Intro to Hematopoietic System

1. Intro to Hematopoietic System Dr. Melanie Osterhouse 1040 – blood/immune

2. Function of blood components • ___ - oxygen transportation (by hemoglobin) • ___ - mobile elements of the body’s defense system • ____ - cell fragments important for blood clotting

3. Blood Components

4. Volume of Blood • __ L of blood circulating • 1/3 of body weight • RBC lifetime = ____ days • RBCs are the heaviest resulting in the bottom layer after centrifuging • Buffy coat - WBC and platelets - layer above RBCs • Plasma - on top after centrifuging

5. Erythrokinetics

6. Marrow Production • All bones - 0-5years of age • Pelvis (40%), vertebrae (28%), cranium/mandible (13%), ribs (8%), sternum (2%) - 20+ years of age • Red marrow = _____ • yellow marrow = _______

7. Overview of ________number of blood cells in the blood stream depends on three factors: • Rate of production • Rate of release • Length of survival

8. Embryogenesis_______________________ • 3rd gestational week - stem cells in yolk sac • 3rd gestational month - liver becomes site blood cell formation, with the help of spleen, lymph nodes, and thymus • 4th gestational month - bone marrow becomes functional

9. Location of cell line • __________ - central marrow • __________ - osteoid/marrow junction • _____________ (discharge platelets) - line sinusoids directly into blood stream

10. Pluripotential stem cell

11. Erythropoesis

12. Three mechanisms to increase erythrocytes: • Increase number of stem cells • decrease maturation time • release ________into the bloodstream earlier

13. _________ Due to oxygen demand, erythropoetin stimulates hastening of RBC maturation and early release of reticulocytes into the bloodstream

14. ___________ • Young RBCs with extruded nucleus but maintaining lots of RNA • Normal reticulocyte count is 1% with an average half-life of 4.8 hours

15. Reticulocytes • The RNA is responsible for producing _______.(RNA is not in mature RBCs) Reticulocyte produces 30% of total hemoglobin The other 70% is made in the pre-reticulocyte stages • Reticulocytes have ________ receptors Transferrin carries iron to hemoglobin-producing immature erythrocytes Mature RBCs don’t have the receptors due to their inability to synthesize hemoglobin

16. RNA and ribosomes transferrin receptors bringing iron via transferrin hemoglobin synthesis Loss or RNA and ribosomes Loss of transferrin receptors No more hemoglobin synthesis (carries previously made Hb from reticulocyte stage) Reticulocytes VS mature RBC

17. ____ – depression_________ - elevation Polycytosis – increase in RBCs Polycytopenia – decrease in RBCs

19. Break down of leukocytes

20. WBC • 5-10,000 = normal range • granulocytes are called polymorphonuclear due to the multilobed nucleus • leukocytes live ______ days, destroyed by lymphatic system and excreted in feces • Function = ____________ • phagocytosis • produce, transport and distribute antibodies

21. WBC • Differential count = number of different types of leukocytes • ________ = WBC>10,000 • severe leukocytosis in: • leukemia • leukemoid reaction = temporary • seen in measles, pertussis, sepsis

22. _________ = WBC<4000 • Seen in: • infection • bone marrow disorders • hypersplenism • IDA • __________ - avoid infection • avoid contamination by fresh fruits and veggies • WBC panic values (<500 or >30,000)

23. WBC value variables • ___________ - low in morning and high in late afternoon • Newborn normal (10-20,000) and gradually decreases until age 21

24. Differential WBC count • ________ -> pyogenic infections • _________ -> allergic disorders and parasitic infection • ________-> parasitic infections • _________ -> viral infecion • __________- -> severe infections by phagocytosis

25. Summary of Immune System • Immune proteins are the most diverse proteins known. • Immune system required to survive infection • Antibodies-aka ___________ • vast number of antibodies made by re-shuffling a small set of gene fragments

26. Immune system • The other immune proteins are ___ receptors • recognizes only cells that have self and nonself markers.

27. Lymphocytes

28. _ cell line Antibodies mark foreign organisms for destruction Complement system responds to this mark by perforating the cell membrane. Antigen-antibody complexes attract macrophages to engulf and digest foreign particles

29. B cell line • Diversity in B cells comes from combinational and mutational mechanisms • Diversity increases the number of distinct antigen binding sites

30. T cell line • ________ T cell =kill target directly • ________T cell=recognize antigen and stimulate B and T cells • ______ T cell=opposite helper T cell.

31. ______________ (MHC) • The third class of proteins in immune system (B and T cells and MHC) • MHC - found on all cell surfaces • T cells require recognition of both antigen and a self MHC protein • MHC causes T cells to be attracted to infected cells not free bacteria (to prevent replication of infection)

32. __________ Smooth discs enclosed in a plasma membrane. Two types of granules inside: 1.alpha containing fibrinogen 2. electron dense bodies-storage site for ADP/ATP, Ca, histamine, serotonin, epinephrine

33. With injury to a vessel, platelets undergo three reactions: • ______- - attachment of platelets to sites of endothelial cell injury • __________-- release of platelet granules • ADP induces platelet aggregation • Platelet ___________ • Thromboxane released by platelets causing aggregation and vasoconstriction

34. ____________ platelet contraction - fused mass stimulated by the combination of ADP, thrombin, and thromboxane Thrombin causes fibrinogen to convert to fibrin within the platelet aggregate making “platelet bricks”

35. Platelet sequence

36. Coagulation sequence transformation of proenzymes to activated enzymes via intrinsic and extrinsic pathway resulting in thrombin formation

37. _________ occurs on the surface of activated platelets

38. ____________ = reduced platelets (normal 150,000-300,000/mm3) spontaneous bleeding occurs below 20,000/mm3 of platelets. Post-traumatic bleeding results in platelets in the range of 20,000-50,000/mm3

39. Thrombocytopenia causes small vessel bleeding m/cly. M/C sites: • skin • mucous membranes of GI and GU • Intracranial bleeding

40. Decreased platelet production marrow dz aplastic anemia leukemia drug/ alcohol AIDS antiplatelet antibodies due to molecular mimicry megaloblastic anemia ineffective megakaryopoiesis Decreased platelet survival autoimmune dz (SLE) drug Infection Sequestration hypersplenism Dilutional mechanical injury prosthetic heart valve Thrombocytopenia - etiology

41. Dilutional ________ - blood stored for longer than 24 hours has virtually no viable platelets

42. Defective platelet function _____ has antiplatelet effect and is thus used in Tx of recurrent MI

43. DIC - _______________ • secondary thrombohemorrhagic disorder • Ch. by activation of the coagulation sequence leading to diffuse formation of microthromi • endothelial injury - major trigger • M/Cly seen in obstetric complications, malignancy, sepsis, and major trauma • malignancies include leukemiaa, CA of lung, pancreas, colon, stomach • tumors releasing thromboplastic substances

44. DIC • deposition of fibrin within microcirculation • causes _____-due to the squeezing of RBCs through the narrowed microcirculation • ischemic organs • bleeding • due to consumption of platelets and clotting factors and plasminogen

45. DIC • ________are found in decreasing order: • brain, heart, lung, kidney, adrenals, spleen, liver • 50% of DIC is from complications of ________ (such as toxemia) • reverses with delivery of fetus

46. Respiratory dyspnea, cyanosis, distress Neurologic convulsions, coma Renal oliguria, acute failure Circulation shock Acute DIC from trauma or obstetric tends to be bleeding dominant Chromic DIC from cancer tends to be thrombotic dominant Signs/Symptoms of DIC

47. DIC Tx • Depends on if bleeding or thrombosis predominates • anticoagulants like heparin • coagulants like fresh-frozen plasma • Sometimes platelet transfusion

48. Specific anemic states Dr. Melanie Osterhouse Logan College of Chiropractic

49. ____________ • Decrease in the red cells caused by too little iron • most common anemia • 20%women, 50%pregnancy,3%men

50. Risk factors for IDA • Women who menstruate • pregnancy or lactation • children in rapid growth phases • low dietary intake (no meat or egg) • Blood loss (peptic ulcer dz, aspirin, colon CA, uterine CA, blood donation