Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 30-y-old female presented with a history of hypertension and a modest degree of hyperkalemia. There was a mild degree of contraction of her ECF volume on clinical examination, with elevated levels of renin and aldosterone in plasma. No causes for secondary hypertension were found. Laboratory investigations revealed a slightly reduced glomerular filtration rate (GFR) and a subnormal kaliuretic response to exogenous mineralocorticoids. When a further degree of ECF volume contraction was induced, she was unable to conserve Na+ and Cl- appropriately. Moreover, expansion of the ECF volume led to a significant suppression of the levels of both renin and aldosterone in plasma. We speculate that these findings could be explained by a diminished net rate of reabsorption of Na+ in the cortical collecting duct. Such a reduction could lead to a diminished generation of an electrical gradient to favour the net secretion of K+ and lead to hyperkalemia with renal salt wasting. The resultant contraction of the extracellular fluid volume with the release of renin and aldosterone (and probably other vasoactive hormones) might have predisposed her to hypertension. This hypothesis was supported by the finding that NaCl supplements led to a significant drop in her blood pressure. This case could represent a new syndrome of hyperkalemia and "salt sensitive" hypertension.
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PMID:Hyperkalemia with mild ECF volume contraction: studies to provide a possible physiologic interpretation. 786 45

Among the causes of secondary hypertension are a group of disorders with a Mendelian inheritance pattern. Recent advances in molecular biology have unveiled the pathogenesis of hypertension in many of these conditions. Remarkably, the mechanism in every case has proved to be upregulation of sodium (Na) reabsorption in the distal nephron, with accompanying expansion of extracellular volume. In one group, the mutations involve the Na-transport machinery in distal tubule cells themselves: the distal convoluted tubule (DCT) cell and the principal cell of the collecting duct. Examples include Liddle's syndrome, with an activating mutation of epithelial Na channel (ENaC); two types of Gordon's syndrome, with mutations in two regulatory kinases [with no lysine (K) serine/threonine protein kinases (WNK)1 or WNK4]; and apparent mineralocorticoid excess (AME), with an inactivating mutation in the glucocorticoid-metabolizing 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11HD2). In another group, abnormal adrenal steroid production leads to inappropriate stimulation of the mineralocorticoid receptor (MR) in the distal nephron. The pathophysiology may involve inappropriate production of aldosterone [in glucocorticoid-remediable aldosteronism (GRA) and familial hyperaldosteronism type II (FH II)], of cortisol (in familial glucocorticoid resistance), or of other steroid metabolites (in congenital adrenal hyperplasia and GRA). In contrast to earlier beliefs, hypertension in many of the inherited disorders may be mild, and electrolyte and acid-base abnormalities are often not present. Monogenic hypertension should therefore enter the differential diagnosis of any child or adolescent with hypertension. Plasma renin activity (PRA) is the appropriate screening tool for all types of inherited hypertension.
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PMID:Heritable forms of hypertension. 1764 25