[PHYSIO]-LC5-Red Blood Cells, Anemia and Polycythemia.docx.pdf

OUTLINE I. RED BLOOD CELL II. SHAPE AND SIZE OF RBC III. CONCENTRATION OF RBC IN THE BLOOD IV. QUANTITY OF HEMOGLOBIN IN THE CELLS V. PRODUCTION OF AN RBC VI. GENESIS OF BLOOD CELLS VII. REGULATION OF RBC PRO...

OUTLINE I. RED BLOOD CELL II. SHAPE AND SIZE OF RBC III. CONCENTRATION OF RBC IN THE BLOOD IV. QUANTITY OF HEMOGLOBIN IN THE CELLS V. PRODUCTION OF AN RBC VI. GENESIS OF BLOOD CELLS VII. REGULATION OF RBC PRODUCTION A. Tissue Oxygenation B. Role of Erythropoietin C. Role of Kidney VIII. REQUIREMENTS FOR RBC MATURATION A. Vitamin B12 (Cyanocobalamin) And Folic Acid IX. LIFESPAN AND DESTRUCTION OF RBC X. ANEMIA AND POLYCYTHEMIA XI. IRON METABOLISM Figure 1. Red blood cell A. Main Tissues Involved In The Regulation Of Systemic Iron Metabolism B. Regulation of Total Body Iron by Controlling Rate of II. SHAPE AND SIZE OF RBC Absorption XII. PERNICIOUS ANEMIA A. Failure Of Maturation Caused By Folic Acid Deficiency - RBCs are biconcave discs having a mean diameter of about 7.8 B. Destruction of Hemoglobin micrometers and a thickness of 2.5 micrometers at the thickest point XIII. ANEMIA: TYPES OF ANEMIAS and 1 micrometer or less in the center. XIV. EFFECTS OF ANEMIA IN THE CIRCULATORY SYSTEM - The average volume of the red blood cell is 90 to 95 cubic micrometers. - The shapes of red blood cells can change remarkably as the cells squeeze through capillaries. I. RED BLOOD CELLS - RBC is like a “bag” that can be deformed into almost any shape. - Deformation does not stretch the membrane greatly and, consequently, does not rupture the cell, as would be the case with - also known as erythrocytes many other cells. Functions of Red Blood Cells (RBC’s): - Major function: transport hemoglobin ○ Hemoglobin Carries oxygen from the lungs to the tissues When it is free in the plasma of the human being, about 3% of it leaks through the: ▪ capillary membrane into the tissue spaces ▪ or through the glomerular membrane of the kidney into the glomerular filtrate each time the blood passes through the capillaries - Other Function: Acid-Base Buffer o RBC contains a large quantity of carbonic anhydrase making it an Figure 2. Shape and size of RBC excellent acid-base buffer. o Carbonic anhydrase is an enzyme that catalyzes the reversible reaction between carbon dioxide (CO2) and water to form Structure of an RBC: carbonic acid (H2CO3), the rapidity of this reaction makes it - Large surface area to volume ratio for rapid gas exchange. possible for the water of the blood to transport enormous - Lack organelles: quantities of CO2 in the form of bicarbonate ion (HCO3-) from the ○ No nucleus tissues to the lungs, where it is reconverted to CO2 and expelled ○ No ribosomes into the atmosphere as a body waste product. ○ No mitochondria (i.e. no electron transport chain): 90% of o The hemoglobin in the cells is an excellent acid-base buffer (as is energy comes from glycolysis, 10% from hexose true of most proteins), so that the red blood cells are responsible monophosphate shunt. for most of the acid-base buffering power of whole blood. - Remarkable ability to deform in order to accommodate small capillaries - Deformability of an RBC is a consequence of: ○ High surface area/volume ratio ○ Viscosity of the cytoplasm (predominantly determined by intracellular hemoglobin (Hgb) concentration) ○ Mechanical properties of the membrane (determined by integral membrane proteins and submembrane cytoskeletal structure including: ankyrin, spectrin, band 3, band 4.1) RBC maturation as the cell matures, 1. Decrease N:C ratio 2. Decrease size Page 1 of 9 [PHYSIOLOGY] 1.05 RED BLOOD CELLS, ANEMIA AND POLYCYTHEMIA- Dr. Ailyn T. Isais Agdeppa 3. Decrease nucleoli number -Prior to the fifth month of fetal development, hematopoiesis begins 4. Decrease / loss of basophilia in the bone marrow cavity. 5. Fine to coarse, clumped, and condensed chromatin pattern -Hematopoiesis occurs in the medulla or inner part of the bone VI. GENESIS OF BLOOD CELLS III. CONCENTRATION OF RBC IN THE BLOOD - In normal men, the average number of red blood cells per cubic millimeter is 5,200,000 (±300,000) - In normal women, it is 4,700,000 (±300,000). - Persons living at high altitudes have greater numbers of red blood cells. - Higher altitudes have less oxygen so the body has to compensate for the low oxygen level, producing more blood, increasing the total red blood cells. IV. QUANTITY OF HEMOGLOBIN IN THE CELLS - RBCs have the ability to concentrate hemoglobin in the cell fluid up to about 34 grams in each 100 milliliters of cells. - This is the metabolic limit of the cell’s hemoglobin-forming mechanism. - In normal people, the percentage of hemoglobin is almost always near the maximum in each cell. Figure 3. Genesis of Blood Cells. Formation of the multiple different blood cells - Decreased hgb formation → decreased percentage of hgb in the RBC from the original pluripotent hematopoietic stem cell (PHSC) in the bone → decreased RBC volume marrow. - When the hematocrit (the percentage of blood that is cells—normally, 40 to 45 per cent) and the quantity of hemoglobin in - The blood cells begin their lives in the bone marrow from a single each respective cell are normal type of cell called the pluripotential hematopoietic stem cell. - Whole blood of men contains an average of 15 grams of hemoglobin - A portion of them remains exactly like the original retained in the per 100 milliliters of cells bone marrow to maintain a supply of these. - For women, it contains an average of 14 grams per 100 milliliters - Most of the reproduced cells differentiate to form the other cell types, the intermediate stage cells are very much like the pluripotent stem cells, committed to a particular line of cells and are called V. PRODUCTION OF AN RBC committed stem cells. - A committed stem cell that produces erythrocytes is called a colony-forming unit–erythrocyte (CFU-E). Areas of the Body That Produce Red Blood Cells: - Colony-forming units that form granulocytes and monocytes have the - In the early weeks of embryonic life, primitive, nucleated red blood designation CFU-GM. cells are produced in the yolk sac. - Growth and reproduction of the different stem cells are controlled by - During the middle trimester of gestation: multiple proteins called growth inducers. o Liver is the main organ for production of red blood cells, but o Growth inducers: reasonable numbers are also produced in the spleen and ▪ interleukin-3 - promotes growth and reproduction of lymph nodes. virtually all the different types of committed stem cells - During the last month or so of gestation and after birth: ▪ others induce growth of only specific types of cells o Bone Marrow exclusively produces RBCs. ▪ Differentiation inducers - promote differentiation of the o The bone marrow of essentially all bones produces red blood cells cells until a person is 5 years old. - Formation of the growth inducers and differentiation inducers is o The marrow of the long bones, except for the proximal itself controlled by factors outside the bone marrow. portions of the humeri and tibiae, becomes quite fatty and o HYPOXIA: For instance, in the case of erythrocytes (red blood produces no more red blood cells after about age 20 years. cells), exposure of the blood to low oxygen for a long time o Beyond 20 years of age, most red cells continue to be produced results in growth induction, differentiation, and production of in the marrow of the membranous bones, such as the greatly increased numbers of erythrocytes vertebrae, sternum, ribs, and iliac. o INFECTION: In the case of some of the white blood cells, o Even in these bones, the marrow becomes less productive as infectious diseases cause growth, differentiation, and eventual age increases. formation of specific types of white blood cells that are needed to fight infection. Mesoblastic or yolk sac phase -considered to begin around the nineteenth day of embryonic development after fertilization -Hematopoiesis occurs intravascularly, or within developing blood vessels Hepatic phase -hematopoiesis begins at 5 to 7 gestational weeks and is characterized by recognizable clusters of developing erythroblasts, granulocytes, and monocytes colonizing the fetal liver, thymus, spleen, placenta. Medullary or myeloid phase Page 2 of 9 [PHYSIOLOGY] 1.05 RED BLOOD CELLS, ANEMIA AND POLYCYTHEMIA- Dr. Ailyn T. Isais Agdeppa Figure 6. Regulation of RBC A. Tissue Oxygenation Is the Most Essential Regulator of Red Blood Cell Production - Any condition that causes the quantity of oxygen transported to the tissues to decrease ordinarily increases the rate of red blood cell production. - Thus, when a person becomes extremely anemic as a result of hemorrhage or any other condition, the bone marrow immediately begins to produce large quantities of red blood cells. - Destruction of major portions of the bone marrow by any means, especially by x-ray therapy, causes hyperplasia of the Figure 4. RBC Production and maturation remaining bone marrow, in an attempt to supply/meet the demand for red blood cells in the body. Stages Of Differentiation Of Red Blood Cells - At very high altitudes, where the quantity of oxygen in the air - CFU-E stem cells (colony forming unit-erythrocytes) is greatly decreased, insufficient oxygen is transported to the - Proerythroblast tissues, and red cell production is greatly increased. o Proerythroblast divides multiple times, eventually forming many mature red blood cells. B. Role of Erythropoietin - The first-generation cells are called basophil erythroblasts because - Various diseases of the circulation that cause decreased blood they stain with basic dyes; the cell at this time has accumulated very flow through the peripheral vessels/cause failure of oxygen little hemoglobin. absorption by the blood as it passes through the lungs, (e.g. - In the succeeding generations, the cells become filled with: prolonged cardiac failure, many lung diseases, tissue hypoxia) o hemoglobin to a concentration of about 34 percent increases red cell production, resultant increase in o the nucleus condenses to a small size hematocrit and total blood volume. o its final remnant is absorbed or extruded from the cell - Erythropoietin o At the same time, the endoplasmic reticulum is also reabsorbed o A glycoprotein with a molecular weight of about (RETICULOCYTE) 34,000 o The principal stimulus for red blood cell production in low oxygen states o In the absence of erythropoietin, hypoxia has little or no effect in stimulating red blood cell production. o 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. C. Role Of The Kidneys In Formation Of Erythropoietin Figure 5. Different stages of Red Blood Cells formation - Reticulocyte still contains a small amount of basophilic material, consisting of remnants of the Golgi apparatus, mitochondria, and a few other cytoplasmic organelles. - During this reticulocyte stage, the cells pass from the bone marrow into the blood capillaries by diapedesis (squeezing through the pores of the capillary membrane). - The remaining basophilic material in the reticulocyte normally disappears within 1 to 2 days, and the cell is then a mature erythrocyte. - Because of the short life of the reticulocytes, their concentration among all the red cells of the blood is normally slightly less than 1 percent. Figure 7. Function of the erythropoietin mechanism to increase production of red blood cells when tissue oxygenation decreased. VII. REGULATION OF RBC PRODUCTION - 90% in kidney, 10% in liver - In the normal person, about 90% of all erythropoietin is formed in the kidneys; the remainder 10% 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 anemic because the 10% of the normal Page 3 of 9 [PHYSIOLOGY] 1.05 RED BLOOD CELLS, ANEMIA AND POLYCYTHEMIA- Dr. Ailyn T. Isais Agdeppa erythropoietin formed in other tissues (mainly in the liver) is sufficient to cause only one third to one half the red blood cell IX. LIFE SPAN AND DESTRUCTION OF RBC formation needed by the body. - The important effect of erythropoietin is to stimulate the - When red blood cells are delivered from the bone marrow into the production of proerythroblasts from hematopoietic stem cells circulatory system, they normally circulate an average of 120 days in the bone marrow. before being destroyed. - Once the proerythroblasts are formed, the erythropoietin causes - Even though mature red cells do not have a nucleus, mitochondria, these cells to pass more rapidly through the different or endoplasmic reticulum, they do have cytoplasmic enzymes that erythroblastic stages than they normally do, further speeding up are capable of metabolizing glucose and forming small amounts of the production of new red blood cells. adenosine triphosphate. - The rapid production of cells continues as long as the person - These enzymes also (1) maintain pliability of the cell membrane, (2) remains in a low oxygen state or until enough red blood cells maintain membrane transport of ions, (3) keep the iron of the cells’ have been produced to carry adequate amounts of oxygen to the hemoglobin in the ferrous form rather than ferric form, and (4) tissues despite the low oxygen; at this time, the rate of prevent oxidation of the proteins in the red cells. erythropoietin production decreases to a level that will maintain - Even so, the metabolic systems of old red cells become progressively the required number of red cells but not an excess. less active, and the cells become more and more fragile, presumably - In the absence of erythropoietin, few red blood cells are formed because their life processes wear out. by the bone marrow. - Once the red cell membrane becomes fragile, the cell ruptures - At the other extreme, when large quantities of erythropoietin during passage through some tight spot of the circulation. are formed, and if there is plenty of iron and other required - Many of the red cells self-destruct in the spleen, where they squeeze nutrients available, the rate of red blood cell production can rise through the red pulp of the spleen. to perhaps 10 or more times normal. - When the spleen is removed, the number of old abnormal red cells o Large quantities of erythropoietin in the body can be circulating in the blood increases considerably. caused by: ▪ administering erythropoietin shots to a person Removal Of RBCs From The Circulation with normal functioning kidneys - Normal removal of aged RBCs predominantly occurs within the ▪ a problem in the regulation of kidneys (the kidneys spleen. could not detect that tissues are already - Accumulated factors requiring their removal include: oxygenated so they still keep on secreting o oxidative damage erythropoietin) o cycles of osmotic swelling and shrinkage o decreased surface area over time, leading to decreased VIII. REQUIREMENTS FOR RBC MATURATION deformability o repetitive deformations from squeezing through capillaries o shearing force from passing through the heart valves A. Vitamin B12 (Cyanocobalamin) And Folic Acid - Important for final maturation of the RBC. - Required for the formation of thymidine triphosphate, one X. ANEMIA AND POLYCYTHEMIA of the essential building blocks of DNA. - Lack of either vitamin B12 or folic acid causes abnormal and A. FORMATION OF HEMOGLOBIN diminished DNA and, consequently, failure of nuclear - Synthesis of hemoglobin begins in the proerythroblasts and maturation and cell division. continues even into the reticulocyte stage of the red blood - The erythroblastic cells of the bone marrow, in addition to cells. failing to proliferate rapidly, produce mainly larger than - When reticulocytes leave the bone marrow and pass into the normal red cells called macrocytes, and the cell itself has a bloodstream, they continue to form minute quantities of flimsy membrane and is often irregular, large, and oval hemoglobin for another day or so until they become mature instead of the usual biconcave disc. erythrocytes. - These poorly formed cells, after entering the circulating - There are several slight variations in the different subunit blood, are capable of carrying oxygen normally, but their hemoglobin chains, depending on the amino acid fragility causes them to have a short life, one half to one composition of the polypeptide portion. third normal. - The different types of chains are designated alpha chains, beta chains, gamma chains, and delta chains. “Therefore, it is said that deficiency of either vitamin B12 or folic acid causes - The most common form of hemoglobin in the adult human maturation failure in the process of erythropoiesis.” being, hemoglobin A, is a combination of two alpha chains and two beta chains. Folate or folic acid - There are four hemoglobin chains in each hemoglobin -consist of a pteridine ring attached to para-aminobenzoate with one molecule, one finds four iron atoms in each hemoglobin or more glutamate residues molecule; each of these can bind loosely with one molecule -function is to transfer carbon units in the form of methyl groups of oxygen, making a total of four molecules of oxygen (or from donors to receptors eight oxygen atoms) that can be transported by each -heat labile hemoglobin molecule. Causes of impaired vitamin B12 absorption (1) failure to separate vitamin B12 from food proteins in the stomach (a.k.a Food- cobalamin malabsorption) (2) failure to separate vitamin B12 from haptocorrin in the intestine due to lack of gastric acidity or trypsin. (3) lack of intrinsic factor, (4) malabsorption, and (5) competition for available vitamin B12 (parasitic infection fish tapeworm, Diphyllobothrium latum) Page 4 of 9 [PHYSIOLOGY] 1.05 RED BLOOD CELLS, ANEMIA AND POLYCYTHEMIA- Dr. Ailyn T. Isais Agdeppa Figure 8. Hemoglobin formation Erythrocytes = Erythro (Red) & Cyte (Cell) - Also known as Red Blood Cells (RBCs) - Most numerous formed element (4-6 million) - Functions in the transport of respiratory gases (O2 and CO2) - Biconcave disc (no nucleus or organelles) o Lost these prior to reticulocyte formation - Contains hemoglobin (280 million/RBC) o Protein found in cytosol Hemoglobin - Protein (4 globins) with associated heme groups and Fe2+ (iron) - Each hemoglobin molecule can bind 4 O2 molecule - O2 binds specifically with Fe2+ Figure 10. RBC Indices - CO2 binds with the globin molecules Table 1. RBC Indices. Formula and definitions Erythropoietin (EPO) - A hormone produced in kidney and acts at bone - Controls erythropoiesis (production of RBCs) - Stimulus – low blood O2 levels Index Definition Formula Iron, B Vitamins (B12), and Amino Acids - Acquired through diet - Necessary for maturation/development MCV Average (Mean volume of a Corpuscular single RBC Volume) MCH Average (Mean amount of Corpuscular hemoglobin Hemoglobin) within a single RBC MCHC Average (Mean concentration Corpuscular of MCH Hemoglobin Figure 9. Heme. Hemoglobin molecule structure Concentration) RDW Measure of (Red Cell variation in (there is a multiple, slightly different Distribution RBC Size quantitative means to define it) Width) Parameter Description MCV - reflects RBC diameter in blood MCHC - reflects RBC staining intensity and amount of central pallor MCH - expresses the mass of hemoglobin, least used to classify anemia RDW - fourth RBC index Page 5 of 9 [PHYSIOLOGY] 1.05 RED BLOOD CELLS, ANEMIA AND POLYCYTHEMIA- Dr. Ailyn T. Isais Agdeppa - The reticuloendothelial system, which includes the splenic macrophages, recycles iron from senescent erythrocytes. - Among many other functions, the liver produces the hormone hepcidin. Hepcidin controls the release of iron from enterocytes and macrophages into the circulation and is regarded as the master regulator of systemic iron metabolism. Figure 11. RDW (differences) XI. IRON METABOLISM - The total quantity of iron in the body averages 4 to 5 grams Figure 13. Regulation of Systemic Iron metabolism - about 65% of which is in the form of hemoglobin - about 4% is in the form of myoglobin - 1% is in the form of the various heme compounds that promote - When iron is absorbed from the small intestine, intracellular oxidation it immediately combines in the blood plasma with a - 0.1% is combined with the protein transferrin in the blood plasma, beta globulin, apotransferrin, to form transferrin, which is and 15 to 30 per cent is stored for later use, mainly in the then transported in the plasma. reticuloendothelial system and liver parenchymal cells, principally in - The iron is loosely bound in the transferrin and, the form of ferritin. consequently, can be released to any tissue cell at any point in the body. - Excess iron in the blood is deposited especially in the liver hepatocytes and less in the reticuloendothelial cells of the bone marrow. - In the cell cytoplasm, iron combines mainly with a protein, apoferritin, to form ferritin. - Ferritin is called storage iron. - Smaller quantities of the iron in the storage pool are in an extremely insoluble form called hemosiderin. - When the quantity of iron in the plasma falls low, some of the iron in the ferritin storage pool is removed easily and transported in the form of transferrin in the plasma to the areas of the body where it is needed. - A unique characteristic of the transferrin molecule is that it binds strongly with receptors in the cell membranes of erythroblasts in the bone marrow. - Then, along with its bound iron, it is ingested into the erythroblasts by endocytosis. - There, the transferrin delivers the iron directly to the mitochondria, where heme is synthesized. - In people who do not have adequate quantities of transferrin in their blood, failure to transport iron to the erythroblasts in this manner can cause severe hypochromic anemia—that is, red cells that contain much less hemoglobin than normal. B. Regulation of Total Body Iron by Controlling Rate of Absorption Figure 12. Iron Metabolism - When the body has become saturated with iron so that essentially all apoferritin in the iron storage areas A. Main Tissues Involved In The Regulation Of Systemic Iron is already combined with iron, the rate of additional iron absorption from the intestinal tract becomes greatly Metabolism decreased. - Duodenal enterocytes are responsible for dietary iron - Conversely, when the iron stores have become depleted, the absorption. Upon absorption, iron circulates around the body rate of absorption can accelerate probably five or more bound to the protein transferrin and is taken up by different times normal. tissues for utilisation. Page 6 of 9 [PHYSIOLOGY] 1.05 RED BLOOD CELLS, ANEMIA AND POLYCYTHEMIA- Dr. Ailyn T. Isais Agdeppa “Thus, total body iron is regulated mainly by altering the rate of A. Failure Of Maturation Caused By Folic Acid Deficiency absorption.” - Folic acid is a normal constituent of green vegetables, some fruits, and meats (especially liver). However, it is easily destroyed during cooking. (Heat labile) - Also, people with gastrointestinal absorption abnormalities, such as the frequently occurring small intestinal disease called sprue, often have serious difficulty absorbing both folic acid and vitamin B12. “Therefore, in many instances of maturation failure, the cause is deficiency of intestinal absorption of both folic acid and vitamin B12.” B. Destruction of Hemoglobin - When red blood cells burst and release their hemoglobin, the hemoglobin is phagocytized almost immediately by macrophages in many parts of the body, but especially by the Kupffer cells of the liver and macrophages of the spleen and bone marrow. - During the next few hours to days, the macrophages release iron from the hemoglobin and pass it back into the blood, to be carried by transferrin either to the bone marrow for the production of new red blood cells or to the liver and other tissues for storage in the form of ferritin. - The porphyrin portion of the hemoglobin molecule is converted by the macrophages, through a series of stages, into the bile pigment bilirubin, which is released into the blood and later removed from the body by secretion through the liver into the bile. XIII. ANEMIA: TYPES OF ANEMIAS ANEMIAS - deficiency of hemoglobin in the blood, which can be caused by either too few red blood cells or too little hemoglobin in the cells. TYPES OF ANEMIAS 1. BLOOD LOSS ANEMIA a. ACUTE BLOOD LOSS Figure 14. RBC Maturation: Vitamin B12 and Folic Acid - After rapid hemorrhage, plasma volume is restored in 1 to 3 days, but this leaves a low concentration of red blood cells. - If a second hemorrhage does not occur, the red blood cell concentration usually returns to normal within 3 to 6 weeks. XII. PERNICIOUS ANEMIA b. CHRONIC BLOOD LOSS - In chronic blood loss, a person frequently cannot absorb - Anemia resulting from failure to absorb Vitamin B12 due to failure of enough iron from the intestines to form hemoglobin as an atrophic gastric parietal cells to secrete intrinsic factor rapidly as it is lost. - A common cause of red blood cell maturation failure is failure to - Red cells are then produced that are much smaller than absorb vitamin B12 from the gastrointestinal tract. normal and have too little hemoglobin inside them, giving - The basic abnormality is an atrophic gastric mucosa that fails to rise to microcytic, hypochromic anemia produce normal gastric secretions. - The parietal cells of the gastric glands secrete a glycoprotein called 2. APLASTIC ANEMIA intrinsic factor, which combines with vitamin B12 in food and makes - Bone marrow aplasia means lack of functioning bone marrow. the B12 available for absorption by the gut. (1) Intrinsic factor binds tightly with the vitamin B12. In this bound 3. MEGALOBLASTIC ANEMIA state, the B12 is protected from digestion by the gastrointestinal - Secondary to deficient of either vitamin B12, folic acid, and intrinsic secretions. factor from the stomach mucosa (2) Still in the bound state, the intrinsic factor binds to specific - Loss of any one of these can lead to slow reproduction receptor sites on the brush border membranes of the mucosal of erythroblasts in the bone marrow. cells in the ileum. - As a result, the red cells grow too large, with odd shapes, and are (3) Then, vitamin B12 is transported into the blood during the next called megaloblasts. few hours by the process of pinocytosis, carrying intrinsic factors - In these states, the erythroblasts cannot proliferate rapidly enough and the vitamin together through the membrane. to form normal numbers of red blood cells, those red cells that are formed are mostly oversized, have bizarre shapes, and have fragile “Lack of intrinsic factor, therefore, causes diminished availability of vitamin membranes. B12 because of faulty absorption of the vitamin.” - These cells rupture easily, leaving the person in dire need of an adequate number of red cells. Page 7 of 9 [PHYSIOLOGY] 1.05 RED BLOOD CELLS, ANEMIA AND POLYCYTHEMIA- Dr. Ailyn T. Isais Agdeppa 4. HEMOLYTIC ANEMIA - Can be hereditary or acquired making the cells fragile, easily ruptures as they pass through the capillaries, spleen - The number of RBC formed may be normal or greater but cell fragility makes its lifespan shorter so that the cells are destroyed faster than they can be formed, and serious anemia results. Examples: - In hereditary spherocytosis, the red cells are very small and spherical rather than being biconcave discs. - In sickle cell anemia: ○ Present in 0.3 to 1.0% of West African and American blacks ○ The cells have an abnormal type of hemoglobin called hemoglobin S, containing faulty beta chains in the hemoglobin molecule. Figure 15. Diagnostic Framework for Anemia: Morphological and Kinetic ○ Exposure to low O2 concentrations of oxygen → beta Approach chains precipitates into long crystals inside the red blood cell → crystals elongate the cell sickle shaped RBC → precipitated hemoglobin also damages the cell membrane → highly fragile → serious anemia ○ Such patients frequently experience a vicious circle of events called a sickle cell disease “crisis,” in which low oxygen tension in the tissues causes sickling, which leads to ruptured red cells, which causes a further decrease in oxygen tension and still more sickling and red cell destruction. Once the process starts, it progresses rapidly, eventuating in a serious decrease in red blood cells within a few hours and, often, death. - In erythroblastosis fetalis ○ Rh-positive red blood cells in the fetus are attacked by antibodies from an Rh-negative mother. ○ These antibodies make the Rh-positive cells fragile, leading to rapid rupture and causing the child to be born with serious anemia. Figure 16. Red Blood Cell Morphology Morphological vs. Kinetic Frameworks ○ In practice, both the MCV and the retic index are typically used together in order to diagnose the etiology of an anemia ○ However, the categorization of etiologies by MCV and the calculation of the retic index (including maturation factors) are based on old data that has generally not been replicated ○ Therefore, cutoffs for specific categories should be considered very approximate ○ Some hematologists recommend using the absolute retic count (retic % x RBC count) instead of the retic index Figure 17. Different types of anemia based on MCV (size) and MCHC (hgb content) Page 8 of 9 [PHYSIOLOGY] 1.05 RED BLOOD CELLS, ANEMIA AND POLYCYTHEMIA- Dr. Ailyn T. Isais Agdeppa viscosity to increase peripheral resistance and, thereby,increase arterial pressure. Beyond certain limits, however, these regulations XIV. EFFECTS OF ANEMIA IN THE CIRCULATORY SYSTEM fail, and hypertension develops. - Because the blood passes sluggishly through the skin capillaries - In severe anemia, the blood viscosity may fall to as low as 1.5 times before entering the venous plexus, a larger than normal quantity of that of water rather than the normal value of about 3. hemoglobin is deoxygenated. The blue color of all this deoxygenated - This decreases the resistance to blood flow in the peripheral blood hemoglobin masks the red color of the oxygenated hemoglobin. vessels, so that far greater than normal quantities of blood flow Therefore, a person with polycythemia vera ordinarily has a ruddy through the tissues and return to the heart, thereby greatly complexion with a bluish (cyanotic) tint to the skin. increasing cardiac output. - Hypoxia resulting from diminished transport of oxygen by the blood causes the peripheral tissue blood vessels to dilate, allowing a References: further increase in the return of blood to the heart and increasing Hall, J. E. (2016). Guyton and Hall Textbook of Medical Physiology (13th ed.). the cardiac output to a still higher level— sometimes three to four Philadelphia: Elsevier, Inc. times normal. - Thus, one of the major effects of anemia is greatly increased cardiac Additional Video References: output, as well as increased pumping workload on the heart. https://youtu.be/bbUlaTApuuI - The increased cardiac output in anemia partially offsets the reduced https://youtu.be/0deCbmh7PHs oxygen-carrying effect of the anemia, because even though each unit https://youtu.be/RYB8W90BKj4 quantity of blood carries only small quantities of oxygen, the rate of https://youtu.be/nyHfCNKaArg https://youtu.be/xEHGIRpGyh4 blood flow may be increased enough so that almost normal https://images.app.goo.gl/NdwxQqkNjNJqkUDi6 quantities of oxygen are actually delivered to the tissues. https://images.app.goo.gl/NdwxQqkNjNJqkUDi6 - However, when a person with anemia begins to exercise, the heart is https://www.mdpi.com/509640 not capable of pumping much greater quantities of blood than it is https://d3i71xaburhd42.cloudfront.net/10dffb91283c63e7d275f1af53d980aa84 already pumping. Consequently, during exercise, which f82620/5-Figure5-3-1.png greatly increases tissue demand for oxygen, extreme tissue https://images.app.goo.gl/sfESCdiPtGcr5yMh9 hypoxia results, and acute cardiac failure ensues. https://images.app.goo.gl/9D4m5wULhtSJ1Kde6 https://youtu.be/GSrPe04NkcI SECONDARY POLYCYTHEMIA https://youtu.be/ODvN_4kloUg https://youtu.be/d0GxAtkBrgQ - Whenever the tissues become hypoxic because of too little oxygen in https://youtu.be/_542TQN_kvA the breathed air, such as at high altitudes, or because of failure of oxygen delivery to the tissues, such as in cardiac failure, the blood-forming organs automatically produce large quantities of extra red blood cells. - This condition is called secondary polycythemia, and the RBC count commonly rises to 6 to 7 million/mm3, about 30% above normal. - A common type of secondary polycythemia, called physiologic polycythemia, occurs in natives who live at altitudes of 14,000 to 17,000 feet, where the atmospheric oxygen is very low. The blood count is generally 6 to 7 million/mm3; this allows these people to perform reasonably high levels of continuous work even in a rarefied atmosphere. POLYCYTHEMIA VERA (ERYTHREMIA) - A pathological condition in which the red blood cell count may be 7 to 8 million/mm3 and the hematocrit may be 60 to 70 percent instead of the normal 40 to 45 per cent. - Caused by a genetic aberration in the hemocytoblastic cells that produce the blood cells wherein blast cells no longer stop producing red cells when too many cells are already present resulting to excess RBC production as well as excess production of white blood cells and platelets - In polycythemia vera, not only does the hematocrit increase, but the total blood volume also increases, on some occasions to almost twice normal. - As a result, the entire vascular system becomes intensely engorged. - Many blood capillaries become plugged by the viscous blood EFFECT OF POLYCYTHEMIA ON CIRCULATION - Increased blood viscosity results to very sluggish blood flow in the peripheral vessels increasing blood viscosity decreases the rate of venous return to the heart. - Conversely, the increased blood volume in polycythemia tends to increase venous return. - The cardiac output in polycythemia is not far from normal, because these two factors more or less neutralize each other. - The arterial pressure is also normal in most people with polycythemia, although in about one third of them, the arterial pressure is elevated. This means that the blood pressure–regulating mechanisms can usually offset the tendency for increased blood Page 9 of 9