Cardiac physiology Flashcards
Which law does each belong to;
1) The tension on the wall of a sphere is the product of the pressure times the radius of the chamber and the tension is inversely related to the thickness of the wall
2) The stroke volume of the left ventricle will increase as the left ventricular volume increases due to the myocyte stretch causing a more forceful systolic contraction
3) The pressure of an incompressible and Newtonian fluid in laminar flow through a long cylindrical pipe will drop as the cross section increases
4) Wall tension is directly proportional to pressure
1) Laplace
2) frank-starling
3) Poisuille
4) Laplace
Which of the following describes the frank starling relationship?
1) The tension on the wall of a sphere is the product of the pressure times the radius of the chamber and the tension is inversely related to the thickness of the wall
2) The stroke volume of the left ventricle will increase as the left ventricular volume increases due to the myocyte stretch causing a more forceful systolic contraction
3) The pressure of an incompressible and Newtonian fluid in laminar flow through a long cylindrical pipe will drop as the cross section increases
4) Wall tension is directly proportional to pressure
it is 2
What are the three types of heat liberated by muscle?
- Maintenance = slow liberation of heat that is unrelated to contraction
- Activity related heat
-> Initial heat – appears during contraction due to:
- Tension-independent heat: caused by membrane depolarisation and repolarisation, Ca2+ cycling in the SR, Ca2+ binding to troponin I, conformational changes in the thin filament, ion transport via the sodium/potassium pump, and oxidative reactions that rephosphorylate ADP
- Tension-dependent heat: (aka shortening heat, tension time heat): caused by contractile protein interactions, muscle shortening and cross-bridge turn over.
-> Recovery heat – liberated once contraction has reached its peak, caused by ADP rephosphorylation by the Mch potential energy degraded to hear as tension falls during relaxation.
How does myosin ATPase concentration affect heat generation in muscle?
Crossbridge cycling rate occurs at rate that is proportional to myosin ATPase activity. Muscles with low Myosin ATPase activity waste less heat as tension-time heat because crossbridge cycling is low. The opposite is true for mm with high myosin ATPase activity.
what is the main energy source of the heart ?
Fasted state; FAs become the main energy source. Use of lipids account for 60-70%of the oxygen uptake in the heart where as CHOs account for <20%.
Fed state; CHO and insulin levels are high, circulating fatty acid concentration is low. The uptake of FAs by the heart is inhibited and glucose becomes the major fuel of the heart. CHOs account for 50% - 75% of the oxygen uptake.
How much of the glucose is converted into energy in the heart?
The rates of glucose oxidation only account to ¼- ½ of the the chemical glucose uptake, the rest may be converted to glycogen.
What shift occurs in energy metablism due to ischaemia?
In ischaemia oxidative metabolism decreases and glycolysis is stimulated but iscahemia results in inhibition of pyruvate dehydrogenase and so glucose cannot enter the TCA cycle. because of this FFAs are better able to capture the residual oxygen uptake. This is inefficient however as FFAs waste oxygen.
what receptors are responsible for glucose uptake into the cardyomyocytes?
What is the hormone which increases uptake of glucose?
GLUT-1 and GLUT-4 – glucose specific transporters
Insulin
what are insulins effects in the cardiomyocyte?
- Reduce FFA release (removing the inhibition to gluc uptake)
- Increase GLUT transporter translocation from the nucleus:
a. Insulin binds to the alpha subunit = autophosphrylation
b. Activation of peptide kinases = phosphorylation of tyrosine
c. Increased activity of insulin receptor subtype 1
d. Activation of IP3
e. Activation of PKB (Akt)
what is HFrEF?
Heart failure with a reduced ejection fraction is when there is a loss in cardyomyocute fucntion, which disrupts the ability of the muscle to generate force, therey prevention normal contraction.
what variations are there in sympathetic and parasympahetic input between healthy and HF people
Healthy persons display low sympathetic discharge at rest and have a high heart rate variability. In patients with HF, however, inhibitory input from baroreceptors and mechanoreceptors decreases and excitatory input increases, with the net result that there is a generalized increase in sympathetic nerve traffic and blunted
what causes elevated norepinerpherine in HF?
- Increased NE production in nerve endings and spillover into plasma
- Reduced NE uptake by nerve endings
Patients with HF have 2-3x the [NE] than normal people, and the plasma levels of NE have been shown to predic mortality in humans.
where is norepinepherine extracted from by the heart and what are the concentrations of this in the blood vessels and myocardium during HF?
Normal peoples hearts will extract NE from the arterial plasma. However, HF patients the coronary sinus [NE] concentration exceeds that of normal peoples arterial blood, suggesting over stimulation of the heart. However, as HF progresses, there is decreased myocardial [NE] concentration.
in HF with increased NE exposure what changes do we see at the level of andrenergic receptors?
there is increased production of ß1 receptors whch this results in increased HR, inotropy (i.e. systolic function) and improved relaxation, i.e. diastolic function – i.e. an attempt to maintain/improve CO.
Additionally we see stimulation of myocardial alpha1 andrenergic receptors, which illicit a medest positive ionotropic effect, as well as peripheral arterial vasoconstriction (improve Bp).
what are deleterious consequences of increased NE release in HF?
Although NE attempts to improve CO and maintain BP, the increased HR and iconography result in increased O2 demands. Additionally, arrhythmias may develop due to intracellular Na and Ca overloading, and ventricular tachycardias can be seen that may lead to sudden death
In addition to the sympathetic stimulation, parasympathetic inhibition withdrawal is thought to play a role in the pathogenesis of HF, by;
o In decreased NO level
o Increased inflammation
o Increased sympathetic activity
o Worsening of the LV remodelling
Presumed mechanisms of RAAS activation in HF include;
- Renal hypoperfusion (decreased CO and peripheral vasoconstriction)
- Decreased filtered Na reaching the macula densa in the distal tubule
- Increased sympathetic activation in the kidney results in increased renin release from the juxtaglomerular cells
describe the RAAS ACE dependent pathways
Renin (juxtaglomerular cells) cleaves four amino acids from circulating angiotensinogen (liver) to form the inactive Angiotensin I. Angiotensin-converting enzyme (ACE) from the lungs and kidney cleaves two aminoacids from angiotensin I to form the active octapeptide (1 to 8) angiotensin II.
