title: Acid-base physiology in uremia.
abstract: Chronic renal failure represents the most common disorder responsible for chronic stable metabolic acidosis. This type of metabolic acidosis has been characterized as "hyperchloremic" in pre-end-stage disease and the "anion-gap" form as the GFR falls below 20 ml/min. The early hyperchloremic, hyperkalemic variety may result from disease of the juxtaglomerular apparatus, a distal acidification defect, or volume depletion. The anion-gap acidosis of advanced renal disease occurs as a result of the inability of the diminished nephron mass to keep pace with the metabolic acid load which depletes extracellular fluid bicarbonate. Total ammonium excretion diminishes despite an adaptive increase in ammonia production per nephron. The observation that the serum bicarbonate rarely falls below 15 mEq/L and the anion gap stays below 20 mEq/L despite positive hydrogen ion balance attests to the important role of extrarenal buffers. Bone buffers, primarily calcium carbonate, titrate a portion of the excess hydrogen ions at the expense of progressive loss of bone salts. Parathyroid hormone (PTH) appears to be involved in the control of bone buffering capacity. Both PTH-dependent and PTH-independent mechanisms must therefore be considered. PTH mediates bone buffering capacity by activating intracellular shifts of calcium, phosphorus, and carbonate or by stimulation of bone carbonic anhydrase. A direct effect of pH on bone mineral mobilization has been demonstrated. Adequate alkali therapy to maintain serum bicarbonate levels of 20-22 mEq/L may prevent bone dissolution and minimize risk of volume overload.
mesh_terms: D000085:Acetates / Q000097:blood; D019342:Acetic Acid; D000137:Acid-Base Imbalance / Q000150:complications* / Q000188:drug therapy; D001639:Bicarbonates / Q000097:blood / Q000627:therapeutic use; D001842:Bone and Bones / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications; D008903:Minerals / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood; D014511:Uremia / Q000150:complications* / Q000503:physiopathology
chemical_list: D000085:Acetates; D001639:Bicarbonates; D008903:Minerals; D010281:Parathyroid Hormone; D019342:Acetic Acid