Oxygen‑Hemoglobin Dissociation Curve and Gas Transport
Concept Name
Oxygen Transport
Genetic Loci
HBA1, HBA2 (16p13.3) encode α‑globin; HBB (11p15.4) encodes β‑globin. Mutations cause thalassemias and hemoglobinopathies (HbS, HbC).
Intracellular Cascade
Oxygen binds cooperatively to heme iron in hemoglobin. The sigmoidal dissociation curve reflects this cooperativity. Right‑shift (increased P₅₀) by H⁺ (Bohr effect), CO₂ (Haldane effect), 2,3‑BPG, and temperature → facilitates O₂ delivery to tissues. Left‑shift by fetal Hb (HbF) facilitates O₂ uptake from maternal blood.
Required Cofactors
Iron (Fe²⁺) is essential for heme synthesis. 2,3‑bisphosphoglycerate (2,3‑BPG) is a glycolytic intermediate that binds to deoxyhemoglobin and lowers O₂ affinity.
Histology Stains
Congo red stain for amyloid deposition in transfusion‑related amyloidosis (rare). Iron stain (Prussian blue) identifies iron overload in thalassemia or hemochromatosis.
EM Findings
Erythrocytes appear as biconcave disks on EM. In sickle cell disease, polymerized HbS fibers form parallel arrays, distorting the cell into a sickle shape.
Knockout Phenotype
Knockout of HBA genes in mice is embryonic lethal. β‑globin knockout mice recapitulate β‑thalassemia major with severe anemia requiring transfusion.
Specific Toxins
Carbon monoxide (CO) binds hemoglobin with 200‑fold higher affinity than O₂, causing left‑shift and reducing O₂ delivery. Methemoglobinemia (Fe³⁺) from nitrites or dapsone reduces O₂‑carrying capacity and is treated with methylene blue.