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Diuretics

7/11/2016

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There are, broadly speaking, 5 different categories of diuretics. I have put them in order of where they act in the nephron. I suppose the main characteristic of most diuretics is that they act to allow water to stay within the tube that leads out to the ureter. The more concentrated with ions that the solution within the tube is, the more it will hang on to water - so by inhibiting the symporter mechanisms that remove the ions from the tubular fluid, you hold water within the tube allowing it to be passed out. However, the actions of aldosterone, angiotensin 2, and ADH also have large roles to play with the reabsorption of water.

ADH is a neurohypophyseal hormone also known as vasopressin. It increases water permeability of the collecting duct and distal convoluted tubule by inducing translocation of aquaporin-CD water channels in the plasma membrane of collecting duct cells.  It also increases peripheral vascular resistance, which in turn increases arterial blood pressure.

Aldosterone, a steroid hormone, is the main mineralocorticoid hormone. Interestingly, it responds to potassium levels, likely stimulated by the carotid sensors. Aldosterone tends to promote Na+ and water retention, and lower plasma K+ concentration by the following mechanisms: 

  1. Acting on the nuclear mineralocorticoid receptors within the principal cells of the distal tubule and the collecting duct of the kidney nephron, it upregulates and activates the basolateral Na+/K+ pumps, which pumps three sodium ions out of the cell, into the interstitial fluid and two potassium ions into the cell from the interstitial fluid. This creates a concentration gradient which results in reabsorption of sodium (Na+) ions and water (which follows sodium) into the blood, and secreting potassium (K+) ions into the urine (lumen of collecting duct).
  2. Aldosterone upregulates epithelial sodium channels (ENaCs) in the collecting duct and the colon, increasing apical membrane permeability for Na+ and thus absorption.
  3. Cl− is reabsorbed in conjunction with sodium cations to maintain the system's electrochemical balance.
  4. Aldosterone stimulates the secretion of K+ into the tubular lumen.
  5. Aldosterone stimulates Na+ and water reabsorption from the gut, salivary and sweat glands in exchange for K+.
  6. Aldosterone stimulates secretion of H+ via the H+/ATPase in the intercalated cells of the cortical collecting tubules
  7. Aldosterone upregulates expression of NCC in the distal convoluted tubule chronically and its activity acutely

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