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What happens to the oxygen-dissociation curve of hemoglobin in response to chronic hypoxia or anemia?
What happens to the oxygen-dissociation curve of hemoglobin in response to chronic hypoxia or anemia?
What is the effect of an increase in pCO2 on the release of oxygen from hemoglobin?
What is the effect of an increase in pCO2 on the release of oxygen from hemoglobin?
What is the role of 2,3-bisphosphoglycerate (2,3-BPG) in the oxygen-dissociation curve of hemoglobin?
What is the role of 2,3-bisphosphoglycerate (2,3-BPG) in the oxygen-dissociation curve of hemoglobin?
What is the effect of a decrease in pH on the oxygen-dissociation curve of hemoglobin?
What is the effect of a decrease in pH on the oxygen-dissociation curve of hemoglobin?
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What is the role of carbonic anhydrase in the Bohr effect?
What is the role of carbonic anhydrase in the Bohr effect?
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What is the effect of carbon monoxide (CO) on the oxygen-dissociation curve of hemoglobin?
What is the effect of carbon monoxide (CO) on the oxygen-dissociation curve of hemoglobin?
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What is the reason for the differential pH gradient between the lungs and peripheral tissues?
What is the reason for the differential pH gradient between the lungs and peripheral tissues?
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What is the mechanism of the Bohr effect?
What is the mechanism of the Bohr effect?
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What is the effect of 2,3-BPG on the oxygen-dissociation curve of hemoglobin?
What is the effect of 2,3-BPG on the oxygen-dissociation curve of hemoglobin?
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What happens to the affinity of hemoglobin for oxygen when 2,3-BPG is expelled?
What happens to the affinity of hemoglobin for oxygen when 2,3-BPG is expelled?
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Why does hemoglobin deficient in 2,3-BPG act as an oxygen 'trap'?
Why does hemoglobin deficient in 2,3-BPG act as an oxygen 'trap'?
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What is the effect of transfusing large quantities of 2,3-BPG-deficient blood?
What is the effect of transfusing large quantities of 2,3-BPG-deficient blood?
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How does inosine prevent the decrease of 2,3-BPG in stored blood?
How does inosine prevent the decrease of 2,3-BPG in stored blood?
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What is the effect of carbon monoxide binding to hemoglobin?
What is the effect of carbon monoxide binding to hemoglobin?
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Why does hemoglobin have a higher affinity for carbon monoxide than oxygen?
Why does hemoglobin have a higher affinity for carbon monoxide than oxygen?
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What can happen to the concentration of 2,3-BPG in red blood cells in response to chronic hypoxia?
What can happen to the concentration of 2,3-BPG in red blood cells in response to chronic hypoxia?
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What occurs to the mRNA precursor sequence before it can serve its function?
What occurs to the mRNA precursor sequence before it can serve its function?
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What is the result of the substitution of valine for glutamate in the β-globin chain?
What is the result of the substitution of valine for glutamate in the β-globin chain?
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What is the consequence of sickled cells blocking the flow of blood in narrow capillaries?
What is the consequence of sickled cells blocking the flow of blood in narrow capillaries?
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What is a factor that increases sickling and the severity of disease?
What is a factor that increases sickling and the severity of disease?
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What is the purpose of intermittent transfusions with packed red cells in patients with sickle cell anemia?
What is the purpose of intermittent transfusions with packed red cells in patients with sickle cell anemia?
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What is the result of the polymerization of HbS inside red blood cells?
What is the result of the polymerization of HbS inside red blood cells?
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What is the benefit of hydroxyurea in sickle cell anemia?
What is the benefit of hydroxyurea in sickle cell anemia?
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What is an example of a hemoglobinopathy caused by the synthesis of insufficient quantities of normal hemoglobin subunits?
What is an example of a hemoglobinopathy caused by the synthesis of insufficient quantities of normal hemoglobin subunits?
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What is the purpose of aggressive antibiotic therapy in the treatment of sickle cell anemia?
What is the purpose of aggressive antibiotic therapy in the treatment of sickle cell anemia?
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Why are heterozygotes for the sickle cell gene less susceptible to malaria?
Why are heterozygotes for the sickle cell gene less susceptible to malaria?
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What is the main difference between hemoglobin S and hemoglobin C?
What is the main difference between hemoglobin S and hemoglobin C?
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What is the characteristic of patients homozygous for hemoglobin C?
What is the characteristic of patients homozygous for hemoglobin C?
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What is the characteristic of patients with hemoglobin SC disease?
What is the characteristic of patients with hemoglobin SC disease?
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What is a characteristic of patients with hemoglobin SC disease compared to sickle cell disease?
What is a characteristic of patients with hemoglobin SC disease compared to sickle cell disease?
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What often triggers an infarctive crisis in patients with hemoglobin SC disease?
What often triggers an infarctive crisis in patients with hemoglobin SC disease?
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Why is the high frequency of the HbS gene maintained among black Africans?
Why is the high frequency of the HbS gene maintained among black Africans?
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What is the primary reason for the premature death of cells initially destined to become mature red blood cells in β-thalassemia?
What is the primary reason for the premature death of cells initially destined to become mature red blood cells in β-thalassemia?
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What is the typical age range for death in individuals with β-thalassemia major if left untreated?
What is the typical age range for death in individuals with β-thalassemia major if left untreated?
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What is the difference between β-thalassemia minor and β-thalassemia major?
What is the difference between β-thalassemia minor and β-thalassemia major?
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What is the effect of the increasing use of bone marrow replacement therapy on patients with β-thalassemia major?
What is the effect of the increasing use of bone marrow replacement therapy on patients with β-thalassemia major?
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What is the characteristic of α-thalassemia?
What is the characteristic of α-thalassemia?
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Why do individuals with β-thalassemia major appear seemingly healthy at birth?
Why do individuals with β-thalassemia major appear seemingly healthy at birth?
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What is the consequence of regular transfusions in individuals with β-thalassemia major?
What is the consequence of regular transfusions in individuals with β-thalassemia major?
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What is the reason for the accumulation of α2γ2(HbF) and γ4(Hb Bart’s) in β-thalassemia?
What is the reason for the accumulation of α2γ2(HbF) and γ4(Hb Bart’s) in β-thalassemia?
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Study Notes
Oxygen-Dissociation Curve
- A sigmoidal oxygen-dissociation curve is essential for hemoglobin (Hb) to release oxygen efficiently in the tissues.
- A hyperbolic oxygen-dissociation curve would result in maximum affinity for oxygen throughout the oxygen pressure range, preventing oxygen delivery to the tissues.
Factors Affecting Oxygen Release
- pH: a decrease in pH enhances oxygen release from Hb (Bohr effect).
- pCO2: an increase in pCO2 enhances oxygen release from Hb.
- 2,3-Bisphosphoglycerate (2,3-BPG): binds to Hb, decreasing its oxygen affinity and shifting the oxygen-dissociation curve to the right.
- Chronic hypoxia or anemia: the oxygen-dissociation curve of Hb shifts to the right to cope with these conditions.
Bohr Effect
- The Bohr effect reflects the fact that deoxyHb has a greater affinity for protons than oxyHb.
- A mutation in one of the residues can result in hemoglobin variants with abnormally high oxygen affinity.
Effect of 2,3-BPG
- 2,3-BPG is expelled on oxygenation of Hb.
- In red blood cells, 2,3-BPG reduces the affinity of Hb for oxygen, shifting the oxygen-dissociation curve to the right.
- The concentration of 2,3-BPG in red blood cells increases in response to chronic hypoxia, enabling Hb to release oxygen efficiently at the partial pressures found in the tissues.
Carbon Monoxide (CO)
- CO binds tightly (but reversibly) to the Hb iron, forming carbon monoxyhemoglobin (HbCO).
- CO binds with an affinity 220 times more than oxygen.
- When CO binds to one or more of the four heme sites, Hb shifts to the relaxed conformation, causing the remaining heme sites to bind oxygen with high affinity.
Hemoglobinopathies
- Hemoglobinopathies are disorders caused by the production of a structurally abnormal Hb molecule, synthesis of insufficient quantities of normal Hb subunits, or both.
- Examples: sickle cell disease (HbS), hemoglobin C disease (HbC), thalassemia syndromes, and methemoglobinemia.
Sickle Cell Anemia
- The substitution of a nonpolar valine for a charged glutamate residue forms a protrusion on the β-globin.
- At low oxygen tension, HbS polymerizes inside the red blood cells, forming a gel, which assembles later to fibrous polymers, producing rigid, misshapen erythrocytes.
- Sickling leads to localized anoxia, causing pain and eventually death of cells in the vicinity of the blockage.
Factors Increasing Sickling
- Decreased oxygen tension
- Increased pCO2
- Decreased pH
- An increased concentration of 2,3-BPG in erythrocytes
Treatment of Sickle Cell Anemia
- Adequate hydration
- Analgesics
- Aggressive antibiotic therapy
- Transfusions in patients at high risk for fatal vasocculsions
- Hydroxyurea (an anti-tumor drug) decreases the frequency of painful crises and reduces mortality
Hemoglobin C Disease
- Patients homozygous for HbC have a relatively mild, chronic hemolytic anemia.
- No specific therapy is required.
Hemoglobin SC Disease
- Patients have both β-globin genes abnormal, although different from each other.
- Compared to sickle cell disease, hemoglobin levels tend to be higher in HbSC disease.
- Patients may remain well until they suffer an infarctive crisis, which can be fatal.
Thalassemias
- β-Thalassemias: synthesis of β-globin chains is decreased or absent, whereas α-globin chain synthesis is normal.
- α-Globin chains cannot form stable tetramers, causing premature death of cells.
- Individuals with β-globin gene defects have either β-thalassemia trait or β-thalassemia major.
- β-Thalassemia minor: individuals make some β-chains, and usually do not require specific treatment.
- β-Thalassemia major: infants require regular transfusions of blood, leading to iron overload and death between the ages of 15 and 25 years.
- Bone marrow replacement therapy has been a beneficial treatment for these patients.
α-Thalassemias
- Defects in which the synthesis of α-globin chains is decreased or absent.
- These defects are less common than β-thalassemias.
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Description
Learn about the sigmoidal oxygen-dissociation curve of hemoglobin and how factors like pH, pCO2, and 2,3-Bisphosphoglycerate affect oxygen release in the tissues.
