A Patient presented with Hypokalemia, Severe Hypertension, and Metabolic Alkalosis. The diagnosis is
(A) Liddle syndrome[?]Liddle's Syndrome: Autosomal dominant & is characterized by activating mutation of collecting duct Na+ channel with enhanced sodium reabsorption.oLow renin, low aldosterone levels.oClinical picture mimics Primary Hyperaldosteronism: Hypertension, Hypokalemia & Alkalosis.oIncreased activity of the Epithelial Sodium Channel (E-Na Ch):-Activating kidneys to excrete potassium retaining excessive sodium & water, leading to hypertension.-Classically manifest severe hypertension with hypokalemia, unresponsive to spironolactone yet sensitive to amiloride.oHypertension & hypokalemia are, however, variable aspects of the Liddle's phenotype; more consistent features include a blunted aldosteirone response to ACTH & reduced urinary aldosterone excretion.oIt is a 'gain of function' mutation in the gene encoding ENaC of the collecting tubule resulting in autonomous function of these channel without the influence of aldosterone.oCan be differentiated from Primary Hyperaldosteronism by normal Na+ level and low aldosterone and reninOther OptionsCONGENITAL HYPOKALEMIA ASSOCIATED SYNDROMES[?]Bartter's Syndrome (BS):-Loss of the transport functions of the TALH nephron segments causes hereditary hypokalemic alkalosis.-Typically suffer from polyuria & polydipsia, due to the reduction in renal concentrating ability. May have an increase in urinary calcium excretion & 20% are hypomagnesemia-Marked activation of the renin-angiotensin-aldosterone axis.-Antenatal patients suffer from marked electrolyte wasting, polyhydramnios, and hypercalciuria with nephrocalcinosis; renal prostaglandin synthesis and excretion are significantly increased, accounting for much of the systemic symptoms.-Presence of five disease genes for BS, all of them functioning in some aspect of regulated Na+,K+ & Cl- transport by the TALH.[?]Gitelman's Syndrome (GS):-Loss of the transport functions of the DCT nephron segments causes hereditary hypokalemic alkalosis.-Genetically homogeneous, caused almost exclusively by loss-of-function mutations in thiazide-sensitive Na+-Cl- co transporter of DCT.-Uniformly hypomagnesemic & exhibit marked hypocalciuria, rather than the hypercalciuria typically seen in BS; urinary calcium excretion is thus a critical diagnostic test in GS.-May suffer from chondrocalcinosis, an abnormal deposition of Calcium Pyrophosphate Dihydrate (CPPD) in joint cartilage.[?]Distal Renal Tubular Acidosis:-Defects in multiple renal tubular transport pathways are associated with hypokalemia.-Loss-of-function mutations in subunits of the acidifying-H+-ATPase in alpha-intercalated cells cause hypokalemic distal renal tubular acidosis, as do many acquired disorders of the distal nephron.[?]Cushing's Syndrome:-Hypokalemia may also occur with systemic increasing in glucocorticoids.-Increase in pituitary ACTH incidence of hypokalemia is only 10%, whereas, 60-100% in patients with ectopic secretion of ACTH.
Liddle syndrome
Bartter syndrome
Gitelman syndrome
Renal tubular acidosis
Fluid & Electrolyte