Table of Contents
Overview of Cardiovascular Physiology ❤️
The cardiovascular system is the transport network of the body. For Step 1, you must understand how the heart generates pressure, how blood flows through vessels, and how the system responds to physiological and pathological changes. This chapter focuses on the unique physiological principles that govern the cardiovascular system. Concepts that belong specifically to diseases or drugs will be detailed in later chapters.
Cardiovascular physiology is built on three central ideas: how the heart pumps, how blood moves through vessels, and how pressure and flow are regulated to meet the needs of tissues at rest and during stress. Everything you will see in pathology and pharmacology later is a modification of these basic rules.
Functional Anatomy for Physiology 🫀
You have already seen structural anatomy elsewhere. Here, the focus is on how the anatomical parts work together during each heartbeat.
The heart has two major functional pumps. The right heart receives systemic venous blood and pumps it to the lungs. The left heart receives oxygenated blood from the lungs and pumps it to the systemic circulation. Within each side, atria are primarily low pressure filling chambers, while ventricles are high pressure pumping chambers.
The valves create one way flow: tricuspid between right atrium and ventricle, pulmonary between right ventricle and pulmonary artery, mitral between left atrium and ventricle, and aortic between left ventricle and aorta. Their opening and closing are passive and depend on pressure differences. A valve opens when the upstream chamber has higher pressure and closes when the downstream pressure becomes higher.
Ventricular walls differ in thickness because of differences in workload. The left ventricle, which must generate systemic arterial pressure, has a thick muscular wall and high systolic pressures. The right ventricle pumps against a much lower resistance pulmonary circulation, so it is thinner and generates lower pressures.
Cardiac Cycle and Heart Sounds 🎧
The cardiac cycle is one complete sequence of contraction and relaxation of the heart. It is usually described for the left ventricle and can be divided into systole, when the ventricle contracts and ejects blood, and diastole, when it relaxes and fills. At normal heart rates, diastole is longer than systole, but as heart rate increases, diastole shortens disproportionately, which can impair ventricular filling and coronary perfusion.
At the start of systole, ventricular pressure rises above atrial pressure, which closes the mitral valve. This closure produces the first heart sound S1. For a brief period, both the mitral and aortic valves are closed while the ventricle generates pressure. This is isovolumetric contraction. When ventricular pressure exceeds aortic pressure, the aortic valve opens and ejection begins. Early ejection is rapid, then slows as the pressure gradient falls.
At the end of systole, when ventricular pressure falls below aortic pressure, the aortic valve closes. This closure produces the second heart sound S2. Again there is a short interval when both mitral and aortic valves are closed, called isovolumetric relaxation. Once ventricular pressure drops below atrial pressure, the mitral valve opens and filling begins.
Diastolic filling has two main parts. Early rapid passive filling occurs due to the pressure gradient from atrium to ventricle. Later, atrial contraction provides an extra contribution to ventricular filling. This atrial kick is important when ventricular compliance is reduced or at higher heart rates. On the pressure volume loop, these phases correspond to the bottom border, where volume increases at relatively low pressure.
Heart sounds correspond to mechanical events. S1 is due to closure of atrioventricular valves at the onset of systole, and S2 is due to closure of semilunar valves at the end of systole. Additional sounds S3 and S4 relate to abnormal or accentuated filling and can indicate pathology, but their detailed clinical interpretation is considered with cardiac diseases.
Pressure Volume Relationships 📈
The pressure volume loop is a central graphical tool to understand ventricular function. It plots left ventricular pressure on the vertical axis against left ventricular volume on the horizontal axis over one cardiac cycle. Each corner of the loop corresponds to a key moment in the cycle.
End diastolic point has the largest volume, called end diastolic volume (EDV), and occurs just before ventricular contraction. The line from this point to the end systolic point is the ejection phase. The smallest volume at the end of systole is the end systolic volume (ESV). The difference between EDV and ESV is stroke volume (SV).
Stroke volume: $SV = EDV - ESV$
The loop boundaries represent mechanical properties. The end diastolic pressure volume relationship (EDPVR) is the bottom curving line that describes how ventricular pressure rises with volume during filling. It reflects ventricular compliance or stiffness. The end systolic pressure volume relationship (ESPVR) is the upper left border that connects end systolic points at different contractile states and is a measure of contractility.
Changes in preload, afterload, and contractility reshape the loop in characteristic ways. Increased preload shifts the loop to the right with a larger EDV and increased stroke volume, assuming contractility and afterload are unchanged. Increased afterload makes the loop taller and narrower, with higher systolic pressure but smaller stroke volume. Increased contractility steepens the ESPVR and reduces ESV, which increases stroke volume at the same preload and afterload.
These graphical effects are highly testable because they directly integrate with concepts of heart failure, valvular disease, and drug effects that will appear later.
Preload, Afterload, Contractility, and Heart Rate ⚙️
Four variables control cardiac output: preload, afterload, contractility, and heart rate. Each has a precise physiological meaning and different mechanisms.
Preload is the load on the ventricle at the end of diastole, which stretches the myocardial fibers before contraction. In practice, preload correlates with end diastolic volume or end diastolic pressure. In the whole circulation, venous return is a major determinant of preload. More venous return increases EDV and therefore increases stretch of the ventricle.
Afterload is the load against which the ventricle must contract to eject blood. For the left ventricle, afterload is closely related to aortic pressure and systemic vascular resistance. An increase in arterial blood pressure or vasoconstriction increases afterload, making the ventricle work harder and often reducing stroke volume if other factors stay constant.
Contractility, also called inotropy, is the intrinsic strength of the myocardium at a given preload and afterload. Positive inotropic influences increase the force of contraction and reduce end systolic volume, which increases stroke volume. Sympathetic stimulation and circulating catecholamines increase contractility. Negative inotropic conditions, such as myocardial ischemia, reduce contractility.
Heart rate is the number of beats per minute. It directly influences cardiac output through its role in the cardiac output formula, but it also modifies filling time. Very high heart rates can reduce diastolic filling and stroke volume.
Cardiac output (CO) is the volume of blood ejected by a ventricle per minute. Stroke volume is the volume ejected per beat. Their relationship is fundamental.
Cardiac output: $CO = HR \times SV$
Systemic blood flow from the left ventricle must match venous return over time. Any chronic mismatch leads to congestion or inadequate perfusion.
Frank Starling Mechanism 📐
The Frank Starling law describes how the heart adjusts its stroke volume to match venous return using intrinsic properties of cardiac muscle. As preload increases within a physiological range, stroke volume increases. This occurs because increased sarcomere length enhances cross bridge formation, which increases the force of contraction.
Graphically, this relationship is shown as a curve of stroke volume or cardiac output on the vertical axis versus end diastolic volume or pressure on the horizontal axis. Moving along a single curve reflects changes in preload. A shift to a higher curve indicates increased contractility or reduced afterload, while a shift to a lower curve indicates decreased contractility or increased afterload.
This intrinsic mechanism helps maintain balance between the outputs of the right and left ventricles. For example, if right ventricular output increases slightly, more blood returns to the left heart, which increases left ventricular preload and thus its stroke volume, restoring equality of flows.
On the exam, Frank Starling curves are often combined with venous return curves to interpret changes in cardiac function due to volume changes, resistance changes, or sympathetic stimulation.
Myocardial Action Potentials and Conduction 🧠
Cardiac electrical activity has two main categories of action potentials: fast response in working atrial and ventricular myocytes and Purkinje fibers, and slow response in pacemaker cells of the sinoatrial (SA) and atrioventricular (AV) nodes. These electrical events initiate and coordinate the mechanical pumping of the heart.
Fast response action potentials have distinct phases. Phase 0 is rapid depolarization due to opening of voltage gated fast sodium channels and sodium influx. Phase 1 is initial repolarization from transient outward potassium current. Phase 2 is the plateau phase caused by a balance between calcium influx through L type calcium channels and potassium efflux. Phase 3 is repolarization due to increased potassium efflux and decreased calcium influx. Phase 4 is the resting membrane potential, which is relatively stable in these cells.
Slow response pacemaker action potentials in SA and AV nodes differ. Phase 0 depolarization is slower and depends on calcium influx through L type calcium channels, not fast sodium channels. Phase 3 is repolarization from potassium efflux. Phase 4 is not stable. It shows spontaneous gradual depolarization called pacemaker potential, largely due to funny current (If), which is a mixed sodium and potassium inward current, and also due to T type calcium channels.
The SA node has the steepest phase 4 depolarization and normally sets the heart rate as the primary pacemaker. The depolarization spreads through the atria to the AV node, where conduction is intentionally slow. This AV nodal delay allows time for atrial contraction before ventricular contraction. From the AV node, the impulse travels rapidly through the His Purkinje system to both ventricles, ensuring nearly simultaneous activation and coordinated contraction.
Sympathetic and parasympathetic inputs modulate these action potentials. Sympathetic stimulation increases the slope of phase 4 in nodal cells, increasing heart rate, and enhances calcium currents, increasing conduction and contractility. Parasympathetic stimulation through the vagus nerve decreases the phase 4 slope, hyperpolarizes nodal cells, and slows AV nodal conduction.
Many antiarrhythmic drugs act by modifying specific ion channels in these action potentials. The classification and pharmacology of these drugs will be addressed in pharmacology and arrhythmia sections.
Cardiac Output, Venous Return, and Vascular Function 🌊
Blood flow through the circulation depends on the interaction between the heart as a pump and the vascular system as a network of resistances and capacitors. Cardiac output must equal venous return at steady state, and both are influenced by vascular properties.
Mean systemic filling pressure is the pressure in the systemic circulation when the heart is stopped and blood has redistributed. It reflects vascular volume and tone. Higher blood volume or venoconstriction increases mean systemic filling pressure and shifts the venous return curve upward, promoting greater venous return at any given right atrial pressure.
Right atrial pressure acts as a back pressure for venous return. When right atrial pressure rises, the gradient between peripheral veins and the right atrium decreases, which reduces venous return. Graphs of venous return show a curve that falls as right atrial pressure rises and intersects the cardiac output curve at an equilibrium point. Interventions that change cardiac function or vascular function move this intersection to new levels of cardiac output and right atrial pressure.
Total peripheral resistance also influences these relationships. Increased resistance reduces venous return and tends to decrease cardiac output at equilibrium, while decreased resistance has opposite effects. These concepts explain how hemorrhage, fluid infusion, vasoconstrictors, and vasodilators change cardiovascular status even before disease mechanisms are considered.
Systemic and Pulmonary Circulation Differences 🌍
The systemic and pulmonary circulations are arranged in series but have very different pressures and resistances. Systemic circulation operates at high pressure with high resistance. Mean arterial pressure is relatively high and drives flow to all body organs. Pulmonary circulation operates at low pressure and low resistance to protect the delicate alveolar capillaries and allow efficient gas exchange.
Systemic arteries have thick muscular walls and small lumens, which contribute to high resistance and allow active regulation of organ blood flow. Pulmonary arteries have thinner walls and more distensible vessels, which allows them to handle the entire cardiac output at low pressure. Any rise in pulmonary vascular resistance or pressure can rapidly lead to right ventricular strain.
Despite these differences, cardiac output through both circuits must be equal in steady state. Changes in one circulation ultimately affect the other through effects on preload and afterload of each ventricle.
Hemodynamics, Flow, Pressure, and Resistance 💧
Hemodynamics describes how blood moves through vessels under pressure. The relationships between flow, pressure, and resistance are highly tested and mathematically simple.
Flow (Q) through a vessel or circulation is proportional to the pressure difference and inversely proportional to resistance. This is analogous to Ohm’s law in electricity.
Basic flow equation: $Q = \dfrac{\Delta P}{R}$
For the systemic circulation, the relevant pressure difference is mean arterial pressure minus right atrial pressure. Because right atrial pressure is usually low, mean arterial pressure is often used as the main driver. Total peripheral resistance (TPR) is the sum of individual organ resistances and determines the relationship between cardiac output and arterial pressure.
Resistance in a single vessel is described by Poiseuille’s law, which shows a powerful effect of vessel radius.
Vascular resistance: $R \propto \dfrac{\text{viscosity} \times \text{length}}{r^4}$
Because resistance is inversely proportional to the fourth power of radius, small changes in radius lead to large changes in resistance and flow. This is why arterioles, which can change radius by smooth muscle contraction and relaxation, are called resistance vessels and are crucial targets of physiological control and drugs.
Blood flow in vessels can be laminar or turbulent. Laminar flow has a parabolic velocity profile and is silent. Turbulent flow produces murmurs and bruits and occurs when the Reynolds number is high. High velocity, large diameter, and low viscosity all promote turbulence. Conditions such as anemia, stenotic valves, or arteriovenous shunts can increase Reynolds number and create audible sounds.
Capillaries have the largest total cross sectional area in the circulation, which leads to low velocity of blood flow in this segment. This slow flow allows adequate time for exchange of gases, nutrients, and waste products.
Arterial Pressure and Its Determinants ⏱️
Arterial pressure fluctuates with each heartbeat but is clinically represented by systolic, diastolic, and mean arterial pressure. Systolic pressure is the peak arterial pressure during ventricular ejection, while diastolic pressure is the lowest pressure during ventricular relaxation just before the next beat. Mean arterial pressure is the average pressure over the cardiac cycle and determines tissue perfusion.
In practice, mean arterial pressure (MAP) is approximated by a weighted average of systolic and diastolic pressures, since diastole occupies more of the cycle at normal heart rates.
Mean arterial pressure (approximation): $MAP \approx \dfrac{SBP + 2 \times DBP}{3}$
Arterial pressure is determined by cardiac output and total peripheral resistance. For the systemic circulation, this relationship parallels the basic flow equation.
Mean arterial pressure: $MAP = CO \times TPR$
An increase in cardiac output at constant resistance will raise arterial pressure, and an increase in resistance at constant cardiac output will also raise pressure. These relationships are central to understanding hypertension mechanisms and drug effects.
Pulse pressure is the difference between systolic and diastolic pressures. It is influenced by stroke volume and arterial compliance. An increase in stroke volume or decrease in arterial compliance, as with stiff arteries, increases pulse pressure. Wide pulse pressure is seen in several valve diseases and in aging-related arterial stiffness.
Large arteries also act as Windkessel vessels. During systole they expand and store some of the stroke volume as elastic energy, which is then released during diastole to maintain flow when the heart is relaxed. Loss of compliance in these vessels reduces this buffering function and increases systolic pressure.
Microcirculation and Capillary Exchange 🧬
The microcirculation consists of arterioles, capillaries, and venules. It is the site of nutrient and gas exchange and is governed by the balance of hydrostatic and oncotic pressures across the capillary wall.
Capillary hydrostatic pressure pushes fluid out of the capillary into the interstitial space, while plasma oncotic pressure, mainly from albumin, pulls fluid into the capillary. Interstitial hydrostatic and oncotic pressures oppose or favor movement in the other direction. The net movement of fluid is described by the Starling equation, which you will see in detail in other sections, but the concept is straightforward. Filtration occurs when outward forces exceed inward forces, and absorption occurs when inward forces exceed outward forces.
Along the length of a capillary, hydrostatic pressure usually falls from the arterial to venous end, while oncotic pressure remains relatively constant. This often results in net filtration at the arterial end and net reabsorption at the venous end. The lymphatic system returns excess filtered fluid and proteins to the circulation, which prevents accumulation of interstitial fluid.
Failure of any component of this system, such as increased hydrostatic pressure in heart failure, decreased plasma proteins in liver disease, increased capillary permeability in inflammation, or lymphatic obstruction, can lead to edema formation. These pathophysiological details will be integrated later with systemic diseases.
Local and Neural Regulation of Blood Flow 🧬🧠
Blood flow must be matched to the metabolic needs of each tissue. This is achieved through local intrinsic mechanisms and systemic neural and hormonal controls.
Local control includes metabolic and myogenic mechanisms. In metabolic regulation, increased tissue metabolism results in accumulation of vasodilator substances such as CO₂, H⁺, adenosine, and low oxygen, which cause local vasodilation and increased blood flow. This active hyperemia ensures that working tissues, such as exercising muscle, receive enough oxygen and nutrients.
Reactive hyperemia occurs when blood flow to a tissue is temporarily blocked then restored. During the occlusion, vasodilator metabolites accumulate. When flow resumes, there is a transient overshoot of blood flow above baseline until these metabolites wash out.
The myogenic response is an intrinsic ability of vascular smooth muscle to contract in response to increased intraluminal pressure and relax when pressure falls. This contributes to autoregulation of blood flow. Organs like brain, kidney, and heart maintain relatively constant blood flow over a wide range of arterial pressures by adjusting arteriolar resistance through these intrinsic mechanisms.
Neural control of blood vessels is dominated by the sympathetic nervous system. Most systemic arterioles receive sympathetic adrenergic fibers that maintain a basal vasoconstrictor tone. Increased sympathetic activity causes vasoconstriction and increases total peripheral resistance. Decreased activity causes vasodilation. In skeletal muscle and some other beds, interactions between different adrenergic receptor subtypes and local metabolic factors create complex patterns of regulation that become critical during exercise and stress.
Hormonal factors such as angiotensin II, vasopressin, epinephrine, and atrial natriuretic peptide further modulate vascular tone and volume status. Their integrated actions will be detailed in endocrine and renal chapters.
Baroreceptor Reflex and Rapid Pressure Control 📡
Short term regulation of arterial pressure is primarily handled by the baroreceptor reflex. Baroreceptors are stretch sensitive mechanoreceptors located in the carotid sinus and aortic arch. They sense changes in arterial pressure through vessel wall stretch and send afferent signals to the cardiovascular center in the medulla.
Increased arterial pressure increases baroreceptor firing. The medulla responds by decreasing sympathetic outflow and increasing parasympathetic activity. This reduces heart rate, decreases contractility, and causes arteriolar and venous vasodilation, which together lower blood pressure back toward normal. Decreased arterial pressure has the opposite effect. Reduced baroreceptor firing leads to increased sympathetic and decreased parasympathetic activity, which raises heart rate, contractility, and vascular resistance to restore pressure.
The carotid sinus baroreceptors send signals via the glossopharyngeal nerve, whereas the aortic arch baroreceptors use the vagus nerve. The reflex is very rapid and can adjust pressure from beat to beat. However, baroreceptors adapt to sustained changes in pressure. In chronic hypertension, their firing rate resets and they accept a higher pressure as normal, which reduces their role in long term control.
Clinical maneuvers such as carotid sinus massage stimulate baroreceptors, which can increase parasympathetic output and slow heart rate, sometimes used acutely to terminate certain tachyarrhythmias. Conversely, conditions that decrease baroreceptor function, such as atherosclerotic stiffening of the carotid sinus, can impair blood pressure stability.
Long Term Regulation and Integration 🧩
While baroreceptors provide rapid adjustments, long term regulation of arterial pressure depends heavily on the kidneys and hormonal systems. The kidneys control blood volume by adjusting sodium and water excretion, and the renin angiotensin aldosterone system links renal function with vascular resistance and volume.
From a cardiovascular physiology perspective, recognize that arterial pressure is the product of cardiac output and total peripheral resistance, and that cardiac output over time must match renal output of fluid. Any persistent rise in cardiac output or resistance without renal compensation leads to chronic hypertension.
During exercise and stress, the cardiovascular system uses an integrated response. Sympathetic activation increases heart rate, contractility, venous return, and vasoconstriction in nonessential vascular beds, while local metabolic vasodilation in active muscles and heart overrides sympathetic tone to increase flow. Mean arterial pressure is usually maintained or slightly increased due to a balance between higher cardiac output and modest decreases in total peripheral resistance from widespread vasodilation.
Understanding these integrated responses helps explain why blood pressure and heart rate change during posture shifts, hemorrhage, exercise, and emotional stress.