Hematology PDF - Overview of Blood Composition & Function

Slide 1 Slide 2 Reference books: 1. Hall, John, E. and Michael E. Hall. Guyton and Hall Textbook of Medical Physiology (14th Edition). 2. Lauralee Sherwood. Human Physiology: From Cells To Systems (9th Edition). 3. Gerard J. Tortora and Bryan Derrickson. Principles Of Human Anatomy & Physiology (...

Slide 1 Slide 2 Reference books: 1. Hall, John, E. and Michael E. Hall. Guyton and Hall Textbook of Medical Physiology (14th Edition). 2. Lauralee Sherwood. Human Physiology: From Cells To Systems (9th Edition). 3. Gerard J. Tortora and Bryan Derrickson. Principles Of Human Anatomy & Physiology (15th Edition) Slide 3 Hematology Body Fluids ** About two-thirds of body fluid is intracellular fluid (ICF). The other third, called extracellular fluid (ECF) is outside cells. ** About 80% of the ECF is interstitial fluid and 20% of the ECF is blood plasma. ** Water content depends on age, gender, and the amount of adipose tissue present in the body. ** In the average 70-kg adult man, the total body water is about 60% of the body weight (42 L). Slide 4 Hematology Body Fluids **In extracellular fluid, the most abundant cation is Na+, and the most abundant anion is Cl−. **In intracellular fluid, the most abundant cation is K+, and the most abundant anions are proteins and phosphates. ** By actively transporting Na+ out of cells and K+ into cells, sodium–potassium pumps (Na+–K+ ATPases) play a major role in maintaining the high intracellular concentration of K+ and high extracellular concentration of Na+. ** The chief difference between the two extracellular fluids—blood plasma and interstitial fluid—is that blood plasma contains many protein anions, in contrast to interstitial fluid, which has very few. Because normal capillary membranes are virtually impermeable to proteins, only a few plasma proteins leak out of blood vessels into the interstitial fluid. This difference in protein concentration is largely responsible for the blood colloid osmotic pressure exerted by blood plasma. Slide 5 Hematology Body Fluids Blood hydrostatic pressure pushes fluid out of capillaries (filtration) Blood colloid osmotic pressure pulls fluid into capillaries (reabsorption) **The processes of filtration, reabsorption, diffusion, and osmosis allow continual exchange of water and solutes among body fluid compartments . Yet the volume of fluid in each compartment remains remarkably stable. Slide 6 Hematology Blood and its components • The average blood volume of adults is about 7% of body weight, or about 5 liters. • Blood is connective tissue. • Blood is denser and more viscous (thicker) than water. • The temperature of blood is 38°C. • Slightly alkaline pH ranging from 7.35 to 7.45 (average = 7.4). • The color saturated (O2)→ bright red unsaturated (O2) → dark red Slide 7 Hematology Hematology Blood and its components Blood smear 1 2 3 4 5 Slide 8 Hematology Blood and its components Created with Biorender.com Slide 9 Hematology Blood and its components Plasma Slide 10 Hematology Blood and its components Plasma Protein 1. Establishment of colloid osmotic pressure. 2. Responsible for plasma’s capacity buffer changes in pH. Albumin Fibrinogen Nonspecifically binds substances that are poorly soluble in plasma (bilirubin) Is an inactive precursor for a clot’s fibrin meshwork & Globulins • Specifically bind poorly water-soluble substances (thyroid hormone, cholesterol, and iron). • Involved in blood-clotting. • Angiotensinogen. Antibodies/ immunoglobulins. Body’s defense mechanism. Plasma proteins are synthesized by the liver, with the exception of antibodies, which are produced by lymphocytes, one of the types of white blood cells. Slide 11 Hematology Blood and its components Slide 12 Hematology Hematology Packed Red Cell Volume Created with Biorender.com Slide 13 Hematology Hematocrit • Hematocrit/ Packed Red Cell Volume • Adult males: 40–54% (avg = 47%). • Adult females: 38–46% (avg = 42%) × 100% Total Height Height of RBC Concentration!! Chapter 18, Boron Medical Physiology (3rd Edition ) **The hematocrit is the fraction of the blood composed of red blood cells, as determined by centrifuging blood in a “hematocrit tube” until the cells become tightly packed in the bottom of the tube. ** HCT values are slightly less than PCV because there is no trapped plasma in an automated hematocrit calculation, as can occur with spun, packed cell values. **The hormone testosterone stimulates synthesis of erythropoietin that in turn stimulates production of RBCs. ** Lower values in women during their reproductive years also may be due to excessive loss of blood during menstruation **Expansion of plasma volume in a pregnant woman reduces the hematocrit, whereas her total red cell volume also increases but less than plasma volume. ** Higher in dehydration. Slide 14 Hematology Hematocrit Polycythemia Anemia Slide 15 Hematology Principle roles of the blood v Transportation • Gases, nutrients, hormones, waste v products. v Regulation • pH, body temperature, water content v (osmotic pressure) v Protection v • Clotting, white blood cells,antibodies Slide 16 Hematology Early fetal life Hematopoiesis (formation of blood cells) Occurs in the yolk sac of an embryo and later in the liver, spleen, thymus, and lymph nodes of a fetus. last 3 gestational *Red bone marrow becomes the primary site of hemopoiesis in the, and continues as the months- death source of blood cells after birth and throughout life. *axial skeleton, pectoral and pelvic girdles, and the proximal epiphyses of the humerus and femur. Slide 17 Hemopoiesis (formation of blood cells) **pluripotent hematopoietic stem cells: constitute a population of adult stem cells found in bone marrow that are multipotent and able to self-renew. **The intermediate-stage cells are very much like the pluripotential stem cells, even though they have already become committed to a particular line of cells and are called committed stem cells (CFU). The different committed stem cells, when grown in culture, will produce colonies of specific types of blood cells. **Growth and reproduction of the different stem cells are controlled by multiple proteins called growth inducers. One of the growth inducers is interleukin-3, promotes growth and reproduction of virtually all the different types of committed stem cells. Slide 18 Hematology Hematopoiesis (formation of blood cells) • Stem cells in bone marrow • Reproduce themselves • Proliferate and differentiate • Formed elements do not divide once they leave red bone marrow • Exception is lymphocytes Slide 19 Hematology Hematopoiesis (formation of blood cells) ✓ Myeloid stem cells • Give rise to red blood cells, platelets, monocytes, neutrophils, eosinophils and basophils ✓ Lymphoid stem cells give rise to • Lymphocytes and natural killer cells ✓ Hemopoietic growth factors regulate differentiation and proliferation • Erythropoietin – RBCs • Thrombopoietin – platelets • Colony-stimulating factors (CSFs) and interleukins – WBCs Slide 20 Hematology RBC Red Blood Cells/ Erythrocytes Slide 21 RBC General characteristics • • • • • • Biconcave disc. Diameter is normally 8 μm. Strong, flexible plasma membrane. Lack nucleus and other organelles Lack mitochondria. Key erythrocyte enzymes: glycolytic enzymes and carbonic anhydrase. • Contain oxygen-carrying protein (hemoglobin). ** The biconcave shape provides a larger surface area for diffusion of O2 from the plasma across the membrane into the erythrocyte than a spherical cell of the same volume would. Also, the thinness of the cell enables O2 to diffuse rapidly between the exterior and innermost regions of the cell. **A second structural feature that facilitates RBCs’ transport function is their flexible membrane (in great excess). Red blood cells, whose diameter is normally 8 um, can deform amazingly as they squeeze through capillaries. Because they are extremely pliant, RBCs can travel through the narrow, tortuous capillaries to deliver their O2 cargo at the tissue level without rupturing in the process. Cannot synthesize new components – no nucleus The third and most important anatomic feature that enables RBCs to transport O2 is the hemoglobin they contain. Slide 22 RBC General characteristics • Oligosaccharides in plasma membrane are responsible for ABO and Rh blood groups. • Count: • 5,200,000/ μL in men; and 4,700,000/ μL in women. • Production = destruction ( 2 million/ sec). Slide 23 RBC Function • Oxygen and CO2 transport (hemoglobin). • Contain a large quantity of carbonic anhydrase → increasing the rate of this reaction several thousand folds. • Responsible for most of the acid-base buffering power of whole blood (hemoglobin). ** Erythrocytes contribute to CO2 transport in two ways—by means of its carriage on hemoglobin and its carbonic anhydrase–induced conversion to HCO3-. **The red blood cells contain a large quantity of carbonic anhydrase, an enzyme that catalyzes the reversible reaction between carbon dioxide (CO2) and water to form carbonic acid (H2CO3), increasing the rate of this reaction several thousandfold. The rapidity of this reaction makes it possible for the water of the blood to transport enormous quantities of CO2 in the form of bicarbonate ion (HCO3−) from the tissues to the lungs, where it is reconverted to CO2 and expelled into the atmosphere as a body waste product. **The hemoglobin in the cells is an excellent acid-base buffer (as is true of most proteins), so the red blood cells are responsible for most of the acid-base buffering power of whole blood. Slide 24 RBC Hemoglobin ** Hemoglobin is a pigment (that is, it is naturally colored). ** Because of its iron content, it appears reddish when combined with O2 and bluish when deoxygenated. Slide 25 RBC Hemoglobin • The different types of chains are designated alpha chains, beta chains, gamma chains, and delta chains. • The most common form of hemoglobin in the ADULT HUMAN, hemoglobin A, is a combination of two alpha chains and two beta chains. • Iron ion can combine reversibly with one oxygen molecule • Also transports 23% of total carbon dioxide (Combines with amino acids of globin). Slide 26 RBC Hemoglobin • Normal blood hemoglobin content is ~14.0 g/dL in the adult female and ~15.5 g/dL in the adult male. Anemia polycythemia Slide 27 RBC RBC life cycle 1 6 2 5 4 3 Created with Biorender.com **Live only about 120 days **Cannot synthesize new components – no nucleus **Ruptured red blood cells removed from circulation and destroyed by fixed phagocytic macrophages in spleen and liver **Bone marrow replaces approximately 1% of the adult RBC every day. Slide 28 Circulation for about 120 days 7 3 Reused for protein synthesis Amino acids Globin 4 5 Fe3+ 2 Fe3+ Transferrin 6 Fe3+ Ferritin Heme Transferrin Bilirubin 9 Biliverdin Bilirubin 1 Red blood cell 11 Liver 10 death and phagocytosis Small intestine Kidney Macrophage in spleen, liver, or red bone marrow red bone marrow 12 Urobilinogen Stercobilin Urine 8 Erythropoiesis in Bilirubin 13 Urobilin + Globin + Vitamin B12 + Erythopoietin Bacteria Key: in blood 14 Large intestine in bile Feces Copyright 2009, John Wiley & Sons, Inc. • • • • • • Once the red cell membrane becomes fragile, the cell ruptures during passage through some tight spot of the circulation. Many of the red cells self-destruct in the spleen, where they squeeze through the red pulp of the spleen. There, the spaces between the structural trabeculae of the red pulp, through which most of the cells must pass, are only 3 micrometers wide, in comparison with the 8-micrometer diameter of the RBC. Red blood cells burst and release their hemoglobin. The macrophages release iron from the hemoglobin and pass it back into the blood, to be carried by transferrin. Porphyrin is converted into the bile pigment bilirubin. Which is later removed from the body by secretion through the liver into the bile. Slide 29 RBC RBC life cycle • Breakdown products: • Globin’s amino acids reused • Iron reused • Non-iron heme ends as yellow pigment urobilin in urine or brown pigment stercobilin in feces Slide 30 Think!!! Hemoglobin A1C (HbA1C) test is a blood test that shows average blood glucose level. As the blood glucose level increases, more of hemoglobin will be coated with glucose. A diabetic patient came to your clinic, with HbA1C=8% that he did one month ago. You want to follow up with the patient, so you ask him to do another one after: A. Two months. B. Six months. C. A year. Slide 31 RBC Erythropoiesis • Starts in red bone marrow with proerythroblast. • Cell near the end of development ejects nucleus and becomes a reticulocyte which develop into mature RBC within 1-2 days. • The remaining basophilic material in the reticulocyte normally disappears within 1 to 2 days, and the cell is then a mature erythrocyte. Nucleus exocytosis **Changes: Hemoglobin accumulation, nuclear condensation, reabsorption of the endoplasmic reticulum. ** When reticulocytes leave the bone marrow and pass into the blood stream, they continue to form minute quantities of hemoglobin for another day or so until they become mature erythrocytes. Slide 32 RBC Reticulocyte count Reticulocyte count = <2% in normal adult Number of reticulocyte ×100% Number of RBCs Importance: Reticulocytes count help in diagnosis and typing of anemia Decreased Aplastic anemia Increased Hemolytic anemia Post hemorrhage A high reticulocyte count implies an accelerated production of RBCs in the bone marrow. Slide 33 RBC Corrected Reticulocyte count Retic = 1% Hct = 45 In the state of anemia, reticulocyte % is not a true reflection of reticulocyte production. Retic = 2% Hct = 22.5 Corrected reticulocyte count = Reticulocyte count × = 1% Actual Hct Normal Hct = 1% ** In the state of anemia, reticulocyte % is not a true reflection of reticulocyte production. ** A correction factor must not be applied to overestimate marrow production because each reticulocyte is released into whole blood containing few RBCs, which means low Hct, thus increasing the percentage. Slide 34 RBC Vitamins requirement • Maturation of red blood cells requires vitamin B12 (Cyanocobalamin) and folic acid. • Both of these are essential for the synthesis of DNA (formation of thymidine triphosphate). • lack of either vitamin B12 or folic acid causes: **abnormal and diminished DNA and, consequently, failure of nuclear maturation and cell division. ** production of larger red cells called macrocytes and the cell itself has a flimsy irregular membrane. ** The bone marrow are among the most rapidly growing and reproducing cells in the entire body. ** Deficiency of vitamin B12 or folic acid causes maturation failure in the process of erythropoiesis → cells are capable of carrying oxygen normally, but their fragility causes them to have a short life. Slide 35 RBC Regulation of Erythropoiesis_ Erythropoietin (EPO) • Negative feedback balances production with destruction. • EPO Is a glycoprotein that normally formed in the kidneys (90%); the remainder is formed mainly in the liver. • It is essential to stimulate the production of proerythroblasts from hematopoietic stem cells in the bone marrow. • EPO causes these cells to pass more rapidly through the different erythroblastic stages. Slide 36 RBC Regulation of Erythropoiesis_ Erythropoietin (EPO) • Hypoxia causes a marked increase in erythropoietin production. • With renal failure, EPO release slows and RBC production is inadequate. This leads to a decreased hematocrit. • P.s. Hypoxia is insufficient O2 at the cellular level **Because O2 transport in the blood is the erythrocytes’ main function, you might logically suspect that the primary stimulus for increased erythrocyte production would be reduced O2 delivery to the tissues. You would be correct, but low O2 levels do not stimulate erythropoiesis by acting directly on the red marrow. Instead, reduced O2 delivery to the kidneys stimulates them to secrete the hormone erythropoietin (EPO) into the blood, and this hormone in turn stimulates erythropoiesis by the red marrow. **Tissue Oxygenation—Essential Regulator of Red Blood Cell Production Conditions that decrease the quantity of oxygen transported to the tissues ordinarily increase the rate of RBC production. *when a person becomes extremely anemic as a result of hemorrhage or any other condition, the bone marrow begins to produce large quantities of RBCs. RBCs. *At very high altitudes, where the quantity of oxygen in the air is greatly decreased, insufficient oxygen is transported to the tissues, and RBC production is greatly increased. In this case, it is not the concentration of RBCs in the blood that controls RBC production but the amount of oxygen transported to the tissues in relation to tissue demand for oxygen. *Various diseases of the circulation that decrease tissue blood flow, particularly those that cause failure of oxygen absorption by the blood as it passes through the lungs, can also increase the rate of RBC production. This result is especially apparent in prolonged cardiac failure and in many lung diseases. Slide 37 RBC RBCs parameters **Factor contributing to decline in hematological parameters in the newborn was due to decrease in blood erythropoietin concentration soon after birth, reducing the erythropoietic rate. Also, transient hemolysis is high during the first days or week after. **Decrease in hemoglobin level between older men and women may be the result of decrease androgen level in older men and decrease in estrogen levels in older women. **Iron deficiency and anemia of chronic disease have usually been responsible for low hemoglobin level in majority of asymptomatic elderly people. Slide 38 RBC RBCs parameters Slide 39 RBC RBCs parameters MCV Mean cell volume (fL/cell) • Is the average volume (size) of the RBCs. • It can be measured, as it is in automated cell counters, or calculated: = Hct [%] x 10 RBC count [in millions/μL] Macrocytic (>100) Normocytic (80-100) Microcytic (<80) Slide 40 RBCs parameters Distribution of RBCs sizes % Occurrence RBC Normal Red Cells 70 80 90 100 MCV 110 120 130 Slide 41 RBCs parameters % Occurrence RBC Distribution of RBCs sizes Increased Size Red Cells (macrocytic) 70 80 90 100 MCV 110 120 130 Slide 42 RBC RBCs parameters Red cell Distribution Width (RDW) • Measurement of RBC size variation (anisocytosis). • RDW = [standard deviation/MCV] x 100. • A high RDW → large variation in RBC sizes • A low RDW → more homogeneous population of RBCs. • A high RDW can be seen in a number of anemias, including iron deficiency, vitamin B12 or folate deficiency. % Occurrence Increased Red Cell Distribution Width 70 80 90 100 MCV 110 120 130 Slide 43 RBC RBCs parameters MCH Mean cell hemoglobin concentration (pg/ cell) • Is the average hemoglobin content in a RBC. = Hemoglobin [g/dL] x 10 RBC count [in millions/μL] • A low MCH is typically reflected in an enlarged area of central pallor in RBCs on the peripheral blood smear (greater than one-third of the RBC diameter) Normochromic (30-34) Hypochromic (<30) Slide 44 RBC RBCs parameters MCHC Mean cell hemoglobin concentration (g/dL RBC) • Is the average hemoglobin concentration per RBC. = Hemoglobin [g/dL] x 100 Hct [%] Normochromic (30-36) Hypochromic (<30) MCHC=MCH/MCV Slide 45 RBC Anemia Anemia Production *Less EPO * BM damage *Iron deficiency Low Reticulocytes count Destruction * Blood loss *Hemolysis High Reticulocytes count Slide 46 RBC Anemia classification MCV < 80 fl MCV 80-100 fl MCV >100 fl Microcytic Anemia Normocytic Anemia Macrocytic Anemia Iron Deficiency Chronic disease Thalassemia Elevated reticulocyte Vitamin B12 Folate Acute blood loss Hemolysis Normal or low reticulocyte Kidney disease Bone marrow Disorder Medication Slide 47 RBC Anemia classification MCV Hb Content (MCH) Causes Normocytic Normochromic Bone marrow failure, renal disease, hemolytic anemia Macrocytic Normochromic vitamin B12, folic acid deficiency Microcytic Hypochromic Iron deficiency, chronic diseases, Thalassemia Slide 48 RBC Effects of Anemia on Function of the Circulatory System • Blood viscosity is decreased. • This decreases the resistance to blood flow in the peripheral blood vessels. • Greater quantities of blood return to the heart. • Increased cardiac output. • Thus, one of the major effects of anemia is greatly increased cardiac output, as well as increased pumping workload on the heart. Slide 49 Blood Groups Blood Types and Transfusion Reaction Created with Biorender Slide 50 Multiplicity of Antigens in the Blood Cells • At least 30 commonly occurring antigens and hundreds of other rare antigens, each of which can at times cause antigen-antibody reactions. • Two particular types of antigens are much more likely than the others to cause blood transfusion reactions. They are the O-A-B system of antigens and the Rh system. Slide 51 Blood Groups ABO System • The ABO blood group is based on two glycolipid antigens called A and B. • ABO blood group genetic locus has three alleles, which means three different forms of the same gene. • These three alleles—IA, IB, and IO. • Only one of these alleles is present on each of the two chromosomes in any individual. • The six possible combinations of genes OO, OA, OB, AA, BB, and AB. Slide 52 O-A-B Blood Types Genotype OA/ AA OB/ BB AB - Antigen A B AB - Blood group A B AB O Slide 53 Relative Frequencies of the Different Blood Types Slide 54 Blood Groups Agglutination Antigen (Agglutinogen) Antibody (Agglutinin) Because the agglutinins have two binding sites (IgG type) or ten binding sites (IgM type), a single agglutinin can attach to two or more RBCs at the same time, thereby causing the cells to be bound together by the agglutinin. This binding causes the cells to clump, which is the process of agglutination. Slide 55 Agglutinins (antibodies) • The agglutinins are gamma globulins, as are almost all antibodies. • Most of them are IgM and IgG immunoglobulin molecules. • When type A agglutinogen is not present in a person’s RBCs, antibodies known as anti-A agglutinins develop in the plasma. Slide 56 O-A-B Blood Types Antigen (Agglutinogen) A B AB - Genotype OA/ AA OB/ BB AB - Blood group A B AB O Antibody (Agglutinins) anti-B anti-A - Anti-A & anti-B Slide 57 Agglutinins (antibodies) • Immediately after birth, the quantity of agglutinins in the plasma is almost zero. • Two to 8 months after birth, an infant begins to produce agglutinins. • A maximum titer is usually reached at 8 to 10 years of age, and this gradually declines throughout the remaining years of life. **Also, the neonate has few, if any, agglutinins, showing that agglutinin formation occurs almost entirely after birth. Slide 58 Agglutinins (antibodies) • But why are these agglutinins produced in people who do not have the respective agglutinogens in their RBCs? • The answer to this is that small amounts of type A and B antigens enter the body in food, in bacteria, and in other ways, and these substances initiate the development of the anti-A and anti-B agglutinins. Slide 59 Agglutination Process in Transfusion Reactions • The clumps plug small blood vessels throughout the circulatory system. • During the ensuing hours to days, physical distortion of the cells or attack by phagocytic white blood cells destroys the membranes of the agglutinated cells, releasing hemoglobin into the plasma, called hemolysis of the RBCs. Agglutination followed by delayed hemolysis Slide 60 Acute Hemolysis Occurs in Some Transfusion Reactions → Immediate intravascular hemolysis. → In this case, the antibodies cause lysis of the red blood cells by activating the complement system, membrane attack complex. →Less common → have to be a high titer of antibodies for lysis to occur, but also a different type of antibody seems to be required, mainly the IgM antibodies. Slide 61 Blood Groups Rh System • There are six common types of Rh antigens, each of which is called an Rh factor. These types are designated C, D, E, c, d, and e. • Each person has one of each of the three pairs of antigens. • The type D antigen is widely prevalent in the population and considerably more antigenic than the other Rh antigens • Anyone who has the D antigen is said to be Rh positive, whereas a person who does not have type D antigen is said to be Rh negative. • The worldwide frequencies of Rh-positive and Rh-negative blood types are 95% and 6%, respectively. However, it must be noted that even in Rh-negative people, some of the other Rh antigens can still cause transfusion reactions, although the reactions are usually much milder. Slide 62 Blood Groups Rh System The major difference between the O-A-B system and the Rh system is the following: In the O-A-B system, the plasma agglutinins responsible for causing transfusion reactions develop spontaneously, whereas in the Rh system, spontaneous agglutinins almost never occur. Instead, the person must first be massively exposed to an Rh antigen. Slide 63 Formation of Anti-Rh Agglutinins • When RBCs containing Rh factor are injected into a person whose blood does not contain the Rh. • Anti-Rh agglutinins develop slowly, reaching a maximum concentration of agglutinins about 2 to 4 months later. • This immune response occurs to a much greater extent in some people than in others. • With multiple exposures to the Rh factor, an Rh-negative person eventually becomes strongly sensitized to Rh factor. Slide 64 Characteristics of Rh Transfusion Reactions. • likely cause no immediate reaction. • Anti-Rh antibodies can develop in sufficient quantities during the next 2 to 4 weeks to cause agglutination of those transfused cells that are still circulating in the blood. • These cells are then hemolyzed by the tissue macrophage system. Thus, a delayed transfusion reaction occurs, although it is usually mild. Slide 65 Characteristics of Rh Transfusion Reactions. • On subsequent transfusion of Rh-positive blood into the same person (sensitized), who is now already immunized against the Rh factor, the transfusion reaction is greatly enhanced and can be immediate and as severe as a transfusion reaction caused by mismatched type A or B blood. Slide 66 Hemolytic Disease of the Newborn Erythroblastosis Fetalis Chegg.com Slide 67 Hemolytic Disease of the Newborn Erythroblastosis Fetalis • The mother is Rh negative and the baby has inherited the Rh-positive antigen from the father. • The mother develops anti- Rh agglutinins from exposure to the fetus’s Rh antigen. • In turn, the mother’s agglutinins diffuse through the placenta into the fetus and cause red blood cell agglutination. • 3% of second Rh -positive babies exhibit some signs of erythroblastosis fetalis • 10% of third babies exhibit the disease; and the incidence rises progressively with subsequent pregnancies. Slide 68 Hemolytic Disease of the Newborn Erythroblastosis Fetalis • Hemolytic anemia. • Jaundice. • The liver and spleen become greatly enlarged. • Presence of nucleated blastic red blood cells. • Permanent mental impairment or damage to motor areas of the brain. Although the severe anemia of erythroblastosis fetalis is usually the cause of death, many children who barely survive the anemia exhibit permanent mental impairment or damage to motor areas of the brain because of precipitation of bilirubin in the neuronal cells, causing the destruction of many of these cells, a condition called kernicterus. Slide 69 Treatment of the Erythroblastotic Neonate • One treatment is to replace the neonate’s blood with Rh-negative blood. • This procedure may be repeated several times during the first few weeks of life • Anti-Rh agglutinins from the mother usually circulate in the infant’s blood for another 1 to 2 months after birth, destroying more and more red blood cells. • This keeps the bilirubin level low and thereby prevent complications. **By the time these transfused Rh-negative cells are replaced with the infant’s own Rh-positive cells, a process that requires 6 or more weeks, the anti-Rh agglutinins that had come from the mother will have been destroyed. Slide 70 Prevention of the Erythroblastotic Neonate • By administration of Rh immunoglobulin globin, an anti-D antibody to the expectant mother starting at 28 to 30 weeks of gestation. **women should receive RhoGAM® before delivery, and soon after every delivery, miscarriage, or abortion. Slide 71 Prevention of the Erythroblastotic Neonate The mechanism whereby Rh immunoglobulin globin prevents sensitization of the D antigen is not completely understood, but one effect of the anti-D antibody is to inhibit antigen-induced, B lymphocyte antibody production in the expectant mother. The administered anti-D antibody also attaches to D antigen sites on Rh-positive fetal RBCs that may cross the placenta and enter the circulation of the expectant mother, thereby interfering with the immune response to the D antigen. Slide 72 Blood Groups Blood Typing Slide 73 Blood Groups Blood Typing AB+ AB+ O- Slide 74 Blood Groups Blood matching • Before giving a transfusion to a person, it is necessary to determine the blood type of the recipient and donor blood so that the bloods can be appropriately matched. • In a cross-match, the possible donor RBCs are mixed with the recipient’s serum. If agglutination does not occur, the recipient does not have antibodies that will attack the donor RBCs. • Alternatively, the recipient’s serum can be screened against a test panel of RBCs having antigens known to cause blood transfusion reactions to detect any antibodies that may be present. Except in extreme emergencies, it is safest to individually cross-match blood before a transfusion is undertaken even though the ABO and Rh typing is already known, because there are approximately 23 other minor human erythrocyte antigen systems, with hundreds of subtypes. Slide 75 Blood Groups Blood matching Blood group B+ (anti-A) O- (anti-A and anti-B) Donate AB+, B+ To all blood group Receive B- (B+) O- (O+) O- AB+ AB+ From all blood group Slide 76 Blood Groups Blood matching o Rh - A B AB Rh + Slide 77 Blood Groups Transfusion reaction Slide 78 Blood Groups Transfusion reaction Slide 79 Transfusion Reactions Resulting from Mismatched Blood Types • If donor blood of one blood type is transfused into a recipient who has another blood type, a transfusion reaction is likely to occur in which the red blood cells of the donor blood are agglutinated. • The plasma portion of the donor blood immediately becomes diluted by all the plasma of the recipient (decreasing the titer of the infused agglutinins) • The small amount of infused blood does not significantly dilute the agglutinins in the recipient’s plasma. Slide 80 Transfusion Reactions Resulting from Mismatched Blood Types • Cause either immediate hemolysis or delayed hemolysis resulting from phagocytosis of agglutinated cells. • Jaundice • Acute Kidney Shutdown ** jaundice usually does not appear in an adult unless more than 400 milliliters of blood are hemolyzed in less than a day. Slide 81 Transfusion Reactions Resulting from Mismatched Blood Types- Acute Kidney Failure After Transfusion Reactions The kidney shutdown seems to have three causes: 1. The antigen-antibody reaction of the transfusion reaction releases toxic substances from the hemolyzing blood that cause powerful renal vasoconstriction. 2. Loss of circulating RBCs in the recipient, along with production of toxic substances from the hemolyzed cells and the immune reaction, often cause circulatory shock. The arterial blood pressure falls very low, and renal blood flow and urine output decrease. 3. Much of the excess free hemoglobin leaks through the glomerular membranes into the kidney tubules. **One of the most lethal effects of transfusion reactions is kidney failure, which can begin within a few minutes to a few hours and continue until the person dies of acute renal failure.