T3 L9: Regulation of homeostasis - fluid balance

• What is the role of the kidney in Homeostasis?

  Volume regulation:

  • Fluid balance
  • Electrolyte balance

  Control of acid-base balance
• What does ADH act on?

  V2 receptors on basal membrane of principal cells in collecting duct

  leads to insertion of AQP2 water channels into apical surface
• What is ADH released in response to?

  plasma osmolarity and effective circulating volume
• What is the mechanism of Plasma osmolality regulation?

  Sensors: Osmoreceptors

  Efferent pathways: ADH, thirst

  Effector: Kidney, brain: drinking behaviour

  What is affected: Renal excretion of water; water intake
• What is the mechanism of effective circulating volume (ECV) regulation?

  Sensors: Baroreceptors

  Efferent pathways: ADH, RAAS, ANP, sympathetic NS

  Effector:

  • Short term: Heart, blood vessels
  • Long term: kidney

  What is affected:

  • Short term: Blood pressure
  • Long term: Na excretion
• What is the 'renal baroreceptor'?

  decreased renal perfusion pressure detected in the afferent arteriole
• What is decreased ECV detected by in the kidney?

  Decreased renal perfusion pressure - renal baroreceptor in afferent arteriole

  Decreased Na concentration - renal Na sensor in macula densa cells in distal tubule

  Decreased systemic BP also triggers effects of the sympathetic nervous

  system supplying the JGA
• What are the important actions of AngII?

  all actions of Ang II are designed to increase ECV:

  • Enhance tubular Na transport in kidney (Na reabsorption)
  • Stimulate aldosterone release from adrenal cortex (so more Na reabsorbed)
  • Acts on hypothalamus to stimulate thirst and ADH release into circulation
  • Vasoconstriction of renal and other systemic vessels (increases systemic BP)
  • Longer term: renal cell hypertrophy (so more protein synthesis of Na transporters and channels)
• What are the important actions of Aldosterone?

  All actions of aldosterone are designed to increase ECV (in collaboration with Ang II)

  • Stimulates Na+ reabsorption (and K+ excretion) in the distal tubule and collecting duct
  • Indirect negative feedback on RAAS by increasing ECV and lowering plasma K concentrations
  • conserving Na levels and preventing large variation in K levels (causing its excretion out of the kidney)
• How does the RAAS go (once again)?

  low ECV → detected by renal baroreceptors on renal Na sensors → activate RAAS → Angiotensin II & Aldosterone → Reduced Na excretion by kidney, increased reabsorption → increased ECV
• How does the ANS regulate volume of blood?

  low ECV → detected by peripheral baroreceptors → signals hypothalamus in brain → activates autonomic (sympathetic) NS → direct effects on renal haemodynamics & activates RAAS → reduced Na excretion by kidney and increased reabsorption → increasd ECV
• How does ADH regulate volume of blood?

  low ECV → detected by peripheral baroreceptors → signals to hypothalamus in brain → release of ADH into circulation → increased water reabsorption in kidney → increased ECV
• What is osmolality?

  Concentration of solute particles in a solution.
• How does Atrial Natriuretic Peptide (ANP) work to regulate ECV?

  Actions of ANP are all designed to lower ECV

  • Atrial myocytes synthesize and store ANP
  • High ECV → atrial stretch → ANP release into circulation
  • ANP promotes natriuresis (increased Na excretion from kidney)
  • Causes vasodilatation → increased blood flow to kidney → increased GFR
  • More Na reaches macula densa → less Renin release by JGA → reduced AngII effects
  • OVERALL: inhibits actions of renin and opposes effects of AngII