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

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 inn...

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