Chapter 046. Sodium and Water (Part 13) pot

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 <1 mmol/L. However, a combination of factors may lead to a significant fall in the plasma K + concentration and may amplify the hypokalemia due to K + wasting. Metabolic alkalosis is often associated with hypokalemia. This occurs as a result of K + redistribution as well as excessive renal K + loss. Treatment of diabetic ketoacidosis with insulin may lead to hypokalemia due to stimulation of the Na + - H + antiporter and (secondarily) the Na + , K + -ATPase pump. Furthermore, uncontrolled hyperglycemia often leads to K + depletion from an osmotic diuresis (see below). Stress-induced catecholamine release and administration of β 2 - adrenergic agonists directly induce cellular uptake of K + and promote insulin secretion by pancreatic islet βcells. Hypokalemic periodic paralysis is a rare condition characterized by recurrent episodic weakness or paralysis (Chap. 382). Since K + is the major ICF cation, anabolic states can potentially result in hypokalemia due to a K + shift into cells. This may occur following rapid cell growth seen in patients with pernicious anemia treated with vitamin B 12 or with neutropenia after treatment with granulocyte-macrophage colony stimulating factor. Massive transfusion with thawed washed red blood cells (RBCs) could cause 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 increased integumentary and renal K + loss. Hyperaldosteronism, secondary to ECF volume contraction, enhances K + excretion in the urine (Chap. 336). Normally, K + lost in the stool amounts to 5–10 mmol/d in a volume of 100–200 mL. Hypokalemia subsequent to increased gastrointestinal loss can occur in patients with profuse diarrhea (usually secretory), villous adenomas, VIPomas, or laxative abuse. However, the loss of gastric secretions does not account for the moderate to severe K + 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 to achieve a K + deficit of 300–400 mmol typically seen in these patients. In fact, the hypokalemia is primarily due to increased renal K + excretion. Loss of gastric contents results in volume depletion and metabolic alkalosis, both of which promote kaliuresis. Hypovolemia stimulates aldosterone release, which augments K + secretion by the principal cells. In addition, the filtered load of HCO 3 – exceeds the reabsorptive capacity of the proximal convoluted tubule, thereby increasing distal delivery of NaHCO 3 , which enhances the electrochemical gradient favoring K + loss in the urine. Renal Loss of Potassium (See also Chap. 336) In general, most cases of chronic hypokalemia are due to renal K + wasting. This may be due to factors that increase the K + concentration in the lumen of the CCD or augment distal flow rate. Mineralocorticoid excess commonly results in hypokalemia. Primary hyperaldosteronism is due to dysregulated aldosterone secretion by an adrenal adenoma (Conn's syndrome) or carcinoma or to adrenocortical hyperplasia. In a rare subset of patients, the disorder is familial (autosomal dominant) and aldosterone levels can be suppressed by administering low doses of exogenous glucocorticoid. The molecular defect responsible for glucocorticoid-remediable hyperaldosteronism is a rearranged gene (due to a chromosomal crossover), containing the 5'-regulatory region of the 11β-hydroxylase gene and the coding sequence of the aldosterone synthase gene. Consequently, mineralocorticoid is synthesized in the zona fasciculata and regulated by corticotropin. A number of conditions associated with hyperreninemia result in secondary hyperaldosteronism and renal K + wasting. High renin levels are commonly seen in both renovascular and malignant hypertension. Renin-secreting tumors of the juxtaglomerular apparatus are a rare cause of hypokalemia. Other tumors that have been reported to produce renin include renal cell carcinoma, ovarian carcinoma, and Wilms' tumor. Hyperreninemia may also occur secondary to decreased effective circulating arterial volume. In the absence of elevated renin or aldosterone levels, enhanced distal nephron secretion of K + may result from increased production of non-aldosterone mineralocorticoids in congenital adrenal hyperplasia. Glucocorticoid-stimulated kaliuresis does not normally occur due to the conversion of cortisol to cortisone by 11β-hydroxysteroid dehydrogenase (11β-HSDH). Therefore, 11β-HSDH deficiency or suppression allows cortisol to bind to the aldosterone receptor and leads to the syndrome of apparent mineralocorticoid excess. Drugs that inhibit the activity of 11β-HSDH include glycyrrhetinic acid, present in licorice, chewing tobacco, and carbenoxolone. The presentation of Cushing's syndrome may include hypokalemia if the capacity of 11β-HSDH to inactivate cortisol is overwhelmed by persistently elevated glucocorticoid levels. . Chapter 046. Sodium and Water (Part 13) Redistribution into Cells Movement of K + into cells may transiently. (see below). Stress-induced catecholamine release and administration of β 2 - adrenergic agonists directly induce cellular uptake of K + and promote insulin secretion by pancreatic islet βcells of their K + during storage. Nonrenal Loss of Potassium Excessive sweating may result in K + depletion from increased integumentary and renal K + loss. Hyperaldosteronism, secondary