Cardiac Pathophysiology Flashcards

Angina Pectoris

  • Definition: Severe pain originating from the heart that occurs in response to an inadequate oxygen supply to the myocardial cells compared to their oxygen demand. It is classified as reversible myocardial ischemia.

  • Pathophysiological Mechanisms:

    • Ischemic Pathophysiology (Process #1):
    • In the presence of atherosclerosis, coronary arteries cannot dilate to meet increased myocardial oxygen demands during higher workloads.
    • Myocardial cells transition to anaerobic glycolysis to satisfy energy requirements.
    • The resulting accumulation of lactic acid lowers myocardial pH, which directly stimulates cardiac pain receptors.
    • When myocardial energy demands decrease, oxygen supply becomes adequate again, allowing muscle cells to revert to oxidative phosphorylation. Lactic acid is cleared, and pain resolves.
    • Mechanical Pathophysiology (Process #2):
    • Mechanical stretching of myocardial cells beyond their normal physiological limit directly triggers surrounding cardiac pain receptors.

  • Types of Angina:

    • Stable Angina (Demand Ischemia / Exertional Angina):
    • Triggers: Occurs with exertion or increased workload by the heart/myocardium at a predictable level of activity.
    • Supply vs. Demand: Oxygen supply is insufficient for the increased demand created by cardiac exertion.
    • Duration & Relief: Typically lasts 3–5 min3\text{--}5\,min and is relieved by rest.
    • Prinzmetal's (Variant) Angina:
    • Triggers: Occurs at rest with no obvious increase in myocardial workload.
    • Etiology: Caused by severe coronary artery vasospasm due to sympathetic nervous system (SNS) hyperactivity (such as emotional stress), increased Ca2+\text{Ca}^{2+} influx into arterial smooth muscle, or impaired local production of vasodilator substances.
    • Duration & Relief: Unrelieved by immediate rest, but typically disappears in about 5 min5\,min.
    • Clinical Progression: Can progress to myocardial infarction if severe or prolonged.
    • Unstable Angina:
    • Triggers: Occurs with exertion or at rest.
    • Etiology: Represents a combination of classic and variant angina seen in advanced atherosclerosis. Caused by transient clot formation and dissolution within a coronary artery, accompanied by vasospasm in response to vasoactive peptides released from platelets attracted to damaged endothelium (free radicals).
    • Duration & Relief: Unrelieved by immediate rest, typically lasting 10\text{--}20\,min$.\n\n* **Neuroanatomy of Cardiac Pain Interpretation:**\n * Pain descriptions and locations vary widely among patients because cardiac pain receptors transmit signals to the spinal cord via afferent sympathetic nerve fibers entering at levels C3totoT4 in the spine (Cervical 3 through Thoracic 4).\n\n# Acute Myocardial Infarction (AMI)\n\n* **Definition:** The necrosis (death) of myocardial cells resulting from prolonged oxygen deprivation.\n\n* **Myocardial Perfusion and Anatomy:**\n * Two main coronary arteries branch off the aorta immediately superior to the aortic valve. These arteries passively fill with blood during diastole.\n * **Course of Coronary Arteries:** They reside on the epicardial surface beneath the pericardial sac, penetrating the heart muscle from exterior to interior to supply the subendocardium.\n * **Layers of the Heart Wall:**\n * **Epicardium:** The outermost layer; blood flows from the outside of the heart muscle inward.\n * **Myocardium:** The middle muscular layer; primarily responsible for cardiac contraction.\n * **Endocardium:** The innermost layer; protects against friction from blood flow within the chambers.\n * **Perfusion Dynamics:**\n * Epicardial-to-subendocardial blood flow occurs during diastole and is governed by pressure differentials.\n * Intra-myocardial pressure in the inner muscle layers is significantly higher than in outer layers during systole, compressing subendocardial vessels to a greater extent.\n * **Pressure Differential Etiology:** Caused by the presence of blood inside the heart chambers and the contractile activity of the cardiac muscle itself.\n * **Local Metabolic Control:** Myocardium extracts 70\% of oxygen from hemoglobin; its primary local autoregulatory response to increased demand is to vasodilate.\n * **Systolic Impact:** Coronary blood flow through the left ventricular system drops during systole due to ventricular contraction; end-diastolic volume increases.\n\n* **Ischemic Heart Disease Pathogenesis:**\n * **Root Cause:** Atherosclerosis, most commonly located in the proximal few centimeters of the coronary arteries.\n * **Primary Vascular Occlusion Mechanisms:**\n 1. An atherosclerotic thrombus formed locally, or an embolus that broke off from another location and lodged in a narrowed vessel.\n 2. Localized smooth muscle spasm of the coronary artery triggered by plaque irritation.\n\n* **Reactive Oxygen Species (ROS) & Free Radicals:**\n * **Definition:** Mediators produced and released by vascular wall layers that drive structural wall changes; normal byproducts of mitochondrial oxygen metabolism.\n * **General Properties:**\n 1. Normal physiological occurrence.\n 2. Beneficial as a metabolic byproduct at physiological levels.\n 3. Harmful when generated in excess due to excess oxygen exposure.\n * **Chemical Species:** Include nitric oxide (\text{NO}),superoxideanion(), superoxide anion (\text{O}_2^{\bullet-}),malondialdehyde(MDA),hydroxylradical,andlipidradicals.Non−radicalderivativesactingsimilarlyincludehydrogenperoxide(), malondialdehyde (MDA), hydroxyl radical, and lipid radicals. Non-radical derivatives acting similarly include hydrogen peroxide (\text{H}_2\text{O}_2), peroxynitrite, and hypochlorous acid.\n * **Physiological Actions (Good Reasons):**\n * Promote smooth muscle relaxation\n * Kill bacteria\n * Kill tumor cells\n * Inhibit platelet aggregation\n * Promote collateral circulation\n * **Pathological Actions of Excess/Oxidized ROS (Bad Reasons):**\n * Increase cellular and vascular permeability\n * Exert cytotoxicity toward all cell types\n * Attract platelets and leukocytes, leading to white cell plugging\n * Exacerbate reperfusion injury by impairing healthy cell membrane formation\n * Decrease \text{Ca}^{2+} release from the sarcomere, resulting in poor cardiac muscle cell depolarization and contractility\n\n* **Collateral Circulation:**\n * Normal hearts possess small arteriolar anastomoses (cross-connections) between coronary pathways.\n * **Acute Occlusion:** Microvascular anastomoses dilate within seconds, restoring up to \sim 50\%ofnecessaryrestingbloodflow.Flowdoubleswithinof necessary resting blood flow. Flow doubles within2\text{--}3\,daysandreachespre−occlusionlevelswithinand reaches pre-occlusion levels within1\,month.\n * **Chronic Progressive Occlusion:** Slowly developing atherosclerosis allows collaterals to enlarge alongside disease progression, preserving myocardial perfusion until collateral vessels themselves succumb to atherosclerosis, culminating in cardiac failure.\n\n* **Classification of Myocardial Infarction:**\n * **Pathological Perspective:**\n * *Subendocardial Infarction:* Necrosis confined to the inner layer of the myocardium at the distal end of capillary beds.\n * *Transmural Infarction:* Necrosis extending through the full thickness of the myocardial wall.\n * **Clinical Perspective:**\n * *Non-STEMI:* Non-ST-segment elevation myocardial infarction; typically associated with transient occlusion or subendocardial necrosis.\n * *STEMI:* ST-segment elevation myocardial infarction; associated with sustained transmural tissue necrosis.\n\n* **Subendocardial Ischemia & Perfusion Perturbations:**\n * **Low Diastolic Pressure:** Hypotension, shock, or aortic regurgitation reduces diastolic driving pressure, preventing blood from overcoming intra-myocardial resistance to reach the subendocardium.\n * **High Diastolic Pressure:** Congestive Heart Failure (CHF) maintains pathologically elevated intra-ventricular pressure during diastole due to reduced ejection fraction. Transferred pressure compresses subendocardial vessels, exacerbating underlying ischemia and worsening CHF.\n\n* **Infarction Timeline & Cellular Pathophysiology:**\n * **Microvascular Changes:** Stagnant collateral blood enters the ischemic site; localized vessel dilation causes blood stasis. Myocytes extract all residual oxygen, turning reduced hemoglobin a bluish-brown color. Engorged vessels become permeable, inducing tissue edema, cell swelling, rupture, and death.\n * **Critical Perfusion Threshold:** Maintaining as little as 15\text{--}30\% of normal resting coronary blood flow prevents myocyte death.\n * **Timeline of Necrosis:**\n * Myocytes begin dying after 20\,min of severe oxygen deprivation.\n * **ATP Degradation:** \text{ATP} \rightarrow \text{adenosine} \rightarrow \text{adenine}(avasodilator).After(a vasodilator). After>30\,minofischemia,of ischemia,\sim 50\% of intracellular adenine leaks into the bloodstream and is washed away.\n * **Irreversible Metabolic Loss:** Aerobic ATP synthesis capacity is lost after 20\text{--}30\,min$.
    • Pump Failure & Lysis: ATP depletion halts the Na+/K+\text{Na}^+/\text{K}^+ ATPase pump, filling myocytes with Na+\text{Na}^+ and water, leading to cell bursting (lysis).
    • Cytotoxic Leakage: Lysed cells release intracellular K+\text{K}^+, Ca2+\text{Ca}^{2+}, H+\text{H}^+, and lysosomal enzymes, injuring adjacent myocytes. Released intracellular proteins elevate interstitial oncotic pressure, driving tissue edema.
    • Inflammatory Response: Platelet aggregation triggers the clotting cascade; mast cell degranulation releases histamine and prostaglandins (thromboxane).
    • Conduction System Impairment: Localized acidosis, hyperkalemia, enzyme release, and direct ischemic trauma disrupt the SA node, AV node, or conduction fibers.
    • Hemodynamic Decline: Progressive loss of contracting myocytes reduces overall stroke volume and cardiac output (CO).

  • Reflex Neurohormonal Responses to Falling Blood Pressure:

    • Baroreceptor suppression activates the Sympathetic Nervous System (SNS), Renin-Angiotensin-Aldosterone System (RAAS), and Antidiuretic Hormone (ADH) secretion:
    1. Increased heart rate
    2. Increased systemic vascular resistance (SVR)
    3. Increased fluid reabsorption and auto-transfusion (fluid shift from interstitial space to intravascular space)
    4. Increased renal sodium reabsorption
    • Net Hemodynamic Effect: Significantly increases myocardial workload and oxygen consumption in an already failing heart, worsening myocardial hypoxia and diminishing CO.

  • Primary Causes of AMI:

    1. Coronary atherosclerotic thrombus
    2. Coronary embolus
    3. Severe chamber hypertrophy causing unmet oxygen demand

  • Diagnostic Modalities:

    • Hemodynamics: Patient may present hypotensive to normotensive.
    • Electrocardiogram (ECG) Evolution:
    • ST-segment elevation and T-wave inversion manifest within 1–2 hours1\text{--}2\,hours of acute injury.
    • Pathological Q-wave deepening develops by 24 hours24\,hours.
    • Progressive stages: Normal trace →\rightarrow Acute ST elevation →\rightarrow ST elevation with T-wave inversion →\rightarrow Deep Q-wave formation with ST returning toward baseline →\rightarrow Symmetrical T-wave inversion with deep Q-wave →\rightarrow Normalization of ST/T waves with persistent pathologic Q-wave.

  ECG evolution during myocardial infarction

  • Cardiac Biomarkers: Release of intracellular proteins into serum secondary to myocyte lysis (levels peak between 4–10 hours4\text{--}10\,hours post-injury):

    1. Troponin I (Cardiac): Highly sensitive and specific marker for myocardial tissue necrosis.
    2. Troponin T: Sensitive cardiac regulatory protein marker.
    3. Troponin C: Non-specific marker found in both skeletal and cardiac muscle.
    4. Myoglobin: Rapidly released non-specific heme protein; utilized in combination with cardiac-specific troponins.
    5. C-Reactive Protein (CRP): Hepatic acute-phase reactant elevated during unstable angina; serves as a prognostic survivability indicator rather than a standard diagnostic marker for AMI.

  • Emerging Biomarkers:

    • Salivary markers (salivary myoglobin and CPK).

    • Heart Fatty Acid-Binding Protein (H-FABP): Released from damaged myocardium within 30 min30\,min of ischemic injury.

    • B-type Natriuretic Peptide (BNP): Predictor of ventricular strain, mortality, and heart failure.

    • Complications of AMI:

  • Thromboembolism

  • Congestive Heart Failure (CHF)

  • Dysrhythmias: Most common complication, caused by altered intracellular pH, electrolyte shifts, and myocardial irritability.

    • Inferior Wall AMI: Frequently associated with bradycardia and conduction blocks.
    • Anterior Wall AMI: Frequently associated with SVT or VT.
    • Ventricular Fibrillation (VFib): Primary cause of sudden cardiac death in the pre-hospital setting.
    • Etiologies of VFib: Localized hyperkalemia from K+\text{K}^+ leakage; re-entry circuits spanning normal and ischemic tissue; intense sympathetic tone; ventricular dilation (akinesis) prolonging conduction pathways.

  • Cardiogenic Shock: Severe drop in CO resulting in acute mortality or delayed death from secondary pulmonary or renal organ failure.

  • Myocardial Rupture: Structural rupture of infarcted ventricular tissue resulting in fatal pericardial tamponade.

  • Pericarditis: Inflammatory involvement of the pericardium secondary to epicardial myocyte injury.

  • Ventricular Aneurysm: Formation of thin, fibrous scar tissue that bulges during systole, increasing risk of late rupture or thrombus formation.

Pericarditis

  • Definition: Inflammation of the fluid-filled pericardial sac surrounding the heart, resulting from direct trauma, AMI, systemic infection, or neoplasms. Acute pericarditis generally self-resolves in 2\text{--}4\,weeks$.\n\n* **Pathophysiological Process:** Inflammatory mediators induce fluid exudation into the interstitial space between pericardial layers.\n\n* **Major Complication:**\n * **Pericardial Tamponade:** Accumulation of pericardial fluid under pressure, compressing heart chambers and restricting diastolic filling.\n\n# Myocarditis\n\n* **Definition:** Non-ischemic, non-atherosclerotic inflammation of the myocardium, most frequently caused by viral infection.\n\n* **Morphological Features:** Causes myocyte weakening and reduced contractility. The heart becomes flabby, dilated, and marked by pinpoint intramyocardial hemorrhages. It is a leading indication for cardiac transplantation in the United States.\n\n* **Major Complications:**\n 1. Heart failure\n 2. Life-threatening dysrhythmias\n\n# Cardiomyopathies\n\n* **Definition:** Non-ischemic heart muscle diseases not attributable to coronary artery disease, systemic hypertension, or congenital structural malformations.\n\n* **Major Complication:**\n * Myocardial Infarction / acute ischemic events\n\n# Rheumatic Fever\n\n* **Definition:** Preventable systemic inflammatory disease occurring 1\text{--}4\,weeksafteruntreatedpharyngitiscausedbyGroupAafter untreated pharyngitis caused by Group A\beta−hemolyticstreptococcus(occurringin-hemolytic streptococcus (occurring in3\% of untreated cases).\n\n* **Epidemiology:** Primary onset occurs in children aged 5\text{--}15\,years.\n\n* **Chronic Progression:** Approximately 10\% of affected individuals develop Rheumatic Heart Disease. Inflammatory healing leaves permanent valvular scarring, fibrosis, or leaflet fusion.\n\n* **Transient Clinical Manifestations (Lasting Weeks to Months):**\n * Migratory polyarthritis (moving joint pain and inflammation)\n * Erythema marginatum (characteristic skin rash on the trunk, inner arms, and thighs)\n * Neurological/behavioral disturbances: Gait instability and Sydenham chorea (rapid, uncoordinated involuntary movements)\n\n# Valvular Disorders\n\n* **Pathophysiology of Valvular Stenosis:**\n * **Definition:** Pathological narrowing of a valve orifice or vessel lumen.\n * **Hemodynamic Sequence:**\n 1. The chamber immediately upstream of the stenosis must generate higher pressures to force blood through the narrowed orifice.\n 2. Upstream cardiac muscle undergoes compensatory concentric hypertrophy over time.\n 3. If the hypertrophied chamber fails to generate sufficient pressure, cardiac output declines.\n 4. Elevated wall tension increases myocardial oxygen demand.\n 5. Over time, required ejection pressures exceed the physiological capacity of the hypertrophied myocardium.\n 6. Blood pools in the upstream chamber, stretching myocardial fibers past their optimal length-tension relationship (Frank-Starling curve), precipitating functional decompensation and heart failure.\n\n* **Mitral Valve Stenosis:**\n * **Etiology:** Narrowing of the mitral valve orifice, typically caused by scar tissue accumulation secondary to rheumatic fever, bacterial endocarditis, or congenital structural defects.\n * **Hemodynamic Progression:** Left atrial hypertrophy \rightarrowpulmonaryvenouscongestionpulmonary venous congestion\rightarrowrightventricularpressureoverloadright ventricular pressure overload\rightarrow right-sided heart failure.\n * **Clinical Manifestations:**\n 1. Pulmonary congestion\n 2. Dizziness and fatigue\n\n* **Aortic Valve Stenosis:**\n * **Etiology:** Narrowing of the aortic valve orifice secondary to rheumatic fever or congenital valve anomalies.\n * **Hemodynamic Progression:** Left ventricular concentric hypertrophy \rightarrowdecreasedleftventricularcomplianceandreducedstrokevolumedecreased left ventricular compliance and reduced stroke volume\rightarrow fluid backup into the pulmonary circulation.\n * **Clinical Manifestations:**\n 1. Pulmonary congestion\n 2. Dizziness and fatigue\n\n* **Pulmonary Valve Stenosis:**\n * **Etiology:** Narrowing of the pulmonic valve orifice, most commonly congenital in origin.\n * **Hemodynamic Progression:** Right ventricular pressure overload \rightarrowrightventricularhypertrophyright ventricular hypertrophy\rightarrow right-sided heart failure.\n * **Clinical Manifestations:**\n 1. Impaired pulmonary oxygenation\n 2. Jugular Venous Distension (JVD)\n 3. Right ventricular hypertrophy progressing to right heart failure\n\n* **Mitral Valve Prolapse / Regurgitation:**\n * **Pathophysiology:** Incompetence of the mitral valve causing retrograde blood flow from the left ventricle back into the left atrium during ventricular systole.\n * **Hemodynamic Progression:** Reduced forward stroke volume and CO \rightarrowhypotensionhypotension\rightarrowbaroreceptoractivationbaroreceptor activation\rightarrowchronicleftatrialandleftventricularvolumeoverloadanddilationchronic left atrial and left ventricular volume overload and dilation\rightarrow$$ heart failure.

    • Clinical Manifestations:
    1. Pulmonary congestion
    2. Dizziness and fatigue secondary to decreased CO
    3. Left ventricular and left atrial hypertrophy leading to heart failure

  • Aortic Valve Regurgitation:

    • Pathophysiology: Incompetence of the aortic valve causing retrograde blood flow from the aorta back into the left ventricle during diastole, markedly increasing left ventricular end-diastolic volume.
    • Clinical Manifestations:
    1. Widened pulse pressure
    2. Hyperkinetic (bounding) peripheral and carotid arterial pulsations
    3. Symptoms of congestive heart failure