Cardiovascular System. Blood Groups and Blood Typing

Transcription

1 Cardiovascular System Blood Groups and Blood Typing 1

2 Blood Transfusions Why? Whole blood or components? Although the human body is pretty good at preventing blood loss (hemostasis), there are times when blood loss can be life-threatening. The loss of 15-30% of the blood volume, such as during surgery or from trauma, can cause anemia, weakness and pallor. A further blood loss puts a person at risk for shock and death. When blood loss is extreme, a blood transfusion is necessary. While whole blood can be given, usually only one component (erythrocytes, plasma, or platelets) is transfused. 2

3 Transfusion Reactions Antigens Immune response Some in RBC membrane Antibodies Antigen-specific In blood plasma Agglutination Unfortunately, a donor s blood must be matched to its recipient before it can be administered. You can t just take blood cells from some random person and inject it into some other random person. If transfused blood is of the wrong type, a transfusion reaction can occur. To understand why, you need to know a little about humoral immunity. We ll cover humoral immunity in detail a little later, but here are the basics: An antigen is any molecule capable of triggering an immune response in the body. Typical antigens include glycoproteins found in the cell walls of bacteria, proteins that make up the capsule of viruses, and even pollen and dust. All of our own body cells, including our red blood cells, have antigens (glycoproteins in this case) embedded in their plasma membranes, but our immune system knows which antigens belong in the body (self-antigens) and which do not (foreign antigens). Red blood cells have at least 30 different antigens embedded in their plasma membranes, but different people may have different natural antigens. Antibodies are protein complexes found in blood plasma. Each Y-shaped antibody has two variable regions that will bind only to a specific antigen. When an antibody binds to its specific antigen, the immune response is provoked and the offending antigen (or the cell that has the antigen in its membrane) is destroyed. (Incidentally, antibodies are how your body remembers pathogens that have infected it before the first time you are infected by a particular pathogen, antibodies are formed that bind to antigens associated with the pathogen; those antibodies remain in the blood plasma even after the infection has passed, so the next time the same pathogen infects you, the antibodies bind to its antigens and trigger the immune response right away). Since antibodies are Y-shaped and have two variable regions, they can bind to antigens on two nearby cells, causing the cells to clump together. This clumping is called agglutination. 3

4 Blood Groups RBC membrane antigens ABO blood groups A & B antigens Preformed antibodies It s worth repeating that even our own body cells have glycoprotein antigens in their plasma membranes. Our lymphocytes do not produce antibodies against these antigens, though, because the body knows which antigens are supposed to be there. The specific antigens found on the membranes of erythrocytes determines a person s blood group. While there are dozens of erythrocyte antigens, only a small number are clinically important and need to be taken into account when doing a blood transfusion. ABO blood groups are one clinically important set of blood groups. A persons ABO blood type is determined by the presence or absence of two specific antigens on the red blood cell membranes: antigen A and antigen B. A person s RBC s can have both antigens (type AB), neither antigen (type O), just the A antigen (type A), or just the B antigen (type B). Please remember that the blood type indicates which antigens are found on the RBC membranes. There s a twist here! Through the miracle of modern human development, your blood will automatically form antibodies against whichever of these antigens you don t have on your RBCs. If you re blood type A (and just have A antigens on the cells), I guarantee you ve got anti-b antibodies in your blood plasma. Likewise, if you have blood type B (and just have B antigens on the cells), your blood plasma has anti-a antibodies. If your blood type is O (so you don t have either A or B antigens on your cells), your plasma will have both anti-a and anti-b antibodies. If your blood type is AB (so you ve got both antigens), your blood will not have formed either antibody. Since these antibodies are formed without (post-natal) exposure, we call them preformed antibodies. 4

5 Blood Groups If someone has blood type A A What antigens are in the RBC membranes? What antibodies are in the plasma? Can she receive blood cells from a type A donor? What about type B? Type AB? Type O? Remember that when an antibody encounters its specific antigen, it will bind to it and cause agglutination. When blood cells are transfused, it is important to make sure that the recipient s blood plasma does not have antibodies against any ABO antigens on the donated blood cells. If someone has blood type A The RBC membranes will have A antigens, which means that their blood plasma will have anti-b antibodies. This person can receive blood cells from another type A donor (because only cells with the B antigen will be attacked). This person cannot receive blood cells from a type B or type AB donor, though, since the B antibodies in the recipient s plasma will bind to the B antigens on those cells and cause agglutination. Type O is fine, since type O cells don t have either A or B antigens. In fact, type O cells are always fine. There are no A or B antigens to bind to. For this reason, type is considered a universal donor. 5

6 Blood Groups If someone has blood type O O What antigens are in the RBC membranes? What antibodies are in the plasma? Can she receive blood cells from a type O donor? What about type A? Type B? Type AB? If a person s ABO blood type is type O, their erythrocytes do not have either A or B antigens. This means that their blood has formed both anti-a and anti-b antibodies, so they can only receive type O blood cells. They cannot receive type A, B, or AB blood cells since those cells will have A antigens, B antigens, or both. 6

7 Blood Groups If someone has blood type AB What antigens are in the RBC membranes? What antibodies are in the plasma? Can she receive blood cells from a type O donor? What about type A? Type B? Type AB? People with type AB blood are considered universal recipients. Since their RBCs have both A and B antigens, their plasma will not have either anti-a or anti-b antibodies. Since neither of these antibodies exist, they can receive blood cells from anyone with type A, B, AB, or O blood. 7

8 Blood Groups This table summarizes the relationship between the ABO antigens and the plasma antibodies. Please do not try to memorize this table. Instead, you should be able to use your understanding of RBC antigens and plasma antibodies to derive the table on your own. Why might blood type O be so common? It has to do with the genetics of the RBC antigens and the allele frequencies in different populations. We ll get to that shortly. 8

9 Blood Groups Rh blood groups Rh antigen No preformed antibodies Hemolytic disease of the newborn (HDN) Rh blood groups are a second important RBC antigen grouping. In this case, we re only concerned with one RBC antigen: the Rh antigen. (In actuality, there are several separate Rh antigens, but we re only going to worry about one of them, called RhD). The Rh antigen got its name because it was first described in the blood cells of rhesus monkeys. Simply speaking, either your blood cells have the Rh antigen (Rh-positive, Rh + ) or they don t (Rhnegative, Rh - ). Unlike with the ABO antigens, though, the blood does not automatically form anti-rh antibodies, even if your Rh blood type is Rh-negative! As with most antigens, exposure to the Rh antigen is required before the lymphocytes start making anti-rh antibodies. The consequences of this are: if you are Rh-positive, your blood will never make anti-rh antibodies (because it knows that the Rh antigen is supposed to be there); if you are Rh-negative, the blood will only start making anti-rh antibodies after being exposed to Rh-positive blood cells. In practical terms, this means that someone with Rh-positive blood can receive blood cells from a donor with either Rh-positive or Rh-negative blood (since they will never make anti-rh antibodies). Someone with Rh-negative blood, though, can receive a blood transfusion from a donor with Rhpositive blood exactly one time. Once the Rh-positive cells are introduced, anti-rh antibodies will start to be produced, but this happens slowly enough that the transfused cells will probably be ok. A special problem related to the Rh blood groups occurs in Rh-negative women when they become pregnant with an Rh-positive fetus. Since anti-rh antibodies don t form until after exposure, the first time this happens, the mother s blood will not have formed anti-rh antibodies. In fact, since blood is not usually exchanged fetus-to-mother until childbirth, anti-rh antibodies won t usually start to form until the Rh-positive baby is born. The problem occurs if the mother becomes pregnant with another Rh-positive child. If this happens, baby s plasma (inherited from the mother) will have anti-rh antibodies that will bind to the Rh antigens on the baby s erythrocytes. This results in a condition called hemolytic disease of the newborn (HDN), in which the baby is anemic and jaundiced and may have heart and/or liver problems. If a child does develop HDN prenatally, blood transfusions often have to be done before the fetus is even born. To prevent HDN, pregnant Rh-negative women are usually given a medicine called RhoGAM, which prevents the formation of anti-rh antibodies. 9

10 Blood Groups Genetics: ABO: Three alleles, I A, I B, i Genotypes: I A I A, I A i,, I B I B, I B i,, I A I B, ii Rh: : Two alleles: Rh +, Rh - Genotypes: Rh + Rh +, Rh + Rh -, Rh - Rh - If you remember Mendel s laws and Punnett squares from biology class, you shouldn t have any problem understanding the genetics behind which antigens your blood cells have. It s helpful to recall that what dominant/recessive really means is either make a working copy of this protein (dominant) or don t make a working copy of this protein (recessive). Each individual has two alleles (which may be the same or may be different) for each gene, and as long as they have at least one copy of the make a working copy of this protein allele, the cells can make it. For the ABO blood groups, there are three alleles: I A (for antigen A), I B (for antigen B), and i (for no antigen). This means that there are six possible allele combinations in each person: the RBC antigens in their blood cells is determined by their genotypes. If a person s genotype is I A I A or I A i, their RBCs will have only A antigens, so their blood type will be type A. If a person s genotype is I B I B or I B i, the RBCs will only have B antigens, so the blood type will be type B. If a person s genotype is I A I B, then the cells have instructions for making both antigens, so the cells will have both A and B antigens (type AB). If a person s genotype is ii, they do not have instructions for making either antigen and the blood will be type O. For Rh, there are just the usual two alleles: Rh + (dominant; instructions for making the Rh antigen) and Rh - (recessive). If a person s genotype is Rh + Rh + or Rh + Rh -, they will have at least one copy of the instructions for making the Rh antigen, so they will have the Rh antigen in their blood cells (Rhpositive). If the genotype is Rh - Rh -, they don t have a good copy of the instructions, so they will be Rh-negative. 10

11 Blood Typing Uses known anti- sera Cross-typing Blood typing is a procedure used to determine the blood groups for an unknown sample of blood. The procedure takes advantage of the fact that when blood cells are mixed with a serum containing antibodies that match their antigens, visible agglutination will occur. (You can see what this looks like in the picture above) For example, if I treat unknown blood cells with a serum containing anti-a antibodies and the blood cells agglutinate, I know that there are A antigens on those RBCs. Even once a blood type is determined, the blood typing is usually double-checked by cross-typing before it is given to a donor. When blood is cross-typed, some of the donor blood cells are mixed with the recipients plasma to make sure that the blood doesn t agglutinate. 11

12 Blood Typing Subject s s blood: To determine the ABO and Rh blood groups for an unknown blood sample, you need three small samples of the unknown blood. One sample will be tested for antigen A, one for antigen B and one for the RhD antigen. A different anti-serum (blood plasma with no clotting factors, but containing known antibodies) is added to each sample to check for agglutination. 12

13 Blood Typing Anti-A A serum (contains anti-a A antibodies) No agglutination! Do the RBC s have A antigens? Here s an example. Suppose anti-a serum (serum containing anti-a antibodies) is added to one of the samples and no agglutination is observed. This means that the blood cells do not have A antigens. 13

14 Blood Typing Anti-B B serum (contains anti-b B antibodies) Agglutination! Do the RBC s have B antigens? What is the ABO blood type? Now to the next sample (from the same person), we add anti-b serum. Suppose we see agglutination. This means that the RBC s have B antigens. Since we know that the blood has B antigens, but not A antigens, we know that the ABO blood group is type B. 14

15 Blood Typing Anti-Rh serum (contains anti-rh antibodies) Agglutination! Do the RBC s have Rh antigens? What is the Rh blood type? Now, we add anti-rh serum to the final sample. Suppose we see agglutination. This means that the RBCs have the Rh antigen, and are therefore Rh-positive. 15