Blood Physiology PDF - ST. DOMINIC SCHOOL

BLOOD Dr. Raquel Jocson, MD, MHPEd 11/20/2024 By: Group 2 Edited by: 2L, 5L OUTLINE...

BLOOD Dr. Raquel Jocson, MD, MHPEd 11/20/2024 By: Group 2 Edited by: 2L, 5L OUTLINE Albumin - responsible for Colloid Oncotic Pressure ○ Ions or Electrolytes ○ Hormones I. Blood ○ Nutrients (Amino acids, Fatty acids Glucose, II. Plasma Vitamins, Minerals) III. Cellular Elements ○ Water (92%) A. White Blood Cells III. CELLULAR ELEMENTS 1. Agranulocytes Includes: 1.1 Lymphocytes ○ RBC or erythrocytes 1.2 Monocytes ○ WBC or leukocytes 2. Granulocytes ○ Platelets - responsible for hemostasis (2nd stage of 2.1 Basophils hemostasis) 2.2 Neutrophils 2.3 Eosinophils A. WHITE BLOOD CELLS B. Red Blood Cells AKA Leukocytes 1. ABO 1. AGRANULOCYTES 1.1 Paternity Testing 2. Rh 1.1 Lymphocytes 2.1 Relevance Of Rh In Pregnancy Responsible for prevention of infection, 3. Transfusion Reaction Further divided into: 3.1 ABO Typing Transfusion Reaction ○ B-Lymphocytes - responsible for humoral immunity 3.2 Rh Typing Transfusion Reaction or antibody production C. Hematopoiesis ○ T-Lymphocytes - responsible for cell-mediated immunity 1. Occurrence During Pregnancy 2. Formation In Bones 1.2 Monocytes 3. Stem Cells When they enter the tissues, they become 4. Erythropoietin macrophages 5. Erythrocyte Cell Stages ○ Macrophages are also phagocytes 6. Platelets 2. GRANULOCYTES 7. Red Blood Cells They have cytoplasmic inclusions that give off their 7.1 Anemia granular appearance 7.2 Polycythemia Flow 2.1 Basophils Sample Questions For inflammation since it releases histamine 2.2 Neutrophils Note: The information in the bulleted content is as stated Acts as phagocytes during bacterial infection by Dr. Jocson was rearranged for organization, and the additional notes were taken from Guyton. 2.3 Eosinophils Important for allergies and parasitism; eosinophils will increase I. BLOOD Consists of plasma and cellular elements Additional Notes (Guyton & Hall) ★ The leukocytes are the mobile units of the body’s II. PLASMA protective system. Consists of: ★ They are formed partially in the bone marrow ○ Proteins (2%), include: (granulocytes and monocytes and a few Immunoglobulines (Ig) or antibodies lymphocytes) and partially in the lymph tissue Clotting Factors (lymphocytes and plasma cells). PHYSIOLOGY BLOOD 1 of 10 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited.  ★ After formation, they are transported in the blood to ○ Thickness of 2.5 mm at the thickest point and 1 different parts of the body where they are needed. micrometer or less in the center. ★ The real value of WBCs is that most of them are ★ The average volume of the RBC is 90 to 95 cubic specifically transported to areas of serious infection mm. The shapes of RBCs can change remarkably as and inflammation, thereby providing a rapid and the cells squeeze through capillaries. Actually, the potent defense against infectious agents. RBC resembles a bag that can be deformed into ★ Granulocytes and monocytes have a special ability to almost any shape. “seek out and destroy” a foreign invader. ★ The normal cell has a great excess of cell membrane for the quantity of material inside, deformation does Concentrations of Different White Blood Cells in not stretch the membrane greatly and, consequently, Blood does not rupture the cell, as would be the case with ★ Adult human = about 7000 WBCs per mL of blood many other cells. ○ In comparison with 5 million RBCs per mL ○ Neutrophils: 62.0% Concentration of Red Blood Cells in the Blood ○ Eosinophils: 2.3% ★ Average number of RBCs per cubic mm in healthy ○ Basophils: 0.4% individuals: ○ Monocytes: 5.3% ○ Men = 5,200,000 (±300,000) ○ Lymphocytes: 30.0% ○ Women = 4,700,000 (±300,000) ★ The number of platelets, which are only cell ★ Persons living at high altitudes have greater numbers fragments, in each mL of blood is normally between of RBCs, as discussed later 150,000 and 450,000, averaging about 300,000. They have antigen on the surface, which is responsible B. RED BLOOD CELLS for the blood type AKA Erythrocytes Two types of Blood Typing: Shape: Biconcave disc ○ ABO ○ Rh ○ Responsible for flexibility of RBC ○ They can squeeze through capillaries and respond 1. ABO to changes in osmotic pressure Based on the presence of antigen, you can determine the blood type of the person Additional Notes (Guyton & Hall) In the serum, you have the antibodies or agglutinins ★ Major function of RBCs is to transport hemoglobin, Type O - universal donor (no antigens) which carries oxygen from the lungs to the tissues. Type AB - universal recipient (no antibodies) ○ Free hemoglobin in human plasma: about 3% of it leaks through the capillary membrane into the tissue spaces or through the glomerular BLOOD GENOTYPE AGGLUTINOGEN AGGLUTININ membrane of the kidney into the glomerular TYPE (Ag) (Ab) filtrate each time the blood passes through the capillaries. A OO A Anti-B ○ Hemoglobin must remain inside RBCs to perform its functions in humans effectively. B OA or AA B Anti-A ★ The RBCs have other functions besides transport of hemoglobin: AB OB or BB A&B None ○ They contain a large quantity of carbonic anhydrase, an enzyme that catalyzes the O AB None Anti-A & reversible reaction between carbon dioxide Anti-B (CO2) and water to form carbonic acid (H2CO3), increasing the rate of this reaction several thousandfold. 1.1 Paternity Testing ○ The rapidity of this reaction makes it possible ABO typing can also be used for paternity testing or for the water of the blood to transport genetic determination enormous quantities of CO2 in the form of ○ Example: if your blood type is A, the alleles or bicarbonate ion (HCO3−) from the tissues to genotype is either OA or AA. You inherit one from the lungs, where it is reconverted to CO2 and each parent expelled into the atmosphere as a body waste product. ○ O is recessive, while A and B are dominant By using blood typing, you can determine whether your ○ The hemoglobin in the cells is an excellent parents are your real parents or the paternity testing acid-base buffer (as is true of most proteins), If your blood type is A and your mother is type O, your so the RBCs are responsible for most of the father should not be blood type B acid-base buffering power of whole blood. If the baby is type A and the mother is type O, and the father is type B, that is an issue regarding paternity Shape and Size of Red Blood Cells testing. That wouldn’t be your real father if the father is ★ Normal RBCs are biconcave discs: type B ○ Mean diameter of about 7.8 mm PHYSIOLOGY BLOOD 2 of 10 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited.  If you are type A, and your mother is type O, your father should not be type B or type AB, your father should be who does not have type D antigen is said to be Rh type A negative. Before it is used for paternity testing, but nowadays we ★ However, it must be noted that even in Rh-negative have DNA which is more specific people, some of the other Rh antigens can still cause transfusion reactions, although the reactions are usually much milder. Additional Notes (Guyton & Hall) ★ About 85% of all whites are Rh positive, and 15% are Rh negative. Genetic Determination of the Agglutinogens ★ In American blacks, the percentage of Rh positives is ★ The ABO blood group genetic locus has three alleles, about 95%, whereas in African blacks, it is nearly which means three different forms of the same gene. 100%. ○ These three alleles—IA, IB, and IO—determine ★ Over 95% of Native Americans and Asians living in the three blood types. We typically call these China, Japan, and Korea are also Rh positive, and it alleles A, B, and O, but geneticists often is estimated that the worldwide frequencies of represent alleles of a gene by variations of the Rh-positive and Rh-negative blood types are 95% same symbol. and 6%, respectively. ○ In this case, the common symbol is the letter “I,” which stands for immunoglobulin. ★ The type O allele is functionless or almost 2.1 Relevance of Rh in Pregnancy functionless, so it causes no significant type O When the mother is Rh (-) and the father is Rh (+), agglutinogen on the cells. during the first pregnancy there will be no reaction or ○ Conversely, the type A and type B alleles do complication. But in the subsequent pregnancy, a cause strong agglutinogens on the cells. Thus, condition known as Erythroblastosis fetalis may occur: the O allele is recessive to both the A and B ○ The baby inherits the antigen from the father and alleles, which show co-dominance. may become Rh (+) ○ Because each person has only two sets of ○ During the first pregnancy, the Rh (+) blood with chromosomes, only one of these alleles is the antigen may cross the placenta, exposing the present on each of the two chromosomes in mother to the antigen and develop antibodies any individual. against the D antigen ○ However, the presence of three different alleles ○ In the subsequent or second pregnancy, since means that there are six possible combinations the mother already has the antibody against D of alleles: OO, OA, OB, AA, BB, and AB. antigen, the antibody may cross the placenta and ★ These combinations of alleles are known as the go to the second baby, which is Rh (+), therefore genotypes, and each person is one of the six causing a reaction. The antibodies will hemolyze or genotypes: attack the RBCs of the baby, therefore there will be ○ OO produces no agglutinogens = type O hemolysis of the RBCs, developing Erythroblastosis ○ OA or AA produces type A agglutinogens = fetalis type A Erythroblastosis fetalis - characterized by: ○ OB and BB = type B ○ AB = type AB ○ Hepatomegaly ○ Jaundice - due to the hemolysis of the RBCs there will be increased production of bilirubin 2. RH Therefore, kernicterus may develop, affecting Antigens present: C D E c d e and damage the neurons of the cerebral cortex How is this prevented? ○ Most common is D, which means you are Rh (+) ○ 98% of filipinos are RH (+) ○ The mother is injected with immunoglobulin against the D antigen also known as Rhogam ○ Africans are RH (-) Additional Notes (Guyton & Hall) Additional Notes (Guyton & Hall) Treatment of Neonates With Erythroblastosis Fetalis Rh Antigens—Rh-Positive and Rh-Negative ★ One treatment for erythroblastosis fetalis is to replace ★ There are six common types of Rh antigens, each of the neonate’s blood with Rh-negative blood. which is called an Rh factor. ★ The Rh-negative blood is infused over a period of 1.5 ○ These types are designated C, D, E, c, d, e. or more hours while the neonate’s own Rh-positive ★ A person who has a C antigen does not have the c blood is being removed. antigen, but the person missing the C antigen always ★ This procedure may be repeated several times during has the c antigen. the first few weeks of life, mainly to keep the bilirubin ○ The same is true for the D-d and E-e antigens. level low and thereby prevent kernicterus. ★ Because of the manner of inheritance of these ★ By the time these transfused Rh-negative cells are factors, each person has one of each of the three replaced with the infant’s own Rh-positive cells, a pairs of antigens. process that requires 6 weeks or more, the anti-Rh ★ The type D antigen is widely prevalent in the agglutinins that had come from the mother will have population and is considerably more antigenic than been destroyed. the other Rh antigens. Anyone who has this type of antigen is said to be Rh positive, whereas a person PHYSIOLOGY BLOOD 3 of 10 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited.  Prevention of Erythroblastosis Fetalis 2. FORMATION IN BONES ★ The D antigen of the Rh blood group system is the primary culprit in causing immunization of an In adults, it is formed in the bone marrow of: Rh-negative mother to an Rh-positive fetus. ○ The proximal ends of your long bones ★ In the 1970s, a dramatic reduction in the incidence of Includes your humerus and femur erythroblastosis fetalis was achieved with the ○ Sternum development of Rh immunoglobulin globin, an ○ Ribs anti-D antibody that is administered to the expectant ○ Vertebra mother starting at 28 to 30 weeks of gestation. ○ Pelvis ★ The anti-D antibody is also administered to Rh-negative women who deliver Rh-positive babies to prevent sensitization of the mothers to the D Additional Notes (Guyton & Hall) antigen. ★ This step greatly reduces the risk of developing large PRODUCTION OF RED BLOOD CELLS amounts of D antibodies during the second pregnancy Areas of the Body That Produce Red Blood Cells ★ The mechanism whereby Rh immunoglobulin globin ★ In the early weeks of embryonic life, primitive prevents sensitization of the D antigen is not nucleated RBCs are produced in the yolk sac. completely understood, but one effect of the anti-D ★ During the middle trimester of gestation, the liver is antibody is to inhibit antigen-induced, B lymphocyte the main organ for RBC production but reasonable antibody production in the expectant mother. numbers are also produced in the spleen and lymph ★ The administered anti-D antibody also attaches to D nodes. 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. 3. TRANSFUSION REACTION 3.1 ABO Typing Transfusion Reaction In transfusion reaction, for ABO typing, when you transfuse blood, that is different for the patient, using ABO typing, the transfusion reaction will be immediate and maybe severe 3.2 Rh Typing Transfusion Reaction If you are Rh negative, and you’re given Rh positive blood, the reaction on the first exposure would be: ★ During the last month or so of gestation and after birth, RBCs are produced exclusively in the bone ○ Sensitization process - the person receiving the marrow. As illustrated in Figure 33-1, the marrow of Rh positive will develop antibodies against the essentially all bones produces RBCs until a person is antigen about 5 years old. ○ For the first exposure, there might be no reaction, ○ The marrow of the long bones, except for the mild reaction or may be delayed, because when proximal portions of the humeri and tibiae, the person developed the antibodies against the D becomes fatty and produces no more RBCs antigen, these antibodies can react with the D after about the age of 20 years. Beyond this antigen. age, most RBCs continue to be produced in the During the second and subsequent exposure, since marrow of the membranous bones, such as the the person already developed antibodies against the D vertebrae, sternum, ribs, and ilia. antigen, exposure will have severe reaction and ○ Even in these bones, the marrow becomes less immediate. productive as age increases. C. HEMATOPOIESIS 3. STEM CELLS What organ produces these cellular elements? ○ These are produced in the bone marrow in adults Hematopoiesis in the bone marrow starts with the The formation of your cellular elements is called Hematopoietic Pluripotential Stem Cell hematopoiesis ○ It will then differentiate into committed stem cells which include your Colony Forming Unit for 1. OCCURRENCE DURING PREGNANCY Erythrocytes Hematopoiesis occurs intra utero during pregnancy in: ○ Colony Forming Unit for Granulocytes and ○ The yolk sac for the first trimester Monocytes ○ Followed in the middle trimester by the liver and by ○ Megakaryocytes which should form your Platelets the spleen We also have your Lymphocyte Stem Cell which will ○ And on the third trimester, it will be the bone be responsible for the formation of your Lymphocytes marrow. PHYSIOLOGY BLOOD 4 of 10 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited.  Additional Notes (Guyton & Hall) ★ Formation of the growth inducers and differentiation inducers is controlled by factors outside the bone Genesis of Blood Cells marrow. ○ RBCs: exposure of the blood to a low oxygen Multipotential Hematopoietic Stem Cells, Growth level for a long time causes growth induction, Inducers, and Differentiation Inducers differentiation, and production of greatly increased numbers of RBCs. ○ WBCs: infectious diseases cause growth, differentiation, and eventual formation of specific types of white blood cells that are needed to combat each infection. 4. ERYTHROPOIETIN Hormone that stimulates the formation of Red Blood Cells Erythropoietin is stimulated by tissue hypoxia ○ Tissue hypoxia will stimulate your kidneys to release erythropoietin, and then erythropoietin will act on bone marrow to form more red blood cells Additional Notes (Guyton & Hall) ★ The blood cells begin their lives in the bone marrow from a single type of cell called the multipotential hematopoietic stem cell, from which all the cells of the circulating blood are eventually derived. ★ Figure 33-2 shows the successive divisions of the multipotential cells to form the different circulating blood cells. ★ As these cells reproduce, a small portion of them remains exactly like the original multipotential cells and is retained in the bone marrow to maintain their supply, although their numbers diminish with age. ★ Most of the reproduced cells, however, differentiate to form the other cell types. ★ The intermediate stage cells are very much like the multipotential stem cells, even though they have already become committed to a particular line of cells; these are called committed stem cells. ○ The different committed stem cells, when grown in culture, will produce colonies of specific types of blood cells. ○ A committed stem cell that produces erythrocytes is called a colony-forming unit–erythrocyte (CFU-E). ○ Likewise, colony-forming units that form granulocytes and monocytes have the designation CFU-GM, and so forth. Hypoxia Increases Formation of Erythropoietin Which ★ Growth and reproduction of the different stem cells Stimulates Red Blood Cell Production are controlled by multiple proteins called growth ★ The principal stimulus for RBC production in a low inducers. At least four major growth inducers have oxygen state is a circulating hormone called been described, each having different characteristics. erythropoietin, a glycoprotein with a molecular ○ One of these, interleukin-3, promotes growth weight of about 34,000. and reproduction of virtually all the different ★ In the absence of erythropoietin, hypoxia has little or types of committed stem cells, whereas the no effect to stimulate RBC production. others induce growth of only specific types of ★ However, when the erythropoietin system is cells. functional, hypoxia causes a marked increase in ★ The growth inducers promote growth but not erythropoietin production and the erythropoietin, in differentiation of the cells, which is the function of turn, enhances RBC production until the hypoxia is another set of proteins called differentiation relieved. inducers. ○ Each of these differentiation inducers causes Erythropoietin Is Formed Mainly in the Kidneys one type of committed stem cell to differentiate ★ Normally, about 90% of all erythropoietin is formed in one or more steps toward a final adult blood the kidneys, and the remainder is formed mainly in cell. the liver. PHYSIOLOGY BLOOD 5 of 10 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited.  ★ It is not known exactly where in the kidneys the ★ The first-generation cells are called basophil erythropoietin is formed. Some studies have erythroblasts because they stain with basic dyes. suggested that erythropoietin is secreted mainly by Hemoglobin first appears in polychromatophil fibroblast-like interstitial cells surrounding the tubules erythroblasts. in the cortex and outer medulla, where much of the ○ In the succeeding generations, the cells kidney’s oxygen consumption occurs. become filled with hemoglobin to a ★ It is likely that other cells, including the renal concentration of about 34%, the nucleus epithelial cells, also secrete erythropoietin in condenses to a small size, and its final remnant response to hypoxia. is absorbed or extruded from the cell. ★ Renal tissue hypoxia leads to increased tissue levels ○ At the same time, the endoplasmic reticulum is of hypoxia-inducible factor-1 (HIF-1), which serves as also reabsorbed. The cell at this stage is called a transcription factor for a large number of hypoxia a reticulocyte because it still contains a small inducible genes, including the erythropoietin gene, amount of basophilic material, consisting of ★ At times, hypoxia in other parts of the body, but not in remnants of the Golgi apparatus, mitochondria, the kidneys, stimulates kidney erythropoietin and a few other cytoplasmic organelles. secretion, which suggests that there might be some ○ During this reticulocyte stage, the cells pass nonrenal sensor that sends an additional signal to the from the bone marrow into the blood capillaries kidneys to produce this hormone. by diapedesis (squeezing through the pores of ○ Norepinephrine and epinephrine and several of the capillary membrane). the prostaglandins stimulate erythropoietin ★ The remaining basophilic material in the reticulocyte production. normally disappears within 1 to 2 days, and the cell is ★ When both kidneys are removed from a person, or then a mature erythrocyte. when the kidneys are destroyed by renal disease, the ○ Because of the short life of the reticulocytes, person invariably becomes very anemic. their concentration among all the RBCs is ○ This is because the 10% of the normal normally slightly less than 1% erythropoietin formed in other tissues (mainly in the liver) is sufficient to cause only one third to half the RBC formation needed by the body. 6. PLATELETS Platelets produced in the bone marrow can be affected 5. ERYTHROCYTE CELL STAGES by the hormone Thrombopoietin which is produced by the liver First we have your proerythroblast Platelets are also called as thrombocytes It will start with the Colony Forming Unit Erythrocyte and The half life of platelets is very short, it is 8 to 12 days then form your Proerythroblast and finally your erythrocytes 7. RED BLOOD CELLS For your red blood cells, half life is 120 days Additional Notes (Guyton) Red blood cells can be decreased Stages of Differentiation of Red Blood Cells Additional Notes (Guyton) ★ When RBCs are delivered from the bone marrow into the circulatory system, they normally circulate an average of 120 days before being destroyed. ○ Even though mature RBCs do not have a nucleus, mitochondria, or endoplasmic reticulum, they do have cytoplasmic enzymes that are capable of metabolizing glucose and forming small amounts of adenosine triphosphate. ○ These enzymes also do the following: (1) maintain pliability of the cell membrane; (2) maintain membrane transport of ions; (3) keep the iron of the cells’ hemoglobin in the ferrous form rather than the ferric form; and (4) prevent oxidation of the proteins in the ★ The first cell that can be identified as belonging to the RBCs. RBC series is the proerythroblast. ○ Even so, the metabolic systems of old RBCs ○ Under appropriate stimulation, large numbers become progressively less active, and the cells of these cells are formed from the CFU-E stem become more and more fragile, presumably cells. Once the proerythroblast has been because their life processes wear out. formed, it divides multiple times, eventually ★ Once the RBC membrane becomes fragile, the cell forming many mature RBCs. ruptures during passage through some tight spot of the circulation. PHYSIOLOGY BLOOD 6 of 10 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited.  ○ Many of the RBCs self-destruct in the spleen, ★ In autoimmune disorders, such as lupus where they squeeze through the red pulp of the erythematosus, the immune system begins attacking spleen. healthy cells such as bone marrow stem cells, which ○ There, the spaces between the structural may lead to aplastic anemia. trabeculae of the red pulp, through which most ★ In about half of aplastic anemia cases the cause is of the cells must pass, are only 3 micrometers unknown, a condition called idiopathic aplastic wide, in comparison with the 8-micrometer anemia. diameter of the RBC. ★ People with severe aplastic anemia usually die ○ When the spleen is removed, the number of old unless they are treated with blood transfusions, which abnormal RBCs circulating in the blood can temporarily increase the numbers of RBCs—or increases considerably by bone marrow transplantation. Megaloblastic Anemia 7.1 Anemia ★ Vitamin B12, folic acid, and intrinsic factor from the When you have decreased RBC, you call that as anemia stomach mucosa = loss of any one of these can lead Causes of anemia: to slow reproduction of erythroblasts in the bone ○ Blood loss marrow. ○ Chronic Kidney Disease ★ As a result, the RBCs grow too large, with odd Because you have no erythropoietin. Also in shapes, and are called megaloblasts. Thus, atrophy CKD, you have increased destruction of red of the stomach mucosa, as occurs in pernicious blood cells anemia, or loss of the entire stomach after surgical Destruction of red blood cells is called as total gastrectomy can lead to megaloblastic anemia. hemolysis ★ It often develops in patients who have intestinal ○ Iron deficiency sprue, in which folic acid, vitamin B12, and other Nutritional; not only iron but also vitamin B12 vitamin B compounds are poorly absorbed. Because and folic acid the erythroblasts in these states cannot proliferate ○ Decreased production by the bone marrow called rapidly enough to form normal numbers of RBCs, the Aplastic Anemia RBCs that are formed are mostly oversized, have There is destruction of bone marrow and bizarre shapes, and have fragile membranes. These therefore bone marrow is not able to produce, cells rupture easily, leaving the person in dire need of not only red blood cells, but also the others like an adequate number of RBCs. white blood cells and the platelets. Hemolytic Anemia Additional Notes (Guyton & Hall) ★ Different abnormalities of the RBCs, many of which ★ Anemia means deficiency of hemoglobin in the are acquired through hereditary, make the cells blood, which can be caused by too few RBCs or too fragile, so they rupture easily as they go through the little hemoglobin in the cells. Some types of anemia capillaries, especially through the spleen. and their physiological causes are described in the ★ Even though the number of RBCs formed may be following sections: normal, or even much greater than normal in some hemolytic diseases, the life span of the fragile RBC is Blood Loss Anemia so short that the cells are destroyed faster than they ★ Rapid hemorrhage: the body replaces the fluid can be formed, and serious anemia results. portion of the plasma in 1 to 3 days, but this ★ Hereditary spherocytosis response results in low RBC concentration ○ The RBCs are very small and spherical rather ★ If a second hemorrhage does not occur, the RBC than being biconcave discs. These cells cannot concentration usually returns to normal within 3 to 6 withstand compression forces because they do weeks. not have the normal loose, baglike cell ★ Chronic blood loss: a person frequently cannot membrane structure of the biconcave discs. absorb enough iron from the intestines to form ○ On passing through the splenic pulp and some hemoglobin as rapidly as it is lost. other tight vascular beds, they are easily ★ RBCs that are much smaller than normal and have ruptured by even slight compression. too little hemoglobin inside them are then produced, ★ Sickle cell anemia giving rise to microcytic hypochromic anemia, which ○ Present in 0.3% to 1.0% of West African and is shown in Figure 33-3. American blacks ○ The cells have an abnormal type of hemoglobin Aplastic Anemia Due to Bone Marrow Dysfunction called hemoglobin S, containing faulty beta ★ Bone marrow aplasia means lack of functioning bone chains in the hemoglobin molecule, as marrow. explained earlier in this chapter. ★ For example, exposure to high-dose radiation or ○ When this hemoglobin is exposed to low chemotherapy for cancer treatment can damage concentrations of oxygen, it precipitates into stem cells of the bone marrow, followed in a few long crystals inside the RBC. These crystals weeks by anemia. elongate the cell and give it the appearance of ★ Likewise, high doses of certain toxic chemicals, a sickle rather than a biconcave disc. such as insecticides or benzene in gasoline, may ○ The precipitated hemoglobin also damages the cause the same effect. cell membrane, so the cells become highly fragile, leading to serious anemia. PHYSIOLOGY BLOOD 7 of 10 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited.  ○ Such patients frequently experience a vicious The blast cells no longer stop producing RBCs when circle of events called a sickle cell disease too many cells are already present. crisis, in which low oxygen tension in the ○ This causes excess production of RBCs in the tissues causes sickling, which leads to ruptured same manner that a breast tumor causes RBCs, which causes a further decrease in excess production of a specific type of breast oxygen tension and still more sickling and RBC cell. destruction. ○ It usually causes excess production of white ○ Once the process starts, it progresses rapidly, blood cells and platelets as well. eventuating in a serious decrease in RBCs ★ Not only does the hematocrit increase, but the total within a few hours and, in some cases, death. blood volume also increases, sometimes to almost ★ Erythroblastosis fetalis twice normal. ○ Rh-positive RBCs in the fetus are attacked by ○ As a result, the entire vascular system antibodies from an Rh-negative mother. becomes intensely engorged. ○ These antibodies make the Rh-positive cells ○ Many blood capillaries become plugged by the fragile, leading to rapid rupture and causing the viscous blood; the viscosity of the blood in child to be born with a serious case of anemia. polycythemia vera sometimes increases from ○ The extremely rapid formation of new RBCs to the normal of 3 times the viscosity of water to make up for the destroyed cells in 10 times that of water. erythroblastosis fetalis causes a large number of early blast forms of RBCs to be released from the bone marrow into the blood. SDCA-SOM BULLETIN BOARD 7.2 Polycythemia When your red blood cells are increased, you call that as Polycythemia Causes of polycythemia: ○ When oxygen level is low, this will stimulate kidneys to produce erythropoietin and therefore red blood cell will increase and you call that secondary polycythemia, which is very common in patients with chronic obstructive pulmonary disease wherein there is chronic hypoxia and therefore excessive production of erythropoietin by the kidneys causing increased red blood cell ○ Polycythemia can be primary. It is a genetic condition wherein there is excessive production of red blood cells, so primary polycythemia or polycythemia vera Additional Notes (Guyton & Hall) Secondary Polycythemia ★ 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 tissues, such as in cardiac failure, the blood-forming organs automatically produce large quantities of extra RBCs. ★ The RBC count commonly rises to 6 to 7 million/mm3, about 30% above normal. ★ A common type of secondary polycythemia, called physiological polycythemia, occurs in those 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, which allows these people to perform reasonably high levels of continuous work, even in a rarefied atmosphere. Polycythemia Vera (Erythremia) ★ The RBC count may be 7 to 8 million/mm3 and the hematocrit may be 60% to 70% instead of the normal 40% to 45%. ★ It is caused by a genetic aberration in the hemocytoblastic cells that produce the blood cells. PHYSIOLOGY BLOOD 8 of 10 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited.  FLOW PHYSIOLOGY BLOOD 9 of 10 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited.  SAMPLE QUESTIONS QUESTION EXPLANATION ANSWER 1 In ABO blood typing, what makes type O blood the Type O blood lacks A and B antigens, which B universal donor? makes it the universal donor. A. It has both A and B antigens. Check 1. ABO B. It has no antigens on its surface. C. It contains no antibodies in the plasma. D. It has both anti-A and anti-B antibodies. 2 Which of the following conditions is a potential Rh incompatibility, especially when the mother is B consequence of Rh incompatibility during pregnancy? Rh-negative and the baby is Rh-positive, can lead to erythroblastosis fetalis in subsequent A. Thrombocytopenia pregnancies. B. Erythroblastosis fetalis C. Polycythemia vera Check 2.1 Relevance Of Rh In Pregnancy D. Aplastic anemia 3 Which of the following is the primary cause of Polycythemia vera is caused by a genetic C polycythemia vera? mutation leading to excessive production of red blood cells. A. Tissue hypoxia B. Excessive erythropoietin production Check 7.2 Polycythemia C. Genetic mutation in hemocytoblastic cells D. Chronic kidney disease 4 Which organ primarily produces red blood cells during During the middle trimester, the liver is the C the middle trimester of pregnancy? primary site of red blood cell production. A. Bone marrow Check 1. Occurrence During Pregnancy B. Yolk sac C. Liver D. Spleen 5 Which antigen determines if a person is Rh-positive? The D antigen is the most antigenic of the Rh C antigens and determines if a person is A. C antigen Rh-positive. B. D antigen C. d antigen Check 2. Rh D. e antigen PHYSIOLOGY BLOOD 10 of 10 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited.  HEMOSTASIS Dr. Raquel Jocson, MD, MHPEd 11/20/2024 By: Group 2 Edited by: 2L and 4L OUTLINE II. 4 MECHANISMS OR STAGES Vasoconstriction or Vascular Constriction I. Hemostasis Platelet Plug Formation II. 4 Mechanisms Or Stages Blood Coagulation of Formation of Blood Clot A. Vasocontriction Fibrous Organization or Disorganization of Blood Cells 1. Local Myogenic Spasm 2. Local Autacoid Factors A. VASOCONSTRICTION 3 Causes: 3. Nervous Reflexes 2. Platelet Plug Formation 1. LOCAL MYOGENIC SPASM B. Blood Coagulation The smooth muscles in the blood vessels contract 1. Trauma To Blood 2. Damage To Vessel Wall 2. LOCAL AUTACOID FACTORS 3. Contact Of Blood With Damages Vessel Wall The release of autacoid substances or factors, includes: III. Mechanism Of Blood Coagulation platelets release thromboxane A2 from the traumatized A. Blood Coagulation General Mechanism tissues, vascular endothelium, and blood platelets 1. Fibrinogen To Fibrin 3. NERVOUS REFLEXES B. Extrinsic Pathway C. Intrinsic Pathway The pain you experience when blood vessels are injured 1. Mechanism Of Intrinsic Pathway will stimulate the sympathetic nervous system causing vasoconstriction D. Fibrous Organization Or Fibrolysis IV. Clotting Factors Additional Notes (Guyton & Hall) A. Clinical Correlations ★ Immediately after a blood vessel has been cut or 1. Hemophilia ruptured, the trauma to the vessel wall causes B. Anticoagulation In The Body smooth muscle in the wall to contract; this instantaneously reduces the flow of blood from the 1. Endothelial Factors ruptured vessel. The contraction results from the 2. Heparin following: 3. Thrombomodulin-ThrombiN COMPLEX ○ (1) local myogenic spasm; ○ (2) local autacoid factors from the traumatized tissues, vascular endothelium, and blood platelets; ○ (3) nervous reflexes Note: The information in the bulleted content is as stated Bood Initiated by pain nerve impulses or by Dr. Jocson was rearranged for organization, and the other sensory impulses that originate from additional notes were taken from Guyton. the traumatized vessel or nearby tissues. ★ However, even more vasoconstriction probably results from local myogenic contraction of the blood I. HEMOSTASIS vessels initiated by direct damage to the vascular wall. And, for the smaller vessels, the platelets are Prevention of blood loss responsible for much of the vasoconstriction by releasing a vasoconstrictor substance, thromboxane Additional Notes (Guyton & Hall) A2. ★ The term hemostasis means prevention of blood ★ The more severely a vessel is traumatized, the loss. Whenever a vessel is severed or ruptured, greater the degree of vascular spasm. The spasm hemostasis is achieved by several mechanisms: (1) can last for many minutes or even hours, during vascular constric-tion; (2) formation of a platelet plug; which time the processes of platelet plugging and (3) formation of a blood clot as a result of blood blood coagulation can take place. coagulation; and (4) eventual growth of fibrous tissue into the blood clot to close the hole in the vessel permanently. PHYSIOLOGY HEMOSTASIS 1 of 8 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited. 2. PLATELET PLUG FORMATION additional activated platelets causes them to When the vessel wall is injured, the platelets will be adhere to the original activated platelets. activated and release substances, such as that will ★ Therefore, at the site of a puncture in a blood vessel attract more platelets to go to the site of injury; release wall, the damaged vascular wall activates of ADP, thromboxane A2, resulting to platelet adherence successively increasing numbers of platelets that and aggregation attract more and more additional platelets, thus if the injured blood vessel is small, this will stop the forming a platelet plug. bleeding, as it can close minute or small ruptures in ○ This plug is loose at first but is usually small blood vessels, therefore, not needing the successful in blocking blood loss if the vascular subsequent stages opening is small. ○ Then, during the subsequent process of blood coagulation, fibrin threads form. Additional Notes (Guyton & Hall) ○ These threads attach tightly to the platelets, thus ★ If the cut in the blood vessel is very small—many constructing an unyielding plug. very small vascular holes develop throughout the body each day—the cut is often sealed by a platelet Importance of Platelet Mechanism for Closing plug rather than by a blood clot. To understand this Vascular Holes process, it is important that we first discuss the ★ The platelet-plugging mechanism is extremely nature of platelets themselves: important for closing minute ruptures in very small blood vessels that occur many thousands of times Mechanism of Platelet Plug Formation daily. Indeed, multiple small holes through the endothelial cells themselves are often closed by platelets actually fusing with the endothelial cells to form additional endothelial cell membranes. ★ Literally thousands of small hemorrhagic areas develop each day under the skin (petechiae, which appear as purple or red dots on the skin) and throughout the internal tissues of a person who has few blood platelets. This phenomenon does not occur in persons with normal numbers of platelets. Figure 37-1. Formation of a platelet plug in a severed blood vessel. Endothelial injury and exposure of the B. BLOOD COAGULATION vascular extracellular matrix facilitates platelet adhesions Formation of a blood clot is initiated by different factors: and activation, which changes their shape and causes release of adenosine diphosphate (ADP), thromboxane 1. Trauma to Blood A2 (TXA2), and platelet-activating factor (PAF). These platelet-secreted factors recruit additional platelets Activates intrinsic pathway (aggregation) to form a hemostatic plug. Von Willebrand factor (vWF) serves as an adhesion bridge between 2. Damage to Vessel Wall subendothelial collagen and the glycoprotein Ib (GpIb) platelet receptor Activates extrinsic pathway ★ Platelet repair of vascular openings is based on 3. Contact of Blood with Damages Vessel Wall several important functions of the platelet. When platelets come in contact with a damaged vascular Activates intrinsic pathway surface, especially with collagen fibers in the vascular wall, the platelets rapidly change their own Additional Notes (Guyton & Hall) characteristics drastically (Figure 37-1). ★ The clot begins to develop in 15 to 20 seconds if the ★ They begin to swell, they assume irregular forms with trauma to the vascular wall is severe and in 1 to 2 numerous irradiating pseudopods protruding from minutes if the trauma is minor. their surfaces, their contractile proteins contract ★ Activator substances from the traumatized vascular forcefully and cause the release of granules that wall, from platelets, and from blood proteins adhering contain multiple active factors, and they become to the traumatized vascular wall initiate the clotting sticky so that they adhere to collagen in the tissues process. and to a protein called von Willebrand factor(vWF), which leaks into the traumatized tissue from the plasma. ★ The platelet surface glycoproteins bind to vWF in the exposed matrix below the damaged endothelium. The platelets then secrete increased quantities of ADP and platelet-activating factor (PAF), and their enzymes form thromboxane A2. ○ Thromboxane is a vasoconstrictor and, along with ADP and PAF, acts on nearby platelets to activate them as well; the stickiness of these PHYSIOLOGY HEMOSTASIS 2 of 8 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited.  Prekallikrein Fletcher factor High-molecular-weigh Fitzgerald factor; t kininogen high-molecular-weight kininogen (HMWK) Platelets III. MECHANISM OF BLOOD COAGULATION A. BLOOD COAGULATION GENERAL MECHANISM Factor X is activated by Calcium and would soon from the prothrombin activator. Once you have your prothrombin activator, this will now Figure 37-2. Clotting process in a traumatized blood convert Prothrombin to Thrombin in the presence of vessel. platelet phospholipids and calcium. ★ Within 3 to 6 minutes after rupture of a vessel, the Once the Thrombin is formed, it will now be responsible entire opening or broken end of the vessel is filled for the polymerization of fibrinogen to fibrin with clot if the vessel opening is not too large. ★ After 20 to 60 minutes, the clot retracts, which closes the vessel still further. 1. FIBRINOGEN TO FIBRIN ★ Platelets also play an important role in this clot This fibrin fibers will form a weak blood clot and this will retraction, as discussed later. be affected upon by your fibrin stabilizing factor produced by the platelets crossing, cross-linking of the fibrin fibers producing a stable blood clot. CLOTTING FACTORS SYNONYM(S) Fibrinogen Factor I Additional Notes (Guyton & Hall) ★ Clotting takes place in three essential steps: Prothrombin Factor II ○ In response to rupture of the vessel or damage to the blood itself, a complex cascade of Tissue Factor Factor III; tissue chemical reactions occurs in the blood involving thromboplastin more than 12 blood coagulation factors. The net result is the formation of a complex of activated Calcium Factor IV substances collectively called prothrombin activator. Factor V Proaccelerin; labile factor; ○ The prothrombin activator catalyzes the Ac-globulin (Ac-G) conversion of prothrombin into thrombin. ○ The thrombin acts as an enzyme to convert Factor VII Serum prothrombin conversion fibrinogen into fibrin fibers that enmesh platelets, accelerator (SPCA); blood cells, and plasma to form the clot. proconvertin; stable factor ★ We will first discuss the mechanism whereby the blood clot is formed, beginning with conversion of Factor VIII Antihemophilic factor (AHF); prothrombin to thrombin, and then come back to the antihemophilic globulin (AHG); initiating stages in the clotting process whereby antihemophilic factor A prothrombin activator is formed CONVERSION OF PROTHROMBIN TO THROMBIN Factor IX Plasma thromboplastin ★ Prothrombin activator is formed as a result of rupture component (PTC); Christmas of a blood vessel or as a result of damage to special factor; antihemophilic factor B substances in the blood. ★ Prothrombin activator, in the presence of sufficient Factor X Stuart factor; Stuart-Prower amounts of ionic calcium (Ca2+), causes conversion factor of prothrombin to thrombin. ★ Thrombin causes polymerization of fibrinogen Factor XI Plasma thromboplastin molecules into fibrin fibers within another 10 to 15 antecedent (PTA); seconds. antihemophilic factor C CONVERSION OF FIBRINOGEN TO FIBRIN — Factor XII Hageman factor FORMATION OF THE CLOT ★ Because of its large molecular size, little fibrinogen Factor XIII Fibrin-stabilizing factor normally leaks from the blood vessels into the PHYSIOLOGY HEMOSTASIS 3 of 8 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited.  interstitial fluids, and because fibrinogen is one of the ★ 3. Effect of Xa to form prothrombin activator-role of essential factors in the coagulation process, factor V. interstitial fluids ordinarily do not coagulate. Yet, ○ The activated factor X combines immediately when the permeability of the capillaries becomes with tissue phospholipids that are part of tissue pathologically increased, fibrinogen does leak into factors or with additional phospholipids released the tissue fluids in sufficient quantities to allow from platelets, as well as with factor V, to form clotting of these fluids in much the same way that the complex called prothrombin activator. Within plasma and whole blood can clot. a few seconds, in the presence of Calt, ★ Thrombin is a protein enzyme with weak proteolytic prothrombin is split to form thrombin, and the capabilities. It acts on fibrinogen to remove four clotting process proceeds as already explained. low-molecular-weight peptides from each molecule of At first, the factor V in the prothrombin activator fibrinogen, forming one molecule of fibrin monomer complex is inactive, but once clotting begins and that has the automatic capability to polymerize with thrombin begins to form, the proteolytic action of other fibrin monomer molecules to form fibrin fibers. thrombin activates factor V. This activation then Therefore, many fibrin monomer molecules becomes an additional strong accelerator of polymerize within seconds into long fibrin fibers that prothrombin activation. Thus, in the final constitute the reticulum of the blood clot. prothrombin activator complex, activated factor X is the actual protease that causes splitting of prothrombin to form throm-bin. Activated factor V greatly accelerates this protease activity, and B. EXTRINSIC PATHWAY platelet phospholipids act as a vehicle that The extrinsic pathway is shorter compared to the further accelerates the process. Note especially intrinsic pathway. the positive feedback effect of thrombin, acting The shortness of the extrinsic pathway allows it to occur through factor V, to accelerate the entire process once it begins. rapidly and simultaneously. Additional Notes (Guyton & Hall) C. INTRINSIC PATHWAY The intrinsic pathway is longer compared to extrinsic pathway. Intrinsic pathway starts with blood trauma or contact of blood with collagen, which will activate your factor XII. 1. MECHANISM OF INTRINSIC PATHWAY Activated factor XII will activate your factor XI, and factor IX, and then factor X. So you have a longer pathway. ○ Once you have your activated factor X, this is the common pathway to both extrinsic and intrinsic pathways. Once you have your activated factor X plus calcium, you now have your Prothrombin activator. Prothrombin activator will convert prothrombin to thrombin in the presence of your platelet phospholipids and calcium. ★ The extrinsic pathway for initiating the formation of This will be acted upon by your fibrin-stabilizing factor, prothrombin activator begins with a traumatized vascular wall or traumatized extravascular tissues causing cross-linking of the fibrin fibers, forming the that come in contact with the blood. stable blood clot. ★ Release of tissue factor. ○ Traumatized tissue releases a complex of several factors called tissue factor or tissue thromboplastin. This factor is composed especially of phospholipids from the membranes of the tissue plus a lipoprotein complex that functions mainly as a proteolytic enzyme. ★ Activation of factor X—role of factor VII and tissue factor. ○ The lipoprotein complex of tissue factor further complexes with blood coagulation factor VII and, in the presence of calcium ions, acts enzymati-cally on factor X to form activated factor X (Xa). PHYSIOLOGY HEMOSTASIS 4 of 8 BATCH 2028 The use of SDCA Batch 2028 transes must be done discreetly. Distribution and publicizing of transes is strictly prohibited.  Additional Notes (Guyton & Hall) activated factor X combines with factor V and platelet or tissue phospholipids to form the complex called prothrombin activator. The prothrombin activator, in turn, initiates the cleavage of prothrombin to form thrombin within seconds, thereby setting into motion the final clotting process, as described earlier. D. FIBROUS ORGANIZATION OR FIBROLYSIS There can be fibrous organization or there can be lysis of the fibrin clot. So the blood clot will become organized and then the blood vessel wall may undergo repair. And once the vessel wall has been repaired, the blood clot will undergo lysis or will be dissolved The enzyme that is responsible for fibrolysis is the plasmin. ○ This is a digestive enzyme that will lyse or dissolve ★ The second mechanism for initiating formation of the blood clot. prothrombin activator, and therefore for initiating ○ It is derived from inactivated plasminogen - which is clotting, begins with trauma to the blood or exposure present in the blood - that has to be activated by a of the blood to collagen from a traumatized blood vessel wall. plasminogen activator produced by the endothelial ★ Blood trauma causes (1) activation of factor XII and cells. (2) release of platelet phospholipids. ○ In the hospital, plasminogen activators are given to ○ Trauma to the blood or exposure of the blood to patients suffering from stroke or myocardial vascular wall collagen alters two important infarction to dissolve blood clots. clotting factors in the blood: factor XII and the platelets. When factor XII is disturbed, such as by coming into contact with collagen or with a wettable surface such as glass, it takes on a Additional Notes (Guyton & Hall) new molecular configuration that converts it into ★ The plasma proteins contain a euglobulin called a proteolytic enzyme called activated factor XII. plasminogen (profibrinolysin) that when activated, Simultaneously, the blood trauma also damages becomes a substance called plasmin (fibrinolysin). the platelets because of adherence to collagen Plasmin is a proteolytic enzyme that resembles or to a wettable surface (or by damage in other trypsin, the most important proteolytic digestive ways); this releases platelet phospholipids that enzyme of pancreatic secretion. contain the lipoprotein called platelet factor 3, ★ Plasmin digests fibrin fibers and some other protein which also plays a role in subsequent clotting coagulants, such as fibrinogen, factor V, factor VIII, reactions. pro-thrombin, and factor XII. Therefore, whenever ★ Activation of factor XI. plasmin is formed, it can cause lysis of a clot by ○ The activated factor XII also acts enzymatically destroying many of the clotting factors, thereby on factor XI to activate this fac-tor, which is the sometimes even causing hypocoagulability of the second step in the intrinsic pathway. This blood. reaction also requires high-molecular-weight kininogen and is accelerated by prekallikrein. ★ Activation of factor IX by activated factor XI. IV. CLOTTING FACTORS ○ The activated factor XI then acts enzymatically Platelets are important for blood clotting, but the most on factor IX to activate this factor as well. important ones are the clotting factors.. ★ Activation of factor X-role of factor VIII. Factor VII is important for the activation of factor 10 for ○ The activated factor IX, acting in concert with the intrinsic pathway. activated factor VIII and the platelet phospholipids and factor III from the traumatized Some clotting factors are produced in the liver and are platelets, activates factor X. It is clear that when vitamin K dependent clotting factors such as: either factor VIII or platelets are in short supply, ○ Fibrinogen this step is deficient. Factor VIII is the factor that