ESSENTIALS OF DIAGNOSIS
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 FGF-23 are associated with urinary phosphorous wasting with rickets or osteomalacia.
Table 21–8.Causes of hypophosphatemia. ||Download (.pdf) Table 21–8. Causes of hypophosphatemia.
Decreased intestinal absorption
Parenteral alimentation with inadequate phosphate content
Malabsorption syndrome, small bowel bypass
Absorption blocked by oral antacids with aluminum or magnesium
Vitamin D–deficient and vitamin D–resistant osteomalacia
Increased urinary excretion
Phosphaturic drugs: theophylline, diuretics, bronchodilators, corticosteroids
Hyperparathyroidism (primary or secondary)
Renal tubular defects with excessive phosphaturia (congenital, Fanconi syndrome induced by monoclonal gammopathy, heavy metal poisoning), alcohol use disorder
Inadequately controlled diabetes mellitus
Phosphatonins of oncogenic osteomalacia (eg, FGF23 production)
Transcellular shift of phosphorus
Administration of glucose
Anabolic steroids, estrogen, oral contraceptives, beta-adrenergic agonists, xanthine derivatives
Hungry bone syndrome
Acute respiratory alkalosis
Abnormal losses followed by inadequate repletion
Diabetes mellitus with acidosis, particularly during aggressive therapy
Recovery from starvation or prolonged catabolic state
Chronic alcohol use disorder, particularly during restoration of nutrition; associated with hypomagnesemia
Recovery from severe burns
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.
While the etiology of hypophosphatemia is often determined from ...