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Rapid hemodialysis of uremic animals may induce a syndrome characterized by increased cerebrospinal fluid (CSF) pressure, grand mal seizures, and electroencephalographic abnormalities. There is a fall in pH and bicarbonate concentration in CSF, and brain osmolality exceeds that of plasma, resulting in a net movement of water into the brain. This syndrome has been called experimental dialysis disequilibrium syndrome. The fall in pH of CSF may be secondary to a fall of intracellular pH (pHi) in brain. Since changes in pHi can alter intracellular osmolality in other tissues, it was decided to investigate brain pHi in uremia, and the effects of hemodialysis. Brain pHi was measured by evaluating the distribution of 14C-labeled dimethadione in brain relative to CSF, while extracellular space was calculated as the 35504=/4 space relative to CSF. In animals with acute renal failure, brain (cerebral cortex) pHi was 7.06+/-0.02 (+/-SE) while that in CSF was 7.31+/-0.02, both values not different from normal. After rapid hemodialysis (100 min) of uremic animals, plasma creatinine fell from 11.8 to 5.9 mg/dl. Brain pHi was 6.89+/-0.02 and CSF pH and 7.19+/-0.02, both values significantly lower than in uremic animals (P less than 0.01), and there was a 12% increase in brain water content. After slow hemodialysis (210 min), brain pHi (7.01+/-0.02) and pH in CSF (7.27+/-0.02) were both significantly greater than values observed after rapid hemodialysis (P less than 0.01), and brain water content was normal. None of the above maneuvers had any effect on pHi of skeletal muscle or subcortical white matter. The data show that rapid hemodialysis of uremic dogs is accompanied by a significant fall in pH of CSF and pHi in cerebral cortex. Accompanying the fall in brain pHi is cerebral edema.

Central nervous system pH in uremia and the effects of hemodialysis.