Diuretics Effects on Kidneys - Anatomy & Physiology
Introduction
Diuretics are a class of drugs which inhibit the reabsorption of water from the tubules and as a result they increase the volume and therefore water loss in the urine. Each class of diuretic acts on a different site to achieve this effect. As a result some cause the excretion of sodium (and usually chlorine) along side the water where as others do not. There are several diseases which cause the accumulation of fluid within the various tissues of the body and it is in these cases where diuretics play a role in managing the condition.
Different Groups of Diuretics
Most diuretics act from within the tubules of the kidney.
Loop Diuretics
Loop diuretics work on the thick ascending limb of the loop of Henle by inhibiting the activity of the sodium/potassium/2-chloride symporter. Approximately 20-25% of sodium is reabsorbed via this symporter, so inhibition of it causes an increase in distal tubular sodium delivery, increased water loss, and increased sodium loss. As a result the hypertonicity of the medulla decreases and therefore water uptake from the loop of Henle also decreases. Increased amounts of all three ions are lost as a result.
As well as reducing the re-uptake of water they also increase renal blood flow via prostaglandin mediated vasodilation. This increases filtration to help lessen fluid retention.
Loop diuretics tend to be bound to plasma protein and therefore are not filtered. They enter the tubule via secretion by the organic acid transport mechanisms.
Side effects of loop diuretic therapy include abnormalities of fluid, electrolyte imbalance, metabolic alkalosis, hypomagnesemia, hypocalcemia, hypokalemia, and other effects typically related to diuretic efficacy.
Metabolic alkalosis can occur secondary to loop diuretic use in a few ways. One is due to increased distal delivery of sodium ions. As sodium travels through the urinary system it eventually reaches the distal tubules and encounters the aldosterone-sensitive sodium channel. This pump exchanges sodium ions for hydrogen ions, the loss of which can lead to alkalosis. This same pump also exchanges sodium ions for potassium ions, leading to hypokalemia. Metabolic alkalosis can also occur secondary to loop diuretic induced hypochloremia. Negatively charged chloride ions leave the body disproportionately to any positively charged counterparts. The body begins to produce bicarbonate (HCO3-) to replace the lost anions and an alkalosis develops.
Thiazides
This class of drugs works on the proximal portion of the distal convoluted tubule and inhibits the sodium chloride co-transporter in the apical membrane. As a result they increase the potassium loss - see picture. They are less effective than loop diuretics but are better tolerated.
As with loop diuretics thiazides are excreted into the tubules via secretion.
Potassium Sparing Diuretics
These diuretics act by blocking the epithelial sodium channel in the collecting duct and therefore reduce sodium and water reabsorption. They do not cause a loss of potassium and thus they get their name as potassium sparing diuretics.
Aldosterone Antagonists
Without Aldosterone the cells of the collecting duct are impermeable to sodium. Therefore if you compete with aldosterone for its receptors you reduce the permeability of the cells to sodium and therefore more sodium and water is excreted. As aldosterone causes the excretion of potassium and calcium from the tubules these two molecules are retained with these drugs.
Osmotic Diuretics
These are compounds which are filtered but not reabsorbed. They increase the osmolarity of the fluid and therefore hold more water in the tubules. However they require intravenous administration. They mainly act on sites freely permeable to water - the proximal tubule, the descending limb of the loop of henle and the collecting ducts. However they also reduce the sodium uptake as relatively sodium concentration drops in the lumen when they are present.
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