMA:
-Bleeding between dura mater and
arachnoides
- Rupture of veins crossing subdural
space Bridging veins
- Image: Concave hematoma
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SUBDURAL HEMATOMA:
- SEEN TYPICALLY IN:
Elderly, demented, alcoholics
- Tx: 1.If small and no symptoms:
OBSERVATION
2. Affect mental status:
SURGERY
SUBDURAL HEMATOMA:
SUBARACHNOID HEMORRHAGE:
- Bleeding between arachnoides and
pia mater.
- MCC: TRAUMA followed by Ruptured
Berry Aneurism (HTN)
- Blood is seen in ventricles and
around brain (NOT IN BRAIN)
SUBARACHNOID HEMORRHAGE:
- MOST SEVERE EVER headache.
- Leaves sequelae like epilepsy,
blindness
- IF VIGNETTE LOOKS FOR Dg:
NEVER USE CONTRAST
SUBARACHNOID HEMORRHAGE:
Tx: If due to anaeurism or AV
malformation, SURGERY
Otherwise: Support, observation or
anti-convulsivats if needed.
SUBARACHNOID HEMORRHAGE:
-No mases
-No ventricules
-Deviation
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INTRACEREBRAL HEMORRHAGE
-Bleeding into brain parenchima
typically in basal ganglia.
-Due to Trauma, HTN, tumor.
- IF VIGNETTE LOOKS FOR Dg:
NEVER USE CONTRAST
INTRACEREBRAL HEMORRHAGE
- Tx: Surgery is reserved for large
bleedings if they are accesible.
INTRACEREBRAL HEMORRHAGE
WHEN DO WE DECIDE FOR
SURGERY IN ANY CASE?
WHEN CT scan OR MRI SHOW
DEVIATION OF MIDDLE
LINE
DIRECT HEAD TRAUMA:
CONSECUENCE:
1
2
3
CONSECUENCE:
- Open or close head injury
- Increased Intracranial Pressure
- Reversible or Irreversible neuronal
damage
- DEAD
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What to do next?
- After ABCs finish PE w/ Glasgow
scale
- Look for signs of Intracranial
Hypertension:
- Decrease in the comma scale
- Anisocoria
- Signs of decerebration
What to do next?
- Elevate head
- Intubate and hyperoxigenate
- Lower CO2
- Mannitol
- Sedation
After stabilization:
- CT scan
- XR of skull (look for fractures)
- If Open Wound (clean and close)
DIFUSE AXONAL INJURY
- High speed injury with stretching or
shearing of brain tissue
- Immage shows petechial hemorrhages in
white matter tracts
- Associated with immediate deep coma,
cerebral edema and elevation of ICP
- High mortality
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DIVIDED IN TWO:
- BLUNT TRAUMA
- PENETRATING TRAUMA
WHAT TO DO IN BLUNT TRAUMA:
- If UNSTABLE: -EXPLORE
Respiratory compromise
Hematoma
Shock
WHAT TO DO IN BLUNT TRAUMA:
- If STABLE: -Look for other symptoms
If patient OK then
REASURANCE
WHAT TO DO IN PENETRATING TRAUMA
- Decide which ZONE is compromised
III
II
I
Necks base to mandibles angle
Mandibles angle to Cricoid
Cricoid to Clavicle
IF ZONE I & III
UNSTABLE:
1)A, B, C always first!
2) Surgical exploration
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IF ZONE I & III
STABLE:
1) Endoscopy of: Respiratory tract
Esophago/Gastro
Artheries
2) Reassurance if nothing found
IF ZONE II
UNSTABLE:
1)A, B, C always first!
2) Surgical exploration
Always explore if
musculocutaneus platysma is
affected
IF ZONE II
UNSTABLE:
Musculocutaneus
Platysma
IF ZONE I & III
STABLE:
1) Endoscopy if hoarseness/hematoma:
Respiratory tract
Esophago/Gastro
Artheries
2) Reassurance if nothing found
PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT
Rib Fracture MCC of injury
Elderly
Fall
History
Pain w/ resp.
Hematoma/open
wound
Costochondral
junction middle
and lower ribs
CXR Pain medication
Flail Chest 4 or more ribs
fractured in 2
places
Major trauma
Caves during
respiration and
bulges in
expiration
CXR Anesthesia and rib
blockage, positive
ventilation and high
oxygen (avoid
barotrauma) surgical
stability not required
Cardiac
tamponade
Liquid between
heart and
pericardium, CA
Trauma, URI
Tachycardia
Hypotension
Pulsus paradoxus
JVD
Echocardiogram Pericardiocentesis,
pericardial window
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PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT
Pericarditis Inflammation of
pericardium
URI
Friction rub
CXR,
echocardiogram,
EKG, CK MB (rule
out MI), ESR very
high
Treat cause, NSAIDS,
pericardiocentesis,
pericardiostomia
Pleuritis
(Pleuresy)
Inflammation of
pleura
URI, CA, LES, RA,
Irritants (asbestos),
Drugs
Stabbing pain
during inspiration
CBC,
thoracocentesis,
CXR, Chest echo
Treat cause, NSAIDS
Tracheal/
Bronchial
rupture
Violent trauma Trauma, gunshot,
infection, object
Cough w/blood
Gas under need
skin of neck, chest
X-rays, CT scan Object: rigid fiber optic
bronchoscopy to
retrieve object
Others: Surgery
if big plus chest tube w/
suction
PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT
Aortic rupture Violent trauma,
deacceleration
Look for wide
mediastinum in
CRX
If CRX not
conclusive and
suspicious is
high, CT scan or
transesophageal
echo
Surgery
Pulmonary
contusion
Violent trauma With flail chest or
rib fracture, but
crackles
CT scan, look for
atelectasia
Fluid restriction and
oxygen. Prolonged
symptoms possible
ARDS
Cardiac
contusion
Violent trauma,
CPR
Abnormalities in
ventricle to
contract
EKG right bundle
branch block)
Sinus tachycardia
Ventricular
dysrhythmia
EKG
Echocardiogram
Supportive
EKG monitorization
PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT
Hemothorax Trauma, CA,
thorax surgery
Respiratory failure
TachycardiaAnxiet
y
CXR
Thoracocentesis
Analysis of fluid
Treat the cause
Stabilize, Stop bleeding,
Thoracic tube,
Pneumothorax Trauma
(spontaneus)
Sudden sharp pain
on respiration,
Tachycardia,
cianosis, nasal
flaring, no air
movement
CXR, ABG Treat the cause, drain
gas w/ needle if
emergency and later w/
thoracic tube
Diaphragmatic
rupture
Trauma, only in
left side
Sounds of bowel in
thorax (left) or no
air in left lung
CXR, Barium
swallow
Surgery
Trachea Expansion Breath Sounds Percussion
Tension
Pneumothorax
Away
Decreased.
Chest may be fixed
in hyper-expansion
Diminshed or
absent
Hyper-resonant
Simple
Pneumothorax
Midline Decreased May be diminished
May be hyper-
resonant. Usually
normal
Haemothorax Midline Decreased
Diminished if large.
Normal if small
Dull, especially
posteriorly
Pulmonary
Contusion
Midline Normal
Normal. May have
crackles
Normal
Lung collapse Towards Decreased May be reduced Normal
PNEUMOTHORAX
CARDIAC TAMPONADE
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14
AORTIC DISECTION BRONCHIAL RUPTURE
DIAPHRAGMATIC RUPTURE
EXPIRATION
INSPIRATION
FLAIL CHEST
ACUTE ABDOMEN: Sudden, severe
abdominal pain that is less than 24
hours in duration
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IMPORTANT POINTS: ALWAYS
1) NPO to reduce risk of aspiration
2) NG tube to decompress abdomen
3) IV hydration/ secure via
4) Analgesia (meperidine)
5) Abdominal X-RAY
LOOK FOR CLUES:
1) How and why of pain, how often
2) Time of iniciation (cronic or acute)
3) Localization and Progresion
4) Irradiation
5) Scale of pain and type
6) AGE, GENDER
PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT
Appendiscitis Inflamation of
apendix, young
people.
Causes:
Inflamation
Fecalith
Parasite
Trauma
Complication:
peritonitis
First periumbilical
and then iliac
fossa (migration)
Tender Mc.
Burneys point,
Rovsings sign,
Obturator sign,
Psoas sign, fever,
anorexia and
vomit
CBC (infection)
Normally clinical,
and only atypical
cases CT scan or
ultrasound to rule
out ectopic
pregnancy or
pregnant ladies
Laparoscopy,
laparotomy
Cholecystitis Due lith in
cystic duct
leading to stasis
Famous FFFs
Pain after fatty
meals radiate to
shoulder
ALK Phos.
Elevation, CBC,
Ultrasound. Best
diagnosis is CT
scan. HIDA if
suspect and
negative US
If acute: surgery
If septic shock:
percutaneus
drainage
If not acute:
elective surgery
PROBLEM SYMPTOM (CLUE) TEST
Biliary colic Cystic duct blocked. Sharp and constant pain
without fever. Negative Murphy's sign.
LFT WNL. Ultrasound
Cholecystitis Cystic duct blocked with infection. Colicky
brief pain at first, then constant pain in RUQ
with fever caused by E coli, klebsiella,
pseudomonas, B fragilis, enterococcus.
Murphy's sign positive.
Increased AST, ALT, AP,
WBC.
Ultrasound
Choledocholithiasis Common bile duct blocked. Colicky pain.
Jaundice.
Increased bilirubin.
Cholangiogram, ERCP
Cholangitis Infection of entire biliary tract. Charcot's triad.
Jaundice and fever
Increased AST, ALT, AP,
bilirubin. Cholangiogram
DIFFERENTIAL DIAGNOSIS
PROBLEM MISCELANEUS SYMPTOM
(CLUES)
TEST TREATMENT
Pancreatitis Peptic ulcer perforation
Alcohol
Neoplasm
Cholelithiasis, CF
Renal Dz
ERCP
Anorexia
Trauma
Infection
Toxins: Prils, HIV, ASA
Incinerations
Scorpion bite
Epigastric pain
radiating to the
back (belt)
Cullens sign:
Periumbilical
Turners sign:
Flanks
High Sens:
Amylase
High Spec:
Lipase
CT Scan
If cyst> 5Cm
Dranaige
If due to
obstruction: ERCP
Pancreatic CA:
Surgery bad prog
Intestinal
Ischemia
Due to Shock, Atrial fib.
Hypercoagulable state
Watershed area SMA and
IMA pancreatic flexure
Bowel
distention, and
bloody diarrhea,
bowel sounds
will be absent
Neutrophilic
leucocitosis (left)
increase amylase.
CT scan Air in
bowel and
inflamation of
watershed area
Surgery
PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT
Diverticuliti
s
Older people w/
diverticulosis becames
inflamed and
perforated(bulging of
colon walldue to
weakness) low fiber diet,
family history.
Left Lowe Q pain,
leucocitosis, fever
CT scan, No
enemas or
contrast
First episode: IV
fluids and
antibiotics
Subsequent:
Surgery
Ectopic
Pregnancy
Prior PID Acute L R or L Q
pain, acute,
maybe shock
(rupture)
localized in area.
Vaginal bleeding,
cullen sign
Positive pregnancy
test, Ultrasound
for evidence
laparoscopy and
laparotomy
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PROBLEM MISCELANEUS SYMPTOM
(CLUES)
TEST TREATMENT
Peritonitis Inflamation of peritoneum
due to perforation
Pain, tenderness
and guarding,
rebound
Complication of
rupture of
viscera
CBC leucocitosis
Plain AXR,
edematous
vicerae, air. Lavage
if doubt
Stabilization with
IV liquids, correct
acidosis and
electrolite
imbalance,
Surgery,
antibiotics broad
spectrum
Volvulus Malrotation of midgut, Bowel
obstruction and
distension and
vomitus. No
passage of
gases, intestinal
silence.
Abdominal X-ray,
upper GI series
Surgery, correct
rotation, if
necrosis resection
of portion.
PANCREATITIS
APPENDISCITIS
CHOLECYSTITIS
PERITONITIS
PELVIC FRACTURE:
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PELVIC FRACTURE:
1) Stabilize patient
2) Military Antishock Trousers
3) Fixate externally
4) If blood loss, Embolize
HAND
HAND:
Sacaphids: Avascular necrosis
Hamate: Rupture of hook, nerve damage
(Ulnar)
HAND:
BOXERS FRACTURE
Tx:
Mild: Immobilize
Severe: Surgery w/ pins
ARM: ARM:
Tx:
- Alignement
- Analgesia
- Close reduction: No complication, no skin break
- Open reduction: Intra-articular fracture is displaced
ORIF Closed reduction was ineffective
Fracture traverses a cancerous lesion
When prolonged immobility
- Surgery: If artery damage is suspected
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- COMPARMENT SYNDROME:
Due to inflamation of tissues
underneed the skin or fascia
Nerve and circulation compression
OPEN THE AREA!
- COMPARMENT SYNDROME:
- GANGRENE:
Infection due to deep entrance of
bacteria to body (diabetic foot, nail)
AMPUTATION!
- GANGRENE:
- OPEN FRACTURES:
1) Clean the area w/ saline and
pressure
2) Verify if nerves or circulations are
intact
3) If < 6 hours, SUTURE AND REDUCT
IN OR
- OPEN FRACTURES:
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- DISLOCATION OF HIP: Shorten leg,
un-anatomical position.
1) Correct position
2) Emergency Reduction
- DISLOCATION OF HIP:
FEVER:
DAYS Famous W LUIDA CAUSE
DAY 1 WIND LUNGS Pneumonia,
Atelectasis
DAY 3 WATER URINE UTI
DAY 5 WOUND INFECTION S. Aureus
DAY 7 WALK DVT
DAY 10 WONDER WHY Abscess
NEUROLOGICAL:
-Hypoxia
ARDS
Post- anesthesia
-Delirium Tremens
-Water intoxication: HypoNA
HyperNA
NEPHROGENIC:
-Post Surgery Urinary Retention
-Hypovolemia
-Clamping of ureter
ABDOMINAL:
- Paralysis of intestine (Ogilvie Synd)
- Adhesions
- Paralytic Ileus due to Anesthesia
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INFECTION:
1)Find the cause with multiple culture
2) Antibiotic Therapy
Do you understand that ABCs always
is first?
Can you do differential diagnosis?
Do you know what to do first?
Do you have a sequence of thinking?
Do you know basically the treatment?
Are you consistent with your thought
process?
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ANTIBIOTICS ANTIBIOTICS
What is an antibiotic? What is an antibiotic?
An agent that inhibits the growth or multiplication An agent that inhibits the growth or multiplication
of, or kills, of, or kills, a a living organism living organism; usually used in ; usually used in
reference to bacteria or other microorganisms. reference to bacteria or other microorganisms.
Who invented them? Who invented them?
Alexander Fleming, in 1928 is the one who Alexander Fleming, in 1928 is the one who
purified PENICILLIN. purified PENICILLIN. THE CAT? THE CAT?
PURE LUCK? PURE LUCK?
Of course not Of course not
Who is the genius? Who is the genius?
OR OR
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BASIC PRINCIPLES BASIC PRINCIPLES
FOR FOR
PHARMACOTHERAPIE PHARMACOTHERAPIE
Learn MOA Learn MOA
Learn SIDE EFFECTS Learn SIDE EFFECTS
Dont kill a mosquito with a gun Dont kill a mosquito with a gun
Cost Cost Benefits law Benefits law
TYPES OF TYPES OF
ANTIBIOTICS ANTIBIOTICS
Cell Wall Inhibitors Cell Wall Inhibitors
P i S h i I hibi P i S h i I hibi Protein Synthesis Inhibitors Protein Synthesis Inhibitors
Metabolite Inhibitors Metabolite Inhibitors
Special Function Inhibitors Special Function Inhibitors
CELL WALL INHIBITORS CELL WALL INHIBITORS
1. 1.-- Penicillin Penicillin
-- Oxa Oxa, , cloxa cloxa dicloxa dicloxa, , nafi nafi-- CILLIN CILLIN
-- Ticarcillin Ticarcillin
-- Aztreonam Aztreonam
2. 2.-- Cephalosporins Cephalosporins
3. 3.- - Carbipenems Carbipenems
4. 4.- - Vancomycin Vancomycin
Where do you get the molds? Where do you get the molds?
1. 1.- -PENICILLINE PENICILLINE 1. 1.--PENICILLINE PENICILLINE
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1. 1.--PENICILLIN PENICILLIN
1. 1.- - Binds to PBP Binds to PBP
22 Disrupt cell wall Disrupt cell wall 2. 2.- - Disrupt cell wall Disrupt cell wall
3. 3.- - Provoke apoptosis Provoke apoptosis
1. 1.--PENICILLINE PENICILLINE
1. 1.- - Binds to PBP Binds to PBP
1. 1.-- PENICILLIN PENICILLIN 1. 1.--PENICILLIN PENICILLIN
2. 2.- - Disrupt cell wall Disrupt cell wall
3. 3.- - Provoke apoptosis Provoke apoptosis
1. 1.--PENICILLINE PENICILLINE 1. 1.--PENICILLIN PENICILLIN
What does it What does it
kill? kill?
Staph. Staph. Aureus Aureus
Staph. Staph. Epidirmidis Epidirmidis
Bacillus Bacillus
Clostridium Clostridium
Staph. Staph. Saprophiticus Saprophiticus
Strep. Strep. Pneumoniae Pneumoniae
Strep. Strep. Pyogenes Pyogenes
Strep. Strep. Sanguis Sanguis
Strep. Strep. Mutans Mutans
Strep. Strep. Agalactiae Agalactiae
Klebsiella Klebsiella
Neisseria Neisseria
Citrobacter Citrobacter
P. P. Auroginosa Auroginosa
H. Influenza B H. Influenza B
Actinomyces Actinomyces israelii israelii
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1. 1.--PENICILLIN PENICILLIN
Or, if you dont remember: Or, if you dont remember:
GRAM GRAM GRAM + GRAM +
Capsulated bacteria Capsulated bacteria
1. 1.-- PENICILLIN PENICILLIN
Side effects: Side effects:
1. 1.-- Typical: Typical: Anemia, Vomiting, Anemia, Vomiting,
Diarrhea Alopecia Photosensitivity Diarrhea Alopecia Photosensitivity Diarrhea, Alopecia, Photosensitivity. Diarrhea, Alopecia, Photosensitivity.
2. 2.- - Special: Special: Allergie Allergie
1. 1.-- PENICILLIN PENICILLIN
Typical side effects: Typical side effects:
D d i f R idl D d i f R idl Due to destruction of Rapidly Due to destruction of Rapidly
dividing cells dividing cells
1. 1.-- PENICILLIN PENICILLIN
Resistance: Resistance:
-- Mutate PBP, so drug cannot bind Mutate PBP, so drug cannot bind
Thi k b d Thi k b d -- Thicker membranes, so drug Thicker membranes, so drug
cannot get in cannot get in
-- Mutate or destroy the drug with an Mutate or destroy the drug with an
enzyme enzyme
1. 1.-- PENICILLIN PENICILLIN 1. 1.-- PENICILLIN PENICILLIN
Oxa Oxa, , Cloxa Cloxa, , Dicloxa Dicloxa, , Nafi Nafi CILLIN CILLIN
1. 1.-- MOA Same as penicillin MOA Same as penicillin
2. 2.- - BULKIER BULKIER -- R R -- Ring Ring
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1. 1.-- PENICILLIN PENICILLIN
What does it mean? What does it mean?
-- Penicillinase Penicillinase cant bind to cant bind to
the R group for being huge the R group for being huge the R group for being huge the R group for being huge
so the antibiotic wont get so the antibiotic wont get
deactivated and will attach deactivated and will attach
PBP PBP
1. 1.-- PENICILLIN PENICILLIN
What do you kill with them? What do you kill with them?
S h S h AA -- Staph. Staph. Aureus Aureus
1. 1.-- PENICILLIN PENICILLIN
Can you kill OTHER gram Can you kill OTHER gram
positives and capsulated positives and capsulated
bacteria? bacteria? bacteria? bacteria?
YES ! YES !
Do you kill them w/ Do you kill them w/ Naficillin Naficillin??
NO ! NO !
1. 1.-- PENICILLIN PENICILLIN
WHY? WHY?
You could use simple You could use simple
penicillin for that penicillin for that penicillin for that penicillin for that
Dont kill a Mosquito with a gun! Dont kill a Mosquito with a gun!
1. 1.-- PENICILLIN PENICILLIN
AMPICILLIN Vs. AMOXICILLIN AMPICILLIN Vs. AMOXICILLIN
1. 1.-- PENICILLIN PENICILLIN
AMPICILLIN Vs. AMOXICILLIN AMPICILLIN Vs. AMOXICILLIN
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1. 1.-- PENICILLIN PENICILLIN
AMPICILLIN Vs. AMOXICILLIN AMPICILLIN Vs. AMOXICILLIN
Ampicillin Ampicillin
80% f d d i d i h P 80% f d d i d i h P 450 450 -- 80% of drug deactivated with P 80% of drug deactivated with P--450 450
Amoxicillin Amoxicillin
-- Gets ACTIVATED with P Gets ACTIVATED with P- -450 450
1. 1.-- PENICILLIN PENICILLIN
AMPICILLIN Vs. AMOXICILLIN AMPICILLIN Vs. AMOXICILLIN
-- Ampicillin Ampicillin: Adults : Adults
-- Amoxicillin: Amoxicillin: Children Children
Liver failure Liver failure
1. 1.-- PENICILLIN PENICILLIN
AMPICILLIN Vs. AMOXICILLIN AMPICILLIN Vs. AMOXICILLIN
A i illi A i illi Cl l i Cl l i Amoxicillin + Amoxicillin + Clavulanic Clavulanic ac.: ac.:
To inhibit B To inhibit B--Lactamase Lactamase
1. 1.-- PENICILLIN PENICILLIN
AMPICILLIN Vs. AMOXICILLIN AMPICILLIN Vs. AMOXICILLIN
MOA SAME MOA SAME MOA: SAME MOA: SAME
SIDE EFFECTS: SAME SIDE EFFECTS: SAME
1. 1.-- PENICILLIN PENICILLIN
AMPICILLIN Vs. AMOXICILLIN AMPICILLIN Vs. AMOXICILLIN
Bugs to kill: Bugs to kill:
GG Gram + Gram +
Capsulated bacteria Capsulated bacteria
E. Coli? E. Coli?
1. 1.-- PENICILLIN PENICILLIN
Ticarcillin Ticarcillin: :
T kill PSEUDOMONA T kill PSEUDOMONA To kill PSEUDOMONA To kill PSEUDOMONA
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1. 1.-- PENICILLIN PENICILLIN
Ticarcillin Ticarcillin: :
WHY? WHY?
1. 1.-- PENICILLIN PENICILLIN
Ticarcillin Ticarcillin: :
WHY? WHY?
1. 1.-- PENICILLIN PENICILLIN
Ticarcillin Ticarcillin: :
P d P d i li ki i li ki Pseudomona Pseudomona is lion attacking, is lion attacking,
so you need a big riffle to kill it so you need a big riffle to kill it
SIDE EFFECS: SAME SIDE EFFECS: SAME
1. 1.-- PENICILLIN PENICILLIN
AZTREONAM: AZTREONAM:
For GRAM For GRAM
S i i l If ld kill S i i l If ld kill Same principle: If you would kill Same principle: If you would kill
a Gram+, then use a smaller a Gram+, then use a smaller
weapon weapon
SIDE EFFECTS: SAME SIDE EFFECTS: SAME
2. 2.-- CEPHALOSPORINS CEPHALOSPORINS 2. 2.-- CEPHALOSPORINS CEPHALOSPORINS
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2. 2.-- CEPHALOSPORINS CEPHALOSPORINS
1st gen
2de gen
+
+
-
-
Cephalexin, cefazolin
Cefuroxime, cefotetan
g
3th gen
4th gen
+
+
-
-
Ceftriaxone, cefotaxime
Cefepime
2. 2.-- CEPHALOSPORINS CEPHALOSPORINS
MOA: SAME AS PNC MOA: SAME AS PNC
SIDE EFFECTS SAME SIDE EFFECTS SAME SIDE EFFECTS: SAME SIDE EFFECTS: SAME
2. 2.-- CEPHALOSPORINS CEPHALOSPORINS 2. 2.-- CEPHALOSPORINS CEPHALOSPORINS
3. 3.-- CARBAPENEMS CARBAPENEMS
THIS IS A BAZOOKA FOR THIS IS A BAZOOKA FOR
TERRORISTS TERRORISTS
IMIPENEM/CILASTATIN IMIPENEM/CILASTATIN
-- To inhibit renal To inhibit renal dihidropeptidase dihidropeptidase
MOA: SAME MOA: SAME
SIDE EFFECTS: SAME SIDE EFFECTS: SAME
$ 450 $ 450 a vial QUID a vial QUID X 10 days X 10 days
4. 4.-- VANCOMYCIN VANCOMYCIN
Inhibits cell wall of ALL GRAM+ Inhibits cell wall of ALL GRAM+
MOA: Inhibit cell wall MOA: Inhibit cell wall MOA: Inhibit cell wall MOA: Inhibit cell wall
mucopeptide mucopeptide formation gen formation gen
DD- -ala ala DD- -ala ala
Resistance: Resistance: mut mut. D . D--ala to D ala to D- -lac lac
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4. 4.-- VANCOMYCIN VANCOMYCIN
RED MAN SYNDROME: RED MAN SYNDROME:
-- Pretreat Pretreat w/ w/ antihistaminics antihistaminics
LOWER INFUSSION LOWER INFUSSION --LOWER INFUSSION LOWER INFUSSION
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
A good business: A good business:
BUY BUY
CC
BUY BUY
AA
TT
EE
LL
LL
30s 30s
50s 50s
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
OR
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
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PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
A good business: A good business:
BUY BUY
CChloramphenichol hloramphenichol
EErithomycin rithomycin
BUY BUY
AAminoglucosides minoglucosides
TTetracyclins etracyclins
EErithomycin rithomycin
((Macrolides Macrolides) )
ccLLindamycin indamycin
LLinezolid inezolid
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
Aminoglucosides Aminoglucosides::
Gentamicin Gentamicin amikacin amikacin streptomycin streptomycin --Gentamicin Gentamicin, , amikacin amikacin, streptomycin , streptomycin
--MOA: Inhibit Initiation complex MOA: Inhibit Initiation complex
--Bactericidal Bactericidal
--Potentiation Potentiation w/ w/ampicillin ampicillin
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
Aminoglucosides Aminoglucosides: (CONT.) : (CONT.)
SIDE EFFECTS: SAME SIDE EFFECTS: SAME -- SIDE EFFECTS: SAME SIDE EFFECTS: SAME
-- PLUS: PLUS: Ototox Ototox and and Nephrotox Nephrotox
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
Tetracyclins Tetracyclins::
--Doxicycycline Doxicycycline: Lyme, Tularemia, : Lyme, Tularemia,
Francicella Francicella ((Fecally Fecally excreted) excreted) Francicella Francicella ((Fecally Fecally excreted) excreted)
--Minocycline Minocycline: : Propionebacterium Propionebacterium Acne Acne
(Not even excreted) (Not even excreted)
--Demeclocycline Demeclocycline: SIADH ( : SIADH (Neprotox Neprotox))
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
Tetracyclins Tetracyclins: (CONT.) : (CONT.)
MOA I hibi i h bi di f MOA I hibi i h bi di f --MOA: Inhibiting the binding of MOA: Inhibiting the binding of
aminoacyl aminoacyl--tRNA tRNA to the to the mRNA mRNA- -
ribosome ribosome complex. complex.
--Bacteriostatic Bacteriostatic
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
Tetracyclins Tetracyclins::
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PROTEIN YNTHESIS PROTEIN YNTHESIS
INHIBITORS INHIBITORS
Tetracyclins Tetracyclins::
SIDE EFFECT SIDE EFFECT SIDE EFFECT: SIDE EFFECT:
IMAGINE.Plus: IMAGINE.Plus: Ototox Ototox Nephrotox Nephrotox
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
Chloramphenichol Chloramphenichol: :
-- MOA: Inhibit peptide bond at 50s MOA: Inhibit peptide bond at 50s
I hibi P I hibi P 450 450 -- Inhibit P Inhibit P--450 450
-- NOT IN USA NOT IN USA
-- SIDE EFFECTS: SAME SIDE EFFECTS: SAME
Plus: BM Sup. A. Anemia, Plus: BM Sup. A. Anemia, GBSynd GBSynd..
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
Erithromycin Erithromycin: MACROLIDES : MACROLIDES
-- Clarithrmomycin Clarithrmomycin, , azithromycin azithromycin
I hibi l i b ibl I hibi l i b ibl -- Inhibit translocation by reversibly Inhibit translocation by reversibly
binding to 23s portion of 50s. binding to 23s portion of 50s.
-- Bacteriostatic Bacteriostatic
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
Erithromycin Erithromycin: MACROLIDES (CONT.) : MACROLIDES (CONT.)
-- Tx Tx for: Atypical pneumonia for: Atypical pneumonia
((Mycoplasma Mycoplasma) Chlamydia 2g N ) Chlamydia 2g N ((Mycoplasma Mycoplasma), Chlamydia 2g, N. ), Chlamydia 2g, N.
Gonorhea Gonorhea 1g. ( 1g. (azithromycin azithromycin) )
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
cLindamycin cLindamycin: :
-- MOA: Inhibit elongation factor of MOA: Inhibit elongation factor of
50s 50s 50s 50s
-- Uses: Anaerobes above Uses: Anaerobes above diapragm diapragm
-- SIDE EFFECTS: SAME SIDE EFFECTS: SAME
Plus: (before) No1. for Pseudo. Colitis Plus: (before) No1. for Pseudo. Colitis
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
Linezolid Linezolid::
-- MOA: Inhibit initiation of 50s AND MOA: Inhibit initiation of 50s AND
30s 30s 30s 30s
-- MRSA w/ resistance to MRSA w/ resistance to Vanco Vanco
-- DONT USE IT...Like pressing the DONT USE IT...Like pressing the
RED BUTTON RED BUTTON
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PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
cLindamycin cLindamycin: :
-- MOA: Inhibit elongation factor of MOA: Inhibit elongation factor of
50s 50s 50s 50s
-- Uses: Anaerobes above Uses: Anaerobes above diapragm diapragm
-- SIDE EFFECTS: SAME SIDE EFFECTS: SAME
Plus: (before) No1. for U. Colitis. Plus: (before) No1. for U. Colitis.
METABOLITE METABOLITE
INHIBITORS INHIBITORS
To destroy nucleotides: To destroy nucleotides: To destroy nucleotides: To destroy nucleotides:
What is a nucleotide? What is a nucleotide?
To destroy nucleotides: To destroy nucleotides:
SS--ADENOSYL ADENOSYL--METHIONINE (SAM) METHIONINE (SAM)
Methilate Methilate or differentiate the nucleotides or differentiate the nucleotides
All of them. All of them.
Except: T ( Except: T (thimidine thimidine) who is ) who is methilated methilated Except: T ( Except: T (thimidine thimidine), who is ), who is methilated methilated
by Folic Acid by Folic Acid
To destroy nucleotides: To destroy nucleotides:
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To destroy nucleotides: To destroy nucleotides:
dUMP dTMP
Thymidylate synthase
5-FU
CH2-THF
DHF
THF DHF reductase
TMX/SMX
OR MTX
METABOLITE METABOLITE
INHIBITORS INHIBITORS
TRIMETHOPRIM TRIMETHOPRIM
MOA: Inhibit DHF MOA: Inhibit DHF MOA: Inhibit DHF MOA: Inhibit DHF
Works?....Not at allAlone Works?....Not at allAlone
METABOLITE METABOLITE
INHIBITORS INHIBITORS
SULFONAMIDES SULFONAMIDES
MOA: Inhibit MOA: Inhibit Dihydropteroato Dihydropteroato MOA: Inhibit MOA: Inhibit Dihydropteroato Dihydropteroato
synthetase synthetase
Works?....Not at allAlone Works?....Not at allAlone
METABOLITE METABOLITE
INHIBITORS INHIBITORS
BUT:TMX + SMX BUT:TMX + SMX
Good for: UTI, Prof and Good for: UTI, Prof and tx tx of of
Pneumocystis Pneumocystis Carinii Carinii, , Shigella Shigella
and Salmonella. and Salmonella.
METABOLITE METABOLITE
INHIBITORS INHIBITORS
METABOLITE METABOLITE
INHIBITORS INHIBITORS
SIDE EFFECTS: SAME SIDE EFFECTS: SAME
The same as B9 The same as B9 defficiancy defficiancy The same as B9 The same as B9 defficiancy defficiancy
-- Neural pores non Neural pores non--fusion fusion
-- Megaloblastic Megaloblastic anemia anemia
-- Kernikterus Kernikterus in neonates in neonates
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SPECIAL FUNCTION SPECIAL FUNCTION
INHIBITORS INHIBITORS
Topoisomerase
SPECIAL FUNCTION SPECIAL FUNCTION
INHIBITORS INHIBITORS
QUINOLONES: QUINOLONES:
MOA:Antitopoisomerase MOA:Antitopoisomerase II II
Inhibit Winding Inhibit Winding unwinding unwinding Inhibit Winding Inhibit Winding-- unwinding unwinding
SPECIAL FUNCTION SPECIAL FUNCTION
INHIBITORS INHIBITORS
NAMES: NAMES:
Cipro Cipro
LLLevo Levo
Gati Gati
Nor Nor
FLOXACIN FLOXACIN
SPECIAL FUNCTION SPECIAL FUNCTION
INHIBITORS INHIBITORS
SIDE EFFECT: SIDE EFFECT:
Besides typical: Besides typical:
T d i i d T d i i d -- Tendonitis or tendon rupture Tendonitis or tendon rupture
-- Myalgia Myalgia in kids in kids
SPECIAL FUNCTION SPECIAL FUNCTION
INHIBITORS INHIBITORS
METRONIDAZOLE: METRONIDAZOLE:
MOA: Free radicals and toxic MOA: Free radicals and toxic
metabolites formation. metabolites formation.
SPECIAL FUNCTION SPECIAL FUNCTION
INHIBITORS INHIBITORS
METRONIDAZOLE: METRONIDAZOLE:
CC M l l M l l ii Covers: Covers: Monocelular Monocelular parasites: parasites:
G. G. Lamblia Lamblia, E. , E. Hystolitica Hystolitica, G. , G.
Vaginalis Vaginalis, anaerobes below , anaerobes below
diapragm diapragm. T. . T. Terapie Terapie H. Pylori. H. Pylori.
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ANTI TB DRUGS ANTI TB DRUGS
RRIFAMPIN: IFAMPIN: MOA:Inhibit MOA:Inhibit
DNA dependent RNA DNA dependent RNA
pol merase Crosses BBB pol merase Crosses BBB polymerase, Crosses BBB. polymerase, Crosses BBB.
PROF. TB and N. PROF. TB and N. Menigitidis Menigitidis
SIDE EFFECT: SIDE EFFECT: Hepatotoxic Hepatotoxic
((Frecuent Frecuent LFT) LFT)
ANTI TB DRUGS ANTI TB DRUGS
RRIFAMPIN: IFAMPIN:
Enhances P Enhances P--450 450
Orange body fluids. Orange body fluids.
ANTI TB DRUGS ANTI TB DRUGS
EEthanbutol thanbutol:: MOA: Obstructs MOA: Obstructs
cell wall formation by disrupting cell wall formation by disrupting
arabinogalactan arabinogalactan s nthesis s nthesis arabinogalactan arabinogalactan synthesis, synthesis,
increases permeability of cell increases permeability of cell
wall. wall.
ANTI TB DRUGS ANTI TB DRUGS
EEthanbutol thanbutol::
SIDE EFFECT: SIDE EFFECT:
--Optic neuritis Optic neuritis
--Red Red- -green color blindness green color blindness
--Peripheral neuropathy Peripheral neuropathy
--Arthtalgia Arthtalgia
ANTI TB DRUGS ANTI TB DRUGS
SStreptomycin: treptomycin: Aminoglucoside Aminoglucoside
ANTI TB DRUGS ANTI TB DRUGS
PPyrazinamide yrazinamide: : MOA: Stops TB MOA: Stops TB
growth by, growth by, in acid media in acid media, ,
ihibiting ihibiting enzime enzime fatt acid fatt acid ihibiting ihibiting enzime enzime fatty acid fatty acid
synthetase synthetase. .
SIDE EFFECTS: SIDE EFFECTS: Arthralgia Arthralgia, ,
hepatotoxicity hepatotoxicity..
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ANTI TB DRUGS ANTI TB DRUGS
IIsoniazid soniazid:: MOA: Inhibit MOA: Inhibit
synthesis of synthesis of mycolic mycolic acid. acid.
hh 4 0 4 0 Enhances P Enhances P--450. 450.
SIDE EFFECTS: SIDE EFFECTS: Hemolys Hemolys in in
G6PD pts, G6PD pts, hepatotoxicity hepatotoxicity, ,
neurotoxicity that can be neurotoxicity that can be
prevented w/ B6. prevented w/ B6.
ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
Amphotericine Amphotericine B: B:
MOA : Binds to MOA : Binds to ergostyerol ergostyerol and and
pokes the cell wall provoking pokes the cell wall provoking pokes the cell wall provoking pokes the cell wall provoking
leakage of leakage of electrolites electrolites. .
ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
Amphotericine Amphotericine B: B:
Used in systemic mycosis Used in systemic mycosis
SIDE EFFECTS H i SIDE EFFECTS H i SIDE EFFECTS: Hypotension, SIDE EFFECTS: Hypotension,
fever and chills, fever and chills, flebitis flebitis if IV if IV
ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
Nystatin Nystatin: Same as : Same as Amphotericine Amphotericine B B
SIDE EFFECTS O l d SIDE EFFECTS O l d ll SIDE EFFECTS: Only used SIDE EFFECTS: Only used topycal topycal
for being very toxic. for being very toxic.
ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
Nystatin Nystatin: SWISH AND SWALOW : SWISH AND SWALOW
For oral For oral candidiasis candidiasis..
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ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
Caspofungin Caspofungin: Disturb integrity of : Disturb integrity of
Cell Wall Disruption. Cell Wall Disruption.
Indication: Indication: Aparagillosis Aparagillosis Indication: Indication: Aparagillosis Aparagillosis
Side effects: Increase Side effects: Increase Crea Crea, ,
hypokalemia hypokalemia, hypersensitivity , hypersensitivity
ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
Caspofungin Caspofungin::
ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
Azoles: Azoles:
--Flucon Flucon
KK --Ketocon Ketocon
--Itracon Itracon
ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
Azo AzoLE LEss::
MOA: Prevent conversion of MOA: Prevent conversion of
LLanosterol anosterol to to EErgosterol rgosterol by by LLanosterol anosterol to to EErgosterol rgosterol by by
inhibiting fungal P inhibiting fungal P- -450. 450.
FUNGISTATIC! FUNGISTATIC!
ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
Terbinafine Terbinafine::
MOA: Inhibit MOA: Inhibit Squalen Squalen epoxidase epoxidase
USES USES O i i O i i USES: USES: Onicomycosis Onicomycosis
Bad cases: ORAL Bad cases: ORAL
ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
AZOLES AND TERBINAFINE AZOLES AND TERBINAFINE
Azoles
Terbinafine
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ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
Flucytosine Flucytosine: :
MOA: MOA: 1) Inhibit microtubules 1) Inhibit microtubules
2) Inhibit 5 2) Inhibit 5--FU FU
Consequence: Inhibit DNA Consequence: Inhibit DNA Synt Synt
ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
Flucytosine Flucytosine: :
Side Side effecs effecs: Typical very strong : Typical very strong
Plus: Hallucinations, Plus: Hallucinations, psycosis psycosis, ,
peripheral peripheral neuropathie neuropathie. .
ANTIFUNGAL ANTIFUNGAL
THERAPY THERAPY
IN ONE GRAPH: IN ONE GRAPH:
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Biochemistry
Glycolysis, Gluconeogenesis
&TCA
Mong-Khanh Le, M.D.
Objective
Glycolysis
Sucrose metabolism
Lactose metabolism
Gluconeogenesis
TriCarboxylic Acid Cycle (TCA)
Focus
Naming enzymes
Where it happens: cytosol vs mitochondria
energy usage and production
Regulations
Clinical significant Dzs
Connections!!!! AS ALWAYS
Why Glycolysis?
Most used pathway in body
Turn food into energy
Start w/ Glu, Lactose, Fructose
Simple Vs Complex Carbo Simple Vs Complex Carbo
Substrate = Glu and production = pyruvate
In cytosol (what does not have Mito will
depend solely on it for ATP!!!!)
Organ effected: RBC, B>>H>>K
What is in our diet
USDA % in Diet Converting
in Calorie
Pathways
Carbohydrate 55% 4Kcal/g Glycolysis
P t i 15% 4K l/ TCA U Protein 15% 4Kcal/g TCA, Urea
Lipid 30%(<10
% sat)
9Kcal/g FAsyn, B-
oxidation
Alc ?????? 7Kcal/g TCA,
Lactate
Name Enzymes Review
Substrate=1
st
name
What was done to substrate= 2
nd
part or
l t last name
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Name Enz (cont)- Move around
Isomerase= create isomer, think Fructose
and Glucose
Epimerase= make epimer, differs around 1
chiral C (glugalactose) chiral C (glugalactose)
Mutase= move P fr one C to another C
Transferase= move sidechain fr 1
substrate to another (interchain)
Name Enz (cont)-Add stuff
Kinase= use ATP to add P, Mg cofactor.
Phosphorylase=Use free P adding to
substrate.
Carboxylase= uses CO2 to add C uses Carboxylase uses CO2 to add C, uses
ATP and Biotin.
Synthase= 2 substrates consumed in
reaction, named after product.
Synthetase= 2 substrates consumed.
Need ATP
Name Enz (cont)-remove stuff
Dehydrogenase= take out H+ with
coFactor (ie. Tender Loving Care For
Nancy).
Phosphatase= breaks phosphate bond Phosphatase= breaks phosphate bond
Hydrolase= break a bond with H2O
Lyase= cut C-C bond with cofactor
Thio= breaks S bond
B-compx
Tender Loving Care For Nancy.
PLAN F.
Dzs.
Glycolysis
Substrates=Glu and end products of
Sucrose and Lactose pathways (also fr
glycerol)
Final product: Pyruvate Final product: Pyruvate
9 steps
3 irrversible steps= Exclusive glycolysis
Triangle at mid way (4
th
reaction)
Glu Transport
GLU 1 & 3: basal uptake most cells.
GLU 2: Storage (liver); Glucose sensor (B-
islet)
GLU 4 i b INSULIN i f t d GLU-4: increase by INSULIN in fat and
muscle. Increase in exercising skeletal
muscle. (Fat, skeletal and heart)
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Glycolysis Glycolysis Regulations
HK: Most Tissues, low Km= works both in
fed and fast. Inhibited by its own product,
G-6-P.
GK: Liver only, High Km=works during fed
only. +++ by insulin
Why Glu has to be phospholation?
PFK-1
Rate Limiting Step
Stimulated by: AMP, F-2,6-BP, Insulin
(FIA) (FIA)
Inhibited by: Citrate, ATP, PEP, Glucagon,
Acidosis (the GA CAP).
PKF-2
Fruct-6-P to F-2,6BP fed state
F-2,6BP to Fruct-6-P fast state
Increases glycolysis
Decreases gluconeogenesis
Stimulated by Insulin
Inhibited by Glucagon
PK
Stimulated by: F1,6-P, Insulin (FI)
Inhibited by: Glucagon Alanine Inhibited by: Glucagon, Alanine,
cAMP, ATP, AcetylCoA (GA AAA)
Glycolysis Regulations Recap
Enzymes Stimulated Inhibited Comments
HK G6P
PFK-1 *AMP
*F-2,6-P
Citrate, ATP
PEP, Glucagon,
RLS
*Insulin
lowPH
Pyruvate
Kinase
*F1,6-P(feed
forward
pos=only
one in
Biochem)
*Insulin
Alanine,
Glucagon,
cAMP, ATP,
AcetylCoA
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Glycolysis Dz=Chronic Hemolysis
Chronic Hemolysis dt RBC lacks of energy fr
glycolysis.
PK Def. leads to elev 1,3BPG, which can
convert to 2,3BPG.
O hift t R (i K d Oxygen curve shift to R (incr Km, decr
Affinity).
Also elevate other glycolytic intermediates in
RBC (inhibition to many steps)
No Heinz bodies
AR
Glycolysis Dz: MODY
Mature Onset Diabetes of the Young:
Liver (= GK)
Glucokinase mutations leads slow down
l l i Pl Gl i d glycolysis. Plasma Glu increased.
Other Glycolysis Dz
Arsenate inhibits Glyceraldehyde-3-P
dehydrogenase
Fl id i hibit E l Shi hit Fluoride inhibits Enolase: Shiny white
teeth
Other Glycolysis Dz
Phosphoglycerate kinase inhibited:
increase 1,3-BPG, which converted to 2,3-
BPG by RBC mutasedecrease Hb
affinitive for O2 (shift to R incre Km) affinitive for O2 (shift to R, incre Km)
Other Glycolysis Dz
Glyceraldehyde-3-P: has disulfide bonds
which can be disrupted by Alc.
Also Mercury can inhibit sulfur group of
(b i l kid ) enzyme (brain, lung, kidney)
Other Glycolysis Dz
ANY glycolysis enz def= HEMOLYSIS
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Glycolysis Connections
In anaerobic state, production of lactate
and NADH reoxidized back to NAD+.
In RBC (no mitochrondria)turns to LDH
solutionLactate pathway solutionLactate pathway.
What are 3 enz exclusively from
glycolysis?
Net fr 1 Glu= 2 pyruvate + 2ATP +2NADH
Sucrose/Fructose Metabolism
Fruits
3 reactions
End products: Glu, DHAP, GA3P
Continues with Glycolysis after trio Rx
Fructose Fructosuria
Essential Fructosuria: FructoKinase Def-
polydipsia, polyuria, and UTI. BENIGN.
Fructose Intolerance: Aldolase B def.- Fructose Intolerance: Aldolase B def.
fructosuria, liver and proximal renal tubular
disorder.
When Fruc-1-P accumulated, it inhibits Glu
production causing severe Hypoglycemia.
Point Upon Wonder
Why Fructose Intolerant Pt has
hypoglycemia when we give them
fructose?
Why DM can eat fruit without increase Why DM can eat fruit without increase
their plasma Glu?
Why diet people can eat lots of fruit w/o
gain wt?
Lactose/Galactose
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Galactose Recap
End with: Glu-1-P and Glu. Both feed into
Glycolysis
Uses 1ATP
4 ti 4 reactions
Enzymes: lactase, GK, G-1-P UT
Lactose Intolerant
Latase Defieciency
Osmotic diarrhea
Bloated, pain
Rx: AvoidSoy milk or Latase added
milk.
Type 1 Galactosuria
Type 1 (Non Classical)
Galactokinase def.
Galactosemia<< galactosuria (polydip &
l i ith UTI!!!!) polyuria with UTI!!!!).
Excess converted to Galactitol via aldose
reductase causes cataract.
Rx: avoid
Type 2 Galactosemia
Type 2 (Classical) Galactosemia
Gal-1-P Uridyl transferase Def.
Increase Gal-1-P will inhibits P-Glu Mutase,
which interferes with glycogen syn and
d d ti H l i degradationHypoglycemic.
Excess converted to Galactitol via aldose
reductase causes cataract.
More severe addition to above. Vomit/diarrhea/
liver/ lethragy/ MR.
Rx: avoid
Clinic Test
Glu has OH which can be reduced for a
positive test in cases of excess Glu
Galactosuria and Fructosuria are urine pos
test test
If stool pos test = malasorption, osmotic
diarrhea or inflammation
Also called reducing substance
Galactose Connections
Babies need a lot of milk (rich lactose)
because of baby uncoupling its ECT.
UDP-Gal can reenter the pathways
If lactose intolerant: Soy milk
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Point upon wonder
Why galactosemia Type 2 pt has
hypoglycemia when we give them lactose?
C i G l t h F t Comparing Galactose, why Fructose can
be given to baby at 6 months?
Gluconeogenesis
A de novo synthesis of Glu from 3C and
4C precusors.
4 irreversible steps
In both Mitochondria and Cytoplasm In both Mitochondria and Cytoplasm.
Occur during fasting state, glycogen
depleted.
Mainly in Liver, Kindney, Adrenal Cortex
and intestinal epithelilium.
Provide Glu to brain and RBC.
Gluconeogenesis
Substrates are:
glucogenic aa (protein fr muscle)
Lactate (fr RBC and anaerobic exercise)
Glycerol 3 P (fr adipose tissue/
triacylglycerol)
Product: Glu
Regulation of Glyconeo.
Pyruvate carboxylase
=RLS*******
+ Acetyl CoA *Anapleurotic enz.
*Biotin
*mitochodria
PEPCK + Glucagon
+ Cortisol
*GTP
*cytosol
F 1,6- BisPtase + ATP
- AMP
- F-2,6-BP (fr PFK2)
*Cytosol
* inhibited by insulin,
stim by glucagon.
G6Ptase *In ER; liver only.
(other tissue Glu with P
grp prevent Glu exit cell)
Gluconeogenesis Von Gierke: G6Ptase deficiency
severe fasting hypoglycemia
Lactic acidosis
HyperLipidemia
Hyperuremia
short stature
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Malate shuttle
To bring NADH (product fr glycolysis) into
mitochondria/ETC
T b i OAA (f t OAA) i t To bring OAA (fr pyruvateOAA) into
cytosol for gluconeogenesis
Malate shuttle
Viral Hepatitis vs. Alc Hepatitis
Viral = lyses/ effects cell membrane
AST to ALT is 1:1
Alc = Lyses/effects cell mb and
mitochondria mb
AST to ALT is 2:1
Pyruvate D.H. Complex
PyruvateAcetyl CoA (Pyr D.H./ B
complex)
P t OAA (PC i i it h d i PyruvateOAA (PC is in mitochondria
matrix, not in muscle)
Inhibited by: ATP, NADH, Acetyl CoA
B complex=PLAN F
B1= TTP- decarboxylase
B5=Lipoic acid- accepts acetyl grp
B4=CoA- final acetyl aceptor
B3=NAD- oxidizes FADH2NADH
B2=FAD- oxidizes Lipoic acidFADH2
DZs!!!!!!
Why TCA???
Intermediates in fasting/ liverGlu
Intermediates in fedFatty Acid
Intermediates also use for syn AA or
converting one AA to another
Potentiate ATP product per Glu eat in!!!
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TCA
In mitochondria
Cindy Is Kind So She Feeds Many
O h Orphans
4 irreversible steps
TCA
TCA Regulation
Enzymes Stimulated
by
Inhibited by Comments
Citrate
Synthase
ATP
Isocitrate
D.H.
ADP ATP
NADH
Major RLS
Alpha KG
D.H.
Succinyl CoA
ATP
NADH
B complex
RLS
Link to other pathways
MalateGluconeogenesis
CitrateFA synthesis
Oxaloacetate and Alpha-KGAA
th i (Gl t t /GABA!!!!) synthesis (Glutamate/GABA!!!!)
Succinyl CoAHeme Synthesis
Fumarateurea cycle
Alpha KGall transaminases AST & ALT
TCA Recap
In mitochondria= aerobic
Substrate: 1 Acetyl CoA + 3NAD + FAD
GDP Pi +GDP + Pi
Product: 2 CO2 + 3NADH + FADH2 +GTP
+ CoA
Net of 1 cycle of 1 Acetyl CoA= 12 ATPs
TCA Connections
No specific Dzs
Problem with TCA is a major low energy
state
N ATP No ATP
No Glu, AA, FA
No intermediates to other linked
pathways
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Summary 5 pathways
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525
526
527
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