Buzz word Volume overload Presure overload Labl excrescences Brown atrophy Signs of aging Cardiovascular dysfunction Series

hypertophy Parallel hypertrophy

denition

as you age you develop lliform processes on mitral and aortic valve, probably from small thrombi Lipofuscin deposits in a small heart More picardial fat, lambl e, lipofushin deposits, basophilic degneration Most common failure of the pump, obstruction to ow is atherscleoris, regurgitant ow is murmurs, shunter ow, disorder of cardiac conduction, rupture of the heart or major vessesl Increased lling volume dilates the heart and enhances contractility Systolic dysfunction Diastolic dysfunction Concentric hypertrophy Ventricular hypertrophy Back up of blood in the lungs, poor peripheral perfusion, pulmonary edema, Kerley B lines, heart failure cells (hemosiderin laden macrophages), orthopnea, dyspnea, prerenal azotemia Always characterized by decreased CO and tissue perfusion Left heart failure Congestive hepatomegaly, centrilobular necrosis, cardiac sclerosis, cardiac cirrhosis, congestive splenomegaly, nutmeg livers, ascites, edema of the periphery

Frank starling mechanism Contraction dysfunction Filling dysfunction Pressure overload hypertrophy Volume overload L heart failure

Chf Most common cause of R heart failure R heart failure

Buzz word Chronic cardiac decomposition Congenital heart disease L to R shunts R to L shunts

denition Both R and L heart failure symptoms Sporadic genetic abnormalities, most common trisomy 21 ASD, Patent foramen ovale, VSD, PDA, AVSD Tetrology of Fallot, transposition of the great arteries, persistent truncus arteriosus, tricuspid atresia, total anomalous pulmonary venous connection VSD, membranous Swiss cheese septum Secundum ASD Late cyanosis, initially L to right shunt that becomes R L Hyperplasia before birth, atrophy after PDA Alprostadil, PGE2 Indomethacin Most from Down syndrome VSD, aorta that overrides, right ventricular hypertrophy, pulmonary stenosis boot shaped Good to have PDA or VSD Increased pulmonary blood ow Unequal divisions of the AV canal Pulmonary veins fail to join L atrium Infantile is proximal, adult is distal (to PDA) Hypoplastic left heart syndrome, hypercalcemia, cognitive abnormalities, and facial anomilies (williams-Beuren syndrome), prominent systolic murmur with thrill Most commonly obstructive athersclerosis

Most commmon Most comon ASD Eisenmengers Hyperplasia, atrophy Machinery like murmur Keeps PDA open Closes PDA ASD Tetrology of Fallot Transposition of the great arteries Persistent truncus arteriosus Tricuspid ateria Total anomalous pulmonary venous connection Coarctation of the aorta Aortic stenosis and atresia

Ischemic heart disease

Buzz word 75% blockage 90% blockage Apex, anterior wall of left ventricle and ventricular septum Posterior of septum, base Lateral Dominant cause of IHD Prinzmetal angina Unstable, crescendo angina MI Most common MI Problems with MI 4-12 hours 1-3 days 10-14 days 2 months Most MI STEMI NSTEMI Triphenyltetrazolium chloride stain Extension Myocytolysis Stable angina Unstable angina LAD

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Right coronary or left circumex Circumex Insufcient coronary perfusion relative to demand Vasospasm Precipitated by progressively lower levels of physical activity preinfarction angina Women more likely after menopause estrogen has cardioprotective effect Thrombosed coronary artery Past 20-30 minutes you get cell death Early coag necrosis Yellow tan infarct Collagen deposition Dense collagenous scar Transmural Transmural ST elevation Subendocardial, non ST elevation MI shows up as pale zone, everything else is brick raid Infarcts may expand beyond their borders following the MI, repurfusion injury At periphery of infarct, vaculoar degeneration

Buzz word Contraction bands Troponin CK-MB Ruptures Dressler syndrome Mural thrombus Chronic IHD Sudden cardiac death Systemic Left sided hypertensive heart disease Pulmonary right sided hypertensive heart disease (cor polmonale) of all valve disease Mitral valve stenosis Mitral insufciency Most common valve disease Calcic aortic stenosis Mitral valve prolapse

denition Eosinophilic intracellular stripes, layer of perfused vs dead tissue Rises 2-4 hours, peaks at 48, stays elevated 7-10 Rises within 2-4 hours, peaks at 24, stays elevated 72 hours More common in free wall than septum, 3-7 days Fibrinous pericarditis, following transmural MI Thrombus originates in the heart chamber Usually enlarged and heavy due to LV hypertrophy hearts Most common cause arrhythmia, Long QT or WPW Initially left ventricular hypertrophy then later its hypertension, Most commonly after pulmonary embolism for acute, chronic results from R ventricular hypertrophy secondary to lung diseases Stenosis of aortic and mitral valves Rheumatic heart disease Mitral valve prolapse (myxomatuous degeneration) Calcic aortic stenosis, age related- wear and tear Heaped-up calcic masses within aortic cusps that ultimately protrude through the outow into valsalva Mid systolic click, key histologic change, myxomatous degeneration, most common surgical repair or replacement of mitral valve

Buzz word Rheumatic fever

denition Aschoff bodies, caterpillar cells, pancarditis, verrucae, MacCallum plaques, leaet thickening, commissural fusion and shortening, and thickening and fusion of the tendinous cords, MITRAL VALVE, STREP A, Jones criteria: migratory polyarthritis, pancarditis, subcutaneous nodules, erythema margination of the skin, sydenham chorea (neruo disorder with rapid involuntary movements) Hallmark is vegitations. Most common on previously damaged valves by strep viridans, S auerus most virulent IV drug users, prosthetic valve- epidermidis. Ring abcesses, emboli may be shed from vegitations leads to septic infarcts, subacute endocarditis is less valvular destruction, develop new fever and murmur is IE. Janeway lesions nontender palms or soles, ossler nodes in pulp of digits, retinal hemorrhages roth spots Noninfected/ sterile vegitations in debilitated patients associated with systemic lupus Episodic ushing of the skin, nausea, vomiting, TRICUSPID Thromboembolic complications, infective endocarditis, WARFARIN for life Less than 40% EF Impaired contractility Systolic dysfuncion Alcohol, preggos, sarcoiosis Mural thrombi Naxos syndrome- disorder characterized by arrhymogenic RV cariomyopathy and hyperkeratosis of planar skin surfaces that is associated with mutations in the gene encoding plakoglobin 50-80% EF Impairment of compliance Diastolic dysfunction Hyptertensive heart disease , aortic stenosis Bananna like conguration- bulgin of the ventricular septum into the lumen Myober disarray Harsh systolic ejection murmur

Infective endocarditis

Liebman-sacks endocarditis Carcinoid heart disease Complications of articial valves Dialated cardiomyopathy

Hypertrophic cardiomyopathy

Buzz word Restrictive cardiomyopathy

denition Decrease in compliance, resuling in impaired ventricular lling during diastole Amyloidosis 45-90% EF Rule of 2s failed involution of vitelline duct Imperforate anus Congenital more common males, 2nd-3rd week of life and new onset regurg nonbillious vomitting Congenital agonglionic megacolon, decient migration of neural crest cells, lacks both gut plexuses, RET mutations, rectum always affected usually limited to rectum and sigmoid colon Membranous sac present Upper upper esophageal sphincter Middle of esophagus Lower of esophagus Most common from scarring from GERD Associated with GERD, normally upper esophagus and dysphagia Webs, glossitis, iron decient anemia Similar to webs but circumferential and thicker Present at the distal esophagus Sqaumous to noncilliated columnar with goblet cells Increased tone of lower esophagus sphincter: incomplete LES relaxation, increased LES tone, and aperistalsis, primary=neurons, secondary= chagas

Meckels diverticulum Most common intestinal developmental Pyloric stenosis Hirshbrung disease

Gastrochisis Zenker diverticulum Traction diverticulum Epiphrenic diverticulum Esophageal stenosis Esophageal webs Plummer-Vinson aka Patterson Brown Kelly Esophageal rings aska Schatzki rings A rings GERD Achalasia

Buzz word Esophagitis

denition Mallory-weiss= longitudinal lacerations with vomiting, Boorhave syndrome= distal esophageal rupture (catastrophic) white grey pseudomembranes Hyperemia, more eosinophils, and basal zone hyperplasia. In preggos, obese, alcohol, hiatal hernia High numbers of intraepithelial eosinophils, failure of high dose PPI and absence of acid reux Increased risk of andenocarcinoma, epithelial dysplasia is considered to be a pre-invasion lesion, presence of Goblet cells Rupture is a medical emergency, pt will have portal hypertension and cirrhosis Typically GERD, lower of esophagus, H pylori assosciated with decreased risk of adenocarcinoma More in african americans, middle of esophagus, from alcohol and tobacco; top is cervical, middle is mediastinal or partracheal, lower is gastric and celiac nodes NSAID, H pylori, surface epithelia is intact, presence of neutrophils and active inammation, erosion denotes the loss of the supercial epithelium, concurrent erosion and hemorrhage is termed acute erosive hemorrhagic gastritis Round small, found anywhere Infection with H pylori Associated with over crowding, predominantly antral gastritis, high acid production, virulence: agella, urease, adhesins, toxins. Multifocal atrophic glossitis, intraepithelial neutrophils and subepithelial plasma cells, lymph aggregates: MALT Severe burns Shock

Candiadasis GERD Eosinophilic esophagitis Barret Esophagus

Esophageal varices Adenocarcinoma Sqaumous cell carcinoma

Acute gastritis

Acute gastric ulceration Most common cause of chronic gastritis H pylori

Curling ulcer Stress

Buzz word Cushing ulcer Autoimmune gastritis

denition Increased intracranial pressure Antibodies to parietal cells and intrinsic factor, usually in the body, invasion of lymphocytes and macrophages, decreased acid production (achloyhydria), increased gastrin, neuroendocrine hyperplasia

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BIOCHEMISTRY!!
BUZZ WORD RLS of TCA Energy generation in TCA Increases rate of TCA cycle NADH inhibits Hydrolysis of thioester bond Alphaketoglutarate dehydrogenase DEFINITION Isocitrate to alpha ketoglutarate, isocitrate dehydrogenas NADH after isocitrate, alphaketoglutarate, and succinate GTP after Succinyl CoA, and FADH2 after succinate ADP and calcium on RLS and increase calcium on alpha ketoglutarate dehydrogenase Isocitrate dehydrogenase, alphaketoglutarate and malate degydrogenas From acteyl coA, drives reaction forward Huge enzyme complex made up of 4 parts: E1: aplhaketoacid decarboxylase contains TPP E2: transcyclase containing lipoate, transfers acyl portion E3: dihydrolipoyl dehydrogenase, contains FAD From thiamine, leads to heart failure because alphakeot dyh. Doesnt work and heart relies on a lot of energy from NADH Beta-oxidation of fatty acids, from pyruvate via PDC, and several AA NADH CoQ oxidoreductase Succinate dehydrogenase CoQ Cytochromes Bc1 to oxidase Never reversible 2 ATP per NADH, 1.5 ATP for FADH2, major source of heat Myoclonic epileptic ragged red ber diease, mitochondria have too many cristae, DNA mutations in Lysine tRNA Amount of ADP present

Decreased TPP

Sources of acetyl coA 1st step of ETC 2nd step of ETC 3rd Step of ETC 4th Step of ETC Oxidate phosphorylation Energy yield MERRF ATP synthesis regulated by

BUZZ WORD UPC1 (thermogenin)

DEFINITION Brown fat, activated by FA, transports protons from cytosolic side of inner mitochondrial membrane to back into mitochondrial matrix without ATP generation, it uncouples oxphos which generates heat Release of cytochrome C and other proteins into the cytosol Commitsit to metabolism in the cell Is rst committed step in glycolysis Inhibits hexokinase Rate limiting step, inhibited by ATP and citrate, stimulated by AMP and F26BP Shuttles pyruvate to acetyl coA, inhibited by NADH and Acetyl coA, stimulated by ADP and Ca2+ Pyruvate to lactate, inhibited by ATP, stimulated by F16BP Inner mitochondrial membrane is impermeable to NADH, you need a way to get the energy out, works through DHAP--> G3p which generates FADH2 for ETC Oxaloacetate cannot cross mitochondrial membrane so it becomes aspartate which can. It is a cytosolic reducing equivalent both sides make NADH Increases PFK1c Shuttles lactate and glucose between the liver and peripheral tissues Prevents pyruvate oxidation in TCA cycle and directs pyruvate to lactate Metabolizes ethanol through CYP2E1 P450 Ethanol-->acetaldehyde-->acetate-->acetyl CoA-->TCA cycle Absolute protection against alcoholism, alcoholics are treated with acetaldehyde dehydrogenase inhibitors

Initiation of apoptosis Initial phosphorylation of glucose F6P to F6BP G6P PFK1 Pyruvate dehydrogenase Pyruvate kinase G3P shuttle

Malate-aspartate shuttle

Increased HIF Cori cycle Increased NADH MEOS Breakdown of ethanol Homozygous ALDH2*2

BUZZ WORD ADH1B*2

DEFINITION Very fast ADH, associated with decreased alcoholism because of negative side effects associated with acetaldehyde accumulations CYP2E1, chronic consumption of alcohol increases these levels and the ER undergoes proliferation ADH 1 and ALDH 2 MEOS Yields more energy! Acute viral hepatitis Chronic alcohol induced hepatitis Increased tiacylglycerol leads to FA metabolism, decreases oxaloacetate in TCA cycle leaving it too low to synthesize citrate, increased lactate production which can lead to hypo or hyperglycemia Acetaldehyde-adduct formation with AA leads to decreased protein synthesis which leads to decreased secretion and increased accumulation which draws in water which causes swelling and portal hypertension which disrupts hepatic architecure Acetaldehyde-adduct formation enhances free radical damage because it binds directly to glutathione and prevents it preventing lipid peroxidation which causes uncoupling of ETC Cause liver to shrink and function less which causes loss of synthetic and detox pathways which increases ammonia in the blood, and increases bilirubin accumulation Acetaldehyde activates kupffer cells which causes an increase in ROS and NO, and activated kupffer cells increase production of TGF bet which both stimulate stellate cells which produce extracellular matrix collagen and metalloproteases which cause brosis Precursor for glycogen and lactose

Highest activity for ethanol Drinking a little bit, metabolized by... Drinking a lot, metabolized by Metabolism through ADH AST/ALT>1 AST/ALT<1 Increased NADH:NAD+

Acetaldehyde and alcohol induced hepatitis

Acetaldehyde and free radical damage

Both of the above

Development of hepatic brosis

UDP glucose

BUZZ WORD Dilichol phosphate I Cell Disease Sphingolipids Hexosaminidase A Sandhoff disease apoB48 apoB100 LPL on capillary walls Remnants Orlistat MTP inhibitors

DEFINITION Transfers branched sugar chains to amide of nitrogen of asparagine residues Lysosomal enzymes lack mannose 6P marker that targets them to lysosomes Produced in the golgi Tests for tay sachs, they will have a decreased amount present, accumulate GM2 but nitgloboside Both A and B hexosaminidase are decient same symptoms as tay sachs with an accelerated time table Intestine Liver Responds to APO CII on chylomicron to digest TG to FA and glycerol Take up through recognition of ApoE Drug that blocks action of pancreatic lipase MPT facilitates making larger B particles by adding lipids and TG, without this you have abetalipoproteinemia, right now they have too many bad side effects Reverse cholesterol transport and biogenisis of HDL, moves cholesterol from inner to outer leaet so that HDL can accept it, while LCAT helps the HDL trap the cholesterol HMG CoA to mevalonate 1. Free cholesterol binds to Scap which inhibits SREBP from binding to DNA to stimulate transcription of DNA for HMGCoA reductase gene 2. Cholesterol and bile salts increase proteolysis and degredation of HMGCoA reductase 3. HMGCoA reductase regulated through phosphorylation Cholesterol ester production in the liver

ABCA1

RLS of Cholesterol metabolism Regulation of HMGCoA

ACAT

BUZZ WORD Bile Salt RLS Familial HDL deciency and Tangiers disease Primary clearance of cholesterol esters LDL receptors reconize Scavenger receptors CAH mutation RLS for Steroid Synthesis Aromatase Vitamin D synthesis Metformin

DEFINITION 7 alphahydroxylase, enzyme activity decreased by an increase in bile salts No ABCA1 so HDL is rapidly degraded Scavenger receptor steals esters from HDL then releases HDL to collect more ApoB100 or ApoE Not subject to down regulation so they will take up and oxidize more cholesterol developing foam cells Mutation in 21alphahydroxylase so no aldosterone or cortisol formation CYPIIA: Cholesterol to pregnenalone Formation of estradiol estrone 1alphahydroxylase conversion to calcitriol in the kidney Decreases blood glucose by inhibiting hepatic gluconeogenesis by activating AMPK through