# Lecture 4: Cardiac Physiology and the Cardiac Cycle

## Anatomy and Physiology II

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## Learning Objectives

By the end of this lecture, students will be able to:

1. Describe the ionic basis of cardiac action potentials in contractile and autorhythmic cells
2. Explain excitation-contraction coupling in cardiac muscle
3. Describe the phases of the cardiac cycle and correlate them with pressure, volume, and valve events
4. Define cardiac output and the factors that regulate it
5. Explain the Frank-Starling mechanism
6. Describe autonomic nervous system regulation of heart function

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## Lecture Content

### I. Cardiac Muscle Cell Physiology

#### Contractile Cell Action Potential (Ventricular Myocytes)

Ventricular contractile cells have a stable resting membrane potential of approximately -90 mV. Their action potential unfolds in five phases. During **Phase 0 (rapid depolarization)**, voltage-gated fast sodium channels open, allowing a rapid influx of sodium ions that depolarizes the cell to approximately +30 mV. **Phase 1 (initial repolarization)** follows as the fast sodium channels inactivate and a transient efflux of potassium begins.

The hallmark of the cardiac contractile action potential is **Phase 2 (the plateau)**, during which voltage-gated slow L-type calcium channels open and allow calcium to enter the cell. This calcium influx is balanced by a slow efflux of potassium through delayed rectifier potassium channels, resulting in a prolonged plateau lasting approximately 200 milliseconds. This plateau phase is unique to cardiac muscle and serves a critical protective function: it prevents tetanic contractions, ensuring that the heart cannot sustain a prolonged contraction that would interfere with its rhythmic pumping.

During **Phase 3 (repolarization)**, the calcium channels close and potassium efflux predominates, returning the membrane potential to its resting level. **Phase 4 (resting potential)** is stable at approximately -90 mV, maintained by potassium leak channels and the sodium-potassium ATPase.

The cardiac action potential features an unusually long **absolute refractory period** of approximately 250 milliseconds, corresponding to Phases 0 through 2, during which the cell cannot be restimulated regardless of stimulus strength. A brief **relative refractory period** follows, during which only a very strong stimulus can elicit a response. This long refractory period is the mechanism that prevents tetanus and ensures the rhythmic contraction and relaxation essential for effective blood pumping.

#### Autorhythmic (Pacemaker) Cell Action Potential

Pacemaker cells, such as those in the SA node, differ fundamentally from contractile cells in that they lack a true stable resting potential. Instead, their membrane potential drifts spontaneously toward threshold in a phase called the **pacemaker potential** (or prepotential). During this **Phase 4**, the membrane gradually depolarizes from about -60 mV to the threshold of approximately -40 mV. This drift is produced by the "funny" sodium current (If) flowing through HCN channels, a decreasing potassium permeability, and the opening of transient (T-type) calcium channels near threshold.

When threshold is reached, **Phase 0 (depolarization)** occurs through the opening of L-type calcium channels rather than fast sodium channels, which explains why the upstroke in pacemaker cells is slower than in contractile cells. **Phase 3 (repolarization)** involves the closure of calcium channels and the opening of potassium channels, restoring the membrane potential to its prepotential level, and the cycle repeats.

#### Excitation-Contraction Coupling

When an action potential travels along the sarcolemma and into the T-tubules of a cardiac muscle cell, the L-type calcium channels in the T-tubule membrane open and admit a small amount of extracellular calcium, called "trigger calcium." This trigger calcium induces a much larger release of calcium from the sarcoplasmic reticulum through ryanodine receptors, a process known as calcium-induced calcium release (CICR). The released calcium binds to troponin C, which shifts the tropomyosin complex to expose myosin binding sites on actin, enabling cross-bridge cycling and contraction. Relaxation occurs when calcium is pumped back into the sarcoplasmic reticulum by SERCA (the SR calcium-ATPase) and out of the cell by the sodium-calcium exchanger and the plasma membrane calcium-ATPase.

<image>A comparative diagram of cardiac action potentials. Panel A: Ventricular contractile cell action potential showing all five phases (0–4) with ion channels labeled — fast Na+ channels at Phase 0, K+ and Ca2+ channels during the plateau at Phase 2, K+ channels during Phase 3, and the resting potential at Phase 4. The absolute and relative refractory periods are shaded beneath the curve. Panel B: SA node pacemaker cell action potential showing the pacemaker potential (Phase 4) with funny current (If) and T-type Ca2+ channels, depolarization (Phase 0) via L-type Ca2+ channels, and repolarization (Phase 3) via K+ channels. Panel C: Excitation-contraction coupling pathway showing the T-tubule, L-type Ca2+ channel, trigger Ca2+, ryanodine receptor on the SR, Ca2+-induced Ca2+ release, troponin-tropomyosin complex, and cross-bridge cycling.</image>

### II. The Cardiac Cycle

One complete cardiac cycle encompasses a full heartbeat, including one period of contraction (systole) and one period of relaxation (diastole) for both the atria and ventricles. At a heart rate of 75 beats per minute, a single cycle takes approximately 0.8 seconds.

#### Phases of the Cardiac Cycle

**Ventricular filling (mid-to-late diastole)** begins with the AV valves open and the semilunar valves closed. Blood flows passively from the atria into the ventricles, accounting for about 80% of ventricular filling. Atrial systole then contributes the final 20%, sometimes called the "atrial kick." At the end of this phase, each ventricle contains its end-diastolic volume (EDV) of approximately 120 mL.

**Isovolumetric contraction** occurs when the ventricles begin to contract. All four valves are closed simultaneously, so ventricular pressure rises rapidly while the volume remains unchanged. This phase continues until ventricular pressure exceeds the pressure in the great arteries.

**Ventricular ejection** begins when ventricular pressure forces the semilunar valves open. Blood is rapidly ejected at first, then the rate slows. The AV valves remain closed throughout. The stroke volume (SV), the volume of blood ejected per beat, is approximately 70 mL, leaving behind an end-systolic volume (ESV) of about 50 mL. The relationship SV = EDV - ESV defines the volume ejected with each contraction.

**Isovolumetric relaxation** follows as the ventricles relax and ventricular pressure drops rapidly. All four valves close again. When ventricular pressure falls below atrial pressure, the AV valves reopen and the cycle starts over.

#### Heart Sounds

The closing of heart valves produces two audible sounds. **S1** ("lub") is generated by the closure of the AV valves and marks the beginning of ventricular systole. **S2** ("dub") results from the closure of the semilunar valves and marks the beginning of ventricular diastole. **Heart murmurs** are abnormal sounds caused by turbulent blood flow through defective valves. Stenosis, a narrowing of the valve, forces blood through a smaller opening, while regurgitation (insufficiency) occurs when an incompetent valve allows blood to leak backward.

<image>A Wiggers diagram showing the events of the cardiac cycle for the left heart. The diagram includes synchronized tracings of: aortic pressure, left ventricular pressure, left atrial pressure, left ventricular volume, ECG (P wave, QRS, T wave), phonocardiogram (S1 and S2 heart sounds). Vertical dashed lines separate the phases: atrial systole, isovolumetric contraction, ventricular ejection (rapid and reduced), isovolumetric relaxation, and ventricular filling (rapid and reduced). Valve opening and closing events are labeled at the appropriate points. The EDV and ESV are marked on the volume tracing.</image>

### III. Cardiac Output

**Cardiac output (CO)** is the volume of blood pumped by one ventricle per minute and is calculated as heart rate (HR) multiplied by stroke volume (SV). At rest, a typical cardiac output is 75 bpm multiplied by 70 mL, yielding approximately 5.25 liters per minute, a volume roughly equal to the total blood volume. The **cardiac reserve** is the difference between resting and maximal cardiac output. Sedentary individuals may increase their CO to 15 to 20 L/min during exercise, while trained athletes can reach 30 to 35 L/min.

#### Regulation of Stroke Volume

Three factors determine stroke volume. **Preload** is the degree of stretch on the heart muscle before contraction, and it is directly related to the end-diastolic volume. The **Frank-Starling law of the heart** states that the greater the stretch (preload), the greater the force of contraction. This occurs because increased stretch optimizes the overlap of actin and myosin filaments and increases calcium sensitivity, ensuring that the heart pumps out whatever volume of blood it receives. Factors that influence preload include venous return, blood volume, venous tone, and the skeletal muscle and respiratory pumps.

**Contractility** (inotropy) refers to the strength of contraction independent of stretch. Positive inotropes, which increase contractility, include sympathetic stimulation via norepinephrine acting on beta-1 receptors, circulating epinephrine, digitalis (digoxin), and increased intracellular calcium. Negative inotropes, which decrease contractility, include acidosis, hyperkalemia, beta-blockers, and calcium channel blockers. Parasympathetic stimulation has minimal direct effect on ventricular contractility.

**Afterload** is the pressure the ventricle must overcome to eject blood, and it is primarily determined by arterial blood pressure. Increased afterload, as seen in hypertension or aortic stenosis, increases cardiac workload and decreases stroke volume. Chronically elevated afterload leads to ventricular hypertrophy as the heart adapts by thickening its wall.

#### Regulation of Heart Rate

The autonomic nervous system is the primary regulator of heart rate. **Sympathetic stimulation**, originating from the cardioacceleratory center in the medulla, releases norepinephrine at the SA node, AV node, and myocardium, acting on beta-1 adrenergic receptors. This increases heart rate (positive chronotropy), increases conduction velocity through the AV node (positive dromotropy), and increases contractility (positive inotropy). **Parasympathetic stimulation**, transmitted via the vagus nerve from the cardioinhibitory center in the medulla, releases acetylcholine at the SA node and AV node, acting on muscarinic (M2) receptors. This decreases heart rate (negative chronotropy) and slows AV node conduction, but has minimal direct effect on ventricular contractility. At rest, vagal tone predominates, which is why the intrinsic SA node rate of about 100 bpm is slowed to approximately 75 bpm.

Other factors also influence heart rate. Fever increases the rate by roughly 10 bpm for every 1 degree Celsius rise in temperature. Thyroid hormones and epinephrine elevate heart rate, while electrolyte imbalances can be dangerous: hyperkalemia decreases heart rate, and hypokalemia increases the risk of arrhythmias. Age, fitness level, and emotional state also contribute.

<image>A diagram summarizing the regulation of cardiac output. A central box labeled "Cardiac Output = HR x SV" branches left to "Heart Rate" and right to "Stroke Volume." The Heart Rate branch shows parasympathetic input (vagus nerve, ACh, M2 receptors) decreasing HR and sympathetic input (norepinephrine, beta-1 receptors) increasing HR. The Stroke Volume branch divides into three factors: Preload (with the Frank-Starling curve showing increasing SV with increasing EDV), Contractility (with arrows showing sympathetic stimulation shifting the curve up and negative inotropes shifting it down), and Afterload (showing that increased arterial pressure decreases SV). Venous return factors feeding into Preload are listed: blood volume, venous tone, skeletal muscle pump, respiratory pump.</image>

### IV. Clinical Correlations

**Congestive heart failure (CHF)** occurs when the heart cannot pump enough blood to meet the body's demands. Left-sided failure leads to pulmonary congestion and edema as blood backs up into the lungs, while right-sided failure causes systemic venous congestion and peripheral edema. The **ejection fraction (EF)**, calculated as SV divided by EDV times 100, normally ranges from 55 to 70%, and a reduced ejection fraction indicates impaired systolic function. **Cardiac catheterization** is a procedure used to measure pressures within the heart chambers and great vessels, while **echocardiography** uses ultrasound to image heart structure and function, including ejection fraction and valve performance.

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