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Questions and Answers
What is the primary function of red blood cells (RBCs)?
What is the primary function of red blood cells (RBCs)?
How do hemoglobin molecules behave in relation to oxygen at varying concentrations?
How do hemoglobin molecules behave in relation to oxygen at varying concentrations?
Which characteristic of RBCs contributes to their lifespan limitation?
Which characteristic of RBCs contributes to their lifespan limitation?
What is the approximate diameter of mature red blood cells?
What is the approximate diameter of mature red blood cells?
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What role do RBCs play in carbon dioxide transport?
What role do RBCs play in carbon dioxide transport?
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What is a common symptom of iron deficiency anemia (IDA)?
What is a common symptom of iron deficiency anemia (IDA)?
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Which group is noted to have virtually no iron stores?
Which group is noted to have virtually no iron stores?
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What is the typical absorption percentage of iron from a meat-containing diet for individuals with iron deficiency?
What is the typical absorption percentage of iron from a meat-containing diet for individuals with iron deficiency?
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Which laboratory finding is characteristic of iron deficiency anemia?
Which laboratory finding is characteristic of iron deficiency anemia?
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What would you expect to find in a peripheral blood smear of someone with severe iron-deficiency anemia?
What would you expect to find in a peripheral blood smear of someone with severe iron-deficiency anemia?
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Which of the following is NOT a sign associated with iron deficiency anemia?
Which of the following is NOT a sign associated with iron deficiency anemia?
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What percentage of iron is typically absorbed from a vegetarian diet compared to a meat-containing diet?
What percentage of iron is typically absorbed from a vegetarian diet compared to a meat-containing diet?
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Which of these factors can lead to iron deficiency anemia due to blood loss?
Which of these factors can lead to iron deficiency anemia due to blood loss?
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What is the role of PfEMP1 in malaria infection?
What is the role of PfEMP1 in malaria infection?
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What percentage of erythrocytes typically leads to severe malaria complications?
What percentage of erythrocytes typically leads to severe malaria complications?
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Which of the following is NOT a feature of cerebral malaria?
Which of the following is NOT a feature of cerebral malaria?
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What is one of the severe complications associated with malaria?
What is one of the severe complications associated with malaria?
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What effect do male gametocytes have in the malaria lifecycle?
What effect do male gametocytes have in the malaria lifecycle?
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What initial changes occur in iron studies during the progression of iron deficiency?
What initial changes occur in iron studies during the progression of iron deficiency?
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What is a late sign of deficient iron stores as seen in iron deficiency anemia?
What is a late sign of deficient iron stores as seen in iron deficiency anemia?
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Which of the following is NOT a cause of absolute iron deficiency?
Which of the following is NOT a cause of absolute iron deficiency?
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Which factor is most likely to lead to functional iron deficiency?
Which factor is most likely to lead to functional iron deficiency?
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In what instance should other causes of blood loss be investigated in a patient suspected of having iron deficiency anemia?
In what instance should other causes of blood loss be investigated in a patient suspected of having iron deficiency anemia?
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What clinical finding is indicative of iron-deficient erythropoiesis?
What clinical finding is indicative of iron-deficient erythropoiesis?
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Which group is most at risk for increased demand for iron leading to deficiency?
Which group is most at risk for increased demand for iron leading to deficiency?
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Which laboratory measurement is NOT typically sensitive to early iron-store depletion?
Which laboratory measurement is NOT typically sensitive to early iron-store depletion?
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What is the most common subtype of Non-Hodgkin's Lymphoma?
What is the most common subtype of Non-Hodgkin's Lymphoma?
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Which factor is NOT commonly associated with an increased risk of Non-Hodgkin's Lymphoma?
Which factor is NOT commonly associated with an increased risk of Non-Hodgkin's Lymphoma?
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What percentage of Non-Hodgkin's Lymphomas are of B-cell origin?
What percentage of Non-Hodgkin's Lymphomas are of B-cell origin?
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Which of the following is a characteristic symptom in 40% of patients with Diffuse Large B-Cell Lymphoma?
Which of the following is a characteristic symptom in 40% of patients with Diffuse Large B-Cell Lymphoma?
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What genetic alteration is common in non-Hodgkin’s lymphoma subtypes?
What genetic alteration is common in non-Hodgkin’s lymphoma subtypes?
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Which statement is true regarding Follicular Lymphoma?
Which statement is true regarding Follicular Lymphoma?
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Which of the following mutations is commonly involved in B-cell lymphomas?
Which of the following mutations is commonly involved in B-cell lymphomas?
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What is a significant clinical feature when there is extensive bone marrow involvement in Non-Hodgkin’s Lymphoma?
What is a significant clinical feature when there is extensive bone marrow involvement in Non-Hodgkin’s Lymphoma?
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Which of the following grades of Follicular Lymphoma indicates a higher number of centroblasts?
Which of the following grades of Follicular Lymphoma indicates a higher number of centroblasts?
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What is a common clinical presentation of Follicular Lymphoma?
What is a common clinical presentation of Follicular Lymphoma?
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Which diagnostic method is NOT typically used for staging Follicular Lymphoma?
Which diagnostic method is NOT typically used for staging Follicular Lymphoma?
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Which of the following is true regarding Hodgkin’s Lymphoma?
Which of the following is true regarding Hodgkin’s Lymphoma?
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Reed-Sternberg cells are characteristic of which type of lymphoma?
Reed-Sternberg cells are characteristic of which type of lymphoma?
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What type of lymphadenopathy is commonly observed in patients with classical Hodgkin's Lymphoma?
What type of lymphadenopathy is commonly observed in patients with classical Hodgkin's Lymphoma?
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Which of the following subtypes of Hodgkin’s Lymphoma is primarily related to indolent B-cell non-Hodgkin’s lymphomas biologically?
Which of the following subtypes of Hodgkin’s Lymphoma is primarily related to indolent B-cell non-Hodgkin’s lymphomas biologically?
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What percentage of patients with classical Hodgkin's Lymphoma show evidence of EBV infection?
What percentage of patients with classical Hodgkin's Lymphoma show evidence of EBV infection?
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Study Notes
BMS 200 - Hematology
- Course covering RBC physiology, iron-deficiency anemia, and hematological concepts
- Objectives include describing hematopoiesis, erythropoiesis, RBC morphology and function, hemoglobin synthesis, the iron cycle, iron deficiency mechanisms, and common causes.
RBC Physiology (Erythrocytes)
- Red blood cells (RBCs) are primarily responsible for oxygen transport throughout the body.
- RBCs contain hemoglobin, binding oxygen in the lungs and releasing it into tissues.
- RBCs remove carbon dioxide, a waste product, transporting it back to the lungs.
- RBC production occurs in bone marrow, with a lifespan of about 120 days.
- Their unique biconcave shape enhances movement through blood vessels and maximizes gas exchange surface area.
- Hemoglobin (Hb) binds reversibly to oxygen, binding at high oxygen concentrations and releasing at low concentrations.
- Hb saturation in arterial blood ranges from 95% to 99% in healthy individuals.
- RBCs are crucial for carbon dioxide transport.
- RBCs contain carbonic anhydrase, an enzyme that aids in carbon dioxide transport.
Hemoglobin and the Hb Dissociation Curve
- The percentage of oxygen saturation in hemoglobin varies with PO2
- Hb saturation and PO2 relationship is presented in a dissociation curve.
- Factors affect the oxygen affinity of hemoglobin which are depicted in the curve's shift to the left or right.
- Factors that shift the curve to the right include temperature, increased PCO2, and decreased pH.
- 2,3-DPG has a high affinity for hemoglobin and affects the curve to the right.
- Fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin because it does not bind easily to 2,3-DPG.
RBCs and Carbon Dioxide Transport
- Carbon dioxide is transported in the blood in three forms: dissolved, bound to hemoglobin, and as bicarbonate ions.
- Carbonic anhydrase catalyzes the conversion of carbon dioxide to bicarbonate ions, allowing for efficient transport.
- Chloride shift aids in bicarbonate transport within the red blood cell.
RBC Formation and Destruction
- Most RBCs are eliminated in the red pulp of the spleen by macrophages as they age and become dysfunctional.
- Hemoglobin is metabolized with iron recycled to the bone marrow, and heme is eliminated in the bile and stool via bilirubin.
- The globin protein part of hemoglobin is recycled into its amino acid components.
Liver - Bilirubin Conjugation
- Senescent RBCs are phagocytosed by macrophages, and heme is broken down to biliverdin and bilirubin.
- Unconjugated bilirubin is bound to albumin and carried to the liver.
- In the liver, bilirubin is conjugated with glucuronic acid.
- Conjugated bilirubin is secreted into bile.
Basic Iron Metabolism
- The body contains 3-4 g of iron, primarily bound to hemoglobin (2.5 g).
- Iron is absorbed through the duodenal mucosa, with heme iron best absorbed, and ferrous iron (Fe2+) absorbed better than ferric iron (Fe3+).
- Transported through a divalent metal transporter, with excess iron regulated by the liver via hepcidin.
- Hepcidin blocks the transporter ferroportin to regulate iron absorption.
- Iron is transported in the bloodstream by transferrin and carries oxidized iron (Fe3+).
Iron Deficiency Anemia
- Globally, 50% of anemia is due to iron deficiency anemia (IDA).
- Causes of IDA include poor iron intake, parasites that steal iron, increased iron demands (pregnancy, growth spurts), or blood loss (menstruation, trauma).
- Characterized by fatigue, dyspnea, exercise intolerance, and symptoms associated with blood loss.
- Signs such as pallor (observing conjunctiva), tachycardia, and flow murmur.
- Laboratory tests indicate reduced RBC count, hemoglobin concentration, and reticulocytes, as well as small and hypochromic RBCs.
- Increased RDW (red cell distribution width) indicates variation in RBC size.
- Peripheral smear shows microcytic and hypochromic red blood cells; a diagnosis characterized by decreased ferritin, elevated total iron-binding capacity, and reduced serum iron.
Erythropoiesis
- Pronormoblast undergoes multiple cell divisions.
- Erythropoietin (EPO) stimulates division at the pronormoblast stage, and is produced by the kidney.
- In high oxygen conditions, hypoxia-inducible factor (HIF) is ubiquinated and degraded by proteasomes
- Conversely, in low oxygen conditions, HIF binds to certain proteins, is translocated to the nucleus, and stimulates EPO production.
RBCs - General Cellular Physiology
- RBC generation relies on sufficient iron, amino acids, and erythropoietin (EPO).
- RBCs solely use glycolysis to produce ATP.
- They possess plentiful glutathione stores to combat free radical production.
- Cytoskeletal proteins maintain RBC shape.
Hemoglobin
- Hemoglobin (Hb) comprises four subunits (two alpha and two beta chains).
- Each subunit contains a heme moiety that binds iron, enabling oxygen binding.
- Adult Hb is primarily HbA, a combination of two alpha and two beta chains.
- Fetal Hb has a higher oxygen affinity due to its different globin chain composition (alpha and gamma).
Hemoglobin Impact
- Many factors influence Hb's oxygen affinity.
- Factors that shift the curve to the right (lower affinity) include increased temperature, increased PCO2, decreased pH, and increased 2,3-DPG.
- Fetal Hb has a higher oxygen affinity because it does not bind easily to 2,3-DPG.
- Carbon monoxide binds to Hb with much higher affinity than oxygen, forming carboxyhemoglobin.
Hemostasis - Summary
- Hemostasis is the process preventing blood loss from damaged blood vessels.
- Processes involved include:
- Vasoconstriction
- Platelet plug formation
- Coagulation cascade activation
Hemostasis – Extrinsic Pathway
- Initiated by tissue factor (TF) exposed when blood vessel integrity is compromised.
- TF activates Factor VII, leading to Factor Xa activation.
- Xa, along with Va, Ca2+, and phospholipids, activate prothrombin, which then converts to thrombin.
- Thrombin activates fibrinogen, creating fibrin, which forms a stable plug.
Hemostasis – Intrinsic Pathway
- Initiated by negatively charged surfaces, activating Factor XII.
- XIIa activates the prekallikrein-HMWK complex, which activates Factor XI.
- The cascade progresses through FXIa, FIXa, and VIIIa, resulting in factor Xa activation.
- Xa, along with Va, Ca2+, and phospholipids, activate prothrombin, which converts to thrombin.
- Thrombin activates fibrinogen, creating fibrin, forming a stable clot.
Platelets
- Essential for hemostasis and coagulation.
- Platelets are derived from megakaryocytes in the bone marrow and regulated by thrombopoietin.
- Anucleate “fragments” with granules containing various factors for coagulation, including ADP, serotonin, and thromboxane A2.
- Granules release mediators to further platelet activation and aggregation, assisting in clot formation.
Platelet Function – Step-by-Step
- Healthy vascular endothelium prevents platelet activation via nitric oxide, prostacyclin, and ADPase enzyme.
- Platelets adhere to collagen and vWF (exposed by damage) via GP receptors (GP Ib/IX and GP VI).
- A platelet release reaction (PlateRR) occurs, releasing granules and activating GP IIb/IIIa to aid in platelet aggregation.
- Platelets release mediators (ADP, serotonin, TXA2) that further activate other platelets, forming a platelet plug.
Down-regulation of Coagulation Cascade
- Antithrombotic/anticoagulant mechanisms involve proteins like antithrombin, activated protein C/S complex, and tissue factor pathway inhibitor (TFPI), inhibiting coagulation factors and thrombin activation.
- Heparin enhances antithrombin action.
Fibrinolytic System
- Activated by tPA and removes clots.
- Plasminogen and tPA generate plasmin to break down fibrin.
Laboratory tests of Coagulation
- Standardized measurements (PT, aPTT, TT), used for diagnosing and monitoring coagulation disorders.
Hemophilia A and B
- X-linked recessive disorders, presenting with defects in FVIII (Hemophilia A) or FIX (Hemophilia B).
- Common in males, resulting in impaired blood clotting.
- Symptoms vary, but severe cases can lead to frequent and severe bleeding episodes.
- Genetic testing can determine mutation presence.
Anemias of Inflammation
- Al is relatively common, arising from inflammatory conditions and characterized by a reduction in red blood cell production.
- Cytokines from various conditions depress erythropoiesis, while iron sequestration reduces iron availability for red blood cell production.
- Clinical presentation is often similar to IDA but with different iron handling.
Anemia of Chronic Kidney Disease
- Decreased erythropoietin (EPO) production, leading to decreased red blood cell production.
- RBCs are usually normocytic and normochromic, but reticulocyte counts are decreased.
Anemias of Abnormal RBC Synthesis
- Genetic metabolic or cytoskeletal disorders.
- Sickle cell anemia: Due to a substitution of glutamate by valine within the beta-globin chain. This causes the hemoglobin to polymerize upon deoxygenation, forming rigid, sickle-shaped RBCs.
- Thalassemia: Decreased or absent production of alpha or beta globin chains. This results in structural abnormalities and premature destruction of red blood cells. The type of mutation can have several different clinical presentations from relatively mild to severe.
- G6PD deficiency: Reduced or absent NADPH production results in oxidative stress impacting RBC survival.
- Hereditary spherocytosis: Cytoskeletal protein defects result in spherocytic RBCs with reduced deformability and shortened lifespan.
Malaria
- Mosquito-borne parasitic disease, with different species causing varying degrees of illness.
- Transmitted via the bite of infected female Anopheles mosquitoes.
- Asexual parasite-RBC invasions and destruction lead to severe complications, such as significant anemia, cerebral involvement, and potential death.
Leukemias and Lymphomas
- Blood cell malignancies.
- Classified into myeloid and lymphoid based on progenitor cell type.
- Different types have different clinical presentations, prognoses, and treatment options.
- These malignancies may be related to genetic alterations.
Objectives of Part II (Leukemias and Lymphomas)
- Understanding the etiology, pathophysiology, clinical presentation, and laboratory assessments for several leukemias and lymphocytic cancers.
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Test your knowledge on iron deficiency anemia, including its causes, symptoms, and effects on red blood cells. This quiz covers essential concepts such as iron absorption rates and characteristics of red blood cells. Perfect for students and healthcare professionals alike!
