Cardiac Pathology

Terms	Definitions
What are the categories of heart diseases? Which ones are increasing in incidence? Decreasing?	Congenital, decreasing Ischemic, decreasing Hypertensive, UNK Valvular, decreasing Nonischemic (1°), increasing
What is cardiac reserve?	At rest, the cardiac output is ~10-20% of maximal output. The 80-90% difference is the cardiac reserve. Cardiac output is able to adjust up to 5-fold increase, according to need. Cardiac reserve is associated with the stretching of cardiac muscle to accommodate an increased ventricular volume. This is important clinically b/c 70-80% of cardiac function is lost before symptomatic.
What are the 5 types of cardiac dysfunction? Give examples of each	Pump failure: ischemic heart disease, 1° myocardiopathy Obstruction to blood flow through heart: Valvular disease (stenosis), Hypertensive disease. Regurgitant flow: Valvular disease (insufficiency), Congenital heart disease (ASD & VSD) Cardiac Conduction: AFib, Sudden Death Syndromes Disruption of circulatory continuity: GSW
Differentiate b/w cardiac hypertrophy, cardiomegaly and hyperplasia	Cardiac hypertrophy is an increase in ventricular muscle size → Increase in ventricular thickness or weight Cardiomegaly is an overall increase in heart size or weight → Looks bigger. Cardiac hyperplasia is an increase in number of cardiac myocytes. This is NOT possible.
What is pressure overload?	Pressure Overload Hypertrophy = Concentric Hypertrophy. The response to increased pressure (HTN or aortic stenosis) results in new sarcomeres in parallel to cell axis → expanding cross sectional area of myocytes. Concentric ↑ in wall thickness.
What is volume overload?	Volume Overload Hypertrophy = Eccentric Hypertrophy. Characterized by ventricular dilation (valvular insufficiency). New sarcomeres are assembled and positioned in series with existing sarcomeres. Wall thickness is normal or ↑ minimally.
What is systolic dysfunction?	Progressive deterioration of myocardial contractility (IHD, dilated cardiomyopathy)
What is diastolic dysfunction?	Inability of heart chambers to relax (distend) sufficiently to fill during diastole (restrictive cardiomyopathy, massive LVH)
Findings and clinical presentation of left-sided heart failure.	Cardiomegaly: hypertrophy, chamber dilation or both. 2° enlargement of L atrium → AFib & mural thrombus Tachycardia, S3 gallup, mitral reguritation Lungs: 2° excessive fluid accumulation → pulmonary edema/congestion. Long term → siderophages Kidney: Renal hypoperfusion → RAAS. Severe → prerenal azotemia. Brain: hypoxic encephalopathy
Findings and clinical presentation of right-sided heart failure.	Most commonly a consequence of left-sided heart failure. Pure right-sided uncommon but may be due to cor pulmonale (with pulmonary HTN). Hypertrophy and dilation. Subcutaneous tissue: "pitting edema" Liver & portal system: Congestive hepatomegaly. Hepatic sinus congestion, centrilobular necrosis, "cardiac cirrhosis" (↑ fibrous tissue in centrilobular zone) Spleen: Congestive splenomegaly Plural & pericardial effusions.
What is the clinical significance of BNP testing?	Produced by ventricles (2° to ↑ pressure) BNP < 100 pg/mL unlikely to be CHF BNP 100-500 pg/mL may be CHF (look for other conditions) BNP > 500 pg/mL are most consistent with CHF
Normal Myocyte Arrowhead = centrally-placed nuclei Double arrow = intercalated disc Arrow: Capillary endothelial cell
Aortic valve with 3 major layers [v] = ventricularis [s] = spongiosa [f] = fibrosa
Gross of left ventricular pressure (concentric) hypertrophy due to left ventricular outflow obstruction
Gross: Transverse section of left ventricular pressure (concentric) hypertrophy
Gross: transverse section of normal heart
Gross: transverse section of volume (eccentric) hypertrophy
Probe varient foramen ovale is not pathological. True or False?	True
Understand transposition of great arteries and coarctation of aorta, their clinical presentation and their sequela	...
List the gene, it's function and congenital cardiac disease in Non-syndromic Congenital Heart Disease	NKX2-5 Transcription factor ASD, VSD, conduction defects
List the gene, it's function and congenital cardiac disease in Syndromic Congenital Heart Disease	TBX1 del 22q11.2 Transcription factor Di George ASD, VSD, Conduction defects
ASD = Atrial Septal Defect Secundum - 90%: involves fossa ovalis L → R Shunt (pink baby) ↑ pulmonary bloodflow with no initial cyanosis RVH Eventually develop pulmonary HTN → R to L shunt w/ cyanosis (Eisenmenger Syndrome)
VSD = Ventricular Septal Defect 90% involve membranous septum Sx depend on size of anomaly L → R Shunt (pink baby) ↑ pulmonary bloodflow with no initial cyanosis RVH Eventually develop pulmonary HTN → R to L shunt w/ cyanosis (Eisenmenger Syndrome)
Eisenmenger syndrome VSD = Ventricular Septal Defect ↑ Pulmonary HTN yields R → L Shunt (shunt reversal)
Gross: VSD (membranous)
PDA = Patent Ductus Arteriosis L → R shunt Usually close @ 1-2 days 2° to ↑PaO₂ 90% are isolated defects, but look for others. Continuous harsh murmur Chronic → pulmonary HTN Rx: NSAID to close or E₂ to keep open
AVSD = Atrioventricular Septal Defect L → R shunt Partial or Complete (1/3 have DS)
Tetralogy of Fallot 1. Venricular Septal Defect (VSD) 2. Subpulmonic stenosis w/ obstruction of RV outflow tract 3. Aorta overrides the VSD 4. R Ventricular Hypertrophy Direction depends on severity Severe: R → L (blue)
Transposition of Great Vessels L: w/ VSD R: w/o VSD (incompatible w/ life) Develop RVH & LV atrophy
Gross: Transposition of Great Vessels
Coarctation of Aorta w/ PDA Infantile form: hypoplasia of aorta prior to PDA. Cyanosis of inferior body & weak femoral pulses
Coarctation of Aorta w/o PDA Adult Form: Ridge-like fold opposite ligamentum arteriosus HTN in UE w/ ↓BP & pulses in LE - also have kidney RAAS activation.
Gross: Coarctation of Aorta - Adult type.
Plaque rupture w/o thrombus
Thrombosis superimposed on plaque w/ focal disruption
Massive plaque rupture with superimposed thrombus
Define cardiac ischemia	Imbalance b/w the supply (perfusion) and demand of the heart for oxygenated blood
MCC of IHD	>90% due to atherosclerotic coronary arterial obstruction
IHD pathogenesis	-Fixed atherosclerotic narrowing (stenosis) of one or more of the epicardial arteries -Intraluminal thrombosis overlying a disrupted plaque -Localized platelet aggregation -Vasospasm -Emboli -Hypotension -Coronary Artery Vasculitis
What precipitates myocardial ischemia underlying ACS?	Abrupt plaque change followed by thrombosis Tends to occur in plaques with large cores and thin caps. 2/3 occur in vessels narrowed <50%
What are the three categories of acute plaque change?	Rupture/Fissuring Erosion/Ulceration Hemorrhage into an atheroma (plaque)
What is the clinical value of C-reactive protein?	non-specific measure of chronic inflammation in serum. used as a predictive value for CAD (1-3 mg/L is moderate risk).
What are the 4 clinical syndromes of IHD?	Sudden Cardiac Death Angina Pectoris Chronic IHD w/ heart failure Myocardial Infaction
Define SCD	Unexpected death from cardiac causes w/in 24 hrs of event. Most often VF (80%)
What is Chronic IHD	Describes progressive heart failure as a consequence of ischemic myocardial damage. LVH & dilation. Scars from previous MI
What is Angina pectoris?	Transient ischemia that falls short of inducing cellular necrosis (infarction). Characterized by paroxysmal and recurrent substernal or precordial chest discomfort.
What are the three types of Angina pectoris?	Stable Angina: ↓ O₂ perfusion 2° to fixed-narrowing of chronic stenosing coronary atherosclerosis. Usually relieved by rest or SL NTG. Most common form. Unstable Angina: disruption of an atherosclerotic plaque with superimposed thrombus partially narrowing the lumen. May occur at rest. Prinzmetal Angina: due to coronary artery spasm. Relieved by rest, NTG or Ca²⁺ Channel Blockers. Cocaine causes vasospasm & ↑ atherosclerosis.
Define MI	Death of cardiac muscle from ischemia
What are the two types of MI?	Transmural Infarction: Ischemic necrosis involves full or near full-thickness (>50%) of the ventricular wall in the distribution of a single coronary artery. Acute plaque change with thrombosis. Subendocardial infarction: Area of ischemic necrosis limited to the inner 1/3 of the ventricular wall or at most the inner 1/2. Acute plaque change with thrombosis or prolonged hypotension (shock).
Describe the pathogenesis of MI	Sudden change in atheromatous plaque. Formation of initial platelet plug over plaque. Vasospasm (vasoactive substance from platelets). Propigation → larger more stable clot. Thrombosis & coronary occlusion.
Describe type of injury in relation to time, gross feature and microscopic features.
One-day-old infarct showing colagulative necrosis and wavy fibers. Widened spaces b/w dead fibers contain edema fluid and scattered neutrophils.
3-4 day old infarct showing dense polymorphic nuclear leukocyte infiltrate. Loads of neutrophils.
7-10 day of infarct showing nearly complete removal of necrotic myocytes by phagocytosis. Macrophages & lymphocytes. This is the weakest stage. Also see recurrent MI's w/ ventricular rupture.
2-3 weeks post MI. Granulation tissue characterized by loose collagen and abundant capillaries.
Months post MI. Well-healed MI with replacement of necrotic fibers by dense collagenous scar. A few residual cardiac muscle cells are present.
Transmural Infarct. Permanent occlusion of LAD. Hint: may see > 1/2 septal infarct.
Transmural infarct Permanent occlusion of LCx.
Transmural infarct Permanent occlusion of RCA or PDA. Hint: <1/2 or 1/3 septal infarct
Regional Subendocardial infarct 2° to transient/partial obstruction
Circumferential Subendocardial infarct 2° to global hypotension.
Microinfarcts 2° small intramural vessel occlusions.
AMI - predominantly of posterolateral LV. Arrow: recent transmural infarct poss 2° to LCx. Lateral margin shows rupture (dark tissue) of ~ 1 wk old. Arrow head: shows old subendocardial infarct poss 2° to LAD
Reperfusion injury: densely hemorrhagic anterior wall MI w/ LAD thrombus Tx w/ streptokinase.
MI Reprefusion injury. Arrow: contraction bands (dark bands spanning some myofibers).
What are the common serum markers used to detect AMI?
What is the suggested schedule for cardiac markers?
Fibrinous pericarditis, showing a dark, roughened epicardial surface overlying an acute infarct.
Early expansion of anteroapical infarct w/ mural thrombus. Arrow: wall thinning.
Large apical LV aneurysm (w/ fibrosis)
Systemic Hypertensive heart disease. Concentric LVH. Arrow: pacemaker
Pulmonary Hypertensive Heart Disease (for pulmonale) Eccentric RVH.