Cardiac Muscle Physiology and Frank-Starling Law

• Cardiac muscle shares striations with skeletal muscle, but is controlled by the autonomic nervous system
• Intercalated discs contain gap junctions, facilitating rapid electrical signal transmission between cardiac cells
• Action potentials prompt voltage-gated L-type Ca2+ channels on the sarcolemma to open in Ca²⁺-Induced Ca²⁺ Release (CICR)
• A small Ca2+ influx triggers Ryanodine Receptors (RyR) on the sarcoplasmic reticulum (SR), resulting in a greater Ca2+ release
• Cytosolic Ca2+ binds to troponin, which initiates muscle contraction
• Relaxation happens when Ca2+ is pumped back into the SR via the SERCA pump, and out of the cell via the Na+/Ca2+ exchanger (NCX)

Frank-Starling Law

• The Frank-Starling Law states that the greater the preload (end-diastolic volume), the greater the stroke volume
• Ventricles that fill more with blood cause cardiac muscle fibers to stretch, this increases the force of contraction
• Cardiac output matches venous return because of the Frank-Starling Law
• Pooling of blood in the veins is prevented by the Frank-Starling mechanism

Path of Blood Flow

• Blood flows from the Vena Cava to the Right Atrium, then through the Tricuspid Valve to the Right Ventricle
• From the Right Ventricle, blood flows to the Pulmonary Arteries, then to the Lungs (Gas Exchange), and then to the Pulmonary Veins
• Oxygenated blood flows from the Pulmonary Veins to the Left Atrium, then through the Mitral Valve to the Left Ventricle, and then to the Aorta, finally undergoing systemic circulation
• Veins have the greatest capacity for blood volume storage, holding about 60-70% of the body's blood
• Arterioles have the greatest resistance and serve as the primary site of blood pressure regulation

Blood Flow Factors

• Blood flow (Q) through an artery is described by the equation Q = ΔP/R
• ΔP (Pressure gradient) is the difference between arterial and venous pressure
• R (Resistance) is determined by vessel diameter, length, and viscosity
• Vasodilation decreases resistance and increases blood flow
• Vasoconstriction increases resistance and decreases blood flow

Intrinsic and Extrinsic Factors

• Metabolic regulation sees increased CO2, decreased O2, and increased H+ (acidosis) which causes vasodilation
• Endothelial factors like nitric oxide (NO) leads to vasodilation
• Myogenic response involves vessels constricting or dilating based on pressure changes
• Sympathetic nervous system activity, including NE & Epi, causes vasoconstriction via α-adrenergic receptors
• Hormonal control that includes Epinephrine, Angiotensin II (vasoconstriction), and ADH, affects blood flow

Cardiac Cycle Events

• P wave represents atrial depolarization (atrial contraction)
• QRS complex represents ventricular depolarization (ventricular contraction)
• T wave represents ventricular repolarization (relaxation)
• End-Diastolic Volume (EDV) is the volume of blood in the ventricle at the end of filling, approximately 120 mL
• End-Systolic Volume (ESV) is the volume of blood in the ventricle after contraction, approximately 50 mL
• Stroke Volume (SV) is calculated as EDV - ESV, which is approximately 70 mL

Heart Rate

• Intrinsic heart rate (HR) is about 100 bpm, as set by the Sinoatrial (SA) node
• Parasympathetic (Vagus Nerve) slows HR to around 60-80 bpm at rest
• Sympathetic activation increases HR

Electrical Conduction

• Electrical conduction pathway is SA Node, AV Node, Bundle of His, Right & Left Bundle Branches, and Purkinje Fibers
• At the myocyte level, depolarization involves fast Na+ influx (Phase 0)
• Plateau phase involves Ca2+ influx (Phase 2), triggering contraction
• Repolarization involves K+ efflux (Phase 3)

Cardiac Output

• Cardiac Output (Q) is equal to HR × SV
• At rest, Q is approximately 5 L/min
• During exercise, Q can exceed 20-30 L/min
• Stroke Volume (SV) is equal to EDV - ESV, which is the blood ejected per beat

Venous Return

• Venous return is maintained by the muscle pump, respiratory pump, and venoconstriction
• Maintaining end-diastolic volume (EDV) ensures stroke volume and supports cardiac output

Ejection Fraction

• Ejection Fraction (EF) is calculated as (SV / EDV) × 100
• Normal EF is around 55-70%

Exercise

• During early exercise, both HR & SV increases and affects Q
• During moderate exercise, SV plateaus, but HR continues to increase
• During maximal exercise, HR maxes out, with Q increasing only through HR
• Increased sympathetic activation and decreased parasympathetic activity facilitates this

Adaptations

• The athlete's heart is a physiological adaptation to long-term endurance or resistance training
• Endurance athletes experience increases in left ventricular chamber size which increase SV & Q
• Strength athletes experience increases in left ventricular wall thickness to increase force generation
• Bradycardia is common among athletes due to high SV

Fick Equation

• The relationship between oxygen consumption (VO2), cardiac output (Q), and arteriovenous oxygen difference is described by the Fick equation VO2 = Q × (a - vO2) difference
• The a-vO2 difference is the quantity of oxygen extracted by tissues
• Higher VO2 max indicates better endurance capacity

Mean Arterial Pressure

• MAP (Mean Arterial Pressure) is equal to (2/3 DBP) + (1/3 SBP)
• Total Peripheral Resistance also describes MAP = Q × TPR

Hemoglobin and Myoglobin Curves

• Right shift decreases affinity and is caused by increased CO2, H+ (Bohr effect), and temperature, which causes more O2 unloading to tissues
• Left shift increases affinity and is caused by decreased CO2, H+, and temperature, which causes more O2 binding
• Myoglobin has a hyperbolic shape and a higher affinity for O2 than hemoglobin, which helps facilitate O2 storage in muscle

Gas Exchange

• Gas exchange occurs via simple diffusion based on partial pressure gradients
• Atmospheric Air: PO2 = 159 mmHg, PCO2 = 0.3 mmHg
• Alveoli: PO2 = 100 mmHg, PCO2 = 40 mmHg
• Arterial Blood: PO2 = 100 mmHg, PCO2 = 40 mmHg
• Venous Blood: PO2 = 40 mmHg, PCO2 = 46 mmHg
• O2 moves from alveoli into blood, while CO2 moves from blood into alveoli

Gas Diffusion

• Both O2 and CO2 diffuse across the alveolar membrane using partial pressure gradients as a driving force
• O2 moves from high PO2 (100 mmHg) to low PO2 (40 mmHg), while CO2 moves from high PCO2 (46 mmHg) to low PCO2 (40 mmHg)
• This is because CO2 diffuses approximately 20x faster than O2 due to higher solubility

Gas Laws

• Dalton's Law states that the total pressure of a gas mixture is the sum of the partial pressures of each gas
• Boyle's Law expresses that P1V1 = P2V2 by stating pressure and volume are inversely related
• Fick's Law states that the rate of gas diffusion depends on surface area, thickness, and partial pressure difference

Ventilation

• VE (Ventilation) is calculated as Breathing Rate × Tidal Volume
• At rest, VE is driven by the medulla & pons, regulated by CO2
• During exercise, VE increases due to neural input, metabolic CO2, chemoreceptors, and temperature

Lung Volumes

• Tidal Volume (TV) is the normal breath volume, approximately 500 mL
• Inspiratory Reserve Volume (IRV) is the extra air inhaled beyond TV
• Expiratory Reserve Volume (ERV) is the extra air exhaled beyond TV
• Residual Volume (RV) is the air remaining after full exhalation
• Total Lung Capacity (TLC) is calculated as TV + IRV + ERV + RV

Exercise

• VE must increase to remove CO2, maintain arterial O2 levels, and prevent oxygen desaturation at high intensities
• VE is controlled by central & peripheral chemoreceptors (CO2, O2, pH changes), mechanoreceptors (muscle movement), and higher brain centers (anticipatory response)

Hormones & Exercise

• Epinephrine & Norepinephrine increases HR, BP, and glycogenolysis
• Cortisol stimulates gluconeogenesis and suppresses immune function
• Growth Hormone (GH) is used for fat metabolism and muscle growth
• Insulin & Glucagon regulates blood glucose
• Aldosterone regulates Na+ retention and BP
• Antidiuretic Hormone increases water retention

Catabolic and Anabolic Hormones

• Catabolic hormones (e.g., cortisol, epinephrine) cause molecules to break down for energy
• Anabolic hormones (e.g., GH, testosterone) encourages muscle growth & repair

Endocrine Control

• Endocrine: Hormone released into bloodstream (e.g., insulin).
• Paracrine: Hormone acts on nearby cells (e.g., immune signaling).
• Autocrine: Hormone acts on the same cell that released it (e.g., IGF-1 in muscles).

G-proteins

• Second Messenger System uses G-protein & cAMP (e.g., epinephrine, glucagon)
• Direct Gene Activation happens when a Hormone enters the nucleus to alter DNA transcription (e.g., testosterone, cortisol)

HPA Axis

• Stress response system is Hypothalamus (CRH), Pituitary (ACTH), and Adrenal glands (Cortisol)
• HPA Axis regulates energy, immune response, metabolism

Renin-Angiotensin System

• The renin-angiotensin system facilitates the increases of BP & fluid balance
• Low BP causes kidney to release renin
• Renin converts angiotensinogen into angiotensin I into angiotensin II, which increases BP & Na+

Hormones

• ANP is released by the heart when BP is too high and promotes Na+ & water excretion, reducing blood volume & BP
• GLUT-4 is a glucose transporter in skeletal muscle & adipose tissue
• Insulin & muscle contraction stimulates GLUT-4 translocation to increase glucose uptake

Thirst

• Hypothalamus detects increasing plasma osmolality, decreasing blood volume/pressure, and increasing Angiotensin II

Glucose During Exercise

• Liver glycogenolysis & gluconeogenesis maintains levels during exercise
• Hormonal regulation with glucagon, epinephrine, cortisol, GH, also helps maintain levels
• Fat utilization increases over time to preserve glucose
• HIIT-Rapid glycogen depletion, increased glucose demand, spikes due to epinephrine
• Endurance-Gradual glycogen use, fat oxidation increases over time, glucose stabilizes

Insulin Resistance

• Cells become less responsive to insulin and reduce glucose uptake
• Insulin Resistance is linked to obesity, inactivity, type 2 diabetes

Plasma Volume

• Fluid shifts from plasma to interstitial spaces & active muscles increases capillary pressure
• Hemoconcentration PV drops, making het look larger (relative) (dehydration)
• Hemodilution PV expands, making het look smaller (heat acclimation)
• Het does not change in either scenario, ratio to plasma changes