Calcitriol metabolism during chronic metabolic acidosis.
Chronic metabolic acidosis causes a profound disturbance in renal proximal tubule 1OHase activity through perturbation of the normal ionic and hormonal controls of the enzyme activity. A lack of enzyme stimulation in response to hypophosphatemia and a paradoxical response of increased 1OHase activity to increased extracellular phosphorus are the important extracellular markers of deranged P control of 1OHase activity during chronic metabolic acidosis. 1OHase activity is down-regulated during chronic metabolic acidosis by an increase in renal cortical tubule mitochondrial calcium content and a functional abnormality in calcium handling, a reduction in extramitochondrial buffering capacity. There is a defect in PTH regulation of 1OHase during chronic metabolic acidosis, despite PTH levels which are inappropriately normal in relation to ionized hypercalcemia. PTH-directed cAMP accumulation is likely normal as well. Metabolic clearance of calcitriol is increased during chronic metabolic acidosis. Thus, the hormonal stimulus to maintain calcium and phosphorus homeostasis, calcitriol, is so altered by chronic metabolic acidosis that it is easy to understand the profound clinical effects of the acidosis on the skeleton of growing children. Chronic metabolic acidosis has allowed a greater understanding of the complex regulatory physiology that underlies renal proximal tubular 1OHase activity and calcitriol metabolism.
Langman
C B
CB
Northwestern University Medical School, Department of Pediatrics, Children's Memorial Hospital, Chicago.
D000141:Acidosis, Renal Tubular / Q000378:metabolism*; D002116:Calcitonin / Q000502:physiology; D002117:Calcitriol / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D013006:Growth Hormone / Q000502:physiology; D006801:Humans; D010281:Parathyroid Hormone / Q000502:physiology; D010758:Phosphorus / Q000502:physiology
D010281:Parathyroid Hormone; D010758:Phosphorus; D013006:Growth Hormone; D002116:Calcitonin; D002117:Calcitriol; D002118:Calcium