W1 Flashcards
Where does the excitation of the heart originate?
In the SA node in the pacemaker cells that naturally depolarise by the decreased efflux of potassium ions, transient calcium ion influx and the funny current (sodium and potassium ion influx). Once this depolarisation reaches the threshold then T type calcium channels open and depolarise the cells causing contraction.
How does excitation spread across the heart?
From the SA node—> AV node—> down bundle of his in intraventricular septum—> left and right branches of bundle of his —> up the purkinje fibres. This signal is transferred across the heart by the gap junctions between cells
What changes the heart rate? What is the term for an increase in heart rate?
The autonomic nervous system. Vagus nerve of the parasymapthetic stimulation uses acetyl choline acting on muscarinic M2 receptor.
Positive chronotropic effect
What are the effects of acetylcholine on heart rate, heart force and electrical conduction of the heart?
- decreased HR (negative chronotropic effect) by increasing the difference between the membrane potential and the threshold potential
- decreased contractility (negative inotropic effect) by decreasing calcium influx in phase 2 plateau of atrial and ventricular myocytes AP.
- decreased conduction velocity in AV node (negative dromotropic response) by increasing the delay in AV node due to decreased activity of voltage gated calcium channels (allowing influx)
What are the effects of noradrenaline on HR, heart force and electrical conduction
- Increased HR (positive chronotropic effect) by decreasing the difference between the membrane potential and the threshold potential
- increased contractility (positive inotropic effect) by increasing calcium influx in phase 2 plateau of atrial and ventricular myocytes AP.
- increased conduction velocity in AV node (positive dromotropic response) by decreasing the delay in AV node due to increased activity of voltage gated calcium channels (allowing influx)
Describe the mechanisms which anti-anginal drugs ivabradine reduce HR
Slow down HR by blocking the HCN channels (that allow calcium influx causing depolarisation) this reduces the frequency of the pacemaker cells reaching the AP
State the process of excitation in contraction of cardiac muscle
Four phases-
Phase 4- constant membrane potential from the inward rectifier potassium current (Iki)
Phase0- voltage activated sodium channel activated, sodium moves into the cell (Ina) so depolarisation to reach AP
Phase 1- brief repolarisation due to transient outward current where potassium exits the cell (Ito)
Phase 2- PLATEAU phase (important in force of contraction of heart due to starlings law) Ical channels inward calcium into cell; Iki causing outward potassium
Phase 3- repolarisation back to resting potential from IK
Explain how beta1 adreoceptors activation causes increased contraction force of the heart
Beta-adrenoceptors are coupled to Gs-proteins, which activate adenylyl cyclase to form cAMP from ATP. Increased cAMP activates a cAMP-dependent protein kinase (PK-A) that phosphorylates L-type calcium channels, which causes increased calcium entry into the cells.
What are clinical uses of adrenaline and dobutamine
positive chronotropic (increase HR)
+ inotropic (increased contractility)
+ dromotropic effect ( increased conduction V in AV node)
What are the two hormone system(s) that can increase BP and the single hormone that can decrease BP?
1- renin- angiotensin-aldosterone system
2- ADH
1- natriuretic peptides ANP and BNP
Where are the three hormones in the RAAS system excreted from?
Renin= from kidney
Angiotensin II- lungs
Aldosterone= adrenal cortex
Where is ADH synthesised from ?
What does it cause?
The hypothalamus and stored in the pituitary gland
Increase in MAP due to the reabsorption of water and vasoconstriction of blood vessels to increase svr and BP
What is the mode of action of natriuretic peptides?
Where are they synthesiseD?
The heart
Cause decrease of MAP due to the increased secretion of salt and water hence reducing blood volume and pressure
Explain how smooth muscle contraction occurs
Calcium influx from sarcoplasmic reticulum occurs, this binds to calmodulin to then activate the Myosin light chain kinase (MLCK). This activated complex then activates myosin light chain (MLC).
This allows myosin to bind to actin and muscle contraction to occur
Same process as striated muscle except not with ATP but instead MLC.
Explain how smooth muscle relaxation occurs
Myosin light chain must become dephosphorylated from the MLCK by myosin light chain phosphatase. This returns the myosin back to a resting conformation
How do calcium antagonists treat angina and hypertension
By reducing the amount of calcium ions entering the cell during phase 2 of the AP cycle this reduces the force of contraction of the heart. Hence reducing CO so reduces MAP
Angina- same thing but in the smooth muscle cells so reduces the tone e.g vasodilation so increases perfusion of the heart
What are the two equations of MAP?
MAP = SVR x CO MAP = (2x diastolic + systolic BP)/3 MAP= diastolic BP + 1/3 pulse pressure
What is the rate of flow dependent on ?
What is the equation for rate?
Blood viscosity
Length of blood vessel
Radius of the blood vessel
R= n (viscosity) x L (length of vessel)/ R^4 (radius of vessel)
What murmur is mid diastolic tapping apex
Mary stuck my dick to apple
Mitral stenosis mid-diastolic tapping apex
What is the murmur for pan-systolic murmur raidiating to the axilla?
Mr robinsons picks silly murmurs always
Mitral regurg pan-systolic murmur axilla
