1 Cardiovascular systemCirculatory system Cardiovascular system Heart Blood vessels Lymphatic system Lymphoid tissue Spleen Lymph nodes Tonsils Thymus vessels Lymphatic

2 General functions of blood – transportation, regulation, protectionHEART & CIRCULATION Homeostatic Functions Transportation: Transports substances to and from capillaries for exchange with tissue fluid a. Respiratory Gases. RBC (erythrocytes) transport O2 to the cells and CO2 away to capillaries b. Nutritive materials. Food digested mechanically & chemically by the GIT. c. Excretory Wastes. Urea, excess water and ions, and other unneeded molecules are carried by blood to kidneys and excreted in the urine. 2. Regulation of hormones & temperature. Buffers body pH, Maintain osmotic pressure 3. Protection. Clotting: Clots prevent blood/fluid loss & Immunity (leukocytes protect against pathogens invasion). Regulation : temperature (blood diversion). Heat is one of byproducts of cell respiration. (ATP production). Blood is warmed by flowing through active organs such as liver and muscles. This heat is transported to cooler parts of the body as blood circulates. General functions of blood – transportation, regulation, protection

3 Characteristics of blood:Amount – 4 to 6 liters (8% of body weight). Color – arterial blood: bright red venous blood: dull red Viscosity – means thickness or resistance to flow; Viscosity is increased by presence of cells and proteins. pH – slightly alkaline. Question: What is the normal pH range of blood? The normal pH range of blood is 7.35 to 7.45. Color – arterial blood: bright red because of high content if O2/ venous blood: dull red . importance: assessment of the source of bleeding pH – slightly alkaline. arterial blood: venous blood: more basic because of high content of CO2 Viscosity : blood is three to 5 times thicker than water.. importance:The thickness contributes to blood pressure

4 Arterial blood: is blood leaving heart (It is bright red except of that going to lungs).Venous blood: is blood returning to the heart (looks dark except for venous blood returning from lungs). Arterial blood: is blood leaving heart (except of that going to lungs). It is bright red due to high O2-Hb concentration. Venous blood: is blood returning to the heart (except for venous blood returning from lungs) . It contains less O2therefore; looks dark.

5 BLOOD COMPOSITION 1-Formed elementsThe blood of mammals has two components: plasma and formed elements (cells and platelets). 1-Formed elements Erythrocytes ( transport O2 & CO2); leukocytes, immune defense; Thrombocytes/platelets, blood clotting). 2-Plasma made of water; plasma proteins; and electrolytes.

6 PLASMA Straw-colored liquid consisting of: (1) Water (91%)(2) Plasma proteins (7-8%) and (3) Ions mainly Na & other materials like nutrients, wastes, salts (< 1%). In addition, plasma contains other organic molecules such as metabolites, hormones, waste products, Antibodies, & other proteins. Salts and proteins buffer the blood: a. They effectively keep the blood pH near 7.4 b. They maintain the blood osmotic pressure which pulls tissue fluid into capillaries. The water of plasma is a solvent. It transports: 1-Plasma proteins 2-ions 3-Nutrients absorbed by GI tract, such as glucose , amino acids and minerals. 4- waste products such as urea and creatinine to kidneys to be execrated by urine. 5-hormones from endocrine glands to the target organ. 6- anti bodies. 7-Gases They maintain the blood osmotic pressure which pulls tissue fluid into capillaries. This is important to maintain normal blood volume and pressure.

7 Plasma Proteins (7-8g/dL of plasma). There are three main types that are produced by liver: Albumins the smallest in size (MW= 70 kd); they function in: A-transports bilirubin, a breakdown product of hemoglobin. B- maintains the blood osmotic pressure so water enters capillaries. 2. Globulins 3 subtypes: α- and β-globulins; they are lipoproteins that transport cholesterol lipids & fat-soluble molecules. γ-globulins: are antibodies produced by lymphocytes. They function in immunity. 3. Fibrinogens 4% of plasma proteins. They are important clotting factors that are converted to fibrin threads. Serum: is plasma that lacks fibrinogen. Alpha and beta globulins – are carriers. Gamma globulins –:are antibodies that initiate the destruction of pathogens.

8 Plasma Volume. If the body loses water:Dehydration plasma becomes concentrated   osmolarity. This is detected by osmoreceptors in the hypothalamus  thirst   ADH release (from posterior pituitary)  ADH release   water retention by kidneys  thirst  increase water intake Both effects   blood Pressure and blood volume.

9 Formed Elements 3 kinds: 1. red blood cells (RBCs),2. white blood cells (WBCs), 3. platelets.

10 The process takes place in: HEMATOPOIESIS. Blood cells are constantly formed by a process called hematopoiesis/hemopoiesis. Hematopoietic stem cells migrate to fetus liver. They then migrate to bone marrow, and shortly after birth the liver ceases to be a source of blood cell production. 500 billion cell per day. The process takes place in: 1-Myeloid tissue (red bone marrow ) in long bones, ribs, sternum, pelvis, vertebrae, and skull produces all blood cells. 2-Lymphoid tissue in lymph nodes, tonsils, spleen, &thymus produces lymphocytes. As stem cells differentiate they develop receptors which determine to which line they are going to commit. (hematopoiesis occurs in fetus liver).

11 Leuko/Thrombo—cytosis means elevated No. HEMATOPOIESIS. Erythropoiesis (RBC formation), is stimulated by hormone called erythropoietin produced by kidneys Leukopoiesis (WBC formation) is stimulated by chemicals called cytokines –Interleukins (secreted by WBC). Thrombopoiesis (platelets formation): Thrombopoietin (cytokine) stimulates platelets formation by stimulating the proliferation and the maturation of megakaryocytes. Leuko/Thrombo—cytosis means elevated No. Leuko/Thrombo—penia means low No. Cytokines (Greek cyto-, cell; and -kinos, movement) are small signaling molecules used for cell signaling. Cytokines can be classified as proteins, peptides, or glycoproteins; the term "cytokine" encompasses a large and diverse family of regulators produced throughout the body by cells of diverse embryological origin.[1] The term "cytokine" has been used to refer to the immunomodulating agents, such as interleukins and interferons. The gene for erythropoietin has been commercially cloned, for treating anemia that results from kidney disease. A recombinant thrombopoietin has been used to treat the thrombocytopenia (low platelet count) that occurs as a result of bone marrow depletion in patients undergoing chemotherapy for cancer.

12 Blood cell formation in red bone marrowMultipotent stem cells give rise to two specialized stem cells. The myeloid stem cell gives rise to still other cells, which become red blood cells, platelets, and all the white blood cells except lymphocytes. The lymphoid stem cell gives rise to lymphoblasts, which become lymphocytes. 12

13 Red Blood Cells The most numerous cells.Red blood cells (erythrocytes) are small biconcave disks (to increase surface area for gas diffusion). When mature, RBCs lack a nucleus and mitochondria (anaerobic respiration). There are million RBCs per mm3 of whole blood in males (females = ). Another way to measure RBC is Hematocrit ; a test to determine the percentage of RBC. Stimulus for production: hypoxiakidneys: erythropoietin.

14 Hematocrit (PCV=packed cell volume) =Percent of RBC volume/Total blood volume in centrifuged blood sample Hematocrit reading is 45% RBC, and 54% of the plasma. The buffy coat consists of WBC & platelets (1%). 36%-46% woman 41%-53% men Both Hematocrit and RBC count are part of CBC count

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16 Function Each RBC contains about 300 million hemoglobin molecules.Hemoglobin contains four globin protein chains, each with an iron-containing heme group (red pigmented molecule that contains iron). The iron atom of a heme group loosely binds with an O2 molecule; thus, blood carries oxygen.

17 The determination of hemoglobin level is also part of CBC.The normal range is 12 to 18 gm per 100 ml of blood. Hemoglobin also carries about 10% of CO2.

18 1-Iron deficiency anemia. Due to reduction in dietary iron Anemia is either a lack of enough RBC (low RBC count ) or insufficient hemoglobin; an individual suffers from a tired, run-down feeling. Anemia types: 1-Iron deficiency anemia. Due to reduction in dietary iron 2-Pernicious anemia due to Vit. B12 or intrinsic factor deficiency, caused by atrophy of stomach glandular mucosa which secretes a protein called intrinsic factor. Intrinsic factor is a chemical that combines with Vit. B12 and enhances its absorption by small intestine. 3-Aplastic anemia due to bone marrow destruction caused by radiation or chemicals i.e benzene and arsenic. Polycythemia means high RBC count. Nutrients needed for production: Protein and iron – Folic acid and vitamin B12 – B12 is called the extrinsic factor. The intrinsic factor is produced by the parietal cells of the stomach lining – Pernicious anemia is caused by a lack of intrinsic factor, which is required to absorb vitamin B12 from food. A lack of intrinsic factor may arise from an autoimmune condition targeting the parietal cells (atrophic gastritis) that produce intrinsic factor or against intrinsic factor itself. These lead to poor absorption of vitamin B12.

19 Sickle Cell Anemia (SCA)Prehepatic jaundice means the problem is before. Hemolysis of RBC is taking place at a more rapid rate. As in Sickle Cell Anemia . Hemolytic anemia” bilirubin is formed at a faster rate than the liver can execrete. Low Oxygen

20 Stimulus for production: hypoxia kidneys: erythropoietin. RBCs are manufactured at a rate of 2.5 million cell per second in the red bone marrow (Myloid tissue) of the skull, ribs, vertebrae, and the ends of long bones (200 billion per day). This process needs iron, vitamin B12, and folic acid. Stimulus for production: hypoxia kidneys: erythropoietin. The growth factor erythropoietin is secreted by the kidneys acts on stem cells and stimulates their mitosis; as a drug it helps people with anemia. Before being released from bone marrow, the reticulocyte lose their nucleus and synthesize hemoglobin. Red blood cells have a life span of about 120 days; then they are destroyed by phagocytic cells in liver, spleen, & red bone marrow. iron is recovered and returned to the bone marrow where it is reused for synthesis of new hemoglobin. If not needed immediately iron is stored in liver. Folic acid (also known as folate, vitamin M, vitamin B9 The human body needs folate to synthesize DNA, repair DNA, and methylate DNA as well as to act as a cofactor in certain biological reactions.[7] It is especially important in aiding rapid cell division and growth, such as in infancy and pregnancy. Children and adults both require folic acid to produce healthy red blood cells and prevent anemia. Megaloblastic anemia, the most common cause of macrocytic anemia, is due to a deficiency of either vitamin B12, folic acid, or both.

21 RBCs are destroyed In macrophages of liver or spleen:Globin portion is broken down into amino acids & used for synthesis of new proteins. The Heme portion cannot be recycled and is a waste product. it undergoes chemical degradation. Heme is converted to bilirubin by macrophages . The liver removes bilirubin from circulation and excretes it into bile. Bile is secreted by the liver into the duodenum, and passes through small intestine and colon then eliminated in feces. If bilirubin is not excreted properly, perhaps due to liver disease , Jaundice develops. Jaundice : excessive accumulation of bilirubin in the blood. Jaundice is a sign of liver diseases such as cirrhosis or hepatitis. Hepatic Jaundice. Heme is converted to bilirubin by macrophages. bilirubin is a bile pigments; it colors the feces. The heme portions undergo chemical degradation: heme split into iron (Fe+3) and biliverdin (green pigment) converted to bilirubin are excreted by the liver as bile pigments; it colors the feces. If bilirubin is not excreted properly, perhaps due to liver disease , Jaundice develops. Jaundice : excessive accumulation of bilirubin in the blood. Jaundice is a sign of liver diseases such as cirrhosis or hepatitis. Hepatic Jaundice.

22 Iron is recovered and returned to the bone marrowIron(Fe+3) transported in blood attached to transferrin protein stored in liver, muscle or spleen attached to ferritin or hemosiderin protein. in bone marrow being used for hemoglobin synthesis When the RBCs are destroyed, the hemoglobin is released; the iron is recovered and returned to the bone marrow where it is reused.

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24 WBC

25 Their production is stimulated by cytokines. White Blood Cells White blood cells (leukocytes) differ from RBCs in being larger and in having a nucleus and mitochondria leukocytes/µl of blood. Their production is stimulated by cytokines. They have amoeboid ability, which enable them to squeeze through pores in capillary walls and move to sites of infection called diapedesis, whereas RBC remain confined. WBC carry out functions in blood, tissue fluid or lymphoid tissue. e. All WBC have general function which is to protect the body from infectious diseases and to provide immunity Note: A newly discovered stem cell growth factor (SGF) increases the production of all WBCs, which helps patients with low immunity. WBCs lack hemoglobin and appear translucent without staining.

26 2. Agranular life span 12hr to 3 days.There are 2 groups: Granular leukocytes also called polymorphonucleocytes contain granules in their cytoplasm and a lobed nucleus. life span days 2. Agranular life span 12hr to 3 days. There are 2 types produced in bone marrow and some in lymphoplastic tissue:

27 Granulocytes Neutrophils most abundant (50-70% of WBC), have faint granules that stain slightly pink& 2-5 lobe nuclei. Spherical cells that readily squeeze through capillary walls. They are amoeboid phagocytize of pathogens (first line-defense). A differential WBC count (part of CBC) is the percentage of each type of WBC.

28 Granulocytes 2) Eosinophils/acidophils 2-4% of WBC; granules are basic so they take up the red dye eosin and appear pinkish; have 2 lobe nucleus. Detoxify foreign proteins and phagocytize anything labeled with antibody. Protect from parasitic worms. Increase in number during allergic reaction. Following activation by an immune stimulus, eosinophils degranulate to release an array of proteins that are capable of inducing tissue damage and dysfunction.

29 Granulocytes 3) Basophils dark blue; <1% of WBC; Have acidic granules that take up a basic dye, staining them deep blue 2 lobe nucleus. Basophils contain granules of heprin and histamine. histamine : released as part of inflammation process, works as vasodilator promotes blood flow to tissues and make capillaries more permeable. Basophils contain anticoagulant heparin, which prevents abnormal clotting within blood vessels. Basophils contain granules of heprin and histamine. histamine : Allergy; secrete the vasodilator that promotes blood flow to tissues.

30 B) Agranulocytes/Mononucleocytes: no granules; have a circular or indented nucleus. two types:1-lymphocytes (20-30% WBC), smallest of all WBC (6-9 μm); for specific immunity. 2-Monocytes largest of leukocytes (14-20 μm); kidney-shaped nuclei; 3-8% of WBC; phagocytic (second line). lymphocytes Monocytes

31 Monocytes Monocytes are amoeboid phagocytic (second line) and able to enter tissues where they transform into macrophages. Neutrophils are more abundant phagocytes, but monocytes are more efficient phagocytes because they differentiate into Macrophages which phagocytized dead or damaged tissue making repair possible. Macrophages release white blood cell growth factors that increase the number of leukocytes.

32 2-lymphocytes (20-30% WBC), smallest of all WBC (6-9 μm); for specific immunity.Lymphocytes play a key role in fighting infection and include two major types. a) T cells are lymphocytes that directly attack virus-infected cells. b) B cells become plasma cell that produce one type of antibody specific for one type of antigen. 5) An antigen is any substance stimulating production of antibodies; antigen is foreign to the body. 6) Antibodies combine with antigens to promote their being phagocytized by a macrophage. 7) A person is actively immune when many B cells produce a specific antibody for an infection. Less numerous third kind is Natural killer cells: destroy foreign cells by chemically rupturing their membrane.

33 Leukemia: is malignancy of blood forming tissueLeukocytosis : is an indication of infections. A large number of immature leukocytes in blood sample is diagnostic of leukemia Leukopenia: low WBC count may result from poor nutrition or from radiation. Patient is susceptible for infection. Leukemia: is malignancy of blood forming tissue Leukopenia: in early stages of diseases such as tuberculosis . Leukemia: immature WBC cannot perform their function when a person is susceptible to infection. Anemia from low RBC/ hemorrhage from low platelets.

34 3. Platelets / ThrombocytesFragments of large bone marrow cells called megakaryocytes. Platelet life span 5-9 days; count 150, ,000 / µl; they are destroyed by spleen & liver; Thrombocytosis: due to the liver secreting more thrombopoietin which occurs under various medical conditions such as inflammation, acute blood loss, and cancer… Thrombopenia: occurs as a result of bone marrow depletion in patients undergoing chemotherapy for cancer

35 Function in: 1- Chemical clotting.2-Vasospasm: platelets in area of rupture in large vessels release serotonin (a chemical which cause vasoconstriction) for blood vessels repair. 3-Platelet plugs – capillaries. When capillaries rupture the damage is too small to initiate the clot formation. The rough surface causes the platelet to change shape becoming spiky and sticky. They stick to the edges of the brake and to each other. Vasospasm: contraction of smooth muscle present in the wall of arty or vein. This is called myogenic response. The diameter is made smaller. The smaller opening may then be blocked by blood clot. If the vessel did not constrict first the clot will be washed by the force of blood pressure. Vascular spasm – large vessels. Platelet plugs – capillaries. 3-secrete growth factors that works in an autocrine fashion to enhance blood vessels integrity. These regulators might be involved in development of atherosclerosis. Would Platelet plugs be effective for breaks in large vessels? No too small they will be washed away. Would Vasospasm be effective in capillaries? No they do not have smooth muscles.

36 Disturbances of HemostasisBLOOD CLOTTING Breakage of the endothelial lining exposes the subendothelial collagen to the blood, initiating 3 overlapping mechanisms: (1) vasoconstriction, (2) formation of a platelet plug (Plt. Adhesion + Plt. Aggregation) (3) fibrin production. Abnormal clotting is prevented by: 1-Normal endothelium : has smooth edges that repels the platelets and cloting factorts. If the lining become rough as in atherosclerosis clotting takes place. 2-Heparin: anticoagulant 3-Antithrombin: inactivate excess thrombin Opened Injured Blood Vessel Formation of Physiological Thrombus

37 BLOOD CLOTTING Functions of Platelets. In intact vessel, endothelial lining produces prostacyclin (a type of prostaglandin PGI2) and nitric oxide NO that 1-act as vasodilators 2-repels platelets from each other & from the endothelium. Vessel damage exposes subendothelial tissue to the blood. Platelets proteins bind to exposed negative collagen. von Willebrand factor (protein secreted by endothelial cells) binds collagen and Platelets thereby hindering blood flow from pulling Platelets away. Platelets contain secretroy granules, when Platelets stick to collagen they degranulate as secretroy granules release their contents: ADP, serotonin, & thromboxane A2 (a type of prostaglandin ). Serotonin, & thromboxane A2 stimulate vasoconstriction to decrease blood flow to the injured vessel. ADP, & thromboxane A2 recruit new platelets which result in plug formation. Aspirin inhibits cyclooxygenase which is the enzyme that catalaze the production of thromboxane A2 by Platelets ADP, & thromboxane A2 recruit new Platelets. These release more ADP, & thromboxane thus recruit new Platelets which result in plug formation. (serotonin, & thromboxane A2 are powerful vasoconstrictors)

38 ADP, & thromboxane A2 recruit new PlateletsADP, & thromboxane A2 recruit new Platelets. The reaction is called platelet release reaction.

39 formation of platelet plug (primary hemostasis)

40 Clotting Factors: Formation of FibrinWhen a blood vessel is damaged, The conversion of fibrinogen into fibrin occurs via either of 2 pathways: (1) intrinsic pathway, where blood left in a test tube will clot without the addition of any external chemicals. (2) extrinsic pathway where damaged tissue release chemicals that initiates a “shortcut” to the formation of fibrin. Because chemicals are not part of blood the pathway is called extrinsic intrinsic & extrinsic pathway finally merge to form a Common Pathway leading to the formation of a fibrin clot ! intrinsic pathway Occurs in damaged blood vessels when collagen is exposed to plasma 40 40

41 Clotting Cascade Participation of 12 different clotting factors (plasma glycoproteins) Factors are designated by a roman numeral Names of some coagulation factors I (fibrinogen) II (prothrombin) VIII (antihemophilic factor) IX (Christmas factor) X (Stuart-Prower factor) XII (Hageman factor)

42 a. When a blood vessel is damaged, platelets clump at the site of the puncture and partially seal the leak. b. The platelets and damaged tissue cells release a clotting factor called prothrombin activator. c. With calcium ions, prothrombin activator catalyzes a reaction converting prothrombin to thrombin. d. Thrombin acts as an enzyme to sever two amino acid chains from each fibrinogen molecule ( soluble precursor of fibrin) in plasma.

43 e. These activated fragments join end-to-end forming long threads of fibrin.f. Fibrin is insoluble protein that threads wind around the platelet plug and provide a framework for a clot. g. RBCs are trapped within the fibrin threads, making the clot appear red. h. When blood vessel repair is initiated, plasmin destroys the fibrin network and restores plasma fluidity. i. When clotting occurs in a test tube, a fluid serum collects above a clot; it has the same composition as plasma except for fibrinogen. In arteries because the blood run fast, RBC do not get trapped therefore its color is gray.

44 d. At least 12 clotting factors in the blood participate in blood clotting. Factors are designated by a roman numeral e. Hemophilia is an inherited disorder where the liver is unable to produce one of the clotting factors. f. In hemophilia, minor bumps can cause internal bleeding; bleeding into the brain causes death. g. Vitamin K is necessary to produce prothrombin; deficiency of vitamin K causes hemorrhagic disorders. Vitamin K is necessary to produce prothrombin and factors 7/9/10. Vitamin K is produced by bacteria in colon. Then it is absorbed and stored in liver.

45 CLOT DISSOLUTION. When blood vessel is repaired, activated factor XII (Hageman factor) promotes kallikrein (plasma protein) formation catalyzes the conversionof inactive plasminogen into active plasmin (enzyme digests fibrin) clot dissolution. Clot retraction – Fibrinolysis – Questions: What is the term for a stationary clot? A moving clot? A stationary clot is a thrombus. A moving clot is an embolus.

46 Hemophilia B: deficiency of factor 9, an X-linked disorders .CLOTTING DISORDERS. Von Willebrand disease (the most common). VWF binds collagen and Platelets Hemophilia A: deficiency of factor 8, an X-linked disorders that affects males much more than females. Hemophilia B: deficiency of factor 9, an X-linked disorders . Hemophilia C: deficiency of factor 11. No factor 8: Prothrombin is not formed. Hemophilia : internal bleeding especially in joints.

47 Blood Type Reactions 1. ABO SystemAntigens: certain molecules ( protein-oligosaccharides) present on the surface of all the cells of the body that can be recognized as foreign by the immune system of another person. The presence or absence of type A or/and B antigens on red blood cells determine a person’s blood type. b. If the person has type A blood, the A antigen is on the red blood cells; if the person is type B, the B antigen is on the red blood cells. The genes A and B are shown as IA and IB while the gene O is shown as I thus type A person is either IA IA or IA i c. In the ABO system, there are four blood types: A, B, AB, O Individuals have antibodies to blood type antigens not present on their blood cells; these are called anti-A and anti-B 2) RBCs with a particular antigen agglutinate then undergo hemolysis when exposed to corresponding antibodies, e.g., type A RBCs will agglutinate in the presence of anti-A antibody (as would be found in the blood of a type B individual). 3) Agglutination is the clumping of red blood cells due to a reaction between antigens on the red blood cells.

48 c) Recipients with type A blood cannot receive B or AB. 4) To receive blood, the recipient’s plasma must not have an antibody that causes donor cells to agglutinate. a) Recipients with type AB blood can receive any type blood; they are the universal recipient. b) Recipients with type O blood cannot receive A, B, or AB; but they are a universal donor. c) Recipients with type A blood cannot receive B or AB. d) Recipients with type B blood cannot receive A or AB. Transfusion error can lead to hemolysis (rupture of RBC which may damage the kidney and other organs O is Universal donor and AB is universal recipients This concept is used in emergencies in small volumes since donor plasma could agglutinate recipient’s RBC if the transfusion volumes were too large hemolysis release free hemoglobin which clog the capillaries of kidneys and lead to renal damage and renal failure. Type O RBCs have neither A or B antigens and will not react with what ever antibodies the recipients may have. If only one unit ( 1 pint) is given ) the anti A and anti B present in type O blood will dilute and in the recipients blood plasma and will not have harmful effects on recipients RBCs

49 ABO System RBCs have glycoproteins (antigens) on their surfaces. The genes for A or B antigens are dominant. ABO Type Genotype Ag Anti-sera A IAIA or IAi Anti-B B IBIB or IBi Anti-A AB IAIB ------ O ii Anti-A+B

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51 Blood Transfusions

52 Rhesus Blood Group 1. Rh factor is an important antigen in human blood types. The Rh antigen is termed D and is indicated as RhoD : 85% of population Rh+; 15% are Rh-. 2. Rh positive (Rh+) has the Rh factor on red blood cells; Rh negative (Rh-) lacks the Rh antigen on RBCs It is consisted of C, D and E antigens C and E are antigenically weak and clinically ignored. The D antigen is commonly called Rh factor and is of clinical importance Antigenic: having the properties of an antigen Having the properties of an antigen (allergen). Synonym(s): allergenic, immunogenic antigenic competitionthe immune response to an antigen may be reduced if an unrelated antigen is administered simultaneously or shortly before. These may be between different molecules (intermolecular) or different determinants on the same molecule (intramolecular). antigenic driftpoint mutations in genes resulting in antigenic change. See also orthomyxoviridae. antigenic mimicrysimilarities between sequences found in microbial proteins and host proteins which may result in cross-reacting immune responses and autoimmune disease. antigenic shiftgenetic reassortment between two subtypes of a viral species resulting in a new subtype with completely different antigenicity.

53 Rh System 3. Rh-negative individuals do not have antibodies to Rh factor but make them if exposed to Rh+ blood. Rh positive is a genetically dominant trait; an Rh negative mother and an Rh positive father pose a Rh conflict. . Rh-negative individuals do not have antibodies to Rh factor but make them if exposed to Rh+ blood just as they would do if exposed to bacteria or viruses.

54 The mother immune system may produce antibodies against Rh antigenRh factor is particularly important if Rh negative mother is pregnant with Rh positive child Erythroblastosis fetalis Hemolytic disease of the newborn is possible if the mother is Rh negative and the father is Rh positive. Normally during pregnancy the maternal blood and the fetal blood are kept separate across the plasenta. At time of birth variable degrees of exposure may occur. The child’s Rh positive RBCs can leak across the placenta into the mother’s circulatory system when the placenta breaks down. The mother immune system may produce antibodies against Rh antigen Anti-Rh antibodies pass across the placenta and destroy the RBCs of the Rh positive child. Baby is born with hemolytic disease of newborn called Erythroblastosis fetalis 1) The injection includes anti-Rh antibodies that attack any fetal RBCs that have entered the mother circulation and inactivate their Rh antigens before they trigger the mother’s immune system. (passive immunity)

56 Hemolytic Disease of the NewbornErythroblastosis fetalis in severe cases is lethal. In less severe cases baby will be born anemic and jaundiced from loss of RBCs

57 Capillary Exchange Arteries and venules are continuous with each other through Capillaries. All Exchanges of fluid nutrients and wastes between blood and tissues occur across the walls of Capillaries.

58 B. Capillary Exchange 1. Two forces control the movement of fluid through the capillary walls. a. Osmotic pressure tends to cause water to move from tissue fluid to the blood. b. Blood pressure (hydrostatic pressure) tends to cause water to move from the blood to tissues. c. At the arterial end of a capillary, blood pressure is higher than osmotic pressure: water exits and moves into tissues. Fluid derived from Plasma is called tissue fluid or ISF d. Along the capillary, O2 and nutrients diffuse out into the tissue fluid, while CO2 and other metabolic wastes diffuse into the capillaries from the tissue fluid.

59 2. Midway along a capillary, there is no net movement of water.3. The tissue fluid is intercellular fluid that surrounds the cells; the circulatory system exchanges materials with this fluid. 4. The exchange between the blood and tissue fluid occurs by diffusion through the one-cell-thick capillary walls. a. At the venule end, osmotic pressure is higher than blood pressure and water moves back into the blood. b. Almost the same amount of fluid that left the capillary returns to it; there is always some excess tissue fluid collected by the lymphatic capillaries. 5. The tissue fluid within lymphatic vessels is called lymph. 6. Lymph nodes positioned along the way , cleanse the Lymph prior to its return to venous blood 7-returns to the systemic venous blood when lymphatic vessels enter the subclavian veins in the shoulder.

60 The movement of fluid between blood capillaries and the interstitial fluid 

61 Capillary Bed 8. Not all capillary beds are open at the same time; precapillary sphincters shunt blood along various pathways. 9. Through capillary dilation and constriction, blood also distributes heat to body parts and conserves heat when cold.

62 (a) Sphincters relaxedPrecapillary sphincters Thoroughfare channel Capillaries Venule Arteriole (a) Sphincters relaxed Figure Blood flow in capillary beds. Arteriole Venule (b) Sphincters contracted

63 Base Balance of the Blood.Blood plasma pH is maintained within a narrow range. The lungs regulate CO2 concentration of the blood; the kidneys regulate HCO3- concentration. The blood plasma within arteries normally has a pH between (aver 7.40). Thus, arterial blood has a H+ concentration of about molar. Some of these hydrogen ions are derived from carbonic acid, which is formed in the blood plasma from carbon dioxide and which can ionize, as indicated in these equations: CO2 + H2O  H2CO3  H2CO3  H+ + HCO3¯

64 A fall in blood pH below 7. 35 is called acidosis, & a blood pH of 7A fall in blood pH below 7.35 is called acidosis, & a blood pH of 7.2 represents serious acidosis. Similarly, a rise in blood pH above 7.45 is called alkalosis. Both of these conditions are categorized into respiratory and metabolic components of acid-base balance.

65 Terms Used to Describe Acid-Base BalanceDefinition Term Increased CO2 retention (due to hypoventilation), cause H2CO3 accumulation   blood pH. Acidosis, respiratory Increased production of "nonvolatile" acids (lactic acid, fatty acids, and ketone bodies), or loss of blood HCO3¯ (diarrhea)   blood pH. Acidosis, metabolic  blood pH due to loss of CO2 and H2CO3 (hyperventilation) Alkalosis, respiratory  blood pH due to loss of nonvolatile acids (excessive vomiting) or excessive accumulation of bicarbonate base. Alkalosis, metabolic Metabolic acidosis/alkalosis are compensated for by changes in blood H2CO3 levels (changes in ventilation). Respiratory acidosis or alkalosis are partially compensated for by increased retention/excretion of bicarbonate in the urine. Compensated acidosis or alkalosis 65 65

66 غير مطلوب Recycling of Hemoglobin Componentsغير مطلوب Recycling of Hemoglobin Components Biliverdin (green) converted to bilirubin (yellow) bilirubin secreted by liver into bile bilirubin converted to urobilinogen  stercobilin (brown pigment in feces) by bacteria of large intestine. bilirubin reabsorbed from intestines into blood is converted to a yellow pigment, urobilin and excreted in urine. 66 66