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

the condition leads to joint stiffness, bone pain, and skeletal deformities consistent with osteomalacia (see Chapter 44). Treatment. The treatment of hypophosphatemia is usually directed toward prophylaxis. This may be accomplished with dietary sources high in phosphorus (one glass of milk contains approximately 250 mg of phosphorus) or with oral or intravenous replacement solutions. Phosphorus supplements usually are contra- indicated in hyperparathyroidism, chronic kidney dis- ease, and hypercalcemia because of the increased risk of extracellular calcifications. Hyperphosphatemia Hyperphosphatemia represents a serum phosphorus concentration in excess of 4.5 mg/dL (1.45 mmol/L) in adults. Moderate hyperphosphatemia exists when serum phosphate is in the range of 4.6 to 6.0 mg/dL (1.49 to 1.94 mmol/L) and severe phosphatemia when serum phosphate levels are greater than 6.0 (1.94 mmol/L). 3 Hyperphosphatemia can result from failure of the kidneys to excrete excess phosphate, rapid redistri- bution of intracellular phosphate to the ECF com- partment, or high phosphate intake. 3,45 Because phosphorus is primarily eliminated by the kidneys, hyperphosphatemia due to impaired renal function is a common electrolyte disorder in persons with chronic kidney disease 3,46 (see Chapter 26). Release of intracellular phosphorus can result from conditions such as massive tissue injury, rhabdomyolysis (muscle dissolution), heat stroke, potassium deficiency, and seizures. The administration of excess phosphate-containing antacids, laxatives, or enemas can be another cause of hyperphosphatemia, especially when there is a decrease in vascular volume and a reduced glomerular filtration rate. Phosphate-containing laxa- tives and enemas predispose to hypovolemia and a decreased glomerular filtration rate by inducing diar- rhea, thereby increasing the risk of hyperphosphate- mia. Serious and even fatal hyperphosphatemia has reportedly resulted from administration of phosphate enemas. 47 Manifestations. Many of the signs and symptoms of a phosphate excess are related to a calcium deficit (see Table 8-7). Because of the reciprocal relationship between calcium and phosphorus levels, a high serum phosphate level tends to lower serum calcium levels, which can lead to tetany and other signs of hypocal- cemia. 3 Inadequately treated hyperphosphatemia in chronic kidney disease can lead to renal bone disease, and extraosseous calcifications in soft tissues (see Chapter 26). A secondary effect of hyperphosphate- mia in chronic kidney disease is stimulation of nodular hyperplasia of the parathyroid glands that results in a secondary hyperparathyroidism. 46 Treatment. The treatment of hyperphosphatemia is directed at the cause of the disorder. Dietary restriction

of foods that are high in phosphorus may be used. Calcium-based phosphate binders are useful in chronic hyperphosphatemia. Sevelamer, a recently approved calcium- and aluminum-free phosphate binder, is as effective as a calcium-based binder, but lacks its adverse effects. 3 Hemodialysis is used to reduce phosphate levels in persons with chronic kidney disease. Disorders of Magnesium Balance Magnesium is the second most abundant intracellular divalent cation. 48–50 Although the average adult has approximately 24 g of magnesium distributed through- out the body, only an estimated 2% is distributed in the ECF. 50,51 The normal serum concentration of magnesium is 1.3 to 2.1 mg/dL (0.65 to 1.1 mmol/L). 3 Regulation of Magnesium Balance Magnesium is ingested in the diet, absorbed from the intestine, and excreted by the kidneys. Intestinal absorp- tion is not closely regulated, and only about 30% to 50% of dietary magnesium is absorbed. 48 The kidney is the principal organ of magnesium regulation. The kidneys filter about 80% of the serum magnesium and only about 3% is excreted in the urine, although this amount can be influenced by other conditions and medi- cations. 48 Renal reabsorption is stimulated by PTH and is decreased in the presence of increased serum levels of magnesium and calcium. Magnesium is a cofactor in hundreds of metabolic reactions in the body. It is required for cellular energy metabolism, functioning of the Na + /K + -ATPase mem- brane pump, membrane stabilization, nerve conduction, and ion transport. It also acts as a cofactor in many intracellular enzyme reactions, including the transfer of high-energy phosphate groups in the generation of ATP from adenosine diphosphate (ADP). It is essential to all reactions that require ATP, for every step related to rep- lication and transcription of DNA, and for translation of messenger RNA. 3,48–50 Magnesium also participates in potassium and cal- cium channel activity. Magnesium blocks the outward movement of potassium in cardiac cells, preventing the development of cardiac arrhythmias. 51 It also acts as a smooth muscle relaxant by altering calcium levels that are responsible for muscle contraction. Because of its smooth muscle relaxing effect, there has been a recent interest in the use of magnesium in the treatment of severe bronchial asthma. 56 In addition, it has been suggested that magnesium may have an anticonvulsant effect. Currently, it is the first-line drug in the prevention and treatment of seizures associated with eclampsia in pregnant women (see Chapter 18). 52 Hypomagnesemia Magnesium deficiency refers to depletion of total body stores and hypomagnesemia to a low serum concentra- tion of less than 1.3 mg/dL (0.65 mmol/L). 3 It is seen in conditions that limit intake or increase intestinal or