[PHYSIO]LEC_005_ANEMIA AND POLYCYTHEMIA.pdf

(005) ANEMIA AND POLYCYTHEMIA DR. AILYN T. ISAIS-AGDEPPA, MD, DPPS | 09/11/2020 OUTLINE normal red cells called macrocytes, and the cell itself has a...

(005) ANEMIA AND POLYCYTHEMIA DR. AILYN T. ISAIS-AGDEPPA, MD, DPPS | 09/11/2020 OUTLINE normal red cells called macrocytes, and the cell itself has a I. QUANTITY OF HEMOGLOBIN IN THE CELLS flimsy membrane and is often irregular, large, and oval A. REQUIREMENTS FOR RBC MATURATION: instead of the usual biconcave disc. VITAMIN B12 (CYANOCOBALAMIN) AND These poorly formed cells, after entering the circulating FOLIC ACID blood, are capable of carrying oxygen normally, but their B. PERNICIOUS ANEMIA fragility causes them to have a short life, one half to one third C. FAILURE OF MATURATION CAUSED BY normal. FOLIC ACID DEFICIENCY “Therefore, it is said that deficiency of either vitamin B12 or II. FORMATION OF HEMOGLOBIN folic acid causes maturation failure in the process of III. IRON METABOLISM erythropoiesis.” A. MAIN TISSUES INVOLVED IN THE REGULATION OF SYSTEMIC IRON -During RBC differentiation it needs Vitamin B12 and folic acid METABOLISM B. REGULATION OF TOTAL BODY IRON BY which results in the final maturation process maturation of RBC in CONTROLLING RATE OF ABSORPTION order for it to have its usual biconcave shape and flexibility. If a IV. DESTRUCTION OF HEMOGLOBIN patient has a lacking diet which their insufficient vitamin B12 and V. ANEMIAS /or folic or a medical condition that prevents to effectively absorb A. TYPES OF ANEMIAS vitamin B12 and/or folic acid it will result in the deficiency of B. EFFECTS OF ANEMIA IN THE CIRCULATORY vitamin B12 and folic acid that will cause the RBC to be larger SYSTEM than normal or defective adult RBC (larger the unusual and VI. POLYCYTHEMIA irregular in shape). It has the same oxygen carrying capacity A. TYPES OF POLYCYTHEMIA however flexibility is compromise leading to a shorter RBC life B. EFFECT OF POLYCYTHEMIA ON span CIRCULATION -Patients will present macrocytic, normochromic anemia which I. QUANTITY OF HEMOGLOBIN IN THE CELLS has increased MCV and normal MCHC RBCs have the ability to concentrate hemoglobin in the cell fluid up to about 34 grams in each 100 milliliters of cells. B. PERNICIOUS ANEMIA Decreased hemoglobin formation → decreased percentage of hemoglobin in the RBC → decreased RBC volume A common cause of red blood cell maturation failure is Whole blood of men: average of 15 grams of hemoglobin per 100 failure to absorb vitamin B12 from the gastrointestinal milliliters of cells tract Whole blood of women: average of 14 grams per 100 milliliters. The basic abnormality is an atrophic gastric mucosa that fails to produce normal gastric secretions. The parietal cells of the gastric glands secrete a glycoprotein called intrinsic factor, which combines with vitamin B12 in food and makes the B12 available for absorption by the gut. (1) Intrinsic factor binds tightly with the vitamin B12. In this bound state, the B12 is protected from digestion by the gastrointestinal secretions. (2) Still in the bound state, intrinsic factor binds to specific receptor sites on the brush border membranes of the mucosal cells in the ileum. (3) Then, vitamin B12 is transported into the blood during the next few hours by the process of pinocytosis, carrying intrinsic factor and the vitamin together through the membrane. Figure 1. Genesis of Red Blood Cells “Lack of intrinsic factor, therefore, causes diminished availability of vitamin B12 because of faulty absorption of the -RBC’s physical features in times of anemia or polycythemia values vitamin.” of the physical features’ changes - Anemia occurs which is secondary to deficiency of vitamin b12, A. REQUIREMENTS FOR RBC MATURATION: secondary to lack of intrinsic factor, secondary to failure to produce VITAMIN B12 (CYANOCOBALAMIN) AND normal amounts intrinsic factor, secondary to atrophic gastric mucosa. FOLIC ACID Important for final maturation of the RBC. The erythroblastic cells of the bone marrow, in addition to failing to proliferate rapidly, produce mainly larger than PREPARED AND EDITED BY: GROUP 8 LUMAYAG, J., MANLONGAT, A. MOJICA, S., PRUDENCIO, J., PUZON, M., QUIAMBAO, C., QUILALA., E  (005) ANEMIA AND POLYCYTHEMIA DR. AILYN T. ISAIS-AGDEPPA, MD, DPPS | 09/11/2020 C. FAILURE OF MATURATION CAUSED BY FOLIC There are four hemoglobin chains in each hemoglobin molecule, one finds four iron atoms in each hemoglobin ACID DEFICIENCY molecule; each of these can bind loosely with one molecule of oxygen, making a total of four molecules of oxygen (or Folic acid is a normal constituent of green vegetables, some eight oxygen atoms) that can be transported by each fruits, and meats (especially liver). However, it is easily hemoglobin molecule. destroyed during cooking. Also, people with gastrointestinal absorption abnormalities, such as the frequently occurring small intestinal disease III. IRON METABOLISM called sprue, often have serious difficulty absorbing both folic The total quantity of iron in the body averages 4 to 5 grams acid and vitamin B12. about 65% of which is in the form of hemoglobin “Therefore, in many instances of maturation failure, the o about 4% is in the form of myoglobin cause is deficiency of intestinal absorption of both folic acid o 1 % is in the form of the various heme compounds and vitamin B12.” that promote intracellular oxidation o 0.1 % is combined with the protein transferrin in the -Vitamin B12 and folic acid deficiency both cause macrocytic type blood plasma, of anemia o 15 to 30 % is stored for later use, mainly in the reticuloendothelial system and liver parenchymal II. FORMATION OF HEMOGLOBIN cells, principally in the form of ferritin. 1. (2) Succinyl-Coenzyme A and (2) glycine combines to form a molecule of pyrrole 2. (4) Pyrrole will form Protoporphyrin IX 3. Protoporphyrin IX and Ferrous iron will form heme 4. Heme plus polypeptide will form a hemoglobin chain which can be (alpha or beta) 5. (2) alpha chains and (2) beta chains will form Hemoglobin A (most common) Figure 2. Hemoglobin Production Synthesis of haemoglobin begins in the proerythroblasts continues even into the reticulocyte stage of the red blood Figure 3. Iron metabolism cells. When reticulocytes leave the bone marrow and pass into the blood stream, they continue to form minute quantities of A. MAIN TISSUES INVOLVED IN THE REGULATION haemoglobin for another day or so until they become mature OF SYSTEMIC IRON METABOLISM erythrocytes. There are several slight variations in the different subunit Duodenal enterocytes are responsible for dietary iron haemoglobin chains, depending on the amino acid absorption. Upon absorption, iron circulates around the body composition of the polypeptide portion. bound to the protein transferrin and is taken up by different The different types of chains are designated alpha chains, tissues for utilisation. beta chains, gamma chains, and delta chains. The reticuloendothelial system, which includes the splenic The most common form of hemoglobin in the adult human macrophages, recycles iron from senescent erythrocytes. being, hemoglobin A, is a combination of two alpha chains Among many other functions, the liver produces the and two beta chains. 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. PREPARED AND EDITED BY: GROUP 8 LUMAYAG, J., MANLONGAT, A. MOJICA, S., PRUDENCIO, J., PUZON, M., QUIAMBAO, C., QUILALA., E  (005) ANEMIA AND POLYCYTHEMIA DR. AILYN T. ISAIS-AGDEPPA, MD, DPPS | 09/11/2020 When iron is absorbed from the small intestine, it “Thus, total body iron is regulated mainly by altering the rate immediately combines in the blood plasma with a beta of absorption.” globulin, apotransferrin, to form transferrin, which is then IV. DESTRUCTION OF HEMOGLOBIN transported in the plasma. When red blood cells burst and release their The iron is loosely bound in the transferrin and, hemoglobin, the hemoglobin is phagocytized almost consequently, can be released to any tissue cell at any point immediately by macrophages in many parts of the body, but in the body. especially by the Kupffer cells of the liver and macrophages Excess iron in the blood is deposited especially in the liver of the spleen and bone marrow. hepatocytes and less in the reticuloendothelial cells of the During the next few hours to days, the macrophages release bone marrow. iron from the hemoglobin and pass it back into the blood, to In the cell cytoplasm, iron combines mainly with a protein, be carried by transferrin either to the bone marrow for the apoferritin, to form ferritin. production of new red blood cells or to the liver and other ferritin is called storage iron. tissues for storage in the form of ferritin. Smaller quantities of the iron in the storage pool are in an The porphyrin portion of the hemoglobin molecule is extremely insoluble form called hemosiderin. converted by the macrophages, through a series of stages, into the bile pigment bilirubin, which is released into the -Hemosiderosis is a pathologic condition where patients require blood and later removed from the body by secretion through chelation or the removal of excess iron in the body the liver into the bile. When the quantity of iron in the plasma falls low, some of the -In patients with cases severe anemia secondary hemolysis iron in the ferritin storage pool is removed easily and (excess amount of ruptured RBC) patients will sometimes or can transported in the form of transferrin in the plasma to the present with jaundice (yellowish discoloration of the skin). The areas of the body where it is needed. jaundice which not due to liver to liver disorder. Which is due to A unique characteristic of the transferrin molecule is that it bilirubin as the degradation product of hemoglobin. This type of binds strongly with receptors in the cell membranes of bilirubin is the indirect type or there is Indirect type of erythroblasts in the bone marrow. hyperbilirubinemia. Then, along with its bound iron, it is ingested into the erythroblasts by endocytosis. -The direct type of bilirubin or direct hyperbilirubinemia is for There the transferrin delivers the iron directly to the obstruction (obstruction of bile duct) causes of high bilirubin level mitochondria, where heme is synthesized. In people who do not have adequate quantities of transferrin V. ANEMIAS in their blood, failure to transport iron to the erythroblasts in - Deficiency of hemoglobin in the blood, which can be caused by either this manner can cause severe hypochromic anemia—that is, too few red blood cells or too little hemoglobin in the cells. red cells that contain much less hemoglobin than normal. - For all patient of anemia will all have the same signs and symptoms Figure 4. Regulation of Iron Metabolism -These manifestations occur during or after times of stress (excessive or activity). -Signs and symptoms are non-specific. -Example of this signs and symptoms are easy fatiguability, Shortness of breath, in physical exam patients show pallor such pale palpebral conjunctivae, pale lips, palms and soles are also pale. -Patient History plays a factor such as family history since some causes of anemia are hereditary type and certain test are done two differentiate and identify the type of anemia. -Treatment depends on the diagnosis on the type of anemia. Example: A. REGULATION OF TOTAL BODY IRON BY Patients with anemia due to vitamin B12 and folic acid CONTROLLING RATE OF ABSORPTION deficiency the treatment is giving the patient supplements of vitamin b12 and folic acid. When the body has become saturated with iron so that In patients with anemia cause by iron deficiency the essentially all apoferritin in the iron storage areas is already treatment is giving the patient iron supplements combined with iron, the rate of additional iron absorption -All cases of anemia have decreased RBC, Hemoglobin, Hematocrit from the intestinal tract becomes greatly decreased. Conversely, when the iron stores have become depleted, the rate of absorption can accelerate probably five or more times normal. PREPARED AND EDITED BY: GROUP 8 LUMAYAG, J., MANLONGAT, A. MOJICA, S., PRUDENCIO, J., PUZON, M., QUIAMBAO, C., QUILALA., E  (005) ANEMIA AND POLYCYTHEMIA DR. AILYN T. ISAIS-AGDEPPA, MD, DPPS | 09/11/2020 -There is a difference in MCV (Mean Corpuscular Volume) which is 3. MEGALOBLASTIC ANEMIA correlated to cell volume or size o Secondary to deficient of either vitamin B12, folic acid, and intrinsic factor from the stomach mucosa Low MCV: Microcytic (Small cell size) o Loss of any one of these can lead to slow Normal MCV: Normocytic (Normal cell size) reproduction of erythroblasts in the bone marrow. High MCV: Macrocytic (Large cell size) o As a result, the red cells grow too large, with odd shapes, and are called megaloblasts. - MCH (Mean Corpuscular Hemoglobin) and MCHC (Mean o In these states the erythroblasts cannot proliferate Corpuscular Hemoglobin Concentration) is correlated to rapidly enough to form normal numbers of red blood hemoglobin content cells, those red cells that are formed are mostly oversized, have bizarre shapes, and have fragile Low MCH and MCHC: Hypochromic membranes. Normal MCH and MCHC: Normochromic o These cells rupture easily, leaving the person in dire need of an adequate number of red cells. A. TYPES OF ANEMIAS 4. HEMOLYTIC ANEMIA 1. BLOOD LOSS ANEMIA o Can be hereditary or acquired making the cells fragile, ACUTE BLOOD LOSS easily ruptures as they pass through the capillaries, o After rapid hemorrhage, plasma volume is restored in spleen 1 to 3 days, but this leaves a low concentration of red o the number of RBC formed may be normal or greater blood cells. but cell fragility makes its lifespan shorter so that the o If a second hemorrhage does not occur, the red blood cells are destroyed faster than they can be formed, and cell concentration usually returns to normal within 3 to serious anemia results 6 weeks. o Examples: CHRONIC BLOOD LOSS a. In hereditary spherocytosis, the red cells are very o In chronic blood loss, a person frequently cannot small and spherical rather than being biconcave absorb enough iron from the intestines to form discs. haemoglobin as rapidly as it is lost. Red cells are then b. In sickle cell anemia produced that are much smaller than normal and have ▪ present in 0.3 to 1.0% of West African and too little hemoglobin inside them, giving rise to American blacks microcytic, hypochromic anemia ▪ the cells have an abnormal type of hemoglobin called haemoglobin S, containing 2. APLASTIC ANEMIA faulty beta chains in the haemoglobin o Bone marrow aplasia means lack of functioning bone molecule. marrow. ▪ Exposure to low O2 concentrations of oxygen - All blood lines (RBC, WBC, Platelets) are decreased → beta chains precipitates into long crystals - We use the term aplastic when we diagnose anemia that is inside the red blood cell → crystals elongate secondary to a problem in the bone marrow the cell sickle shape RBC → precipitated - Patients have decreased reticulocyte or normal, since hemoglobin also damages the cell membrane patients cannot produce sufficient amount of RBC to release → highly fragile → serious anemia in the circulation - Patients with normal or functioning bone marrow, the bone c. Such patients frequently experience a vicious marrow will adjust or meet the demand of RBC by the body circle of events called a sickle cell disease “crisis,” if there is decreased in RBC in which low oxygen tension in the tissues causes sickling, which leads to ruptured red cells, which Causes: causes a further decrease in oxygen tension and exposure to high-dose radiation or chemotherapy still more sickling and red cell destruction. Once the for cancer treatment. process starts, it progresses rapidly, eventuating in high doses of certain toxic chemicals, such as a serious decrease in red blood cells within a few insecticides or benzene in gasoline hours and, often, death. autoimmune disorders, such as lupus ery- thematosus. -In about half of aplastic anemia cases the cause is unknown, a condition called idiopathic aplastic anemia. - People with severe aplastic anemia usually die unless they are treated with blood transfusions—which can temporarily increase the numbers of RBCs—or by bone marrow transplantation. PREPARED AND EDITED BY: GROUP 8 LUMAYAG, J., MANLONGAT, A. MOJICA, S., PRUDENCIO, J., PUZON, M., QUIAMBAO, C., QUILALA., E  (005) ANEMIA AND POLYCYTHEMIA DR. AILYN T. ISAIS-AGDEPPA, MD, DPPS | 09/11/2020 d. In erythroblastosis fetalis ▪ Rh-positive red blood cells in the fetus are attacked by antibodies from a 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. -Occurs in interracial union -Pregnant mothers are given Immunoglobulin (Rhogam) to prevent this B. EFFECTS OF ANEMIA IN THE CIRCULATORY SYSTEM In severe anemia, the blood viscosity may fall to as low as 1.5 times that of water rather than the normal value of about 3. This decreases the resistance to blood flow in the peripheral blood vessels, so that far greater than normal quantities of blood flow through the tissues and return to the heart, thereby greatly increasing cardiac output. Hypoxia resulting from diminished transport of oxygen by the blood causes the peripheral tissue blood vessels to dilate, allowing a further increase in the return of blood to the heart and increasing the cardiac output to a still higher level— sometimes three to four times normal. Thus, one of the major effects of anemia is greatly increased cardiac output, as well as increased pumping workload on the heart. The increased cardiac output in anemia partially offsets the reduced oxygen-carrying effect of the anemia, because even though each unit quantity of blood carries only small quantities of oxygen, the rate of blood flow may be increased enough so that almost normal quantities of oxygen are actually delivered to the tissues. However, when a person with anemia begins to exercise, the heart is not capable of pumping much greater quantities of blood than it is already pumping. Consequently, during exercise, which greatly increases tissue demand for oxygen, extreme tissue hypoxia results, and acute cardiac failure ensues. PREPARED AND EDITED BY: GROUP 8 LUMAYAG, J., MANLONGAT, A. MOJICA, S., PRUDENCIO, J., PUZON, M., QUIAMBAO, C., QUILALA., E  (005) ANEMIA AND POLYCYTHEMIA DR. AILYN T. ISAIS-AGDEPPA, MD, DPPS | 09/11/2020 VI. POLYCYTHEMIA Because the blood passes sluggishly through the skin capillaries before entering the venous plexus, a larger than normal quantity of hemoglobin is deoxygenated. The blue A. TYPES OF POLYCYTHEMIA color of all this deoxygenated hemoglobin masks the red color of the oxygenated hemoglobin. Therefore, a person with polycythemia vera ordinarily has a ruddy complexion 1. SECONDARY POLYCYTHEMIA with a bluish (cyanotic) tint to the skin. o Whenever the tissues become hypoxic because of too little oxygen in the breathed air, such as at high altitudes, or because of failure of oxygen delivery to the TEST YOUR KNOWLEDGE tissues, such as in cardiac failure, the blood-forming 1. Idiopathic aplastic anemia is due to a. Drug reaction organs automatically produce large quantities of extra b. Benzene exposure red blood cells c. Inherited mutation in stem cells o RBC count commonly rises to 6 to 7 million/mm3, about d. Unknown cause 30% above normal. o A common type of secondary polycythemia, called 2. Hepcidin is produce in where? physiologic polycythemia, occurs in natives who live a. Kidney at altitudes of 14,000 to 17,000 feet, where the b. Lungs atmospheric oxygen is very low. The blood count is c. Liver generally 6 to 7 million/mm3; this allows these people to d. Brain perform reasonably high levels of continuous work even in a rarefied atmosphere. 3. In anemia that is caused by hemolytic disease RBC is ________, MCV is_______, MCHC is __________ 2. POLYCYTHEMIA VERA (ERYTHREMIA) a. Decreased, Increased, Increased o A pathological condition in which the red blood cell count b. Decreased, Normal, Normal may be 7 to 8 million/mm3 and the hematocrit may be 60 c. Normal, Decrease, Decrease to 70 per cent instead of the normal 40 to 45 per cent. d. Increased, Normal, Normal o caused by a genetic aberration in the hemocytoblastic cells that produce the blood cells wherein blast cells no 4. How many Oxygen atom can a single Hemoglobin longer stop producing red cells when too many cells are molecule transport? already present resulting to excess RBC production as a. 8 well as excess production of white blood cells and b. 4 platelets c. 2 o In polycythemia vera, not only does the haematocrit d. 1 increase, but the total blood volume also increases, on some occasions to almost twice normal. 5. Which is not a cause of microcytic hypochromic o As a result, the entire vascular system becomes anemia? intensely engorged. a. Iron deficiency o many blood capillaries become plugged by the viscous b. Thalassemia blood c. Transferrin Deficiency d. Deficiency in folic acid B. EFFECT OF POLYCYTHEMIA ON CIRCULATION Answer Keys: D,B,B,A,D Increased blood viscosity results to very sluggish blood flow in the peripheral vessels increasing blood viscosity REFERENCES decreases the rate of venous return to the heart. Conversely, the increased blood volume in polycythemia Hall, J. E., & Guyton, A. C. (2011). Guyton and Hall tends to increase venous return the cardiac output in textbook of medical physiology. Philadelphia, PA: Saunders polycythemia is not far from normal, because these two Elsevier. factors more or less neutralize each other. Harmening, D., Baldwin, A. J., & Sohmer, P. R. The arterial pressure is also normal in most people with (1983). Modern blood banking and transfusion practices. 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 viscosity to increase peripheral resistance and, thereby, increase arterial pressure. Beyond certain limits, however, these regulations fail, and hypertension develops. PREPARED AND EDITED BY: GROUP 8 LUMAYAG, J., MANLONGAT, A. MOJICA, S., PRUDENCIO, J., PUZON, M., QUIAMBAO, C., QUILALA., E