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Intro to Hematopoietic System Dr. Melanie Osterhouse 1040 – blood/immune
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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
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Blood Components
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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
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Erythrokinetics
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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 = _______
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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
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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
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Location of cell line 4 __________ - central marrow 4 __________ - osteoid/marrow junction 4 _____________ (discharge platelets) - line sinusoids directly into blood stream
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Pluripotential stem cell
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Erythropoesis
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Three mechanisms to increase erythrocytes: 4 Increase number of stem cells 4 decrease maturation time 4 release ________into the bloodstream earlier
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_________ Due to oxygen demand, erythropoetin stimulates hastening of RBC maturation and early release of reticulocytes into the bloodstream
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___________ 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
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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
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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)
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____ – depression _________ - elevation Polycytosis – increase in RBCs Polycytopenia – decrease in RBCs
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Break down of leukocytes
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§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
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§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
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§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
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§___________ - low in morning and high in late afternoon §Newborn normal (10- 20,000) and gradually decreases until age 21 WBC value variables
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§________ -> pyogenic infections §_________ -> allergic disorders and parasitic infection §________-> parasitic infections §_________ -> viral infecion §__________- -> severe infections by phagocytosis Differential WBC count
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§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
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§The other immune proteins are ___ receptors l recognizes only cells that have self and nonself markers. Immune system
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Lymphocytes
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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
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§Diversity in B cells comes from combinational and mutational mechanisms §Diversity increases the number of distinct antigen binding sites B cell line
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§________ T cell =kill target directly §________T cell=recognize antigen and stimulate B and T cells §______ T cell=opposite helper T cell. T cell line
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§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)
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__________ 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
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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
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____________ 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”
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Platelet sequence
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Coagulation sequence transformation of proenzymes to activated enzymes via intrinsic and extrinsic pathway resulting in thrombin formation
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_________ occurs on the surface of activated platelets
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____________ = 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
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Thrombocytopenia causes small vessel bleeding m/cly. M/C sites: 4 skin 4 mucous membranes of GI and GU 4 Intracranial bleeding
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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
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Dilutional ________ - blood stored for longer than 24 hours has virtually no viable platelets
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Defective platelet function _____ has antiplatelet effect and is thus used in Tx of recurrent MI
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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
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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
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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
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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
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DIC Tx 4 Depends on if bleeding or thrombosis predominates 4 anticoagulants like heparin 4 coagulants like fresh-frozen plasma 4 Sometimes platelet transfusion
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Specific anemic states Dr. Melanie Osterhouse Logan College of Chiropractic
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____________ 4 Decrease in the red cells caused by too little iron 4 most common anemia 4 20%women, 50%pregnancy,3%men
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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
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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
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___________ Failure of blood cell forming capacity in marrow affecting all blood cell types
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Causes Aplastic Anemia 4 Chemotherapy/ drugs 4 radiation 4 toxins 4 pregnancy 4 congenital disorders 4 SLE 4 infectious hepatitis 4 idiopathic
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Aplastic anemia symptoms 4 Fatigue 4 pallor 4 SOB 4 tachycardia 4 arrhythmia 4 rash 4 bruising/bleeding
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Signs 4 Enlarged spleen 4 tender sternum 4 low Hb and hematocrit 4 low retic 4 low platelet 4 abnormal marrow biopsy
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Tx 4 Bone marrow transplant 4 transfusions 4 prognosis is death without treatment
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Complications 4 Infection 4 cerebral hemorrhage 4 bleeding
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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
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macrocytosis results from: Erythropoietin-mediated acceleration of erythrocyte production, cell wall synthesis defects and aberrant responses to erythropoietin stimulation
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symptoms 4 Anorexia 4 diarrhea 4 paresthesia 4 pallor 4 fatigue 4 Headache 4 glossitis 4 jaundice
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__________ causes polyneuropathy, myelopathy and altered mental state due to: Damage in the dorsal and lateral columns of the spinal cord
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signs 4 Abnormal reflexes 4 decreased proprioception and vibration 4 low hematocrit with high MCV 4 low B12 4 Elevated ferritin
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Tx of B12 def 4 Intramuscular B12 injections 4 Normal hematology in 2 months 4 Neurological compromise can be permanent
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