Cardiac Muscle Structure and Function

Cardiac Muscle Overview

• Cardiac muscle is what comprises the heart
• The muscle is arranged into atria and ventricles
• Atria are the top, small chambers: right (RA) and left (LA); they rapidly change dimension and volume
• Ventricles are the bottom, large chambers: right (RV) and left (LV); the myocardium is made of cardiac muscle cells
• The ventricles rapidly change dimension and volume with atrial contraction

Cellular Structure

• Regular arrangement of myofilaments (sarcomeres) creates striations
• Cells tend to be branched at their ends
• Intercalated disks offer mechanical and electrical connections
• Desmosomes at intercalated disks give structural support
• Gap junctions at intercalated disks are protein channels linking the cytosols of adjacent cells, allowing for the quick passage of small molecules like ions from cell-to-cell
• Cardiac muscle forms a functional syncytium due to gap junctions, where many cells act as one

Excitation-Contraction (EC) Coupling

• Electrical signal (action potential) triggers a chemical signal (intracellular Ca2+ release or Ca2+ transient) which leads to a mechanical signal (contraction)

Action Potential in Ventricular Cardiac Cells

• Highly negative resting membrane potential (-89 mV) exists because of significant K+ leak
• Current enters from neighboring cells through gap junctions, permitting current to flow from cell-to-cell without graded potentials
• Rapid opening of voltage-gated Na+ channels causes rapid depolarization
• Slow, prolonged opening of voltage-gated Ca2+ channels results in the prolonged "plateau" of depolarization; these channels are called L-type channels, also known as dihydropyridine receptors (DHPRs)
• Repolarization occurs due to the slower opening of voltage-gated K+ channels
• Action potential duration is long, about 300 ms which is due to the L-type channels

Molecular Players in Cardiac EC-Coupling

• Sarcolemma includes T-tubules
• Sarcoplasmic reticulum (SR) is made of lateral sacs (terminal cisternae) and longitudinal SR (LSR)
• Dihydropyridine receptor (DHPR) is also called the L-type Ca2+ channel
• Ryanodine receptor (RyR) releases calcium
• SERCA (SR Ca2+-ATPase) pumps move calcium

Excitation Steps

• The membrane is depolarized by Na+ entry, functioning as an action potential
• Depolarization opens L-type Ca2+ channels in the T-tubules
• A small amount of "trigger" Ca2+ enters the cytosol, contributing to cell depolarization, triggering Ca2+ binding and opening of ryanodine receptors (RyR Ca2+ channels) in the sarcoplasmic reticulum membrane
• Ca2+ flows into the cytosol, increasing Ca2+ concentration

Steps in Excitation-Contraction (EC) Coupling

• Gain of function: 1 Ca2+ through L-type Ca2+ channel results in 10 Ca2+ from SR through RyR - known as Calcium-Induced Calcium Release (CICR)

Contraction Steps

• Binding of Ca2+ to troponin exposes cross-bridge binding sites on thin filaments
• Cross-bridge cycling causes force generation and sliding of thick and thin filaments which results in contraction
• Thin filament regulation of contraction occurs just like in skeletal muscle

Relaxation Steps

• Ca2+-ATPase pumps return Ca2+ to the sarcoplasmic reticulum.
• Ca2+-ATPase pumps and Na+/Ca2+ exchangers remove Ca2+ from the cell
• ↑ Calcium SERCA Pumps results in ↓ Intracellular Calcium and promotes relaxation
• Reduction in Intracellular Calcium is also created by its Extrusion by Sarcolemma and extrusion by the Sodium / calcium exchanger

Repolarization of the Membrane

• Repolarization of the membrane occurs when K+ exits the cell, ending the action potential.

Action Potentials and Twitch Tension

• Skeletal muscle can have tetanus or sustained contractions
• Cardiac muscle has a prolonged refractory period that prevents tetanus
• Cardiac muscle cannot summate force, which allows the ventricles time to relax and fill with blood prior to the next heartbeat
• Skeletal muscles have an action potential for 1-2ms while Cardiac action potential last for 300ms

Three Muscle Types

• Skeletal (Sk), Smooth (Sm), and Cardiac (Card) muscles all:
  • Contain myosin thick filaments and actin thin filaments
  • Has troponin and tropomyosin
  • The same 4 steps of cross-bridge cycle
  • Undergo sliding filament mechanism of contraction
  • Have ATP powering the generation of force
  • Depend on elevated cytosolic Ca2+ to initiate contraction
• Small and uni-nucleated: Smooth, and Cardiac
• Arranged in layers and surrounds hollow cavities: Smooth and Cardiac

Cardiovascular System

• Plays a main transport role in homeostasis
• Organ systems that benefit from it are: GI, Respiratory, Renal, Skin/Muscles, and Endocrine
• The circulatory system is essential because diffusion of solutes over distances of 100 µm or more is too slow for large, multicellular organisms to function
• Diffusion equilibrium happens within seconds to minutes, within 100um or more, through the Interstitial Fluid

Components of Circulatory System

• The Heart, Blood Vessels, and Blood
• Heart: biological pump that generates force to move the blood; mainly electrical and mechanical
• Blood: the fluid connective tissue through which O2/CO2, wastes, nutrients, and messengers such as hormones are transported
• Blood vessels: the 'tubing' through which the blood flows; they play an active role in blood movement

Blood Components

• Total blood volume averages 5.5 L
• Plasma averages 3.0 L or 55-58%; like ISF, but has plasma proteins; it is part of the ECF
• "Buffy coat" has leukocytes (WBCs) and platelets; insignificant volume.
• Erythrocyte (RBC) volume averages 2.5 L or 42-45% L, is called the hematocrit
• RBCs are mainly involved in gas transport

Erythrocytes (Red Blood Cells)

• Biconcave discs
• Large surface area and smaller volume promote rapid diffusion
• 7 µm in diameter
• High hemoglobin content
• Hemoglobin binds oxygen
• Organelles are extruded, so has no DNA; the buffy coat is used for forensics.

Blood Makeup

• Oxygen is transported by red blood cells
• Clotting uses platelets
• Immunity depends on WBCs

Cardiovascular System and Homeostasis Maintenence

• ↓O₂ delivery to kidneys results in ↑ Erythropoietin secretion to ↑ Plasma erythropoietin
• ↑ Plasma erythropoietin results in ↑ Production of erythrocytes from the bone marrow
• ↑ Production of erythrocytes in the bone marrow leads to a ↑ Blood Hb concentration and ↑ Blood O2-carrying capacity
• ↑ Blood O2-carrying capacity causes Restoration of O2 delivery

Systemic vs. Pulmonary Circulations

• 2 pumps and 2 circulatory systems comprise the heart: pulmonary moves blood to the lungs, and systemic circulates everywhere else in the body
• Arteries carry blood away from the heart and veins carry blood toward the heart
• There is a difference in heart wall thickness when analyzing right vs. left sides
• Perfusion moves blood through a vascular bed from high to low pressures along a pressure gradient
• Vascular beds are mostly in parallel, but pulmonary circulation is in series

If Capillary Beds (Organs) are In Series

• Quality of blood is same" to all organs
• Flow regulation to individual organs and there is an amount of initial pressure required

If Capillary Beds (Organs) are In Parallel

• Systemic veins connect to the pulmonary and arterial arteries

Heart Anatomy

• The superior vena cava is #1
• #2 is the interatrial septum
• #3 is the right AV (tricuspid) valve
• #4 is chordae tendineae
• #7 is the Aorta and the location of the Right pulmonary artery
• #8 is the location of right pulmonary veins
• The pulmonary artery is #6 location
• The pericardium is #9 location
• Interventricular septum is above #11
• The myocardium (heart muscle) connects with the epicardium
• #5 is at the Pulmonary and semilunar valve

Cardiac Muscle Cells

• Pacemaker cells have automaticity; the SA node normally determines the heart rate: SA node (100-120 APs/min), AV node (60-80 APs/min), Conducting cells (30-50 APs/min)
• Conducting cells conduct action potentials and are specialized to rapidly spread the electrical stimulus throughout the chambers: bundle of HIS, right and left bundle branches, & Purkinje fibers
• Contractile cells (99% of cardiac muscle cells) allow blood to be pumped out of the heart by developing tension to pump blood
• All Cardiac muscle cell types have a specific functional role in a normal heartbeat and have gap junctions

Coronary Circulation

• Coronary arteries branch directly off the aorta behind the aortic valve cusps as the first vessel
• Blood inside pumps oxygen and nutrients through coronary capillaries to the heart muscle cells
• Coronary veins return blood into the right atrium

Blood Flow

• Blood passes from Typically starting in Right Ventricle
• Blood has a valve to go backwards
• In the left atrium
• Every cell is within 1-10 µm of a capillary except for the cornea and lens

Cross Section of Heart

• During atrial, there is contraction
• The flow has to keep the vessels open
• The pulmonary has to get it to the aorta

Heart Valves

• Chordae tendineae attached to papillary muscles
• Is designed to Prevent prolapse but Can also rupture

Valves

• When there is a pressure difference between atrium and ventricle you have to promote it and either open or close valve

Sounds Made

• When turbulent flow equals a murmur
• When allow leak, build up of pressure results in insufficient valve
• You hear “gurgle” from the Leaky valve
• You hear a Stenotic valve with poor opening will sound with “whistle”
• A whistle in the heart before the typical heart sound is Stenotic
• When there is a gurgle always the typical heart comes after the sound. Then that is Diastolic.
• A vessel that is Insufficient is always diastolic.

Isovol/Ejection

• Isovol equal Systole
• AV Closed
• SL opens

Heart Sounds and Valve Defects

• If both are insufficient then it is S1
• S1 ("lub") occurs during isovolumetric ventricular contraction, represents AV valves closing
• S2 ("dup") occurs during isovolumetric relaxation, represents semilunar valves closing.
• In General* -S1 has Aortic stenosis and and -S2 has aortic regurg
• Specifics*
• A Lub-Whistle-Dup implies stenotic Sl
• A Lub-Gurgle-Dup implies AV is Insufficient
• A Lub-Dup-Whistle implies stenotic AV
• A Lub-Dup- Gurgle implies SL insufficient

Atrial Activation

• A node is "true" pacemaker. and it Reaches threshold

AV Node Activation is Electrical Connection Between Atria and Ventricles

• Slow the action potential and cells are in a Chain
• There is less ion channel density ->delays activation of the Ventricles

Bundle of His, Bundle Branches & Purkinje Fibers

• All are made of conducting cells so action potential propagation is fastest; also is is relatively fast in ventricular contractile cells

Conduction Pathway

• Atrial contractile is excited and contracted
• AV is at a slow phase for AP propagation
• The order is SA Node to contract, then goes through A and V system to contract bundle of this/ purkinje fibers to ventricular contractile

Gap Junctions/Electrical Syncytium

-The Implications of heart Coordination: -One cell starts each action potential (heartbeat) One diseased cell can cause a fatal arrhythmia -Artificial pacemakers are possible to install -No recruitment for stronger heart beats as in the cell contracts with every heartbeat!

ECG Basics

• The Leads use electricity
• To do that you can get Lead II Lead 3 etc.

Wave Interpretation

• Depolarization (right left) To go any To go is the recording Electrode is a positive Deflection. If any way of de pull is it to left right is a nagative deflection

ECG

• It helps look a the front wall as its a big axis
• And the other planes will look at things more laterally
• Depolarization occurs 1st wave SA before getting in the way, and you have atrial Q, Then R which is ventricular in you have your heart is going to move through this and to end up with something like that.

Nodal Conduction

• Nodal cells are pacemakers and the membrane is supposed to always be Changing

Here is label review:

• Q is for getting the electrical of The first deflection

• You do the same for ventricular

• Q is the negative and so it

Axis and Wave

• If that is the case the way that you should be thinking
• Is it any way that is approaching what is in that general area that's going to be a positive deflection.
• In A positive reflection means the Right arm or a positive deflection.

Axis Deviation

• For example the heart in a hypertrophic patient could be a left shift, that would mean their blood vessels would be smaller

Cardiac potentials

• All channels are activated -If are to activated channels then the conduction velocity would be affected.

Rhythms

• We're gonna talk about you know what is to find a sinus rhythm what ist eine what and what does an ectopic pacemaker mean. Ectopic
• A rhythm does not start when there is an SA node or When there is something, Then there's a node. Something happened like a failure and then you could actually get and something

Tachycardia vs Bradycardia

• Tachycardia has high rate of about 100bmp
• Bardycardia os show and about is over 60bpm
• Untreated , You would have an undo fibrillation

SA Node

• There is different pathways going through it
• And that why the electrical impulses travel

The Cardiac Output

• Cardiac output with CO is the amount of blood coming from the heart
• To increase amount of coming is the rate times the amount of blood the ventricle goes
• At test there average of 70 times in the ventricles =5% rate. -At most It Will be 10 minutes per cycle

Nervous System

• The sympathetic release from atrial medulla, not as much of the ventricles .

The Pacemakers

• A body at has has an average to body in that state

Intrinsic rate

• There is some for the most side in the sympathetic
• With the help of a ion channels and potentials
• We' talk about there are three alteration

Conduction

• That has a conduction city changes.
• It is by this formula in this type conduction , then that's the name.

Controls

• Some are Intrinsic some are Exterisic
• So what do by now is that when the cardio output is a that are the changes
• Are the are then it does do it or The amount to preload, we mean to
• Is called that starting at then starting as those will change the of the cardio the

Implication

• there there Is less chance of you will also to not have to back out of the