Comprehensive Overview of Cardiac Muscle and the Cardiovascular System

I. Cardiac Muscle Characteristics

Myogenic Nature: Cardiac muscle contraction is initiated intrinsically by specialized pacemaker cells, rather than requiring external nervous stimulation.
Interconnected Cells: Cardiac muscle cells are physically and electrically linked via gap junctions, which are components of intercalated disks. These junctions allow for rapid propagation of electrical signals throughout the heart, enabling synchronized contraction.
Antagonistic Autonomic Control: The heart's activity is regulated by the autonomic nervous system, which exerts antagonistic control:
- Parasympathetic System: Generally decreases heart rate.
- Sympathetic System: Generally increases heart rate and contractility.
Endocrine Regulation: Hormones also play a role in modulating cardiac function.

II. Components of the Cardiovascular System

A. Blood Vessels (Vasculature)

Arteries vs. Veins:
- Arteries: Carry blood away from the heart, typically under high pressure.
- Veins: Carry blood back to the heart, typically under lower pressure.
Capillaries: Microscopic vessels that form networks between arterioles and venules, facilitating the exchange of gases, nutrients, and wastes between blood and tissues.
Portal System: A unique arrangement where two capillary beds are joined in series, allowing for direct transport of substances between specific organs (e.g., hepatic portal system).

B. Heart Structure

Septum: A muscular wall that divides the heart into two distinct halves:
- Left Half: Pumps oxygen-rich blood to the body.
- Right Half: Pumps oxygen-poor blood to the lungs.
Atrium (Plural: Atria): Upper chambers of the heart that receive blood returning to the heart.
Ventricle: Lower, thicker-walled chambers of the heart that pump blood out of the heart.

C. Blood Composition

Cells: Include red blood cells (oxygen transport), white blood cells (immune function), and platelets (clotting).
Plasma: The liquid matrix of blood, containing water, proteins, electrolytes, nutrients, hormones, and waste products.

D. Types of Circulation

Pulmonary Circulation:
- Transports oxygen-poor blood from the right side of the heart to the lungs via pulmonary arteries.
- Returns oxygen-rich blood from the lungs to the left side of the heart via pulmonary veins.
Systemic Circulation:
- Transports oxygen-rich blood from the left side of the heart to the rest of the body via the aorta.
- Returns oxygen-poor blood from the body to the right side of the heart via the inferior vena cava (from lower body) and superior vena cava (from upper body).

III. Functions of Bulk Flow in the Organism

Definition: Bulk flow refers to the transport of large amounts of a medium (like blood) over great distances in relatively short periods of time.
Transportation:
- Gases (oxygen, carbon dioxide).
- Wastes (metabolic byproducts).
- Nutrients (glucose, amino acids, lipids).
- Signaling molecules (hormones).
- Immune cells (leukocytes).
Regulation:
- Thermoregulation: Distributing heat throughout the body.
- Buffer pH: Maintaining acid-base balance in tissues.
Protection:
- Immunity: Leukocytes defend against pathogens.
- Clotting: Thrombocytes (platelets) prevent blood loss.

IV. Hemodynamics: Principles of Blood Flow and Pressure

A. Blood Pressure and Vessel Diameter

If blood vessels dilate (widen), blood pressure decreases.
If blood vessels constrict (narrow), blood pressure increases.

B. Pressure Gradient (ΔP)

The difference in pressure between two regions.
Blood flows from an area of high pressure to an area of low pressure.
Blood flows out of the heart (highest pressure) into the closed loop of vessels (lower pressure).

C. Fluid in Motion

Fluid in motion has two components:
- Dynamic Component: Represents the kinetic energy of the moving fluid.
- Lateral Component: Represents the hydrostatic pressure exerted by the fluid on the vessel walls.
The pressure of a fluid in motion decreases with distance due to friction as blood moves through vessels.
Hydrostatic Pressure: Pressure exerted by a fluid not in motion, exerted in all directions.

D. Key Hemodynamic Variables

Blood Flow (Q):
- Definition: Volume of blood flowing through a vessel per unit time (mL/min).
- Formula: Q = \frac{\Delta P}{R} (where ΔP is pressure gradient, R is resistance).
Blood Pressure (P):
- Definition: Force per unit area exerted on a vessel wall (mm Hg).
Resistance (R):
- Definition: Opposition to flow, representing the friction blood encounters as it moves through vessels.
- Formula for resistance: R \propto \frac{L\eta}{r^4}
  - L: Length of the vessel.
  - \eta: Viscosity of the blood.
  - r: Radius of the vessel (most significant factor, as it's to the power of 4).
Velocity (v):
- Definition: Speed of blood flow.
- Formula: v = \frac{Q}{A} (where Q is flow, A is cross-sectional area).

V. Mean Arterial Pressure (MAP) and Cardiac Output (CO)

A. Mean Arterial Pressure (MAP)

Definition: The average force per unit area exerted on a vessel wall over a cardiac cycle (mm Hg).
Formula: MAP = TPR \times CO

B. Total Peripheral Resistance (TPR)

Definition: The sum of resistance to flow from all blood vessels in the systemic circulation, from the aorta to the vena cava.
Represents the overall opposition to blood flow encountered by the heart.

C. Cardiac Output (CO)

Definition: The amount of blood the heart pumps per unit time (L/min).
Formula: CO = SV \times HR

D. Stroke Volume (SV)

Definition: The amount of blood the heart pumps with each beat.

E. Heart Rate (HR)

Definition: The number of times the heart beats per minute.

VI. Heart Anatomy and Blood Flow Pathway

A. Heart Chambers and Structure

The heart has four chambers: two atria and two ventricles.
It is primarily composed of myocardium, the cardiac muscle tissue.
The heart is encased in the pericardium, a protective sac.
Paired Atria: Thin-walled upper chambers that receive blood.
Paired Ventricles: Thick-walled lower chambers that pump blood out.
Connective Tissue Rings: Serve as the origin and insertion points for cardiac muscles, providing structural support and electrical isolation between atria and ventricles.

B. Major Blood Vessels Connected to the Heart

Aorta: Carries oxygen-rich blood from the left ventricle to the systemic circulation.
Pulmonary Trunk: Carries oxygen-poor blood from the right ventricle to the pulmonary arteries.
Vena Cava (Superior and Inferior): Return oxygen-poor blood from the systemic circulation to the right atrium.
Pulmonary Veins: Return oxygen-rich blood from the lungs to the left atrium.

C. Detailed Blood Flow Pathway

Oxygen-Poor Blood Pathway (Right Side - Pulmonary Circuit):
1. Vena Cavae (Superior and Inferior) return oxygen-poor blood to the Right Atrium.
2. Blood passes through the Tricuspid Valve into the Right Ventricle.
3. The Right Ventricle pumps blood through the Pulmonary Semilunar Valve into the Pulmonary Trunk.
4. The Pulmonary Trunk branches into pulmonary arteries, carrying blood to the Lungs for oxygenation.
Oxygen-Rich Blood Pathway (Left Side - Systemic Circuit):
1. Pulmonary Veins return oxygen-rich blood from the lungs to the Left Atrium.
2. Blood passes through the Bicuspid (Mitral) Valve into the Left Ventricle.
3. The Left Ventricle pumps blood through the Aortic Semilunar Valve into the Aorta.
4. The Aorta distributes oxygen-rich blood to the Rest of the Body.

VII. Heart Valves

Function: Prevent the backflow of blood, ensuring unidirectional flow through the heart.
Two Atrioventricular (AV) Valves: Located between the atria and ventricles; prevent backflow into the atria.
- Tricuspid Valve: On the right side, between the right atrium and right ventricle.
- Bicuspid (Mitral) Valve: On the left side, between the left atrium and left ventricle.
- Mechanism: These are "active" valves, meaning their closure is reinforced by the contraction of papillary muscles, which pull on the valve cusps via fibrous cords called chordae tendinae, preventing them from prolapsing into the atria during ventricular contraction.
Two Semilunar Valves: Located at the exits of the ventricles into the great arteries; prevent backflow into the ventricles.
- Aortic Semilunar Valve: Between the left ventricle and the aorta.
- Pulmonary Semilunar Valve: Between the right ventricle and the pulmonary trunk.
- Mechanism: These are "passive" valves, opening and closing based on pressure gradients. They do not have chordae tendinae or papillary muscles.

VIII. Cardiac Cell Types and Properties

A. Autorhythmic Cells (Pacemakers)

Generate the electrical signals for contraction.
Are smaller and have fewer contractile fibers compared to contractile cells.
Do not have organized sarcomeres, as their primary role is electrical conduction, not force generation.

B. Contractile Cells

Form the bulk of the heart muscle.
Are striated fibers organized into sarcomeres, enabling them to generate force and contract.

C. Comparison of Cardiac Muscle vs. Skeletal Muscle

Size and Nuclei: Cardiac muscle cells are smaller and typically have a single nucleus per fiber, unlike larger, multinucleated skeletal muscle fibers.
Branching and Interconnections: Cardiac muscle cells branch and join neighboring cells through specialized structures called intercalated disks.
Gap Junctions: Intercalated disks contain gap junctions, which allow for direct electrical communication between adjacent cells, enabling the heart to function as a syncytium.
T-Tubules: Cardiac T-tubules are larger and branch more extensively than those in skeletal muscle.
Sarcoplasmic Reticulum (SR): The SR in cardiac muscle is smaller and less extensive compared to skeletal muscle.
Mitochondria: Mitochondria occupy a significant portion (one-third) of the cardiac cell volume, reflecting the high metabolic demand and reliance on aerobic respiration.

IX. Excitation-Contraction Coupling in Myocardial Contractile Cells

This process links the electrical signal (action potential) to muscle contraction.

Action Potential (AP) from Pacemaker Cells: An AP originating from autorhythmic cells spreads to adjacent contractile cells via gap junctions.
Calcium-Induced Calcium Release (CICR):
- The AP opens voltage-gated L-type Ca²⁺ channels in the cell membrane.
- Extracellular Ca²⁺ influx through these channels triggers the opening of ryanodine receptor (RyR) channels on the sarcoplasmic reticulum (SR).
- This causes a rapid release of Ca²⁺ from the SR, creating a localized "Ca²⁺ spark."
- Summed Ca²⁺ sparks generate a larger Ca²⁺ signal throughout the cell.
Ca²⁺ Binding to Troponin: The increased cytosolic Ca²⁺ binds to troponin, initiating the crossbridge cycle.
Crossbridge Cycle: Similar to skeletal muscle, Ca²⁺ binding to troponin moves tropomyosin, exposing actin binding sites for myosin heads, leading to muscle contraction.
Relaxation (Ca²⁺ Removal):
- Ca²⁺ is actively pumped back into the SR by Ca²⁺-ATPase pumps.
- Ca²⁺ is also removed from the cell by the Na⁺-Ca²⁺ exchanger (NCX), which uses the Na⁺ gradient (secondary active transport) to move Ca²⁺ out of the cell.

X. Action Potential of Myocardial Contractile Cells

The action potential in contractile cells is characterized by a prolonged plateau phase, which is crucial for cardiac function.

Phase 4: Resting Membrane Potential: The cell is at its resting potential, typically around -90 mV.
Phase 0: Depolarization:
- Initiated by the spread of depolarization from pacemaker cells.
- Voltage-gated Na⁺ channels open rapidly, causing a massive influx of Na⁺ and rapid depolarization.
Phase 1: Initial Repolarization:
- Na⁺ gates close.
- Some K⁺ leaks out, causing a slight, transient repolarization.
Phase 2: Plateau Phase:
- Slow voltage-gated L-type Ca²⁺ channels open, allowing Ca²⁺ influx.
- Fast K⁺ channels close, reducing K⁺ efflux.
- The balance between Ca²⁺ influx and reduced K⁺ efflux maintains the membrane potential at a plateau, prolonging the action potential.
Phase 3: Rapid Repolarization:
- Ca²⁺ gates close.
- Slow voltage-gated K⁺ channels open, leading to a rapid efflux of K⁺, causing repolarization.
Phase 4: Resting Membrane Potential: The cell returns to its resting potential, ready for the next excitation.

A. Extended Refractory Period

The prolonged Phase 2 (plateau) due to Ca²⁺ influx results in an extended refractory period.
This extended refractory period is critical because it:
- Prevents Tetanus: Ensures that the cardiac muscle cannot be restimulated before it has fully relaxed, preventing sustained contraction (tetanus) which would impair the heart's pumping ability.
- Allows for Full Relaxation: Provides sufficient time for the ventricles to fill with blood between contractions.
- Aids in Timing Cardiac Events: Contributes to the precise coordination of atrial and ventricular contractions.

XI. Action Potential of Pacemaker Cells (Autorhythmic Cells)

Pacemaker cells exhibit an unstable resting potential, allowing them to spontaneously depolarize and set the heart rate.

"Funny" Channels (If):
- These channels are permeable to both Na⁺ and K⁺.
- They open at the "resting membrane potential" (which is not truly stable in pacemakers).
- Na⁺ influx through If channels is greater than K⁺ efflux, leading to a slow, gradual depolarization (pacemaker potential).
Threshold and T-type Ca²⁺ Channels:
- As the membrane potential reaches threshold, If channels close.
- T-type Ca²⁺ gates (transient calcium channels) open, contributing to further depolarization.
Depolarization (L-type Ca²⁺ Channels):
- During the main depolarization phase, L-type Ca²⁺ gates (long-lasting calcium channels) open, causing a rapid influx of Ca²⁺, which is responsible for the rising phase of the action potential.
Repolarization (K⁺ Channels):
- At the peak of the action potential, all Ca²⁺ gates close.
- Slow K⁺ gates open, leading to K⁺ efflux and repolarization.
Return to "Rest":
- At the lowest point of the repolarization, K⁺ gates close, and the If channels open again, restarting the cycle.
Heart Rate Alteration: The speed of depolarization in pacemaker cells can be altered by changing ion permeability, thereby changing the heart rate.

XII. Electrical Conduction System of the Heart

Electrical signals coordinate the contraction of the heart chambers.

Sinoatrial (SA) Node:
- Located in the right atrium.
- The primary pacemaker of the heart, setting the pace of the heartbeat.
- Generates electrical impulses that spread across the atria.
Internodal Pathway:
- Conducts electrical signals from the SA node to the atrioventricular (AV) node, initiating atrial contraction.
Atrioventricular (AV) Node:
- Located near the junction of the atria and ventricles.
- Introduces a crucial delay in signal conduction (AV nodal delay) due to slower conduction through its nodal cells. This delay allows the atria to complete their contraction and ventricular filling before ventricular systole begins.
Bundle of His (AV Bundle):
- Receives the signal from the AV node.
- Splits into the left and right bundle branches, which extend down the interventricular septum.
Purkinje Fibers:
- Transmit electrical signals rapidly up the ventricle walls, ensuring synchronized ventricular contraction.
Pacemakers and Heart Rate: The autorhythmic cells within the conduction system, particularly the SA node, ultimately set the heart rate.

XIII. Electrocardiogram (ECG/EKG)

An ECG is a non-invasive recording of the overall electrical activity of all heart cells, as detected from the body surface. It is not the same as a single action potential.

A. Waves of the ECG

P Wave: Represents the depolarization of the atria, leading to atrial contraction.
QRS Complex: Represents the wave of ventricular depolarization, leading to ventricular contraction.
- Atrial repolarization also occurs during the QRS complex but is usually masked by the larger ventricular depolarization signal.
T Wave: Represents the repolarization of the ventricles, leading to ventricular relaxation.

B. Segments of the ECG

P-R Segment: The flat line between the end of the P wave and the beginning of the QRS complex, representing the AV nodal delay.
T-P Segment: The flat line between the end of the T wave and the beginning of the next P wave, representing the period of ventricular and atrial relaxation (diastole).

C. Distinction: Depolarization vs. Contraction

It is important to remember that ECG waves represent electrical events (depolarization/repolarization), which *precede* the mechanical events (contraction/relaxation).

D. ECG Interpretation

ECG analysis involves assessing several parameters:

Heart Rate:
- Determined by the time between two consecutive P waves or two consecutive Q waves.
- Tachycardia: Faster than normal heart rate.
- Bradycardia: Slower than normal heart rate.
Rhythm:
- Assesses if the heart's rhythm is regular or irregular.
- Arrhythmia: Any abnormal heart rhythm.
- Atrial Fibrillation: Characterized by a loss of SA node pacemaking, leading to irregular and often rapid atrial contractions.
Wave Morphology: Checks if the normal waves (P, QRS, T) are present and in recognizable form.
P-R Segment Constancy:
- Checks if there is one QRS complex for each P wave.
- Assesses if the P-R segment is constant in length, indicating consistent AV nodal conduction.

E. Heart Blocks

First-Degree Heart Block: Characterized by a very slow depolarization through the AV node, resulting in a prolonged P-R segment.
Second-Degree Heart Block:
- Type I (Wenckebach): The signal slows progressively through the AV node until a beat is skipped.
- Type II: Characterized by erratic transmission, where some P waves are not followed by a QRS complex.
Third-Degree (Complete) Heart Block: Involves a complete loss of signal transmission from the atria to the ventricles. The ventricles then act as their own pacemaker, typically at a much slower rate.

XIV. Cardiac Cycle

The cardiac cycle describes the sequence of mechanical and electrical events that occur with each heartbeat.

Systole: The contraction phase of the heart chambers, resulting in forced movement of blood.
Diastole: The relaxation phase of the heart chambers, allowing for passive filling with blood.

A. Phases of the Cardiac Cycle

The Heart at Rest: Atrial & Ventricular Diastole (Late Ventricular Diastole):
- All chambers are relaxed.
- The atria are filling with venous blood.
- AV valves are open, allowing ventricles to fill passively (approximately 80% of ventricular filling occurs here).
Completion of Ventricular Filling: Atrial Systole:
- Atria contract, pushing the last 20% of blood volume into the ventricles.
- End-Diastolic Volume (EDV): The maximum volume of blood in the ventricle at the end of ventricular relaxation (and atrial contraction).
Early Ventricular Contraction & the First Heart Sound ("Lub"):
- Ventricular contraction begins.
- The rising ventricular pressure pushes the AV valves closed, producing the first heart sound ("Lub").
- This phase is called isovolumic ventricular contraction because no blood enters or exits the ventricles (all valves are closed), but ventricular pressure increases rapidly.
- Concurrent atrial diastole occurs, where atria relax and begin to fill with blood again.
The Heart Pumps: Ventricular Ejection (Ventricular Systole - Second Phase):
- As ventricular pressure exceeds the pressure in the great arteries (aorta and pulmonary trunk), the semilunar valves open.
- Blood is ejected from the ventricles into the arteries.
- End-Systolic Volume (ESV): The volume of blood remaining in the ventricle at the end of ventricular contraction.
Ventricular Relaxation & the Second Heart Sound ("Dup"):
- Ventricular muscles relax, and ventricular pressure drops.
- Arterial blood begins to flow back towards the heart, causing the semilunar valves to shut, producing the second heart sound ("Dup").
- This phase is called isovolumic ventricular relaxation because no blood enters or exits the ventricles (all valves are closed), but ventricular pressure continues to drop.
- When ventricular pressure drops below atrial pressure, the AV valves open, allowing passive ventricular filling to begin again (returning to phase 1).

B. Wiggers Diagram Components

The Wiggers diagram visually correlates electrical events (ECG), pressure changes, volume changes, and heart sounds during the cardiac cycle.

A. Semilunar valves open (start of ventricular ejection).
B. Semilunar valves close (start of isovolumic ventricular relaxation, second heart sound).
C. Atrioventricular valves close (start of isovolumic ventricular contraction, first heart sound).
D. Atrioventricular valves open (start of passive ventricular filling).
E. End-diastolic volume (volume at the end of ventricular filling).
F. End-systolic volume (volume at the end of ventricular ejection).

XV. Cardiac Control

A. Cardiac Control Center

Located in the medulla oblongata of the brainstem.
Receives input from various receptors and integrates signals to regulate heart rate and contractility.

B. Parasympathetic Control (Vagal Tone)

Main avenue of tonic (continuous) control, primarily decreasing heart rate.
Neurotransmitter: Acetylcholine (ACh).
Receptors: Muscarinic receptors on pacemaker cells.
Mechanism:
- Increases K⁺ permeability in pacemaker cells, leading to a lower "resting rate" (hyperpolarization) and making it harder to reach threshold.
- Decreases Ca²⁺ permeability, which slows the rate of pacemaker depolarization.

C. Sympathetic Control

Increases heart rate and contractility.
Neurotransmitters/Hormones: Norepinephrine (NE) as a neurotransmitter from sympathetic nerves; Epinephrine (E) as a hormone from the adrenal medulla.
Receptors: Beta-1 (β1) adrenergic receptors on pacemaker and contractile cells.
Mechanism:
- Causes If (funny) channels to stay open longer, increasing the rate of Na⁺ and K⁺ influx.
- Increases Ca²⁺ permeability, leading to faster Ca²⁺ influx.
- These actions result in a faster pacemaker depolarization and thus an increased heart rate.

XVI. Stroke Volume (SV) Regulation

Stroke volume, the amount of blood pumped per beat, is influenced by several factors.

A. Frank-Starling Law of the Heart

States that the more the ventricles are stretched (i.e., the greater the preload or end-diastolic volume, EDV), the larger the force of contraction.
Essentially, the heart pumps all the blood returned to it.
EDV directly impacts contraction strength.

B. Contractility

Cardiac muscle has intrinsic contractility, meaning it can generate tension at any starting length.
Ionotropic Agents: Chemicals that impact contractility.
- Positive Inotropes: Increase contractility (e.g., epinephrine, norepinephrine, digitalis).
  - Catecholamines (epinephrine, norepinephrine) activate phospholamban, which increases Ca²⁺-ATPase activity in the SR. This leads to increased SR Ca²⁺ stores and increased Ca²⁺ entering the cells during an action potential, resulting in stronger contractions.
- Negative Inotropes: Decrease contractility.

C. Factors Determining End-Diastolic Volume (EDV) / Venous Return

EDV is primarily determined by venous return, which is affected by:

Skeletal Muscle Pump: Contraction of skeletal muscles compresses veins, pushing blood towards the heart.
Respiratory Pump: Changes in intrathoracic pressure during breathing help draw blood into the thoracic veins and the heart.
Sympathetic Innervation of Veins: Sympathetic stimulation causes venoconstriction, reducing venous capacitance (the ability of veins to hold blood) and increasing venous return.

D. Afterload

Definition: The combined load of EDV and arterial resistance that the ventricles must overcome to eject blood during contraction.
High afterload makes it harder for the heart to eject blood, potentially reducing stroke volume.

E. Ejection Fraction

Definition: The percentage of the end-diastolic volume (EDV) that is ejected with one contraction.
Formula: Ejection\ Fraction = \frac{Stroke\ Volume}{EDV}
A key indicator of ventricular efficiency.

XVII. Cardiac Output (CO) Summary

Cardiac output is the product of stroke volume and heart rate: CO = SV \times HR.
Regulation of both SV and HR allows the body to precisely control the amount of blood pumped by the heart to meet metabolic demands.