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  • Severe hypophosphatemia may cause tissue hypoxia and rhabdomyolysis.

  • Renal loss of phosphate can be diagnosed by calculating the fractional excretion of phosphate (FEPO4).

  • PTH and FGF23 are the major factors that increase urine phosphate.


The etiology of hypophosphatemia can be categorized as decreased intestinal absorption, increased urinary excretion, or transcellular shift (Table 21–8). Hypophosphatemia may occur in the presence of normal phosphate stores. Serum phosphate levels decrease transiently after food intake, which stimulates endogenous insulin release. In patients with depleted phosphate stores, such as alcoholic or malnourished patients, carbohydrate intake can induce severe hypophosphatemia (refeeding syndrome). Acute respiratory alkalosis can lower serum phosphate concentrations by stimulating glycolysis. Several drugs can impair intestinal absorption of phosphate, particularly calcium-, magnesium-, and aluminum-containing antacids. Elevated PTH causes hypophosphatemia by inhibiting reabsorption in the kidney. Vitamin D deficiency decreases intestinal phosphate and calcium absorption with the resultant hypocalcemia stimulating PTH release, increasing urinary phosphate excretion. Generalized dysfunction in the proximal tubule (Fanconi syndrome) is characterized by hypophosphatemia, metabolic acidosis, glucosuria, and aminoaciduria. Mutations in FGF23 are associated with urinary phosphorous wasting with rickets or osteomalacia.

Table 21–8.Causes of hypophosphatemia.


A. Symptoms and Signs

Phosphorous is a key ingredient component of adenosine triphosphate (ATP), and clinical manifestations are related to ATP deficiency. Symptoms are rare until blood phosphate levels fall below 1.0 mg/dL and are more prominent with acute declines. Symptoms include weakness, paresthesias, and encephalopathy (irritability, confusion, dysarthria, seizures, and coma). Respiratory failure or failure to wean from mechanical ventilation may occur because of diaphragmatic weakness. Decreased myocardial contractility is uncommon but a serious manifestation. Chronic severe depletion may cause anorexia, pain in muscles and bones, and fractures.

B. Laboratory Findings


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