Chronic respiratory alkalosis induces renal PTH-resistance, hyperphosphatemia and hypocalcemia in humans

Abstract

The effects of chronic respiratory alkalosis on divalent ion homeostasis have not been reported in any species. We studied four normal male subjects during a four-day control period (residence at 500 m), during six days of chronic respiratory alkalosis induced by hypobaric hypoxia (residence at 3450 m), followed by a six-day eucapnic recovery period (500 m) under metabolic balance conditions. Chronic respiratory alkalosis (delta PaCO2, -8.4 mm Hg, delta[H+] -3.2 nmol/liter) resulted in a sustained decrement in plasma ionized calcium concentration (delta[IoCa++]p, -0.10 mmol/liter, P less than 0.05) and a sustained increment in plasma phosphate concentration (delta[PO4]p, +0.14 mmol/liter, P less than 0.005) associated with increased fractional excretion of Ca++ (+0.5%, P less than 0.005), decreased phosphate clearance (-6.1 ml/min, P less than 0.025) and decreased excretion of nephrogenous cAMP (-1.5 nmol/100 ml GFR, P less than 0.0025). Urinary phosphate excretion decreased by 15.4 mmol/24 hr on day 1 of chronic respiratory alkalosis (P less than 0.0025), but returned to control values by day 6 despite hyperphosphatemia. Serum intact [PTH] did not change. Sustained hypomagnesuria (-0.8 mmol/24 hr, P less than 0.05) occurred during chronic respiratory alkalosis and was accounted for, at least in part, by decreased fractional excretion of Mg++ (-0.7%, P less than 0.05) in the absence of change in plasma magnesium concentration. Serum 1,25(OH)2D levels were unchanged by chronic respiratory alkalosis. In conclusion, the decrease in nephrogenous cAMP generation despite unchanged serum intact PTH concentration suggests that chronic respiratory alkalosis results in impaired renal responsiveness to PTH as manifested by alterations in PTH-dependent renal calcium and phosphate transport.(ABSTRACT TRUNCATED AT 250 WORDS)

The interrelationship of serum 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in pregnancy at term: a meta-analysis

“…16,46 Many hormones such as PTH, estrogens, prolactin, and human placental lactogen may apparently be involved in the regulation of calcium homeostasis in pregnancy, while it has been suggested that vitamin D does not have an important role in the increased intestinal calcium absorption during pregnancy. 16 The possibility that the hypercortisolism of pregnancy 47 may be a cause of some degree of vitamin D resistance and the effects on calcium homeostasis of the chronic respiratory alkalosis 48 commonly affecting pregnant women should also be considered.…”

The Human Response to Acute Enteral and Parenteral Phosphate Loads

“…Electrolyte values in plasma and urine were determined as described previously. [35][36][37] Blood and urine pH and PCO 2 were measured with a Radiometer (Copenhagen model ABL 500 or 700) and HCO 3 calculated. Urinary ammonium was analyzed by ion chromatography.…”

Mechanisms of Hypocalcemia in Alcoholic Patients

“…Furthermore, in 2 patients with calciuria, severe respiratory alkalosis (arterial pH 17.50) and hyperphosphatemia (serum phosphorus 4.7 and 4.95 mg/dl) were observed. It has been suggested that severe respiratory alkalosis could induce renal PTH resistance resulting in hyperphosphatemia, calciuria and hypocalcemia [8].Finally, a further cause of hypocalcemia in 3 patients with chronic pancreatitis could be vitamin D 3 deficiency due to its decreased intestinal absorption [9].We conclude that hypocalcemia is frequently observed in alcoholic patients due to various pathophysiologic mechanisms. …”