Cardiac Specializations, Aging, CHF, Congenital Heart Dz, Ischemic Heart Dz Flashcards
Atrial myocytes have storage granules that contain ANP which promotes arterial vasodilation and stimulates natriuresis and diuresis, which is beneficial in the setting of ___ and ____
HTN; CHF
Due to their thin structure, heart valves derive most of their nourishment via _____; normal leaflets and cusps’ vessels are limited to the ____ portions
Diffusion; proximal
3 general types of damage that occur in valves
Collagen —> mitral prolapse
Nodular calcification —> calcific aortic stenosis
Fibrotic thickening —> rheumatic heart dz
During ventricular diastole, closure of the ____ valve leads to _____
Aortic; blood flow to myocardium
Describe cardiac stem cells
Bone marrow derived precursors and stem cells are present in the myocardium but only replace about 1% each year — thus no significant recovery in zone of necrosis
Effects of aging on myocardium and chambers of the heart
Increased LV chamber size, increased left atrial cavity size, sigmoid shaped ventricular sepum
Increased epicardial fat
Myocardium changes include lipofuscin, basophilic degeneration, and possible amyloid deposition
Effect of aging on heart valves
Aortic and mitral valves undergo annular calcification
Fibrous thickening
Mitral leaflets buckle towards left atrium —> increased left atrium size
Lambl excrescences = small filiform processes that form on closure lines of aortic and mitral valves, probably resulting from organization of small thrombi
Vascular changes that occur with aging
Coronary atherosclerosis
Stiffening and dilation of the aorta, elastic fragmentation and collagen accumulation
____ occurs when the heart is unable to pump blood at a rate to meet peripheral demand, OR can only do so with increased filling pressure
May result from loss of myocardial contractile function (systolic dysfunction) or loss of ability to fill the ventricles during diastole (diastolic dysfunction)
CHF
Cardiac myocytes become hypertrophic in the setting of sustained pressure or volume overload (such as in ____ or _____), or in the setting of sustained ____ signals (such as beta-adrenergic stim)
Systemic HTN; aortic stenosis
Trophic
In the setting of ______ overload hypertrophy, myocytes become thicker and the LV increases in thickness concentrically
In the setting of _____ overload hypertrophy, myocytes elongate and ventricular dilation is seen
Pressure
Volume
Hypertrophy of myocytes isn’t accompanied by a matching increase in blood supply despite increased energy demand — thus what is a major complication of cardiac hypertrophy?
Ischemia-related decompensation
Left sided heart failure can be systolic or diastolic; it is most commonly a result of what conditions?
Myocardial ischemia
HTN
Left-sided valve dz
Primary myocardial dz
What are the clinical effects of left sided heart failure? What causes them?
Clinical effects include paroxysmal nocturnal dyspnea, elevated pulmonary capillary wedge pressure, pulmonary congestion (cough, crackles, wheezes, blood-tinged sputum, tachypnea), restlessness, confusion, orthopnea, tachycardia, exertional dyspnea, fatigue, cyanosis
These occur d/t decreased tissue perfusion and congestion in pulmonary circ
Left-sided heart failure is characterized by left ventricular hypertrophy. Left ventricular dysfunction leads to left atrial dilation, resulting in what potential complications?
Atrial fibrillation, stasis, thrombus
The decreased ejection fraction associated with left sided heart failure may result in what complications concerning the kidneys?
Decreased EF —> decreased glomerular perfusion —> renin release —> increased volume
Prerenal azotemia
Histologic finding with left-sided heart failure
Heart failure cells = hemosiderin-laden macrophages
Advanced CHF may lead to decreased cerebral perfusion —> ____ ____
Hypoxic encephalopathy
Most common cause of right sided heart failure
Left sided heart failure
Isolated right sided heart failure may result from what conditions?
Anything that causes pulmonary HTN — parenchymal lung dz, primary pulmonary HTN, or pulmonary vasoconstriction
Clinical features of right-sided heart failure
In primary right sided failure, pulmonary congestion is minimal
The venous system is markedly congested, leading to: Liver congestion (nutmeg liver)
Splenic congestion (splenomegaly)
Effusions involving peritoneal, pleural, and pericardial spaces
Edema, especially in dependent areas (e.g., ankles)
Renal congestion
Other Symptoms: fatigue, distended jugular vv, anorexia and complaints of GI distress, weight gain
Sporadic genetic abnormalities are the major known causes of congenital heart disease. What are the major examples?
Turner syndrome, trisomies 13, 18, and 21
The single MOST COMMON genetic cause of congenital heart disease is TRISOMY 21 — about 40% of pts with Down syndrome have at least one heart defect
Describe heart defects associated with trisomy 21
Usually derived from second heart field (arterioventricular septae) — most commonly defects of the endocardial cushion, including ostium primum, ASDs, AV valve malformations, and VSDs
What congenital heart diseases are associated with the Notch pathway?
Bicuspid aortic valve (NOTCH1)
Tetralogy of Fallot (JAG1 and NOTCH2)
______ mutations are associated with Marfan syndrome which is associated with ____ defects and aortic aneurysms
Fibrillin; valvular
Most common type of congenital cardiac malformation
Ventricular septal defect (VSD)
Genes associated with the nonsyndromic congenital heart defects
ASD or conduction defects (NKX2.5)
ASD or VSD (GATA4)
Tetralogy of fallot (ZFPM2 or NKX2.5)
Note that tetralogy of fallot when associated wtih alagille syndrome is associated with JAG1 or NOTCH2
What type of shunt is considered the most common congenital heart dz?
Left-to-right shunts — including ASD, VSD, and PDA
Of the common congenital left-to-right shunts, the _____ causes increased outflow volume from the RV and pulmonary system, while the ____ and _____ both cause increased pulmonary blood flow and pressure
ASD; VSD, PDA
T/F: Atrial septal defects tend to be rapidly fatal
False — ASDs are usually asymptomatic until adulthood
3 types of atrial septal defects
Secundum ASD: 90% of all ASDs — occurs at center of atrial septum; may be multiple or fenestrated
Primum anomaly: 5% of all ASDs — occurs adjacent to AV valves; often associated with AV valve abnormalities and/or VSD
Sinus venosa defects: 5% of all ASDs — occurs near entrance of SVD; can be associated with anomalous pulmonary venous return to the R atrium
Clinical consequences of congenital left to right shunting
Left-to-right shunting causes volume overload on the right side, which may lead to pulmonary HTN, right heart failure, or paradoxical embolization
May be closed surgically with normal survival
80% of PFOs close permanently by 2 y/o, in the remaining 20% the flap can open if there is an increase in ____-sided pressure, inducing brief periods of ___-___ shunting, such as with pulmonary HTN, bowel movement, coughing, or sneezing. One of the complications of most concern is the possibility for ________ _______
Right; R-L; paradoxical embolus
T/F: the majority of VSDs are infundibular (occuring below pulmonary valve or within muscular septum)
False - 90% of VSDs are membranous
Clinical effects of a VSD
Effects depend on size and presence of other heart defects (those that manifest as children are often associated with other heart anomalies)
Many small VSDs close spontaneously
Large VSDs may cause significant shunting, leading to right ventricular hypertrophy and pulmonary HTN which can ultimately reverse flow through the shunt, leading to cyanosis
Patent ductus arteriosus may fail to close when infants are ______, and/or have defects associated with increased ______ pressure (such as with VSD)
Hypoxic; pulmonary vascular
Major clinical findings with patent ductus arteriosus
PDA produces harsh, machine-like murmur
Effect is further determined by shunt’s diameter — large shunts can increase pulmonary pressure and eventually shunt reversal and cyanosis
Cyanosis early in postnatal life may occur as a result of what cyanotic congenital heart diseases?
Tetralogy of fallot (most common) Transposition of the great arteries Persistent truncus arteriosus Tricuspid atresia Total anomalous pulmonary venous connection
Clinical presentation of a child with TOF
Squatting
Cyanosis
Clubbing
Syncope
[clinical severity depends on degree of subpulmonary stenosis which obstructs the RV outflow tract. Mild stenosis causes L to R shunt. Classic TOF is R to L shunting with cyanosis. Most infants are cyanotic from birth, or soon thereafter]
4 cardinal pathologic features of TOF
VSD
Obstruction of RV outflow tract
Aorta overrides the VSD
RV hypertrophy (heart is enlarged and “boot-shaped” because of this)
Describe prognosis and comorbidities associated with transposition of the great vessels
Transposition of the great vessels results in 2 separate circuits and is incompatible with life unless a shunt is present for mixing of blood from the 2 circuits
Approximately 1/3 have a VSD
2/3 have a PFO or PDA
Right ventricule becomes hypertrophic (supports systemic circulation), and the left ventricle atrophies
Without surgery, pts will die in a few months
Differentiate presentation of coarctation of the aorta (narrowing of the aorta) in infants vs. adults
Infantile form: generally seen WITH a PDA, manifests at birth; may produce cyanosis in lower half of the body
Adult form: generally seen WITHOUT a PDA; usually asymptomatic but can see hypERtension in UEs and hypOtension in LEs. LEs may also exhibit coldness and claudication; may eventually see concentric LV hypertrophy
[regardless of type, degree of narrowing is variable with variable clinical effect — clinical severity depends on degree of stenosis and patency of ductus arteriosus]
What patient populations are at higher risk for coarctation of the aorta?
Males > females
Turner syndrome (45,XO)
Ischemic heart dz results from insufficient perfusion to meet metabolic demands of the myocardium. Blood to the myocardium is supplied by the coronary arteries, so any disruption of coronary flow may result in ischemia. Ischemia may lead to what complications?
Myocardial infarction
Angina pectoris
Chronic IHD with heart failure
Sudden cardiac death
Ischemic heart dz is the leading cause of death in the US, and >90% are secondary to _______
Atherosclerosis
[associated with chronic vascular occlusion; acute plaque change —> thrombus]
Transient, often recurrent chest pain induced by myocardial ischemia insufficient to induce myocardial infarction
Angina pectoris
3 clinical varians of angina pectoris
Stable angina
Prinzmetal variant angina
Unstable (or “crescendo”) angina
Describe stable angina variant
Stenotic occlusion of coronary artery
“Squeezing” or burning sensation, relieved by rest or vasodilators
Induced by physical activity or stress
Describe prinzmetal variant angina
Episodic coronary a. spasm, relieved with vasodilators
Unrelated to physical activity, HR, or BP
Describe unstable (crescendo) variant angina
Frank pain, increasing in frequency, duration, and severity at progressively lower levels of physical activity, eventually even at rest
Usually rupture of atherosclerotic plaque with partial thrombus
~50% may have evidence of myocardial necrosis; ACUTE MI MAY BE IMMINENT
In terms of myocardial infarction, age distribution and risk factors mirror those of atherosclerosis in general because nearly 90% of infarcts are caused by an atheromatous plaque. What are some other potential causes of MI?
Embolus
Vasospasm
Ischemia secondary to vasculitis, shock, or other hematologic abnormalities
Classic presentation of MI
Prolonged CP (>30 min) described as crushing, stabbing, squeezing, tightness, radiating down left arm or left jaw
Diaphoresis
Dyspnea
N/V
HOWEVER - up to 25% are asymptomatic
The location, size, and features of an acute MI depend on what factors?
The site, degree, and rate of occlusion of the artery
Size of the area perfused
Duration of the occlusion
Metabolic and oxygen needs of the area at risk
Extent of collateral blood flow
Presence of arterial spasm
Physiologic changes that occur following severe myocardial ischemia
How long until onset of irreversible injury?
Onset of ATP depletion within seconds and loss of contractility within 2 minutes; increase in lactic acid
Onset of irreversible injury around 20minute mark; microvascular injury takes about 1 hr
T/F: upon occlusion of coronary artery, the area of necrosis begins in the area directly adjacent to the occluded vessel first
False — the necrotic area begins in region of endocardium furthest from occluded vessel and extends back toward area of obstruction
Most common coronary vessels occluded in acute MI and the subsequent areas of infarction
LAD (40-50%) —> apex, LV anterior wall, anterior 2/3 of septum
RCA (30-40%) —> RV free wall, LV posterior wall, posterior 1/3 of septum
LCX (15-20%) —> LV lateral wall
What occlusion locations result in transmural infarcts?
Permanent occlusion of LAD branch
Permanent occlusion of left circumflex branch
Permanent occlusion of RCA (or its posterior descending branch)
What occlusion locations result in non-transmural infarcts?
Transient/partial obstruction in coronary vessels —> subendocardial infarct
Global hypotension —> circumfirential subendocardial infarct
Small intramural vessel occlusions —> microinfarcts
Gross features, light microscope, and electron microscope findings immediately following MI
Gross features: none
Light microscope: none
Electron microscope: relaxation of myofibrils, glycogen loss, mitochondrial swelling
Gross features, light microscope, and electron microscope findings within 30 minutes—4hours following an MI
Gross features: none
Light microscope: usually none; variable waviness of fibers at border
Electron: sarcolemmal disruption, microchondrial amorphous densities
Gross features and light microscope findings within 4-12 hours of acute MI
Gross features: occasional dark mottling
Light micro: early coagulation necrosis; edema; hemorrhage
Gross features and light microscope findings within 12 hours—3 days of acute MI
Gross features: dark mottling with yellow-tan infarct center
Light micro: ongoing coagulation necrosis; pyknosis of nuclei, myocyte HYPEREOSINOPHILIA, marginal contraction band necrosis; early neutrophilic infiltrate. Within 1-3 days there is loss of nuclei and striations + brisk interstitial infiltrate of NEUTROPHILS
Gross features and light microscope findings within 3-10 days of acute MI
Gross features: hyperemic border; central yellow-tan softening. Within 7-10 days becomes maximally yellow-tan and soft with depressed red-tan margins
Light micro: beginning disintigration of dead myofibers with dead neutrophils, early phagocytosis of dead cells by macrophages at infarct border. Within 7-10 days there is well-developed phagocytosis of dead cells and GRANULATION TISSUE appears at margins
Gross features and light microscope findings within 10-14 days of acute MI
Gross findings: red-gray depressed infarct borders
Light mico: well-established granulation tissue with NEW BLOOD VESSELS and collagen deposition
Gross features and light microscope findings within 2-8 weeks of acute MI
Gross findings: gray-white scar, progressive from border toward core of infarct
Light micro: increased collagen deposition with decreased cellularity
How long does it take for dense collagenous scarring to be complete after acute MI?
> 2 months
After acute MI, it takes 24+ hours to see _____ necrosis, _____ nuclei, and loss of cross ______
Coagulative; pyknotic; striations
Areas surrounding necrosis following MI can rupture, causing blood to fill the pericardial sac leading to ____ ____ and further decreased heart function
Cardiac tamponade
Timeline for PMNs, macrophages, and granulation tissue to form after MI
3-4 days = PMNs
7-10 days = macrophages
10 days = granulation tissue
Gross findings of hemorrhage and Contraction bands seen on light micro are signs of ____ injury following MI
Reperfusion
Lab evaluation of an MI consists of measuring the blood levels of proteins that leak out of irreversibly damaged myocytes. The most sensitive and specific biomarkers of myocardial damage are ____ and _____. ______ can also be used
cTnT and cTnI; CK-MB
T/F: the MB form of creatine kinase (CK-MB) is sensitive but not specific, since it can also be elevated after skeletal muscle injury
True
[while MM homodimers are found predominantly in cardiac and skeletal muscle, and BB homodimers in brain, lung, and many other tissues, MB heterodimers are principally localized to cardiac muscle, but there is still some in skeletal muscle, albeit low amounts]
Time to elevation, peak, and return to normal of cardiac biomarkers/enzymes following MI
Time to elevation of CKMB, cTnT, and cTnI is 3-12 hours
CKMB and cTnI peak at 24 hours
CKMB returns to normal in 48-72 hours
cTnI returns to normal in 5-10 days
cTnT returns to normal in 5-14 days
Half of MI deaths occur within 1 hr of onset, and are usually secondary to ________
Arrhythmia
[arrhythmia can be a longer-term complication of MI, depending on site and extent of lesion; can result from permanent damage to the conducting system, or from myocardial “irritability” following the infarct]
Complications of MI other than arrhythmia
Contractile dysfunction
Fibrinous pericarditis
Myocardial rupture
Infarct expansion
Ventricular aneurysm
Myocardial rupture is a complication of MI that typically requires a _____ infarct. It occurs 2-4 days post MI, when inflammation and necrosis have weakened the wall. Risk factors include increased age, large transmural anterior MI, first MI, and absence of ____ hypertrophy
Transmural; LV
Describe process of infarct expansion
Muscle necrosis —> weakening, stretching, and thinning of the wall
Mural thrombus is often seen
Describe ventricular aneurysm as a complication of MI
Late complication of large transmural infarcts with early expansion
Composed of thinned wall of scarred myocardium
Also associated with mural thrombus
Rupture does NOT usually occur
