Heart Beats and Why: Exhaustive Study Guide

Overview of the Cardiovascular System and Heart Gross Anatomy

Definition and Function: The heart serves as the central pump for the cardiovascular system, facilitating the transport of oxygen ( $O_2$ ) and carbon dioxide ( $CO_2$ ) throughout the body.
Systemic Circulation Components: * Head and Arms: Oxygenated blood is delivered via the carotid and subclavian arteries; deoxygenated blood returns via the jugular and subclavian veins. * Lungs: Facilitate gas exchange where $CO_2$ is released and $O_2$ is absorbed. * Liver: Receives blood through the hepatic artery and hepatic portal vein; blood exits via the hepatic vein. * Digestive Tract: Supplied by mesenteric arteries. * Kidneys: Supplied by renal arteries; blood drains through renal veins. * Trunk and Legs: Supplied by iliac arteries; blood returns via iliac veins.
Anatomic Location: The heart is situated in the Mediastinum, the region of the thoracic cavity between the pleural sacs. It extends from the sternum to the spine and is positioned between the $2nd$ and $6th$ ribs.
Physical Specifications: * Weight: Varies by gender. Males average ~ $310\,g$ ; females average ~ $225\,g$ . * Size: Generally corresponds to individual stature, with average dimensions of $12 \times 9 \times 6\,cm$ . * Normal Heart Rate: Typically ranges between $60$ and $100\,bpm$ .
Protective Layers: The heart is surrounded by the Pericardium.

Cardiac Anatomy and Valvular Function

Chambers of the Heart: * Right Atrium: Receives deoxygenated blood from the Superior Vena Cava (upper body) and Inferior Vena Cava (lower body). * Right Ventricle: Pumps deoxygenated blood to the lungs via the pulmonary artery. * Left Atrium: Receives oxygenated blood from the pulmonary veins. * Left Ventricle: Pumps oxygenated blood to the rest of the body via the aorta.
Septum: The muscular wall that divides the right and left sides of the heart.
Directional Valve System: Valves prevent backflow and ensure unidirectional blood flow. * Atrioventricular (AV) Valves: * Tricuspid Valve: Located between the right atrium and right ventricle. * Mitral (Bicuspid) Valve: Located between the left atrium and left ventricle. * Semilunar Valves: * Pulmonary Valve: Located at the exit of the right ventricle leading to the pulmonary artery. * Aortic Valve: Located at the exit of the left ventricle leading to the aorta.
Structural Support of AV Valves: * Chordae Tendineae: Fibrous "heart strings" that anchor the valve leaflets. * Papillary Muscles: Contract to prevent valve prolapse during ventricular contraction. * Commissure: The site where the valve leaflets meet.

Heart Sounds and Valvular Pathologies

Auscultatory Findings: * $S3$ Sound: Characterized as a "gallop rhythm." It is caused by turbulent flow and is frequently associated with left heart failure or severe mitral regurgitation. * $S4$ Sound: Represents forceful atrial contraction attempting to overcome a stiff ventricle.
Mitral Valve Disorders (Murmurs): * Mitral Valve Prolapse: Often described as a "floppy" valve; can be mild and asymptomatic. * Mitral Regurgitation/Incompetence: Backflow from the left ventricle into the left atrium. Causes include degenerative myxomatous changes, rheumatic heart disease (post-Streptococcus infection), and Marfan’s syndrome (connective tissue disease). * Mitral Stenosis: Narrowing that makes it difficult to fill the ventricle or empty the lungs, leading to fluid accumulation in the lungs, cough, fatigue, and dyspnea during exercise.
Aortic Valve Disorders: * Aortic Stenosis: Obstructs blood flow from the heart. Causes include congenital defects (e.g., bicuspid valve with only two cusps instead of three), rheumatic fever, and degenerative calcification. It results in left ventricular hypertrophy. * Aortic Insufficiency (Regurgitation): Backflow into the ventricle. Causes include aortic dilation, infective endocarditis, and Marfan’s syndrome.

The Walls of the Heart and Cardiac Myocytes

Histological Layers: * Pericardium: Consists of a fibrous outer layer and a serous inner layer. The serous layer includes the parietal (fused to fibrous) and visceral (epicardium) layers. * Pericardial Space: Contains pericardial fluid for lubrication. * Epicardium: The outermost protective layer of connective tissue. * Myocardium: The thick, contractile layer of cardiac muscle. * Endocardium: The smooth inner lining forming the chambers and valves. In atria, fibroblasts are dominant.
Characteristics of Cardiac Myocytes: * Dimensions: Tubular shape, width of $20 - 30\,\mu m$ , and length of $100\,\mu m$ . * Structure: Contains one central nucleus, numerous mitochondria, and glycogen granules. * Capillary Ratio: Myocytes exist in a $1:1$ ratio with capillaries to satisfy high metabolic demands. * Electromechanical Coupling: * T-tubules: Sarcolemma extensions that conduct electrical signals deep into the cell. * Sarcoplasmic Reticulum (SR): Stores calcium; abuts T-tubules to form triads. * Intercalated Discs: Contain gap junctions for electrical coupling and desmosomes for mechanical adhesion. * Sarcomeres: The functional units of contraction composed of actin (thin) and myosin (thick) filaments.

Molecular Mechanism of Contraction (Myosin ATPase Cycle)

Cross-Bridge Attachment: The myosin head (in high-energy configuration) attaches to the actin myofilament.
Power Stroke (Working Stroke): The myosin head pivots and bends, pulling the actin filament toward the M line. $ADP$ and inorganic phosphate ( $P_i$ ) are released.
Cross-Bridge Detachment: A new $ATP$ molecule attaches to the myosin head, causing it to release from the actin.
Cocking of the Myosin Head: $ATP$ is hydrolyzed into $ADP$ and $P_i$ , returning the head to its high-energy configuration for the next cycle.

Calcium Regulation: * $TN-I$ (Troponin I): Inhibits the actin-myosin interaction. * $TN-C$ (Troponin C): Binds calcium ( $Ca^{2+}$ ), which removes the $TN-I$ inhibition, allowing contraction.

Electrophysiology and the Conduction System

Major Components: * Sino-atrial (SA) Node: Modified myocytes with minimal contractile elements. Intrinsic rate: $100 - 110\,bpm$ . * Atrioventricular (AV) Node: Intrinsic rate: $40 - 60\,bpm$ . * Bundle of His: Located in the ventricular septa. * Ventricular Conduction System: Includes bundle branches and Purkinje fibers (filled with glycogen). Intrinsic rate: $30\,bpm$ .
Membrane Potentials and Ion Gradients: * Sodium ( $Na^+$ ): Extracellular $135 - 145\,mM$ , Intracellular $10\,mM$ (Ratio $14:1$ ). * Potassium ( $K^+$ ): Extracellular $3.5 - 5.0\,mM$ , Intracellular $135\,mM$ (Ratio $1:30$ ). * Chloride ( $Cl^-$ ): Extracellular $95 - 110\,mM$ , Intracellular $10 - 20\,mM$ (Ratio $4:1$ ). * Calcium ( $Ca^{2+}$ ): Extracellular $2\,mM$ , Intracellular $10^{-7}\,mM$ (Ratio $200,000,000:1$ ).
SA Node Pacemaker Potential Phases: * Phase 4: Spontaneous depolarization via slow inward $Na^+$ current ( $I_f$ "funny" current). At $-45\,mV$ , T-type (transient) $Ca^{2+}$ channels open. L-type (long-lasting) channels open as threshold ( $-40$ to $-30\,mV$ ) is reached. * Phase 0: The spike (upstroke) triggered by L-type $Ca^{2+}$ channels. * Phase 3: $K^+$ channels open for repolarization to $-60\,mV$ .
Ventricular Action Potential (AP) Phases: * Phase 0: Rapid depolarization via fast inward $Na^+$ current. * Phase 1: Partial repolarization via outward $K^+$ current. * Phase 2 (Plateau): Long-lasting inward $Ca^{2+}$ current (L-type) counteracts outward $K^+$ flow. * Phase 3: Rapid repolarization as $K^+$ channels open and $Ca^{2+}$ channels close. * Phase 4: Resting state; gradients restored by $Na^+-K^+$ ATPase.
Refractory Periods: * Absolute Refractory Period (ARP): Phases 1, 2, and partial 3. Fast $Na^+$ channels are gated closed; no new AP possible. * Relative Refractory Period (RRP): Phase 3. Large $K^+$ efflux occurs; a strong stimulus may trigger a smaller AP.

Autonomic Regulation and Pharmacology

Key Regulatory Terms: * Chronotropy: Heart rate (HR). * Dromotropy: Conduction velocity. * Inotropy: Contractility (strength of contraction). * Lusitropy: Rate of relaxation.
Parasympathetic Stimulation: * Mediated by the Vagus Nerve (cholinergic). * Acetylcholine (ACh) binds to Muscarinic ( $M2$ ) receptors in the SA and AV nodes. * Effects: Negative chronotropy and dromotropy (reduces HR to typical $70\,bpm$ ). Excess stimulation causes bradycardia or conduction block, treated by atropine.
Sympathetic Stimulation: * Noradrenaline (NE) binds to $\beta 1$ and $\beta 2$ receptors. * $\alpha 1$ Receptors: Majority of cardiac effects; positive chronotropy and inotropy. * $\beta 2$ Receptors: Relevant in heart failure when $\beta 1$ is downregulated. * Beta Blockers (e.g., Propranolol): Prevent overworking of the heart in response to sympathetic triggers (hypertension, angina).

Excitation-Contraction (E-C) Coupling and Ion Transport

Mechanism: Depolarization allows $Ca^{2+}$ entry, which triggers " $Ca^{2+}$ -induced $Ca^{2+}$ release" from the SR via ryanodine receptors.
Ion Shifts: Free cytosolic $Ca^{2+}$ rises from $10^{-7}\,M$ to $10^{-5}\,M$ during contraction.
Relaxation Processes: * $Ca^{2+}$ is sequestered back into the SR by SERCA (ATP-dependent pump). * $Ca^{2+}$ is removed via $Na^+-Ca^{2+}$ exchange and $Ca^{2+}-ATPase$ across the sarcolemma.
Modifying Inotropy (Strength of Contraction): * Increase Inotropy: Sympathetic stimulation, catecholamines (adrenaline, dobutamine), calcium sensitizers (levosimendan), and Phosphodiesterase inhibitors (milrinone). * Digoxin (Digitalis): Blocks $Na^+-K^+$ ATPase to maintain intracellular $Ca^{2+}$ levels.

Clinical Rhythm and Conduction Disruptions

Heart Rate Abnormalities: * Bradycardia: Resting adult HR < $60\,bpm$ (common in athletes or during sleep). * Tachycardia: Resting adult HR > $100\,bpm$ (caused by stress, fever, or disease).
Conduction Failures: * Nodal Block: If the SA node fails, the AV node takes over at a slower rate. If both fail, Purkinje fibers set a very slow pace. * AV Block: Interruption between atria and ventricles, causing them to contract at different rates.
Specific Syndromes: * Atrial Fibrillation: Rapid, irregular atrial contraction leading to poor pumping efficiency. * Wolff-Parkinson-White Syndrome: An extra electrical circuit between the atria and ventricles causing supraventricular tachycardia. * Ventricular Fibrillation: Complete loss of pumping function; ECG shows total disorganization with no QRS complexes.