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Discerning students have for years sensed there was something missing in understanding of linkage between buffering in extra- and intracellular fluids. At this time one can pinpoint the area
of confusion to the process of buffering of metabolic change by tissues other than blood. Unlike the red cell, utilization of buffer in the tissues can be clearly dissociated from the
change in the absolute value of pH. This dissociation is shown by the following data obtained in experiments with dogs. Intracellular pH of muscle was estimated by the bicarbonate method.
When the intracellular pH was lowered by 0.24 units with respiratory acidosis, the full equivalence of the tissue buffer utilization amounted only to 7.5 mEq. On the other hand, with
metabolic acidosis, 30 mEq were neutralized in the tissues while the muscle pH decreased a mere 0.04 units. In place of absolute values, metabolic buffering in the tissues relates to change
in the gradient of hydrogen ion concentrations across the cell membrane and hence to a unique and undescribed reaction sequence.
Despite the lack of understanding of mechanism, simple rationales meet requirements for clinical diagnosis. Change in the extracellular bicarbonate is proportional to the metabolic disorder
in the complete system. Small adjustments provide suitable correction for abnormal tensions of CO2: 1.0-1.3 mEq/liter in the bicarbonate concentration for each deviation of 10 mm Hg in the
Pco2. (NSF Grant GB 35524).
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