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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.
J Lab Clin Med. 1984 Aug; 104(2):146-59.JL

Abstract

Findings that polymerization of hemoglobin S is an oxygen-linked function, and that CO2 has an O2 affinity-independent effect on deoxyhemoglobin S polymerization suggests that varying PCO2 might have different effects on respiratory functions and other red blood cell properties of blood in sickle cell anemia (SS) compared with normal blood (AA). We examined the O2 affinity, Bohr effect, transmembrane pH gradient, mean cell hemoglobin concentration, and red blood cell sickling at half O2 saturation in whole SS and AA blood during CO2 titration and acid-base titration at three PCO2 levels, 10, 40, and 80 mm Hg. The CO2-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 PCO2 of 40. In contrast to AA blood, SS blood showed an increased O2 affinity when PCO2 was raised from 40 to 80, and at half O2 saturation showed biphasic or sigmoid Bohr curves, a fall in transmembrane pH gradient with rising PCO2, and an absence of the normal cell volume increase at low pH and PCO2. Sickling of SS cells at half O2 saturation was partly inhibited by increasing PCO2, 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 O2-affinity by polymerization, low pH and increased CO2 binding, inhibition of hemoglobin S polymerization by CO2 binding to beta s-chain amino termini, differences between hemoglobin S and A in competitive binding of CO2 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 PCO2 might have a beneficial effect by inhibiting red blood cell sickling, whereas a metabolic acidosis, with low blood pH and PCO2, would be very hazardous.

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

6431043

Citation

Ueda, Y, and R M. Bookchin. "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." The Journal of Laboratory and Clinical Medicine, vol. 104, no. 2, 1984, pp. 146-59.
Ueda Y, Bookchin RM. 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. J Lab Clin Med. 1984;104(2):146-59.
Ueda, Y., & Bookchin, R. M. (1984). 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. The Journal of Laboratory and Clinical Medicine, 104(2), 146-59.
Ueda Y, Bookchin RM. 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. J Lab Clin Med. 1984;104(2):146-59. PubMed PMID: 6431043.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Ueda,Y, AU - Bookchin,R M, PY - 1984/8/1/pubmed PY - 1984/8/1/medline PY - 1984/8/1/entrez SP - 146 EP - 59 JF - The Journal of laboratory and clinical medicine JO - J Lab Clin Med VL - 104 IS - 2 N2 - Findings that polymerization of hemoglobin S is an oxygen-linked function, and that CO2 has an O2 affinity-independent effect on deoxyhemoglobin S polymerization suggests that varying PCO2 might have different effects on respiratory functions and other red blood cell properties of blood in sickle cell anemia (SS) compared with normal blood (AA). We examined the O2 affinity, Bohr effect, transmembrane pH gradient, mean cell hemoglobin concentration, and red blood cell sickling at half O2 saturation in whole SS and AA blood during CO2 titration and acid-base titration at three PCO2 levels, 10, 40, and 80 mm Hg. The CO2-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 PCO2 of 40. In contrast to AA blood, SS blood showed an increased O2 affinity when PCO2 was raised from 40 to 80, and at half O2 saturation showed biphasic or sigmoid Bohr curves, a fall in transmembrane pH gradient with rising PCO2, and an absence of the normal cell volume increase at low pH and PCO2. Sickling of SS cells at half O2 saturation was partly inhibited by increasing PCO2, 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 O2-affinity by polymerization, low pH and increased CO2 binding, inhibition of hemoglobin S polymerization by CO2 binding to beta s-chain amino termini, differences between hemoglobin S and A in competitive binding of CO2 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 PCO2 might have a beneficial effect by inhibiting red blood cell sickling, whereas a metabolic acidosis, with low blood pH and PCO2, would be very hazardous. SN - 0022-2143 UR - https://www.unboundmedicine.com/medline/citation/6431043/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_ DB - PRIME DP - Unbound Medicine ER -