Uremic Acidosis and Intracellular Buffering

Abstract

Skeletal muscle biopsies were performed in 16 controls and 15 non-dialysed end-stage chronic renal failure (CRF) patients presenting untreated metabolic acidosis. Intracellular bicarbonate, pH, water compartments and electrolytes were determined. In 8 of 15 patients muscle ATP and lactate were measured. Intracellular bicarbonate (HCO3i) and pH (pHi) were obtained by means of muscle total carbon dioxide method: a significant (p less than 0.001) reduction in both intracellular acid--base indexes was found in all patients (pHi 6.82 +/- 13 vs. 7.04 +/- 0.05; HCO3i 6.28 +/- 2.07 vs. 11.86 +/- 0.87). Total muscle as well as extracellular water was increased. Muscle sodium and chloride contents were also increased, while no change in potassium and magnesium was detected. A significant decrease of both muscle ATP and lactate was found. The data lead to the conclusion that chronic retention of acids in CRF results in a depletion of the muscle buffer pool and consequently in intracellular acidosis: the latter could be the main cause of the cell energy metabolism derangement described in uremia.

The Role of the Endocrine System in the Regulation of Acid–Base Balance by the Kidney and the Progression of Chronic Kidney Disease

“…This results in a bicarbonate space, a measure of acid buffering, of approximately 50% body weight measured in kilograms. Muscle provides the largest reservoir of buffers as it accounts for 40% of the body weight and is rich in physiological intracellular buffers such as bicarbonate, phosphate, proteins and metabolic intermediates of glucose oxidation which by tissue buffering can mitigate the impact of acid loads on systemic pH in individuals with normal kidney function and CKD [14,15]. Interestingly, the severity of the acidity of the intracellular compartment observed in uremic individuals did not correlate tightly with the extracellular pH so that extracellular pH did not appear to be a good indicator of the pH within muscle cells (6.82 in intreated CKD compared to 7.04 in individuals without CKD) [14].…”