CMWM633 WESTERN MEDICAL LABORATORY & IMAGING Credit hour: 3 Credits, 45 Hours Prerequisite: BS -525 Patho

1. CMWM633 WESTERN MEDICAL LABORATORY & IMAGING Credit hour: 3 Credits, 45 Hours Prerequisite: BS-525 Pathology Concurrent: BS-524 Microbiology

2. Contents • Composition of Blood • Production of Blood cells • Functions of Blood cells • Hemostasis • Hemogram(CBC)

3. The lab test

4. BLOOD STUDIESHematology and Coagulation

5. Cardiovascular System Blood

6. Composition of Blood Average person circulates about 5L of Blood , of which 3L is plasma and 2L is cells. Plasma Fluid derives from the intestines and lymphatic systems and provides a vehicle for cell movement.

7. Adult ♂ contains 5-6L • Adult ♀ contains 4-5L • T is about 100.4 F • Is this higher or lower than normal body T? • 5 times as viscous as water • Is it more or less resistant to flow than water? • What accounts for its viscosity? • pH ranges from 7.35 – 7.45 (slightly alkaline) • Color ranges from scarlet (oxygenated blood) to a deep red (deoxygenated blood).

8. BLOOD is composed of plasma (~55%), and the formed elements which are: • The erythrocytes (RBCs) (~45%) • Contain hemoglobin • Function in the transport of O2 and CO2 • The Leukocytes (WBCs) and platlets (thrombocytes) (~1%) • Leukocytes are involved in the body’s defense against the invasion of foreign antigens. • Platlets are involved in hemostasis which forms a barrier to limit blood loss at an injured site.

9. Composition of Blood

10. Components of Blood • 55% plasma • 45% cells • 99% RBCs • < 1% WBCs and platelets

11. Plasma • Liquid part of blood • Pale yellow made up of 91% water, 9% other • Colloid: Liquid containing suspended substances that don’t settle out • Albumin: Important in regulation of water movement between tissues and blood • Globulins: Immune system or transport molecules • Fibrinogen: Responsible for formation of blood clots

12. Formed Elements • Red blood cells (erythrocytes) • White blood cells (leukocytes) • Granulocytes • Neutrophils • Eosinophils • Basophils • Agranulocytes • Lymphocytes • Monocytes • Platelets (thrombocytes)

13. Formed Elements of Blood • Red blood cells ( erythrocytes ) • White blood cells ( leukocytes ) • granular leukocytes • neutrophils • eosinophils • basophils • agranular leukocytes • lymphocytes = T cells, B cells, and natural killer cells • monocytes • Platelets (special cell fragments)

14. The cells are primarily produced by bone marrow and account for blood “solids”. Blood cells are classified as white cells (leukocytes),red cells(erythrocytes) and platelets(thrombocytes)

15. Hematopoiesis is a term describing the formation and development of blood cells. • Cells of the blood are constantly being lost or destroyed. Thus, to maintain homeostasis, the system must have the capacity for self renewal. This system involves: • Proliferation of progeny stem cells • Differentiation and maturation of the stem cells into the functional cellular elements. • In normal adults, the proliferation, differentiation, and maturation of the hematopoietic cells (RBCs, WBCs, and platlets) is limited to the bone marrow and the widespread lymphatic system and only mature cells are released into the peripheral blood.

17. Hematopoiesis begins as early as the 19th day after fertilization in the yolk sac of the embryo • Only erythrocytes are made • The RBCs contain unique fetal hemoglobins • At about 6 weeks of gestation, yolk sac production of erythrocytes decreases and production of RBCs in the human embryo itself begins.

18. The fetal liver becomes the chief site of blood cell production. • Erythrocytes are produced • The beginnings of leukocyte and thrombocyte production occurs • The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. • The lymph nodes will continue as an important site of lymphopoiesis (production of lymphocytes) throughout life, but blood production in the other areas decreases and finally ceases as the bone marrow becomes the primary site of hematopoiesis at about 6 months of gestation and continues throughout life. • When the bone marrow becomes the chief site of hematopoiesis leukocyte and thrombocyte production become more prominent.

19. Hematopoiesis 6

20. Hematopoiesis in the bone marrow is called medullary hematopoiesis • Hematopoiesis in areas other then the bone marrow is called extramedullary hematopoiesis • Extramedullary hematopoiesis may occur in fetal hematopoietic tissue (liver and spleen) of an adult when the bone marrow cannot meet the physiologic needs of the tissues. This can lead to hepatomegaly and/or splenomegaly (increase in size of the liver of spleen because of increased functions in the organs). Hematopoietic tissue includes tissues involved in the proliferation, maturation, and destruction of blood cells

21. Bone marrow – is located inside spongy bone • In a normal adult, ½ of the bone marrow is hematopoietically active (red marrow) and ½ is inactive, fatty marrow (yellow marrow). • The marrow contains both Erythroid (RBC) and Myeloid (WBC) precursors as well as platlet precursors. The normal M:E ratio is 1.5:1 to 4:1. • Early in life most of the marrow is red marrow and it gradually decreases with age to the adult level of 50%.

22. Glassy hyaline cartilage Compact+spongy (remanent of plate-hyaline cartilage Causes the lengthwise growth) (red marrow) (yellow marrow-fat) Compact bone Fibrous connective tissue

24. In certain pathologic states the bone marrow can increase its activity to 5-10X its normal rate. • When this happens, the bone marrow is said to be hyperplastic because it replaces the yellow marrow with red marrow. • This occurs in conditions where there is increased or ineffective hematopoiesis. • The degree to which the the bone marrow becomes hyperplastic is related to the severity and duration of the pathologic state. • Pathologic states that cause this include: • Acute blood loss in which there is a temporary replacement of the yellow marrow • Severe chronic anemia – erythropoiesis (RBC production) may increase to the extent that the marrow starts to erode the bone itself. • Malignant disease – both normal red marrow and fatty marrow may be replaced by proliferating abnormal cells.

25. The hematopoietic tissue may also become inactive or hypoplastic. This may be due to: • Chemicals • Genetics • Myeloproliferative disease that replaces hematopoietic tissue with fiberous tissue

26. Blood cell differentiation

27. Production of Formed Elements • Hematopoiesis or hemopoiesis: Process of blood cell production • Stem cells: All formed elements derived from single population • Proerythroblasts: Develop into red blood cells • Myeloblasts: Develop into basophils, neutrophils, eosinophils • Lymphoblasts: Develop into lymphocytes • Monoblasts: Develop into monocytes • Megakaryoblasts: Develop into platelets

28. Blood cell differentiation Megakaryoblast Magakaryocyte Platelets Lymphoblast Bcells Tcells plasma Active cell Tcell Myeloblast Neutrophil Eosinophil Basophil Promyelocyte Myelocyte Metamyelocyte Stab Cell Netrophil Eosinophil Basophil Monoblasts Monocyte Proerytroblast Reticulocyte Erythrocyte

29. Hematopoiesis summary

30. Hematopoiesis

31. Hematopoiesis

32. Functions of Blood • Transport of: • Gases, nutrients, waste products • Processed molecules • Regulatory molecules • Regulation of pH and osmosis • Maintenance of body temperature • Protection against foreign substances • Clot formation

33. Red blood cells transport oxygen • Red blood cells contain hemoglobin • Hemoglobin enables the transport of O2 Figure 23.14

34. White blood cells help defend the body • White blood cells function both inside and outside the circulatory system • They fight infections and cancer Basophil Eosinophil Monocyte Neutrophil Lymphocyte

35. Thrombocytes • Cell fragments pinched off from megakaryocytes in red bone marrow • Important in preventing blood loss • Platelet plugs • Promoting formation and contraction of clots

36. Hemostasis • Arrest of bleeding • Events preventing excessive blood loss • Vascular spasm: Vasoconstriction of damaged blood vessels • Platelet plug formation • Coagulation or blood clotting

37. Blood clots plug leaks when blood vessels are injured • When a blood vessel is damaged, platelets respond • They help trigger the formation of an insoluble fibrin clot that plugs the leak

38. Platelet Plug Formation

39. 1 Injury to lining of bloodvessel exposes connectivetissue; platelets adhere 2 Platelet plug forms 3 Fibrin clot trapsblood cells Connectivetissue Plateletplug Platelet releases chemicalsthat make nearby platelets sticky Clotting factors from: Platelets Calcium andother factorsin blood plasma Damaged cells Prothrombin Thrombin Fibrinogen Fibrin Figure 23.16A

40. Platelet plug formation • Platelets store a lot of chemicals in granules needed for platelet plug formation • ADP, Ca+2, serotonin, fibrin-stabilizing factor, & enzymes that produce thromboxane A2 • Steps in the process • (1) platelet adhesion (2) platelet release reaction (3) platelet aggregation

41. 1. Platelet Adhesion • Platelets stick to exposed collagen underlying damaged endothelial cells in vessel wall

42. 2. Platelet Release Reaction • Platelets activated by adhesion • Extend projections to make contact with each other • Release thromboxane A2, serotonin & ADP activating other platelets • Serotonin & thromboxane A2 are vasoconstrictors decreasing blood flow through the injured vessel. ADP causes stickiness

43. 3. Platelet Aggregation • Activated platelets stick together and activate new platelets to form a mass called a platelet plug • Plug reinforced by fibrin threads formed during clotting process

44. Coagulation • Stages • Activation of prothrombinase • Conversion of prothrombin to thrombin • Conversion of fibrinogen to fibrin • Pathways • Extrinsic • Intrinsic

45. Blood Clotting • Blood drawn from the body thickens into a gel • gel separates into liquid (serum) and a clot of insoluble fibers (fibrin) in which the cells are trapped • If clotting occurs in an unbroken vessel is called a thrombosis • Substances required for clotting are Ca+2, enzymes synthesized by liver cells(clotting factors) and substances released by platelets or damaged tissues • Clotting is a cascade of reactions in which each clotting factor activates the next in a fixed sequence resulting in the formation of fibrin threads

47. Clot Formation

48. Plasminogen (plasmin) • Plasminogen is a glycoprotein, synthesized in the liver, present in plasma.Under normal conditions,plasminogen is part of any clot because of the tendency of fibrin to absorb plasminogen from plasma.When plasminogen activators perform their function plasmin is formed within the clot;this gradually dissolves the clot while leaving time for tissues repair,free plasmin is also released to the plasma;however,antiplasmins there immediately destroy any plasmin released from the clot.

49. FUNCTION:Determines plasminogen activity in persons with thrombosis or DIC, in these conditions excessive free plasmin is released to the plasma, In these situations antiplasmin is depleted and plasmin begins destroying components other than fibrin,including fibrinogen, factors V and VIII, and other factors

50. D-Dimer is an assay used to assess possible intravascular clotting. D-Dimer is a cleavage product of fibrin and is elevated in disseminated intravascular coagulation, in thromboembolic events and after surgery.