Physiology LC5: Red Blood Cells, Anemia & Polycythemia Vera PDF

PHYSIOLOGY LC5: RBC, ANEMIA, AND POLYCYTHEMIA VERA Dr. UJANO, S. 09/10/2024 C. CHEMICAL FORMATION OF HEMOGLOBIN D. HEMOGLOBIN CHAIN ABNORMALITIES Hemoglobin A - most common form of...

PHYSIOLOGY LC5: RBC, ANEMIA, AND POLYCYTHEMIA VERA Dr. UJANO, S. 09/10/2024 C. CHEMICAL FORMATION OF HEMOGLOBIN D. HEMOGLOBIN CHAIN ABNORMALITIES Hemoglobin A - most common form of 1. Sickle Cell Anemia hemoglobin in the adult human being Mutation: Valine replaces glutamic acid in beta Oxygen Binding Capacity: chains ○ Four heme groups + one iron atom each (4 iron atoms) Hemoglobin S, an aberrant form of hemoglobin ○ Oxygen Binding: each hemoglobin with defective beta chains in the hemoglobin molecule can bind up to 4 oxygen molecule, is found in the cells. molecules (8 oxygen atoms) Formation of elongated crystals in low oxygen condition Hemoglobin formation: Consequences: Difficulty in passing through capillaries and potential rupture of cell membrane Such patients frequently experience a vicious cycle of events known as a sickle cell disease "crisis," in which low oxygen tension in the tissues causes sickling, which leads to ruptured red cells, which causes another decrease in oxygen tension and even more sickling and red cell destruction. Once started, the process Figure 4. Formation of Hemoglobin moves quickly, resulting in a significant drop in red blood cells within a few hours and, in many ○ succinyl-CoA binds with glycine to form a pyrrole molecules cases, death. ○ 4 pyrroles combine to form protoporphyrin IX then combines with iron to form the heme ○ each heme molecule combine with a long polypeptide chain, a globin ○ Tetrameric Structure: Hemoglobin is a tetramer consisting of two alpha chains and two beta chains in adults (HbA). Each subunit contains one heme group and one Table 1. Alpha-Thalassemia Syndrome globin chain. ○ Oxygen Transport: When oxygen binds to E. HEMOGLOBIN’S REVERSIBLE BINDING WITH the iron in one heme group, it induces a OXYGEN conformational change in the hemoglobin molecule that makes it easier for oxygen to Oxygen binds loosely with one of the bind to the remaining heme groups. This is known as cooperative binding. coordination bonds of the iron atom in hemoglobin NOT IONIC Oxygen Transport: Oxygen combines with hemoglobin in the lungs where oxygen tension is high Release Mechanism: In tissues with lower oxygen tension, hemoglobin releases oxygen into the tissue fluids F. IRON METABOLISM Roles: Essential for forming hemoglobin, myoglobin, cytochromes, cytochrome oxidase, peroxidase, and catalase Total Iron Content Average Quantity: 4 to 5 grams in the body Distribution of Iron: ○ Hemoglobin: About 65% of total body iron Figure 5. Basic structure of the heme moiety, showing one of the ○ Myoglobin: Approximately 4% four heme chains that along with globin polypeptide, bind together ○ Heme Compounds: Around 1% involved in to form the hemoglobin molecule. intracellular oxidation ○ Transferrin: About 0.1% in the blood BATCH 2028 1B 6  PHYSIOLOGY LC5: RBC, ANEMIA, AND POLYCYTHEMIA VERA Dr. UJANO, S. 09/10/2024 plasma A. BLOOD LOSS ANEMIA ○ Ferritin: 15 to 30% stored mainly in the reticuloendothelial system and liver Acute Blood Loss: parenchymal cells, storage iron ○ Initial Response: Replacement of plasma ○ Absorption: Iron absorbed from the small fluid occurs within 1 to 3 days intestine ○ RBC Concentration: Low initially; Transport: Iron combines with apotransferrin to normalizes within 3 to 6 weeks if no form transferrin, which carries iron in the plasma additional hemorrhage occurs Storage: Iron binds to apoferritin in cell ○ Type of Anemia: Normocytic, cytoplasm to form ferritin in liver hepatocytes normochromic anemia and reticuloendothelial cells in the bone marrow Chronic Blood Loss Storage Forms: ○ Iron Absorption: Insufficient iron 1. Ferritin: Iron combines with apoferritin in absorption from the intestines the cytoplasm to form ferritin; can store ○ RBC Characteristics: Production of varying amounts of iron smaller-than-normal RBCs with low 2. Hemosiderin: An insoluble form of iron hemoglobin that accumulates when iron levels exceed ○ Type of Anemia: Microcytic, hypochromic ferritin capacity; forms large clusters visible anemia under a microscope B. APLASTIC ANEMIA Due to Bone Marrow Dysfunction Lack of functioning bone marrow Causes: ○ High-Dose Radiation/Chemotherapy: Damages bone marrow stem cells ○ Toxic Chemicals: Exposure to substances like insecticides or benzene ○ Autoimmune Disorders: E.g., lupus erythematosus, attacking bone marrow stem cells ○ Idiopathic: Unknown causes in about half of the cases Treatment: Blood transfusions for temporary relief, bone marrow transplantation for a potential cure Figure 6. Iron transport and metabolism C. MEGALOBLASTIC ANEMIA Anemia caused by abnormal erythroblasts VIII. ANEMIA Causes: Deficiency of hemoglobin in the blood ○ Vitamin Deficiency: Lack of vitamin B12, Causes: few RBCs or insufficient hemoglobin folic acid, or intrinsic factor ○ Conditions Leading to Deficiency within RBCs. Pernicious Anemia: Atrophy of the stomach mucosa, preventing intrinsic factor production Gastrectomy: Complete removal of the stomach Intestinal Sprue: Poor absorption of folic acid and vitamin B12 RBC Characteristics: ○ Size and Shape: Oversized, bizarre-shaped RBCs with fragile membranes ○ Consequence: Increased fragility and rupture of RBCs, leading to severe anemia Figure 7. Genesis of normal red blood cells and characteristics of D. HEMOLYTIC ANEMIA RBCs in different types of anemias Abnormalities of the RBCs, that make cells fragile, so they rupture easily as they go through the capillaries. BATCH 2028 1B 7 PHYSIOLOGY LC5: RBC, ANEMIA, AND POLYCYTHEMIA VERA Dr. UJANO, S. 09/10/2024 1. Hereditary spherocytosis ○ Very small and spherical rather than biconcaves ○ Easily ruptured be even slightly compression 2. Sickle cell anemia Figure 8. Sickle cell Figure 9. Hemolyitic disease of Newborn Prevalence: Affects 0.3 to 1.0 percent of West African and American black populations Pathophysiology: IX. EFFECTS OF ANEMIA ON FUNCTION ○ Hemoglobin Type: Abnormal hemoglobin S OF THE CIRCULATORY SYSTEM with faulty beta chains. 1. Viscosity - blood is 3x more viscous than ○ Effect of Low Oxygen: Hemoglobin S water, it can drop up to 1.5x due to anemia precipitates into long crystals, causing 2. Hemodynamic changes: a. Decreased resistance to blood flow → cells to elongate into a sickle shape b. Increased blood flow through peripheral Consequences: vessels → ○ Damaged cell membranes lead to rapid c. Increased return of blood to the heart → destruction d. Increased cardiac output and pumping ○ Sickle Cell Crisis: A cycle of low oxygen, workload → sickling, cell rupture, and worsening e. High-output heart failure and Acute Heart anemia. Failure ○ 3. Erythroblastosis Fetalis X. POLYCYTHEMIA ○ Cause: Rh-positive fetal RBCs attacked by When the blood-forming organs automatically antibodies from an Rh-negative mother. produce large quantities of extra RBCs ○ Effect: Antibodies cause RBC fragility and Polycythemia is a misnomer: rapid destruction. ERYTHROCYTOSIS Symptoms: XI. POLYCYTHEMIA VERA ○ Anemia: Serious anemia at birth ○ Bone Marrow Response: Rapid production of new RBCs with many early blast forms released into the blood. Specific term used for genetic aberration in JAK2 (Janus Kinase 2) gene. Jak 2 gene mutation causes the hemocytoblastic cells to cause non-stop production of RBC even if there are too many cells that are already present. Increase in RBC production, hematocrit, and total blood volume, leading to more viscous blood. Patients have arterial pressure that is usually normal, 1/3 are hypertensive. BATCH 2028 1B 8 PHYSIOLOGY LC5: RBC, ANEMIA, AND POLYCYTHEMIA VERA Dr. UJANO, S. 09/10/2024 Due to increased blood viscosity, blood Jaundice implies that there are cells that is circulation becomes slow, reason why most dying or bursting caused by overproduction of patients have normal arterial pressure despite bilirubin, leading to anemia and decreased increased blood volume hemoglobin and hematocrit Patients have very engorged arm and feet Very large MCV and MCHC indicates that the because most blood capillaries become patient might be having a very fragile RBC plugged by the viscous blood. which causes the bursting of cells Clump of RBC are very viscous that they Patient has macrocytic anemia because of high cannot readily pass on capillaries leading to MCV, indicating very round and fragile red engorged veins blood cells leading to hemolysis and jaundice Ruddy complexion with a bluish (cyanotic) tint to the skin CASE NO. 3: 29/F, left sided body weakness with Blue color of deoxygenated hemoglobin masks cardiac murmur the red color of oxygenated hemoglobin leading to ruddy complexion with a bluish tint skin Increased Decreased RBC Erythrocytosis Anemia Platelets Thrombocytosis Thrombocytopenia WBC Leukocytosis Leukopenia RBC Number of RBC MCV Mean red blood cell volume; indicates the size of RBC MCHC Mean amount of hemoglobin relative to the size of the cell; Indicates the Cardiac murmur indicates heart complication color of RBC caused by the problem in oxygen delivery Could be congenital heart disease since the Low MCV : Microcytic patient is young High MCV : Macrocytic Isolated increase in RBC indicates secondary Low MCHC : Hypochromic erythrocytosis that is most likely caused by High MCHC : Hyperchromic congenital valvular heart disease, which acts as compensatory mechanisms because most XII. CASE EXAMPLES likely, the blood of the patient is mixed or the CASE NO. 1: 42/M, alcoholic drinker with oxygenation is very low. Thus, hypoxia leads to hematemesis and melena secondary erythrocytosis. CASE NO. 4: 42/F, left sided body weakness CBC indicates acute bleeding because of low RBC and normal MCV and MCHC. That means, the blood is not yet diluted. The amount of blood going out to that bleeding has not Increase in all cell lineage indicates been compensated yet by the shifting of the Polycythemia. plasma implying that this happens within just Since CBC result shows high RBC, WBC, and 24 hours. Platelets, the patient was diagnosed to have Polycythemia CASE NO. 2: 45/F, with dyspnea and jaundice Note: Polycythemia vera is also characterized by increased RBC, WBC, and platelet counts. However, in this case, you cannot tell if the patient has polycythemia vera unless you have BATCH 2028 1B 9 PHYSIOLOGY LC5: RBC, ANEMIA, AND POLYCYTHEMIA VERA Dr. UJANO, S. 09/10/2024 proof that there is a gene mutation. CASE NO. 5: 72/M,fainting, no sign of bleeding, +weightloss RBC volume is very low. You see that in MCV. The MCV talks about volume, talks about the content. It has very low content. It is very low. It is microcytic. Where do you usually interpret the color? Its usually in the MCH. Clinically what we use is the MCHC. We are always talking about its concentration relative to the blood so that what is more important here is the MCHC. So the color should be based on the MCHC. Its hypochromic because its very low. Explanation: Heme is red color.If you do not have enough iron you will not form your heme that will now lead to your hypochromia. And now since you have not formed heme at all. That means your hemoglobin chains are very unstable. There are low in amounts, lets say they are not forming a very formed hemoglobin so the structure is very small now. Kase kulang ka na nang molecule. So that will now make your RBC very small. That’s why you have microcytic cell RBC. So what is this condition? MICROCYTIC HYPOCHROMIC ANEMIA. Most likely the patient has iron deficiency. Because the patient have no signs of weight loss. Most likely it's an occult bleeding. Example is malignancy or cancer sa colon. Ibig sabihin non a cancer a malignant tumor has a very lot of blood vessel. That has a lot of blood supply that are very fragile in your colon because of abrasion. You lose them one by one. You lose all those blood cells. Occult bleed. You do not know that you are losing it. Your intake is not enough to compensate with the losses leading now to your Iron deficiency anemia. That ‘s why it's not normal for you to see an adult with iron deficiency anemia alone. There should be something causing that iron deficiency anemia. Reference(s): Dr. S. Ujano (September 10, 2024). Red blood cells, Anemia, & Polycythemia Vera lecture and powerpoint Hall, J. E., & Hall, M. (2020). Guyton And Hall Textbook Of Medical Physiology, International Edition. (14th ed.). Elsevier - Health Science. BATCH 2028 1B 10