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Questions and Answers
What is one of the primary morphologic changes in the nucleus associated with red blood cell maturation?
What is one of the primary morphologic changes in the nucleus associated with red blood cell maturation?
Loss of nucleoli.
Describe the change in the cytoplasm as red blood cells mature.
Describe the change in the cytoplasm as red blood cells mature.
There is an increase in the proportion of the cytoplasm.
What pathway is responsible for the majority of ATP production in red blood cells?
What pathway is responsible for the majority of ATP production in red blood cells?
The Embden-Meyerhof pathway.
What is the role of NADPH in the Hexose Monophosphate pathway?
What is the role of NADPH in the Hexose Monophosphate pathway?
What enzyme deficiency is commonly associated with the production of Heinz bodies?
What enzyme deficiency is commonly associated with the production of Heinz bodies?
How does the Methemoglobin reductase pathway contribute to hemoglobin function?
How does the Methemoglobin reductase pathway contribute to hemoglobin function?
What is indicated by the decrease in the N:C ratio during the maturation of erythrocytes?
What is indicated by the decrease in the N:C ratio during the maturation of erythrocytes?
Name one of the four morphologic changes in the nucleus associated with overall maturation.
Name one of the four morphologic changes in the nucleus associated with overall maturation.
What are the primary components of hemoglobin?
What are the primary components of hemoglobin?
Where does heme synthesis begin, and what is the first product formed?
Where does heme synthesis begin, and what is the first product formed?
What is the final step in the production of heme, and which enzyme facilitates this step?
What is the final step in the production of heme, and which enzyme facilitates this step?
Identify the pathway taken from D-ALA to heme synthesis by listing at least two intermediate products.
Identify the pathway taken from D-ALA to heme synthesis by listing at least two intermediate products.
What role does the mitochondria play in heme synthesis?
What role does the mitochondria play in heme synthesis?
What is the role of 2,3 diphosphoglycerate (2,3-DPG) in oxygen delivery by hemoglobin?
What is the role of 2,3 diphosphoglycerate (2,3-DPG) in oxygen delivery by hemoglobin?
How does the composition of the RBC membrane contribute to RBC elasticity?
How does the composition of the RBC membrane contribute to RBC elasticity?
What happens to RBCs when hemoglobin viscosity increases?
What happens to RBCs when hemoglobin viscosity increases?
Describe the mechanism of macrophage-mediated hemolysis.
Describe the mechanism of macrophage-mediated hemolysis.
What is the effect of cholesterol levels on RBC tensile strength and elasticity?
What is the effect of cholesterol levels on RBC tensile strength and elasticity?
What is the importance of membrane proteins like Spectrin and Actin in RBCs?
What is the importance of membrane proteins like Spectrin and Actin in RBCs?
Explain how mechanical hemolysis occurs in blood vessels.
Explain how mechanical hemolysis occurs in blood vessels.
How does the permeability of the RBC membrane affect ionic balance?
How does the permeability of the RBC membrane affect ionic balance?
What is erythropoiesis and which hormone primarily regulates this process?
What is erythropoiesis and which hormone primarily regulates this process?
How long does it typically take for reticulocytes to mature from pronormoblasts?
How long does it typically take for reticulocytes to mature from pronormoblasts?
What is the primary stimulus for erythropoietin production?
What is the primary stimulus for erythropoietin production?
Describe a pronormoblast's characteristics in terms of size and nucleus.
Describe a pronormoblast's characteristics in terms of size and nucleus.
At which stage of erythropoiesis does hemoglobin synthesis become detectable?
At which stage of erythropoiesis does hemoglobin synthesis become detectable?
What is the N/C ratio for the polychromatophilic normoblast stage and why is it significant?
What is the N/C ratio for the polychromatophilic normoblast stage and why is it significant?
What happens to the nucleus of the orthchromic normoblast?
What happens to the nucleus of the orthchromic normoblast?
What is the lifespan of a mature erythrocyte?
What is the lifespan of a mature erythrocyte?
In what way can reticulocytes be distinguished from mature erythrocytes?
In what way can reticulocytes be distinguished from mature erythrocytes?
What color appearance do normal erythrocytes have and why?
What color appearance do normal erythrocytes have and why?
What is the primary function of hemoglobin in red blood cells?
What is the primary function of hemoglobin in red blood cells?
List the components of the molecular structure of Gower I hemoglobin.
List the components of the molecular structure of Gower I hemoglobin.
How does the oxygen affinity of hemoglobin change with partial pressure of oxygen?
How does the oxygen affinity of hemoglobin change with partial pressure of oxygen?
What effect does alkalinity have on the oxygen dissociation curve of hemoglobin?
What effect does alkalinity have on the oxygen dissociation curve of hemoglobin?
What is the normal hemoglobin concentration percentage for HbA in adults?
What is the normal hemoglobin concentration percentage for HbA in adults?
Describe the impact of low body temperature on hemoglobin's affinity for oxygen.
Describe the impact of low body temperature on hemoglobin's affinity for oxygen.
What changes occur in hemoglobin affinity under conditions that produce hypoxia?
What changes occur in hemoglobin affinity under conditions that produce hypoxia?
What is the oxygen-carrying capacity of 1 gram of hemoglobin?
What is the oxygen-carrying capacity of 1 gram of hemoglobin?
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Study Notes
Erythropoiesis
- Erythropoiesis is the differentiation of erythroid precursor cells into mature red blood cells (RBC).
- Erythropoietin (EPO) is the primary regulator, stimulated by hypoxia.
- The process from pronormoblasts to reticulocytes takes 3-5 days; reticulocytes mature further in the circulation for one day.
Stages of Erythropoiesis
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Pronormoblast/Rubriblast:
- Size: 14-20 µm; Nucleus: 1-2 nucleoli, fine chromatin; Cytoplasm: deeply basophilic; N/C ratio: 8:1.
- Intensive globin production, yielding up to 16 RBCs.
-
Basophilic Normoblast/Prorubricyte:
- Size: 12-17 µm; Nucleus: nucleoli typically not visible, slightly coarse chromatin; N/C ratio: 6:1.
- Detectable hemoglobin synthesis begins.
-
Polychromatophilic Normoblast/Rubricyte:
- Size: 10-15 µm; Nucleus: occupies half of the cell; N/C ratio: 4:1.
- Last stage capable of mitosis, first where hemoglobin synthesis is visible.
-
Orthochromic Normoblast/Metarubricyte:
- Size: 7-12 µm; Nucleus: small and non-functional; N/C ratio: 1:2.
- Near complete hemoglobin production; nucleus ejection occurs in this stage.
-
Reticulocyte/Diffusely Basophilic Erythrocyte:
- Size: 7-10 µm; Non-nucleated; Cytoplasm: pink to slightly pinkish-gray, visible RNA reticulum with supravital stain.
-
Erythrocyte/DiscoCYTE:
- Size: 6-8 µm; Non-nucleated; Biconcave shape, salmon pink appearance; lifespan of 120 days.
Morphologic Changes in Maturation
- Nucleus: Loss of nucleoli, size decrease, chromatin condensation, possible shape change, and eventual loss.
- Cytoplasm: Decrease in basophilia, increased cytoplasm proportion, appearance of granules.
Erythrocyte Nomenclature
- Terms include Pronormoblast, Rubriblast, Basophilic normoblast, Polychromatic normoblast, and Erythrocyte, each reflecting developmental stages.
Erythrocyte Metabolism
-
Embden-Meyerhof Pathway:
- Major energy source, anaerobic glycolysis yielding 2 ATP per glucose; common deficiency in pyruvate kinase.
-
Hexose Monophosphate Pathway:
- Aerobic glycolysis (10%); NADP reduction prevents hemoglobin denaturation; G6PD deficiency leads to Heinz bodies.
-
Methemoglobin Reductase Pathway:
- Maintains functioning hemoglobin (Fe2+) through NADPH reduction.
-
Rapoport-Luebering Pathway:
- Produces 2,3-DPG, regulating oxygen delivery by shifting hemoglobin’s oxygen affinity.
RBC Membrane Properties
- Deformability: Enables RBCs to stretch; decreased viscosity reduces flexibility.
- Elasticity: Membrane composition of 8% Carbohydrate, 52% Proteins, 40% Lipids; enzyme deficiencies affect tensile strength.
- Membrane Proteins:
- Integral: Glycophorin A for membrane negativity.
- Peripheral: Spectrin and actin maintain biconcavity.
- Osmotic Balance: Membrane impermeable to Na, K, Ca; permeable to water, HCO3, Cl. Damage leads to swollen RBCs.
Erythrocyte Destruction
-
Macrophage-mediated Hemolysis (Extravascular):
- Occurs in the spleen; glucose and ATP levels drop, leading to RBC phagocytosis.
-
Mechanical Hemolysis (Intravascular):
- Small RBC rupture due to turbulence; haptoglobin and hemopexin salvage hemoglobin, preventing iron loss.
Hemoglobin Metabolism
-
Structure: Composed of 4 globin chains and 4 heme groups (64,000 Da).
-
Synthesis:
- Heme synthesis involves multiple enzymatic steps in mitochondria and cytoplasm, where ferrous iron binds to protoporphyrin IX.
- Globin produced on ribosomes in cytoplasm; subunit composition determines hemoglobin type.
Normal Human Hemoglobins
- Types: Include Gower I, Gower II, Portland, fetal (HbF), adult (HbA), A2.
- Concentration: Typically 92-95% HbA, 2-3% HbA2, 1-2% HbF in adults.
Hemoglobin Function
- Responsible for oxygen transport (1g Hgb = 1.34 ml O2) and CO2 excretion.
Oxygen Dissociation Curve
- Describes relation between pO2 and hemoglobin oxygen content; sigmoid shape reflects affinity changes.
- Bohr Effect: pH changes shift the curve to alter oxygen delivery.
Factors Influencing Oxygen Affinity
- Left Shift: Increased affinity, leading to decreased delivery (factors: alkalinity, low 2-3 DPG).
- Right Shift: Decreased affinity, enhancing oxygen delivery (factors: acidity, high CO2, high temperature).
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