Heart Blood Flow and Valves

Here are the updated study notes:

Blood Flow Through the Heart

• The heart has four chambers: Right Atrium (RA), Right Ventricle (RV), Left Atrium (LA), and Left Ventricle (LV).
• Deoxygenated blood flows from the Superior & Inferior Vena Cava to the Right Atrium (RA).
• From the RA, blood flows through the Tricuspid Valve to the Right Ventricle (RV).
• Blood then goes through the Pulmonary Valve to the Pulmonary Arteries, reaching the Lungs for oxygenation.
• Oxygenated blood returns from the Lungs via the Pulmonary Veins to the Left Atrium (LA).
• Blood flows from the LA through the Mitral (Bicuspid) Valve to the Left Ventricle (LV).
• From the LV, blood flows through the Aortic Valve to the Aorta and then to the Body, supplying oxygen.

Heart Valves and Their Function

• Atrioventricular (AV) Valves prevent backflow into the atria
  • The Tricuspid Valve regulates flow between the Right Atrium (RA) and Right Ventricle (RV).
  • The Mitral (Bicuspid) Valve regulates flow between the Left Atrium (LA) and Left Ventricle (LV).
• Semilunar Valves prevent backflow into the ventricles
  • The Pulmonary Valve regulates flow between the Right Ventricle (RV) and the Pulmonary Artery.
  • The Aortic Valve regulates flow between the Left Ventricle (LV) and the Aorta.

Coronary Blood Supply

• The heart has its own circulation, with Coronary Arteries supplying oxygenated blood to the heart muscle.
• The Right Coronary Artery (RCA) supplies the Right Atrium, Right Ventricle, SA Node, and AV Node.
• The RCA branches into the Posterior Descending Artery (PDA), which supplies the posterior heart.
• The Left Coronary Artery (LCA) splits into the Left Anterior Descending (LAD) Artery, supplying the anterior LV and septum.
• The LCA also splits into the Left Circumflex (LCX) Artery, which supplies the lateral LV and LA.
• Blue blood (deoxygenated) enters RA → RV → Pulmonary Artery → Lungs.
• Red blood (oxygenated) returns via Pulmonary Veins → LA → LV → Aorta → Body.
• Coronary arteries branch from the aorta to feed the heart itself.

Relationship Between Blood Pressure, Resistance, and Flow

• Blood pressure (BP), resistance (R), and flow (F) are related through Ohm's Law for circulation: BP = F × R.
• Blood Pressure (BP) is the force exerted by blood on vessel walls.
• Flow (F) is the volume of blood moving through a vessel per unit time.
• Resistance (R) is the opposition to blood flow, primarily determined by vessel diameter and blood viscosity.
• Increasing resistance decreases flow (if BP stays the same).
• Increasing BP increases flow (if resistance stays the same).
• Vasoconstriction (↑R) increases BP, while vasodilation (↓R) decreases BP.

Concept of Vascular Resistance & Determinants of Resistance to Blood Flow

• Vascular resistance opposes blood flow within vessels and is determined by Poiseuille's Law.
• R = 8ηL/πr^4
• Vessel Diameter (r) is the most important factor: small changes in radius lead to large changes in resistance.
• Vasoconstriction increases resistance and decreases flow.
• Vasodilation decreases resistance and increases flow.
• Thicker blood (↑ viscosity, like in polycythemia) increases resistance.
• Thinner blood (↓ viscosity, like in anemia) decreases resistance.
• For Vessel Length (L): Longer vessels increase resistance (obesity increases vascular length).

Role of Resistance Vessels in Regulating BP & Vascular Resistance

• Arterioles (small arteries) are called resistance vessels and have small diameters and muscular walls, allowing them to regulate BP.
  • Constriction of arterioles (↑ Resistance) increases BP and decreases blood flow to tissues.
  • Dilation of arterioles (↓ Resistance) decreases BP and increases blood flow to tissues.

Regulation Mechanisms:

• Sympathetic Nervous System (SNS): NE (α1 receptors) causes vasoconstriction, increasing BP.
• Epinephrine (β2 receptors) causes vasodilation, decreasing BP in muscles.
• Local Metabolic Factors: ↑ CO2, ↓ O2, ↑ H+ cause vasodilation (to increase blood flow).

Hormonal Control

• Angiotensin II and Vasopressin cause vasoconstriction and increase BP.
• Atrial Natriuretic Peptide (ANP) causes vasodilation and decreases BP.

Relationship Between Cardiac Output, Heart Rate, & Stroke Volume

• Cardiac output (CO) is the total volume of blood pumped by the heart per minute: CO = HR × SV
• CO (Cardiac Output) is measured in liters per minute.
• HR (Heart Rate) is measured in beats per minute.
• SV (Stroke Volume) is the blood ejected per beat.
• Increasing HR and/or SV increases CO (more blood pumped per minute).
• Decreasing HR and/or SV decreases CO (less blood pumped per minute).
• Regulation:
  • SNS (ẞ1 stimulation) increases HR & SV and increases CO.
  • Parasympathetic (Vagus Nerve) decreases HR and decreases CO.
  • Preload (Venous Return) increases SV and increases CO.
  • Afterload (Resistance) increases and decreases SV and CO.

Laminar vs. Turbulent Flow & Variables Predicting Turbulence

• Laminar Flow: Smooth, layered blood flow with minimal resistance, silent and efficient (normal arteries).
• Turbulent Flow: Disordered blood movement with eddies and swirls, causing murmurs and bruits (e.g., in stenosed arteries, aneurysms).
• Predicted by Reynold's Number (Re):
  • Re = ρvd/η
  • ρ = Blood density v = Velocity of blood d = Vessel diameter η = Viscosity
• Turbulence Increases When:
  • ↑ Velocity (High Flow States) – Seen in anemia, hyperthyroidism.
  • ↑ Diameter (Aneurysms)
  • ↓ Viscosity (Anemia)
  • Obstructions (Atherosclerosis, Valvular Stenosis)
• Summary
  • ↑ HR or ↑ SV = ↑ CO ↓ HR or ↓ SV = ↓ CO SNS stimulation (β1 receptors) = ↑ HR & ↑ SV = ↑ CO Parasympathetic activation (Vagus Nerve) = ↓ HR = ↓ CO Changes in Pressure, Volume, and Flow During the Cardiac Cycle
• Already covered in section 4: CO = HR * SV
• Heart Rate (HR): Faster heartbeats = more blood pumped per minute.
• Stroke Volume (SV): More blood ejected per beat = higher cardiac output. Cardiac Output (CO): Total blood pumped by the heart per minute.

Changes in Pressure, Volume, and Flow During the Cardiac Cycle

• The cardiac cycle consists of systole (contraction) and diastole (relaxation), leading to changes in pressure, volume, and flow in the heart.

Phases of the Cardiac Cycle & Key Events:

• Atrial Systole (Late Diastole)
  • Atria contract increasing atrial pressure.
  • Blood flows into ventricles (final 20% of ventricular filling).
  • AV valves are open, and semilunar valves are closed.
• Isovolumetric Contraction (Early Systole) Ventricles contract, but all valves are closed (no volume change). Ventricular pressure increases sharply No blood flow occurs during this phase.
• Ventricular Ejection (Mid to Late Systole)
  • Aortic & Pulmonary valves open, blood is ejected into arteries.
  • Ventricular volume decreases sharply.
  • Peak ventricular & arterial pressures occur.
  • AV valves remain closed.
• Isovolumetric Relaxation (Early Diastole)
  • Ventricles relax and pressure drops rapidly. -Semilunar valves close (dicrotic notch on aortic pressure curve).
  • All valves are closed, and there is no change in volume.
• Ventricular Filling (Mid to Late Diastole)
  • AV valves open, blood passively fills ventricles (from atria).
  • Ventricular volume increases.
  • No major pressure change initially, then a gradual increase.

Key Pressure, Volume, and Flow Changes:

• Ventricular pressure rises in systole and falls in diastole.
• Ventricular volume decreases during ejection and increases in filling.
• Blood flow occurs when pressure gradients open valves.

Ejection Fraction & Calculation

• Ejection Fraction (EF) is the percentage of blood ejected from the left ventricle per heartbeat. EF = SV/EDV × 100 SV (Stroke Volume) = EDV - ESV EDV (End-Diastolic Volume) = Blood volume in LV before contraction. ESV (End-Systolic Volume) = Blood volume in LV after contraction. Clinical Significance: Normal EF: 55-70% Heart Failure (HFrEF - Systolic Dysfunction): EF <40% HFpEF (Diastolic Dysfunction): EF ≥50%, but impaired filling

Right vs. Left Side Pressures in the Heart

• The left side of the heart has higher pressures than the right due to systemic vs. pulmonary circulation differences.
• Pressure Differences:
  • Atria Left Side (Systemic Circulation) ~8-10 mmHg and the Right Side (Pulmonary Circulation) ~2-6 mmHg.
  • Ventricles (Diastolic Pressure) Left Side (Systemic Circulation) ~8-12 mmHg and the Right Side (Pulmonary Circulation) ~0-6 mmHg.
  • Ventricles (Systolic Pressure) Left Side (Systemic Circulation) ~120 mmHg and the Right Side (Pulmonary Circulation) ~25 mmHg. Arterial
• Pressure (Aorta/Pulmonary Artery) Left Side (Systemic Circulation) ~120/80 mmHg and the Right Side (Pulmonary Circulation) ~25/10 mmHg.
• Left heart pumps blood to the entire body, which requires high pressure (120/80 mmHg).
• Right heart pumps blood only to the lungs, which has lower resistance and requires lower pressure (25/10 mmHg).

How Aortic Pressure & Vascular Compression Affect Coronary Flow

• Coronary blood flow is unique because it is affected by aortic pressure and myocardial contraction.
• Aortic Pressure & Coronary Flow: Coronary arteries fill during diastole because the aortic valve closes causing blood to flow back toward the heart. Systolic contraction compresses coronary vessels, temporarily reducing flow.

Vascular Compression & Flow Changes:

• During systole, the heart muscle contracts which compresses coronary arteries (especially in LV) to reduce coronary flow.
• During diastole, the heart relaxes, coronary vessels open, and blood flows freely.
• Left Coronary Artery (LCA) flow is highest in diastole because LV contracts strongly in systole and compresses its vessels.
• Right Coronary Artery (RCA) flow occurs throughout the cardiac cycle since the RV has less forceful contraction, so less compression occurs. Tachycardia (fast HR) decreases diastolic time leading to decreased coronary perfusion and risk of ischemia. Aortic Stenosis raises LV pressure leading to more compression and decreased coronary flow and angina.

Contrast of Sympathetic & Parasympathetic Divisions: Neurotransmitters & Receptors

• The autonomic nervous system (ANS) includes the sympathetic (SNS) and parasympathetic (PNS) divisions, which differ in neurotransmitters and receptor types.
• Neurotransmitters and Receptors:
  • Sympathetic (SNS)
  • Ganglionic Synapse (Pre → Post): Acetylcholine (ACh) → Nicotinic (Nn) Receptors
  • Target Organ Synapse (Post → Effector): Norepinephrine (NE) → Adrenergic Receptors (α1, α2, β1, β2)
  • Para sympathetic (PNS)
  • Ganglionic Synapse (Pre → Post): Acetylcholine (ACh) → Nicotinic (Nn) Receptors
  • Target Organ Synapse (Post → Effector): Acetylcholine (ACh) → Muscarinic Receptors (M2, M3) SNS = "Fight or Flight" uses norepinephrine (NE) at target organs. PNS = "Rest and Digest” uses acetylcholine (ACh) at target organs.

Functional Responses to Autonomic Receptor Stimulation (Cardiovascular System)

α1 (Adrenergic) Location: Vascular smooth muscle Effect When Stimulated: Vasoconstriction increasing BP α2 (Adrenergic) Location: Presynaptic nerve terminals Effect When Stimulated: Decreased Sympathetic outflow (negative feedback) β1 (Adrenergic) Location: Heart (SA node, AV node, Myocardium, Kidneys) Effect When Stimulated: Increased HR, Contractility, Renin release ẞ2 (Adrenergic) Location: Skeletal muscle vessels, Bronchi Effect When Stimulated: Vasodilation, Bronchodilation M2 (Muscarinic) Location: Heart (SA & AV nodes) Effect When Stimulated: Decreased HR and Contractility M3 (Muscarinic) Location: Vascular endothelial cells Effect When Stimulated: Vasodilation (via NO release)

Sympathetic vs. Parasympathetic Control of Heart Rate, Contractility, & Vascular Tone

• Sympathetic (SNS) Heart Rate (HR): Increased HR (ẞ1 receptor, SA node stimulation)
  • Contractility (Strength of Contraction): Increased Contractility (ẞ1 receptor activation)
  • Vascular Tone (BP Control): Increased Vasoconstriction (α1 receptors), Vasodilation in skeletal muscle (B2 receptors)
• Parasympathetic (PNS) Heart Rate (HR): Decreased HR (M2 receptor, SA node inhibition) Contractility (Strength of Contraction): Decreased Contractility (weak effect via M2) Vascular Tone (BP Control): Minimal direct effect (but indirectly vasodilates via ↓HR and cardiac output)

Cardiovascular Consequences of Altering Sympathetic & Parasympathetic Activity

• Increased Sympathetic Activity Effect on Cardiovascular System: Increased HR, BP, and Contractility (Vasoconstriction → ↑Afterload)
• Decreased Sympathetic Activity Effect on Cardiovascular System: Decreased HR, BP, and Contractility (Vasodilation → Afterload)
• Increased Parasympathetic Activity Effect on Cardiovascular System: Decreased HR, Mild Decreased Contractility (Vasodilation indirectly via ↓CO)
• Decreased Parasympathetic Activity Effect on Cardiovascular System: Increased HR (minimal effect on contractility or BP)
• Example Clinical Effects: ẞ1-blockers decrease HR and BP. α1-blockers cause Vasodilation decreasing BP. Muscarinic blockers (e.g., Atropine) increase HR.

Location of Autonomic Receptors in the Cardiovascular System

• β1
  • Location: SA & AV Nodes, Myocardium
  • Effect: Increased HR and Contractility
• β2
  • Location: Skeletal muscle arteries, Lungs
  • Effect: Vasodilation and Bronchodilation
• α1
  • Location: Arterioles (skin, gut, kidney)
  • Effect: Vasoconstriction increasing BP
• α2
  • Location: Presynaptic SNS neurons
  • Effect: Decreased Sympathetic output
• M2
  • Location: SA & AV Nodes
  • Effect: Decreased HR
• M3
  • Location: Vascular endothelial cells
  • Effect: Vasodilation (via NO release)

Role of the Autonomic Nervous System in Cardiovascular Response to Exercise

• During exercise, the ANS regulates blood flow to maintain oxygen delivery to muscles.
• Sympathetic Effects (Primary Response) Increased HR & Contractility (β1) increasing CO. Vasoconstriction in non-essential organs (a1) shunts blood to muscles. Vasodilation in active muscles (β2) improves oxygen delivery.
• Parasympathetic Effects (During Recovery) Decreased HR (M2) prevents excessive HR. Allows vasodilation (via decreased SNS activity).
• Summary of Exercise Response: Early Exercise: SNS activation increases HR, BP, and vasoconstriction. During Exercise: Local metabolic factors (↑CO2, ↓O2, ↓pH) drive muscle vasodilation. Post-Exercise: Parasympathetic dominance decreases HR and vasodilation.

Vascular Smooth Muscle Contraction

• Vascular smooth muscle (VSM) contraction and relaxation regulate vascular tone, which influences blood pressure and blood flow, controlled by intracellular calcium (Ca²⁺) levels, second messengers, and phosphorylation pathways.
• Extracellular Ca²⁺ enters via voltage-gated Ca²⁺ channels (L-type channels).
• Intracellular Ca²⁺ release from the sarcoplasmic reticulum (SR) via IP3 receptors.
• Calcium Binds Calmodulin (CaM), forming a Ca²⁺-calmodulin complex, which activates myosin light chain kinase (MLCK).
• MLCK phosphorylates myosin light chains (MLC) enabling actin-myosin cross-bridge cycling.
• Actin-myosin interaction generates tension and vasoconstriction leading to increased VSM contraction and blood pressure.

Vascular Smooth Muscle Relaxation

• Calcium is pumped out of the cell via the Na⁺/Ca²⁺ exchanger (NCX) and SERCA pump storing Ca²⁺ in SR.
• Myosin Light Chain Phosphatase (MLCP) Activation via MLCP dephosphorylates myosin, preventing cross-bridge formation which decreases actin-myosin interaction, resulting in Relaxation.
• Role of Nitric Oxide (NO) & cGMP: Endothelial cells release NO, which activates guanylyl cyclase in VSM. Increasing cGMP activates Protein Kinase G (PKG) stimulating MLCP to promote Relaxation.
• Role of cAMP: β2-adrenergic receptor activation increases cAMP which inhibits MLCK.

Role of Endothelial Dysfunction in Cardiovascular Disease

• The endothelium (inner lining of blood vessels) plays a crucial role in vascular homeostasis by releasing factors that regulate vasodilation, vasoconstriction, inflammation, and thrombosis, crucial for cardiovascular health.
• Endothelial dysfunction is a major contributor to cardiovascular diseases (CVDs).
• Causes of Endothelial Dysfunction:
  • Oxidative Stress: Increased free radicals degrade NO decreasing vasodilation, seen in hypertension, diabetes, smoking, and aging.
  • Inflammation: Chronic inflammation (↑ cytokines like TNF-a, IL-6) damages endothelial cells, atherosclerosis begins with endothelial injury. → Impaired NO Production: decreased NO causes vasodilation increases Vasoconstriction, High cholesterol, hypertension, and diabetes impair NO production. → Hyperlipidemia & Atherosclerosis: LDL oxidation triggers macrophage infiltration forming plaques which leads to narrowed arteries & ischemia.
• Hypertension: Chronic high BP causes endothelial damage angiotension and endothelin vasoconstriction.
• Insulin Resistance & Diabetes: High blood glucose damages endothelium, decreasing NO production, and increases inflammation.

Consequences of Endothelial Dysfunction in Cardiovascular Disease

• Hypertension decreased NO and increased endothelin lead to vasoconstriction.
• Atherosclerosis inflammation, LDL oxidation which forms plaque.
• Heart Attack (MI) Plaque rupture forms a thrombus causing Coronary artery occlusion. Stroke Endothelial damage causes clots or vessel rupture.
• Peripheral Artery Disease (PAD) decreased NO and arterial plaques cause reduced blood supply to limbs.

Organ-Specific Mechanisms of Blood Flow Regulation

• Blood flow to different organs is regulated by intrinsic (local) and extrinsic (systemic) mechanisms to match metabolic demand.

Key Mechanisms

• Autoregulation: Organs maintain constant blood flow despite BP changes.
• Metabolic Control: Blood flow adjusts based on tissue oxygen & metabolite levels.
• Myogenic Response: Smooth muscle contraction/dilation in response to pressure. Neurohumoral Control: SNS, hormones (NE, Epi, Ang II, ANP).
• Organ
  • Brain (Cerebral); Primary Regulation Mechanism: Metabolic, Autoregulation; Key Factors: CO2, O2, H+ levels
  • Heart (Coronary); Primary Regulation Mechanism: Metabolic, Autoregulation; Key Factors: O2 demand, Adenosine
  • Kidneys (Renal); Primary Regulation Mechanism: Myogenic, Tubuloglomerular Feedback; Key Factors: BP, NaCl levels
  • Skeletal Muscle; Primary Regulation Mechanism: Metabolic (exercise), SNS (rest); Key Factors: Lactate, K+, H+, Epi
  • Lungs (Pulmonary); Primary Regulation Mechanism: Hypoxic Vasoconstriction; Key Factors: O2 levels
  • Skin; Primary Regulation Mechanism: SNS (temperature control); Key Factors: Body temperature

Mechanisms of Edema Formation

• Edema is an excessive accumulation of fluid in the interstitial space due to imbalances in Starling forces.

Starling Forces Regulating Fluid Movement

• Capillary Hydrostatic Pressure (Pc) pushes fluid out of capillaries.
• Interstitial Hydrostatic Pressure (Pi) pushes fluid into capillaries.
• Capillary Oncotic Pressure (πc) pulls fluid in (due to plasma proteins).
• Interstitial Oncotic Pressure (πi) pulls fluid out of capillaries.
• Net Filtration = (Pc - Pi) - (πc - πί)

Causes of Edema

• Increased Capillary Hydrostatic Pressure (Pc): Increases filtration out of capillaries; causes Heart failure and DVT.
• Decreased Capillary Oncotic Pressure (πc): Increases Reabsorption, causes Liver disease, and Nephrotic syndrome.
• Increased Capillary Permeability: Increases Protein leakage, decreasing Oncotic Gradient; causes Inflammation and Sepsis.
• Lymphatic Obstruction: Decreases Lymph Drainage, causes Lymphedema, and Cancer.

Organ-Specific Local Blood Flow Regulation

• Organ
  • Cerebral: Regulation Mechanism: Metabolic (CO2, O2)
  • Key Features: Increased CO2 leads to Vasodilation and ensures O2 delivery
• Coronary: Regulation Mechanism: Metabolic (Adenosine, O2 demand)
  • Key Features: Increased Demand leads to Vasodilation (e.g., during exercise)
• Renal: Regulation Mechanism: Autoregulation (Myogenic, Tubuloglomerular Feedback)
  • Key Features: Maintains GFR despite BP changes
• Skeletal Muscle: Regulation Mechanism: Metabolic (Exercise), SNS (Rest)
  • Key Features: Vasodilation in exercise (lactate, H+, K+)
• Pulmonary: Regulation Mechanism: Hypoxic Vasoconstriction
  • Key Features: Decreased O2 leads to Vasoconstriction (redirects blood to ventilated areas)
• Skin: Regulation Mechanism: SNS (Temperature Control) -Key Features: Vasodilation (heat dissipation), Vasoconstriction (cold)

Morphologic Characteristics of Cardiac Muscle & Their Functional Role

• Cardiac muscle is specialized for continuous contraction and has unique features that support automaticity, coordination, and resistance to fatigue.
• Morphologic Characteristics & Function
  • Striated Muscle
    • Description: Actin & Myosin arranged in sarcomeres
    • Functional Role: Generates force like skeletal muscle
  • Intercalated Discs
    • Description: Gap junctions & desmosomes
    • Functional Role: Electrical syncytium (rapid AP conduction)
  • Branched Fibers
    • Description: Short, Y-shaped fibers
    • Functional Role: Allows force distribution in multiple directions
  • Single Nucleus per Cell
    • Description: Unlike multinucleated skeletal muscle
    • Functional Role: Efficient cellular function
  • Mitochondria-rich
    • Decription ~30% of Cell Volume.
    • Functional Role fatigue resisting a high Atp production.
  • Involuntary Control
    • Function role regulated by Autonomic nervous system which is modulating HR & contractility.

Conduction System of the Heart: SA & AV Nodes

• The conduction system ensures sequential depolarization and contraction of the atria and ventricles. Key Components & Their Functional Roles
  • Sinoatrial (SA) Node
    • Location: Right atrium (near SVC)
    • Function: Pacemaker (sets HR at ~60-100 bpm)
    • Autonomic Innervation: Increased HR (SNS - β1), Decreased HR (PNS - M2 via vagus nerve)
  • Atrioventricular (AV) Node
    • Location: Interatrial septum (near tricuspid valve)
    • Function: Delays conduction allows ventricles to fill
    • Autonomic Innervation: Increased Conduction (SNS - ẞ1), Decreased Conduction (PNS - M2)
  • Bundle of His
    • Location: Interventricular septum
    • Function: Carries AP to ventricles
    • Autonomic Innervation: Minimal ANS influence
  • Purkinje Fibers
    • Location: Ventricular walls
    • Function: Rapid conduction coordinating Contraction
    • Autonomic InnervationMinimal ANS influence

Fast-Response vs. Slow-Response Action Potentials

• Cardiac action potentials (APs) differ between contractile cardiomyocytes (fast-response) and nodal pacemaker cells (slow-response).
• Fast-Response (Contractile Cells: Atria, Ventricles, Purkinje)
  • Resting Membrane Potential: -85 mV
  • Phase 0 (Depolarization): Na⁺ Influx (Fast Na⁺ Channels)
  • Phase 1 (Initial Repolarization): K⁺ Efflux (Transient K⁺ Channels)
  • Phase 2 (Plateau): Ca²⁺ Influx (L-type Ca²⁺ Channels)
  • Phase 3 (Repolarization): K⁺ Efflux (Delayed Rectifier K⁺ Channels)
  • Phase 4 (Resting/Pacemaker Potential): Stable (Maintained by K⁺ channels)
  • Function: Strong, rapid contraction
• Slow-Response (Pacemaker Cells: SA & AV Node)
  • Resting Membrane Potential: -60 mV
  • Phase 0 (Depolarization): Ca²⁺ Influx (Slow L-type Ca²⁺ Channels)
  • Phase 1 (Initial Repolarization): Absent
  • Phase 2 (Plateau): Absent
  • Phase 3 (Repolarization): K⁺ Efflux
  • Phase 4 (Resting/Pacemaker Potential): Unstable: Slow Na⁺ influx
  • Function: Spontaneous firing (automaticity)

Mechanism of Cardiomyocyte Contraction & Relaxation

• Cardiac contraction follows the Excitation-Contraction Coupling (ECC) process.

Steps in Cardiomyocyte Contraction

 - Depolarization:
      AP spreads via gap junctions
      L-type Ca²⁺ channels open enabling Ca²⁺ influx.
 - Calcium-Induced Calcium Release: Ca²⁺ triggers release from the sarcoplasmic reticulum via ryanodine receptors.
 - Troponin Activation & Contraction:
      Ca²⁺ binds troponin C shifting tropomyosin and enables Myosin binds actin Cross brige Contractoion.

Steps in Cardiomyocyte Relaxation Calcium is pumped out if the cell vaii the SERCA to block the myosin binding

Mechanisms by Which Sympathetic & Parasympathetic Tone Influence Heart Rate & Contractility

• The autonomic nervous system (ANS) modulates heart function through the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS). Sympathetic Influence (SNS – “Fight or Flight")
  • Neurotransmitter: Norepinephrine (NE)
  • Receptor: β1-adrenergic receptors (SA node, AV node, myocardium)
  • Mechanisms: Increased Heart Rate (Chronotropy)
  • NE ↑ CAMP activates HCN channels FacilitatesFaster Sa node depolarization INCREASESContractility

Increases Contractility:

IncreasesPKA and CA to cause influx to and MORE Ca is released and STRONG contraction has and increased conduction and speed Speeds up Av node increased relaxation and phosphlamb increase faster uptakes

Parasympathetic: Acetyl Decreasing Camp and Longer Pr interveal and minimal

Starling laws and Ca sensittity and high co

Preload & Afterload: Definitions & Effects on Myocardial Performance

• In the EDV and Myocyte strech

• To help

• Adapts Co to venous returns Preload (Filling Pressure of the Heart) Determined

• Arterial increases

• Examples

• Fluid, hemorrhage SV to failur

Sympathetic & Decreasing the vessels which mycite can cause and help delievew O2 and decrease O2 the need