Mechanics 1 Flashcards
What do cardiac myocytes require to beat?
external Ca
skeletal muscle can beat without this
Describe a single cardiac myocyte
rod shape
striated
100 micrometres long, 15 micrometres wide
T tubules form invaginations along the myocyte at Z line to carry surface depolarisation into the cell = 200 micrometres deep, 2 apart
What pumps/channels are found on the T tubule surface facing the RyR of the sarcoplasmic reticulum?
VGCC (L type)
Na/Ca exchanger
Na + channel (Na/K ATPase)
Describe excitation contraction coupling
- Depolarisation detected by L type Ca channels to cause external Ca to enter cell
- Some Ca directly causes contraction or binds to RyR to cause Ca release from SR
- Ca taken back up into SR by Ca ATPase channels
- Same amount of Ca that entered is effluxed by NCX in a passive process using Na downhill energy gradient
What is used to reuptake Ca into SR?
SERCA
sarcoendoplasmic reticulum CaATPase channels
active process
against [] gradient
How does efflux of Ca work?
passive process
use downhill energy gradient of Na (high Na outside cell)
What are the 4 events including the action potential initiation?
AP Ca influx crossbridge cycle fibre shortening contraction
What is the function of the T tubules?
facilitate the transmission of the AP to the centre of the cell
What forms the communication interface?
SR and RyR
What is the SR?
huge intracellular store of Ca
Ca is critical for myofilament contraction
What is the relationship between force and Ca?
sigmoidal curve
around 10micromol of intracellular Ca needed to produce maximal force
What reduces the [] of Ca needed to generate a given contraction?
Ca [] needed is reduced by stretch because Ca sensitivity increases with stretch
What is the [] of Ca needed to generate a 50% of maximal contraction?
[Ca] 50%
What causes an increase in potential free energy?
increase muscle length
Why does active force curve decrease after increase?
point where stretch does not generate more force because there is not enough overlap between the filaments
What is the passive force based on?
muscles’ resistance to stretch
What does stretch do to cardiac myocytes?
increase Ca sensitivity
unlike in skeletal muscle
Why does skeletal muscle produce less force whilst cardiac produces more?
cardiac muscle is more resistant to stretch due to ECM, cytoskeleton leading to more passive force generated
cardiac muscle is also less compliant
Which limb of length tension relationship is important for cardiac muscle only?
ascending limb
the pericardium resists overstretching that is characteristic of the descending limb
What is isometric contraction of the heart?
no change in length, increase tension
valves are closed
during diastole, ventricles fill and pressure increases in ventricles which exerts a preload on cardiac cells
What is the effect of preload on isometric contraction?
increase preload –> increase IC
What is isotonic contraction of the heart?
change in length, same tension
AV closed, SL open
fibres shorten
during ejection phase (late systole)
What is the effect of afterload on isotonic shortening?
increase afterload decreases shortening
What is concentric?
shortening
most common form of isotonic contraction in heart
What is eccentric?
lengthening
What is the isometric length tension relation?
preload enhances contractile force
(increase in contractile energy with stretch = Starling’s Law)
stretch is set by the diastolic ventricular filling pressure (diastole determines the preload)
filling of ventricles with blood causes stretching and generates isometric contraction
What is the isotonic afterload shortening relation?
afterload impairs shortening
an increase in afterload causes the rate and degree of shortening to decrease
What happens if there is the same afterload with a large preload?
shortens the muscle more as the cardiac cells compensate for the greater volume of blood
What governs the amount of force a muscle can produce?
preload
What is ventricular filling equivalent to?
preload
Describe preload in the heart?
Diastole the walls stretch as blood fills the ventricles and pressure increases –> stretch determines preload –> preload dependent on VENOUS RETURN TO THE HEART
What are 3 measures of preload?
end diastolic volume
end diastolic pressure
right atrial pressure
Describe afterload in the heart?
Afterload is the force the heart must over come to eject blood from the ventricles
What is the measure of afterload?
diastolic arterial BP must be overcome by pressure in ventricles for blood to be ejected
What is the change in afterload in hypertensive patients:
they have an increased afterload
increase BP
increased risk of high pressure in heart
What is Frank Starling relationship?
increased diastolic fibre length increases ventricular contraction
increased stretching/preload increases speed of shortening
Why does stretch actually increase strength of contraction?
it reduces interference by myosin heads that are pulling in the wrong direction beyond the sarcomere midpoint
Why is Starling’s Law important?
larger preload means ventricles need to increase SV to ensure CO balances venous return
The law means that the heart can adapt to changes in preload (venous return)
Factor 1 that contributes to Starling’s Law?
Changes in number of myofilament crossbridges that interact
- at shorter lengths actin filaments overlap
- reduced number of myosin crossbridges that can be made because some are pulling in the opposite direction to majority which reduces net tension generated
But this is also the case in skeletal muscle so which is cardiac muscle more sensitive than skeletal? FACTOR 2
Factor 2 that contributes to Starling’s Law?
Increased Ca sensitivity with increased length
At physiological [Ca] lower active tension as only fraction of crossbridges are activated - force increases more steeply with stretch
Why does increased length increase Ca sensitivity?
- Troponin C (TnC) is a thin filament binding to Ca and regulate cross bridge formation
- longer sarcomere increases TnC affinity for Ca
- conformational protein change
- less Ca needed for same force - Stretch causes lattice spacing (space between A and M filaments ) to decrease
- increase chance of forming strong cross bridges
- and so more force is produced for same amount of Ca
What is the Anrep effect?
a sudden increase in afterload on the heart causes an increase in ventricular inotropy
if stretch is maintained there is a further slow increase in force over 5 minutes due to increased Ca transients (slow force response)
Stroke work?
= work done by heart to eject blood under pressure into aorta and pulmonary artery
Formula for stroke work?
SV x Pressure
preload and afterload influence SV
cardiac structure influences the pressure at which blood is ejected
What is the Law of Laplace?
when pressure in a cylinder is constant, tension in walls increases with radius
T (wall tension) = P (pressure in vessel) x R (radius) /h
tension is constant
h takes into account wall thickness
What is Law of Laplace used for?
ventricles and blood vessels
What is kept the same in the heart? How?
wall tension kept same between L and R ventricle despite higher pressure in LV
- radius of curvature of LC less than RV so higher pressures generated with similar wall tension
- heart does not rip despite high pressures generated
Wall tension in giraffe?
wall stress kept low by long narrow thin walled ventricle and a small radius to allow for a high pressure
Wall tension in frogs?
pressures are lower so ventricles are spherical to give a larger radius
What happens to wall tension in a failing heart?
dilated cardiomyopathy
enlarged radius
increase wall stress
bad –> aneurysm
