Ses 4 Embryological Defect And Membrane Potential Cvs Flashcards
Acyanotic Congenital HD
atrial septal defect (ASD) - opening in the wall between the two atria - failure to close of septum primum or secundum.
patent foramen ovale (PFO) - generally clinically silent since the higher left atrial pressure causes functional closure of the flap valve.
ventricular septal defect (VSD) - abnormal opening in the interventricular septum failure of membranous portion to develop.
patent ductus arteriosus (PDA) - failure to close of ductus arteriosus
Coarctation of aorta
AV septal defect - failure of endocardial cushions to develop.
Aortic/pulmonary stenosis
Cyanotic Defects
Tetralogy of Fallot - VSD, overriding aorta(gets blood from both ventricles) and a variable degree of pulmonary stenosis and right ventricular hypertrophy.
Increased pressure on the right side due to stenosis so VSD and overriding aorta allow right to left shunting and mixing of deoxygenated blood with the oxygenated blood going to the systemic circulation, resulting in cyanosis - dec pO2.
Tricuspid atresia (lack of development of the tricuspid valve) leaves no inlet to the right ventricle.
There must be a right to left shunt from right atrium (ASD or PFO) and a VSD or PDA to allow blood flow to the lungs.
Transposition of the great arteries results in two unconnected parallel circulations - failure of development of spiral septum. Right ventricle is connected to the aorta and the left ventricle to the pulmonary trunk.
Hypoplastic left heart - left ventricle and ascending aorta fail to develop properly. PFO or ASD are also present and blood supply to the systemic circulation is via a PDA.
Univentricular heart - no v septum
Pulmonary atresia- need VSD and PDA
explain the effects of a left to right shunt
Blood from the left heart is returned to the lungs instead of going to the body.
Increased pulmonary artery pressure is damaging so pulmonary hypertension and oedema.
If the pressure in the pulmonary circulation becomes high enough due to incresistance, the pressure in the right atrium will exceed that in the left.
Flow of blood wil reverse, and deoxygenated blood will mix with oxygenated blood in the left atrium. The patient will become cyanotic due to the reduced pO2 in the systemic circulation. This is called Eisenmenger’s syndrome.
describe the functional importance of transposition of the great vessels
The aorticopulmonary septum forms, but does not spiral.
Aorta arises from the right ventricle, and the pulmonary trunk arises from the left ventricle.
Need ASD and PDA to allow some oxygenated blood to enter the systemic circulation.
This is a neonatal emergency and prostaglandins must be given to the baby quickly in order to maintain the PDA and allow some oxygenated blood into the systemic circulation until surgery can be performed.
describe the functional importance of stenosis and atresia of the aorta and pulmonary valve
Pulmonary valve atresia:
1 No RV outlet
2 R to L atrial shunt of entire venous return
3 Blood flow to lungs via PDA.
Presenting as Neonatal emergencies, often due to reduced pulmonary blood flow
Aortic/Pulmonary Stenosis:
One or both semilunar valves don’t develop properly and are narrow when the baby is born.
In the case of the aortic valve, a common defect is that the valve has only two leaflets.
This will result in left/right ventricular hypertrophy as the heart is having to generate more force to push blood though the stenosed valve. This hypertrophy can lead to heart failure.
explain the significance of a patent ductus arteriosus
DA exists in the fetus to shunt blood from the pulmonary artery to the aorta before the lungs are functioning.
This vessel should close shortly after birth as the pressure in the pulmonary artery drops following perfusion of the lungs.
Blood flow through a PDA will be from aorta to pulmonary artery after birth (high to low pressure).
describe the effects of coarctation of the aorta
This is a congenital narrowing of part of the aorta, commonly around the ductus arteriosus area.
Upstream of the coarctation (towards the heart), blood pressure is high because it struggles to flow past the coarctation.
Can cause:
aneurysms of the aortic arch
aortic root dilation which can lead to aortic valve regurgitation.
Downstream of the coarctation (towards the body), patients will have weak pulses and claudication (cramping in the legs in this case due to reduced perfusion).
Can cause:
Radial-femoral delay (if narrowing after 3 branches of aorta as upper body will have high BP and lower body will have lower BP so radial pulse before femoral pulse).
Radial-radial delay - if narrowing between brachiocephalic trunk and left SA - right radial pulse before left).
describe how the resting membrane potential of cardiac cells is generated
Cardiac myocyte permeability to K+ ions at rest is the main determinant of RMP.
Sodium potassium pump means high Na+ out and high K+in.
K+ flows out down conc gradient.
Taking away positive charge so inside of cell is more negative.
Electrical gradient established.
Ek reached - membrane potential.
draw the changes in membrane potential notion
describe action potential of ventricular cells
RMP is -90mV. Reaches threshold by Ca2+ which comes in through intercalated discs.
Phase 0
When it reaches threshold VG Na+ channels open. There is an upstroke - depolarisation. Reaches +10mV.
Phase 1
K+ moves out so slight drop to 0mV - slight repolarisation.
Phase 2
Plateau as L type Ca 2+ channels open (stimulated by 0mV) and are moving in but K+ channels also open and moving out.
Phase 3
Repolarisation as only K+ channels open and Ca2+ pumped out by H+/Ca2+ ATPase and Na+/Ca2+ exchanger. Reaches RMP.
Phase 4
Stays at RMP until Ca2+ flows in from nodal gap junctions.
describe the processes of excitation - contraction coupling in ventricular myocardial cells.
Cardiac myocytes are electrically coupled to each other.
Action potential in another myocyte or nodal myocyte causes Ca2+ to flow in from gap junction and increase cytosolic [Ca2+] and eventually AP.
Depolarisation opens L-type Ca2+ channels in T-tubule system
Opens Calcium-Induced Calcium Release (CICR) channels in the SR
This allows actin and myosin interaction as Ca2+ binds to Troponin C which causes conformational change so Troponin T moves tropomyosin from actin binding sites so myosin heads can bind.
describe the factors influencing the changes in intracellular free calcium concentration of ventricular cells during the action potential
Ca2+ from neighbouring myocyte
L type Ca2+ channels
SERCA
Ca2+ATPase
Na+/Ca2+ exchanger
explain the effects of hyper and hypokalaemia on the heart
Must be 3.5 – 5.5 mmol/L.
Hyperkalaemia depolarises the myocytes and slows down the upstroke of the action potential.
High K+ means Ek less neg so slight membrane potential depolarisation. This inactivates VG Na+ so slows upstroke and smaller AP.
The heart can stop – asystole. May initially get an increase in excitability.
Treatment - Calcium gluconate, Insulin + glucose.
Hypokalemia lengthens AP. Early after depolarisations (EADs). This can lead to oscillations in membrane
potential. Can result in ventricular fibrillation (VF).
describe the membrane potential changes in pacemaker cells
associated with increases and decreases in heart rate.
Pacemaker cells of the SA node and AV node spontaneously fire action potentials.
SA node cells are the fastest to depolarise - leakiest Na+ channels- pacemaker.
Initial slow depolarisation is due to funny current - HCN (Hyperpolarisation-activated, Cyclic Nucleotide-gated) channels open which allow influx of Na+ ions. Activated at membrane potentials that are more negative than -50mV.
Than faster depolarisation- opening of voltage-gated Ca2+ channels - reach threshold and upstroke of AP.
Repolarisation - VG K+ opens
The triggering of a single action potential which spreads throughout the heart
is responsible for contraction.
describe the process of excitation contraction coupling in smooth muscle cells
Tone of blood vessels is controlled by contraction and relaxation of vascular smooth muscle cells. Located in tunica media.
Contraction of vascular smooth muscle cells initiated by depolarisation (opens VGCCs) or activation of α-adrenoceptors ( bind to Gq receptors).
Ca2+ binds to calmodulin
– Activates Myosin Light Chain Kinase (MLCK)
– MLCK phosphorylates the myosin light chain to permit interaction with actin
• Relaxation as Ca2+ levels decline – Myosin Light Chain Phosphatase (MLCP) dephosphorylates the myosin light chain
