Mechanisms of Renal Function Regulation

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Tubuloglomerular Feedback[edit]

  • Juxtaglomerular apparatus - a structure in the kidney composed of:
  • Juxtaglomerular cells (JG cells) in the wall of the afferent arteriole
  • Macula densa in the wall of the distal tubule
  • The function of the JG cells is pressure regulation by:
  • Acting as an intra-renal baroreceptor - to sense afferent arteriolar pressure
  • Secrete renin to activate the renin-angiotensin system
  • The macula densa is involved in tubuloglomerular feedback:
  • Senses fluid flow rate in the distal tubule
  • Produces locally active vasoconstrictor
  • This allows GFR to be controlled by a feedback signal from the tubules, and is important in GFR autoregulation

Regulation of Na+ Excretion[edit]

  • Filtered in large amounts, but actively transported out of all portions of the tubule other than the descending thin limb of Henle's loop
  • Normally ~99% of filtered Na+ reabsorbed
  • Amount of Na+ in the body is the prime determinant of ECF volume, because:
  • Na+ is the most abundant cation in the ECF
  • Na+ salts account for 90% of osmotically active solute in the plasma/interstitial fluid
  • The body adjusts Na+ excretion to match Na+ ingestion over a wide range of dietary intakes
  • With high salt intake, or when ECF is reduced, natriuresis occurs
  • When ECF volume is reduced, Na+ excretion is decreased
  • Variation in Na+ excretion is caused by small changes in GFR and tubular reabsorption, mainly in the 3% of Na+ that reaches collecting ducts
  • Factors regulating Na+ reabsorption include:
  • Circulating aldosterone level
  • Circulating levels of ANP and other natriuretic hormones
  • Rate of tubular secretion of H+ and K+
Adrenal mineralocorticoids:
  • Increase tubular reabsorption of Na+ in association with secretion of K+ and H+ as well as Na+ reabsorption with Cl-
  • Act by altering protein synthesis via their action on DNA, but may also have more rapid membrane-mediated effects
  • Act primarily in the collecting ducts to increase synthesis of active epithelial sodium channels (ENaCs) in this part of the nephron
  • Liddle syndrome - mutations in genes coding for ENaC cause the channels to become constitutively active in the kidney, leading to Na+ retention and hypertension
  • Prolonged mineralocorticoid exposure doesn't cause oedema due to the escape phenomenon - due to increased secretion of ANP
  • This response is reduced or in heart failure/cirrhosis/nephrosis
  • Reduction of dietary salt intake increases aldosterone secretion, producing slow but marked decreases in Na+ excretion
  • A variety of other humoral factors affect Na+ reabsorption:
  • PGE2, ANP, ouabain, endothelin and IL-1 cause natriuresis
  • Angiotensin II increases Na+ and HCO3- by action on the proximal tubules
  • ECF volume is determined primarily by total amount of osmotically active solute in the ECF
  • Na+ amount in the ECF is the most important determinant of ECF volume , therefore the Renin-Angiotensin-Aldosterone system is vital in response to hypovolaemia

Natriuretic Hormones

  • ANP - atrial natriuretic peptide - secreted by the atria in response to stretch
  • BNP - brain/B-type natriuretic peptide - secreted mainly by the heart (by the ventricles in response to stretch), but first isolated in brain
  • CNP - C-type natriuretic peptide - in brain, pituitary and kidneys, but very little is present in the heart
  • ANP and BNP act on the kidneys to increase Na+ excretion by dilating afferent arterioles and relaxing mesangial cells, therefore increasing glomerular filtration
  • They also inhibit Na+ reabsorption in the renal tubules, increase capillary permeability causing fluid extravasation and a decline in blood pressure, as well as vasodilating arterioles and venules
  • Also inhibit renin secretion and decrease pressor effects of catecholamines and angiotensin II

Regulation of Water Excretion (Defense of Tonicity)[edit]

  • See Regulation of Osmolality section

Regulation of K+ Excretion[edit]

  • Proximal tubules - much of the filtered K+ is removed from tubular fluid by active reabsorption
  • Thick ascending loop - 15% is absorbed by Na-K-Cl channels - inhibited by frusemide
  • Collecting ducts
  • Intercalated cells in medullary collecting ducts absorb most of the remaining K+ - 97-99% of all filtered K+
  • Principle cells are the main site of K+ secretion, which is increased by
  • ↑ECF [K]
  • ↑ECF [K] acts directly on basal Na/K ATPase to ↑uptake into cell.
  • Down concentration gradient to lumen via apical K channels.
  • Adrenal cortical cells detect ↑ECF [K] to ↑Aldosterone
  • ↑Aldosterone
  • ↑Apical K channel expression → ↑Secretion
  • ↑Basal membrane Na/K ATPase channel → ↑ Secretion
  • ↑ Tubule flows ↓[K] in lumen therefore greater concentration gradient. ↑Secretion
  • Diuretics → ↑K Secretion
  • This occurs at a rate proportional to the rate of flow of filtrate through the tubule, as more rapidly moving fluid has less chance to reach higher concentrations of K+ which will decrease the concentration gradient and slow further K+ transport
  • Amount secreted is about equal to intake, and balance is roughly maintained
  • In collecting duct, there is general reabsorption of Na+ and secretion of K+, although much of it is passive, not strict one-for-one exchange
  • Some coupling occurs, in that intracellular migration of Na+ from lumen into cells causes a lower potential difference across the tubular cell, favouring movement of K+ into the tubule lumen
  • K+ excretion is decreased when only small amounts of Na+ are reaching the distal tubule
  • If H+ secretion from collecting duct cells is increased, K+ reabsorption will increase due to the action of H,K-ATPase


  • Water and ethanol inhibit vasopressin secretion
  • Carbonic anhydrase-inhibiting drugs - only moderately effective as diuretics, but by decreasing supply of carbonic acid they cause decreased H+ secretion, resulting in increased Na+ excretion, decreased HCO3- reabsorption, and increased excretion of K+ due to decreased competition from H+ for Na+ exchange
  • Frusemide inhibits Na-K-2Cl cotransporter in the thick ascending limb of Henle's loop causing marked natriuresis and kaliuresis
  • Thiazides inhibit Na-Cl cotransport in the distal tubule, however their diuresis is less marked
  • Both frusemide and thiazides cause increased delivery of Na+ to collecting ducts, causing K+ excretion and long term K+ depletion and hypokalaemia
  • K+ sparing diuretics - spironolactone (inhibits aldosterone) and amiloride (inhibits ENaCs)