Blood volume regulation

• how does the RAAS system affect the body to increase blood pressure?

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• constriction of the afferent arteriole causes a decrease in GFR -> as there is reduced filtration pressure
• dilation of the afferent arteriole causes an increase in the GFR -> increased pressure driving ultrafiltration
• constriction of the efferent arteriole causes an increase in GFR -> increased pressure, increased filtration pressure
• dilation of the efferent arteriole causes a decrease in GFR -> blood can easily leave the capillary and pressure falls
• 6 mechanisms to regulate blood flow:

  1. Sympathetic nervous system
  2. Angiotensin II
  3. Arterial and brain natriuretic peptide ( ANP and BNP )
  4. Prostaglandins
  5. Dopamine
  6. Nitric Oxide
• the sympathetic nervous system -> renal sympathetic nerve -> sympathetic nerve fibres that innervate both the afferent and efferent arterioles -> produce vasoconstriction via (alpha) a 1 receptors
• the sympathetic nervous system has a rapid onset and stabilises the mean arterial blood pressure
• • Angiotensin II is a potent vasoconstrictor of both afferent and efferent

  •Efferent arterioles are more sensitive to angiotensin II than afferent

  •Low levels of angiotensin II produce an increase in GFR

  •High levels of angiotensin II produce a decrease in GFR
• In hemorrhage, blood loss leads to decreased arterial pressure, which activates the renin-angiotensin-aldosterone system. The high level of angiotensin II, together with increased sympathetic nerve activity, constricts afferent and efferent arterioles and causes a decrease in RBF and GFR.
• ANP and BNP:

  • dilation of afferent arterioles and constriction of efferent arterioles

  • The dilatory effect of ANP on afferent arterioles is > constrictor effect on efferent arterioles

  •Overall decrease in renal vascular resistance and resulting increase in RBF -> increased GFR
• Prostaglandins

  • produced in kidneys
  • vasodilation of both afferent and efferent
  • activated by same stimuli as sympathetic nervous system and Ang II ( haemorrhage )
  • Prostaglandins are protective for RBF
  • NSAIDS in haemorrhage -> reduction in RBF
• prostaglandins attenuate the vasoconstriction produced by the sympathetic nervous system and angiotensin II. Unopposed, this vasoconstriction can cause a profound reduction in RBF, resulting in renal failure. 
• dopamine: precursor of norepinephrine
• dopamine

  • Low levels dilates cerebral, cardiac, splanchnic, and renal arterioles BUT constricts skeletal muscle and cutaneous arterioles

  • Low dosage of dopamine can be administered in treatment of haemorrhage -> protective (vasodilatory) effect on blood flow in critical organs including kidneys.
• nitric oxide

  • Synthesised by renal endothelial cells
  • dilation of afferent and efferent arterioles
  • protect from vasoconstrictor effects of sympathetic nervous system
• 3 mechanisms to autoregulate blood flow:

  1. myogenic response
  2. tubuloglomerular feedback
  3. relationship between Pa , renal flow and GFR
• what is the myogenic response?

  increased arterial blood pressure -> stretch of vascular smooth muscle cells of afferent arterioles -> activate stretch-sensitive Ca-permeable channels -> increased cytosolic Ca -> smooth muscle contraction -> afferent arteriole vasoconstricts
• myogenic response follows the myogenic hypothesis explaining autoregulation of RBF: Increased renal arterial pressure -> stretches afferent arterioles walls -> respond by contracting -> increased afferent arteriolar resistance -> balances the increase in arterial pressure, and RBF is kept constant.
• •RBF is autoregulated over a wide range of mean arterial pressures (Pa ).

  •As renal arterial pressure increases or decreases, renal resistance must increase or decrease proportionately (recall that F = ΔP/R)

  • done by changes to the arterioles


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• Pa, renal flow and GFR

  Changes in mean arterial blood pressure increase flow through the renal artery and hence the afferent arteriole -> increases blood flow to glomerular capillaries -> increased hydrostatic pressure in the glomerular capillaries -> increases GFR -> compensatory mechanisms must take place to keep GFR constant (it already filters 180L a day!)
• Tubuloglomerular feedback: mechanism for autoregulation

  increased renal arterial pressure -> both RBF and GFR increase

  increased GFR -> increased delivery of solute and water to macula densa in early distal tubule -> senses some of the increased delivered load -> macula densa (part of the juxtaglomerular apparatus) responds by secreting a vasoactive substance -> constricts afferent arterioles via a paracrine mechanism -> reduces RBF and GFR back to normal
• Tubuloglomerular feedback: mechanism for autoregulationincreased renal arterial pressure -> both RBF and GFR increase increased GFR -> increased delivery of solute and water to macula densa in early distal tubule -> senses some of the increased delivered load -> macula densa (part of the juxtaglomerular apparatus) responds by secreting a vasoactive substance -> constricts afferent arterioles via a paracrine mechanism -> reduces RBF and GFR back to normal


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