Cardiac Pump Function Flashcards
What are the four similarities between cardiac and skeletal muscle cells?
- made up of sarcomeres (z-line to z-line) that contain thick filaments composed of thick filament myosin (A band) and thin filaments containing actin
- thin filaments extend from z-line (anchored) through I band to interdigitate with thick filaments
- shortening occurs through the sliding filament mechanism (requires ATP)
- actin filaments slide along adjacent myosin filaments by cycling intervening cross bridges (bring z-lines closer together)
How do cardiac cells resemble a syncytium?
branching interconnecting fibres
How does the myocardium function as a syncytium?
a wave of depolarization followed by contraction of the entire myocardium occurs when a suprathreshold is applied to any one site (all or nothing response)
Why is the myocardium not a true anatomical syncytium?
laterally sarcolemmas separate fibres and dense intercalated disks separate each fiber at the end
What does the spread of excitation depend on between cardiac cells?
the electrical conductance of the boundary between the two cells
What are gap junctions (nexi)?
present in intercalated disks between adjacent cells with high conductance
mediate conduction between cells
made up of connexons - hexagonal structures that connect the cytosol of adjacent cells
What is the function of the cytosol between cells?
the fluid that helps transmit electric signals
serves as a low-resistance pathway for cell-to-cell conduction
How does the number of mitochondria differ between skeletal and cardiac cells?
fast skeletal muscle - relatively few mitochondria (anaerobic - can build an O2 deficit)
cardiac muscle - very rich in mitochondria, requires continuous O2 (repetitive contraction)
Why are cardiac muscle cells rich in mitochondria?
repetitive contraction
intolerant to anaerobic metabolism, rely in oxidative
rapid oxidation of substrate with the synthesis of ATP can keep pace with myocardial energy requirements because of increased mitochondria
Why does the myocardium have a rich capillary supply?
to provide adequate O2 and substrates
about 1 capillary per fiber
How does a rich capillary supply enhance O2 and substrate diffusion?
short diffusion distance
molecules can move more rapidly between myocardial cells and capillary
What is the transverse tubular system?
deep invaginations of sarcolemma into the fiber at z-lines for substance exchange
lumina (endothelial SA) are continuous with the bulk of the interstitial fluid
play a key role in excitation-contraction coupling
What are the two pumps of the heart in series?
right heart - RA, RV, pumps venous blood to the pulmonary circulation
left heart - LA, LV, pumps oxygenated blood into systemic circulation at relatively high pressure
What are the characteristics of the atria?
thin-walled
low-pressure chamber
What is the function of the atria?
function as large reservoirs of blood for ventricles than pumps for forward propulsion of blood
What are the characteristics of the ventricles?
continuum of muscle fibers originating from the fibrous skeleton at the base of the heart (where A and V meet)
What is the orientation of the ventricle muscle fibers?
fibers sweep toward the apex at the epicardial surface, as they pass toward the endocardium they gradually undergo a 180 degrees change in direction to lie parallel to epicardial fibers and forn the endocardium and papillary muscles
How are papillary muscles formed?
at apex fibers twist and turn inward to form papillary muscles
Why do fibers form muscles at the base of the heart and around valve orifices?
form thick powerful muscles that decrease ventricular circumference for ejection of blood and narrow AV valve orifices to aid in valve closure
How do cardiac muscle fibers contract?
apex and the base rotate in different directions = twist
fibers push/pull against each other decreasing the circumference and shortening the venticle
What happens to titan as the heart twists?
titan molecules become compressed and release energy during untwisting
When does peak twist occur?
during ejection
When does peak untwist occur?
when the mitral valve opens
generates suction to pull blood to the apex of the LV -> generates a pressure gradient within the ventricle from the apex to the base
How do peak twisting and untwisting differ during exercise?
The peak twist is a bit earlier
the peak untwist is great = greater pressure gradient
*greater magnitude of twist
What is the advantage of exercise by having a greater pressure gradient?
increased filling of the LV in a shorter time due to increased untwisting (pressure gradient)
as HR increases, the diastolic period (filling) is shorter
EDV increases during exercise
What are the atrioventricular valves?
tricuspid valve - RA -> RV, three cusps
mitral valve - LA -> LV, two cusps
Why is the total area of the AV valves cusps 2x of their orfices?
creates considerable overlap so if the heart enlarges the valve will still seal shut
What are the chordae tendineae?
strong ligaments attached to free edges of valves, rise from the papillary muscles of ventricles and prevent eversion of valves during ventricular systole
What are the semilunar valves?
valves between the right ventricles and pulmonary artery and between left ventricles and aorta
consist of three cup like cusps attached to valve rings
How do the cusps of the semilunar valves prevent regurgitation?
at the end of the reduced ejection phase of ventricular systole, there is a brief reversal of blood flow toward the ventricles that snaps the cusps together and into shape
Where to the cusps of the semilunar valves rest during ventricular systole?
they float in the bloodstream about midway between the vessel walls and the closed positions
Why don’t the cusps of the semilunar valves lie flat against the wall during ventricular systole?
creates a small outpocketing of the pulmonary artery and aorta (sinuses of Valsalva), where eddy currents develop that tend to keep the valve cusps away from the vessel walls
What is the function of the sinuses of Valsalva and the eddy currents?
ensures the cusps of the valves won’t block the orifices of the coronary arteries that are behind the cusps of the aortic valve
During ventricular systole what valves are open?
pulmonary and aortic valves
During ventricular diastole what valves are open?
mitral and tricuspid
What is ectopic foci?
AP events not part of the normal pathway (depolarization not produced in the SA node)
When can ectopic foci occur?
when atria gets stretched out and after atrial remodelling due to regurgitation (worsened during exercise)
What do multiple ectopic foci lead to?
unsynchronized contraction fo the atria = fibrilation
What are the two layers of the pericardium?
visceral layer - adheres to epicardium
parietal layer - is separated from the visceral layer by a thick layer of fluid (provides lubrication for continuous movement of the heart - decreases friction)
What are the functions of the pericardium?
small distensibility strongly resists a large rapid increase in cardiac size (can adapt with exercise)
prevents sudden distension of chambers
(without pericardium, cardiac function will remain within physiological limits)
What is the main role of the pericardium?
when an increase in diastolic pressure occurs in one ventricle = there is an increase in pressure and a decrease in compliance of the other ventricle
What is pericardial-mediated ventricular interaction?
increase in LV EDV -> increase EDP -> stretch pericardium on left side -> pull on right side -> decrease in RV volume
What is Laplace’s law?
T = change in P x r / 2w
increase in r = increase T
increase in w = decrease in T
What is the contraction of the heart triggered by?
the spread of electrical excitation throughout the syncytium of muscle cells
What does the heart require optimal concentrations of?
NA+
K+
Ca2+
What does EC-coupling determine?
contractility of the heart (rate of contraction/time)
* highly Ca2+ dependent
What will occur without enough Na+?
the heart is not excitable (AP depends on extracellular Na+)
*resting membrane potential is independent of Na+ gradient across the membrane
What will a moderate decrease in K+ cause?
flatten the T-wave on ECG
What will a severe decrease in K+ cause?
weakness, paralysis, cardiac arrest
What will a large increase in K+ cause?
dysrhythmias, depolarization, loss of excitability of myocardial cells, cardiac arrest in diastole
What will Ca2+ removal cause?
a decrease in contractile force and eventually arrest in diastole
*moderates strength/magnitude of contractility
What will an increase in Ca2+ cause?
enhance contractile force
very high Ca2+ induce cardiac arrest in systole (rigour)W
What is the free intracellular concentration of Ca2+ responsible for?
the contractile state of the myocardium
What occurs during the plateau (phase 2) of an AP in regards to Ca2+?
Ca2+ permeability of sarcolemma increases, Ca2+ enters the cell through voltage-dependent L-type Ca2+ channels in the sarcolemma and T-tubules
How do the T-tubules aid when Ca2+ enters the cell?
increase SA so more Ca2+ enters
What is the opening of Ca2+ channels facilitates by?
phosphorylation of channel proteins by cyclic adenosine monophosphate (cAMP) - dependent protein kinase
What is the primary source of extracellular Ca2+?
interstitial fluid
- some may also be bound to sarcolemma
How does Ca2+ serve as a tigger?
amount of Ca2+ released from sarcolemma is not enough for contraction, serves as a trigger for intracellular Ca2+ release from SR
Explain Ca2+ induced Ca2+ release
Ca2+ leaves SR through release channels (ryanodine receptors), Ca2+ bind with troponin C
Ca2+-troponin complex interacts with tropomyosin to unblock active sites between actin and myosin to allow for cross-bridging
What is the strength of contraction determined by?
amount of Ca2+ available
- availability of channels in the heart
How do catecholamines increase Ca2+?
increase Ca2+ entering the cell by phosphorylation of Ca2+ channels via a cAMP-dependent protein kinase
How does catecholamines alter the sensitivity of contractile force?
they decrease the sensitivity of the heart to contract by phosphorylation of troponin I
What will increase systolic Ca2+?
increased Ca2+ or decreased Na+ gradient across sarcolemma
How can the Na+ gradient be decreased across the sarcolemma?
by increasing intracellular Na+ or decreasing extracellular Na+
How is intracellular Na+ increased?
cardiac glycosides inhibit the Na-K pump, and Na+ accumulates in the cells
How does increased intracellular Na+ increase systolic Ca2+?
increased cytosolic Na+ reverses the Na+ Ca2+ exchanger so less Ca2+ is removed from the cell, it is stored in the SR
How does decreased extracellular Na+ increase systolic Ca2+?
results in less Na+ entry into the cell, less exchange of Na+ for Ca2+
How is developed tension diminished?
by decreasing the extracellular Ca2+, by increasing the Na+ gradient across sarcolemma that prevents Ca2+ from entering the cell
at the end of systole, Ca2+ influx stops, and SR is not stimulated to release Ca2+
How does the SR take up Ca2+ at the end of systole?
through an ATP pump-regulated by phospholamban
What results when phospholamban is phosphorylated?
the inhibition of Ca2+ pump is relieved
What is the result of the phosphorylation of troponin I?
inhibits Ca2+ binding of troponin c -> tropomyosin blocks the site for interaction of actin and myosin -> relaxation (diastole) occurs
What is the strength of relaxation dependent on?
phosphorylation process (unbinding)
Inotropy vs lusitropy
Inotropy - strength of contraction
lusitropy - strength of relaxation
* factors that increase one increase the other
How do catecholamines and adenylyl cyclase activation accelerate cardiac contraction and relaxation?
- increases cAMP activates cAMP-dependent protein kinase, which phosphorylates the Ca2+ channel in the sarcolemma
- allows for increased influx on Ca2+ into the cell -> increase contraction
- also, phosphorylates phospholamban, which increases Ca2+ uptake by SR and phosphorylating troponin I, which inhibits Ca2+ binding of troponin C -> increased relaxation
How is Ca2+ that enters the cell removed during diastole?
exchange of 3 Na+ for 1 Ca2+
also by a pump that uses ATP to transport Ca2+ across sarcolemma
What 3 interventions are typically used for heart failure (dilated heart, decreased CO, fluid retention, increased venous pressure, enlarged liver, peripheral edema)?
- diuretic - decrease extracellular fluid -> decreased preload, venous pressure, liver congestion, edema
- angiotensin-converting enzyme inhibitor/angiotensin receptor antagonists - decreased afterload
- beta-blockers - decrease HR and energy expenditure, interference with hypertrophy of the heart
- Sometimes, digitalis glycoside (digoxin) is used to inhibit the Na-K pump to indirectly increase intracellular Ca2+ stores through Na-Ca exchange -> enhancing contractile force
What factors of cardiac contractile force does preload determine?
strength
What is preload?
force (load) on the muscle prior to it being activated to contract
What does preload result in?
applies tension to the muscle and passively stretches it to a new length
muscle may be forced to isometrically contact by the addition of a large afterload the muscle can’t lift
upon electrical stimulation, the muscle isometrically contracts and develops maximum active force capable from initial length
What does increased preload cause?
the muscle to stretch further, increasing initial length and active force (to a point)
What is the total tension at peak contraction?
sum of passive and active tension
What does increased contractility cause?
by norepinephrine (stimulates beta-adrenergic receptors) greatly increases total tension
What causes decreased contractility?
by blocking Ca2+ channels decreased total tension, largely accounted for by decreased active tension development
What is the equation for contractility?
change in pressure / change in time
What is the force and length relationship with muscle?
as length increases force increases to a point
too much stretch = decreases force (descending limb)
What is heart specific preload?
stress exerted on the ventricle during diastole (Laplace equation)
*wall stress
How does active tension rise with increases in initial muscle length?
rises steeply with initial muscle length, allows the heart to contract stronger when stretched by an increased volume of blood prior to contraction
What is the optimal initial length of the sarcomere?
2.2
optimal overlap of filaments and maximal number of potential cross bridges to develop maximal force
What is the optimal range of length of the sarcomere?
1.8-2.0
significant increase of contractile activation -> steep rise in force
What do sarcomeres stretched beyond the optimal length cause?
decreased force (myofilaments overlap less)
What do sarcomeres to short cause?
decreased force (filaments overlap to much in central region)
What do stretch of cardiac cells cause (not in skeletal) to increase cross bridging?
increases the affinity of troponin c for Ca2+ -> increases the binding of Ca2+ to troponin c and increases cross bridges
What is the proposed theory behind the stretch of cardiac cells increasing the affinity for Ca2+?
thick and thin filaments are brought closer together as the muscle fibre diameter narrows during the stretch (constant volume)
titan may help as it forms a scaffold to which actin and myosin bind
How does the amount of Ca2+ released from the SR change with sarcomere length?
increases with increased sarcomere length
What are the three cellular mechanisms contributing to the length of dependence of cardiac muscle contraction from 1.8 to 2.0?
- changes in myofilament overlap
- increases activation as result of increased chemical affinity of troponin c for Ca2+
- increased activation as a result of release of Ca2+ from SR
What factors of cardiac contractile force does after load determine?
velocity of shortening
What is afterload?
additional load (force) heart must contract against after it is activated
*represents LV ejection into the aorta
What is afterload during ejection?
the impedance (resistance) due to aortic and intraventricular pressure (virtually the same)
*the stress applied to the ventricle during ejection
What happens if afterload is to much that the muscle can’t generate force to lift?
it contracts isometrically until it generates enough force to live, then shortens
When is velocity of shortening maximal?
with no afterload
decreased to zero if force is to great for the muscle to lift at all
What does norepinephrine cause in regards to the velocity of shortening?
increased velocity of shortening at every level of afterload
What does the pressure-volume relationship reflect?
the properties of myocardial cells and provides hemodynamics characterization of the heart
What changes in the PV relationship can result in changes to SV?
changes in preload, afterload, cardiac contractility
How is the PV relationship plotted?
passive and active pressure-volume loops plotted on the same graph
*reflect the passive and active length-tension relationships
What does the passive (diastolic) PV relationship tell us?
as pressure increases in LV (stretching LV) sarcomere length increases
high compliance becomes stiffer as stretched out
Why is the passive LV relationship quite flat initially?
a large increase in volume can be accommodated with only small increases in pressure
When is considerable systolic pressure developed?
lower filling pressure
What does the sharp rise of diastolic curves at large intraventricular volumes indicate?
the ventricle becomes much less distensible with greater filling
In a normal heart, at what filling pressure is the peak force attained?
12 mmHg
2.2 um (sarcomere)
Where does the resistance to stretch of the myocardium at high filling pressures reside and what is its purpose?
non-contractile constituents of tissue (connective tissue) and serves to protect against overloading the heart in diastole
What is the typical ventricular diastolic pressure?
0 to 7 mmHg
What is the average diastolic sarcomere length?
2.2 um
Where does the normal heart operate on a frank-starling curve?
the ascending limb
What does the upper curve of PV relationship represent?
peak pressure that could develop during systole at each degree of filling
*arises from frank-starling relationship
What is indicated by the width of the PV loop?
SV
What does contractility represent?
the performance of the heart at a given preload and afterload, and it depends on the state of the EC coupling processes within cells
How can drugs augment contractility?
increase contraction frequency
How can a reasonable index of myocardial contractility be obtained?
from the contour of ventricle pressure curves
What are the characteristics of a hypodynamic heart?
elevated EDP
a slowly rising ventricular pressure
somewhat reduced ejection phase
What are the characteristics of a hyperdynamic heart?
reduced EDP
fast-rising ventricular pressure
brief ejection phase
What does the slope of the ascending limb of a ventricle pressure curve indicate?
maximal rate of force development by ventricle
*maximal rate of pressure change in time = contractility
When is slope maximal in a ventricle pressure curve?
isovolumic phase of systole
How can the contractile state of the myocardium be obtained?
from the maximum velocity of blood flow in the ascending aorta during the cardiac cycle
*also ejection fraction
What is ejection fraction?
EDV - ESV/EDV
how much blood leaves the heart for its size when filled (EDV)
~50% is normal
