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CARDIOVASCULAR SYSTEM - Comprehensive Integrated Study Notes

Sources

• Guyton and Hall Textbook of Medical Physiology (14th Ed, ISBN 9780443111013) - "Guyton"
• Robbins, Cotran & Kumar Pathologic Basis of Disease (10th Ed, ISBN 9780443264528) - "Robbins"

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PART I: PHYSIOLOGY (GUYTON & HALL)

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MODULE 1: CARDIAC MUSCLE PHYSIOLOGY

1.1 Core Anatomy of the Heart

1. Atrial muscle - contractions pump blood into ventricles
2. Ventricular muscle - provides the major pumping force
3. Specialized excitatory/conductive fibers - contain few contractile fibrils; generate and conduct action potentials

Guyton, Ch. 9 (Block 1, line 3572)

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1.2 Structural Features of Cardiac Muscle

• Subepicardial fibers spiral leftward; subendocardial fibers spiral rightward (double helix)
• During systole: apex rotates counterclockwise, base rotates clockwise (viewed from apex)
• Creates a "wringing" motion - maximizes ejection efficiency
• At end-systole, LV acts as a loaded spring; untwists during diastole to facilitate rapid filling

Guyton, Ch. 9 (Block 1, lines 3575-3613)

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1.3 Action Potential of Cardiac Muscle

VENTRICULAR MUSCLE ACTION POTENTIAL
Phase 0 (Rapid depolarization): Fast Na⁺ channels open → rapid Na⁺ influx → membrane potential 
                                  rises from -90 mV to +20 mV
Phase 1 (Early repolarization): Fast Na⁺ channels close; transient K⁺ outward current (Ito)
Phase 2 (Plateau): L-type Ca²⁺ channels open (slow Ca²⁺-Na⁺ channels) → sustained Ca²⁺ influx 
                   balances K⁺ efflux → UNIQUE to cardiac muscle (lasts ~0.3 sec)
Phase 3 (Rapid repolarization): Ca²⁺ channels close; K⁺ channels (IKr, IKs) open → 
                                  K⁺ efflux repolarizes membrane
Phase 4 (Resting potential): -85 to -90 mV in ventricular cells

• Absolute refractory period: ~0.25-0.3 sec - virtually the entire period of systole
• Relative refractory period: ~0.05 sec after
• Prevents summation and tetanus - the heart MUST relax between beats to fill

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1.4 Excitation-Contraction Coupling

Action potential → T-tubule depolarization
        ↓
L-type Ca²⁺ channels open on T-tubule membrane
        ↓
Ca²⁺ entry triggers Ca²⁺-induced Ca²⁺ release (CICR) from SR via ryanodine receptors (RyR2)
        ↓
Cytosolic Ca²⁺ rises 100-fold (10⁻⁷ → 10⁻⁵ mol/L)
        ↓
Ca²⁺ binds troponin C → conformational change in troponin-tropomyosin complex
        ↓
Tropomyosin moves off actin binding sites
        ↓
Myosin heads attach to actin (cross-bridge formation) → Power stroke → Contraction
        ↓
Relaxation: Ca²⁺ pumped back into SR (SERCA2a, stimulated by phospholamban) 
           + expelled via Na⁺-Ca²⁺ exchanger (NCX)

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MODULE 2: ELECTRICAL ACTIVITY OF THE HEART

2.1 Cardiac Conduction System

SA Node (pacemaker, 60-100 bpm)
      ↓ (internodal pathways + Bachmann's bundle)
AV Node (delay 0.1-0.12 sec)
      ↓
Bundle of His
      ↓ ↓
Left Bundle Branch    Right Bundle Branch
      ↓                       ↓
Left anterior/posterior      Right ventricular
fascicles                    Purkinje fibers
      ↓
Ventricular muscle (endocardium → epicardium)

Guyton, Ch. 10 (Block 2, lines 341-370)

2.2 SA Node - The Natural Pacemaker

• Resting membrane potential is only -55 to -60 mV (vs. -90 mV in ventricles) because the cell membrane is "leaky" to Na⁺ and Ca²⁺
• If (funny current): Hyperpolarization-activated Na⁺ current → slow spontaneous depolarization (Phase 4)
• When threshold (~-40 mV) is reached: L-type Ca²⁺ channels open → upstroke (no fast Na⁺ channels in nodal cells)
• Repolarization: K⁺ channels open

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2.3 The Electrocardiogram (ECG)

• ST elevation → acute transmural ischemia/STEMI (injury current from ischemic cells)
• ST depression → subendocardial ischemia / NSTEMI
• T wave inversion → myocardial ischemia, ventricular hypertrophy
• Wide QRS (>0.12 sec) → bundle branch block, ventricular rhythm
• Prolonged PR → first-degree AV block
• Delta wave + short PR → Wolff-Parkinson-White (accessory pathway)

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MODULE 3: THE CARDIAC CYCLE

Guyton, Ch. 9 (Block 1, lines 3707-3727)

3.1 Phases of the Cardiac Cycle (Heart Rate 72 bpm = 0.83 sec/cycle)

DIASTOLE (≈0.5 sec total)
├── Isovolumetric relaxation: All valves closed; ventricle relaxes → pressure falls
├── Rapid ventricular filling (70%): Mitral/tricuspid open when LV pressure < LA pressure
├── Slow filling (diastasis): Blood trickles in
└── Atrial systole ("atrial kick"): Adds 20-30% of filling; ESSENTIAL at high heart rates

SYSTOLE (≈0.3 sec)
├── Isovolumetric contraction: All valves closed; LV pressure rises rapidly
├── Rapid ejection: Aortic valve opens when LV > Aortic pressure; fast SV ejected
└── Reduced ejection: Slower ejection; LV begins to relax

3.2 Pressure-Volume Relationships

• S1 ("lub"): Closure of mitral + tricuspid valves at start of systole
• S2 ("dub"): Closure of aortic + pulmonary valves at end of systole
• S3 (ventricular gallop): Rapid ventricular filling; normal in young; pathological in heart failure
• S4 (atrial gallop): Atrial contraction against stiff ventricle; seen in LVH, diastolic dysfunction

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MODULE 4: HEMODYNAMICS AND CARDIAC OUTPUT

4.1 Key Hemodynamic Equations

4.2 Frank-Starling Mechanism and Venous Return

Guyton, Ch. 20 (Block 3, lines 379-414)

• Venous return is the primary controller of cardiac output under normal conditions
• The heart has a built-in mechanism to pump whatever blood arrives (Frank-Starling)
• Mean circulatory filling pressure (MCFP): ~7 mmHg - the pressure that drives venous return when the heart stops
• Cardiac output curve: CO rises as right atrial pressure increases (Starling mechanism)
• Venous return curve: VR falls as right atrial pressure increases (less pressure gradient)
• Equilibrium point: Intersection of CO and VR curves = actual cardiac output

• Increased blood volume (↑ MCFP → ↑ venous return)
• Sympathetic stimulation (↑ contractility + ↑ HR)
• Exercise (muscle pump, ↓ resistance, ↑ metabolic vasodilation)
• Hyperthyroidism, AV fistulas, Paget's disease, anemia (high-output states)

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MODULE 5: BLOOD PRESSURE REGULATION

5.1 Short-Term Regulation

↑ Arterial BP
     ↓
Carotid sinus + aortic arch baroreceptors (stretch) → ↑ afferent impulses to NTS (medulla)
     ↓
↑ Vagal tone → ↓ HR (negative chronotropy)
↓ Sympathetic tone → ↓ HR, ↓ contractility, ↓ vasomotor tone → vasodilation
     ↓
↓ CO + ↓ TPR → BP normalizes

• Responds within seconds; resets over days with sustained hypertension (explains why it doesn't cure chronic HTN)

• Chemoreceptor reflex (peripheral: carotid + aortic bodies; central: medullary)
• CNS ischemic response (Cushing response: last resort - activated when ICP rises)
• Stress relaxation of vessels

5.2 Long-Term Regulation - Pressure-Natriuresis

↑ Arterial BP
     ↓
↑ Renal perfusion pressure
     ↓
↑ Urinary Na⁺ and water excretion (pressure-natriuresis)
     ↓
↓ Blood volume → ↓ CO → ↓ BP

↓ Renal perfusion / ↓ Na⁺ delivery to macula densa / ↑ SNS
        ↓
Juxtaglomerular cells release RENIN
        ↓
Angiotensinogen → Angiotensin I (ACE, lung) → Angiotensin II
        ↓
• Vasoconstriction (AT1 receptor)
• Aldosterone release (↑ Na⁺ + H₂O retention)
• ADH release (↑ water retention)
• Sympathetic activation
• Cardiac/vascular hypertrophy (remodeling)

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MODULE 6: CORONARY CIRCULATION

Guyton, Ch. (Block 3, lines 1017-1055)

6.1 Anatomy

• Left coronary artery (LCA): Divides into LAD (anterior wall, septum) + LCx (lateral wall)
• Right coronary artery (RCA): Supplies RA, RV, inferior LV, SA node (in 60%), AV node (in 85%)
• Normal coronary blood flow: ~250 mL/min = ~5% of cardiac output
• Coronary flow mainly occurs in diastole (systolic compression of intramyocardial vessels)
• Subendocardium is most vulnerable to ischemia (highest wall tension, lowest perfusion pressure)

6.2 Autoregulation and Control

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MODULE 7: MICROCIRCULATION AND LYMPHATICS

• Capillary exchange: Starling forces govern fluid movement
  • Filtration forces: Capillary hydrostatic pressure (Pc) + interstitial oncotic pressure (πi)
  • Reabsorption forces: Plasma oncotic pressure (πp) + interstitial hydrostatic pressure (Pi)
• Net filtration pressure = (Pc + πi) - (πp + Pi)
• Slightly more fluid filters than is reabsorbed → lymphatics return excess ~2-4 L/day
• Edema = filtration > reabsorption + lymphatic capacity
  • Increased Pc (↑ venous pressure, heart failure)
  • Decreased πp (hypoalbuminemia)
  • Increased capillary permeability (inflammation)
  • Lymphatic obstruction (lymphedema)

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PART II: PATHOLOGY (ROBBINS & COTRAN)

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MODULE 8: ATHEROSCLEROSIS

Robbins, Ch. 11 (Block 5, lines 2764-3058)

8.1 Definition and Epidemiology

• Responsible for ~50% of deaths in Western world
• Leading cause globally: coronary artery disease → MI, sudden death
• Death rate from CAD in Eastern Europe is 7-12x higher than Japan

8.2 Risk Factors

8.3 Pathogenesis - Response-to-Injury Hypothesis

STEP 1: ENDOTHELIAL INJURY / DYSFUNCTION
• Risk factors (HTN, hyperlipidemia, smoking, diabetes) cause endothelial activation
• ↓ Nitric oxide production → vasoconstriction, platelet aggregation
• ↑ Permeability + ↑ adhesion molecule expression (VCAM-1, ICAM-1, E-selectin)

STEP 2: LIPID ACCUMULATION IN INTIMA
• LDL enters and becomes oxidized (oxLDL) in the intima
• oxLDL is proinflammatory and cytotoxic to endothelium/SMCs
• "Fatty streak" (earliest lesion): flat, lipid-filled macrophages (foam cells) in intima
  → Appears in aorta as early as age 10

STEP 3: MONOCYTE RECRUITMENT AND FOAM CELL FORMATION
• Monocytes adhere to EC, transmigrate into intima, differentiate to macrophages
• Macrophages take up oxLDL via scavenger receptors (SR-A, CD36) → FOAM CELLS
• Foam cells secrete cytokines (TNF, IL-1, IL-6) → amplify inflammation

STEP 4: SMC MIGRATION AND PROLIFERATION
• Growth factors (PDGF, FGF from platelets, macrophages) → SMC migration from media to intima
• SMCs produce ECM (collagen, proteoglycans) → fibrous cap formation
• SMC proliferation + ECM = the fibrous cap

STEP 5: PLAQUE EVOLUTION
• Fibrous plaque: Central lipid/necrotic core + fibrous cap (collagen, SMCs, T cells)
• Calcification, hemorrhage, necrosis → complex (advanced) plaque

8.4 Stable vs. Vulnerable (Unstable) Plaques

8.5 Complications of Atherosclerosis

• Plaque rupture → acute thrombosis → MI, stroke
• Plaque erosion (more common in women, diabetics) → thrombosis without rupture
• Calcification → stenosis
• Aneurysm formation (media ischemia from increased diffusion distance)
• Embolism from mural thrombus

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MODULE 9: ISCHEMIC HEART DISEASE (IHD)

Robbins, Ch. 12 (Block 6, lines 1077-1469)

9.1 Definition and Overview

9.2 Clinical Presentations of IHD

CORONARY ATHEROSCLEROSIS (slow, decades-long progression)
           ↓
     Plaque rupture / thrombosis
           ↓
   ┌────────────────────────────────────────────────────────┐
   │                                                          │
Stable Angina      Unstable Angina     Acute MI         Sudden Cardiac
(>70% fixed         (non-occlusive      (complete         Death
 stenosis;           mural thrombus;     occlusion;        (ventricular
 exertional          rest pain)          necrosis)         fibrillation)
 chest pain)
   └────────────────────────────────────────────────────────┘
                           ↓
              Chronic IHD / Heart Failure

9.3 Myocardial Infarction

• LAD territory (40-50%): Anterior wall + apex + anterior septum
• RCA territory (30-40%): Inferior + posterior LV
• LCx territory (15-20%): Lateral LV wall

Ischemia → ↓ O₂ → ↓ Oxidative phosphorylation → ↓ ATP
           → Switch to anaerobic glycolysis → lactic acidosis
           → Na⁺/K⁺-ATPase failure → ↑ intracellular Na⁺, Ca²⁺, water
           → Cell swelling → membrane blebbing
           
>20-30 minutes of ischemia → IRREVERSIBLE INJURY (point of no return)
           ↓
Lysosomal enzyme release + Ca²⁺ overload → myocyte necrosis (coagulative necrosis)

9.4 Morphologic Evolution of MI

Robbins, Table 12.5 (Block 6, lines 1286-1288)

• Reactive oxygen species (ROS) from re-energized cells + infiltrating neutrophils
• Calcium overload
• Mitochondrial permeability transition pore (mPTP) opening
• Manifests as contraction band necrosis (hypercontracted sarcomeres), arrhythmias

9.5 Complications of MI

EARLY (within hours-days):
• Arrhythmias (most common cause of death in first hour) - VF
• Cardiogenic shock (large MI >40% LV)
• Pericarditis (fibrinous, 2-4 days post-MI) → Dressler's syndrome (autoimmune, weeks later)

EARLY-INTERMEDIATE (days-2 weeks):
• Cardiac rupture:
  - Free wall rupture (1-3 days, 3-5 days most common) → hemopericardium → tamponade
  - Septal rupture → VSD → acute left-to-right shunt
  - Papillary muscle rupture → acute mitral regurgitation
  → All more common with FIRST MI, no prior infarction/scar

LATE (weeks-months):
• Ventricular aneurysm (mural - fibrous thin wall; contains thrombus)
• Mural thrombus (akinetic wall → stasis → emboli)
• Chronic heart failure (ischemic cardiomyopathy)

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MODULE 10: HEART FAILURE

Robbins, Ch. 12 (Block 6, lines 635-774)

10.1 Definition

10.2 Compensatory Mechanisms (Initially Adaptive, Then Maladaptive)

Cardiac Injury / Overload
         ↓
1. Frank-Starling mechanism: ↑ EDV → ↑ stretch → ↑ contractile force
2. Neurohormonal activation:
   • SNS: ↑ NE → ↑ HR + contractility + vasoconstriction
   • RAAS: ↑ Angiotensin II + Aldosterone → Na⁺/water retention → ↑ preload
   • ADH: ↑ water retention
   • ANP/BNP: Counterregulatory (natriuresis, vasodilation) - elevated in CHF → useful biomarker
3. Cardiac hypertrophy and remodeling
         ↓
  (Over time → maladaptive)
• Neurohormonal overdrive → fibrosis, apoptosis, further dysfunction
• Pathologic hypertrophy → myocyte disorganization, fibrosis
• Ventricular dilation → geometric disadvantage (↓ efficiency per Laplace's law)
         ↓
         DECOMPENSATED HEART FAILURE

10.3 HFrEF vs. HFpEF

10.4 Left-Sided Heart Failure

Robbins, Block 6, lines 711-747

• LV dilation and hypertrophy (eccentric or concentric depending on etiology)
• LA dilation (pulmonary congestion)
• Lungs: edema, "brawny induration" (chronic congestion), hemosiderin-laden macrophages ("heart failure cells") in alveolar spaces

• Forward failure: ↓ CO → fatigue, weakness, ↓ exercise tolerance, renal hypoperfusion (prerenal azotemia), cool extremities
• Backward failure: ↑ pulmonary venous pressure → pulmonary edema → dyspnea, orthopnea, PND, crackles

10.5 Right-Sided Heart Failure

• JVD (jugular venous distension)
• Peripheral pitting edema (dependent)
• Hepatomegaly, ascites
• Anorexia, nausea (bowel congestion)

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MODULE 11: CARDIOMYOPATHIES

Robbins, Ch. 12 (Block 6, lines 1966-2215)

11.1 Classification and Comparison

11.2 DCM - Key Points

• Progressive dilation + systolic dysfunction; ALL 4 chambers enlarged
• 50% familial (mutations in cytoskeletal proteins: titin, lamin A/C, dystrophin, desmin)
• Other causes: viral myocarditis (Coxsackie B), alcohol (direct toxicity + thiamine deficiency → beriberi), cobalt, chemotherapy (anthracyclines, trastuzumab), peripartum, HIV
• Microscopy: hypertrophied + atrophied fibers; interstitial/perivascular fibrosis; vacuolar change; no necrosis (unless from ischemia)

11.3 HCM - Key Points

• Prevalence 1 in 500 - most common genetic cardiovascular disease
• AD with variable penetrance; gain-of-function mutations in sarcomeric proteins → hypercontractility
• Classic: asymmetric septal hypertrophy + SAM (systolic anterior motion of mitral valve) → LVOTO
• Microscopy: "myocardial disarray" (cardinal feature - disorganized bundles, chaotic myocyte arrangement) + interstitial fibrosis
• Leading cause of sudden cardiac death in young athletes (arrhythmia from disarrayed myocytes)
• Novel therapy: Mavacamten - allosteric inhibitor of cardiac myosin ATPase (reduces hypercontractility)

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MODULE 12: VALVULAR HEART DISEASE

Robbins, Ch. 12 (Block 6, lines 1591-1665)

12.1 Overview

12.2 Calcific Aortic Stenosis

Robbins, Block 6, lines 1618-1637

• Most common valvular disease requiring surgery in developed world
• Degenerative calcification of normally tricuspid valve (age >70) or congenitally bicuspid valve (age 40-60s)
• Pathogenesis similar to atherosclerosis: lipid deposition, macrophage/lymphocyte infiltration, fibrosis, calcification
• Symptoms (SAD triad): Syncope, Angina, Dyspnea (in order of increasing severity)
• Once symptomatic: median survival - syncope 3 years, angina 5 years, dyspnea/CHF 2 years
• Murmur: Systolic ejection murmur - harsh, crescendo-decrescendo, radiates to neck

12.3 Rheumatic Heart Disease

• Follows streptococcal pharyngitis by 2-4 weeks
• Autoimmune: molecular mimicry - anti-strep antibodies cross-react with cardiac antigens (M protein vs. cardiac myosin, valvular glycoproteins)
• Acute Rheumatic Fever (Jones Criteria):
  • Major: Carditis, Polyarthritis, Chorea, Erythema marginatum, Subcutaneous nodules
  • Minor: Fever, elevated CRP/ESR, prolonged PR interval
• Acute lesion: Aschoff bodies (granulomatous foci with fibrinoid necrosis, macrophages/Anitschkow cells "owl-eye" caterpillar cells, lymphocytes)
• Verrucous endocarditis: Small fibrinous vegetations along valve leaflet lines of closure
• Chronic: Fibrous thickening and fusion of leaflets + commissure fusion → mitral stenosis ("fish mouth" valve)

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MODULE 13: HYPERTENSION AND HYPERTENSIVE HEART DISEASE

13.1 Hypertension

• Genetic factors (dozens of alleles; affects Na⁺ handling, RAAS, SNS)
• Increased Na⁺ retention → volume expansion (environmental: high-salt diet + genetic susceptibility)
• RAAS overactivation
• SNS overactivity
• Endothelial dysfunction (↓ NO, ↑ ET-1)
• Insulin resistance / metabolic syndrome

13.2 End-Organ Damage in Hypertension

13.3 Hypertensive Heart Disease

• Sarcomeres added in parallel → increased wall thickness without increase in cavity size
• Initially compensatory → maintains systolic function
• Over time → diastolic dysfunction (stiff ventricle) → HFpEF
• Eventually systolic dysfunction as decompensation occurs → HFrEF

• Sarcomeres added in series → cavity dilates + wall thins

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MODULE 14: PERICARDIAL DISEASES

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MODULE 15: ANEURYSMS AND DISSECTION

Robbins, Ch. 11 (Block 5, lines 3061-3200)

15.1 Definitions

• True aneurysm: Involves all three layers (intima, media, adventitia); e.g., atherosclerotic AAA, ventricular aneurysm post-MI
• False aneurysm (pseudoaneurysm): Defect in wall → extravascular hematoma communicating with vessel; e.g., post-MI free-wall rupture contained by pericardium
• Dissection: Blood enters defect in wall and tunnels through media; does NOT require prior aneurysm

15.2 Abdominal Aortic Aneurysm (AAA)

• Most common location: Infrarenal aorta (between renal arteries and bifurcation)
• Risk factors: Male sex (5:1), age >50, smoking, HTN, atherosclerosis
• Size threshold for repair: ≥5.5 cm (risk of rupture increases exponentially)
• Morphology: Severe atherosclerosis with medial destruction; mural thrombus; fusiform or saccular
• Rupture risk: Abrupt onset tearing/ripping abdominal/back pain → hemorrhagic shock; mortality >80% if ruptured, ~5% for elective repair

15.3 Aortic Dissection

• Most common life-threatening aortic catastrophe
• Blood enters media through intimal tear → splits media longitudinally
• Main risk factor: HYPERTENSION (>90%)
• Also: Marfan syndrome (cystic medial degeneration → elastic fiber fragmentation), bicuspid AV, pregnancy, Ehlers-Danlos
• Stanford Classification:
  • Type A: Involves ascending aorta (±descending) → emergency surgery
  • Type B: Only descending aorta (distal to L subclavian) → medical management initially
• DeBakey Classification: Type I (entire aorta), Type II (ascending only), Type III (descending only)
• Clinical: Sudden severe "tearing" or "ripping" chest pain radiating to back/abdomen; asymmetric pulses and BP in arms; aortic regurgitation murmur (Type A)
• Complications: Cardiac tamponade (Type A), aortic regurgitation, coronary/brachiocephalic artery occlusion, spinal ischemia, renal/mesenteric ischemia

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MODULE 16: VASCULITIS

Robbins, Ch. 11 (Block 5, lines 3246-3250)

16.1 Classification by Vessel Size

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MODULE 17: THROMBOSIS, EMBOLISM, AND INFARCTION

Robbins, Ch. 4 (Block 2, lines 296-570)

17.1 Virchow's Triad - Pathogenesis of Thrombosis

       THROMBOSIS
      ↗     ↑     ↖
Endothelial  Abnormal  Blood flow
 Injury     blood flow  abnormality
(exposure   (stasis or  (hypercoagulability)
of TF,       turbulence)
collagen)

17.2 Embolism Types

17.3 Shock

Robbins, Ch. 4 (Block 2, lines 651-756)

1. Compensated/Reversible: SNS activation → tachycardia, vasoconstriction, pallor, ↑ ADH/RAAS → oliguria. BP maintained.
2. Progressive: Tissue hypoxia → anaerobic metabolism → lactic acidosis → cell injury. Compensatory mechanisms fail.
3. Irreversible: Widespread cell death; vital organ failure; DIC; MODS; death.

Infection (gram +/-, fungi) → pattern recognition (TLRs) → macrophage activation
     ↓
Cytokine storm: TNF-α, IL-1, IL-6, IL-12 → massive vasodilation + ↑ permeability
     ↓
• iNOS overactivation → excess NO → refractory vasodilation
• Endothelial activation → DIC
• Mitochondrial dysfunction → energy failure
• Multi-organ dysfunction syndrome (MODS)

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MODULE 18: VASCULAR TUMORS

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PART III: INTEGRATED CLINICAL CORRELATIONS

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FLOWCHART A: Chest Pain - Differential Diagnosis Approach

ACUTE CHEST PAIN
        ↓
ECG ← →  12-lead ECG + Troponin + CXR
        ↓
┌─────────────────────┬───────────────────────┐
ST Elevation          Normal ECG +            Pleuritic pain
(STEMI)               Rising Troponin         (worse with inspiration)
    ↓                 (NSTEMI/UA)                    ↓
Emergent             Anti-ischemic Rx        Pulmonary embolism?
PCI/thrombolysis     + Cath within 24-72h    Pericarditis?
                                             Pneumonia?
└─────────────────────────────────────────────┘
  Also consider: Aortic dissection (tearing, ± unequal BP)
                 PE (sudden dyspnea, hypoxemia)
                 Tension pneumothorax (absent breath sounds)

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FLOWCHART B: Pathophysiology of Left-Sided Heart Failure

LV Systolic/Diastolic Dysfunction
            ↓
        ↑ LV EDP (end-diastolic pressure)
            ↓
        ↑ LA pressure → ↑ Pulmonary venous pressure
            ↓
    ↑ Pulmonary capillary hydrostatic pressure
            ↓
    Fluid transudation into alveoli (pulmonary edema)
            ↓
    Dyspnea, orthopnea, PND, crackles, frothy sputum
            ↓         ↓
    Chronic:         Forward failure:
    Hemosiderin-     ↓ CO → fatigue, ↓ exercise
    laden macroph.   tolerance, prerenal azotemia
    ("HF cells")     cool extremities
    Brown induration
    of lungs
            ↓
    ↑ Pulmonary arterial pressure (reactive) → RV overload
            ↓
    RIGHT-SIDED HEART FAILURE
    (Peripheral edema, JVD, ascites, hepatomegaly)

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TABLE: High-Yield Comparison - Major Cardiomyopathies

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TABLE: ECG Changes in Key Conditions

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TABLE: Key Cardiac Enzymes, Biomarkers, and Clinical Use

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SUMMARY: HIGH-YIELD FACTS FOR EXAMINATIONS

1. Frank-Starling Law: The heart pumps whatever blood it receives; EDV is the main determinant of stroke volume under normal conditions.
2. Coronary Flow: 75% occurs in diastole; subendocardium is most vulnerable to ischemia.
3. Action Potential Plateau (Phase 2): Due to L-type Ca²⁺ channels; responsible for long refractory period → prevents cardiac tetanus; absent in nodal cells.
4. Irreversible MI injury: >20-30 minutes of ischemia; coagulative necrosis; troponin release.
5. MI Morphology Timeline: Wavy fibers (0.5-4 hr) → coagulative necrosis + neutrophils (1-3 days) → macrophages + granulation tissue (3-7 days) → scar (>2 months).
6. Most common cause of MI: Rupture of a non-critically stenosed atherosclerotic plaque (<50% stenosis) → acute thrombosis.
7. Vulnerable plaque: Thin fibrous cap, large lipid core, dense inflammation, high MMP activity.
8. HCM: Autosomal dominant; gain-of-function sarcomere mutations; myocardial disarray on biopsy; leading cause of SCD in young athletes.
9. DCM: Cytoskeletal protein mutations (TTN most common); dilated all 4 chambers; systolic dysfunction.
10. Most common cause of mitral stenosis: Rheumatic heart disease (Aschoff bodies; molecular mimicry).
11. Most common cause of mitral regurgitation (US): Mitral valve prolapse (myxomatous degeneration).
12. AAA: Infrarenal; male smokers >50; repair if ≥5.5 cm; classic: painless pulsatile abdominal mass; rupture = surgical emergency.
13. Aortic dissection Type A: Involves ascending aorta → surgical emergency; Type B → medical (BP control).
14. Cardiac tamponade: Beck's triad = hypotension + JVD + muffled heart sounds; pulsus paradoxus >10 mmHg.
15. Ventricular free wall rupture: Most common 3-7 days post-MI; hemopericardium → tamponade.
16. Septic shock hallmark: Refractory vasodilation via NO; cytokine storm; high or normal CO (distributive); DIC.
17. Virchow's Triad for Thrombosis: Endothelial injury + Stasis/turbulence + Hypercoagulability.
18. Kaposi Sarcoma: HHV-8 + HIV; spindle cells + slit-like vessels.
19. Cardiac pressure overload → concentric hypertrophy (sarcomeres added in parallel, thick wall); volume overload → eccentric hypertrophy (sarcomeres in series, cavity dilates).
20. BNP (B-type natriuretic peptide): Released by stretched ventricles; gold standard test for heart failure diagnosis; ↑ in both HFrEF and HFpEF.

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REFERENCES

Guyton and Hall Textbook of Medical Physiology (14th Edition)

Robbins, Cotran & Kumar Pathologic Basis of Disease (10th Edition)

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