Cardiac Physiology: Origin of Heartbeat

Properties of Cardiac Muscle

• Myocardial fibers have a resting membrane potential (RMP) of -90mV
• Individual fibers are separated by membranes, but depolarization spreads rapidly through them as if they were a syncytium due to the presence of gap junctions
• Action potential in cardiac myocytes/contractile cells (ventricle, atrial) has five phases:
  • Rapid depolarization (phase 0): activation of fast Na+ channels, inward Na+ current
  • Initial rapid repolarization (phase 1): inactivation of fast Na+ channels, inward Na+ current ceases, outward K+ current through T-type K+ channels
  • Plateau (phase 2): slow inward Ca2+ current through L-type Ca2+ channels, slow outward K+ current
  • Repolarization (phase 3): decreased inward Ca2+ current, increased outward K+ current
  • Resting membrane potential (phase 4): maintained by opening of leaky K+ channels

Action Potential in Pacemaker Cells (SA Node)

• SA node exhibits automaticity (ability to spontaneously generate AP without neural input)
• Unstable resting membrane potential, no sustained plateau
• Prepotential (phase 4):
  • First half: opening of funny Na+ channels, increase inward Na+ current, closure of K+ channels
  • Last half: decrease inward funny Na+ current, increase Ca2+ current through T-type Ca2+ channel
• Phase 0: decrease inward Ca2+ current through T-type Ca2+ channel
• Phase 3: decrease inward Ca2+ current through L-type Ca2+ channel

Spread of Cardiac Excitation

• Atrial excitation (AP originating in SA node):
  • Complete in 1 second
  • Interatrial pathway extends from SA node within the right atrium to the left atrium
• Conduction between atria and ventricles:
  • The impulse is delayed about 0.1 seconds (AV node delay) to allow the atria to become completely depolarized and contract, emptying their content into ventricles
• Ventricles excitation:
  • Impulse travels rapidly down the septum via the right and left branches of the bundle of His and through the ventricular myocardium via Purkinje fibers
  • Depolarization of ventricular muscle starts at the left side of the interventricular septum and moves to the right side
  • Wave of depolarization spreads down the septum to the apex of the heart and returns along the ventricular wall to the AV groove
  • Last part of the heart to be depolarized is the posterobasal portion of the left ventricle, the pulmonary conus, and the uppermost portion of the septum

Refractory Period

• Refractory period: where a second AP cannot be triggered until the membrane has recovered from the preceding AP
• Cardiac muscle has a long refractory period because of the prolonged plateau phase, ensuring that the cardiac muscle cannot be restimulated until contraction is almost over
• This is a protective mechanism because pumping blood requires alternating periods of contraction (emptying) and relaxation (filling)

ECG

• P wave: atrial depolarization
• PR segment: AV node delay to ensure atrial complete depolarization and contraction, emptying their content into ventricles
• QRS complex: ventricular depolarization, where atrial repolarization occurs simultaneously
• ST segment: time during which ventricles are contracting and emptying
• T wave: ventricular repolarization
• TP segment: time during which ventricles are relaxing and filling
• Characteristic of a normal ECG:
  • Heart rate: 60-100 bpm
  • PR interval: 0.12-0.2 seconds
  • QRS complex: 0.06-0.1 seconds
  • QT interval: varies with heart rate

Pulmonary Compliance and Work of Breathing

• Compliance of the lungs (C): the ease with which the lungs can expand
• Factors affecting compliance:
  • Elasticity of connective tissue
  • Surface tension
• Surfactant: a mixture of lipid and protein produced by type II alveolar cells that decreases surface tension, increases lung compliance, and decreases the work of inflating the lungs

Airway Resistance

• Increased in viscosity and airway resistance
• Bronchoconstriction: decreased radius, increased airway resistance
• Bronchodilation: increased radius, decreased resistance to airflow

Lung Volume and Capacities

• Tidal volume (TV): the amount of air inhaled or exhaled with each breath under resting conditions
• Inspiratory reserve volume (IRV): the amount of air that can be forcefully inhaled after a normal tidal volume
• Expiratory reserve volume (ERV): the amount of air that can be forcefully exhaled after a normal tidal volume
• Residual volume (RV): the amount of air remaining in the lungs after a forced exhalation
• Inspiratory capacity: the maximum volume of air that can be expired after a normal expiration
• Functional residual capacity (FRC): the amount of air remaining in the lungs after a normal tidal volume expiration
• Vital capacity (VC): the maximum amount of air that can be expired after a maximum inspiratory effort
• Total lung capacity (TLC): the maximum amount of air that the lungs can hold
• Forced Expiratory Volume (FEV) in 1 second: the volume of air that can be expired during the first second of expiration in VC determination### Control of Breathing
• Dorsal respiratory group (DRG) in medulla oblongata: mainly inspiratory neurons
• Ventral respiratory group (VRG) in medulla oblongata: both inspiratory and expiratory neurons
• Pneumotaxic centers in pons: send impulses to DRG to switch off inspiratory neurons
• Apneustic centers in pons: prevent inspiratory neurons from being switched off, providing an extra boost to inspiratory area
• Chemoreceptors:
  • Central chemoreceptors: sensitive to changes in CO2-induced H+ concentration in brain ECF and pH
  • Peripheral chemoreceptors: sensitive to increased H+ concentration in arterial blood, increased Pco2, and decreased Po2

Abnormalities in Arterial Blood Gases

• Hypoxic hypoxia: decreased PaO2, inadequate Hb saturation
• Anaemic hypoxia: reduced oxygen-carrying capacity of blood
• Ischemic hypoxia: inadequate oxygen delivery to tissue
• Histotoxic hypoxia: inability of cells to use available oxygen
• Hypercapnea: excess CO2 in arterial blood, caused by hypoventilation
• Hypocapnea: low CO2 in arterial blood, caused by hyperventilation

Respiratory Adjustment During and After Exercise

• Receptors involved in ventilation during exercise:
  • Central chemoreceptors: detect changes in CO2 and pH
  • Joint and muscle receptors: stimulated during muscle contraction, reflexly stimulating respiratory center
• Ventilation changes during and after exercise:
  • During exercise: increased Pco2, decreased pH and Po2, increased firing rate in afferent nerves, stimulating respiratory muscles
  • After exercise: decreased ventilation as alveolar Pco2 decreases, and arterial pH returns to normal

Respiratory Adjustment at High Altitude

• Acclimatization:
  • Increased pulmonary ventilation (hyperventilation)
  • Increased RBCs and hemoglobin concentration
  • Increased diffusing capacity of the lung
  • Increased vascularity of peripheral tissue
  • Increased ability of tissue cells to use O2 despite low Po2
• Effects of high altitude:
  • Alveolar PO2 decreases due to barometric pressure
  • Arterial PO2 decreases (hypoxemia)
  • Ventilation rate increases (hyperventilation)
  • Arterial pH increases (alkalosis)
  • Haemoglobin concentration increases (polycythaemia)
  • 2,3-DPG concentration increases, decreasing Hb affinity for O2
  • O2-hemoglobin dissociation curve shifts to the right

Respiratory Adjustment at Low Altitude (Diving)

• Effects of compressed air:
  • Oxygen toxicity: high partial pressure of O2 in tissue, leading to muscle twitching, nausea, and dizziness
  • Nitrogen narcosis: high partial pressure of N2, reducing neuronal excitability and leading to euphoria, drowsiness, and loss of consciousness
• Decompression sickness:
  • Rapid ascent causing dissolved nitrogen to form bubbles in blood and tissue, leading to damage and blockage of blood vessels
  • Symptoms: paralysis, muscle weakness, difficulty urinating, dizziness, and shortness of breath
  • Prevention: gradual ascent to enable dissolved nitrogen to be eliminated through respiration
  • Treatment: tank decompression