Physiology LC8 - Blood Types, Transfusion, Tissue Transplantation PDF

OUTLINE II. O-A-B BLOOD TYPES I. ANTIGENICITY A. A and B Antigens—Agglutinogens II. O-A-B BLO...

OUTLINE II. O-A-B BLOOD TYPES I. ANTIGENICITY A. A and B Antigens—Agglutinogens II. O-A-B BLOOD TYPES - Two antigens—type A and type B—occur on the surfaces of the RBCs A. A and B Antigens—Agglutinogens in a large proportion of people. It is these antigens (also called B. Major O-A-B Blood Types and Genetic Determination agglutinogens because they often cause RBC agglutination) that of the Agglutinogens cause most blood transfusion reactions. C. Relative Frequencies of the Different Blood Types - The blood type is genetically predetermined. A person inherits an D. Agglutinins allele from the father and another allele from the mother which E. Agglutination Process in Transfusion Reactions would determine the blood type. But they can predict possible blood F. Blood Typing types depending on the allele a person received. III. RH BLOOD TYPE A. Erythroblastosis Fetalis IV. ACUTE KIDNEY INJURY AFTER TRANSFUSION REACTION V. TRANSPLANTATION OF TISSUE AND ORGANS VI. ATTEMPTS TO OVERCOME IMMUNE REACTIONS IN TRANSPLANTED TISSUE A. Human Leukocyte Antigen Complex of Antigens B. Prevention of Graft Rejection by Suppressing the Immune System I. ANTIGENICITY - Antigen is the external force and the antibody is the soldier - Antigenicity causes an immune reaction Figure 2. Genetic determination of agglutinogens. - At least 30 commonly occuring antigens and hundreds of other rare antigens which cause antigen-antibody reaction in the surfaces of of B. Major O-A-B Blood Types and Genetic Determination of the cell membranes of human blood cells Agglutinogens - Releasing of hemoglobin may occur leading to hemolysis - In transfusing blood from one person to another, the bloods of - Due to the different blood types donors and recipients are normally classified into four major O-A-B - Two particular types of antigens are much more likely than the blood types. others to cause blood transfusion reactions (O-A-B system of - When neither A or B agglutinogen is present = type O antigens and the Rh system) - A agglutinogen only = type A - B agglutinogen only = type B - Both A and B agglutinogen present = type AB - The ABO blood group genetic locus has three alleles, which means three different forms of the same gene. These three alleles, IA, IB, and IO, determine the three blood types. We typically call these alleles “A,” “B,” and “O,” but geneticists represent the allele with the common symbol letter “I” which stands for immunoglobulin. - The type O allele is either functionless or almost functionless, so it causes no significant type O agglutinogen on the cells. Conversely, the type A and type B alleles do cause strong agglutinogens on the cells. Thus, the O allele is recessive to both the A and B alleles, which show co-dominance. - Presence of three different alleles means that there are six possible combinations of alleles: OO, OA, OB, AA, BB, and AB. These are what you call genotypes. Figure 1. Different blood groups. Vaccination - Antigen will enter the body and they will be presented by the antigen presenting cells (APC) and as a response, the body will produce antibodies. On the next exposure, antibodies are present already and thus a person will have less severe symptoms. Figure 3. Blood Types with Their Genotypes and Their Constituent Agglutinogens - Antibody is present in the plasma and the antigens are present in and Agglutinins. the rbc. - In emergency cases we can administer blood type O for massive C. Relative Frequencies of the Different Blood Types blood loss patients. O = 47% B = 9% A = 41% AB = 3% Page 1 of 4 [PHYSIOLOGY] 1.08 BLOOD TYPES, TRANSFUSION, TISSUE AND ORGAN TRANSPLANTATION - Dr. Navid Roodaki D. Agglutinins - When you have your blood type you have “A+”, the positive (+) part is - When an agglutinogen is not present in a person’s RBCs, antibodies the Rh blood type or phenotype. (agglutinins) develop in the plasma. - Rh meaning Rhesus: first discovered in a type of primate known as - Titer of Agglutinins at Different Ages: the rhesus macaque which is often used in research because of their Immediately after birth: the quantity of agglutinins in the similar blood to humans plasma is almost zero. 2-8 mos after birth: infant begins to produce agglutinins Erythroblastosis fetalis/Rh Disease/Hemolytic Disease of the Newborn 8-10yrs: maximum titer is usually reached - In most cases of erythroblastosis fetalis, the mother is Rh negative Remaining years: titer of the agglutinins decline and the father is Rh positive. The baby has inherited the Rh- positive - Origin of Agglutinins in the plasma: The agglutinins are gamma antigen from the father, and the mother develops anti- Rh globulins, as are almost all antibodies, and they are produced by the agglutinins from exposure to the fetus’s Rh antigen. In turn, the same bone marrow and lymph gland cells that produce antibodies to mother’s agglutinins diffuse through the placenta into the fetus and any other antigens. Most of them are IgM and IgG immunoglobulin cause RBC agglutination. molecules. - Incidence of Erythroblastosis Fetalis in Rh+ babies with Rh- mothers: - Why are agglutinins produced in people who do not have the 1st child: usually no disease development respective agglutinogens in their RBCs? 2nd child: 3% of Rh+ babies exhibit some signs of Small amounts of type A and B antigens enter the body in food, Erythroblastosis Fetalis in bacteria, and in other ways, initiating the development of 3rd child: 10% of third babies exhibit the disease anti-A and anti-B agglutinins. Subsequent pregnancies: incidence of disease rises progressively E. Agglutination Process in Transfusion Reactions - Effect of mother's antibodies on the fetus: - When bloods are mismatched so that anti-A or anti-B plasma After anti-Rh (IgG) antibodies have formed in the mother, they agglutinins are mixed with RBCs that contain A or B agglutinogens, diffuse slowly through the placental membrane into the fetus’s blood respectively, the RBCs agglutinate as a result of the agglutinins and cause agglutination on the fetus’s blood. The agglutinated RBCs attaching themselves to the RBCs. subsequently hemolyze, releasing hemoglobin into the blood. The - Agglutinins have 2 binding sites (IgG type) or 10 binding sites (IgM fetus’s macrophages then convert the hemoglobin into bilirubin, type), a single agglutinin can attach to two or more RBCs at the same which causes the baby’s skin to become yellow (jaundiced). 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.” - These clumps plug small blood vessels throughout the circulatory system. Physical distortion or attack by phagocytic cells cause the membrane to lyse and release hemoglobin, resulting in hemolysis. F. Blood Typing - Process of determining the blood type of the recipient’s blood and the blood type of the donor blood so that the bloods can be appropriately matched. Figure 5. How Rh hemolytic disease develops. - The jaundiced, erythroblastosis newborn baby is usually anemic at birth. The liver and spleen become greatly enlarged and produce RBCs in the same manner that they normally do during the middle of gestation. - Rapid production of RBCs to compensate for the hemolyzed RBCs results in nucleated blastic forms, thus calling the disease erythroblastosis fetalis. - 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 destruction of many, a condition called kernicterus. - Treatment for erythroblastosis fetalis: Replacement of neonate's blood with Rh- blood (400mL every 1.5 hrs or more) while Rh+ blood of neonate is being removed. Replacement of blood is repeated several times in the first week of life to prevent kernicterus (too much bilirubin in the blood which causes permanent brain damage) Figure 4. Blood typing results. By the time that the transfused Rh- cells are replaced with the infant's own Rh+ cells, a process that requires 6 or III. RH BLOOD TYPE more weeks, the anti-Rh agglutinins that had come from the mother will have been destroyed. - Prevention: Administration of Rh immunoglobulin globin, an anti-D - Antigens refer only to the presence or absence of antigen D on the antibody to expectant mothers starting 28 to 30 weeks of gestation RBC surfaces, that are termed “D-positive” and “D-negative”. can prevent this disease. - 95% of the population is a Rh positive Page 2 of 4 [PHYSIOLOGY] 1.08 BLOOD TYPES, TRANSFUSION, TISSUE AND ORGAN TRANSPLANTATION - Dr. Navid Roodaki - The administered anti-D antibody also attaches to D-antigen sites on Autograft- A transplant of a tissue or whole organ from one part of Rh-positive fetal RBCs that may cross the placenta and enter the the same animal to another part. They usually do this with skin and circulation of the expectant mother, thereby interfering with the sometimes bone marrow transplant. immune response to the D antigen. Isograft- from one identical twin to another. - Autograft and isograft has the least rejection. Allograft- from one person to another or from an animal to another animal of the same species. Xenograft - from a nonhuman animal to a human or from an animal of one species to one of another species. Figure 6. Erythroblastosis fetalis Figure 7. Types of Transplant. IV. ACUTE KIDNEY INJURY AFTER TRANSFUSION Transplantation of Cellular Tissues: - In the case of autografts and isografts , cells in the transplant contain - One of the most lethal effects of transfusion reactions is kidney virtually the same types of antigens as in the tissues of the recipient failure, which can begin within a few minutes to a few hours and and will almost always continue to live normally and indefinitely if an continue until the person dies of acute renal failure. adequate blood supply is provided. - Because there is hemolysis, the hemolysis of the red blood cell - At the other extreme, immune reactions almost always occur in causes release of endogenous substances such as hemoglobin. xenografts, causing death of the cells in the graft within 1 day to 5 hemoglobin will cause the formation of bilirubin, and the bilirubin weeks after transplantation unless some specific therapy is used to will eventually cause the jaundice. prevent the immune reactions. - Also, because there is an increase in hemolysis, acute injury will occur. Sometimes it could also cause chronic kidney disease, if you Bone Marrow Transplant don't act on it immediately. - For bone marrow transplant, what they do is to collect the bone - So, the possible pathophysiology of this would be the marrow either through the bone or apheresis machine which would antigen-antibody reaction causing the toxic release of substances. collect the stem cells. In bone marrow transplant, they don’t give it The RBC contains the hemoglobin and the hemoglobin, when through the bone, they give it like a blood transfusion because there released, can react. is this principle in our blood that they go where they are supposed to - Also, if there is loss of circulating RBC, there would be a decrease in be, so if you are a stem cell, even if you injected it through the vein, blood flow on your kidneys and oxygen delivery and it will cause it will return to the bone. injury. Remember that oxygen is the food of our body. It also leads to a low blood pressure and subsequently an increase in hemoglobin. For bone marrow transplant, how do they detect if they are rejected already? - Given that the bone marrow is kind of a liquid/ semi-liquid, they test Kidney shutdown after transfusion reaction may come from these the DNA. The DNA of the recipient when tested should be the DNA causes: of the donor. Once the DNA of the donor did not appear or is 1. The antigen-antibody reaction of the transfusion reaction decreasing or more than 50% this means that the recipient is releases toxic substances from the hemolyzing blood that rejecting the bone marrow already. Because prior to doing the bone cause powerful renal vasoconstriction. marrow transplant, they will destroy all the remaining marrow of the 2. Loss of circulating RBCs in the recipient, along with patient and they would give a very high dose of chemotherapy for production of toxic substances from the hemolyzed cells the marrow to suppress and to die before giving the new marrow. and the immune reaction, often cause circulatory shock. e arterial blood pressure falls very low, and renal blood flow and urine output decrease. 3. Increase free hemoglobin in the circulation causes kidneys VI. ATTEMPTS TO OVERCOME IMMUNE REACTIONS IN TRANSPLANTED to reabsorb more water in the glomerular membranes of TISSUE the kidney tubules causing tubular hemoglobin to rise so high and block the kidney tubules. A. Human Leukocyte Antigen Complex of Antigens. - The most important antigens for causing graft rejection are a V. TRANSPLANTATION OF TISSUES AND ORGANS complex called human leukocyte antigen (HLA) antigens. - The HLA antigens are on the white blood cells, as well as on the tissue cells. Therefore, tissue typing for these antigens is done on the membranes of lymphocytes that have been separated from the person’s blood. The lymphocytes are mixed with appropriate antisera Page 3 of 4 [PHYSIOLOGY] 1.08 BLOOD TYPES, TRANSFUSION, TISSUE AND ORGAN TRANSPLANTATION - Dr. Navid Roodaki and complement; after incubation, the cells are tested for membrane damage, usually by determining the rate of transmembrane uptake by the lymphocytic cells of a special dye. B. Prevention of Graft Rejection by Suppressing the Immune System i. Glucocorticoid - hormones from adrenal cortex glands (or drugs with glucocorticoid-like activity), which inhibit genes that code for several cytokines, especially interleukin-2 (IL-2). IL-2 is an essential factor that induces T-cell proliferation and antibody formation. ii. Drugs that suppress T cell proliferation - Azathioprine iii. Inhibit formation of T helper cells - cyclosporine and tacrolimus - these agents have proved to be highly valuable drugs because they do not depress some other portions of the immune system. iv. Immunosuppressive antibody - specific antilymphocyte or IL-2 receptor antibodies. - HLA is tested before they go with transplantation because this is the most important antigen for causing graft rejection - Even if you have HLA match, you cannot assure that the immune system will not destroy it, remember the body is built in a way that it protects itself, so whatever you put inside your body, your body will try to expel it out, so even if you have matched HLA or same DNA you cannot assure that your body will not expel or cause the immune system to activate and destroy. So what they do is to use glucocorticoids, drugs that suppress the T cell proliferation, inhibition of T helper cells, and immunosuppressive antibodies like cyclosporine. Remember that they focus on the T cells because they are the one that reacts when you have a reaction. References: Guyton and Hall Textbook of Medical Physiology 13th ed. Page 4 of 4