PHYSIOLOGY_LC5_RED BLOOD CELLS, ANEMIA & POLYCYTHEMIA VERA.pdf

COURSE OUTLINE II. RED BLOOD CELLS (ERYTHROCYTES) I. OBJECTIVES II. RED BLOOD CELLS (ERYTHROCYTES) A. Functions A. FUNCTIONS B. Shape and...

COURSE OUTLINE II. RED BLOOD CELLS (ERYTHROCYTES) I. OBJECTIVES II. RED BLOOD CELLS (ERYTHROCYTES) A. Functions A. FUNCTIONS B. Shape and Size C. Other Characteristics of RBC III. RBC PRODUCTION A. Early Embryonic Life B. Middle Trimester of Gestation C. Late Gestation and Post-Birth D. Bone Marrow Activity by Age IV. GENESIS OF BLOOD CELLS A. Blood Cell Formation B. Pluripotential Hematopoietic Most abundant cells of the blood Stem Cells 1. To transport hemoglobin C. Differentiation and Committed carries oxygen from the lungs to the Stem Cells tissues D. Growth Inducers E. Differentiation Inducers 2. Acid-base Buffer V. RBC DIFFERENTIATION contain a large quantity of carbonic A. Early Differentiation Stages anhydrase, an enzyme that catalyzes the VI. RBC PRODUCTION REGULATION reversible reaction between carbon A. Erythropoietin dioxide (CO2) and water to form carbonic B. Normal Response acid H2CO3) → transport enormous C. Location of Erythropoietin quantities of CO2 in the form of Production bicarbonate ion (HCO3) from tissues to D. Hypoxia-Inducible Factors-1 the lungs as CO2 (HIF-1) Red blood cells are also known as your E. Kidney Removal or Disease erythrocytes. So, they are the most abundant F. Tissue Oxygenation cells in the blood. They mainly act to transport VII. ROLE OF VITAMIN B12 AND FOLIC your hemoglobin. So, it means they carry your ACID IN RBC MATURATION oxygen. Not only oxygen, but they carry your A. Effects of Deficiency carbon dioxide outside of the body by B. Hemoglobin Synthesis respiration, through the process of respirations. C. Chemical Formation of These are the two functions of your RBCs. Hemoglobin They need to transport hemoglobin and act as D. Hemoglobin Chain Abnormalities an acid buffer. So, RBCs are very important in E. Hemoglobin’s Reversible Binding your acid buffering or your acid-base buffer with Oxygen system. So that, in case of your, for example, F. Iron Metabolism respiratory problem or respiratory acidosis or VIII. ANEMIA alkalosis, your metabolic acidosis or your A. Blood Loss Anemia metabolic alkalosis, they are the ones mainly B. Aplastic Anemia acting in the buffering of your blood pH. C. Megaloblastic Anemia They use the respiratory system to buffer your D. Hemalocytic Anemia acid-base imbalance, which is an abnormal IX. EFFECT OF ANEMIA ON FUNCTION OF thing in your kidney. THE CIRCULATORY SYSTEM X. POLYCYTHEMIA B. Shape and Size XI. POLYCYTHEMIA VERA XII. CASE EXAMPLES I. OBJECTIVES At the end of this lecture, one should be able to: 1. Describe the function of red blood cells Biconcave disks 2. Explain how red blood cells are produced Diameter: 7.8 micrometers 3. Define and describe the types of anemias Thickness: 2.5 micrometers (thickest point) ≤1 and explain its etiology micrometer (center) 4. Differentiate polycythemia vera, Average Volume: 90 to 95 cubic micrometer polycythemia and erythrocytosis Average Concentration ○ Men: 5,200,000 (±300,000) mm3 ○ Women: 4,700,000 (±300,000) mm3 BATCH 2028 1B 1 PHYSIOLOGY LC5: RBC, ANEMIA, AND POLYCYTHEMIA VERA Dr. UJANO, S. 09/10/2024 Average Hemoglobin and catheter system responsible for the ○ Men: 15 grams/100 milliliter RBC's innocence or their death. On the other ○ Women: 14 grams/100 milliter hand, the hemoglobin are also being phagocytized Biconcave because it has an indentation on the One important thing to know about that is that center on both sides. They are very pliable. when they die, you are producing your Because of that, they can just fold anytime. bilirubins. So, this comes from your porphyry When they go to your capillaries, which is the ring. Bilirubin is very important, because: site of your gas exchange and nutrients exchange. In your tissues, they can readily A. It can be an index of your red cell lysis. squeeze themselves into those capillaries ○ That means your red cells are dying. You are producing much bilirubin. Bilirubin is a easily. So, they can fold because of that central pigment that causes yellowish cavity. discoloration or jaundice. You can excrete The size of the RBCs are very important that through your urine, that's why it's color because a lot of diseases of your RBC would yellow, and your feces. be having an abnormality in the size. ○ If you have too much of the bilirubin, to the Anything more than 90 to 95 cubic micrometers extent that your body is having difficulty in is abnormal. excreting it, if that is overwhelming more than what you can metabolize, it will accumulate in your other tissues like eyes C. OTHER CHARACTERISTICS OF RBC or skin–makes you appear jaundiced. Life Span: 120 days Do not have a nucleus, mitochondria, or III. RBC PRODUCTION endoplasmic reticulum, but has cytoplasmic enzymes 1. maintain pliability of the cell membrane A. EARLY EMBRYONIC LIFE 2. Maintain membrane transport of ions 3. keep the iron of the cells' hemoglobin in Site of Production: Yolk sac the ferrous form rather than ferric form, Characteristics: Primitive, nucleated RBCs and 4. Prevent oxidation of the proteins in the B. MIDDLE TRIMESTER OF GESTATION RBCs. (12 weeks- 18 weeks) Main Organ: Liver Additional Sites: Spleen and lymph nodes C. LATE GESTATION AND POST-BIRTH Primary Site: Bone marrow Production Sites: Initially, all bones; exclusive to bone marrow towards the end of gestation and birth D. BONE MARROW ACTIVITY BY AGE Figure 1. Prosthetic Heme group of hemoglobin Self-destruct in the spleen Hemoglobin phagocytosis ○ Kupffer cells of the liver ○ Macrophages of the spleen Figure 2. Relative rates of red blood cell production in the bone ○ Macrophages of the bone marrow marrow of different bones at different ages Bilirubin ○ Converted porphyrin ring of hemoglobin Up to Age 5: RBCs produced in the marrow by macrophages of nearly all bones The ion forms stored in your RBC are in the Around Age 20: Marrow of long bones ferrous form. becomes fatty; RBC production ceases in →Ferrous- soluble iron form most long bones →Ferric- insoluble iron form Post Age 20: RBC production shifts to RBCs have a lifespan of 120 days, in one marrow of membranous bones (vertebrae, month, they die. Most of your RBCs die in the sternum, ribs, ilia) spleen. So, your spleen is mainly a reticulum Aging Effect: Decreased marrow productivity with increasing age. BATCH 2028 1B 2 PHYSIOLOGY LC5: RBC, ANEMIA, AND POLYCYTHEMIA VERA Dr. UJANO, S. 09/10/2024 At age of 20, it is mostly produced by long bones C. DIFFERENTIATION AND COMMITTED like femur or tibia. But at age after 20, your bone STEM CELLS marrow closes. They are being replaced by fatty Process: Reproduced cells differentiate into cells. Now, it is mainly produced by flat bones. specific blood cell types. Example: ilium, ribs, sternum. Even in these bones, Committed Stem Cells: intermediate-stage the marrow becomes less productive as age cells committed to specific blood cell lines. increases Examples: Colony-forming unit-erythrocute (CFU-E) for erythrocytes, CFU-GM for granulocytes and monocytes. IV. GENESIS OF BLOOD CELLS If the stem cell is not committed to making this type of cell, there is a problem with the maturity of the other cells. D. GROWTH INDUCERS Function: Proteins that stimulate growth and reproduction of stem cells. Major inducers: ○ At least four types, including interleukins-3, which supports growth and reproduction of all different types of stem cells. ○ Other inducers target growth of specific cell types. E. DIFFERENTIATION INDUCERS Function: Proteins that guide committed stem cells through stages of differentiation into mature blood cells. Role: Facilitate the transfusion from committed stem cells to final blood cell types. Regulation by external factors Figure 3. Formation of the multiple different blood cells from the Growth and Differentiation Control: original multipotent hematopoietic stem cell in the bone marrow. influenced by factors outside the bone marrow. RBCs are also produced by external factors not A. BLOOD CELL FORMATION only internal factors. Examples: Origin: Blood cells originate from ○ Erythrocytes: low oxygen levels trigger pluripotential hematopoietic stem cells in the increased production of RBCs. To supply bone marrow. the tissues with oxygen. ○ White Blood Cells: Infections prompt growth and differentiation to produce B. PLURIPOTENTIAL HEMATOPOIETIC specific types of white blood cells needed STEM CELLS to address the infection. Characteristics: Single type of cell capable of differentiating into various blood cell types. V. RBC DIFFERENTIATION Function: These stem cells give rise to all types of circulating blood cells. Formed from CFU-E stem cells under Maintenance: A portion of these cells remains appropriate stimulation in the bone marrow to sustain the stem cell pool, though their numbers decrease with age. A. EARLY DIFFERENTIATION STAGES The blood cells begin their lives in the bone marrow from a single type of cell called the 1. Proerythroblast (Contains intracellular multipotential hematopoietic stem cell, from organelles) which all the cells of the circulating blood are First identifiable cell in the RBC series Divides multiple times to form mature eventually derived. RBCs Pluripotent, that means they have full potential 2. Basophil Erythroblast to develop in any cells. So any of these stem First-generation cell in the differentiation cells has different end results or end products. process. They are very capable of forming any other Characteristics: blood cells. Differentiating means they can ○ Stains with basic dyes ○ Minimal hemoglobin accumulation make another type of cell. BATCH 2028 1B 3 PHYSIOLOGY LC5: RBC, ANEMIA, AND POLYCYTHEMIA VERA Dr. UJANO, S. 09/10/2024 3. Reticulocytes Stage hypoxia-inducible genes, including the Characteristics: erythropoietin gene. ○ Contains remnants of Golgi Mechanism: binds to the hypoxia response apparatus, mitochondria, and other elements in the erythropoietin gene, inducing organelles renalA transcription and increased ○ Called a reticulocytes due to erythropoietin synthesis. residual basophilic material Formation begins within minutes to hours in ○ Moves from bone marrow to blood low oxygen conditions, with maximum capillaries by diapedesis production within 24 hours ○ Constitute slightly less than 1 New RBCs are not seen in the blood until percent of total RBCs die to their approximately 5 days after erythropoietin short lifespan. production starts. Diapedesis is the movement of cell to the Erythropoietin primarily stimulates the membranes, specifically the blood cells to the production of proerythroblast and speeds bloodstream and to the capillary membranes. up their development through erythroblastic stages. 4. Erythrocytes Final stage, when reticulocytes material E. KIDNEY REMOVAL OR DISEASE disappears within 1 to 2 days -> Mature erythrocytes Significant anemia due to reduced Mature means devoid of organelles, which erythropoietin production shrinks down to become biconcave disc shape. Remaining Production: Liver’s contribution Is it normal to see nucleated cells outside the of erythropoietin (10% of normal) is blood? No, because only the reticulocyte and insufficient, leading to only 33-50% of the the mature cells should be found there. Hence, necessary RBC production. the maturity of RBCs happens in the blood, not in the bone marrow. F. TISSUE OXYGENATION The most essential regulator of RBC VI. RBC PRODUCTION REGULATION production. Purpose: maintain RBC mass within narrow limits. Factors affecting oxygenation 1. Ensures enough RBCs are available for 1. Anemia and Hemorrhage effective oxygen delivery ○ Response: increased RBC production in 2. Avoids excessive RBC numbers that could the bone marrow to compensate for low impede circulation oxygen levels. ○ Any situation that reduces the amount of A. ERYTHROPOIETIN oxygen supplied to the tissues typically increases the rate of red blood cell An example of differentiation inducer and a formation. Thus, when a person becomes hormone for RBC production highly anemic due to a bleed or another Regulates RBC production to maintain balance ailment, the bone marrow rapidly begins Adjusts RBC production based on current to create a huge number of red blood needs cells. Principal hormones stimulating RBC production 2. Bone Marrow Destruction Glycoprotein with a molecular weight of ○ Cause: conditions like x-ray therapy approximately 34,000. ○ Response: hyperplasia of remaining bone marrow to meet RBC demands B. NORMAL RESPONSE However, the problem arises if the increase production of hyperplastic cells or immature In Low Oxygen States: Erythropoietin cells, there will be a problem in cell maturity. production increases in response to hypoxia. Leading now to development malignancies. Without Erythropoietin: Hypoxia has minimal Destruction of substantial parts of the bone effect on RBC production. marrow, particularly through x-ray therapy, results in hyperplasia of the remaining bone C. LOCATION OF ERYTHROPOIETIN marrow in an attempt to supply/meet the PRODUCTION body's demand for red blood cells. 1. Kidneys: main site, accounting for about 90% 3. High Altitude of erythropoietin production. (Mostly at the ○ Reduced oxygen in the air interstitial cell of the renal cortex and outer ○ Response: Increase RBC production due medulla) to decrease oxygen transport to tissue. 2. Liver: secondary site, responsible for the When the tissues become hypoxic because of remaining 10% too little oxygen in the inhaled air, such as at high altitudes, or because of failure of oxygen D. HYPOXIA-INDUCIBLE FACTORS-1 (HIF-1) supply to the tissues, such as in heart failure, the blood-forming organs immediately Acts as a transcription factors for generate significant amounts of additional red BATCH 2028 1B 4 PHYSIOLOGY LC5: RBC, ANEMIA, AND POLYCYTHEMIA VERA Dr. UJANO, S. 09/10/2024 blood cells. massive, and oval as opposed to the typical biconcave disc. 4. Pulmonary and Circulatory Disease ○ Conditions Affecting Blood Flow: 1. Pernicious Anemia ○ Examples: ○ Prolonged cardiac failure, lung Poor absorption of vitamin B12 from the disease gastrointestinal tract due to atrophic gastric Anemia occurs when tissues become hypoxic mucosa leading to inadequate gastric due to insufficient oxygen in the air or failure of secretion. oxygen supply, such as heart failure. Intrinsic Factor Blood-forming organs generate more red blood cells to compensate for the reduced Secreted by parietal cells in the gastric glands oxygen-carrying effect. Anemia partially offsets Intrinsic factor binds tightly with vitamin B12, this by increasing cardiac output, allowing protecting it from digestion almost normal oxygen delivery to tissues. Some people have asymptomatic anemia and Intrinsic factor- vitamin B12 complex binds only experience the effect during exercise. to specific receptors on the brush border However, when exercising, the heart is unable membranes of ileal mucosal to pump more blood than it is already pumping, Vitamin B12 -> blood via pinocytosis, carrying leading to extreme tissue hypoxia and acute both intrinsic factor and vitamin B12 cardiac failure. ○ Elevated hematocrit and often increased Anemia resulting from failure to meet Vitamin total blood volume due to tissue hypoxia B12 requirements in the body due to failure of Tissue hypoxia, caused by lung diseases, high an atrophic gastric parietal cells to secret altitude, or heart conditions, results in elevated intrinsic factor hematocrit and increased total blood volume. Vitamin B12 Storage and Requirements This compensatory mechanism improves ○ Storage: Liver- about 1000 times the oxygen delivery to tissues but may increase the daily requirement risk of complications like blood clots due to thicker blood. ○ Daily requirement: 1-3 micrograms daily Progression to anemia ○ 3-4 years to defective B12 absorption VII. ROLE OF VITAMIN B12 AND FOLIC usually required to cause anemia ACID IN RBC MATURATION Megaloblastic anemias are abnormal red blood cells in the bone marrow and blood, primarily Both are crucial for the synthesis for the due to impaired DNA synthesis. synthesis of DNA Required for the formation of thymidine 2. Folic Acid Deficiency triphosphate, a key DNA building block Green vegetables, some fruits, and meats A lack of vitamin B12 or folic acid leads to (particularly liver) contain folic acid naturally. aberrant and reduced DNA, resulting in However, it is easily accessible and cooking failure of nuclear maturation and cell causes destruction. division. Easily destroyed during cooking Causes maturation failure Small intestinal disease called tropical sprue - A prominent reason for red blood cell decreases absorption. maturation failure is a lack of vitamin B12 Deficiency of folic acid leads to impaired RBC absorption from the gastrointestinal maturation system. Additionally, people with gastrointestinal absorption abnormalities, such as the common A. EFFECTS OF DEFICIENCY small intestinal disease known as Tropical sprue, frequently struggle to absorb both folic Abnormal DNA synthesis acid and vitamin B12. Impaired nuclear maturation and cell division Produces larger-than-normal RBCs B. HEMOGLOBIN SYNTHESIS (macrocytes) with flimsy membranes and irregular shapes. Initiation: Begins in proerythroblast Fragile and have a shortened lifespan (one-half Continuation: Continues into the reticulocyte to one-third of normal) stage The bone marrow's erythroblastic cells produce Post-Bone Marrow: Reticulocytes in the mostly macrocytes, which are larger than bloodstream continue hemoglobin synthesis for typical red blood cells. The cell itself has a an additional day or so until maturation fragile membrane and is frequently irregular, BATCH 2028 1B 5 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