cardio lect

8/13/2019 Cardio Lect

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Physiology Lecture Outline: Cardiovascular Physiology

The Cardiovascular SystemIn simplest terms, the cardiovascular system consists of a central pump (the heart) and a series of tubes

(blood vessels) connected to this pump which pushes fluid (blood) through these tubes. It's primary

function is the transportation of these materials between all parts of the body and the heart. These materials

include nutrients, water, waste, signal molecules, immune cells and gases (O2and O2).

The HeartThe heart is a muscular organ that lies in the center (left) of the thoracic cavity. It is composed mostly ofmyocardium (cardiac muscle) and is enclosed in the pericardial sac. The heart has four chambers, divided

into left and right halves. !ach half contains an upper chamber, the atrium(for receiving blood) and a

lower chamber, the ventricle(for pumping blood).One"way flow in the heart is ensured by # heart valves$

1)the right(tricuspid)atrioventricular(%&) valve.

2)the left(bicuspid/mitral) atrioventricular(%&) valve.

3)thepulmonary semilunar valvein between the right ventricle and the pulmonary trun.

4)the aortic semilunar valvein between the left ventricle and the aorta.

The pulmonary trun leaves the right ventricle and aorta leaves the left ventricle. lood between the two

sides do not mi. !ach of the sides contract together in a coordinated fashion, first both of the atriacontract, this is then followed by both of the ventricles contracting.

Arteries" are vessels that carry blood away from the heart.

Veins" are vessels that carry blood toward the heart.

% ring of fibrous connective tissue (called the fibroskeleton) surround the openings between the top andbottom chambers. The fibroseleton has several functions$

1. *rovides a site of attachment for %& valves and helps eep theses openings patent during contraction.2. +aintains integrity of the shape of the heart when ventricles contract, while allowing the ape and the

base to be pulled together

3. It electrically separates (insulates) the atria from the ventricles, thus guarding against the spread of

electrical signals that are not through the intrinsic electrical conduction system (discussed later).

The Heart Functions as a Dual Pump: The Circuits of the Heartithin the cardiovascular system there are two circuits or circulations " thepulmonaryandsystemic.

Pulmonary Circulation" *umps blood to and from the -ungs. Often termed the right side of the heart.

This circuit can also be thought of as starting at the / ventricle and ending at the - atrium.

Systemic Circulation" *umps blood to and from the body. Often termed the left side of the heart. This

circuit can also be thought of as starting at the - ventricle and ending at the / atrium.

&olumes and *ressures of the 0ual *ump

The cardiovascular system is a closed circulatory system, and for that to eist, the volume of blood in both

sides of the pump must be equal. The pressures of the fluid in either side of the heart, however, are verydifferent. The proimity of the lungs to the heart (about # inches) means that the right pump (/ ventricle)


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does not have to wor very hard to move the blood to the lung tissue. The minimum pressure re1uired from

the pulmonary circuit is normally about 25 mmH.The systemic circuit, however, is much more involved and the left pump (- ventricle) needs to wor very

hard to move the blood to every part of the body. The minimum pressure re1uired from the systemic circuit

is normally about !" mmH. Therefore, the pressure generated by the left side of the heart is over threetimes greater than that generated by the right side. %s a conse1uence, the muscular wall of the left ventricle

is about three times thicer than the right ventricle.

CA#$%AC &'SC( A*$ +H HA#+

There are two types of cardiac muscle cells (myocardiocytes) in the heart$ 1)autorhythmic myocardiocytes

and 2) contractile myocardiocytes.

%bout 3 of myocardial cells are autor,yt,micand they spontaneously generate action potentials (%*s)

without nervous stimulation. In this way, control of heart rate is considered intrinsic myogenic control "that is, derived from within the heart muscle itself. In contrast, seletal muscle is neurogenic" that is, it

re1uires stimulation by the nervous system to initiate contraction. In cardiac muscle, input from autonomic

neurons and hormones can modify the contraction rate set by the pacemaer cells and modifies the force of

contraction. 4owever, the heart will contract in the absence of all neural input.

%utorhythmic cells are anatomically distinct from contractile myocardiocytes. They are smaller, have few

contractile fibers, organelles and contain no organi5ed sarcomeres " so they don't contribute to forcegeneration. %bout 663 of cardiac muscle cells are contractile myocar-iocytes. These cells are striated,

have organi5ed sarcomeres and have high energy demands, 78 of cell volume is mitochondria.

% characteristic of cardiac muscle are that they contain intercalate- -isks, which are interdigitated

membranes 9oined by desmosomesandgap junctions. The desmosomes are a type of cell attachment, so

that ad9acent cells are physically attached to each other to cope with the stressful mechanical activity of theheart. :ap 9unctions are simply protein channels connecting ad9acent myocardiocytes, they allow ions to

pass though and thus waves of depolari5ation to spread throughout the muscle tissue " creating nearlysimultaneous contraction.

citation/Contraction Cou0lin in Car-iac &uscle is Similar to Skeletal &uscle

ontraction occurs by the same sliding filament activity as in seletal muscle. 4owever, an important

difference is that the %* opens membrane voltage"gated a 2;channels for etracellular a2;entry. Thisentry of a2;from the !< is re1uired for cardiac muscle contraction.

Ca2/ %n-uce- Ca2#elease

In cardiac muscle, about 6=3 of the a2;used in contraction is stored in the >/, and about =3 comes

from the !/ a2;stores, without the !< a2;, no

a2;

would be released from the >/. The a2;

diffuses through cytosol to contractile elements and bindtroponin allowing crossbridge cycling and contraction. a2; removal re1uires a2;"%T*ase (>/). a2;

removal also achieved by ?a;" a2;indirect active transporter (!


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@a2;A is increased, more crossbridges formed giving additional force generated. Thus, the strength of

myocardial contraction is directly related to the amount of a2; present in the cytosol. The more a2;freeinside the cell the, the stronger the contraction. The cytosolic concentration of a 2;can be increased two

ways$

1)by increasing the amount of a2;that enters the cell through voltage"gated calcium channels.

2)by storing more a2;in the sarcoplasmic reticulum.

Catec,olamines an- lectrical Activity

?orepinephrine (?!) and epinephrine (!) are atecholamines. These catecholamines regulate the amount

of a2;available for cardiac muscle contraction. ! and ?! bind (beta"l) receptors on cardiac muscle

membrane to increase force of contraction.

?! and ! increase the open probability of a 2;channels in the myocardial contractile cell, but at the same

time they also increase the B;permeability, enhancing outward B;flow and terminating the plateau. Thus,! and ?! increase a2;entry and enhance intracellular sarcoplasmic reticulum stores of a 2; without

increasing the duration of the contraction. ince ! and ?! also increase

heart rate, it would be counterproductive to lengthen the time of cardiac contraction.

?! and ! also activate second messenger systems in myocardiocytes and trigger signal transduction which

causes phosphorylation of proteins inside the cell, including a2;channels. *hosphorylated voltage"gated

a2;channels increase the probability of them opening, this allows more a2;to enter cell.

P,os0,olambanis a regulatory protein on the >/ and helps to concentrate a 2;in the >/. >timulation of

?! receptors () triggers phosphorylation of phospholamban, which then enhances the a2;"%T*ase

activity on the >/. This means that more a2;can be stored in the >/ and more 1uicly. The net result is astronger contraction and a shorter duration of cardiac contraction (heart beats faster).

%nother property of cardiac muscle is that when it is stretched, it contracts more forcefully. This is due to

the length"tension relationship that we have already seen in seletal muscle. The degree of overlap betweenthic and thin filaments will effect the tension generated by that muscle cell. >tretching myocardial cells

also allows more a2; entry, this also leads to a stronger contraction. The degree of stretch of

myocardiocytes at any one time depends on blood volume in the chambers when filling is occurring.

Action Potentials in &yocar-ial Cells

ontractile cells and autorhythmic cells show distinctive %* generation. a2;is important in the %*, incontrast to seletal muscle and neurons.

&yocar-ial Contractile Cells

>table resting membrane potential ("6= m&). %ction potentials similar to those of seletal muscles and

neurons. /apid depolari5ation is due to ?a;entry and repolari5ation due to B;efflu. % uni1ue feature of%*s in myocardial contractile cells is the absence of a hyperpolari5ation phase at the end. The myocardial

cell returns directly to its stable resting membrane potential of "6= m& (the e1uilibrium potential forpotassium). ecause efflu and influ are eactly balanced at "6= m&, there is no driving force to cause B;

to leave the cell and hyperpolari5e it. The myocardiocyte %* is lengthened compared to seletal muscle

%*, due to a2;entry creating the elongated plateau phase before repolar5ation. Typical seletal muscle %*duration is "C msec but for contractile myocardial cells %* duration is about 2C= msec. +ost of this %* is

in the absolute refractory periodand this helps to prevent tetanus and allows chambers to fill.

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C,annels in Contractile &yocar-ioicytes

There are multiple forms of B;channel in myocardial cells, each with different properties. There are 8

channels involved in the contractile cell action potential. 1) iBlchannel (inward rectifier)$ This channel isopen during the resting phase. They are voltage"sensitive and begin to close when the cell depolari5es, but

they are slow and do not actually close until the beginning of the plateau phase. 2) itochannel (transient

outward rectifier)$ This channel opens at the end of depolari5ation and closes very rapidly. B; effluthrough this channel is the reason for the 1uic drop in membrane potential 9ust before the plateau. 3) iBchannel (delayed outward rectifier)$ This channel open at the end of the plateau and is responsible for the

repolari5ation phase. They are activated by the depolari5ation but are slow to react.

Autor,yt,mic &yocar-iocytes

*acemaer ability results from unstable membrane potential. It starts at "D= m& and drifts upward, this can

be called apacemaker potential. hen it reaches threshold ("#=m&), the cell fires an %*. The membranepotential instability is caused by funny (If) cation channels that allow ?a

;and B;permeability at "D=

m&, this channel allows more ?a;in than B;out and induces current flow and the drifting membrane.

Open Ifchannels creates net influ of positive charge, depolari5ing autorhythmic cells. 0epolari5ation thencloses If channels and opens a

2;channels. %t threshold, many a2;channels open, thus creating a2;

influ and rapid depolari5ation. /epolari5ation is due to B;efflu through open B;channels.

The timing of %*s in these cells can be influenced by norepinephrine and epinephrine. These stimulate receptors and increase ion flow in Ifand a

2;channels. This then increases the rate of depolari5ation, which

increases heart rate. %h acts on muscarinic receptors (as part of the parasympathetic division of %?>) toslow heart rate by altering B;and a2;permeability.

lectrical Con-uction System

The electrical conduction system in the heart coordinates contraction. The %*s originates in one part of the

strategically located autorhythmic cells and then spreads this signal between cells via gap 9unctions inintercalated diss. The depolari5ation of muscle cells is followed by a wave of muscle contraction that

passes across the atria then moves into the ventricles. The electrical conduction system consists of fivema9or sites$

1)sinoatrial (>%) node nodeE

2)atrioventricular (%&) nodeE

3)%& undle (of 4is)E

4)right and left bundle branchesE and

5)*urin9e fibers.

The sinoatrial (>%) node, in the superior, posterior portion of the right atrium, initiates contraction of the

heart because it fires %*s at the highest rate (see table below). % node to atrioventricular (%&) node, located in the floor of rightatrium. This connects to the %& undle (of 4is) located in the I& septum. This then splits into right and

left bundle branches running down the I& septum and finally into *urin9e fibers at the ape of the heart.

0ue to the electrical insulation of the fibroseleton, the direction of the %* is controlled and results inape"to"base contraction of ventricles. Thus, blood is s1uee5ed out of the ventricles from the bottom to the

top of the chambers. lood e9ection is also aided by the spiral arrangement of muscles in the walls.

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The slow conduction of the electrical signal through %& node cells lengthens their refractory period, this

helps to create the AV nodal delayand allows the atria to complete their contraction before ventricularcontraction begins. If the >% pacemaers malfunction and fire at a very rapid rate, %& nodal delay prevents

every action potential from passing into the ventricles, in this way permitting the ventricles to function at a

slower pace so that they have time to fill with blood. The >% node sets the heart rate because it fires %*s atthe fastest rate and the other regions follow the lead of the >% node. If the >% node is damaged, then

another pacemaer sets the heart rate.

+able 1.The rate of action potentials7min for the autorhythmic myocardiocytes.These are average values for a intact heart inside a healthy individual at rest.

lectrical Con-uction

#eion

S0ontaneous #ate of

Action Potentialsminutes

>% ?ode F="G=

%& ?ode """""

%& undle #="D=

/ and - undle ranches """""

*urin9e "T segment. ommon terms include$ tac,ycar-ia" fast heart rate (above ==)E bra-ycar-ia "

slow heart rate (below D=). %t very rapid heart rates, there may be less blood pumped per beat because themuscle has not had time to rela completely, but remember, the longer refractory period of myocardial cells

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prevents tetanusL Tetanus would not allow the heart to rela at all. In that state, no blood would be pumped

to the brain and the rest of the body. Arr,yt,miascan result from benign etra beats or more seriousconditions discussed in lab.

+H CA#$%AC C9C(

The cardiac cycle is the period of time from the beginning of one heartbeat to the beginning of the net.

There are two main stages$ $iastole" the time during which cardiac muscle relaes and Systole" the time

during which cardiac muscle is contracting. %tria and ventricles do not contract at same time, but each sideof the heart contracts at the same time. % node, as a wave of

depolari5ation (electrical signal) across the atria is followed by a wave of contraction that pushes blood intothe ventricles to complete ventricular filling. >ome blood is forced bac into veins, creating a small

retrograde blood movement, measured as a pulse in the 9ugular vein.

%t this time, 9ust prior to ventricular systole (the net stage), the ventricles are full of blood, this istermed !nd 0iastolic &olume ($V) and represents the maimum ventricular volume. %t rest in a F= Bg

male, this value is typically 8Cml in each ventricle.

Clinical Note: Because most of ventricular filling occurs passively pathologies in !hich atrial contraction

is disturbed may have very little effect on overall cardiovascular function" #t is not uncommon for people

!ith atrial fibrillation to have fe! symptoms"

arly Ventricular Systole ;0art one) an- t,e :irst Heart Soun-&entricular systole begins at the ape of the heart as spiral bands of muscle s1uee5e blood upward

toward the base. The increasing pressure of the blood in the ventricles forces the %& valves closed "

creating the first heart sound, the lub of lub dub.

oth ventricles are now 'sealed' compartments in that the %& and semilunar valves are closed. The

ventricles are continuing to contract, but if all valves are closed, the blood goes nowhere. The heart is in

%sovolumic Ventricular Contraction. This occurs when the blood volume inside the ventricles remains

the same (prefi iso" means 'same'), but pressure is increasing. 0uring this phase, the atria repolari5e andrela as the ventricles continue to contract.

Ventricular Systole ;0art t6o)7 Ventricular


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remaining in the ventricles after e9ection is termed !nd >ystolic &olume (SV). % typical value for a F=

Bg male at rest is about DCml per ventricle that remains in the heart after e9ection. e can calculate howmuch blood left the heart (called Stroke Volume) if we now the maimum volume, !0&, and subtract the

volume remaining after contraction, !>&. This means that about F=ml of blood is e9ected per beat. >ee

calculation below from this formula$ Stroke Volume ;SV) = $V / SV

Ventricular $iastole an- t,e Secon- Heart Soun-%s the ventricles rela, the pressure of the blood inside decreases. The blood in the large arteries

leaving the ventricles falls bac toward the heart as the driving force subsides. This reversal of bloodtoward the heart fills the cusps of the semilunar valves, slamming them closing them " creating the second

heart sound, dub of lub dub.

The %& valves remain closed because ventricular pressure is still greater than the atrial pressure. %s

the ventricles rela, the pressure of the blood inside decreases and once the semilunar valves close, thecompartment is again 'sealed'. ?ow the ventricles are undergoing %sovolumetric Ventricular #elaation.

This is a state where pressure is decreasing but volume remains constant. hen ventricular pressure

becomes less than atrial pressure, the weight of the blood in the atria opens the %& valves (lie a trap door)and blood moves into ventricles. The cardiac cycle is now complete because it is at the filling stage again,

where we started.

$isor-ers of Heart Valves&alvular >tenosis refers to a narrowing of the opening of the valves, often associated with stiffness of the

valve. In cases such as %& valve stenosis, atrial systole becomes significant. The atria must contract moreforcefully to get the blood through a narrower opening into the ventricle. This causes turbulent blood flow

which can be detected as sound, commonly referred to as a heart murmur. This reduces the heart's

efficiency and thus increases its wor load.

&alvular *rolapse " occurs when there is incomplete closure of the %& valves, allowing retrograde flow of

blood. These are often called incompetent or insufficient valves. It is an inherited weaness of the chordae

tendineae (the 'cords' that attach to the 'flaps' of the %& valve) so that during ventricular sytole, there is sumbac flow into the atria. Typically is maes a clickfollowed by as!ishsound when blood leas bac into

atria. These murmurs can range from harmless to severe. +ost valvular disorders commonly occur on theleft side of the heart because these valves are sub9ected to greater forces during contraction of the powerfulleft ventricle. % node, but modulated by neural and hormonal input. In anormal adult heart, the resting rate of the >% node is about F= action potentials (%*s) per minute, this

translates to a heart rate of about F= bpm. The parasympathetic and sympathetic branches of the %?> eert

antagonistic control over heart rate. *arasympathetic activity slows heart rate and >ympathetic activityincreases heart rate and force of contraction. If the heart were separated from %?> innervation, the intrinsic

rate of the >% node would actually be about 6="== %*s per minute, but inside the body it is brought down

to about F= by parasympathetic modulation via the vagus nerve. The parasympathetic division releases%h from the vagus nerve on to muscarinic receptors at autorhythmic cells of the >% and %& nodes to

decrease heart rate, by increasing B;efflu. The sympathetic division releases ?! and ! on receptors to

increases heart rate (via %& node conduction). This can elevate heart rate up to 2= bpm and greater.

Stroke Volume is t,e Volume of >loo- Pum0e- by ?ne Ventricle in ?ne Contraction

>troe volume (ml7beat) M %mount of blood pumped by one ventricle during a single contraction.

It is calculated as$ Stroke Volume ;SV) = $V / SV

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&. If !0& M

8Cml and !>& M DCml, then >& M !0& " !>&E MN 8Cml " DCml M F=ml7beat (per beat).

>troe volume isn't constant, it is homeostatically regulated. It can decrease when you are at rest and

increase greatly during eercise.

&ulti0le :actors %nfluence Stroke Volume>troe volume is directly related to the force generated by cardiac muscle during contraction. :reater forcemeans greater stroe volume. The force is affected by 2 parameters, 1) the length of muscle fiber at

beginning of contraction and 2)the contractility of the heart. ontractility is the intrinsic ability of cardiac

muscle fiber to contract at any given fiber length.

(ent,/+ension #elations,i0s an- Starlin@s (a6 of t,e Heart

%s the sarcomere length in cardiac muscle increases, the tension generated by the contracting muscleincreases. This leads to increases in stroe volume, as the more forceful the contraction, the greater amount

of blood can be e9ected. %s additional blood flows into ventricles, this causes muscle fibers to stretch,

lengthening the fibers and hence increasing the force of contraction. >tretch and force are related by the

everal factors affecting venous return, such as the

seletal muscle contractions (seletal muscle pump), this s1uee5es low pressure veins and push blood

toward heart. The /espiratory pump is also a factor in venous return. It is created by the movement ofthora during respiration. Increases in pressure in abdominal veins, flow 'down' into the decreased pressure

in thoracic veins. The result is that the lower thoracic pressure draws more blood in from the abdominalveins. %lso, the constriction of veins via sympathetic activity has an important impact on moving more

blood into heart. >ympathetic innervation of veins allows also allows for redistribution of venous blood tothe arterial side of the cardiovascular circulation.

Car-iac ?ut0ut is a &easure of Car-iac Performance

ardiac output (O) is an indicator of total blood flow through the circulation. It doesn't describe blood

distribution among tissues. O (-7min) M %mount of blood pumped per ventricle per unit time.

It is calculated as$ C? = Heart #ate ;H#) Stroke Volume ;SV)

%t rest in a F= Bg man, O is about C -7min (average). ?ormally, both sides have e1ual O. If for some

reason O's become une1ual, blood will pool behind the weaer side of the heart.

Blood Flow through the Cardiovascular System

Pressure Volume :lo6 an- #esistance

-i1uids and gases flow from areas of higher pressure to areas of lower pressure " that is to say, they flow

do!n their pressure gradients. The high pressure generated when the ventricles contract forces blood to

flow into vessels that eist at lower pressure. The pressure of the fluid (blood pressure) continues to fall asblood moves away from the heart. The vessels with the highest pressure are the aorta and other large

systemic arteries. The vessels with lowest pressures are the veins the superior and inferior venae cavae.

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Com0ressin a :lui- #aises its Pressure

The 4ydrostatic *ressure (4*) of blood falls over distance as energy is lost to friction. &entricular

contraction attempts to decrease volume of the ventricle as the pressure is increased.

0riving *ressure " is created within the ventricles to drive blood through the vessels. %s the heart chambers

rela, pressure falls and allows blood to flow in (thus volume increases). lood vessel volume can also

change. In the body, when vasodilation (increase in blood vessel diameter) occurs this results in increasedblood volume and decreased pressure. hen vasoconstriction (decrease in blood vessel diameter) occurs,this results in decreased blood volume and increased pressure.

loo- :lo6s $o6n its Pressure ra-ient

lood flows from an area of higher pressure to one of lower pressure. 0ifferences in pressure between 2

ends of a tube creates a pressure gradient (*).


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4owever, in humans this can be simplified to$ / 7r# as blood vessel radius becomes the main

determinant. Vasoconstriction leads to increased resistance and decreased flow. Vaso-ilation leads todecreased resistance and increased flow. Therefore, blood flow is described by this formula$

Flo

If the driving force remains constant, flow varies inversely with resistance (determined by radius).

!"

P

#

P

!$r4!"

cardio lect

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