Cardiac Pathology I&II - Zaloga

Question 1

intercalated discs

Answer 1

-gap junctions that join cardiomyocytes forming a syncytium for communication b/w cells

Question 2

conduction system

Answer 2

• myocytes used to conduct electrical impulses

- maintain rhythm and rate –> arrythmia if altered

Question 3

blood supply of the heart

Answer 3

• myocardium vulnerable to ischemia –> needs constant O2 supply (metabolically active)
• blood flows through coronary arteries during DIASTOLE

Question 4

cardiac pathophysiology

Answer 4

1. pump failure - inadequate CO
2. flow obstruction - lesions obstructing flow or or preventing valve opening
3. regurge - overloads affected atria or ventricles
4. shunted flow - cardiovascular defects b/w blood vessels (ex. PDA)
5. cardiac conduction disorders - inefficient myocardial contractions
6. rupture of heart or major vessels

Question 5

heart failure aka CHF

Answer 5

• progressive, poor prognosis**
• unable to provide adequate perfusion to tissues due to decreased CO (forward failure)
• low CO –> increase venous pool congestion (backward failure)
• changes in workload (pressure/volume overload)–> ventricular remodeling –> thin wall, dilated, hypertrophy (variable)
• overstretch heart –> less actin/myosin overlap –> decrease contraction*
• systolic dysfunction –> decreased ejection fraction
• no chamber expansion with stiff ventricle –> diastolic dysfunction (decreased filling)
• hypertrophic myocytes –> enlarged “boxcar” nuclei and associated with interstitial fibrosis

Question 6

what is an independent risk factor for sudden death?

Answer 6

• cardiomegaly**

- can predispose you to cardiac dysrhythmias

Question 7

how does cardiac hypertrophy progress to heart failure?

Answer 7

1. pressure-overload hypertrophy –> sarcomeres assebled in parallel
2. volume-overload hypertrophy –> sarcomeres assembled in series

-increasing cardiac workload and O2 demand with hypertrophy, but NO increase in blood supply to myocytes –> ischemia –> cardiac death/failure

Question 8

left sided heart failure

Answer 8

• usually due to ischemia*, systemic HTN, or mitral/aortic valve problems
• lung problems** –> pulmonary congestion/edema
• systemic hypoperfusion –> renal and brain dysfunction
• secondary dilation of LA –> Afib and stasis of blood (thrombi)
• Afib –> exacerbate CHF and diminish renal perfusion –> + RAAS exacerbating pulmonary edema**
• hemosiderin laden macrophages (heart failure cells)**
• Kerley B lines** from lung interstitial edema

Question 9

right sided heart failure

Answer 9

• usually due to left sided heart failure* (pulmonary HTN)*
• peripheral edema and organ congestion –> affect extremities and visceral organs**
• hepatic and portal vein congestion –> congestive hepatomegaly (nutmeg liver)** and splenomegaly
• venous congestion –> pitting edema, ascites, pleural effusions

Question 10

most common congenital heart diseases

Answer 10

-VSD and ASD 50% of cases

Question 11

genetic abnormalities in congenital heart disease

Answer 11

• tuner syndrome (monosomy X)
• trisomy 21 (most common) –> down syndrome**
• VSD –> GATA4, TBX5, NKX2-5 gene mutations
• bicuspid aortic valve –> NOTCH1
• tetralogy of fallot –> JAG1 and NOTCH2
• marfan –> fibrillin mutation
• DiGeorge –> chromosome 22q11.2 deletion and TBX1 TF –> neural crest migration (heart, cleft palate, abnormal face)

Question 12

left to right shunts (most common)

Answer 12

• lead to reversal of flow (Eisenmenger syndrome)**
• elevate pressure/volume in pulmonary circulation

1. ASD
   - murmur present
   - secundum ASD most common (primum affects AV valves and VSD)
   - sinus venous defects where IVC and SVC attach
2. patent foramen ovale (PFO)
   - close by age 2 by septum primum and secundum
3. VSD (most common)
   - 90% membranous VSD
   - higher pressure on left side
4. patent ductus arteriosus (PDA)
   - closes 1-2 days due to declining PG2 forming ligamentum arteriosum
   - continuous harsh murmur
   - no cyanosis initially –> want closure to prevent reversal of flow
   - can give PGE2 to keep the duct open in someone with pulmonary or systemic outflow obstruction**

Question 13

right to left shunts

Answer 13

• lead to cyanosis and hypoxemia (bypass pulmonary circulation)
• venous emboli enter systemic circulation directly
• clubbing and polycythemia

1. tetralogy of fallot (most common)**
   - large VSD, overriding aorta, pulmonary stenosis, RV hypertrophy**
   - boot shaped heart*
   - pressure on right side increases
2. transposition of great arteries (TGA)
   - aorta from RV, pulmonary artery from LV
   - deoxygenated blood into systemic circulation
   - need shunt –> give PGE2 for PDA
3. tricuspid atresia
   - complete tricuspid occlusion –> RV hypoplasia
   - maintain circulation with right to left shunting
   - cyanosis

Question 14

Eisenmenger syndrome

Answer 14

reversal of blood flow due to pulmonary HTN –> becomes a right to left shunt

Question 15

obstructive diseases

Answer 15

1. coarctation of the aorta
   - constriction of aorta around PDA
   - infantile (associated with PDA) –> coarctation distal to aortic arch and proximal to PDA –> lower extremity cyanosis**
   - adult (not associated with PDA) –> coarctation distal to aortic arch –> HTN in upper extremities, hypotension and weak pulses in lower extremitites**
2. aortic stenosis/atresia
   - severe –> obstructed LV flow causes hypoplasia of LV and ascending aorta (hypoplastic left heart syndrome)
   - PDA duct closure is lethal

Question 16

ischemic heart disease (IHD)

Answer 16

• myocardial ischemia (imbalance b/w supply and demand)
• can lead to CHF
• usually from atherosclerotic lesions in coronary arteries (CAD if >75% obstruction)
• may be due to chronic vascular occlusion or acute plaque change (abrupt occlusion of vessel)

can see acute coronary syndrome with downstream myocardial ischemia

• stable angina –> no plaque disruption
• unstable angina –> has plaque disruption
• MI
• sudden cardiac death (ventricular arrythmia)

Question 17

angina pectoris

Answer 17

-recurrent chest discomfort from myocardial ischemia

1. stable –> brought on by exertion, relieved with rest
2. unstable –> brought on by exertion or rest –> incomplete occlusion is high risk for MI
3. Prinzmetal –> coronary artery spasm not related to physical activity

Question 18

MI

Answer 18

• necrosis of cardiac tissue from prolonged ischemia
• acute plaque change –> microthrombi –> tissue factor and coagulation –> complete occlusion of coronary artery
• diabetic neuropathy patients asymptomatic of chest pain, nausea, dyspnea

risk factors: age, atherosclerosis, post-menopause

Question 19

progression of ischemic necrosis after coronary artery occlusion

Answer 19

• subendocardium 1st –> myocardium –> epicardium
• transmural branches reach subendocardium last
• transmural ischemia within 6 hr.

Question 20

distribution of myocardial necrosis

Answer 20

• occlusion of epicardial vessels –> transmural infarct if untreated (usually involves LV)
• transmural infarct aka ST elevation MI (STEMI)
• subendocardial infarct aka non ST elevation MI (NSTEMI)
• LAD most commonly infarcted (anterior wall of LV near apex)
• multifocal microinfarction –> affect small transmural vessels

Question 21

myocardial ischemia

Answer 21

• stop aerobic metabolism and ATP production –> build up of metabolites and lose contractility
• disruption of sarcolemma membrane 1st sign of myocyte necrosis –> proteins leak into blood
• irreversible injury in 20-40 min.

Question 22

cardiac biomarkers in MI

Answer 22

• tropinin I and tropinin T most sensitive* (peak in 5-14 days)
• CK-MB (peak in 24 hr. and back to normal in 3 days)

all elevated in 3-12 hours

Question 23

morphologic changes in heart in acute MI

Answer 23

-4-24 hr. –> dark mottling and coagulation necrosis
-1-3 days –> yellow pallor, neutrophil infiltrate
-4-7 days –> yellow pallor, macrophage infiltrate to clean up neutrophils
1-3 weeks –> red gray infarcted borders, formation of granulation tissue
-months –> scar formation

Question 24

acute MI

Answer 24

• necrosis of cardiac myocytes

- myocardial hemorrhage with cardiac rupture

Question 25

reperfusion

Answer 25

• better salvage with early reperfusion –> restores flow and removes the infarct
• can sometimes trigger arrythmias and induce damage (Ca2+ overload, oxidative stress, activate complement)
• abnormalities may persist in stunned myocardium (prolonged failure) even though they are being perfused

Question 26

chronic ischemic heart disease

Answer 26

• acute plaque change –> coronary artery thrombosis and myocardial ischemia
• heart muscle replaced with fibrous connective tissue
• leads to progressive CHF –> cardiomegaly with LV hypertrophy

Question 27

sudden cardiac death (SCD)

Answer 27

• unexpected death from cardiac issues
• acute ischemia from CAD is common cause**
• usually due to fatal ventricular arrythmias**
• may see coronary artery atherosclerosis, previous scars, and myocyte vacuolization

Question 28

hypertensive heart diseases (HHD)

Answer 28

• increase heart demands/work load
• high pressure induce myocyte hypertrophy (“box car” nuclei) and interstitial fibrosis –> wall thickness/stiffness
  1. systemic HTN –> pressure overload and LV hypertrophy with LA dilation
• induce Afib or progressive CHF
  2. pulmonary HTN –> pressure overload and RV hypertrophy with LA dilation
• due to lung disorders (emphysema, HTN, etc.)

Question 29

major functional valvular lesions

Answer 29

1. Aortic stenosis: Calcification and sclerosis from “wear and tear”
2. Aortic insufficiency: Dilation of ascending aorta, often due to hypertension
3. Mitral stenosis: Rheumatic heart disease
4. Mitral insufficiency: Myxomatous degeneration (mitral valve prolapse)

valvular insufficiency –> volume overload
valvular stenosis –> pressure overload –> hypertrophy

Question 30

mitral valve prolapse (MVP)

Answer 30

• myxomatous degeneration of the mitral valve
• floppy leaflets that prolapse and balloon into RA
• causes: marfan syndrome or secondary to regurgitation
• mid systolic clicks murmur
• can lead to infective endocarditis, mitral insufficiency, arrythmia, SCD
• see spongiosa thickening with deposition of collagen/fibrosis

Question 31

rheumatic fever (RF) and rheumatic heart disease (RHD)

Answer 31

• inflammatory disease from host immune response to GAS pharyngitis**
• see pancarditis and polyarthritis*
• inflammatory lesions called Aschoff bodies (plasma cell lymphocyte) with Anitschkow cells (activated macs)*
• cause mitral stenosis** –> buttonhole stenosis and LA dilatation

Question 32

infective endocarditis (IE)

Answer 32

-microbial infection (usually bacterial) of heart valves or endocardium –> cause vegetations on heart valves (thrombotic debris of organisms)

1. acute IE –> caused by staph aureus; infection of previously NORMAL valve**
   - IV drug users
   - splinter hemorrhage, janeway lesions (tender), osler nodes (nontender), roth spots**
   - glomerulonephritis
2. subacute IE –> caused by strep viridans (low virulence); infection of once DAMAGED valve**
   - increased risk with cardiac and vascular abnormalities

-prosthetic valve endocarditis caused by staph epidermidis

Question 33

cardiomyopathies

Answer 33

• intrinsic diseases of myocardium with mechanical or electrical dysfunction
• usually genetic and lead to CHF or arrythmias
• dilated cardiomyopathy (most common)–> systolic dysfunction**
• restrictive and hypertrophic cardiomyopathy –> diastolic dysfunction**

Question 34

dilated cardiomyopathy

Answer 34

• causes: myocarditis, toxins (ex. EtOH), pregnancy, Fe overload, persistent tachycardia, catecholamines, contraction band necrosis, mutations in dystrophin
• myocarditis from secondary infection of Coxsackie A and B viruses** –> immune rxn that affects myocytes
• dilation of atria and ventricles –> decreased contraction (systolic dysfunction) –> lower ejection fraction

Question 35

restrictive cardiomyopathy

Answer 35

• stiff, non-compliant myocardium from deposition of amyloid, interstitial fibrosis from radiation, or endomyocardial scarring
• apple green birefringents on Congo red stain is diagnostic for amyloidosis (accumulation of protein fibrils)*
• Loeffler endomyocarditis –> eosinophil infiltrate releasing toxic substance on subendocardium causing necrosis and scarring*
• impaired ventricular filling during diastole

Question 36

hypertrophic cardiomyopathy

Answer 36

• usually genetic; autosomal dominant mutations of B-myosin heavy chain**
• also mutations in troponin T, tropomyosin, myosin binding protein C
• caused by obstructed outflow of aortic valve –> systolic ejection murmur
• poor compliance of LV (less filling) due to thick wall –> diastolic dysfunction –> decreased SV
• also asymmetric septal hypertrophy from thickening of ventricular septum

Question 37

Arrhythmogenic right ventricular cardiomyopathy (ARVC)

Answer 37

• inherited disease of myocardium causing RV failure/tachycardia/fibrillation or sudden death
• loss of myocytes replaced with connective tissue (fibrosis) and fat

Question 38

most common cause of myocarditis**

Answer 38

• coxsackie A and B virus**

- can develop dilated cardiomyopathy

Question 39

pericardial diseases

Answer 39

-cause fluid accumulation, inflammation, fibrous constriction

1. pericardial effusion - accumulate fluid in parietal pericardium either slowly or suddenly (hemopericardium)
   - fatal cardiac tamponade with sudden effusion
2. acute pericarditis
   - serous pericarditis –> noninfectious inflammatory disease; rare fibrous adhesions
   - fibrinous and serofibrinous –> serous fluid with fibrinous exudate (more intense inflammation with serofibrinous)
3. purulent or suppurative pericarditis
   - active infection from lobar pneumonia or blood –> acute inflammatory rxn
   - cloudy fluid with pus
   - have scarring and fibrosis that limits diastole –> constrictive pericarditis (restrictive pericarditis mimick)
4. hemorrhagic pericarditis
   - exudate composed of blood caused by spread of malignant neoplasm

Question 40

what is the most common tumor of the heart?

Answer 40

• Myxoma**
• arises from primitive multipotent mesenchymal cells*
• 90% arise in left atria near fossa ovalis
• ball valve obstruction (obstruct mitral valve or form thrombus in lungs)