Cardiovascular physiology
Cardiovascular physiology is the study of the functions and mechanisms of the cardiovascular system, which provides blood supply throughout the body by responding to various stimuli to control the velocity and amount of blood carried through the vessels.[1] This system ensures the delivery of oxygen and nutrients to tissues while removing metabolic waste products, maintaining homeostasis under diverse physiological conditions.[1] The cardiovascular system comprises three primary components: the heart, blood vessels, and blood itself. The heart acts as a muscular pump that propels blood into the arteries, with the left ventricle ejecting oxygenated blood into the aorta for systemic circulation and the right ventricle sending deoxygenated blood into the pulmonary artery for oxygenation in the lungs.[1] Blood vessels form a network including elastic arteries that distribute blood under high pressure, capillaries where exchange of gases and nutrients occurs, and veins that return blood to the heart, often aided by one-way valves to prevent backflow.[1] Blood, consisting of plasma and cellular elements like erythrocytes and leukocytes, serves as the transport medium, with veins holding up to 70% of the total circulating volume at rest.[1] Key physiological processes in the cardiovascular system include the cardiac cycle, hemodynamics, and regulatory mechanisms. The cardiac cycle involves sequential phases of contraction (systole) and relaxation (diastole), generating pressure changes that drive blood flow through the heart's chambers and into the vasculature.[2] Cardiac output, defined as the product of stroke volume (the volume of blood ejected per beat) and heart rate, typically ranges from 4 to 8 liters per minute in adults at rest and is a critical determinant of overall perfusion.[3] Regulation occurs via the autonomic nervous system—parasympathetic input slows heart rate while sympathetic input accelerates it—along with hormonal influences like epinephrine and local factors such as electrolytes and blood volume.[1] The system operates in two interconnected circuits: pulmonary circulation, which oxygenates blood in the lungs, and systemic circulation, which distributes it to peripheral tissues.[1] These circuits maintain an ejection fraction greater than 55% under normal conditions, ensuring efficient tissue perfusion and adaptation to demands like exercise or stress.[1] Disruptions in these processes can impair overall function, underscoring the system's integrated role in sustaining life.[1]Cardiac Physiology
Anatomy of the Heart
The heart is a muscular organ situated in the mediastinum of the thoracic cavity, with approximately two-thirds of its mass positioned to the left of the body's midline and resembling the size of a closed fist. It functions as the central pump of the cardiovascular system, enclosed by the rib cage and resting on the diaphragm. The heart connects to major vessels that facilitate blood entry and exit: the superior and inferior venae cavae deliver deoxygenated blood to the right side, pulmonary veins carry oxygenated blood to the left side from the lungs, the pulmonary trunk directs deoxygenated blood from the right ventricle to the lungs, and the aorta distributes oxygenated blood from the left ventricle to the systemic circulation.[4] The interior of the heart is divided into four chambers: two superior atria and two inferior ventricles, separated by the interatrial and interventricular septa to prevent mixing of oxygenated and deoxygenated blood. The right atrium, a thin-walled chamber, receives deoxygenated blood from the systemic circulation via the venae cavae and forwards it to the right ventricle. The left atrium, similarly thin-walled, collects oxygenated blood from the four pulmonary veins and passes it to the left ventricle. The right ventricle, with moderately thick walls, pumps deoxygenated blood through the pulmonary trunk to the lungs for oxygenation. The left ventricle, featuring the thickest walls due to the high pressure required for systemic circulation, ejects oxygenated blood into the aorta. These chambers are lined with endocardium and connected by valved openings to ensure efficient, one-way blood flow.[4] To maintain unidirectional blood movement and prevent regurgitation, the heart incorporates four valves: two atrioventricular (AV) valves and two semilunar valves. The tricuspid AV valve, located between the right atrium and ventricle, consists of three cusps anchored by chordae tendineae to papillary muscles, closing during ventricular systole to block backflow into the right atrium. The mitral (or bicuspid) AV valve, between the left atrium and ventricle, has two cusps similarly secured, ensuring no retrograde flow during left ventricular contraction. The pulmonary semilunar valve, positioned at the junction of the right ventricle and pulmonary trunk, features three cusps that open under ventricular pressure and close to prevent blood return from the pulmonary arteries. The aortic semilunar valve, at the left ventricle-aorta interface, also has three cusps and functions analogously to safeguard ventricular filling during diastole. These valves operate passively, driven by pressure gradients across them.[4] The heart wall comprises three primary layers—the endocardium, myocardium, and epicardium—surrounded by the protective pericardium. The endocardium, the innermost layer, is a thin sheet of simple squamous endothelial cells overlying a subendothelial layer of loose connective tissue, collagen, elastin, and occasional smooth muscle cells or vessels; it lines all chambers and valves, providing a smooth, non-thrombogenic surface for blood contact and is thicker in the left atrium due to elevated pulmonary venous pressures.[5] The myocardium forms the bulky middle layer, consisting of specialized cardiac muscle tissue that enables the heart's pumping action. It is built from branched, striated cardiomyocytes, each typically mononucleated with a central nucleus, abundant mitochondria for aerobic metabolism, and myoglobin for oxygen storage; these fibers are shorter and more extensively branched than skeletal muscle fibers, arranged in interwoven spiral layers aligned with ventricular axes for efficient twisting contraction. Adjacent cardiomyocytes connect end-to-end via intercalated discs, complex junctions of the sarcolemma that include desmosomes for mechanical adhesion (preventing cell separation during forceful contractions) and gap junctions for low-resistance electrical coupling, allowing rapid ion flow and synchronized depolarization across the myocardium to form a functional syncytium.[5][6] The epicardium, the outermost myocardial covering, is a visceral layer of the serous pericardium composed of mesothelial cells atop fibroelastic connective tissue and adipose deposits; it houses coronary vessels, lymphatics, and nerves while providing a slippery external surface. Enclosing the entire heart, the pericardium is a fibroserous sac with an outer tough fibrous layer anchoring the heart to the mediastinum and diaphragm, and an inner serous layer divided into visceral (epicardium) and parietal components separated by the pericardial cavity, which contains 15–50 mL of lubricating fluid secreted by mesothelial microvilli to minimize friction during cardiac motion.[5][4] The myocardium receives its nutrient supply via the coronary circulation, a network of arteries and veins embedded in the epicardium and penetrating deeper layers. The right coronary artery (RCA) originates from the right sinus of Valsalva in the aortic root, travels along the right atrioventricular (coronary) sulcus, and supplies the right atrium, right ventricle, portions of the left ventricle's posterior wall, and often the sinoatrial (SA) and atrioventricular (AV) nodes through branches like the SA nodal artery (supplying ~60% of SA nodes), right marginal artery (lateral right ventricle), and posterior descending artery (in ~70% of right-dominant hearts, perfusing the posterior interventricular septum). The left main coronary artery arises from the left aortic sinus, courses briefly before bifurcating into the left anterior descending (LAD) artery—which runs in the anterior interventricular sulcus to nourish the anterior two-thirds of the interventricular septum, anterior left ventricle, and apex via septal and diagonal branches—and the left circumflex (LCx) artery, which follows the left atrioventricular sulcus to vascularize the left atrium, lateral and posterior left ventricle, and potentially the SA node or posterior descending artery in left-dominant (~10%) or codominant (~20%) variants. Coronary veins, including the great, middle, and small cardiac veins, converge into the coronary sinus along the posterior atrioventricular sulcus, draining ~75% of myocardial blood into the right atrium; the remainder returns via anterior cardiac veins or Thebesian veins directly into chambers. This system ensures oxygenated blood delivery primarily during diastole, when myocardial compression is minimal.[7][8]Electrical Conduction System
The electrical conduction system of the heart is a specialized network of cells that generates and propagates electrical impulses to coordinate myocardial contractions, ensuring efficient pumping of blood. This system originates in the sinoatrial (SA) node, located in the right atrial wall near the superior vena cava entrance, which serves as the primary pacemaker due to its inherent automaticity. The impulse then spreads through the atria, pauses at the atrioventricular (AV) node in the interatrial septum, and rapidly conducts to the ventricles via the bundle of His, bundle branches, and Purkinje fibers.[9][10][11] The key components include the SA node, composed of pacemaker cells that spontaneously depolarize; the AV node, which delays the impulse to allow atrial emptying; the bundle of His (or atrioventricular bundle), a tract extending from the AV node along the interventricular septum; left and right bundle branches that diverge to the ventricular walls; and Purkinje fibers, which distribute the signal across the ventricular myocardium for synchronized contraction. These elements form a hierarchical pathway where the SA node's faster firing rate (intrinsic 60-100 beats per minute) dominates over subsidiary pacemakers like the AV node (40-60 beats per minute). Automaticity in pacemaker cells arises from specialized ion channel activity, particularly the funny current (If) mediated by hyperpolarization-activated cyclic nucleotide-gated channels, enabling gradual diastolic depolarization.[9][10][12] In cardiac myocytes, electrical activity manifests as action potentials with five phases: phase 0 (rapid depolarization) driven by influx of Na⁺ through voltage-gated sodium channels; phase 1 (early repolarization) due to transient outward K⁺ current; phase 2 (plateau) sustained by Ca²⁺ entry via L-type channels balanced against K⁺ efflux; phase 3 (repolarization) dominated by delayed rectifier K⁺ currents; and phase 4 (resting potential) maintained by inward rectifier K⁺ channels, with pacemaker cells showing a slower phase 4 upstroke. Unlike neuronal action potentials, the cardiac version's prolonged plateau (phase 2) prevents tetanus and links excitation to contraction via Ca²⁺-induced Ca²⁺ release. Ion channel composition varies: working myocytes rely heavily on fast Na⁺ channels for conduction velocity up to 1 m/s, while Purkinje fibers express high densities of Na⁺ and gap junctions (connexin-43) for rapid spread.[13][14][15] Impulse propagation begins with SA node depolarization spreading via internodal pathways and atrial myocardium at 0.3-0.4 m/s, causing atrial contraction. At the AV node, conduction slows to 0.05 m/s due to fewer gap junctions and reliance on Ca²⁺-dependent channels, introducing a 0.1-0.2 second delay critical for ventricular filling. The signal then accelerates through the bundle of His (1-2 m/s) and Purkinje system (2-4 m/s), reaching endocardial ventricular surfaces before epicardial activation for apex-to-base contraction. This rapid ventricular conduction ensures near-simultaneous depolarization, minimizing dyssynchrony.[10][12][11] Normal sinus rhythm reflects SA node dominance, producing a heart rate of 60-100 beats per minute at rest, with each cycle initiating from the SA node. Automaticity ensures rhythmic firing without external stimuli, though modulated by intrinsic factors like temperature or electrolytes. Deviations, such as rates below 60 bpm (bradycardia) or above 100 bpm (tachycardia), may indicate conduction issues but fall outside intrinsic system norms.[9][16][13] Electrocardiography (ECG) noninvasively records this activity via surface leads, with the P wave representing atrial depolarization (0.08-0.11 seconds duration); the QRS complex depicting ventricular depolarization (0.06-0.10 seconds, masking atrial repolarization); and the T wave indicating ventricular repolarization (0.10-0.25 seconds). The PR interval (0.12-0.20 seconds) encompasses AV nodal delay, while the QT interval reflects overall ventricular action potential duration. These waveforms provide diagnostic insights into conduction integrity.[17][18][19]Mechanical Events of the Cardiac Cycle
The mechanical events of the cardiac cycle describe the sequence of pressure, volume, and valve dynamics in the heart during a single heartbeat, initiated by electrical depolarization from the sinoatrial node. These events ensure efficient blood propulsion through alternating contraction (systole) and relaxation (diastole) of the atria and ventricles. Systole and diastole encompass distinct subphases that coordinate to maintain unidirectional flow and prevent regurgitation.[20] Ventricular systole begins with isovolumetric contraction, where all valves are closed, and ventricular pressure rises rapidly without volume change until it exceeds aortic pressure, allowing ejection. The ejection phase follows, divided into rapid and reduced ejection, during which blood is expelled into the aorta and pulmonary artery, reducing ventricular volume. Ventricular diastole starts with isovolumetric relaxation, where ventricular pressure falls below atrial pressure with valves still closed, followed by rapid filling as atrioventricular valves open and blood flows passively from the atria. Slower filling then occurs until atrial systole completes the cycle by adding a final boost to ventricular volume. Atrial systole precedes ventricular systole, but the ventricles dominate mechanical output.[20] Pressure-volume loops graphically represent these mechanical events in the left ventricle, plotting ventricular pressure against volume across the cardiac cycle. The loop's bottom-right corner marks end-diastolic volume (EDV), the maximum preload volume after filling, typically around 120-130 mL in adults at rest. The top-left corner indicates end-systolic volume (ESV), the residual volume after ejection, usually 50-60 mL. Stroke volume (SV), the ejected blood per beat, is the difference between EDV and ESV, forming the loop's width and averaging 70 mL. The loop's area quantifies stroke work, influenced by contractility and load.[21][3] Heart sounds arise from valve closures and vibrations during these phases, audible on auscultation and clinically significant for diagnosing abnormalities. The first heart sound (S1), a low-frequency "lub," results from closure of the mitral and tricuspid valves at the onset of ventricular systole, marking the end of isovolumetric contraction. The second heart sound (S2), a higher-frequency "dub," occurs with semilunar valve closure at the end of ejection, signaling the start of diastole; its splitting (A2 before P2) reflects asynchronous aortic and pulmonary valve closure. These sounds provide insights into valve integrity and timing disorders like murmurs.[22][23] The Frank-Starling mechanism links mechanical preload to contractile force, ensuring stroke volume adjusts to venous return. As EDV increases, sarcomere stretch enhances actin-myosin overlap and calcium sensitivity, boosting contractility and SV up to a physiological limit. This intrinsic autoregulation maintains balance between right and left ventricular outputs without neural input.[24][25] Atrial contraction contributes actively to ventricular filling, accounting for approximately 20-30% of EDV in healthy individuals at rest, beyond the 70-80% from passive diastolic filling. This "atrial kick" augments preload, particularly during exercise or upright posture when venous return varies. Loss of atrial contribution, as in atrial fibrillation, reduces SV by up to 20%, highlighting its mechanical importance.[20][26]Determinants of Cardiac Output
Cardiac output (CO) represents the total volume of blood pumped by the heart per minute and is a critical measure of cardiovascular performance. It is calculated as the product of heart rate (HR), the number of beats per minute, and stroke volume (SV), the volume of blood ejected per beat:CO = HR \times SV
In healthy adults at rest, CO typically ranges from 5 to 6 L/min, varying with body size and activity level.[3] This formula underscores the interdependence of HR and SV in determining overall circulatory output. Stroke volume is modulated by three primary intrinsic factors: preload, contractility (or inotropy), and afterload. Preload refers to the end-diastolic volume or pressure in the ventricles, which stretches myocardial fibers and influences the force of contraction via the Frank-Starling mechanism. According to the Frank-Starling law, increased preload enhances SV up to an optimal point on the Starling curve, beyond which excessive stretch impairs function; this intrinsic property allows the heart to match output to venous return on a beat-to-beat basis.[25] Venous return, the primary determinant of preload, is governed by the venous return curve, which plots cardiac output against right atrial pressure. This curve is shaped by mean systemic filling pressure (MSFP), the pressure driving blood toward the heart when it stops beating (typically 7 mmHg), and vascular compliance, which affects how blood volume is distributed; higher MSFP or lower compliance steepens the curve, promoting greater return and thus higher CO at equilibrium.[27] Contractility reflects the intrinsic strength of ventricular contraction independent of preload or afterload, often enhanced by sympathetic stimulation, while afterload is the resistance against which the ventricle ejects blood, primarily arterial pressure; elevated afterload, such as aortic pressure, reduces SV by impeding ejection.[3] The interaction between HR and SV ensures adaptive responses to physiological demands. During exercise, for instance, CO can increase fivefold or more (up to 25-35 L/min in trained individuals) through simultaneous elevations in HR (via autonomic acceleration) and SV (via augmented preload from venoconstriction and contractility from catecholamines), with reduced afterload from peripheral vasodilation further facilitating output.[28] This integration maintains balance between cardiac pumping and systemic needs, preventing venous congestion or inadequate perfusion. Clinical measurement of CO relies on established techniques like the Fick principle and echocardiography. The Fick method, the historical gold standard, estimates CO by dividing oxygen consumption by the arterial-venous oxygen content difference, requiring catheterization for mixed venous sampling but providing accurate invasive assessment.[29] Noninvasively, echocardiography derives CO from SV (via left ventricular outflow tract velocity-time integral and cross-sectional area) multiplied by HR, offering real-time imaging but subject to operator variability and geometric assumptions.[30]