Renal physiology

• Glomerular blood flow is controlled by the myogenic mechanism which involves monitoring the performance of the nephron through tubuloglomerular feedback
• A special zone of the distal tubule, called the macula densa, forms where the distal tubule comes into contact with the afferent and efferent arterioles at the glomerulus.
• The juxta-glomerular cells release adenosine to constrict the afferent arterioles and also release renin unless the macula densa cells are pumping out large amount of sodium.
• Decreased blood pressure leads to decreased filtration rate, decreased ions in the distal tubule, decreased ions resorption by the macula densa cells, increased renin production by the juxta-glomerular cells.
• Renin converts angiotensinogen from the liver into angiotensin 1.
• Angiotensin 1 is converted into angiotensin 2 by angiotensin converting enzyme in the lungs.
• Angiotensin 2 causes increased:

  • sympathetic nervous system activity
  • tubular sodium and chloride resorption,
  • potassium excretion and water retention
  • adrenal gland activation
  • arterial vasoconstriction
  • secretion of ADH (from posterior pituitary)
• the tubuloglomerular feedback includes the macula densa cells sensing the sodium concentration that has been resorbed from the distal tubule
• the myogenic mechanism, is an arteries/arteriole's ability to contract to relax to keep the blood pressure with a certain range
• adrenal gland activation leads to increased aldosterone, causing more tubular:

  • sodium and chloride reabsorption
  • potassium excretion
  • water retention
• aldosterone causes increased gene expression for proton ATPase in the type A intercalated cells of the collecting duct
• aldosterone causes increased gene expression (ASC/ENaC gene) for the sodium channels on the apical side, and sodium/potassium ATPase on the basement side, in the principal cells of the collecting duct (leads to increased sodium resorption and potassium secretion)
• angiotensin 2 causes lead to:

  • water and salt retention
  • effective circulating volume increase
  • profession of the juxta-glomerular apparatus increase
• renal nerves (sympathetic) secret noradrenaline which constriction both afferent and efferent vessels to reduce flow and increase renin
• atrial natruietic peptide (ANP) from the heart blocks the sodium reuptake channels in the collecting ducts and causes more sodium loss
• special cells called the juxta-glomerular apparatus coat the afferent and efferent arterioles and result in the blood pressure control through muscle contraction and renin release
• high BP leads to increased filtration rate and less time for solute recovery, more ions in distal tubule and thus more ions resorbed leading to decreased release of renin from the juxtaglomerular cells
• Blood calcium is monitored by the parathyroid gland, and low plasma calcium triggers the parathyroid gland to release parathyroid hormone (PTH).
• The PTH acts by binding in two regions of the nephron:

  • distal tubule
  • proximal tubule
• In the proximal convoluted tubule the PTH acts by inhibiting the sodium/phosphate pump to decrease phosphate by stopping its resorption from the lumen
• PTH leads to increased calcium recovery and decreased phosphate recovery, balancing out plasma calcium levels, causing a feedback effect on the parathyroid gland.
• Fall in intracellular pH leads to increased activity of apical sodium/proton exchange pump, which causes increased proton excretion to decrease acid level.
• Around 90% of potassium is resorbed before the collecting duct with little regulation, resorption by intercalated cells in the collecting duct is constant with the proton/potassium anti-porter
• If the body is in chronic alkalosis, there will be less protons, thus less potassium will be resorbed leading to hypokalaemia, in alkalosis the potassium channel in the principal cell is increased.
• If the body is in acute acidosis, there will be more protons, thus more potassium will be resorbed leading to hyperkalaemia, the potassium channels in principal cells become less active.
• Excretion by principal cells is regulated by aldosterone, high tissue potassium increases potassium excretion, low potassium diets leads to tyrosine (removed from membrane) of apical potassium channels, high potassium diet causes loss of tyrosine and potassium channels accumulate in membranes.
• At the DCT, the PTH acts by:

  • increasing the activity of the TRPV5 calcium uptake channel at the apical membrane to drive resorption
  • increasing the export of calbindin (binds calcium) back into the plasma (calbindin binding and export require vitamin D)
• phosphate typically binds to calcium and makes it inactive, PTH decreases phosphate resorption to increase the amount of active calcium in the plasma