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Questions and Answers
During erythropoiesis, which of the following cellular changes contributes MOST directly to the cell's increased oxygen-carrying capacity?
During erythropoiesis, which of the following cellular changes contributes MOST directly to the cell's increased oxygen-carrying capacity?
- Decrease in the number of mitochondria.
- Condensation of chromatin within the nucleus.
- Gradual increase in hemoglobin synthesis. (correct)
- Extrusion of the nucleus.
A researcher is investigating factors affecting erythropoiesis. They observe that a cell line exhibits a normal decrease in cell volume and chromatin condensation, but fails to reduce cytoplasmic RNA levels. What is the MOST likely consequence of this failure on the cell's development?
A researcher is investigating factors affecting erythropoiesis. They observe that a cell line exhibits a normal decrease in cell volume and chromatin condensation, but fails to reduce cytoplasmic RNA levels. What is the MOST likely consequence of this failure on the cell's development?
- Increased mitochondrial activity.
- Uncontrolled cell division and proliferation.
- Inhibited hemoglobin synthesis. (correct)
- Premature extrusion of the nucleus.
Consider a cell undergoing erythropoiesis. If the process is interrupted such that the nuclear-to-cytoplasmic ratio remains abnormally high, which of the following cellular functions would be MOST directly compromised?
Consider a cell undergoing erythropoiesis. If the process is interrupted such that the nuclear-to-cytoplasmic ratio remains abnormally high, which of the following cellular functions would be MOST directly compromised?
- Production of ribosomal proteins.
- DNA repair mechanisms.
- Oxygen transport to peripheral tissues. (correct)
- Cellular respiration efficiency.
During erythropoiesis, a cell is observed to maintain a high number of mitochondria relative to its stage of development. How would this MOST likely affect the cell's ability to effectively perform its primary function once mature?
During erythropoiesis, a cell is observed to maintain a high number of mitochondria relative to its stage of development. How would this MOST likely affect the cell's ability to effectively perform its primary function once mature?
Which of the following changes occurring during erythropoiesis is LEAST likely to be directly involved in preparing the cell for efficient oxygen transport after it enters circulation?
Which of the following changes occurring during erythropoiesis is LEAST likely to be directly involved in preparing the cell for efficient oxygen transport after it enters circulation?
What is the role of transferrin in hemoglobin synthesis?
What is the role of transferrin in hemoglobin synthesis?
In erythropoiesis, what would be the most likely consequence of a genetic mutation that impairs the function of vitamin B6?
In erythropoiesis, what would be the most likely consequence of a genetic mutation that impairs the function of vitamin B6?
If porphyrin synthesis decreases, what compensatory mechanism ensures balanced hemoglobin production?
If porphyrin synthesis decreases, what compensatory mechanism ensures balanced hemoglobin production?
Why is the precise amino acid sequence in globin chains critical for hemoglobin function?
Why is the precise amino acid sequence in globin chains critical for hemoglobin function?
A patient is found to have a genetic defect resulting in the absence of beta-globin chain synthesis. Which compensatory mechanism would most likely occur to maintain oxygen transport?
A patient is found to have a genetic defect resulting in the absence of beta-globin chain synthesis. Which compensatory mechanism would most likely occur to maintain oxygen transport?
Which of the following scenarios would necessitate the careful consideration of geographic location as a diagnostic factor in determining anemia?
Which of the following scenarios would necessitate the careful consideration of geographic location as a diagnostic factor in determining anemia?
What is the consequence if the ferrous iron within the heme group of hemoglobin is replaced by ferric iron?
What is the consequence if the ferrous iron within the heme group of hemoglobin is replaced by ferric iron?
In hemoglobin synthesis, what is the origin of protoporphyrin IX, and how does the synthesis occur?
In hemoglobin synthesis, what is the origin of protoporphyrin IX, and how does the synthesis occur?
How does the quaternary structure of hemoglobin contribute to its function, and what is the significance of having both alpha and beta globin chains?
How does the quaternary structure of hemoglobin contribute to its function, and what is the significance of having both alpha and beta globin chains?
If a genetic mutation impairs the synthesis of porphyrin ring, what immediate effect would this have on the structure and function of hemoglobin?
If a genetic mutation impairs the synthesis of porphyrin ring, what immediate effect would this have on the structure and function of hemoglobin?
In cases of severe chronic anemia, what adaptation occurs in the bone marrow to compensate for the increased demand for erythrocytes?
In cases of severe chronic anemia, what adaptation occurs in the bone marrow to compensate for the increased demand for erythrocytes?
How does the reticulocyte differ from a mature erythrocyte in terms of its cytoplasmic composition and what staining technique is used to visualize this difference?
How does the reticulocyte differ from a mature erythrocyte in terms of its cytoplasmic composition and what staining technique is used to visualize this difference?
What is the significance of elevated reticulocyte counts in an adult patient, and what underlying physiological process does it typically indicate?
What is the significance of elevated reticulocyte counts in an adult patient, and what underlying physiological process does it typically indicate?
How do the normal red blood cell (RBC) reference ranges typically vary based on demographic factors, and what is the underlying physiological basis for these differences?
How do the normal red blood cell (RBC) reference ranges typically vary based on demographic factors, and what is the underlying physiological basis for these differences?
What is the role of erythropoietin (EPO) in the maturation of erythrocytes, and at which specific stage of erythropoiesis does it exert its primary influence?
What is the role of erythropoietin (EPO) in the maturation of erythrocytes, and at which specific stage of erythropoiesis does it exert its primary influence?
Which characteristic is exclusive to stem cells in the context of hematopoiesis, differentiating them from committed progenitor cells such as CFU-GEMM, BFU-E, and CFU-E?
Which characteristic is exclusive to stem cells in the context of hematopoiesis, differentiating them from committed progenitor cells such as CFU-GEMM, BFU-E, and CFU-E?
A researcher is investigating the bone marrow of a patient with acute anemia and observes a significant increase in cellularity. Which underlying mechanism would most likely explain this observation?
A researcher is investigating the bone marrow of a patient with acute anemia and observes a significant increase in cellularity. Which underlying mechanism would most likely explain this observation?
What morphological and functional distinctions differentiate a mature erythrocyte from a reticulocyte, specifically concerning their presence in circulation and oxygen-carrying capacity?
What morphological and functional distinctions differentiate a mature erythrocyte from a reticulocyte, specifically concerning their presence in circulation and oxygen-carrying capacity?
Flashcards
Erythropoiesis
Erythropoiesis
The process of red blood cell production.
Anaemia
Anaemia
A condition characterized by a deficiency of red blood cells or hemoglobin in the blood, resulting in pallor and fatigue.
Cell volume change in erythropoiesis
Cell volume change in erythropoiesis
During erythropoiesis, the cell volume decreases as the cell matures.
Chromatin during erythropoiesis
Chromatin during erythropoiesis
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Nucleus during erythropoiesis
Nucleus during erythropoiesis
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Male RBC Range
Male RBC Range
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Female RBC Range
Female RBC Range
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Stem Cell
Stem Cell
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CFU-GEMM
CFU-GEMM
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Reticulocyte
Reticulocyte
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Where does Haemoglobin Synthesis occur?
Where does Haemoglobin Synthesis occur?
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What delivers iron to the bone marrow?
What delivers iron to the bone marrow?
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Mature Erythrocyte
Mature Erythrocyte
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Hyperplastic Bone Marrow
Hyperplastic Bone Marrow
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Where does protoporphyrin synthesis occur?
Where does protoporphyrin synthesis occur?
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What is globin synthesis proportional to?
What is globin synthesis proportional to?
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What chains are included in the hemoglobin molecule?
What chains are included in the hemoglobin molecule?
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Hemoglobin Structure
Hemoglobin Structure
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Hemoglobin Synthesis
Hemoglobin Synthesis
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Heme Group
Heme Group
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Porphyrin Ring
Porphyrin Ring
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Study Notes
- Erythropoiesis is the process of red blood cell development
- As cells develop, their volume decreases along with chromatin condensation and nuclear to cytoplasmic ratio
- Nucleoli are lost, RNA in the cytoplasm decreases, and the amount of mitochondria decreases
- Hemoglobin synthesis gradually increases, and the nucleus is eventually extruded
Red Blood Cell Maturation
- Hematopoietic stem cells become common myeloid progenitor cells
- These become CFU-Mg/E cells which mature into BFU-E cells and then CFU-E cells
- CFU-E cells continue to develop
- A hematopoetic stem cell is an unspecified cell that gives rise to a specific specialized cell, such as a blood cell
- Stem cells are multipotential, cannot be morphologically identified, self-renew, and differentiate
- CFU-GEMM: Granulocyte, erythrocyte, monocyte, megakaryocyte
- BFU-E: Burst forming unit
- CFU-E: Colony forming unit
Stages of Red Blood Cell Development
- Pronormoblast: Round, 15-20 μm, dark basophilic cytoplasm, central nucleus with slightly clumped chromatin and 2-5 nucleoli
- Basophilic normoblast: Round, 12-18 μm, less basophilic cytoplasm than pronormoblast, coarse chromatin, no nucleoli seen
- Polychromatic normoblast: Round, 10-15 μm, polychromatic cytoplasm due to hemoglobinization, deep staining and coarse chromatin, no nucleoli
- Orthochromatic normoblast: Round, 7-12 μm, well hemoglobinized cytoplasm, nucleus begins to condense and become pyknotic, eccentric or partially extruded
- Reticulocyte: Cells stain bluish and are larger than normal red cells, stains with brilliant cresyl blue or new methylene blue; has no nucleus and circulates for 1-2 days, percentage can indicate anemia
- Red blood cell: Normal RBC is a biconcave disc of 7-7.7 μm
Mature Erythrocytes
- Biconcave disc with a size of 7-8 μm, volume of 80-100 fL
- Mature erythrocytes have pink/red cytoplasm and no nucleus
- They circulate for approximately 120 days
Reference Ranges for Erythrocytes
- Reference ranges for erythrocytes vary with sex, age, and geographic location
- Normal RBC counts in adults are 4.5-5.5 x 10^12/L for males and 4.0-5.0 x 10^12/L for females
- Infants and children have age-dependent normal values
Bone Marrow
- Bone marrow activity can increase 5-10 times in certain pathologic states, leading to increased hematopoiesis
- This increase is known as "Hyperplastic," where more yellow marrow is replaced by red marrow
- Hyperplasia occurs with ineffective or increased hematopoiesis, such as in acute or severe chronic anemia, or malignant disease where abnormal cells replace red and yellow marrow
Anemia
- Anemia prevents blood from supplying adequate oxygen for proper metabolic function
- Clinically, anemia is defined as a decrease in the normal concentration of hemoglobin, erythrocytes, or hematocrit
- The diagnosis of anemia depends on age, sex, geographic location, and other factors like lung disease, but functional/causative types of anemia
- Those from survival defects due to increased red bloodcell destruction or loss
- Proliferation defects with decreased red blood cell production
- Maturation defects from ineffective or decreased production of red blood cells
Anemia Types
- Hypoproliferative anemia involves decreased erythropoietin, iron, or marrow damage
- Hyperproliferative anemia involves hemolysis
- Ineffective anemia involves microcytic, normocytic, or macrocytic
Anemia Classifications
- Bone marrow can increase RBC production by 5-10 times the normal rate
- RBC survival time cannot be increased, only decreased
- Anemia develops if bone marrow production remains constant but RBC survival time decreases
- Increased erythropoiesis in bone marrow may increase reticulocytes
- Morphologic classification uses erythrocyte indices for classifying anemia; includes
- Macrocytic, Normochromic anemias caused by Folate or B12 deficiency, liver disease, or alcoholism
- Normocytic, Normochromic anemias caused by bone marrow failure, haemolytic anaemia, chronic renal failure, leukaemia, or metastatic malignancy
- Microcytic, Hypochromic anemias (most common) caused by iron deficiency, sideroblastic anemia, thalassemia, or chronic diseases
Diagnosis of Anemia
- Microcytic anemias can be further classified by hemoglobin amount: hypochromic or normochromic Clinical history and physical signs such as pallor, fatigue, weakness, dizziness, and dyspnea (shortness of breath) are useful in diagnosis
- Laboratory tests include: CBC, blood smear examination, reticulocyte count, iron studies (iron, TIBC, ferritin), Vitamin B12 and folate levels, erythropoietin level, and bone marrow examination (smear and trephine biopsy)
Hemoglobin Structure
- Hemoglobin has 4 polypeptide subunits
- Hemoglobin’s Heme group contains a porphyrin ring (protoporphyrin) and ferrous iron (which binds O2)
- Hemoglobin has two alpha chains and two beta chains
Hemoglobin Synthesis
- Hemoglobin is a tetrameric molecule, each subunit has a heme group and a globin chain
- Ferrous iron and the porphyrin ring (protoporphyrin IX) are in heme
- Protoporphyrin IX comes from glycine and succinyl coenzyme A in mitochondria
- One protoporphyrin binds iron to make heme
- Heme is a tetrapyrrole ring with ferrous iron in the center
- Ferrous iron binds oxygen; each heme subunit carries one oxygen molecule bound to ferrous iron
- Hemoglobin has two alpha and two beta globin chains
- Synthesis occurs in the mitochondria of developing red cells in bone marrow
- This depends on adequate iron supply and delivery, protoporphyrin synthesis, and globin synthesis
- Iron is delivered to the marrow by transferrin
- Protoporphyrin synthesis occurs in mitochondria of RBC precursors, mediated by EPO and vitamin B6
- Protoporphyrin + iron makes heme
Globin Synthesis
- The rate of globin synthesis is proportional to the rate of porphyrin synthesis
- Proper globin synthesis depends on genes
- Precise order of amino acids in the globin chains is critical to the structure and function of hemoglobin
- Chain designations are as follows: Alpha α, beta β, delta 6, epsilon ɛ, gamma y, zetaζ
- The globin chains consist of two alpha chains and two beta chains
- Hb A is the major (96-98%) normal adult Hb
- It consists of 2 identical α-chains, each with 141 amino acids; and 2 identical β-chains, with 146 amino acids each
- Hb F (<1.0% in adult) is the major hemoglobin of the fetus and the new born infant
- It has 2 α-chains (identical to those of Hb A)
- It has 2 γ-chains, with 146 amino acids residues, differ from β-chains
- Hb A2 (2% to 3.5%) of normal adult hemoglobin
- It contains 2 a-chains are the same as in Hb A and Hb F
- It contains 2 8-chains differ from β-chains in only 8 of their 146 amino acids
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