Water and electrolyte balance

• Describe sodium intake and distribution

  Sodium is the most abundant ion in the extracellular fluid Typically salt intake is around 10g per day and it is lost in sweat (0.25g), urine (9.5g) and faeces (0.25g).
• Describe the hormones responsible for excretion and reabsorption

  • Aldosterone: steroid hormone produced in the adrenal cortex from cholesterol In response to a fall in NaCl intake or rise in K+ concentration in the interstitial fluid. Stimulate by angiotensin II and inhibited by ANP.
  • ACTH- released in response to severe loss of Na+ by posterior pituitary gland

  These hormones increase Na+ retention, K+ excretion and secondary retention of water.
• Describe the role of the renin-angiotensin system in GFR control

  1. Specialised cells surrounding the afferent arteriole detect changes in BP and the macula densa detects changes in Na+ and Osmolality.
  2. This stimulates renin secretion from renin granular cells, which cleaves angiotensinogen to angiotensin I.
  3. ACE converts angiotensin I to angiotensin II, which is a powerful vasodilator and triggers ADH release from posterior pituitary gland, which increases water reabsorption. Also triggers aldosterone release.
• Describe the action of aldosterone

  Its main site of action is the distal convoluted tubule and the collecting duct where it stimulates the insertion of Na+ channels, ENaC. It also activates Na+ K+ pumps and Na+ H+ pumps, which increases the amount of sodium pumped into the cell.
• Describe ANP

  Atrial Natriuretic Peptide (ANP) is produced in the heart and stored within atrial cells. ANP release is triggered by stretching of the atrium and its actions are:

  • Inhibits NaCl reabsorption in medullary CD
  • Inhibits ADH stimulated water reabsorption in CD
  • Inhibits ADH secretion from posterior pituitary
  • Inhibits angiotensin II and aldosterone
• What is urodilatin?

  This is secreted by DCT and CD cells and inhibits Na+ reabsorption. It is similar to ANP but much more potent.
• Describe how ECV is controlled by sweating

  Sweat: hypo-osmotic fluid, consisting of mainly water and NaCl

  1. Prolonged sweating leads to decreased plasma volume, which decreases GFR and increases aldosterone.
  2. This results in a decrease in Na+ excretion and Na+ is reabsorbed in the CD
  3. Sweating also increases plasma osmolality, which increases ADH leading to decreased water excretion.
• Describe how ECV is controlled by thirst

  1. Decrease in blood volume or increase in plasma osmolality stimulates baroreceptors and osmoreceptors respectively.
  2. This triggers the release of angiotensin II, which triggers thirst centres in the hypothalamus and causes the person to drink.
• What are diuretics?

  These are substances that cause enhanced excretion of water and solutes by inhibiting Na+ reabsorption in the nephron. They are used to treat hypertension, pulmonary oedema and chronic heart failure. These can be split into clinical and non-clinical diuretics.
• Describe osmotic diuretics

  This is a type of clinical diuretic that acts on the PCT and enters the tubule via filtration. It cannot be reabsorbed so it exerts osmotic pressure in the tubule. This inhibits reabsorption of solute and water by altering osmotic driving forces. Osmotic diuretics do not act on specific membrane proteins. Example: mannitol
• Describe carbonic anhydrase inhibitors

  These act primarily on PCT where enzyme carbonic anhydrase is most abundant, but also acts on principal and intercalating cell in the CD. Inhibition of carbonic anhydrase leads to less formation of HCO3-, which means less Na+ is absorbed. An example of a CA inhibitor is acetazolamide.
• Describe loop diuretics

  These act on the LOH and enter the tubule lumen via secretion. They block Na+ K+ 2Cl- symporter on apical membrane of the ascending limb, hence preventing Na+ reabsorption and disrupting the counter current multiplier as the ascending limb is impermeable to water. This impairs the kidneys role of diluting and concentrating urine. Example: bumetanide
• Describe thiazide diuretics

  These enter the tubule via filtration and inhibt Na+ reabsorption by blocking Na+ Cl- symporters on the DCT apical membrane. This therefore inhibits water reabsorption. Example: Bendroflumethiazide
• Describe the problems with diuretics

  • If overabused it can lead to dehydration
  • Can cause electrolyte imbalance