Porth's Essentials of Pathophysiology, 4e

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Disorders of Fluid, Electrolyte, and Acid–Base Balance

C h a p t e r 8

Diuretics and sodium chloride can be administered to increase urinary elimination of calcium after the ECF volume has been restored. Loop diuretics commonly are used rather than thiazide diuretics, which increase calcium reabsorption. The initial lowering of calcium levels is followed by measures to inhibit bone reabsorption. Drugs that are used to inhibit calcium mobilization include bisphos- phonates, calcitonin, and corticosteroids. 3,40 The bisphosphonates, which act mainly by inhibiting osteo- clastic activity, provide a significant reduction in cal- cium levels with relatively few side effects. Calcitonin inhibits osteoclastic activity, thereby decreasing bone resorption. The corticosteroids inhibit the conversion of vitamin D to its active form and are used to treat hypercalcemia due to vitamin D toxicity and hemato- logic malignancies. Disorders of Phosphorus Balance Phosphorus is mainly located in bone (about 85%) and in the ICF (about 14%). 3 Only about 1% is in the ECF compartment, and of that, only a minute propor- tion is in the plasma. In the adult, the normal serum phosphorus level ranges from 2.5 to 4.5 mg/dL (0.8 to 1.45 mmol/L). 3 Levels in children are greater, prob- ably because of increased levels of growth hormone and decreased levels of gonadal hormones. Regulation of Phosphorus Balance Phosphorus is ingested in the diet and eliminated in the urine. It is derived from many dietary sources, includ- ing milk and meats. About 50% to 65% of ingested phosphorus is absorbed in the intestine, primarily in the jejunum. 35 Absorption is diminished by concurrent ingestion of substances that bind phosphorus, includ- ing calcium, magnesium, and aluminum. Renal elimi- nation of phosphate is then regulated by an overflow mechanism in which the amount of phosphate lost in the urine is directly related to phosphate concentrations in the blood. Phosphorus exists in two forms within the body— inorganic and organic. The inorganic form (phosphate [H 2 PO 4 – or HPO 4 2 –]) is the principal circulating form of phosphorus and is the form that is routinely mea- sured (and reported as phosphorus) for laboratory pur- poses. 3,36 Most of the intracellular phosphorus is in the organic form (e.g., nucleic acids, phospholipids, adenos- ine triphosphate [ATP]). Phosphorus is essential to many bodily functions. 35 It plays a major role in bone formation; is essential to a number of metabolic processes, including the forma- tion of ATP and the enzymes needed for glucose, fat, and protein metabolism; is a necessary component of several vital parts of the cell, being incorporated into the nucleic acids of DNA and RNA and the phospholipids of the cell membrane; and serves as an acid–base buffer in the ECF and in the kidney. Delivery of oxygen by the red blood cell depends on organic phosphorus in ATP and 2,3-diphosphoglycerate (2,3-DPG). Phosphorus is

The milk-alkali syndrome is caused by the ingestion of calcium (often in the form of milk) and absorable ant- acids, particularly calcium carbonate. 42 The condition is characterized by hypercalcemia, hyperphosphatemia, alkalosis, and progressive renal failure. Because of the availability of nonabsorbable antacids, the condition is seen less frequently than in the past, but it may occur in women who are overzealous in taking calcium prepa- rations for osteoporosis prevention. Discontinuation of the antacid repairs the alkalosis and increases calcium elimination. A variety of drugs elevate calcium levels. 36 The use of lithium to treat bipolar disorders has been shown to cause hyperparathyroidism and hypercalcemia in some people. The thiazide diuretics increase calcium reab- sorption in the distal convoluted tubule of the kidney. Although the thiazide diuretics seldom cause hyper- calcemia, they can unmask hypercalcemia from other causes such as underlying bone disease and conditions that increase bone resorption. Manifestations. The signs and symptoms of calcium excess reflect a decrease in neural excitability, alterations in cardiac and smooth muscle function, and exposure of the kidneys to high concentrations of calcium 3,35,40 (see Table 8-6). There may be a dulling of conscious- ness, stupor, weakness, and muscle flaccidity. Behavioral changes may range from subtle alterations in personality to acute psychoses. The heart responds to elevated lev- els of calcium with increased contractility and ventricu- lar arrhythmias. Digitalis accentuates these responses. Gastrointestinal symptoms include constipation, anorexia, nausea, and vomiting, reflecting a decrease in smooth muscle activity. Bone pain can occur with hyper- parathyroidism or malignancy. Excess PTH can lead to bone reabsorption with development of bone cysts or osteoporosis. High calcium concentrations in the urine filtrate impair the ability of the kidneys to concentrate urine by interfering with the action of ADH (an example of nephrogenic DI). This causes salt and water diuresis and an increased sensation of thirst. Hypercalciuria also predisposes to the development of renal calculi. Pancreatitis is another potential complication of hyper- calcemia and is probably related to stones in the pan- creatic ducts. Hypercalcemic crisis describes an acute life- threatening increase in the serum calcium level. 43 Hyperparathyroidism and malignant disease are the major causes of hypercalcemic crisis. Manifestations reflect those of severe hypercalcemia including polyuria, excessive thirst, dehydration, excessive muscle weak- ness, cardiac arrhythmias, disturbed mental state, and altered levels of consciousness. Treatment. Treatment of calcium excess usually is directed toward rehydration and use of measures to increase urinary excretion of calcium and inhibit release of calcium from bone. 40 Fluid replacement is needed in situations of volume depletion. The excre- tion of sodium is accompanied by calcium excretion.