[PHYSIO]LEC_004_RED BLOOD CELLS.pdf

(004) RED BLOOD CELLS DR. AILYN ISAIS-AGDEPPA|10/13/2020 II. SHAPE AND SIZE OF RBC OUTLINE...

(004) RED BLOOD CELLS DR. AILYN ISAIS-AGDEPPA|10/13/2020 II. SHAPE AND SIZE OF RBC OUTLINE I. RED BLOOD CELLS Biconcave discs having a mean diameter of about 7.8 micrometres and a thickness of A. Haemoglobin 2.5 micrometres at the thickest point and 1 II. SHAPE AND SIZE OF RBC micrometer or less in the centre. A. Areas that Produce RBCs The average volume of the red blood cell is III. CONCENTRATION OF RBC IN BLOOD 90 to 95 cubic micrometres. The shapes of red blood cells can change IV. QUANTITY OF HAEMOGLOBIN IN CELLS remarkably as the cells squeeze through V. GENESIS OF BLOOD CELLS capillaries. VI. STAGES OF DFFERENTIATION OF RBCs RBC is like a “bag” that can be deformed into almost any shape. VII. REGULATION OF RBC PRODUCTION Deformation does not stretch the A. Role of Erythropoietin membrane greatly and, consequently, does B. Erythropoietin not rupture the cell, as would be the case VIII. ROLE OF KIDNEYS IN THE FORMATION with many other cells. Shape of the RBC is easily detected on OF ERYTHROPOIETIN peripheral blood smear. IX. REQUIREMENTS FOR RBC MATURATION A. AREAS OF THE BODY THAT PRODUCE I. RED BLOOD CELLS RED BLOOD CELLS Also known as erythrocytes Major Function: Transport Haemoglobin In the early weeks of embryonic life, Other Function: acid-base buffer primitive, nucleated red blood cells are RBC contain a large quantity of carbonic produced in the yolk sac. anhydrase making it an excellent acid-base During the middle trimester of gestation, the buffer. liver is the main organ for production of red Carbonic anhydrase is an enzyme that catalyses blood cells, but reasonable numbers are the reversible reaction between carbon dioxide also produced in the spleen and lymph (CO2) and water to form carbonic acid (H2CO3), nodes. the rapidity of this reaction makes it possible for During the last month or so of gestation and the water of the blood to transport enormous after birth, red blood cells are produced quantities of CO2 in the form of bicarbonate ion exclusively in the bone marrow. (HCO3) from the tissues to the lungs, where it is The bone marrow of essentially all bones reconverted to CO2 and expelled into the produces red blood cells until a person is 5 atmosphere as a body waste product. years old. The haemoglobin in the cells is an excellent acid- The marrow of the long bones, except for base buffer (as is true of most proteins), so that the proximal portions of the humeri and the red blood cells are responsible for most of the tibiae, becomes quite fatty and produces no acid-base buffering power of whole blood. more red blood cells after about age 20 A. HAEMOGLOBIN years. carries oxygen from the lungs to the tissues Beyond 20 years of age, most red cells When it is free in the plasma of the human continue to be produced in the marrow of being, about 3% of it leaks through the: the membranous bones, such as the - capillary membrane into the tissue vertebrae, sternum, ribs, and ilia. spaces Even in these bones, the marrow becomes - or through the glomerular less productive as age increases. membrane of the kidney into the glomerular filtrate each time the blood passes through the capillaries. If hemoglobin is not bound to RBC, it leaks to the capillaries PREPARED AND EDITED BY: ACSHAH, E. KANNAN, S. KUMAR R. MONCADA, R. MOTIC, G. MUNAR C. PRINCE J.  (004) RED BLOOD CELLS DR. AILYN ISAIS-AGDEPPA|10/13/2020 The blood cells begin their lives in the bone marrow from a single type of cell called the pluripotential hematopoietic stem cell. A portion of them remains exactly like the original retained in the bone marrow to maintain a supply of these. Most of the reproduced cells, differentiate to form the other cell types, the intermediate stage cells are very much like the pluripotential stem cells, committed to a particular line of cells and are called Figure: Relative rates of red blood cell production in committed stem cells. the bone marrow of different bones at different ages. A committed stem cell that produces erythrocytes is called a colony-forming unit– III. CONCENTRATION OF RBCs IN erythrocyte (CFU-E). BLOOD Colony-forming units that form granulocytes In normal men, the average number of red and monocytes have the designation CFU- blood cells per cubic millimetre is GM. 5,200,000 (±300,000). Growth and reproduction of the different In normal women, it is 4,700,000 stem cells are controlled by multiple (±300,000). proteins called growth inducers. Persons living at high altitudes have Growth inducers: greater numbers of red blood cells. o interleukin-3, promotes growth and reproduction of virtually all IV. QUANTITY OF HAEMOGLOBIN IN the different types of committed stem cells CELLS RBCs have the ability to concentrate haemoglobin in the cell fluid up to about 34 grams in each 100 millilitres of cells. This is the metabolic limit of the cell’s haemoglobin- forming mechanism. In normal people, the percentage of haemoglobin is almost always near the maximum in each cell. Decreased hgb formation- decreased percentage of hgb in the RBC- decreased RBC volume. When the haematocrit (the percentage of blood that is cells—normally, 40 to 45 per cent) and the quantity of haemoglobin in each respective cell are normal. Whole blood of men contains an average of 15 grams of haemoglobin per 100 millilitres of cells For women, it contains an average of 14 grams per 100 millilitres. Hemoglobin can accommodate 1.34 ml of oxygen if 100% saturated. o others induce growth of only On average man, a maximum of about 20 specific types of cells ml of oxygen can be carried in combination o Differentiation inducers - promote with hemoglobin in every 100 ml of blood, differentiation of the cells and in a woman, 19 ml of oxygen can be Growth inducers promote growth but not carried. differentiation of the cells. Each of these differentiation inducers V. GENESIS OF BLOOD CELLS causes one type of committed stem cell to PREPARED AND EDITED BY: ACSHAH, E. KANNAN, S. KUMAR R. MONCADA, R. MOTIC, G. MUNAR C. PRINCE J.  (004) RED BLOOD CELLS DR. AILYN ISAIS-AGDEPPA|10/13/2020 differentiate one or more steps toward a ✓ At the same time, the final adult blood cell endoplasmic reticulum is also Formation of the growth inducers and reabsorbed. (RETICULOCYTE) differentiation inducers is itself controlled by factors outside the bone marrow. Reticulocyte still contains a small amount of For instance, in the case of erythrocytes basophilic material, consisting of remnants (red blood cells), exposure of the blood to of the Golgi apparatus, mitochondria, and a low oxygen for a long-time results in growth few other cytoplasmic organelles. induction, differentiation, and production of During this reticulocyte greatly increased numbers of erythrocytes stage, the cells pass from In the case of some of the white blood cells, the bone marrow into the infectious diseases cause growth, blood capillaries by differentiation, and eventual formation of diapedesis (squeezing specific types of white blood cells that are through the pores of the needed to fight infection. capillary membrane). The remaining basophilic VI. STAGES OF DIFFERENTIATION OF material in the reticulocyte RBCs normally disappears The first cell that can be identified as within 1 to 2 days, and the belonging to the RBC series is the cell is then a mature proerythroblast. erythrocyte. Hemoglobin first appears in Because of the short life of polychromatophilia erythroblasts. the reticulocytes, their CFU-E stem cells (colony forming unit- concentration among all the red cells of the erythrocytes) blood is normally slightly less than 1 percent. Proerythroblast Reticulocyte and erythrocyte can only be proerythroblast divides multiple times, seen in the peripheral blood smear eventually forming many mature red blood Reticulocyte has little endoplasmic cells. reticulum The first-generation cells are called Retic-count- used to determine if the bone basophil erythroblasts because they stain marrow is responsive or functional to with basic dyes; the cell at this time has anemia. accumulated very little haemoglobin. In the succeeding generations, the cells become filled with: ✓ haemoglobin to a concentration of about 34 per cent ✓ the nucleus condenses to a small size ✓ its final remnant is absorbed or extruded from the cell VII. REGULATION OF RBC PRODUCTION Tissue Oxygenation is the Most Essential Regulator of Red Blood Cell Production. PREPARED AND EDITED BY: ACSHAH, E. KANNAN, S. KUMAR R. MONCADA, R. MOTIC, G. MUNAR C. PRINCE J.  (004) RED BLOOD CELLS DR. AILYN ISAIS-AGDEPPA|10/13/2020 Any condition that causes the quantity of The principal stimulus for red blood cell oxygen transported to then tissues to production in low oxygen states decrease ordinarily increases the rate of red In the absence of erythropoietin, hypoxia blood cell production. has little or no effect in stimulating red blood Thus, when a person becomes extremely cell production. anaemic as a result of haemorrhage or any When the erythropoietin system is other condition, the bone marrow functional, hypoxia causes a marked immediately begins to produce large increase in erythropoietin production, and quantities of red blood cells. the erythropoietin in turn enhances RBC Decrease the quantity of oxygen production until the hypoxia is relieved. transported to the tissues ordinarily increase the rate of RBC production VIII. ROLE OF KIDNEYS IN THE FORMATION OF ERYTHROPOIETIN 90% kidney - 10% liver In the normal person, about 90% of all erythropoietin is formed in the kidneys; the remainder is formed mainly in the liver. At times, hypoxia in other parts of the body, but not in the kidneys, stimulates kidney erythropoietin secretion, which suggests that there might be some nonrenal sensor that sends an additional signal to the kidneys to produce this hormone. When both kidneys are removed from a person or when the kidneys are destroyed by renal disease, the person invariably becomes very anaemic because the 10 per cent of the normal erythropoietin formed in Figure: Production of red blood cells when tissue other tissues (mainly in the liver) is sufficient oxygenation decreases. to cause only one third to one half the red blood cell formation needed by the body. Destruction of major portions of the bone the important effect of erythropoietin is to marrow by any means, especially by x-ray stimulate the production of proerythroblasts therapy, causes hyperplasia of the from hematopoietic stem cells in the bone remaining bone marrow, in an attempt marrow supply/meet the demand for red blood cells once the proerythroblasts are formed, the in the body. erythropoietin causes these cells to pass At very high altitudes, where the quantity of more rapidly through the different oxygen in the air is greatly decreased, erythroblastic stages than they normally do, insufficient oxygen is transported to the further speeding up the production of new tissues, and red cell production is greatly red blood cells. increased. The rapid production of cells continues as long as the person remains in a low oxygen A. ROLE OF ERYTHROPOIETIN state or until enough red blood cells have Various diseases of the circulation that been produced to carry adequate amounts cause decreased blood flow through the of oxygen to the tissues despite the low peripheral vessels/cause failure of oxygen oxygen; at this time, the rate of absorption by the blood as it passes through erythropoietin production decreases to a the lungs, (e.g. prolonged cardiac failure, level that will maintain the required number many lung diseases, tissue hypoxia) of red cells but not an excess. increases red cell production, resultant Some studies have suggested that increase in haematocrit and total blood erythropoietin is secreted mainly by volume. fibroblast-like interstitial cells surrounding B. ERYTHROPOIETIN the tubules in the cortex and outer medulla, A glycoprotein with a molecular weight of about 34,000 PREPARED AND EDITED BY: ACSHAH, E. KANNAN, S. KUMAR R. MONCADA, R. MOTIC, G. MUNAR C. PRINCE J.  (004) RED BLOOD CELLS DR. AILYN ISAIS-AGDEPPA|10/13/2020 where much of the kidney’s oxygen “Therefore, it is said that deficiency of either consumption occurs. vitamin B12 or folic acid causes maturation In the absence of erythropoietin, few red failure in the process of erythropoiesis.” blood cells are formed by the bone marrow. Aging plays a key role in RBC fragility At the other extreme, when large quantities Bone marrow is among the most rapidly of erythropoietin are formed available, and growing and reproducing cells in the entire if there is plenty of iron and other required body nutrients available, the rate of red blood cell production can rise to perhaps 10 or more TEST YOUR KNOWLEDGE times normal. 1. (T/F) Erythrocyte and reticulocyte IX. REQUIREMENTS FOR RBC can be seen in the bone marrow. MATURATION 2. (T/F) RBC does not have any nucleus, enzymes and mitochondria. VITAMIN B12 (CYANOCOBALAMIN) 3. (T/F) Many RBC self-destruct in the AND FOLIC ACID spleen. Important for final maturation of the RBC. Required for the formation of thymidine 4. Which of the following is not included triphosphate, one of the essential building in gestation. blocks of DNA. a) Liver Lack of either vitamin B12 or folic acid b) Lymph nodes causes abnormal and diminished DNA and, consequently, failure of nuclear maturation c) Lungs and cell division. d) Spleen The erythroblastic cells of the bone marrow, 5. Which is not included in the following: in addition to failing to proliferate rapidly, a) Low blood volume produce mainly larger than normal red cells b) Anemia called macrocytes, and the cell itself has a flimsy membrane and is often irregular, c) High hemoglobin large, and oval instead of the usual d) Poor blood flow biconcave disc. 6. How will the absence of These poorly formed cells, after entering the erythropoietin affect the production of circulating blood, are capable of carrying RBCs formed by the bone marrow? a) No effect b) Decreased production c) Increased production d) None of the above 7. The stage before erythrocyte in the differentiation process is: a) Proerythroblast b) Basophilic erythroblast c) Orthochromatic Erythroblast d) Reticulocyte 8. (T/F) Growth inducers promote growth and differentiation of the cells 9. Decrease in the atmospheric oxygen level a) Increases the RBC production oxygen normally, but their fragility causes b) Doesn’t affect the RBC them to have a short life, one half to one production third normal. c) Decreases the RBC production PREPARED AND EDITED BY: ACSHAH, E. KANNAN, S. KUMAR R. MONCADA, R. MOTIC, G. MUNAR C. PRINCE J.  (004) RED BLOOD CELLS DR. AILYN ISAIS-AGDEPPA|10/13/2020 d) Keeps it balanced to the outer environment 10. (T/F) When the erythropoietin system is functional, hypoxia causes a marked increase in erythropoietin production, and the erythropoietin in turn enhances RBC production until the hypoxia is relieved. Answers: 1. F 2. F 3. T 4. C 5. C 6. B 7. D 8. F 9. A 10. T REFERENCES 1. Hall, J. E., & Hall, M. E. (2016). Red Blood Cells, Anemia, and Polycythemia. In Guyton and Hall Text Book of Medical Physiology (14th ed., pp. 439-447). Philadelphia: Elsevier. PREPARED AND EDITED BY: ACSHAH, E. KANNAN, S. KUMAR R. MONCADA, R. MOTIC, G. MUNAR C. PRINCE J.