Cardiac Muscle and Pacemaker Cells

Cardiac Muscle Features

• Presence of sarcomeres gives it a striated appearance
• Intercalated disks connect the cells ensuring coordinated movements
• Desmosomes within intercalated disks offer structural support and prevent cell separation
• Gap junctions allow direct ion flow for synchronized electrical signaling and contraction
• Found in atria and ventricles

Autorhythmic Pacemaker Features

• Autorhythmic pacemaker cells don't contribute to contractile force
• Spontaneous depolarization contains funny channels that allow heart contraction independent of the nervous system
• Pacemakers set the pace of heart rhythm
• Located in the SA node, AV node, Bundle of His, and Purkinje bundle

Contractile Cell Action Potential Stages

• Resting potential is at -90 mV
• Action potential is generated by pacemakers and spreads through gap junctions
• Voltage-gated Na+ channels open, causing rapid depolarization to +20 mV
• Na+ channels close, and fast K+ channels open, releasing K+ for initial repolarization
• Voltage-gated Ca2+ channels open, balancing the K+ efflux during the plateau phase
• Prolonged depolarization causes sustained contraction and a long refractory period
• Prevents tetanic contraction, ensuring one contraction at a time
• Prevents premature repolarization allowing adequate contraction time for effective blood pumping
• Enhances Ca2+ entry, offsetting K+ and stabilizing voltage before depolarization
• Ca2+ channels close, K+ permeability increases, and slow K+ channels open for repolarization
• Rapid K+ efflux allows cells to reach resting potential again

Excitation-Contraction Coupling

• Action potentials spread to contractile cells through gap junctions from pacemaker cells
• L-type Ca2+ channels on the sarcolemma and T-tubules depolarize
• Ca2+ influx triggers RyR receptor activation, releasing Ca2+ from the sarcoplasmic reticulum
• Localized Ca2+ release from the SR summates provides a global Ca2+ signal detectable via fluorescent light
• Ca2+ binds to troponin initiating contraction
• Ca2+ detaches from troponin, relaxing the muscle
• SERCA pump moves Ca2+ back into the SR
• NCX removes Ca2+ by exchanging it with Na+
• Na+/K+ ATPase maintains the Na+ gradient for the NCX function

Skeletal vs. Cardiac Muscle

• Skeletal muscle exhibits voluntary movements controlled by the nervous system; cardiac muscle shows involuntary movements not controlled by the nervous system
• Skeletal muscle cells are long, unbranched, and multinucleated; cardiac cells are branched, interconnected, with intercalated disks
• Both skeletal and cardiac muscle contact via actin/myosin and are striated with sarcomeres

Pacemaker Cell Action Potential

• Starts at -60mV pacemaker potential, which is unstable
• Negative membrane potential triggers If channel (funny channel) opening
• Funny channels open during membrane hyperpolarization
• Funny channels are permeable to Na+ and K+ but Na+ influx exceeds K+ efflux
• Slight inward depolarization results in threshold being reached
• Voltage-gated Ca2+ channels open at threshold, allowing Ca2+ influx
• Rapid depolarization and action potential generation result
• Action potential spreads through gap junctions to adjacent cells
• Action potential peaks at +20 mV, causing voltage-gated Ca2+ channels to close and K+ channels to open
• K+ repolarizes the membrane through K+ efflux
• Once -60mV is reached, funny channels reactivate

Heart Rate Modulation

• What sets the heart rate is the pacemaker cells in the SA node
• Pacemaker cells receive antagonistic signals from sympathetic and parasympathetic divisions of the brain
• SA node rate is 65 bpm
• AV node rate is 50 bpm
• Bundle of His rate is 40 bpm
• Parasympathetic input dominates at rest
• Sympathetic system dominates during stress or exercise

Autonomic Nervous System Effects on Heart Rate

• Sympathetic system features Beta adrenergic receptors and norepinephrine/epinephrine neurotransmitters
• Parasympathetic system features muscarinic receptors and acetylcholine
• Norepinephrine binds to B adrenergic receptors which activates Gs proteins and stimulates adenylyl cyclase, increasing cAMP production and enhancing the funny current
• Increases depolarization of pacemaker potential, leading to faster threshold and increased firing rate
• Heart rate increases during Tachycardia
• Increased cAMP leads to more If current and greater pacemaker depolarization
• Acetylcholine binds to muscarinic receptors, activating Gi proteins
• Activated Gi proteins lowers adenylyl cyclase, decreasing cAMP and opening K+ channels that increases K+ permeability
• Leads to hyperpolarization of the membrane
• Shifts pacemaker potential to a more negative value slowing depolarization, AP generation, and Ca2+ permeability
• Slows heart rate during Bradycardia
• Decreased cAMP slows If current, causing hyperpolarization and slower depolarization
• Atropine prevents parasympathetic inhibition leading to an increased heart rate
• Propranolol reduces sympathetic stimulation causing a mild decrease in heart rate

SA/AV Node Blockage

• AV node takes over as the pacemaker if the SA node is blocked
• AV node takeover results in slow heart rate of 40 bpm
• Purkinje fibers take over the pacemaker, which decreases the heart rate to 20-40 bpm (severe bradycardia)

Heartbeat Coordination Steps

• SA node depolarization initiates electrical signalling for contraction
• Electrical signal spreads through gap junctions
• Electrical conduction is quick via internodal pathways for atrial transmission
• Atrial depolarization spreads slowly allowing time for atrial contraction
• AV node momentarily delays conduction allowing the atria to fully contract before ventricles activate
• Electrical signal passes to the ventricles through the AV node only
• Electrical signal travels from AV node through AV bundle branches to the apex
• Sending signals from the apex is important because contraction at the top would cause insufficient blood ejection
• Purkinje fibers rapidly transmit impulses ensuring all contractile cells in the apex contact simultaneously
• Contraction spreads from apex to base optimizing blood ejection via a depolarization wave

Echocardiogram Setup

• Negative electrode on the right arm
• Positive electrodes on the left arm and leg
• Following Einthoven's Triangle
• Lead I shows potential differential between right and left arm
• Lead II shows potential differential between right arm and right leg
• Lead III shows potential differential between left arm and left leg

ECG Signal Interpretation

• Depolarization toward a positive electrode gives an upward deflection
• Repolarization toward a positive electrode gives a downward deflection
• Depolarization toward a negative electrode gives a downward deflection
• Repolarization toward a negative electrode gives an upward deflection

ECG Measurements

• Heart rate
• Heart rhythm
• Conduction system function

ECG Waves

• P wave: atrial depolarization
• P-R segment: conduction through AV node and bundle
• QRS complex: ventricular depolarization
• T-wave: ventricular repolarization

Events in EKG Waves

• P wave has an upward deflection because the direction of depolarization is towards the positive electrode
• Depolarization spreads to the AV node, indicated by the fall of the P wave peak followed by atrial contraction
• Contractions are not visualized by peaks on an EKG
• The signal passes through the AV node signalling contraction
• Septum depolarizes away from the positive electrode with a downward Q wave
• Ventricular depolarization causes ventricular contraction with net current flow gives R wave
• Depolarization starts at the apex of the ventricles which is more efficient
• Repolarization of atria is masked as ventricles have greater mass
• Depolarization travels away from apex which gives downward S wave deflection
• The S-T segment follows systole of the ventricles
• Upward T wave deflection shows ventricle repolarization
• Ventricular diastole occurs after contraction which is after the T Wave

EKG Abnormality Types

• Atrial Fibrillation (A-Fib) manifests as an uncontrolled movement of charge in the atria causing rapid and uncoordinated contractions reducing a distinct P Wave with high clotting risk
• Ventricular Fibrillation (V-Fib) manifests as uncontrolled movement of charge causing the ventricles to quiver, but can be solved via defibrillation through AEDs
• AV Block manifests as delayed or blocked electrical signals dependent on the degree of the block, and is solved through slower conduction or artificial pacemakers

Blood Pressure Factors

• Blood flows due to pressure differentials therefore Pressure = Flow x Resistance where Flow = Pressure/Resistance
• Stroke volume can be calculated to see show much blood flows from the ventricle
• Vstroke = End diastolic volume (EDV) - End systolic volume (ESV)
• EDV = how much blood there is during the filling
• ESV = how much blood left after ejection
• Cardiac Output = stroke volume x heart rate
• Poiseullie’s Law: R= 8Ln/πr4
• When the radius of an object decreases and pressure stays constant, there will be an increase in resistance, and flow decreases, and vice versa
• Fluid Velocity (V) = Flow/ Cross sectional area
• the flow will remain equivalent throughout varying cross sectional areas, but narrower objects accelerate velocity while the wider an object slows down

Blood Flow

• Flow throughout arteries, arterioles, and capillaries stays constant, though velocity varies
• Heart valves regulate blood flow, the flow in one direction
• AV valves are tricuspid and bicuspid
• Semilunar valves are pulmonic and aortic
• Systole describes cardiac muscle contraction
• Diastole: Cardiac muscle relaxation
• Atrial and ventricular events occur at different times

Cardiac Cycle Phases

• Phase 1 (Filling or Diastole): Atrioventricular valves are open, while aortic and pulmonary valves are closed
• Phase 2 (Isovolumic Contraction): All valves are closed, atria contracts to close atrioventricular valves
• Phase 3 (Ventricular Ejection): Left atrium is closed as rising ventricular pressure forces the atrioventricular valve to shut
• Phase 4 (Isovolumic Relaxation): All valves are closed

AV Valve and Semilunar Valve Action

• During atrial systole the atria contracts
• High pressure during ventricular systole forces blood into the semilunar valve
• Open AV Valve - blood flows from atria to ventricle, and diastole begins
• Closed Semilunar Valve - isovolumic as ventricular pressure rises and the ventricles release and begin diastole

Key Concepts During Heart Muscle Contractions

• Semilunar valves are closed if the pressure of the atria > ventricles
• When the pressure in the atria is less than ventricles: semilunar open and AV are closed
• They are equal in pressure, both are closed and signals a transition from either filling to pumping or vice versa
• Isovolumic contraction phase allows the ventricle to build up enough pressure
• Aorta pressure should never drop below ventricle
• On the left side of the heart, left Ventricular pressure is higher than the right side

Blood Vessels

• The left side of the heart has the higher pressure
• Left side has high resistance throughout the systemic circulatory system requiring friction as opposed to right side’s lower friction due to lung travelling
• End-Diastolic volume (EDV) volume is affected by factors during diastole
• ventricular pressure reaches the aorta's pressure therefore a AV valves must always open
• End-systolic volume describes how much the ventricle remains after systole

Blood Vessel Types and Functions

• Arteries have a thick and elastic layer to withstand high blood pressure
• Arterioles constrict and vasodilate to control TPR
• Capillaries undergo simple diffusion for material exchange
• Venules transition between capillary and vein
• Veins are a reservoir

Vessel Compliance and Elasticity

• Compliance describes expansion capability
• Elasticity - describes how well one returns to its original state
• Arteries - High elasticity and low compliance
• Veins - Low elasticity and high compliance
• Heart generates pressure, so arterial elasticity helps propel forward
• Lower extremities require back pressure and are prone to Orthostatic hypotension

Autonomic Blood Pressure Control

• Located in the ganglios, Aortic arch, and artery
• Dendrites contains mechanoreceptors, the Piezo channels
• During blood pressure changes, the autonomic sends error correction
• More Arterial pressure means more action potential firing creating less more activity of baroreceptors

Actions for Low Blood Pressure Output

• B1 adrenergic activate output for SA Node creating a fast heart rate
• Skeletal muscles help more blood flow through valves
• Increase inspiration as one breathes

Force and Pressure Relationship

• Starling's Law describes how stretched ventricles can undergo stronger contractions via camp, l-type channels, and more ca2+ release

Vasoconstriction and Vasodilation

• Vasodilation/ vasocontriction occurs as Nor-epinephrene triggers alpha 1 receprot
• Pressure triggers parasympathetic so NE/E act independently through receptors
• Alpha 1 are located on the smooth muscle
• NE/E triggers dilation
• During vasoconstricting, NE triggers the smooth muscles to contract while activating the beta causes dilation

Gas Transportation

• Cells consume oxygen and exhale C02
• During exercise, C02 level in cells increases which trigger the epiphenine release
• C02+H+ activates piezo receptors signals triggering a vaso diameter switch
• If one oxygen binds to hemoglobin, then dilation stops

Paracrine Resistance Modulators

• Oxygen constricts blood flow in order to lower aerobic demand
• vasodilation can dissolve H+ concentration
• Nitrous oxide causes smooth muscles to dilate
• A lack Of nitric oxide means that can cause High bp

PDE5 Usage

• PDE5 promotes vasodilation to increase blood flow with VIAGRA but can lead to the dysfunction

Capillaries

• All Capillaries need to be small.ions
• Fenetrates- contains large fluid Gaps
• water soluble has pores for diffusion
• Lipids can diffuse, but larger proteins cannot
• Extracellular moves through to absorb via.hydrostatic pressure
• Water and proteins are important to control.edema by pushing into capillaries

Lymphatic System

• Lymph carries nutrients and fluid to the vein
• 3L/3 day fluid gets filtered
• Blood pressure must increase, but edema must decrease
• Failure to do either, leads to lower oxygen and pressure increasing the Hydrostatic Pressure

Cardiovascular Ailments:

• High blood pressure causes clots, so high
• Increased BP through water excess triggers hormone increase
• Aortic Valve closes off the heart therefore they have to press very high
• Reduce sodium and relax muscles

Vessel Thickness

• Aortic stenosis- low stroke
• MI- blocked blood, which is combatted with aspirin
• Cholesterol builds plasma for plasma membrane with hormone for Vitamin D building
• HDL is good, macrophages are bad