Chapter 046. Sodium and Water (Part 13)

Redistribution into Cells Movement of K+ into cells may transiently decrease the plasma K + concentration without altering total body K+ content. For any given cause, the magnitude of the change is relatively small, often
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Chapter 046. Sodium and Water (Part 13) Chapter 046. Sodium and Water (Part 13) Redistribution into Cells Movement of K+ into cells may transiently decrease the plasma K +concentration without altering total body K+ content. For any given cause, themagnitude of the change is relatively small, often secretion by pancreatic islet βcells. Hypokalemic periodic paralysis is a rarecondition characterized by recurrent episodic weakness or paralysis (Chap. 382).Since K+ is the major ICF cation, anabolic states can potentially result inhypokalemia due to a K+ shift into cells. This may occur following rapid cellgrowth seen in patients with pernicious anemia treated with vitamin B 12 or withneutropenia after treatment with granulocyte-macrophage colony stimulatingfactor. Massive transfusion with thawed washed red blood cells (RBCs) couldcause hypokalemia since frozen RBCs lose up to half of their K + during storage. Nonrenal Loss of Potassium Excessive sweating may result in K+ depletion from increasedintegumentary and renal K+ loss. Hyperaldosteronism, secondary to ECF volumecontraction, enhances K+ excretion in the urine (Chap. 336). Normally, K + lost inthe stool amounts to 5–10 mmol/d in a volume of 100–200 mL. Hypokalemiasubsequent to increased gastrointestinal loss can occur in patients with profusediarrhea (usually secretory), villous adenomas, VIPomas, or laxative abuse.However, the loss of gastric secretions does not account for the moderate to severeK+ depletion often associated with vomiting or nasogastric suction. Since the K +concentration of gastric fluid is 5–10 mmol/L, it would take 30–80 L of vomitus toachieve a K+ deficit of 300–400 mmol typically seen in these patients. In fact, thehypokalemia is primarily due to increased renal K+ excretion. Loss of gastriccontents results in volume depletion and metabolic alkalosis, both of whichpromote kaliuresis. Hypovolemia stimulates aldosterone release, which augmentsK+ secretion by the principal cells. In addition, the filtered load of HCO 3– exceedsthe reabsorptive capacity of the proximal convoluted tubule, thereby increasingdistal delivery of NaHCO3, which enhances the electrochemical gradient favoringK+ loss in the urine. Renal Loss of Potassium (See also Chap. 336) In general, most cases of chronic hypokalemia are dueto renal K+ wasting. This may be due to factors that increase the K + concentrationin the lumen of the CCD or augment distal flow rate. Mineralocorticoid excesscommonly results in hypokalemia. Primary hyperaldosteronism is due todysregulated aldosterone secretion by an adrenal adenoma (Conns syndrome) orcarcinoma or to adrenocortical hyperplasia. In a rare subset of patients, thedisorder is familial (autosomal dominant) and aldosterone levels can be suppressedby administering low doses of exogenous glucocorticoid. The molecular defectresponsible for glucocorticoid-remediable hyperaldosteronism is a rearrangedgene (due to a chromosomal crossover), containing the 5-regulatory region of the11β-hydroxylase gene and the coding sequence of the aldosterone synthase gene.Consequently, mineralocorticoid is synthesized in the zona fasciculata andregulated by corticotropin. A number of conditions associated withhyperreninemia result in secondary hyperaldosteronism and renal K + wasting.High renin levels are commonly seen in both renovascular and malignanthypertension. Renin-secreting tumors of the juxtaglomerular apparatus are a rarecause of hypokalemia. Other tumors that have been reported to produce renininclude renal cell carcinoma, ovarian carcinoma, and Wilms tumor.Hyperreninemia may also occur secondary to decreased effective circulatingarterial volume. In the absence of elevated renin or aldosterone levels, enhanced distalnephron secretion of K+ may result from increased production of non-aldosteronemineralocorticoids in congenital adrenal hyperplasia. Glucocorticoid-stimulatedkaliuresis does not normally occur due to the conversion of cortisol to cortisone by11β-hydroxysteroid dehydrogenase (11β-HSDH). Therefore, 11β-HSDHdeficiency or suppression allows cortisol to bind to the aldosterone receptor andleads to the syndrome of apparent mineralocorticoid excess. Drugs that inhibit theactivity of 11β-HSDH include glycyrrhetinic acid, present in licorice, chewingtobacco, and carbenoxolone. The presentation of Cushings syndrome may includehypokalemia if the capacity of 11β-HSDH to inactivate cortisol is overwhelmedby persistently elevated glucocorticoid levels.