Physiology Topics
Diseases of fluid balance include essential hypertension and Liddle's disease. Homeostatic imbalances of glucocorticoid or mineralocorticoid hormones, like Cushing's syndrome, Addison's syndrome and others, also have a large fluid imbalance component.
Essential hypertension is more common in African Americans and people over 70 yrs old. There is a failure to reverse the condition in 50% of cases, even with treatment, diet and exercise. The causes of essential hypertension are not known, but it seems to have something to do with the kidneys If a kidney from a healthy person is transplanted into a patient with essential hypertension, the condition will improve. The opposite has been observed in rats. Essential hypertension may have something to do with the amiloride-sensitive Na+ channels, as evidence by Liddle's syndrome.
Liddle's syndrome is a very rare disease characterized by low blood K+ and high Na+ reabsorption, but with low aldosterone levels. Only a few families have this congenital disease. Patients are non-responsive to anti-hypertensive therapy and develop renal failure at an early age (early 20's). After a kidney transplant the hypertension can be controlled. Liddle's syndrome is due to a mutation in the amiloride- sensitive Na+ channel. A mutation at the C-terminus of the beta subunit results in a more active channel.
Cushing's syndrome is due to an excess of glucocorticoids, which induces muscle breakdown, fat deposition, and overstimulation of the mineralocorticoid receptors. Symptoms include a particular body structure due to little muscle mass and excess fat deposits, fluid and Na+ retention and K+ loss. Cushing's syndrome is usually due to adrenal tumor or glucocorticoid therapy. A similar toxicity may develop by licorice inhibition of 11-beta-HSDL.
Addison's syndrome is due to insufficient secretion of both glucocorticoids and mineralocorticoids. It leads to hypotension, hyperkalemia and dangerous natriuresis and water loss. It can be treated with steroid hormone replacement therapy. Spironolactone will cause similar symptoms by blocking the mineralocorticoid receptors, and is used as a diuretic.
Pseudohypoaldosteronism presents symptoms similar to Addison's syndrome. It occurs in neonates and is fatal if not treated immediately. Aldosterone and renin levels are normal, as well as the levels of their receptors. But there is a loss of function due to mutations in the ___ channels. A congenital defect in 11-beta-HSD2 will cause the opposite effect (?).
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