Week 5 (Diseases of Cardiovascular Structures) Flashcards

Question

Type I Familial Hyperchylomicronemia

Answer 1

High **chylomicrons**, high **TG**, high **cholesterol** **Creamy** plasma **AR**, **deficient** in **lipoprotein** **lipase** or altered **ApoCII** (rare) Causes **pancreatitis** (this can kill kids), hepatosplenomegaly, eruptive/pruritic **xanthomas** (no increased risk for atherosclerosis) Treatment is low fat diet (no drug therapy)

Answer 2

High **LDL**, high **cholesterol** **Clear** plasma **AD**, absent or **decreased LDL receptors** Causes accelerated **atherosclerosis**, tendon (Achilles) **xanthomas**, corneal arcus Treatment is low cholesterol and low saturated fat in diet; drug therapy to lower LDL

Answer 3

Similar to IIa but **VLDL** also increased, in addition to **TGs** and **cholesterol** Plasma often **turbid** Caused by **overproduction of VLDL by the liver** Treatment is dietary restriction of cholesterol, saturated fat and alcohol; Drug therapy (maybe target TGs too)

Answer 4

High **VLDL**, **TGs** Plasma turbid **AD**, hepatic **overproduction of VLDL** or **decreased removal** of VLDL TG Causes **pancreatitis** Treatment is weight reduction, dietary restriction of carbs, modified fat, low alcohol consumption; drug therapy More common now because associated with **diabetes**

Answer 5

**Exogenous** (**dietary**) lipid pathway: TG and cholesterol packaged into **chylomicrons** in **epithelial cells of intestines** --\> chylomicrons circulate in **lymph** then get into **blood** --\> **LPL** located on **luminal surface of capillary endothelial cells** releases **FFA** from TGs from chylomicrons to go into **adipose** and **muscle** **cells** --\> chylomicron remnant particles removed from plasma via receptors on the liver **Endogenous** lipid pathway: **Liver** synthesizes TG and cholesterol ester and packages them into **VLDL** to be released into blood --\> **LPL** located on **luminal surface of capillary endothelial cells** releases FFA to be taken up by **adipose** and **muscle** **cells** --\> some VLDL remnants are taken back up by liver via LDL receptor but remaining remnant particles become **IDL** --\> some IDL reabsorbed by liver via LDL receptor but other IDL particles hydrolyzed by hapatic lipase (**HL**) to form **LDL** --\> some LDL taken up by liver via LDL receptor but some LDL is taken up by peripheral tissue cells that have LDL receptors --\> **free cholesterol** is released and accumulates within cells

Answer 6

**Half-life** for clearance of **LDL** is **24 hours** Every day about half of circulating LDL is removed via receptor mediated endocytosis

Answer 7

LDL binds its **receptor** because **ApoB100 on LDL** recognizes the **LDL receptor** on **liver** or **tissue** cells Once bound, entire LDL molecule is **engulfed** by the cell in **clathrin coated** **pits** via **receptor mediated endocytosis** **Endosomes** turn into **lysosomes** and LDL is **degraded**

Answer 8

**Cholesterol absorption inhibitors** (CAIs): 18% decrease LDL, 8% decrease TGs **FIbrates**: 5-20% decrease LDL, 10-35% increase HDL, 20-50% decrease TGs **Niacin**: 5-25% decrease LDL, **15-35% increase HDL,** 20-50% decrease TGs **Resins**: 15-30% decrease LDL, 3-5% increase HDL **Statins**: **18-60% decrease LDL**, 5-15% increase HDL, 7-30% decrease TGs

Answer 9

**HMG-CoA Reductase inhibitors** (statin is a false substrate/competitive inhibitor) Inhibit HMG-CoA to mevalonate Have **shallow dose response curve**, so initial dose is great but doubling the dose thereafter only gives 5-8% increase in efficacy

Answer 10

**Pregnancy category X!!** Think **liver** and **muscle** problems because this is where **cholesterol metabolized** Headache, rash, GI disturbance (dyspepsia, cramps, flatulence, constipation, abdominal pain) **Hepatotoxicity** (d/c med if LFTs more than 3x upper normal limit; check LFTs at baseline, 6 wks then periodically after) **Myopathy** (0.5% of patients) risk highest with lovastatin and especially in combination with fibrates CYP3A4 drug interactions with many statins FDA advice 2012 said new risk of T2DM and cognitive impairment (reversible within a few weeks of stopping drug), **risk to liver was called rare**

Answer 11

Fermented rice product on which red yeast has grown RYR contains several compounds collectively known as **monacolins** **Monacolin K** is an **HMG-CoA reductase inhibitor** and is the same chemical as **lovastatin** (same risks too) Large **variation** in **active** **compounds** in RYR supplements (some supplements contaminated with citrinin, a **nephrotoxic** mycotoxin)--dirty preparation

Answer 12

**Ezetimibe** is the only CAI **Blocks cholesterol absorption** at **intestinal brush border**; localize to the **intestinal** **wall**, enterohepatic circulation, minimal systemic exposure No effect on absorption of lipid-soluble vitamins Indications: high LDL Pros: once daily, **additive** in combination **with statin**, limited systemic exposure, very well tolerated Cons: some systemic exposure, 3-fold increase incidence of **LFT** **abnormalities** in combination with statins, **no outcomes data** Despite **LDL lowering**, Ezetimibe has not been shown to decrease **CV risk** above what is provided by statins so seldom used in monotherapy but may be useful in combination therapy with statins

Answer 13

**Cholestyramine**, colesevelam, colestipol **Bind bile acid** in the **intestines**, interrupting enterohepatic circulation and **increasing** fecal **excretion** of the acid --\> liver **uses more cholesterol** to make more bile acid --\> decrease intrahepatic cholesterol pool --\> causes some **increased HMG-CoA reductase expression**, increased VLDL production/secretion and LDL production, but mostly **increases LDL receptors** to increase LDL clearance from blood and **reduce plasma LDL** **Reduces LDL 20-30%** Indications: high LDL Can be used to **relieve** **pruritis** in pts with cholestasis and/or to relieve diarrhea in post-cholecystectomy patients Used in **children** because **NOT systemic**

Answer 14

Must be taken with **fluid** (dispensed in powder or large tablet form) **Constipation**, **bloating**, indigestion, nausea Large doses may **decrease** **absorption** of fats or **fat soluble vitamins** **Drug interactions** common (decrease drug concentration) so must take other drugs 1 hour before resin or 4 hours after

Answer 15

Appears to **suppress** **synthesis** of **VLDL, IDL** and **LDL** in the liver; may **increase TG catabolism** and **decrease HDL catabolism** (in the kidney), reduces ApoB, increasees ApoA and **increases HDL** **Inhibits lipolysis** in adipose tissue; **reduces hepatic VLDL secretion** into circulation (this is what FA says) Indications: high LDL and/or high TG, combined hyperlipidemia No additional benefit if given with statins, and also small unexplained **increase in ischemic stroke** with niacin May not be used anymore since no benefit shown to pharmacologic elevation in HDL

Answer 16

**Flushing**: harmless cutaneous vasodilation but very uncomfortable, can give aspirin 30 min before dose Pruritis, **rashes**, dry skin **Acanthosis** **nigricans** (velvet warty hyperpigmentation associated with insulin resistance) **Nausea** and abdominal discomfort Peptic disease **Hepatotoxicity**: rare fulminant hepatic necrosis occurs with older OTC sustained release forme **Hyperuricemia** in 1/5 patients that may precipitate gout **Glucose intolerance**

Answer 17

**Gemfibrozil**, clofibrate, bezafibrate, fenofibrate **Agonist of PPAR-alpha** (control **gene** **expression**) to **increase mitochondrial beta oxidation** of FFA and **decrease TG secretion** and to **decrease ApoCIII production** (which usually inhibits TG metabolism) but increase ApoA-V production to **increase TG clearance** --\> all lead to **decreased TGs** **Increase clearance of VLDL** by increasing action of LPL; decrease VLDL production **Increase ApoA1** secretion and **upregulate ABC-A1** to **increase HDL** Indications: high TG and low HDL

Answer 18

**Rashes** **GI upset** **Gallstones** (upper abdominal discomfort, intolerance of fried food, bloating): increased biliary cholesterol saturation, use with caution in patients with biliary disease **Displaces warfarin** from plasma albumin since drug is highly protein bound, so **decrease warfarin dose** to reduce myopathy? Will **increase risk of statin-induced myopathy** when used together (rhabdomyolysis rarely)

Answer 19

**CYP3A4 inducers** (cause decreased activity of statins): **GCs**, **rifampin**, **phenytoin**, **carbamazepine** **CYP3A4 inhibitors** (cause increased blood levels of statins): nefazodone, fluvoxamine, **ketoconazole**, **itraconazole**, **erythromycin**, **sertraline**, **grapefruit juice**

Answer 20

**Protective sac** around the heart Made up of **visceral** (inside; fine, shiny) which goes around heart then reflects back on itself to form **parietal** (outside) layer Contains **5-15 mL of clear fluid**

Answer 21

**Abnormal collection of fluid** in the pericardial space Causes: **pericarditis, hemopericardium, chylopericardium**

Answer 22

**Idiopathic** **Infectious** (viral, bacterial, mycobacterial, fungal) **Autoimmune** (SLE, RA, scleroderma, PAN) **Dressler's syndrome** **Neoplastic** disease (breast, lung, thyroid, lymphoma/leukemia, melanoma) **Uremia** **Hypothyroidism** (leaky capillaries cause pericardial effusion) **Drugs** (INH, procainamide, hydralazine, cyclosporine)

Answer 23

**No** Symptoms depend on **size** of effusion and **rate** of accumulation **Slowly** accumulating effusions initially asymptomatic but **eventually** cause **cough, hoarseness, dyspnea, dysphagia** **Rapidly** accumulating effusions can cause **hemodynamic compromise** (cardiac **tamponade**) with collection of as little as 100mL of fluid

Answer 24

**Increase in pericardial pressure** that **impairs cardiac function** Think of it as **diastolic** **dysfunction**, since increased pericardial **pressure is** so high that the ventricles **cannot fill** so **diminished** **preload** and **decreased stroke volume** Physiologic consequences: **impaired filling** of cardiac chambers, **SV** **declines**, compensatory activation of **sympathetic** nervous system with **tachycardia** and **increased SVR** Often presents as **shock** (obstructive shock), have **muffled heart sounds** due to abnormal layer of fluid around heart **Beck's triad:** low BP, increased JVD, distant/muffled heart sounds Have **pulsus paradoxus** **Echo** findings: **compression of RA and RV** in diastole (because they have less muscle and easier to compress than left side), **increased flow into RV** with **bulging** of **intraventricular** **septum** **into LV** and **decreased LV filling during inspiration**, **IVC distended** and difficulty draining into right heart **Catheterization** findings: **pressure** in atria and diastolic pressure in ventricles **elevated** and **equalized** in **all 4 chambers**, **equal** to elevated **pericardial pressure** Treatment: **volume** **resuscitation**, vasopressors, **pericardiocentesis** (stick needle under xyphoid process directed toward L shoulder to drain fluid), **surgical management**

Answer 25

**Inflammation** of **both** **layers** of pericardium (visceral and parietal) Classic presentation is **sharp chest pain relieved with leaning forward** (keeping inflamed pericardium from rubbing against firm structures including spine behind it), pain may radiate to **left trapezius ridge** **Pericardial rub** on exam (three components: rapid ventricular filling, atrial systole, ventricular systole) sounds like **choo-choo-train**; evanescent and will **disappear** if pericardial effusion separates inflamed visceral and parietal layers so they can't rub against each other **EKG** changes: **diffuse ST** segment **elevation** (often in all leads except aVR and V1), **PR** segment **depression**, **T** wave **inversions**, if large effusion, heart swinging back and forth in effusion can create QRS complexes that increase and decrease in size as it goes to and away from electrodes If thought to be **viral/idiopathic** then treat with **NSAIDs, colchicine** or GCs (rarely, and increase risk of recurrence of pericarditis)--don't need to know what virus it is because no virus-specific therapy For patients with recurrent effusions, consider **pericardial window** (hole in pericardium to let it drain) that provides continuous drainage into pleural or peritoneal cavity where it will be reabsorbed

Answer 26

**EKG** and **echo** **CBC** **Troponin I** **BUN/creatinine** Only if you think necessary: ESR/CRP, ANA, rheumatoid factor, complement levels, thyroid function tests, PPD or quantiferon gold, HIV serology

Answer 27

AKA postmyocardial infarction syndrome Seen **2 weeks to several months** after MI **Autoimmune** mechanism resulting in **fibrinous pericarditis** Low grade **fever**, pleuritic **chest** **pain**, pericardial **friction** **rub** (3 components, with 1 systolic and 2 diastolic) and/or **pericardial** **effusion** Treated with **NSAIDs**

Answer 28

Chronic inflammation leads to **thick** fibrotic or **calcified** pericardium Causes: **tuberculous** pericarditis, **viral** infection, **connective** **tissue** disorders, **radiation**, viral pericarditis where inflammation did not completely respove Chronic inflammatory that develops over **months to years** Symptoms: **abdominal pain**, **ascites**, lower extremity **swelling**, **dyspnea** Physical findings: **Kussmaul** **sign** (paradoxic rise in JVP with inspiration because vena cava accommodates increased fluid but heart doesn't so fluid reflects back into jugular vein), **pericardial** **knock** heard along left sternal border due to abrupt cessation of early, rapid diastolic filling; **no pulsus paradoxus** because RA can't expand to let more fluid in Diagnostic testing: **CXR** for pericardial calcification, **echo** for thickened pericardium with reduced mobility and abnormalities of ventricular septal wall motion, **CT** or **MRI** to look at pericardial thickness, **R heart cath** for **square root sign** of diastolic ventricular pressure curve (top of square root sign is because ventricular pressure stays flat because can't fill any more)

Answer 29

**Inflammation** in **myocardium** **Non-viral infectious** causes of myocarditis: borrelia (**Lyme** disease) which presents as conduction system disorder, trypanosoma cruzi (**Chagas** disease), **trichinosis** (trichinella spiralis) Most comonly associated with **viral** **infections**: **coxsackie B, adenoviruses, parvovirus B19, CMV, HIV** **Symptoms**/signs of viral myocarditis: early sx of acute viral infection (**fevers**, **myalgias**, **fatigue**), sx of **heart failure** several weeks later (tachycardia, hypotension, elevated JVP, S3, crackles, peripheral edema) Labs and imaging: elevated **troponin**, rising **viral titers**, on EKG see sinus tachycardia and nonspecific ST and T wave abnormalities; pericarditis findings if patient has myopericarditis, **echo** to look for enlarging chamber size, **MRI to** look for focal changes in myocardial tissue suggesting inflammation Treatment of viral myocarditis: antivirals and immunosuppressants are not successful, treat pts with decreased EF with **beta blockade, ACEI, aldosterone antagonists** and **diuretics** as needed Prognosis of viral myocarditis: **1/3** patients **recover** **fully**, 1/3 **stabilize** on medical therapy but have permanent decrease in EF, 1/3 **advance** and should be considered for **heart transplantation**

Answer 30

**Cocaine** **Alcohol** Anthracyclines (chemotherapy): **doxorubicin, danorubicin**

Answer 31

Often reaction to a drug: **antibiotics, diuretics, antihypertensives** Path: **eosinophilic** infiltrate in **perivascular** and **interstitial** spaces in the heart

Answer 32

**Iron overload** Heart is **dilated** and **rust-brown** in color Iron deposition is most prominent in ventricles Marked accumulation of **hemosiderin** seen in cardiac myocytes with use of **Prussian blue stain**

Answer 33

Advanced hypothyroidism (**myxedema**) causes heart to be **flabby** and **dilated**

Answer 34

Disorders that lead to **increased myocardial stiffness** Patients present with predominantly **RV failure** (and **LV** failure) **without cardiomegaly** **or** **systolic dysfunction** Causes: **amyloidosis, sarcoidosis, carcinoid heart disease, scleroderma, radiation**

Answer 35

Subtle radiographic manifestations since significant cardiac enlargement uncommon, but **LA enlargement** causes **straightening of L superior cardiac border**, **elevating L mainstem bronchus** and may produce **"double density"** caused by superimposition of ovoid density of increased volume of blood in chamber **LA enlargement** may have **broad and notched P waves** in **V1, II,** or large fibrillatory waves if afib present; **vertical or right axis** in frontal plane due to normal/underdeveloped LV because of diminished inflow, but **pressure-burdened RV** Can get **RV hypertrophy** and thus **increased R wave** in R precordial leads (V1-3?)

Answer 36

The **velocity** of blood and the **pressre** **gradient** between 2 areas (use **4v²** to calculate pressure gradient)

Answer 37

**Murmurs** best heard **downstream** **Valve** clicks/sounds reflect back and are heard best **upstream**

Answer 38

**Higher HR** means **LA pressure increases** because **shortened diastolic emptying period** so LA doesn't have any time to decompress Patient can build up so much pressure they get **pulmonary edema** and cannot breathe Opening snap, mid-diastolic murmur, presystolic murmur and S1 all get **louder** Give **beta blockers** to bring down HR and get LA pressure lower

Answer 39

**RILE** **Right** side murmurs (pulmonic and tricuspid) louder on **inspiration** (increases RA return) **Left** side murmurs (aortic and mitral) louder on **expiration** (increases LA return)

Answer 40

**PCSK9** is an **enzyme** that **eats up LDL receptors** If you're lucky you're born with low PCSK9 and will have tons of LDL receptors and clear LDL from the blood really well **REGN727** (and the drug Shannon is working on!) is an **antibody** that **binds** and **neutralizes** **PCSK9** so it can't eat up LDL receptors --\> **lowers cholesterol** (could be a good new cholesterol-lowering drug!)

Answer 41

**Inflate BP cuff** above pts anticipated systolic BP and **listen for first Korotkoff sound** **At first,** hear Korotkoff sound that is **intermittent** rather than regular, and this is because you **CANNOT** hear sound during **inspiration** because systolic BP during inspiration is lower. This is because when you **inhale**, RA and RV fills more and pushes interventricular septum into **LV** which then has **smaller** size, less preload, **less SV** and thus **lower systolic BP** Bring pressure in BP cuff down more and listen until Korotkoff sounds are regular, **heard** **during** **inspiration** also. If difference between when first Korotkiff sound heard only during expiration and when it is heard during both inspiration and expiration is **more than 10 mmHg**, then have **pulsus** **paradoxus** which is suggestive of **cardiac tamponade**

Answer 42

**MI** and **pericarditis** are **retrosternal** but **PE** can be pain **all over** All are sudden onset **PE** and **pericarditis** are **sharp stabbing pain** but **MI** is elephant on chest, **pressure** Pain **doesn't change with respiration** for **MI**; for **pericarditis** lungs rubbing will cause pain with inspiration and **doesn't completely go away when exhale**; for **PE** if you **hold your breath pain goes away**

Answer 43

**"Broken heart syndrome"** **Catecholamine** surge from acutely traumatic incident can lead to **myocyte** **toxicity** with **apical** **ballooning** of the heart seen on echocardiogram

Answer 44

**Inflammatory** disease of heart, joints, CNS and subcutaneous tissue that develops **after** an infection with Group A beta hemolytic streptococci (**S. pyogenes**) Cumulative long term damage to heart valves from **recurrent ARF** (with preceding strep infection) results in **rheumatic heart disease** (RHD)

Answer 45

**25-40%** of all **CV** **disease** in the world, affecting 15.6 million worldwide **50%** of those who **have** **ARF** develop **chronic valvular damage (RHD)** 2% of Australian Aboriginal population affected RHF occurs most commonly in **ages 5-15**, recurrences also occurring most frequently in this group but can occur into adulthood (but usually occur within first 5 years)

Answer 46

Result of **infection** with a **rheumatogenic** **strain** (M proteins, antigenic subtypes, emm genes have all been implicated) in a susceptible host Triggering specific **T cell activation** and humoral **responses** against epitopes in **myosin** and **laminin** that are similar to Strep M protein (**molecular** **mimicry**)

Answer 47

Mean **latency** after initial infection is **3 weeks** (in **2/3** of cases the initial infection is **asymptomatic**) **Fever** **Polyarthritis** in 50-75% **Carditis** in 40-60%

Answer 48

**Pericardium**: **rub** or **effusion** **Myocardium**: usually **asymptomatic** but can see conduction delays with **prolonged PR interval** **Endocardium**: **new** **murmur**, often mitral, or aortic regurgitation in children; in late **adolescence** **stenotic lesions** common

Answer 49

Marks **acute rheumatic carditis** **Granulomatous** inflammation Aschoff **giant** **cell**: large cell with two or more nuclei with prominent nucleoli Scattered **inflammatory** **cells** accompany Aschoff giant cells

Answer 50

**Migratory**, **asymmetrical**, most commonly **knees, ankles, elbows, wrists** **Painful** **swollen** joints which may contain **sterile** **exudative** **effusions** Responds well to **NSAIDs**

Answer 51

Latency may be as long as **6 months** Predominantly in **females** Involves **arms** and **face** most Associated with **emotional** **lability**, personality change and obsessive/compulsive behaviors

Answer 52

**Positive throat culture** **OR** Elevated or increasing streptococcal antibody titer (**ASO**) **AND** **2 major** or **1 major and 2 minor** manifestations **Major** criteria: **carditis**, **polyarthritis**, **chorea**, **subQ nodules**, **erythema marginatum** **Minor** criteria: **fever**, **arthralgia**, elevated **acute phase reactants**, **prolonged PR**

Answer 53

Treat underlying **strep** with **penicillin** Arthritis and/or mild carditis: **aspirin** 80-100mg/kg for 2 weeks, then reduced doses for 2-4 more weeks **Corticosteroids** no proven benefit, but used to treat **symptomatic** carditis Ensure **secondary** **prophylaxis** to prevent further cardiac damage Likelihood of rheumatic heart disease is associated with severity of acute carditis and recurrent episodes of rheumatic fever **75%** of **recurrences** occur within **2 years** and 90% within 5 years Appropriate **prophylaxis** for **dental** and medical procedures to prevent infectious endocarditis

Answer 54

Treatment of an **initial** **pharyngitis** or skin infection within **9 days** to **prevent** initial episode of **rheumatic fever** Requires access to medical care, and does not prevent ARF in persons with ARF triggered by **asymptomatic** strep infection (2/3 of cases)

Answer 55

**Prevention** of **subsequent strep infections** with: Injections of **IM benzathine penicillin G** (every 3 to 4 weeks) Daily adminitstration of **oral penicillin, sulfadiazine, or erythromycin** For **5 years** after last attack or until age 21, whichever is longer **10 years** after last attack in persons with **residual RHD** and at least until age 40

Answer 56

**Mortality 20-30%** **25%** of cases due to **underlying RHD** in developed countries (used to be 75%?) More **prosthetic** **valve** replacements More **nosocomial** acquisition (**S. aureus** and **S. epidermidis**) \>50% of patients **over 50yo** **Degenerative** **lesions** assuming greater importance especially in persons \>60 More **males** than females

Answer 57

**Native valve** **Prosthetic valve** Special risk factors are **IV drug** use and **nosocomial bacteremia**

Answer 58

1) Portal of **entry** 2) **Transient** **bacteremia** with organisms that can adhere to valves 3) **Turbulent** **flow/abnormal valve** that facilitates adhesion and propagation of the organism and vegetation

Answer 59

**Dental infections/procedures** **Surgical procedures** **Line infections** **Trauma** **IVDU** **UTI** **Pneumonia**

Answer 60

**Streptococci** 55-68% **Staphylococcus** 20-35% Enterococci 5-18% Other bacteria (HACEK, pseudomonas): 2-13% Fungi 2-4% Culture negative 5-24%

Answer 61

**Right sided** common (52%; because injecting into veins so gets to R heart first), aortic valve (25%), mitral valve (20%) Infection of **more than 1 valve** occurs **S aureus** predominates **Yeast** and **pseudomonas** species more common in this group Mortality higher if **HIV+** and increases with declining T cell counts

Answer 62

**Early** (first 60 days post op): **S epidermidis** predominates, followed by **S aureus** probably from **perioperative** contamination Progressive **endothelialization** over 6 months **reduces** susceptibility to IE (cells depositing over the valve) **Late**: organisms include **staph**, **strep**, **enterococci**, **HACEK** group

Answer 63

Secondary to invasive procedures especially **intracardiac** **devices** and **intravascular** **access** (central lines), so **S aureus** is a common causative organism **\<50%** have **predisposing** cardiac conditions Bacteremia from **GI** or **GU** source may be the cause (**enterococci** or **yeast**) **Mortality \>50%** (but not all attributable to endocarditis, but to predisposing conditions)

Answer 64

**Turbulent** **flow** from congenital abnormality (**MVP**, **bicuspid** **AV**), **scarring** from **RHD** or age related sclerosis, **prosthetic** **valves** Direct mechanical damage from **catheters**, **pacemaker** **leads** **Inflammatory** **lesions from** **IVDU** **Erosion** of the valve surface allows for direct contact between blood and the subendothelium, exposing **extracellular matrix proteins**, **thromboplastin** and **tissue factor** (TF) triggering **coagulation**, also resulting in **adherence** of bacteria/fungi, **persistence**, **proliferation** causing local damage and growth of the vegetation, **hematogenous dissemination**

Answer 65

Complex series of interactions between **vascular** **endothelium**, **microorganism** (surface properties, enzyme and toxin production), **hemostatic** mechanisms, **host immune system** **Bacterial** **factors**: ability of an organism to bind to **fibrinogen**, **fibronectin** or **platelets** on damaged endothelium facilitates colonization during transient bacteremia; **resistance** to **complement-mediated bactericidal** activity of serum allows organism to persist **Host** factors: **fibronectin**, a major surface glycoprotein produced by endothelial cells, **platelets** and **fibroblasts** in response to vascular injury; **laminin** and **vWF** have also been identified as important host factors in adherence (these all provide opportunity for bacteria to bind and also protection for ongoing proliferation) **Propagation**: in response to inflammation, endothelial cells bind **fibronectin**; bacteria that can bind to the adhesive fibronectin are then **internalized** by endothelial cells triggering production of **tissue factor** (TF) and **cytokines**, promoting more **coagulation** and inflammation, rapidly creating a **protective sheath** of fibrin and platelets, an ideal niche for the **bacteria to reproduce** and further the **propagation of the vegetation** **Tissue** **invasion** and **abscess** **formation**: bacteria produce **exoenzymes** and **exotoxins** that promote bacterial growth and local tissue breakdown leading to **cardiac** **dysfunction** and **septic** **emboli** can seed other organs causing complications at distant sites

Answer 66

**Valvular** **insufficiency** from **erosion** or **perforation** of a leaflet, **rupture** of chordae, papillary muscle **Fistula** into myocardium or the pericardial sac **Valvular stenosis** **Myocardial infarction** (rare) **Conduction** **disturbances** from perivalvular abscess

Answer 67

Acute IE **incubation** is **\<2 weeks** **Subacute** IE **symptoms** last a median of **5 weeks** and immunologic manifestations predominate **Fever \>1 week** **New or changing murmur** (MR, AR) **Cardiac dysfunction** **Embolic** or **immunopathologic** events (**splenomegaly** (septic emboli to spleen), elevated **sed** **rate**, **leukocytosis**, **hematuria**, **anemia**)

Answer 68

70-95% of persons in preantibiotic era had demonstrable embolic events Currently **15-35% have embolic complications** (bc people present earlier with fevers and get treatment earlier) Emboli to liver, **skin**, **brain** (occur in 20%, cause infarction, abscess, mycotic aneurysm, SAH, meningitis, focal neuro deficit similar to stroke sx)

Answer 69

**20-40%** have **petechiae** **Janeway** **lesions** (small, painless, erythematous lesions on palm or sole) due to septic **emboli** with bacteria, neutrophils and **SQ hemorrhage** and necrosis **Osler** **nodes** (tender raised lesions on finger or toe pads) diffuse infiltrate of **neutrophils** and **monocytes** in the dermal vessels with immune complex deposition; **tender** and **erythematous**

Answer 70

**RF** (IgG/IgM) develops in 50% of patients who have **infection \> 6 weeks** Diffuse **glomerulonephritis** from deposition of **circulating immune complexes** in the kidney **Osler** **nodes** from cutaneous immune complex deposition **Splenomegaly**, **arthralgias** are common

Answer 71

70-90% have **anemia** 5-15% have thrombocytopenia 20-30% have leukocytosis 90%+ have **ESR elevated** 40-50% have RF elevated 40-50% have UA abnormal (hematuria, pyuria, bacteria)

Answer 72

**Valvular lesion** and an **organism** **Blood cultures negative** in **10%** of cases: due to antibiotics in prior 2 weeks, due to fastidious organisms which may not grow well in media used or may not respond to standard empiric treatment

Answer 73

Combined **microbiologic** and **echocardiographic** criteria Negative echo does not rule out and positive does not rule in disease (lupus causes fibrin and platelet deposition that could look like endocarditis on echo) **Major** Duke criteria: **\>2/2+** **blood** **cultures** with typical organisms in absence of primary focus; **endocardial** **lesion** on **TEE** or **TTE** (oscillating mass, abscess, new dehiscence of prosthetic valve), new valvular **regurgitation** **Minor** Duke criteria: **predisposing** condition (RHD), **fever**, **vascular** **lesions** (emboli, mycotic aneurysm, pulmonary infarct, intracranial hemorrhage, conjunctival hemorrhage, Janeway lesion), **immunologic** (glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor) **Definite**: surgical **pathology**/bacteriology of vegetation, abscess or emboli; **2 major** criteria; **1 major + 3 minor** criteria; **5 minor** criteria **Possible**: **1 major** criteria + **1 minor** criteria; **3 minor** criteria

Answer 74

Bacteremia from daily activities more likely to cause IE Extremely small number of cases of IE potentially prevented even if prophylaxis is 100% effective Risk of antibiotic adverse events may **exceed potential benefit** At **highest** **risk**: previous IE, prosthetic valve, complex congenital heart disease, post-transplant valvulopathy **Prophylaxis for highest risk group** **only** but **no data** actually demonstrates that prophylactic antibiotics prevent IE **No prophylaxis recommended** for uncomplicated GI/GU procedures

Answer 75

**Infection** of the **endocardial** surface of the heart Most commonly affects **heart valves** **Usually** **bacteria**, but can be chlamydia, rickettsia, fungi, mycoplasma... Any **structural** **defect** that causes **turbulence** increases the risk of endocarditis

Answer 76

**Aneurysms** **Dissections** **Dissecting aneurysms** **Dissections** that **become aneurysmal**

Answer 77

Three layers of aorta: **Intima**: thin layer lined by endothelium (this is the layer that **tears** to cause dissection) **Media**: thickest layer with **elastic** fibers arranged in spiral fashion for tensile strength (this is where **dissection** occurs) **Adventitia**: thin fibrous layer with **vasa vasorum**

Answer 78

**Degenerative diseases** **Connective tissue disorders** **Atherosclerosis** **Infection**

Answer 79

**Cystic medial necrosis**: necrosis of **elastic** fibers (pink) of media replaced by **mucoid** **material** (blue)

Answer 80

**Marfan** **Syndrome**: mutation in gene encoding **fibrillin-1** on **chromosome 15**; most patients **die** of **aortic** **complication** in 3rd decade if untreated; associated with MVP, ectopia lentis, elongated globe, pectus excavatum and carinatum, wrist and thumb sign, arm span-height ratio \>1.05 **Ehlers-Danlos Syndrome**: mutation of COL3A1 gene encoding **Type III collagen**

Answer 81

**3 aortic sinus, 2 cusps** **Fusion of** R and L cusps, or others 1-2% of population **Familial** clustering Associated with premature **degenerative** changes of **media**

Answer 82

**Abdominal aortic aneurysm**

Answer 83

**S aureus** **S epidermidis** **Salmonella** **Streptococcus** **Syphillis**: spirochetal organisms destroy media

Answer 84

**Giant cell** **Takayasu's** **Ankylosing spondylitis** **Reiter's syndrome** **PAN** **Bechet's disease**

Answer 85

Clinical presentation: **asymptomatic**, **chest** **pain** (impending rupture or compression of overlying sternum), **SVC** or **airway** **compression**, **high** **output failure** (rupture into RA or SVC), **hoarseness** Physical exam findings: **normal**, **aortic** **insufficiency**, extremis, concomitant aneurysms Indication for operation in non-emergent: **ascending** aorta **5.5cm**; **descending** aorta **6.5cm**; growth of \>**1.0cm/yr**, operate early for pts with connective tissue disease Emergency: dissection, rupture

Answer 86

Incidence 3/100,000 per year Up to **40% die prior to reaching hospital**; overall surgical in house **mortality 23.9%** (actually now more like 10%) Presentation: **tearing/ripping chest pain radiating to back**, confusion with MI, rupture, occlusion, retrograde dissection (AR), AI, rupture with tamponade, MI from coronary occlusion Treatment of **Type A** (involves ascending aortaa) is **surgical** emergency: rupture, pericardial tamponade, coronary ischemia Treatment of **Type B** (does not involve ascending aorta) is **aggressive BP reduction**, particularly with reduction of dP/dt (beta blockade!)

Answer 87

**Rupture** **Malperfusion**: dynamic (occlusion with every heart beat), static (complete obstruction all the time) Treatment: **stent, fenestration** (make pressure same in true and false lumen to alleviate malperfusion)**, open repair** Note: Type B does **not** involve ascending aorta

Answer 88

**Surgical emergency** Timely diagnosis is key: CT angio, TEE Approximately 30% of cases are misdiagnosed Note: Type A involves **ascending aorta**

Answer 89

Prevent intra-pericardial **rupture** Prevent involvement of **coronary** **ostia** and **aortic valve**: coronary ischemia, **AI** Keep patient alive!

Answer 90

**Unstable** patients had nearly **2x mortality risk** (30% vs 15%) Cardiac **tamponade**, **shock**, **CHF**, CVA/**stroke**/coma, myocardial ischemia or **MI** (EKG with new Q waves or ST elevation), **ARF**, mesenteric ischemia or infarction at surgery

Answer 91

Aneurysm **\> 6cm** (earlier if symptomatic) **Chronic** **dissection** with **aneurysm** **Ulcer** **Ruptured** acute **dissection** **Traumatic** **transection**

Answer 92

Aneurysm **\> 6.5cm** (earlier if symptomatic) **Chronic dissection** with **aneurysm** **Ulcer** **Ruptured** acute dissection **Traumatic transection**

Answer 93

With **dissection**, see **intimal** **tear**; have **flow communication**; false lumen expands and can see intimal flap With **intramural** **hematoma** (IMH) you **cannot find the site of intimal tear**; **no continuous flow communication**; also you have full true lumen and hematoma forms outside circular shape of vessel **Penetrating** **ulcer**: **atherosclerosis** forms ulcer that penetrates aortic wall, can resemble an aneurysm or dissection Note: IMH or penetrating ulcer can convert to a dissection!

Answer 94

Repair needs to take into account **concomitant** **injuries** (closed head injury, rib fracture/pulm contusion, abdominal/spleen/liver/bowel injury, extremity, pelvis) **Contained** **rupture** (adventitial layer) often comes as delayed presentation Most common location is **isthmus** because it is **tethered** and has lots of shear force Open vs. endograft repair: steep arches, graft infolding

Answer 95

Primary **genetic** factors: **chromosomal** aberrations (5%) vs. **single mutant gene** (3%) Primary **environmental** factors: **rubella**, maternal **diabetes**, maternal **alcohol** **abuse**, lupus etc (1%) **Genetic-Environment** interaction (90%)

Answer 96

**Acyanotic**: **L to R** shunt; **VSD**, **PDA**, **ASD**, **atrioventricular** **septal** **defect** (ASD, VSD, and mitral and tricuspid valves fuse?) **Cyanotis**: **R to L** shunt; **truncus** **arteriosus**, total anomalous pulmonary venous return (**TAPVR**), D-transposition of great arteries (**TGA**), **double** **outlet** **RV**, **single ventricle**

Answer 97

**Pulmonary stenosis/atresia** **Tetralogy of fallot (TOF)** **Double outlet right ventricle** **Aortic stenosis** **Coarctation of aorta** **Interrupted aortic arch**

Answer 98

**VSD** **PDA** (remember, all babies born with PDA) **Tetralogy of Fallot** **ASD** Pulmonic stenosis Coarctation of aorta Transposition of great arteries Endocardial cushion defect Aortic stenosis Total anomalous pulmonary venous connection

Answer 99

WIndow-like opening between **upper two chambers** of the heart **Fixed split S2** (inhalation does not cause a greater split, but is just always split) **No murmur** unless **HUGE** ASD and RV pumps a lot of blood through **pulmonary** valve to create **murmur** Poor growth, pneumonia, heart failure, PHT, arrhythmias 7-10% of CHD Closed with **Amplatxer septal occluder device**

Answer 100

Window like opening between the **lower two chambers** of the heart Often **without symptoms** but can have **CHF** (poor growth, pneumonia, heart failure, PHT, arrhythmias) Can progress to **Eisenmenger's** Often these **close** **spontaneously**, some need surgery or device closure Asymptomatic **holosystolic murmur** (S1 coincident, as soon as mitral closes, murmur starts and barely even hear S1) Get **LV dilation** because right side has pressure load but blood goes back to left side so LV has volume overload and dilates

Answer 101

A failure of the **mitral** and **tricuspid** valves to form into 2 valves, so they **remain as one** common valve with a **primum ASD** and an **"inlet" VSD** (basically heart is one big chamber?!) Physiology of a large VSD--requires **full surgical repair** Can progress to **Eisenmenger's** Associated with **Down Syndrome**

Answer 102

Severe **narrowing** of the aorta behind the heart **High** **BP** (in **upper** extremities, but low BP/pulses in femoral artery!), **heart** **failure**, strokes 7% of CHD Treatment by **stent** implantation or **surgery** Often presents with **poor femoral pulse** (but normal radial pulses because flow to subclavian is good/high) Preductal and postductal refer to before or after ductus arteriosus, but both of these are after the subclaviam

Answer 103

**Fused**, **thickened** aortic valve with small opening Heart failure, shock, poor growth, asymptomatic 3-6% of CHD, males much more likely 4:1 **Balloon aortic valvuloplasty** or **surgery** (replacement repair, Ross) Mild aortic stenosis can be observed At risk for **endocarditis** Physical findings: systolic murmur, thrill, click, decreased pulse pressure

Answer 104

1) **Tachycardia** Low BP, so try to: 2) **Increase** **preload** to **increase** **volume** (retain fluid and get **edema**, **tachypnea**, **respiratory** **distress**, peripheral edema rare in kids) 3) **Increase** **afterload** to **normalize** **BP** (vasoconstriction causes you to be **cold** and **clammy**)

Answer 105

Can present like hypovolemic shock but if you give volume (10cc/kg fluid bolus) patient may not improve and may deteriorate For high preload give **diuretics** (furosemide) For poor contractility give **digoxin**, **beta agonists** (dobutamine, epi), **phosphodiesterase** **inhibitors** (milrinone) For high afterload, give **vasodilators** (ACEI), phosphodiesterase inhibitors (milrinone)

Answer 106

**Tetralogy of fallot** (TET or TOF) **Transposition of the great arteries** (TGA) **Tricuspid atresia** (TA): absence of tricuspid valve and hypoplastic RV; requires ASD and VSD for viability **Truncus arteriosus** (TRUNC): failure of truncus arteriosus to divide into pulmonary trunk and aorta; most have accompanying VSD **Total anomalous pulmonary venous return** (TAPVR): pulmonary veins drain into right heart circulation (SVC, coronary sinus, etc); have ASD and PDA to allow R to L shunt to survive

Answer 107

**Blue** discoloration of the skin and/or mucous membranes due to **reduced (unsaturated) hemoglobin** (usually \>3 gm%) in the peripheral circulation Mechanisms of cyanosis: Unsaturated hemoglobin in peripheral arterial circulation due to **intrapulmonary** shunting and **intracardiac** **shunting** **Alveolar hypoventilation** due to CNS depression **Polycythemia**

Answer 108

**Aorta** arises from **pulmonary** **ventricle**, **pulmonary** artery from **systemic** **ventricle** In order to survive, have to have **PDA** and/or **ASD**, and **ASD is better** to have (need to get mixing of red and blue blood) **"Blue baby"** (cyanosis) 5% of CHD Palliation by **balloon** **atrial** **septostomy** Treated with the **arterial switch operation** TGA along with TOF are most **common** cyanotic heart lesions

Answer 109

**P**ulmonary stenosis **R**VH **O**verriding aorta: overrides VSD; aortic valve is right about VSD so communicates with both ventricles **V**SD Presentation: **murmur** with or without cyanosis Physical exam: +/- cyanosis, **clubbing**, increased **RV impulse**, **single loud S2** (aortic valve only?), **harsh midsystolic murmur** (pulmonary stenosis) **Boot shaped heart** on CXR (due to RVH) Clinical course: **benign** or **progressive** **cyanosis** and/or **hypercyanotic (Tet) spells** Pathophysiology of Tet spell: **increased** **RV outflow tract obstruction**, decreased peripheral systemic resistance, possible acidemia and anemia Transcatheter pulmonary valve replacement

Answer 110

**True** lumen is **smaller**, more **bright** on CT angio False lumen is bigger, less bright on CT angio

Answer 111

**Trisomy 21**: VSD, AV canal **Turner's syndrome**: bicuspid aortic valve, coarctation of aorta (preductal, before ductus arteriosus) Noonan's syndrome (AD): pulmonic stenosis Tuberous sclerosis (AD): myocardial rhabdomyoma Single gene mutations on **chrom 6 and 14**: hypertrophic cardiomyopathy **Alcohol**: VSD, PDA, ASD **Rubella**: peripheral pulmonic stenosis, PDA, VSD, ASD **Diabetes**: TGA, VSD, CA **High blood sugar** during pregnancy: thick hypertrophied heart that resolves spontaneously **Lupus**: heart block

Week 5 (Diseases of Cardiovascular Structures) Flashcards

(135 cards)