Chronic respiratory alkalosis induces renal PTH-resistance, hyperphosphatemia and hypocalcemia in humans.
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)
Krapf
R
R
Department of Medicine, Insel University Hospital, Berne, Switzerland.
Jaeger
P
P
Hulter
H N
HN
D000328:Adult; D000472:Alkalosis, Respiratory / Q000097:blood / Q000503:physiopathology*; D001274:Atmospheric Pressure; D002908:Chronic Disease; D004351:Drug Resistance; D006706:Homeostasis; D006801:Humans; D006887:Hydroxycholecalciferols / Q000097:blood; D006996:Hypocalcemia / Q000209:etiology* / Q000378:metabolism; D016857:Hypocapnia / Q000503:physiopathology; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood / Q000502:physiology*; D010710:Phosphates / Q000097:blood* / Q000378:metabolism
D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D010710:Phosphates