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

2. Function of blood components 4 ___ - oxygen transportation (by hemoglobin) 4 ___ - mobile elements of the body’s defense system 4 ____ - cell fragments important for blood clotting

3. Blood Components

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

5. Erythrokinetics

6. Marrow Production 4 All bones - 0-5years of age 4 Pelvis (40%), vertebrae (28%), cranium/mandible (13%), ribs (8%), sternum (2%) - 20+ years of age 4 Red marrow = _____ 4 yellow marrow = _______

7. Overview of ________ number of blood cells in the blood stream depends on three factors: 4 Rate of production 4 Rate of release 4 Length of survival

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

9. Location of cell line 4 __________ - central marrow 4 __________ - osteoid/marrow junction 4 _____________ (discharge platelets) - line sinusoids directly into blood stream

10. Pluripotential stem cell

11. Erythropoesis

12. Three mechanisms to increase erythrocytes: 4 Increase number of stem cells 4 decrease maturation time 4 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. ___________ 4 Young RBCs with extruded nucleus but maintaining lots of RNA 4 Normal reticulocyte count is 1% with an average half-life of 4.8 hours

15. Reticulocytes 4 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. Reticulocytes VS mature RBC 4 RNA and ribosomes 4 transferrin receptors bringing iron via transferrin 4 hemoglobin synthesis 4 Loss or RNA and ribosomes 4 Loss of transferrin receptors 4 No more hemoglobin synthesis (carries previously made Hb from reticulocyte stage)

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

19. Break down of leukocytes

20. §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 = ____________ l phagocytosis l produce, transport and distribute antibodies WBC

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

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

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

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

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

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

27. Lymphocytes

28. 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 _ cell line

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

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

31. §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) ______________ (MHC)

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: 4 ______- - attachment of platelets to sites of endothelial cell injury 4 __________-- release of platelet granules –ADP induces platelet aggregation 4 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: 4 skin 4 mucous membranes of GI and GU 4 Intracranial bleeding

40. Thrombocytopenia - etiology 4 Decreased platelet production –marrow dz aplastic anemia leukemia –drug/ alcohol –AIDS antiplatelet antibodies due to molecular mimicry –megaloblastic anemia ineffective megakaryopoiesis 4 Decreased platelet survival –autoimmune dz (SLE) –drug –Infection 4 Sequestration –hypersplenism 4 Dilutional 4 mechanical injury –prosthetic heart valve

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 - _______________ 4 secondary thrombohemorrhagic disorder 4 Ch. by activation of the coagulation sequence leading to diffuse formation of microthromi 4 endothelial injury - major trigger 4 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 4 deposition of fibrin within microcirculation –causes _____-due to the squeezing of RBCs through the narrowed microcirculation –ischemic organs 4 bleeding –due to consumption of platelets and clotting factors and plasminogen

45. DIC 4 ________are found in decreasing order: –brain, heart, lung, kidney, adrenals, spleen, liver 4 50% of DIC is from complications of ________ (such as toxemia) –reverses with delivery of fetus

46. Signs/Symptoms of DIC 4 Respiratory –dyspnea, cyanosis, distress 4 Neurologic –convulsions, coma 4 Renal –oliguria, acute failure 4 Circulation –shock 4 Acute DIC from trauma or obstetric tends to be bleeding dominant 4 Chromic DIC from cancer tends to be thrombotic dominant

47. DIC Tx 4 Depends on if bleeding or thrombosis predominates 4 anticoagulants like heparin 4 coagulants like fresh-frozen plasma 4 Sometimes platelet transfusion

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

49. ____________ 4 Decrease in the red cells caused by too little iron 4 most common anemia 4 20%women, 50%pregnancy,3%men

50. Risk factors for IDA 4 Women who menstruate 4 pregnancy or lactation 4 children in rapid growth phases 4 low dietary intake (no meat or egg) 4 Blood loss (peptic ulcer dz, aspirin, colon CA, uterine CA, blood donation

51. IDA symptoms 4 Pallor 4 fatigue 4 irritability 4 weakness 4 SOB 4 low BP 4 sore tongue 4 brittle nails 4 pica 4 decreased apetite 4 headache

52. ___________ Failure of blood cell forming capacity in marrow affecting all blood cell types

53. Causes Aplastic Anemia 4 Chemotherapy/ drugs 4 radiation 4 toxins 4 pregnancy 4 congenital disorders 4 SLE 4 infectious hepatitis 4 idiopathic

54. Aplastic anemia symptoms 4 Fatigue 4 pallor 4 SOB 4 tachycardia 4 arrhythmia 4 rash 4 bruising/bleeding

55. Signs 4 Enlarged spleen 4 tender sternum 4 low Hb and hematocrit 4 low retic 4 low platelet 4 abnormal marrow biopsy

56. Tx 4 Bone marrow transplant 4 transfusions 4 prognosis is death without treatment

57. Complications 4 Infection 4 cerebral hemorrhage 4 bleeding

58. Causes of ____________ 4 Alcohol abuse 4 folate or B12 def 4 chemotherapy/drugs 4 hemolysis/bleeding 4 Liver dz (defective DNA synthesis with accelerated erythropoiesis) 4 bone marrow disorders 4 hypothyroidism

59. macrocytosis results from: Erythropoietin-mediated acceleration of erythrocyte production, cell wall synthesis defects and aberrant responses to erythropoietin stimulation

60. symptoms 4 Anorexia 4 diarrhea 4 paresthesia 4 pallor 4 fatigue 4 Headache 4 glossitis 4 jaundice

61. __________ causes polyneuropathy, myelopathy and altered mental state due to: Damage in the dorsal and lateral columns of the spinal cord

62. signs 4 Abnormal reflexes 4 decreased proprioception and vibration 4 low hematocrit with high MCV 4 low B12 4 Elevated ferritin

63. Tx of B12 def 4 Intramuscular B12 injections 4 Normal hematology in 2 months 4 Neurological compromise can be permanent