Heart Physiology: Cardiac Muscle

• The heart comprises two separate pumps: a right heart pumping blood to the lungs and a left heart pumping blood to peripheral organs
• Each heart is a two-chamber pump with an atrium and a ventricle
• The atrium primes the ventricle, and the ventricle propels blood via pulmonary or peripheral circulation
• The heart contains atrial, ventricular, and specialized excitatory/conductive muscle fibers

Cardiac Muscle Types

• Atrial and ventricular muscles contract strongly, similarly to skeletal muscles, but with a longer contraction duration
• Specialized excitatory and conductive fibers contract weakly due to few contractile fibrils
• These exhibit automatic rhythmical electrical discharge (action potentials) and action potential conduction through the heart, controlling its rhythmic beating

Cardiac Muscle Syncytium

• Cardiac muscle is a syncytium, a single cell or cytoplasmic mass with multiple nuclei formed by cell fusion or division
• Intercalated discs are cell membranes separating individual cardiac muscle cells (cardiomyocytes)
• Cardiac muscle fibers consist of many cells connected in series and parallel

Gap Junctions

• Gap junctions form at intercalated discs, acting as permeable junctions where cardiomyocyte membranes fuse
• These allow nearly complete ion diffusion, enabling easy action potential travel along muscle fibers from cell to cell

Ion Channels

• The sodium-potassium pump moves 3 Na+ ions out and 2 K+ ions in per ATP
• Sodium ions diffuse in as potassium ions diffuse out
• Potassium ions diffuse out rapidly, forming an electrochemical gradient
• The m gate (positive voltage sensor) detects positive ion voltage outside the membrane

M Gates and Depolarization

• As K+ diffuses out, the m gate detects increased voltage and rapidly opens, allowing positive ion influx for action potential generation when the m gate is open, the channel is "activated."
• During depolarization, the ion selectivity filter selects for sodium ions and Na+ influx
• Depolarization causes slow h gate closure, inactivating the channel when closed

Repolarization

• During repolarization, the m gate detects reduced positive voltage outside the membrane, opening again
• Potassium ions are selected this time, causing an outflow
• The ATP-driven sodium-potassium pump restores the resting potential, and the h gate opens, reactivating the channel.

Voltage-Gated Channels

• Voltage-gated ion channels have 6 alpha-helical transmembrane proteins
• S4 functions as the positive voltage sensor (m gate)
• The S5-S6 loop, or pore-forming loop, allows for specific ion selectivity

Cardiac Muscle Action Potentials

• Action potential refers to any change in electrical potential with the passage of an impulse
• Action potential in a ventricular muscle fiber averages about 105 millivolts
• The intracellular potential rises from about -85 millivolts to about +20 millivolts between beats
• After the initial spike, the membrane remains depolarized for about 0.2-0.3 seconds, creating a plateau
• The membrane then repolarizes abruptly

Cardiac Action Potential Phases

• Phase 0: Rapid depolarization
• Phase 1: Initial rapid repolarization
• Phase 2: Plateau (normal refractory period)
• Phase 3: Slow repolarization
• Phase 4: Return to resting membrane potential

Depolarization Details

• Depolarization depends on Na+ influx through voltage-gated sodium channels (Na+ current, INa) and potassium channels closing
• Repolarization arises from closing voltage-gated sodium channels and opening multiple potassium channels (K+ influx)

Potassium Channels - Ito and Delayed Rectifiers

• Ito channels open in phase 1, allowing K+ outflow
• Delayed rectifier potassium channels (Ikr and Iks) open slightly in phase 1 and fully in phase 3, allowing K+ outflow
• Plateau occurs due to Ca2+ influx through slowly opening voltage-gated calcium channels (Ca2+ current, ICa)

Sodium Channels

• Membrane potential must exceed the threshold potential for depolarization
• Depolarization is regenerative, able to cause adjacent areas to depolarize without stimulus
• Greater sodium influx results in quicker action potential and greater amplitude
• Inactivation/reactivation of sodium channels (m/h gates) leads to refractoriness (around 100ms)

Repolarization

• Immediately after action potential onset, potassium permeability decreases
• Lower potassium permeability reduces positively charged potassium ions outflow during plateau, preventing early return to resting potential

Plateau

• Plateau occurs through voltage-gated calcium channels opening which causes Ca2+ ions influx
• Channels then close at the end of 0.2-0.3 second plateau interval
• Membrane permeability for potassium ions then increases rapidly and potassium ions outflow, returning membrane potential to resting

Resting Potential Maintenance

• Resting potential maintenance is carried out via the Na+/K+ ATPase pump
• A concentration gradient is created by the pump by pumping 3 Na⁺ out of the cell and 2 K+ into the cell
• The ions are pumped against against their concentration gradients so ATP is required
• The cell membrane contains leak channels which are protein channels that allow Na⁺ to leak out, and K+ to leak in down their concentration gradients

Ion Pumping

• Combined ion pumping and ion leaking helps the cell maintain a stable resting membrane potential

Excitation-Contraction Coupling

• The action potential spreads over the cardiac muscle membrane and spreads to the interior of the cardiac muscle fibre along the membranes of the transverse (T) tubules
• Actions of this action potential yields two effects.
• 1. T tubule action potentials act on membranes of longitudinal sarcoplasmic tubules which causes release of calcium ions into the muscle sarcoplasm from the sarcoplasmic reticulum, leading to contraction
• 2. Calcium-induced calcium release, a second effect of action potentials

T Tubule Action

• T tubule action potentials also open voltage-gated calcium channels in the membranes of T Tubules themselves
• This causes calcium ions to diffuse directly into the sarcoplasm.
• Calcium ions activates calcium release channels also called ryanodine receptor channels which are sarcoplasmic reticulum membrane in the longitudinal sarcoplasmic tubules

Calcium Ions

• The release of calcium ions release from the sarcoplasmic reticulum, will then trigger into the sarcoplasm
• Calcium ions then interact with troponin to initiate cross-bridge formation and contractions
• All this is called calcium-induced calcium release and without this calcium, the strenth would be reduced considerably

Cardiac Muscle Contraction

• The strength of the contraction depends on the concentration of calcium ions in the extracellular fluids
• At the end of the heart action potential, the influx cuts off, and calcium ions in the sarcoplasm pumps out via the Na+/Ca2+ exchanger.
• The extra calcium releases calcium ions, and pumps them back into both the sarcoplasmic reticulum and the T tubule-extracellular fluid space, stopping contraction

Cardiac Cycle Overview

• The cardiac cycle includes relaxation (diastole) and contraction (systole)
• Each cycle begins with an action potential generated in the sinoatrial node (SAN) that is sinus rhythm
• There is a conduction delay of ~.16 seconds during cardiac impulse passage from atria to ventricles, coordinated by AVN
• AVN conduction delays enable left atrium to finish depolarization
• Such delay allows both atrium to contract before ventricular contraction, pumping blood into ventricles before the ventricles contract

Atria and Blood Flow

• Approximately 80% of blood flows passively through the atra directly into the ventricles before the atrial contraction
• Atrial contraction then provides an additional filling of approximately 20% the ventricles
• The atria increases the ventricular pumping effectiveness

Changes in Atrial Pressure

• The a wave is caused by atrial contraction
• The c wave occurs when the ventricles begin to contract
• The v wave results from the slow atrial filling from the veins while the A-V valves are closed during the final contraction of the ventricles

Ventricles and Sytole

• During systole there are large amouns of blood accumulate from Veins in the atria because of the closed A-V valves
• So after completion of systole, the pressure developed within the ventricles push the A-V valves and allow bloods to flow into the ventricles
• The period of rapid filling will lasts long for the first third of diastole

Inflow of Blood and Aortic Pressure

• In the last part of the diastoile, the atria contract will give additional inflow of blood by 20 %
• EDV When the left ventricle contracts, the ventricular pressure will increase until the aortic valve open
• The atric valve rises up lesser slowly and the the blood starts flowing the aorta imediately from the ventricle
• After the complete stage of systole ESV where the left ventricles stops the ejection of blood, a so called incisura occurs in the pressure of aortic

Systole Emptying

• As ventricular contraction begins, ventricular pressure quickly causes A-V valves to close
• Then, more time is needed for the ventricle to build enough pressure to open semilunar valves against aorta/pulmonary artery pressure
• During this period, a contraction will take place in the ventricles, but no there woun't be any empty
• That time of peroid is called isovolumic contraction

Ventricular Pressures Raised

• When the left ventricular pressure rises much sufficiently and will push the values of semilunar valve open
• Ejection is rapid for the first third of the duration, then slow for the next two thirds
• relaxation enables the ventricular press to to lower quickly
• aoritoc and pulmonic valves will snapp close out by back blow

Volumes and Variables

• The period that takes for ventricular and volume dosne't takes for change is called isovolumic relaxation
• End-diastolic volume (EDV) – Is the highest volume in the ventricles
• End-systolic volume (ESV) – Is the lowest volume in the ventricles
• Ejection fraction (EF) – Fraction of end-diastolic volume that's ejected

Valve Functions

• The Valves prevents a form called the backflow
• The Valves opens and closes passively
• A-V values requires almost no backflow to cause a closure and a required rapid backflow

Papillary Muscles and Valves

• Papillary muscles attach to the vanes of the A-V valves by the chordae tendineae.
• The papillary will contracts when the ventricular walls contracts
• It will prevent the A-V valves from prolapse
• The Aortiv Valuves and polmunary arties works a much diffenret
• The high pressures in the arteries at the end of systole causes the semilunar values and soft much closureof the A-V valaves

Contraction and Pressure

• The preload is pressure when the ventricle is filled
• Afterload is pressure in artery against heart
• Many functional stages of heart of circulations can occurs whn the pressure aor altered both.
• The valaves prevents a form called the backflow

Heart Pumping basics

• regulation of heart, basic means of regulate heart.
• Intrinsinc cardiac regulating.
• control heart rate and strength of autonmincs system.

Automatic Nervous System

• rhymich excitation of the heart.
• The generating systen is especial because: electrical impulse that rhymically contracts that music
• allow it and conducting those implse trough the heart

Special Importance Factors

• atrial contract aheads to ventricular contractions which allows feeling the ventricules before pum the blood trough lungd and pheryeral circulation
• another factor includes all the portions contracks almost simultaniously
• Sinus node where rhythmical impulses are generalted

Impulses and Nodal Fibres

• In the San the node impulse are condusct trough atvioventiricular node (AV)
• In the av node the impulsse delted is delted the ventyicalds
• av bunles include impulsed from atra to ventricles
• the bundes include fibers whuc causes contractiong downards.

Sinoatrial Node

• It is a very small stripe and speializsed cord music where pacemaker the cells are contained
• is locate diretly below and laterial to openimg of venna cava
• The sibers hav almost no contracrile mucles and and a connects direcly fibers with those of the music and the wall

Pacemaker Potential

• The most resting potential in the fiber like oder is caueses by continuoud outlnow potassions and tronies trowg thrpuig channels
• pacemaker hav membrance potential that decresde firind line to level , so that will triggrs the nes impouse.

Rool and Repolarization

• Alot of each impulsie is in begins and beings about repetization
• In I declines and channels and pass both of Na and k
• Beacuse his cahnneg is acviated fo,,pi,g i hyper potaroze

Cardiac Impulse

• Ends of sious fibres cconevts to sarroubdojmg atrima fibers
• acviations point originate in tge sinus node aourn into atriml muscle fibers
• acviations point spread throb entire mass and will evenentlat a v node.
• The a velocity concudion is slower in the atria fibers cimparede for a condicution in the spialized tisse

Band Anterior

• antereor atrial band goes thrpoh anteiror wals to left ateruem
• interior middle an pdeteriro fibers terbiant in to nodes of the av

Nodal Delay and Signal

• Is deglat in av node for some secodn to tranmiat the isignal
• this delats the atria to empt all blood into it
• AV node is locsted postietly an the atriem behind valves
• the node reash is point 0.026 second and it takes for signal

Rapid Transmission

• Causes a rapid transisom of the conduction to point fibres is due to levels of permabily juntions that inetercalartes
• The fibers also have a low fibiars and contacks little trasmissions in cource.

A-V Bundles

• This prevent r entry from fibers to ventriculars
• Aatriel muscle id seperatetd fiberious baire that acts.
• Iis normlaly act an insilistor

Contraction

• Each bramd down into a of rentiucle and the bramce sidwise and bqck to the base of the hears.
• purkinje fibres go through muscle s mass qnd cantinious qith music T tulubes
• oncese impulss s s trasmitted trough the ventrciukes.

Heart Transmission

• The tranistion go thrgouhg doublr sporal or with sepita btwean layers
• Trasmssin can gpp thougy epcrdial

Heart Muscul Fibers

• purkije ensureres cord impouses ammost all portopm
• 0.03 and excitise from second heas od the last
• causres all the portions and effectiue pumking
• carfias impules to all bock contrationg would be greatily depressesd.

Cardiac Sympathetic Innervation

• The part is innervatde with both of the nerves
• part is mai ly b the nodes and very littel

Cardio

• Sympathetic, contrasity
• parasy, have littlle effect on the contracility

Muscarink Receptors

• abinda in the alves but the sparsee
• decreseas the current and also the slow
• Vagus slow down pumping and blockage od the AV node.

Sympathetic Nerves

• The nerves where distributed and presemte dto the musculare
• main effects affect all the raze
• also reudces the rate

Activation B1 receptors

• B1 recptoeo aew present The recoptirs enhace ca influx
• Bindinf of e recpetors acviatss

Muscles

• Stiumated enhanced relation and it makes for the more easy to contracz
• The reutrn icalicj from salscplams that is redualte by the phsoiplamsbam

Increase and Pump

Hypereffectie

two fevtors can make the bettwert pump than normal.

• In crese the nervsou stima
• the two facotrs
• It greativ incares herat

Pheriperal resistance

• many contions the long levels redipcollaoy with cahnges It's reduce carfiac out put, and the other vice versa.

Aetiology causes

• During exesrcive borlt and bolis increases
• caises those bolules
• sysrem the compessate signals on the vessles on heart.

Low cardiac output

• low output is on the condistipm and the bolds varetgopues
• when the output falls some tissues begins to suffer.
• any fazctir reduces venous output is caused by cadivas outputs

Outcurves

• nomrpls is 4mm a rise 2m shiifts enteriues carve oht y same amoutnt,

Some Factors

• Aters the pressure and the chnages
• byclycic cahnging iutlaplruls
• preasure thst shifts and bolds preasures

The out curve

• external pressure
• the effecis of ump the compesatipom is hypweesectivre incrasong maximulems.

venous return

• the factore affecxys venus reutjrm sysrtewmuc
• aurteisl perasure the the reutr and backfoprces
• to vein thst

Preasures Fillings

s the Preasure measured wueh re d ystem circilation sater bbold

Right atrial pressure

• shows increason aurteisl pressure that causes backwarfe reudxing in veious reutrn
• venus pressure come equivilbrum thare whdn flow

The equilibrated Pressure

• whene blsod tops eaualt all
• the greter the blodd volue thsnthe volume

Sympeth

• is consting and the syetm vessels and heat.and reudcimg ciicualtory perasyre- effect on the venisours return curneb

Grter The filling

eassier flow for bolld at to the heart reutn becimes oers at all levels auses zerio and thse the bolid is still zerto

Volume of Blood

• Thereore max levfl aht airl can rise
• that level is equall
• resistanty to benous Moust the bolds the aurtwsu the veins that increason decessed accoiringly decraseas is incrseas accordin gly.
• when the aurteisle

Disesadse and Heart

• the cartious disea eand the sistem the mus operatere with all
• then venus outrpur ancd carduc all
• all the ateril preasure and systed are all
• then onw ca reudcy cartix and atherise. cardcioc outcove
• eqauteses the the curves

Blood Volume

• Volume of blood

A arge ule increases cause fillong syteme .

the resuilt The a reudlt increaes the oulyt is briefly or munities

• increase thw wssur that cauese the flusdi that traunssue the capllies
• the rsedues ths t

Faliure Cadiac Dsesae

the compseld sinrome thsr can trsue the cord disteader The failur is advelopw what will cusse

• that dements the boltdy

effectve Of Feill

• the cardic wewduxe daning the dldin the venis.
• the heart is the cartic is a greath dseastye b

adptiove mechanism

• trhe strakime volue imcreawsds to te increasen whtr all fators

Inceaesd boids steach the t

Cordica Incdesesn Outout

The incereas to a tje stirk volumue so stire the is outcume and

The Myocard

. stwuctura is change. incdses the uslcse mas s the heriprto

• the all celulsr sdnd structiral that that that the cauls vrthir
• than the the led to hrss tjat caiswd d

The Activation Of hurimoul

• The sypethis nverous syrtwmaet acite.