T1 L9: Cardiac pressure-volume cycle & ion action potentials

• Cerebral Circulation - Special Aspects

  Brain maintains all vital functions, so needs constant flow and pressure.

  Auto-regulation to achieve this.

  Circle of Willis: arteries of brain's inferior surface organised into a circle. redundancy of blood supply. 'back-up system of blood supply'

  
• Renal Circulation - Special Aspects

  • Portal system: glomerular capillaries to peritubular capillaries
  • 20-25% or cardiac output
  • makes both ACE and RENIN:
  • endocrine functions
  • controlling blood volume
  • responding to renal blood pressure
• Skeletal Muscle - Special Aspects

  Adrenergic input causes vasodilatation

  Can use 80% of cardiac output during strenuous exercise

  Major site of peripheral resistance

  Muscle pump: augments venous return
• Skin Circulation - Special Aspects

  • Role in thermoregulation (perfusion can increase 100x)
  • Arterio-venous anastomoses: direct connection between small arteries and small veins without capillaries. Primary role in thermoregulation
  • Sweat glands: role in thermoregulation, produce sweat (plasma ultrafiltrate)
  • Response to trauma: red reaction, flare, wheal

  
• Four stages of the Cardiac cycle / "Pressure-Volume Loop"

  1. Ventricular filling
  2. Isovolumic ventricular contraction
  3. Ejection
  4. Isovolumic ventricular relaxation
• Valve Sounds: S1 & S2


  S1 'lub': heard during isovolumic contraction (mitral valve closes)

  S2 'dub': heard during isovolumic relaxation (aortic valve closes)

  
• Isovolumic contraction and relaxation only occur when both aortic and mitral valves are closed.
• PV loop for mitral stenosis: decreased preload and afterload


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• PV Loop for Aortic stenosis: increased afterload


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• PV loop for mitral regurgitation: increased preload, decreased afterload


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• PV loop for aortic regurgitation: increased preload 


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• Auscultation: valve sounds

  Systolic murmur:

  • fluid leaves ventricle
  • so AV regurgitation or SL valve stenosis

  Diastolic murmur:

  • fluid enters ventricle
  • so AV stenosis or SL regurgitation
• K+ channels

  • Delayed rectifier K+ Channels: open when membrane depolarises with a delay.
  • Inward rectifier K+ channels: open when Vm goes below -60mV (when cells are at rest). Clamps membrane potential at rest, preventing depolarisation
• Ventricular myocyte action potential phases:

  0. Depolarisation: Na+ gates open in response to wave of excitation from pacemaker

  1. Transient outward current: tiny amount of K+ leaves cell
  2. Plateau phase: inflow of Ca2+ just about balances outflow of K+, until membrane potential becomes too negative and the Ca2+ channels close
  3. Rapid repolarisation phase: Vm falls as K+ leaves cell
  4. Back to resting potential

  
• QRS complex shows:

  ventricular depolarisation
• T wave shows:

  ventricular repolarisation
• Action potentials in SA node and AV node

  • spontaneously depolarise at rest: not stable because there is no inward rectifier channels
  • upstroke of action potential due to a brief increase in Ca2+ current - not Na+!
  • Only has 3 phases:
  • Depolarisation (influx of Ca2+)
  • Repolarisation (K+ exiting)
  • Pacemaker (diastolic) potential
• Pacemaker potential

  Resting membrane potential of myocytes in SA and AV node

  it is in a slope bc lack of inward rectifier channels

  Slope of pacemaker potential determines rate of firing

  
• Funny current If

  • makes the SA node channel spontaneously active
  • HCN channel (non-specific cation): opens upon hyperpolarisation and closes upon depolarisation
  • leads to a net inward current; lots of Na+ going in and tiny K+ going out
  • Depolarises cell towards 0mV
  • Ivabradine partially inhibits funny current, which slows heart rate in angina and heart failure
• Blocking ion channels of cardiac action potentials

  Na+ channel block:

  • decreases conduction velocity: changes the organisation of firing in different regions of the heart
  • does NOT prevent depolarisation or affect heart rate
  • used to treat arrhythmias

  Ca2+ channel block:

  • decreases heart rate
  • decreases contractile force