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Effects of carbon dioxide and pH variations in vitro on blood respiratory functions, red blood cell volume, transmembrane pH gradients, and sickling in sickle cell anemia

Journal Article · · J. Lab. Clin. Med.; (United States)
OSTI ID:6166141

An examination was made of the O/sub 2/ affinity, Bohr effect, transmembrane pH gradient, mean cell hemoglobin concentration, and red blood cell sickling at half O/sub 2/ saturation in whole sickle cell (SS) and normal (AA) blood during CO/sub 2/ titration and acid-base titration at three Pco/sub 2/ levels, 10, 40, and 80 mm Hg. The CO/sub 2/-induced Bohr effect of SS blood was considerably larger than normal (maximum, 0.91, referred to cell pH) and similar to that found with acid-base titration at Pco/sub 2/ of 40. In contrast to AA blood, SS blood showed an increased O/sub 2/ affinity when Pco/sub 2/ was raised from 40 to 80, and at half O/sub 2/ saturation showed biphasic or sigmoid Bohr curves, a fall in transmembrane pH gradient with rising Pco/sub 2/, and an absence of the normal cell volume increase at low pH and Pco/sub 2/. Sickling of SS cells at half O/sub 2/ saturation was partly inhibited by increasing Pc/sub 2/, particularly in the higher pH ranges. These complex differences in the behavior of SS blood are interpreted in terms of the balancing of several effects: the lowering of hemoglobin O/sub 2/-affinity by polymerization, low pH and increased CO/sub 2/ binding, inhibition of hemoglobin S polymerization by CO/sub 2/ binding to ..beta../sup s/-chain amino termini, differences between hemoglobin S and A in competitive binding of CO/sub 2/ and 2,3-diphosphoglycerate at different pH levels, and an increased net negative charge exhibited by intracellular deoxyhemoglobin S polymers. From a clinical standpoint, in the absence of hypoxia or acidosis, an increased blood Pco/sub 2/ might have a beneficial effect by inhibiting red blood cell sickling, whereas a metabolic acidosis, with low blood pH and Pco/sub 2/, would be very hazardous.

Research Organization:
Albert Einstein Coll. of Medicine, Bronx, NY
OSTI ID:
6166141
Journal Information:
J. Lab. Clin. Med.; (United States), Journal Name: J. Lab. Clin. Med.; (United States) Vol. 104:2; ISSN JLCMA
Country of Publication:
United States
Language:
English