Cardiovascular System

Heart Anatomy and Conduction

The heart is a four-chambered muscular organ: right atrium and ventricle (pulmonary circuit, low pressure) and left atrium and ventricle (systemic circuit, high pressure). The left ventricular wall is thicker because it must generate higher pressure to overcome systemic resistance. Blood flow is one-way, directed by four valves: two atrioventricular (AV) valves—tricuspid (right) and mitral/bicuspid (left)—and two semilunar valves—pulmonary and aortic. Valves open and close passively based on pressure gradients. The cardiac conduction system generates and propagates action potentials: the sinoatrial (SA) node in the right atrium is the natural pacemaker (~60–100 bpm), depolarizing spontaneously via funny Na⁺ channels (If) and T-type Ca²⁺ channels. The wave of depolarization spreads across both atria (P wave on ECG), pauses at the slow-conducting atrioventricular (AV) node (~0.1 s delay to allow ventricular filling), then travels rapidly through the bundle of His, bundle branches, and Purkinje fibers to depolarize the ventricles from apex upward (QRS complex). Repolarization produces the T wave. The autonomic nervous system modulates heart rate: sympathetic stimulation (norepinephrine, β₁ receptors) increases SA node firing rate and conduction velocity; parasympathetic stimulation (acetylcholine via vagus nerve, muscarinic receptors) slows the SA node and AV conduction.

Cardiac Cycle

The cardiac cycle is one complete heartbeat: systole (contraction and ejection) followed by diastole (relaxation and filling). The Wiggers diagram plots left atrial pressure, left ventricular pressure, aortic pressure, ventricular volume, and ECG against time—mastering it is essential. Five phases: (1) Isovolumetric contraction: ventricles contract, pressure rises rapidly above atrial pressure closing AV valves (S1 heart sound, 'lub'), but semilunar valves remain closed until ventricular pressure exceeds aortic/pulmonary pressure. (2) Rapid ejection: semilunar valves open, ~70% of stroke volume ejected. (3) Reduced ejection: pressure gradient declines, flow slows. (4) Isovolumetric relaxation: ventricles relax, ventricular pressure falls below aortic/pulmonary pressure closing semilunar valves (S2 heart sound, 'dub'); all valves closed briefly. (5) Filling: ventricular pressure falls below atrial pressure, AV valves open; ~70% of filling is passive (rapid filling), the final ~20% comes from atrial systole (atrial kick, P wave). End-diastolic volume (EDV) ≈ 120 mL, end-systolic volume (ESV) ≈ 50 mL, stroke volume (SV) = EDV − ESV ≈ 70 mL. Ejection fraction = SV/EDV × 100 ≈ 58% (normal ≥ 55%). The pressure-volume loop plots LV pressure vs. volume: left border = isovolumetric contraction, top = ejection, right = isovolumetric relaxation, bottom = filling.

Blood Pressure and Cardiac Output

Cardiac output (CO) = heart rate (HR) × stroke volume (SV), normally ~5 L/min at rest. Stroke volume is regulated by three factors: (1) Preload (end-diastolic volume): determined by venous return. Frank-Starling mechanism: increased venous return → increased EDV → increased stretch of ventricular muscle fibers → increased contractile force (optimal sarcomere length, increased Ca²⁺ sensitivity) → increased SV. This is intrinsic—no neural input required. (2) Afterload: the pressure the ventricle must overcome to eject blood (essentially aortic pressure). Increased afterload (hypertension, aortic stenosis) → decreased SV. (3) Contractility (inotropy): the force of contraction at a given preload. Increased by sympathetic stimulation (norepinephrine), circulating catecholamines, and positive inotropes (digitalis); decreased by hypoxia, acidosis, and negative inotropes. Blood pressure = CO × total peripheral resistance (TPR). Systolic pressure (~120 mmHg) reflects ventricular contraction force and aortic compliance; diastolic pressure (~80 mmHg) reflects TPR and aortic recoil. Mean arterial pressure (MAP) = diastolic + 1/3 pulse pressure (≈93 mmHg). Baroreceptors in the carotid sinus and aortic arch detect stretch (pressure); firing rate is proportional to MAP. Increased MAP → increased baroreceptor firing → medullary cardiovascular center → decreased sympathetic outflow, increased parasympathetic → decreased HR, decreased contractility, vasodilation → MAP falls.

Vessel Structure and Hemodynamics

The vascular tree transitions from elastic arteries → muscular arteries → arterioles → capillaries → venules → veins. Each segment is structurally adapted to its function. Arteries have thick walls with abundant elastin and smooth muscle to withstand and dampen pulsatile pressure. Arterioles are the resistance vessels—diameter controlled by sympathetic vasoconstriction (α₁ receptors) and local metabolic factors—and are the primary site of TPR regulation. Capillaries consist of a single layer of endothelial cells on a basement membrane, maximizing surface area for exchange. Veins have thin walls, large lumens, and venous valves; they are compliance (capacitance) vessels, holding ~65% of blood volume at rest. Hemodynamics is governed by physical laws. Flow (Q) = ΔP/R (Ohm's law analogue). Resistance: Poiseuille's law states R = 8ηL/πr⁴, meaning resistance is inversely proportional to the fourth power of radius—a 50% decrease in radius increases resistance 16-fold. Total cross-sectional area increases from aorta to capillaries (slowest velocity) and decreases from venules to vena cava. Velocity (v) = Q/A; slowest in capillaries to maximize exchange time. Blood flow can be laminar (silent, organized layers) or turbulent (noisy, produces bruits/Korotkoff sounds; predicted by Reynolds number > 2000). Compliance (C) = ΔV/ΔP; veins are ~20× more compliant than arteries. In systole, arteries expand storing energy; in diastole, elastic recoil maintains flow—the Windkessel effect.

Capillary Exchange

Capillaries are the site of nutrient, gas, and waste exchange between blood and interstitial fluid. Exchange occurs by three mechanisms. (1) Diffusion: the primary mechanism. Lipid-soluble substances (O₂, CO₂) diffuse directly through the endothelial membrane. Small water-soluble solutes (glucose, ions, amino acids) pass through intercellular clefts or fenestrations. Diffusion rate is governed by Fick's law: rate = (DA ΔC)/Δx, where A is surface area and ΔC is concentration gradient. (2) Bulk flow (Starling forces): net fluid movement across the capillary wall is determined by the balance of four Starling forces: capillary hydrostatic pressure (Pc, pushes fluid out, ~35 mmHg at arteriolar end → ~15 mmHg at venular end), interstitial fluid hydrostatic pressure (Pif, normally near zero), capillary oncotic pressure (πc, pulls fluid in, ~25 mmHg, primarily due to plasma proteins, especially albumin), and interstitial oncotic pressure (πif, small). Net filtration pressure = (Pc − Pif) − (πc − πif). At the arteriolar end, net pressure is positive (~10 mmHg outward), favoring filtration. At the venular end, net pressure is negative (~−7 mmHg inward), favoring reabsorption. Normally ~90% of filtered fluid is reabsorbed; the remaining ~10% enters lymphatic capillaries as lymph. (3) Transcytosis: large molecules (some proteins, hormones) are transported across endothelial cells in vesicles.

Blood Composition and Clotting

Blood is a connective tissue composed of plasma (~55% of volume) and formed elements (~45%, the hematocrit). Plasma is 92% water, 7% proteins (albumin for oncotic pressure and transport, globulins including antibodies, fibrinogen for clotting), and 1% electrolytes, nutrients, hormones, and wastes. Formed elements include: erythrocytes (red blood cells, ~5 million/μL), anucleate biconcave discs containing hemoglobin—four heme groups each with Fe²⁺ that reversibly binds O₂ with cooperative binding (sigmoidal dissociation curve). CO₂ is transported as bicarbonate (~70%, via carbonic anhydrase in RBCs: CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻), bound to hemoglobin as carbaminohemoglobin (~23%), and dissolved (~7%). Leukocytes (WBCs, ~5,000–10,000/μL) mediate immunity. Thrombocytes (platelets, ~150,000–400,000/μL) are megakaryocyte fragments essential for hemostasis. Hemostasis proceeds in three steps: (1) Vascular spasm: immediate vasoconstriction reduces blood loss. (2) Platelet plug formation: platelets adhere to exposed collagen (via von Willebrand factor), activate, release ADP and thromboxane A₂ recruiting more platelets, and aggregate via fibrinogen-GPIIb/IIIa bridges. (3) Coagulation cascade: a series of zymogen activations culminating in thrombin converting fibrinogen to fibrin. The intrinsic pathway (contact activation, measured by aPTT) and extrinsic pathway (tissue factor, measured by PT) converge at Factor Xa, which with Factor Va converts prothrombin to thrombin. Thrombin then activates Factor XIII to cross-link fibrin. Fibrinolysis: plasminogen is activated to plasmin by tissue plasminogen activator (tPA), which degrades fibrin clots.

How it works

The cardiovascular system is a hydraulic circuit driven by pressure gradients. The heart's pacemaker cells generate rhythmic electrical impulses that spread through a specialized conduction system, triggering coordinated contraction. As the ventricles squeeze, pressure rises above arterial pressure, forcing the semilunar valves open and ejecting blood—this is systole. When ventricles relax, pressure falls below atrial pressure, allowing passive and then active filling—this is diastole. The ejected blood flows down a pressure gradient through arteries, arterioles, capillaries, and veins, with flow rate governed by Poiseuille's law (R ∝ 1/r⁴). At the capillary level, Starling forces determine net fluid movement between blood and interstitium. Nearly everything is regulated: heart rate and contractility by the autonomic nervous system, vessel diameter by local and systemic controls, blood volume by renal mechanisms, and clotting by a precisely balanced cascade of activators and inhibitors. The system's elegance is in its integration—a change in any one variable (heart rate, vessel radius, blood volume, clotting factors) is detected by sensors and countered by reflexes that restore equilibrium.

How it works

The cardiovascular system is a hydraulic circuit driven by pressure gradients. The heart's pacemaker cells generate rhythmic electrical impulses that spread through a specialized conduction system, triggering coordinated contraction. As the ventricles squeeze, pressure rises above arterial pressure, forcing the semilunar valves open and ejecting blood—this is systole. When ventricles relax, pressure falls below atrial pressure, allowing passive and then active filling—this is diastole. The ejected blood flows down a pressure gradient through arteries, arterioles, capillaries, and veins, with flow rate governed by Poiseuille's law (R ∝ 1/r⁴). At the capillary level, Starling forces determine net fluid movement between blood and interstitium. Nearly everything is regulated: heart rate and contractility by the autonomic nervous system, vessel diameter by local and systemic controls, blood volume by renal mechanisms, and clotting by a precisely balanced cascade of activators and inhibitors. The system's elegance is in its integration—a change in any one variable (heart rate, vessel radius, blood volume, clotting factors) is detected by sensors and countered by reflexes that restore equilibrium.

Comparisons

• C/P (Fluid dynamics): Poiseuille's law (R = 8ηL/πr⁴), Bernoulli's principle, and the continuity equation (A₁v₁ = A₂v₂) apply directly to blood flow—radius changes have the most dramatic effects on resistance and velocity.
• C/P (Gas laws and hemoglobin): Cooperative oxygen binding to hemoglobin produces the sigmoidal O₂ dissociation curve; Bohr effect (pH/CO₂ shift), temperature, and 2,3-BPG modulate affinity—all rooted in protein allostery thermodynamics.
• B/B (Action potentials): SA node pacemaker potentials rely on If (funny Na⁺ channels), T-type Ca²⁺, and L-type Ca²⁺ channels; ventricular myocyte action potentials feature a prolonged plateau (Phase 2) due to L-type Ca²⁺ influx balancing K⁺ efflux—a unique cardiac feature.
• B/B (Enzyme cascades): The coagulation cascade is a classic biological amplification system—one activated Factor Xa molecule generates thousands of thrombin molecules, each converting thousands of fibrinogen to fibrin—analogous to signal transduction cascades.
• P/S (Stress and health): Chronic sympathetic activation (stress) elevates heart rate and blood pressure; behavioral interventions (meditation, exercise) lower sympathetic tone—a behavioral-biological feedback loop directly testable on the MCAT.
• C/P (Electrochemistry): ECG electrodes measure extracellular voltage changes from propagating action potentials; Nernst and Goldman equations govern the ion gradients that produce cardiac electrical activity.

Common confusions

• Confusing which valves are open/closed during each phase. AV valves are open during filling (diastole) and closed during systole; semilunar valves are closed during diastole and open during ejection. S1 = AV valve closure, S2 = semilunar valve closure.
• Misapplying Poiseuille's law. Resistance is proportional to 1/r⁴—doubling the radius decreases resistance by 16-fold, not 2-fold. Atherosclerotic narrowing has a much larger effect on flow than intuition suggests.
• Forgetting the Frank-Starling mechanism is intrinsic. Increased venous return increases stroke volume even without neural input—it's a property of cardiac muscle itself (length-tension relationship), not a reflex.
• Mixing up hydrostatic and oncotic pressures. Hydrostatic pushes fluid OUT of capillaries; oncotic (due to proteins, especially albumin) pulls fluid IN. Net filtration = (Pc − Pif) − (πc − πif). Liver disease (low albumin) reduces oncotic pressure → edema.
• Overlooking that the SA node is the normal pacemaker but any cardiac cell can be a pacemaker. If the SA node fails, the AV node (~40–60 bpm) or Purkinje fibers (~20–40 bpm) will take over—but at a slower intrinsic rate.
• Treating EDV and ESV as constants. Preload changes EDV (increased venous return → increased EDV); afterload changes ESV (increased afterload → increased ESV → decreased SV). Both affect stroke volume, but through different mechanisms.
• Confusing the intrinsic vs. extrinsic clotting pathways. Intrinsic = contact activation, measured by aPTT; extrinsic = tissue factor, measured by PT. Both converge at Factor Xa. Heparin affects intrinsic (aPTT); warfarin affects extrinsic (PT).
• Forgetting that MAP ≠ (systolic + diastolic)/2. MAP = diastolic + 1/3 pulse pressure because diastole lasts roughly twice as long as systole. MAP = diastolic + (systolic − diastolic)/3.

Quick review

• Cardiac output (CO) = HR × SV; normal ~5 L/min. SV = EDV − ESV ≈ 70 mL.
• SA node is the pacemaker (If, T-type Ca²⁺); AV node delays ~0.1 s; Purkinje fibers conduct rapidly through ventricles.
• S1 (lub) = AV valve closure at start of systole; S2 (dub) = semilunar valve closure at start of diastole.
• Frank-Starling: ↑ EDV → ↑ stretch → ↑ contractile force → ↑ SV. This is intrinsic, not neural.
• MAP = diastolic + 1/3 pulse pressure; BP = CO × TPR.
• Poiseuille's: R = 8ηL/πr⁴. Resistance ∝ 1/r⁴—small radius changes cause large resistance changes.
• Starling forces: net filtration = (Pc − Pif) − (πc − πif). Hydrostatic pushes out; oncotic (albumin) pulls in.
• O₂ dissociation curve: sigmoidal (cooperative binding). Bohr effect: ↓ pH or ↑ CO₂ shifts curve right (↓ affinity → ↑ unloading).
• Coagulation: intrinsic (aPTT) + extrinsic (PT/INR) converge at Factor X → prothrombin → thrombin → fibrinogen → fibrin (cross-linked by Factor XIIIa).
• Sympathetic (NE, β₁): ↑ HR, ↑ contractility, ↑ conduction. Parasympathetic (ACh, muscarinic): ↓ HR, ↓ AV conduction.
• Arterioles = resistance vessels; veins = capacitance vessels (~65% of blood volume); capillaries = exchange vessels.
• Ejection fraction = SV/EDV × 100; normal ≥ 55%. Reduced in systolic heart failure.