S4: congenital heart defects + cellular & molecular events in the CVS

Question 1

Describe the common types of congenital malformation of the heart and great vessels

Answer 1

Acyantoic defects = atrial septal defect, patent foramen ovale, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta
Cyanotic defects = tetralogy of fallot, tricuspid atresia, transposition of the great arteries, hypoplastic left heart

Question 2

Describe the consequences of ventricular and atrial septal defects

Answer 2

Atrial septal defects = opening in the septum between the two atria; as left atrial pressure > right atrial pressure, flow will mainly be from left to right
Therefore, no mixing of deoxygenated blood with the oxygenated blood being pumped around the systemic circulation

Question 3

Explain the effects of a left to right shunt

Answer 3

Patent ductus arteriosus = blood flow is from aorta to pulmonary artery
Eisenmenger syndrome = condition of severe pulmonary vascular obstruction that results from chronic left to right shunting through a congenital cardiac defect
Elevated pulmonary vascular resistance causes reversal (right to left) of the original shunt and systemic cyanosis

Question 4

Explain the causes of congenital cyanotic heart defect

Answer 4

Congenital heart defects which result in a low blood oxygen level
Caused by tetralogy of fallot, transposition of the great vessels, tricuspid atresia, hypoplastic left heart

Question 5

Describe the functional importance of transposition of the great vessels

Answer 5

Results in two unconnected parallel circulations instead of two circulations in series
Right ventricle connected to the aorta, left ventricle connected to the pulmonary trunk
If all the shunts have been closed, it would result in death (need to keep foramen ovale & ductus arteriosus open)

Question 6

Describe the functional importance of stenosis and atresia of the aorta and pulmonary valve

Answer 6

Aortic and pulmonary atresia is when the valves themselves do not form
Pulmonary stenosis = causes right ventricular hypertrophy
Aortic stenosis = causes left ventricular hypertrophy

Question 7

Explain the significance of a patent ductus arteriosus

Answer 7

Ductus arteriosus exists in the fetus to shunt blood from the pulmonary artery to the aorta before the lungs are functioning (should close shortly after birth)
Patent ductus arteriosus = failure to close the ductus arteriosus
Can lead to Eisenmenger syndrome

Question 8

Describe the effects of coarctation of the aorta

Answer 8

Narrowing of the aortic lumen in the region of the ligamentum arteriosum
Increases the afterload on the left ventricle -> left ventricular hypertrophy
Blood flow to the body is reduced (except head and upper limbs as they usually emerge proximal to the coarctation)
Femoral pulses are weak and delayed, elevated BP in upper body

Question 9

Describe how the resting membrane potential of cardiac cells is generated

Answer 9

K+ permeability sets the RMP
K+ ions move out of the cell down their concentration gradient
Net outflow until Ek is reached but RMP doesn’t equal Ek because there is very small permeability to other ion species at rest

Question 10

Describe the ionic currents underlying the cell action potential of ventricular cells

Answer 10

Opening of voltage-gated Na+ channels causes upstroke
Transient outward K+ current (initial repolarisation)
Opening of voltage-gated Ca2+ channels (some K+ channels also open) = plateau
Ca2+ channels inactivate, voltage-gated K+ channels open = repolarisation

Question 11

Describe the ionic currents underling the cell action potential of pacemaker cells

Answer 11

Pacemaker potential If (funny current) = influx of Na+
Opening of voltage-gated Ca2+ channels causes upstroke
Opening of voltage-gated K+ channels causes repolarisation

Question 12

Explain the pacemaker potential

Answer 12

Initial slope to threshold
Activated at membrane potentials that are more negative than -50mV
HCN channels = allow influx of Na+ ions which depolarise the cell

Question 13

Describe the processes of excitation - contraction coupling in ventricular myocardial cells

Answer 13

Depolarisation opens L-type Ca2+ channels in T-tubule system
Localised Ca2+ entry opens CICR channels in the SR
Ca2+ binds to troponin C, conformation change shifts tropomyosin to reveal myosin binding site of actin filament (SLIDING FILAMENT)
Relaxation = Ca2+ pumped back in SR (SERCA), some exits across cell membrane

Question 14

Explain the effects of hyperkalaemia on the heart

Answer 14

Ek gets less negative so membrane depolarises a bit
Inactivates some of the voltage-gated Na+ channels -> slows upstroke & shorter AP due to rapid repolarisation
Risks: heart can stop, initially get an increase in excitability
Treatment: calcium gluconate

Question 15

Explain the effects of hypokalaemia on the heart

Answer 15

Lengthens the action potential & delays repolarisation
Longer AP can lead to EADs -> lead to oscillations in membrane potential
Can results in VF

Question 16

Describe the membrane potential changes in pacemaker cells associated with increases and decreases in heart rate

Answer 16

Action potentials fire too slowly -> bradycardia
Action potentials fail -> asystole
Action potentials fire too quickly -> tachycardia
Electrical activity becomes random -> fibrillation

Question 17

Describe the process of excitation contraction coupling in smooth muscle cells

Answer 17

Increased intracellular Ca2+ concentration
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
MLCP dephosphorylates the myosin light chain

Question 18

How is contraction of smooth muscle cells regulated?

Answer 18

MLCP can be phosphorylated by PKC during alpha1 noradrenergic signalling (inhibits MLCP to maintain contraction)
Phosphorylation of MLCK by PKA inhibits the action of MLCK (inhibits contraction)