Blood

1. ivyanatomy.com Blood Chapter 14, Section 1 of 2. Functions of Blood: Transports gasses, (O2 and CO2) Transport nutrients, wastes, electrolytes, and hormones Distributes heat throughout the body Contains buffers Immunity

2. Introduction • Characteristics of Blood: • Blood is a connective tissue • Cells are called= formed elements • Red Blood Cells • White Blood Cells • Platelets • Liquid Matrix = plasma • Centrifuged Blood: • Plasma, 55% • Buffy Coat, <1% • Proteins and WBCs • Red Blood Cells, 45% • Hematocrit = packed RBCs

3. Hematopoiesis • Hematopoiesisis the formation of new blood cells. • Occurs within red bone marrow • Blood stem cells are called, hemocytoblasts ( or hematopoietic stem cells) • Hemocytoblasts can give rise to additional blood stem cells • Can differentiate into any of the blood cells • The fate of hemocytoblast depends on hematopoietic growth factors Example: Erythropoietin (EPO = growth factor) Hemocytoblast erythroblast reticulocyte erythrocyte (RBC)

4. Erythrocytes: red blood cells (corpuscles) • Characteristics of erythrocytes • Biconcave cells • anucleated (nucleus dislodged during formation) • Average diameter = 7.5µm • 1/3 volume is hemoglobin • Oxyhemoglobin – bright red • Deoxyhemoglobin – dark brick red Red Blood Cell Counts RBC counts is the number of RBCs in a cubic millimeter or microliter of blood Male 4.6 - 6.2 million cells per µL Female 4.2 - 5.4 million cells per µL Child 4.5 - 5.1 million cells per µL

5. Erythropoiesis: RBC production • Sites of Erythropoiesis • Adult – Erythropoiesis occurs primarily in red bone marrow, which is found within • flat bones (sternum, pelvis, ribs, skull) • Proximal end of long bones (femur, humerus) • Child • Erythropoiesis occurs within the yolk sac, liver, and spleen Example of erythropoiesi: Erythropoietin (EPO) In red bone marrow circulation

6. Erythrocytes: feedback loop • Erythopoiesisis stimulated by low blood oxygen. • Decreased blood O2 may cause the • kidneys and the liver (to a lesser extent) • to release erythropoietin (EPO) • EPO stimulates RBC production • This is a negative feedback • mechanism • Within a few days many new blood • cells appear in the circulating blood Dietary Factors of Erythropoiesis • Iron – required for hemoglobin production • Vitamin B12 & Folic Acid – required for DNA synthesis (and thus, cell production)

7. Lifespan of Red Blood Cells • Red blood cells survive about 120 days in circulation. • With age, RBCs become fragile and easily rupture. • Old RBCs are removed by the liver and spleen • Hemoglobin is liberated and recycled in new RBCs

8. Hemoglobin breakdown + Hemoglobin Heme Globin + • Amino acids • recycled by body • Iron (Fe2+) • Reused by liver in synthesis of new hemoglobin Biliverdin • Bilirubin • Excreted as bile pigment Jaundice: yellowish staining of skin caused by the accumulation of bile pigments. Jaundice may indicate increased RBC destruction, destruction of liver tissue, or blockage of the biliary tract.

9. Red Blood Cell Disorders • Erythrocytosis(polycythemia) is an excess number of RBCs in the blood. • Causes include • Genetic mutations • Poor blood oxygen levels or delivery • tumor Polycythemia. The surplus of RBCs causes the blood to be more viscous and it slows its flow through the body. This increases the likelihood of clot formation. • Anemia • Low oxygen capacity of blood, several types • Iron deficiency – body cannot form hemoglobin • Hemolytic – excess RBC destruction • Sickle cell – sickle-shaped RBCs • Aplastic – inability to produce RBCs Sickle cell anemia. RBCs take on a thin sickle shape when deoxygenated. The sickle cells sludge in capillaries, further reducing blood flow and oxygen levels

10. Leukocytes (White Blood Cells) • Functions of WBCs • Protect against infection • Remove worn out cells & debris • immunity Colony Stimulating Factors and Interleukins are growth factors that promote the development of white blood cells. There are five types of white blood cells within 2 categories • Granulocytes • Visible lysosomes “granules” in cytoplasm • Neutrophil • Eosinophil • Basophil • Agranulocytes • No visible granules in cytoplasm • Monocyte • Lymphocyte

11. Neutrophils • Overview: • Neutrophils stain in acid-base stains • Constitutes 54-62% of WBCs • Also called polymorphonuclear leukocytes “polymorphs” • Contain 2-5 nuclei + fine purple granules • 12 hour lifespan • Functions • Phagocytosis • Kill bacteria, protozoa, fungi, parasites • Remove dead cells, debris, and foreign particulate • First to arrive at the site of infection • Fast moving cells neutrophil, 1000x

12. Eosinophils • Overview: • Constitute 1-3% of all WBCs • Bi-lobed nucleus • Granules stain bright red in acid stain • Functions • Defend against parasitic worms (tapeworm, hookworm, fluke worm, ect) • mediates allergic reaction and asthma attacks eosinophil, 1000x

13. Basophils • Overview: • Constitutes <1% of WBCs • Deep blue granules stain in basic dye • Bilobed nucleus is usually obscured by the darkened granules • Functions • Secretes histamines • Histamines promote inflammation • Secretes heparin • Heparin is an anticoagulant “prevents clotting” basophil, 1000x

14. Monocytes • Overview: • Constitutes 3-9% of WBC • Largest of all WBCs • Large kidney-shaped nucleus • May live for several weeks up to a month • Functions • Leave the blood to become macrophages • Phagocytize bacteria, dead cells and other debris platelet monocyte, 1000x

15. Lymphocytes • Overview: • Constitutes 23-33% of all WBCs • Formed in red bone marrow and in lymphatic tissues • Large spherical nucleus with a thin sliver of cytoplasm • May live for many months to several years • Includes T-cells & B-cells • Functions • Lymphocytes provide immunity • T-cells directly attack microorganisms and tumor cells • B-cells produce antibodies lymphocyte, 1000x

16. Functions of white blood cells • 1. Leukocytes (primarily neutrophils & monocytes) are motile • Exhibit amoeboid movement • Neutrophils & Monocytes are the most mobile of WBCs • 2. Leukocytes are capable of diapedesis. • They can squeeze between the cells of a capillary wall and enter the tissue space • outside the blood vessel. • 3. Leukocytes exhibit chemotaxis. • They are attracted to chemicals released by damaged tissues. • 4. Leukocytes contribute to the formation of pus. • Pus is the accumulation of bacteria, damaged tissue, and dead white blood cells. Figure 14.15 illustrates diapedesis of a WBC from a capillary into the surrounding connective tissue.

17. Activation of WBCs Figure 14.16 When bacteria invade the tissues, leukocytes migrate into the region and destroy the microbes by phagocytosis.

18. White Blood Cell Counts A typical white blood count contains 4,500-10,000 WBCs per µL (mm3) • Leukopeniais a low WBC count (below 4,500 cells/µL) • Often associated with viral infections (influenza, chicken pox, measles, AIDS) • Leukocytosisis a high WBC count (above 10,000 cells/µL) • Acute infection, exercise, emotional distress • DIFF (differential WBC count) • Measures the percentages specific types of WBC Table 14.4 illnesses associated with various DIFF counts

19. Thrombocytes (platelets) TPO Overview Platelets are cell fragments released from Megakaryocytes within red bone marrow Approximately 150,000 - 450,000 platelets per µL (mm3) of blood. Thrombopoietin (TPO) = growth factor that promotes formation of platelets. Functions include blood coagulation and blood vessel repair Figure 14.4. Development of platelets from hemocytoblasts. Exposure to TPO promotes the formation of megakaryocytes, which release thrombocytes from their plasma membrane.

20. Overview of Blood Cells End of Section 1 of 2.

21. Plasma Overview Plasma is the liquid portion of blood Makes up 55% of blood volume Straw colored Components include Plasma proteins, Dissolved gasses, Wastes, Electrolytes, Nutrients, Hormones Chapter 14, Section 2 of 2.

22. Plasma proteins • Albumin • 60% of plasma proteins • Synthesized in liver • Creates an osmotic that helps maintain blood pressure • Globulins • 36% of plasma proteins • Alpha & Beta globulins • Are produced by liver • Transports lipids • Gamma globulins • Are produced by lymphatic tissues • function as antibodies • Fibrinogen • 4% of plasma proteins • Primary role in blood coagulation

23. Plasma proteins

24. Plasma Gasses & Nutrients • Blood Gasses: • Oxygen • Most is bound to hemoglobin. Less than 2% of oxygen is dissolved in plasma • Carbon dioxide • Most CO2 is transported as bicarbonate (HCO3-) • About 7% is dissolved in plasma • Nutrients: • Amino acids • Simple sugars • Nucleotides • Lipids • Hydrophobic lipids are bound to plasma proteins • within the plasma

25. Nonprotein Nitrogenous Substances • These are molecules containing nitrogen but are not proteins • In plasma they include: • Urea – product of protein catabolism; about 50% of nonprotein • nitrogenous substances • Uric acid – product of nucleic acid catabolism • Amino acids – product of protein catabolism • Creatine – biproduct of creatine phosphate metabolism • Creatinine – product of creatine metabolism • Common tests that evaluate kidney functions: • Creatinine test – measures creatinine • BUN – blood urea nitrogen; indicates health of kidney

26. Plasma Electrolytes • Plasma contains a variety of these ions called electrolytes • They are absorbed from the intestine or released as by-products of cellular metabolism • They include: • Sodium (most abundant with chloride) • Potassium • Calcium • Magnesium • Chloride (most abundant with sodium) • Bicarbonate • Phosphate • Sulfate

27. Hemostasis • Hemostasis refers to the stoppage of bleeding • Actions that limit or prevent blood loss include: • Blood vessel spasm (vasospasm) • Platelet plug formation • Blood coagulation

28. hemostasis, step 1: vasospasm • Blood vessel spasm (vasospasm) • Cutting or breaking a vessel wall stimulates the smooth muscles in its walls to contract. • Vasospasm reduces blood loss almost immediately, and may close small blood vessels completely.

29. hemostasis, step 2: platelet plug formation • Platelet adhesion – platelets adhere to collagen fibers that become exposed due to the damage in a vascular walls • Platelets undergo a shape change, producing several processes to which additional platelets bind. • In addition, platelets secrete thromboxanes, which attract additional platelets to the site of injury. • A platelet plug may control blood loss from a small break.

30. hemostasis, step 3: coagulation • Blood coagulation • Is triggered by cellular damage and blood contact with foreign surfaces • Coagulation is a cascade reaction involving several biochemicals (clotting factors) • The major event is formation of a blood clot when fibrin (a thread-like protein) • forms a mesh surrounding the damaged vessel. • The cascade is divided into three events • Extrinsic mechanism • Intrinsic mechanism • Common pathway

31. Coagulation • Extrinsic clotting mechanism • A chemical released from tissue outside the blood vessels trigger the extrinsic pathway • Damaged tissues releases thromboplastin • (also called factor III) • Factor III initiates a cascade reaction that, in the presence of Calcium, activates factor X. • Activation of factor X initiates the common pathway

32. Coagulation • Intrinsic clotting mechanism • An inactive clotting factor within the blood (Hageman, or factor XII) is activated when foreign tissue, such as collagen enters the bloodstream. • Factor XII proceeds through a cascade of reactions in the presence of Calcium to activate factor X. • Activation of factor X initiates the common pathway.

33. Coagulation • Common Pathway • Is the point at which intrinsic & extrinsic pathways converge • Activated factor X (with help of Calcium & factor V) leads to the release of prothrombin activator from platelets. • Prothrombin activator converts prothrombin into thrombin. • Thrombin, in turn converts fibrinogen into long threads of fibrin. • Fibrin forms an insoluble clot at the site of injury.

34. Coagulation Figure 14.19c. Schematic of the common pathway in the blood clotting mechanism Figure 14.18 A scanning electron micrograph of fibrin threads. The insoluble fibers trap blood cells and platelets, which contribute to the blood clot formation.

35. hemostasis: review

36. Blood Clot Dissolution • After a blood clot forms it retracts and pulls the edges of a broken blood vessel together while squeezing the fluid serum from the clot • Platelet-derived growth factor stimulates smooth muscle cells and fibroblasts to repair damaged blood vessel walls • Plasmin digests the blood clots

37. Blood Clot Disorders • A thrombus is an abnormal blood clot • Deep vein thrombosis – prolonged immobility causes blood to pool, especially in the deep veins of the legs or pelvis. • An embolus is a blood clot moving through the blood vessels • Pulmonary embolism – may occur when part of a thrombus breaks away from the clot and lodges in a pulmonary artery. Rapidly fatal. • Atherosclerosis – accumulation of fatty deposits along arterial lining • May cause inappropriate clotting • Most common cause of thrombosis in medium-sized arteries • Arteriosclerosis – hardening of an artery. • Stenosis – abnormal narrowing of a passage in a body • Atherosclerosis of an artery narrows the passage through which blood flows in an artery, and increases the likelihood of an embolism at that site.

38. Blood Clot Disorders Figure 14.20 Artery cross sections. (a) light micrograph of a normal artery. (b) The inner wall of an artery changed as a result of atheroclerosis. Ultrasound image of stenosis within the internal carotid artery.

39. Blood Typing Blood typing is the process of identifying an individual’s blood group. (eg. Type A, B, AB or O) • Terms to become familiar with: • Antigen– a chemical (or membrane protein) that stimulates cells to produce antibodies • Foreign antigens in the body stimulate the immune response. • Antibodies – a plasma protein that reacts against a specific antigen • Agglutination – clumping of red blood cells in response to a reaction between an antibody and an antigen

40. ABO Blood Group • This blood group is based on the presence (or absence) of two antigens on red blood cell membranes: Antigen A & Antigen B antigens Type A blood contains A-antigens on the surface of its RBCs. Type B blood contains B-antigens on the surface of its RBCs. and anti-A antibodies in its plasma. Type AB blood contains A-antigens and B-antigens on the surface of its RBCs. and has neither antibody Type O blood contains neither A or B antigen on the surface of its RBCs

41. Blood Typing antibodies Type A blood plasma contains anti-B antibodies. Type B blood plasma contains anti-A antibodies. Type AB blood plasma contains neither antibody Type O blood plasma contains both anti-A and anti-B antibodies.

42. ABO Blood Group

43. Rh Blood Group • The Rh blood group was named for the rhesus monkey • Rhpositive (Rh+) indicates the presence of D-antigen (or other Rh antigen) on the red blood cell membranes • Rhnegative (Rh-) lacks the D-antigen • When Rh- blood is exposed to the D antigen, it becomes sensitized and develops anti-D antibodies • Anti-D antibodies are formed only after a person is exposed to D-antigen (Rh sensitization).

44. erythroblastosisfetalis • The seriousness of the Rh blood group is evident in a fetus that develops the condition erythroblastosisfetalis or hemolytic disease of the newborn. • If the mother is Rh- and has been sensitized to the D-antigen, her own antibodies may attack the red blood cells of a fetus that is Rh+.

45. erythroblastosisfetalis • Erythroblastosisfetalis can be prevented for women at high risk by administering a serum that contains anti-D antibodies into the mother during the pregnancy and after birth (before she becomes sensitized to D-antigen). • The injected antibodies quickly agglutinate any fetal red blood cells, thereby preventing her from becoming sensitized to the D-antigen. End of Section 2 of 2.