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134 Cards in this Set
- Front
- Back
Function of Red Blood Cells
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Transport of Hemoglobin
and along with it, oxygen Contain carbonic anhydrase – which catalyses CO2 and H2O to form H2CO3 Hb is a good acid-base buffer – as is any protein |
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hct
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45-men
40 women |
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Hemoglobin:
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~34 gm/100 ml red cells
15-16 (male) gm Hb/100 ml blood 13-14 (female) gm Hb/100 ml blood |
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Oxygen carrying capacity:
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gm Hg/100 ml blood * 1.34 ml O2/gm Hb
~21 ml O2/ 100 ml blood for men ~19 ml O2/ 100 ml blood for women |
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Normal Values
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WBC count x 103 ~7.8 ± 3
RBC count x 106 ~5.4 male/mm3 (higher at altitude) x 106 ~4.8 female/mm3 Hemoglobin 16 gm Hb/100ml cells - male 14 “ “ female hematocrit 47 ± 5 male 42 ± 5 female RBC indices MCV ~90 cubic microns MCH 32 gm/10ml of cells Platelet count x 103 140-440 |
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Regulation of Red Cell Mass
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Balance between production and destruction
~ 1% produced/day ~ 1% destroyed/day Produced in bone marrow sternum, pelvis, vertebrae, ribs in adults (flat bones) Production regulated by erythropoietin |
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Sites Of Hemopoietic Activity
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CHANGES FROM LONG BONE TO FLAT BONES as we age
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RBC production
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Total RBC mass in circulation must:
1. supply an adequate # of cells to provide O2 2. control the # of cells so as not to impede flow Erythropoietin is released from kidney in response to low renal oxygenation. (it’s a glycoprotein) Stimulates stem cells to form pronormoblasts Promotes release of reticulocytes Red cell production increases within 24 hours Erythropoietin life span is 4-12 hours Increase in red cell number in 5 days Folic acid and B12 are essential for the maturation of RBCs. Failure to absorb B12 is pernicious anemia. (intrinsic factor from the gastric glands of the stomach wall binds B12, protects it from acidic denaturation in the stomach and allows its absorption through the gut wall). No stomach wall, no B12 absorption. |
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RBCs
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Biconcave discs
~7.7 um in diameter Cell membrane is a bag that can deform and resume its original shape Excess of cell membrane relative to its contents, the membrane doesn’t stretch much when the cell distorts and therefore doesn’t rupture as easily as any other cell would. |
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Erythropoietin
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Any drop in tissue O2 levels will cause an increase in RBC production,
if EPO is present in circulation 90% EPO produced in peritubular interstitial cells of the kidney Also produced in the liver ~10% No preformed stores of erythropoietin High hematocrit suppresses erythropoietin production but does not abolish it Erythropoietin is always present in the plasma In individuals with damaged or removed kidneys, EPO drops and anemia increases |
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Hb
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Hb formation begins in the proerythroblasts
Subunit Hb chains are alpha, beta, gamma, and delta – each has a slightly different a.a. sequence In adults, Hb has two alphas and two betas, each on associated with a heme group. Each heme binds one molecule of O2 loosely Different types of Hb have different affinities for O2. Sickle cell has an a.a. mis-read in the beta chains and exposed to low O2, it forms crystals – distorting shape, affecting circulation, causing hemolysis and anemia Our hbg is 2 alphas and 2 beta Sicke cell helps fight malaria, but not the other way around. |
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Destruction of Red Blood Cells
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< 100 days survival hemolysis
Decrease in enzyme activity, ATP levels, and MCH Decreased deformability (spherocytosis) Binding by IgG Ingested by macrophage in spleen extravascular hemolysis Iron release to transferrin Hemoglobin excreted as bilirubin 120 day life The iron gets recycled to transferrin…then reused or excreted can be stored by hemociterin |
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Iron Metabolism
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Fe important for Hb, myoglobin, cytochrome, several oxidative enzymes
7 mg/1000 calories ~ 10% absorbed, 1-1.5 mg/day absorption enhanced by meat, poultry, fish inhibited by carbonates, tannate (tea), oxalate (spinach, rhubarb), phosphates (vegetables), clay duodenum and upper jejunum major site absorption HCl promotes absorption loss 1 mg/day males average menstruating women additional 14 mg/period loss Odd turds d/t weird bilirubin, biliverdin |
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Iron Transport and Storage
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Transferrin in plasma
Two iron binding sites Responsible for pink color of plasma 1/3 of sites are occupied, TIBC = 300 ug/ml, 30% saturation, 100 ug/ml Ferritin in cellular cytoplasm 30% of total iron Hemosiderin collects in cells Water insoluble |
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Anemias
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Blood loss anemia – Hct is normal
Aplastic anemia – bone marrow failure – no cells Megaloblastic anemia – deficiency of B12, folate or intrinsic factor – cells grow too big and don’t function well Hemolytic anemia – fragile RBCs, sickle cell, Rh response in pregnancy, some microorganisms, rough sample handling Anemia is failure of blood to carry oxygen |
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Reticulocyte Index
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Retic = relative percent of cells that are reticulocytes
Need to correct to get absolute percentage RI= Retic (%) * Hc(patients)/Hc (normal) |
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Anemias
Normochromic,normocytic |
Bone marrow failure, renal disease, hemolytic anemia
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Anemias
macrocytic, normochromic |
megaloblastic
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Anemias
microcytic, hypochromic |
iron deficiency, chronmic disease
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Hypoproliferative
Aplastic anemia |
Primary
idiopathic Secondary Drugs - chemotherapy, antibiotics, antidepressants, ethanol Chemicals - benzene Radiation Immune suppression of stem cell Malignancy (non-hematopoietic tumors and transformation of hematopoietic stem cells) Aplastic Anemia decrease in all cells RBC, WBC ,platelets Primary is idiopathic 40-70~ of total |
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Hypoproliferative
Reduced erythropoietin response |
Acute inflammatory state
acute, chronic bacterial infections AIDS Renal Disease Hypometabolic state protein deprivation endocrine deficiency hypothyroidism hypopituitarism |
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Maturation defects
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Thalassemia
South European, African, Asian defect in hemoglobin synthesis microcytic, hypochromic transfusions, folic acid |
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Megaloblastic Anemias
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Large fragile red blood cells
Impaired DNA synthesis Increased utilization Folic Acid Deficiency Inadequate diet, Dialysis, cirrhosis, vegetarian Impaired absorption Folate very heat labile Vitamin B12 Deficiency Inadequate diet Dialysis Impaired absorption Intrinsic factor (glycoprotein secreted by gastic parietal cells) (Pernicious anemia) Increased MCV increased MCH Folate and B12 are required for DNA synthesis Folic acid green leafy vegetables, dairy products 3-6 months stored B12 diet not a problem 3-6 years B12 not in fruits and vegetables Absorbed in ileum after binds to intrinsic factor Prenicious anemia (lack intrinsic factor) mucosal damage, endocrine, immune, partial excision of stomach. |
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Hemolytic, Blood Loss
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Hereditary
Sickle cell (hemoglobin) Spherocytosis (membrane) Acquired Microangiopathic hemolytic anemia Immune responses, mismatch typing Blood Sickle cell become ridig, rupture spherocytosis membrane defect that decreased lipid content, impaired flexibility |
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Polycythemias
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2o Caused by tissue hypoxia – whatever the reason – up to 30% h in RBCs
Vera – blasts don’t respond to high RBC levels and continue making all formed elements |
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Polycythemia
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Three Pathophysiological Categories of Polycythemia
Relative Polycythemia (Red Blood Cell Mass Normal, Plasma Volume Decreased) Secondary Polycythemia (Red Blood Cell Mass Increased) Polycythemia vera (Red Blood Cell Mass Increased) |
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Mechanical & chemical resistance of the body to infection
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Gut---Mucous, acid, normal gut flora and fast transit time
Lung--ciliary elevator Also – intact, acidic, dry surface skin |
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Leukocytes / White Blood Cells
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Granulocytes (65%)
neutrophils, eosinophils, basophils formed in bone marrow Monocytes (5%) tissue macrophages formed in bone marrow Lymphocytes (30%) formed in lymph tissue |
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Leukocytes Classification
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Granulocytes Non- Granulocytes
Neutrophils - Monocytes Eosinophils - Lymphocytes Basophils Polymorphonuclear Mononuclear Neutrophils - Monocytes Eosinophils - Lymphocytes Basophils Phagocytes Non-phagocytes Neutrophils, monocytes - Lymphocytes Macrophages, eosinophils - Basophils |
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Phagocytic Cells
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Polymorphonuclear Neutrophils
non-dividing, short-lived dominant number in bloodstream Monocytes/Macrophages long-lived cells do not circulate present in tissue, particularly in lungs, spleen, liver, lymph nodes tissue macrophage system Neutrophils 9-10 days 5-7 days in maturation and storage, 2-3 days in bone marrow |
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EOSINOPHILS
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~ 2% of total white blood cells
active against parasites, skin diseases, chronic infections phagocytic and immunomodulatory, decrease inflammation – long term |
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BASOPHILS
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~ 0.5% of total white blood cells
basophils similar to mast cells release primarily histamine, some bradykinin release due to binding of IgE |
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Monocyte-Macrophage System
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Monos and Macs phagocytize: large quantities of bacteria, viruses, necrotic tissue, and any foreign particle
Monocytes precursors of osteoclasts Atherosclerosis (foam cells are macrophages) Responsible for fever - along with other molecules Tissue macrophages macrophages of lymph system alveolar macrophages Kupffer cells in the liver macrophages of the spleen and bone marrow Monocytes formed from same cells as neutrophils |
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liver phagocytic cells?
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Kupffer
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phagocytic cells only in blood
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monocytes
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Actions of Phagocytic Cells (which live weeks to months, in and out of circulation)
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1. Margination
2. Diapedesis 3. Ameboid Motion 4. Chemotaxis 5. Phagocytosis |
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Antigenic microbe activates binding molecules on the endothelial wall of the cap. Allowing for margination, diapedesis, and chemotaxis
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Antigen-any protein anywhere--generates and antibody response (implies it’s not a native protien
The markers on cells are called Major Histocompatiboility Comple (MHC) All of your cells are genetically marked cells-1.2 from mom and 1/2 from dad. Up to about 14 months you can add protiens and they become ‘yours’ after that, it’s a no go 340-360 different one in humans-possible there fore there are billions of possible combinations. Your cell can recognize your cells…..and the fact that other cells are not yours. HLA- human leukocyte antigens can ‘flash a badge that say’s I’m OK’ These are MHC’s that apple to white cells. |
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Neutrophilic (or macropage) response to antigen- first line of defense
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ER makes lysosomes
Neutrophils ingest, macros grab hold and squirt--affects cell neighborhood. neutros have a grater change of being killed offf. |
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An antigen is a
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protien that can induce
an immune response when introduced into an immunocompetent host and that can react with the antibody produced from that response Macromolecule Protein polysaccharide Most antigens have variety of antigenic determinants |
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Agglutination process needed to remove antigens from circulation
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Must have both antibdy and atigen for agglutyination
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adaptive (specific immunity)
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involved B cell stimulation to produce specific antibodies
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first neutrophill, then monocytes, thenm t-lunpohocytes
[troop surge] |
Monocytes become macrophages
T’s and b’s T’s don’t make antibodies B’s make them |
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B-lympho.s stimulated to become plasma cells and memory cells
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Plasma and memory cells are still B’s
Parts of the B clone become memory cells and don’t produce antibody, but maintain the genes that are effective against that group of antigen. The rest of the B clone become plasma cells and produce specific effective, antibody |
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One pathogen has many different surface antigens – each of which can stimulate different B-cell responses
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Complement attatchment-will be destroyed.
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Serum electrophoresis. A=albumin, and the others in order of size and charge. Immunoglobulins are all gamma
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Our immunologic antibodies/antigens are gammaglobulin,
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IgG
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main form of antibodies in circulation
productin increased after i mmunizatin, secreted during secondary response |
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IgA
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main antibody in external secretions
saliva, mother's mimlk |
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IgE
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responsibloe for allergy sx in allergic reactions, hypersenstivity
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IgM
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function as antigen receptors on lymphocyute surface prior to immunization.
secreteed during primary response |
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IgD
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Function as antigen recptors on lypmphocyte surface prior to immunization.
other functions unknown |
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Memory B Cells--- stronger antigen binding
Memory T-cells--- production of cytokines Tolerance to self-antigens 1) do not generate receptors to self antigens 2) learn not to respond to self antigens ****** kill self-reacive lymphocytes inactivate lymphocytes Tolerance to self antigen someties breaks down Autoimmune diseases |
antigen B is product of secondary response (40-45 days)
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Complement System
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Series of ~ 20 proteins
Activated by microorganisms Will coat the microorganisms Adherence reactions phagocytic cells have receptors for C3 Biological active fragments produce reactive oxygen intermediates Membrane lesions Activate mast cells Inactivated---specific inhibitory proteins if complement doesn’t bind quickly then ecome inactivated Complement marks antigen for explosion and is ever present in the plasma |
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Antibody attaches to bad guy. Complement (a protein) attaches to antibody. C4 complement splits and attaches to bad guy membrane. Other “C” operatives rendezvous at C4 and set up a pore (cell explosive device) on the perimeter boundary of the target. Cell lysis by influx of surrounding water. The whole process is “opsonization’.
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Porforins-they bore a pore in the cell membrane
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fucntions of complement activation?
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1. lysis
2. chemotaxix 3. opsonization |
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An antigen will stimulate both B & T cell production, and the presence of Ts further stimulates Bs specific for more antigens on the bad guy surface
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Killer T’s are destryed by HIV. (all t’s are susceptible to HIV)
bacterial infection=granulocyte response Lymphos are more viral |
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Crude amount of exposure will determine if the infection is clinical or sub-clinical, or fatal, along with the magnitude of the immune response
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With vaccination, we try to present the attenuated (slowed down) version.
The vaccine gets rid of the DNA, but retains the outer structure, per se. The antigen cannot replicate. The release of IG’s after a vaccination cause the HA, etc …… |
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B cells are made in burst cells (bone)
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humoral immunity (secretes antibodies)
memory cells, plasma cells receptors present short LIFE SPAN low in blood 10-15% of lyphocytes transfromed to plasma cells secretes antibodies |
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T’s programmed in Thymus
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cell mediated immunity
cytotoxic, helper cells no surface antibodies long life spam lots in blood and lymph transfromed to activated lymphocytes secretes lymphokines |
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Antigen presenting dendritic cells carry antigen to lymphoid organs for the programming of T cells
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Interaction between helper Ts, Bs and antigen presenting dendritic cells
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T-cells
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Act over a short range
Interact with another cell in body Can kill or signal other cell Only recognize antigen when presented on surface of target cell Interleukin is very effective against viruses……in prostaglandin case Cytotoxic Cells kill infected cells Helper Cells (two types) activate macrophages and B-cells Suppressor Cells regulate activity |
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MHC-molecules
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MHC-I
present foreign peptides to cytotoxic cells MHC-II present foreign peptides to helper cells MHC-I on all cells because cytotoxic cells must act against all cells MHC-II on B cells, macrophages, dendritic, and antigen presenting cells. Have CD4 and CD8 to help binding CD4 helper bind MHC-II CD8 cytotoxic cell bind MHC-I CD8 on cytotoxic t cells CD4 on helper cells Cytotoxic cell recognize viral particles Infected cells are all nucleated cells antigen presenting cells are B-Cells and macrophages Cytotoxic cells focus attack on cells that make foreign antigens (menace) helper t-cells focue help on cells that take up foreign antigens (essential for immune response) |
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Helper T-cells
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Helper T-Cells stimulate macrophages and B-cells
Helper T-Cells recognize foreign antigen bound to MHC-II proteins on surface of antigen-presenting cells Two signals are required for activation of Helper T-Cells |
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Cytotoxic T-cells
Pore forming protein |
Cytotoxic T-Cells recognize viral protein fragments on
surface of infected cells. Cytotoxic T-Cells induce infected cells to kill themselves Bind to infected cells Induce cell death Punch holes in cell membrane |
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Natural Killer
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destroy virus-infected cells
do not express antigen specific receptors cells with low levels of MHC I induce cells to undergo apoptosis |
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Make interleukins
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Helper Ts
Interleukins=cytokines Interleuikin in a product of helper T’s |
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Inflammation
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1. Vasodilation
2. Increased capillary permeability 3. Clotting of interstitial fluid 4. Swelling of tissue 5. Pain Substances involved bradykinin, histamine, serotonin, complement, coagulation factors, lymphokines- interleukins from Helper Ts “Walling off” effect of inflammation 5 cardinal signs of inflammation Color-heat Dolor-pain Tumor-swelling Rubor-redness |
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Cell-mediated Response to Inflammation
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1. Tissue macrophages
already present in tissue 2. Neutrophil invasion margination, diapedesis, chemotaxis stimulation of bone marrow to release stored leukocytes, 4-5 hours 3. Macrophage proliferation invasion by circulating monocytes (several hours to increase size) 4. Stimulation of granulocyte and monocyte production growth factors produced by tissue macrophages: Granulocyte colony stimulating factor GCSF Interleukins IL (several flavors) Monocyte colony stimulating factor MCSF Tumor necrosis factor TNF and many more…. |
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Neutropenia
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Neutropenia: decreased number of neutrophils
Decreased production Increased neutrophil destruction (chronic infections) Agranulocytosis: severe neutropenia due to production failure due to irradiation, exposure to chemicals, drugs, bone marrow failure Decrease production inherited stem cell disorders chemical toxicity Increased destruction infections, immune mechanisms |
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Killer T contacting a cancer cell. It looks for specific cancer cell antigens on the cell surface and….
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Releases lymphokines that destroy the cancer cell
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Allergy
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Hypersensitivity to some antigenic protein
Immediate hyper – abnormal B response – releases high levels of IgE Allergic rhinitis, conjunctivitis, asthma, dermatitis, urticaria, hives. Immediate and treated with antihistamines Delayed – abnormal T cell response Hours to days Treat with cortisone |
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IgE and Histamine Release
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IgE binds to mast cells release histamine and other agents which activae eosinophils.
Histamine help increase premeability, activation of complement |
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allergic reaction
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first B, IgE,
then T and cell mediated |
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autoimmune diseases
sympathetic opthalmia |
UVEA
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autoimmune diseases
hasimoto's |
thryglobulin
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autoimmune diseases
graves |
TSH receptor protiens
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autoimmune diseases
thrombocytopenici purpura |
I, rH and other on RBC surface
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autoimmune diseases
myesthenia Gravis |
ACH receptors
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autoimmune diseases
rhematic fever |
strep
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autoimmune diseases
glomerulonephritis |
strep
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autoimmune diseases
RA |
IgG
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autoimmune diseases
Lupus |
DNA, RNA, nucleprotien
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autoimmune diseases
DM -1 |
beta cells-pancreatic islet
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autoimmune diseases
MS |
myelin shealth components
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HIV?
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Reverse transcriber-go make DNA
More Americans have died from AIDS than died in both World Wars 40 million world wide are infected Aids has a latency period of ~ 8 years Intracellular – so most immune response mechanisms don’t work Virus is specific for killing WBCs particularly T cells Drugs that are effective block reverse transcriptase and block viral particle attachment in the first place |
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Leukemias
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Lymphocytic leukemia – cancerous production of lymphoid cells. In any lymph tissue like nodes or lymphocytic tissue in gut
Myelogenous leukemia – cancerous production of bone marrow stem cells. They circulate anywhere and begin making inappropriate WBCs. Cells usually bizarre and undifferentiated. Common symptoms of both are: infection, anemia, bleeding disorders. Starves out normal cell growth |
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Blood Groups
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Red blood cell surface antigens: glycolipids or glycoproteins
A-B-O System antigens: surface antigens (A,B) genes (A, B, O) inherited (two surface chromosomes OO OA OB AA BB AB also present on all cells in the body antibody in plasma: gamma globulins, anti-A, anti-B, IgM, IgG |
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O
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geno OO
no atigen anti-a, anti B antibodies |
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A
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geno OA or AA
antigen A anti-b antibody |
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B
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geno OB or BB
antigen B anti-a antibody |
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AB
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geno AB
antigen AB no antibodies |
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Hemophillia A (factor 8-ahf)
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recessive on X
delayed formation of fibrin |
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von willibrands (factor 8-vwf)
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dominant train on autosomal
impaired ability of platelets to adhere to collagen in sunendothelial connective tissue |
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hemophilia B (factor 9)
aka x-mas tree disease |
recessive on X
delayed formation of fibrin |
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ASA
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inhibits protaglandin production resulting in a defective platelet release reaction
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coumarin
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inactivates vik K
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heparin
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inhibits activity of thrombin
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citrate
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combines with ca++ and thus inhibits the activity of many clotting factors
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Rhesus System
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antigens on RBCs: 6 rhesus factors (C, D, E, c, d, e)
inherited as triplets CDE, CDe, Cde, CdE, cDE, cDe, cde antigen D =Rhesus positive antibody in plasma: do not occur spontaneously, only after exposure to Rh antigens Rh+ blood into Rh negative person: sensitization to further Rh+ transfusion Treatment If severe transfusions from 26th wek to delivery Prevention administer anti Rh antibodies immediately after delivery, amniocentesis |
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Hemolytic Disease of the Newborn or
Erythroblastosis fetalis |
Fetal blood enters maternal circulation
Rh positive fetus and a Rh negative mother Anti-D antigens form in mother More critical with 2nd Rh positive child Treatment- injection of IgG anti-D into mother after delivery to destroy fetal RBCs in mom O mother and A or B fetus IgG anti-A and anti-B cross placenta very mild effects |
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Transfusion Reaction
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Transfusion reaction due to agglutination of donor blood
Agglutination of red blood cells due to antigen-antibody reaction Activation of complement system Agglutination destroyed by white cells, with hemoglobin released into plasma Shock, chills, fever, shortness of breath, renal shutdown Activation of complement ABO activation is immediate Delayed due to Rh |
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Transplantation
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HLA System ----- surface antigens >100
on all nucleated cells Rejection ---- mainly due to activation of T-cells Suppressive therapy---- inhibit immune response glucocorticoids-- limits movement of granulocytes into tissue and suppresses lymphoid tissue growth azathioprine - inhibits the functioning lymphocytes – toxic to lymph tissue cyclosporine --- inhibits T-cell formation |
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Hemostasis, Coagulation
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1. Vascular Spasm
2. Platelet plug 3. Formation of clot |
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Platelets
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Formed in bone marrow, 150-350,000 /µl
Sequestered in spleen (30%) 2-4 μm in diameter, life span 8-12 days, no nucleus Active cytoplasm adhere to collagen in damaged tissue actin + myosin – able to contract enzyme synthesis + storage of calcium synthesis & release of prostaglandins (Thromboxane A2) dense granules containing ADP and ATP α-granules (fibrinogen, PDGF, vWF, fibronectin) fibrin stabilizing factor |
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Activators of platelets
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Collagen and microfibrillar proteins
ADP released from damaged RBCs and activated platelets Thromboxane from activated platelets Platelet activating factor from basophils Epinephrine (stress) Thrombin |
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Platelets
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Vessel injury or atherosclerotic plaque rupture
subendothelial protein layer exposed platelets bind to subendothelial vWF, and collagen via surface glycoproteins. platelets swell release platelet agonists from granules generate thrombin activation of new platelets crosslinking of platelet aggregate by surface glycoprotein contractile elements pull fibrin threads |
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Platelets
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Leukotrienes (chemoattractants)
Thromboxane (release more granules) Release of thrombospondin (stabilizes platelet-fibrin) Release of PDGF (stimulates smooth muscle proliferation) (platelet dependant growth factor) Release of ADP (attracts more platelets) |
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All cells produce prostaglandins
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Leukotrienes and prostaglandins are autocrine regulators
PGE2 – vasodilation – redness and swelling of inflammation PGF2alpha – bronchiolar constriction TXA2 – produced by platelets – vasoconstriction and platelet aggregation PGI2 (prostacyclin) - produced by endothelial cells- inhibit aggregation and vasodilates vessels |
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Prostaglandins
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Promote most aspects of the inflammatory process – including pain and fever
Big role in repro – ovulation, corpus luteum formation, labor, cramps, bloating.. Produced by stomach and intestinal walls where they inhibit secretion of HCl. High aspirin = peptic ulcers Opposing prostaglandins in bronchiolar smooth MM response Opposing Prostaglandins in circ. System PGE2 causes ductus arteriosus to remain open in the fetus. Prostaglandins in/ from the kidneys cause increased renal blood flow and increased excretiion of water & electrolytes |
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Extrinsic Pathway
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Damaged vascular wall
Release of tissue thromboplastin – Factor III (it’s mostly phospholipids from the damaged cell membrane) VII, X and Ca++ V and Ca++ Prothrombin is II Fibrinogen is I Ca++ is IV |
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Intrinsic Pathway
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Blood cells damaged or in contact with an unusual surface
XII and damaged platelets XI and IX IX, VII, and phospholipids activates X X, V and down through the common pathway |
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factor-1
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fibronogen
converted to fibrin common |
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factor-2
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prothrombin
converted to thrombin common |
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factor-3
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tissue thromboplastin
cofactor extrinsic |
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factor-4
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Ca ions
cofactor common |
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factor-5
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praccerlerin
cofactor common |
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factor-6
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no longer referenced
the same as 5 |
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factor-7
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proconvertin
enzyme extrinsic |
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factor-8
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antihemophillic factor
cofactor intrinsic |
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factor-9
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plasma thromboplastin component (xmass tree factor)
ENZYME INTRINSIC |
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factor-10
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stuart-power factor
enzyme common |
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factor-11
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plasma thromboplastin antecedent
enzyme intrinsic |
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factor-12
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hageman factor
enzyme intrinsic |
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factor-13
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fibrin stabilizing factor
enzyme common |
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Fibrin
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Polymerization catalyzed by Factor XIIIa
XIIIa crosslinks fibronectin Fibronectin promotes in growth fibroblasts XIIIa crosslinks a2-antiplasmin a2-antiplasmin protects from plasmin Clots dissolove because plasmin (digests the fibrin in clots) |
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Conversion of prothrombin into thrombin
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prothrombin (factor II) --- formed in the liver
and requires Vitamin K Split in two thrombin --- proteolytic enzyme a) acts on fibrinogen b) stimulates fibrin stabilizing factor c) acts on prothrombin + clotting factors (positive feedback) |
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Conversion of fibrinogen into fibrin threads
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fibrin is split into fibrin monomers
b) automatic polymerization into long fibrin threads (weak) c.) fibrin stabilization (strong bonds requires Factor XIII) |
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Formation of Prothrombin Activator
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I. Extrinsic pathway
tissue trauma tissue thromboplastin (+VII) X activation Rapid and explosive in nature (15 seconds) II. Intrinsic pathway blood cell trauma, contact with collagen or activated platelets XII XI IX (+VIII) X activation slower (2-6 minutes) many components (cascade) Common pathway Xa combined with V and platelet phospholipids (PF3) + Ca++ prothrombin activator: prothrombin thrombin fibrinogen |
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Intravascular Anticoagulants
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I. Endothelial Cells – negatively charged
smooth surface + glycocalyx II. Antithrombin action of FIBRIN (absorbs thrombin) and keeps the clot local III. Antithrombin III (alpha-globulin, combines with heparin) in circulation. Antithrombin deactivates thrombin IV. Heparin: conjugated polysaccharide, negative charge little action unless combined with antithrombin III Increases effect of antithrombin |
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Fibrinolytic System
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Plasminogen = circulating globulin
Plasmin = proteolytic enzyme, similar to trypsin digest fibrin threads, fibrinogen, and other clotting factors Significance: removal of tiny little clots Plasminogen activators: Tissue Plasminogen Activator (TPA), urokinase, streptokinase released from damaged tissue after a few days converts plasminogen into plasmin after the clot has resolved begins to break down fibrin |
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Coagulation Defects
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I. Vitamin C deficiency
lack of stable collagen (elderly, alcoholics) II. Hepatic failure almost all clotting factors are made in the liver III. Vitamin K deficiency required for II (prothrombin), VII, IX, and X production fat malabsorption - and along with it, fat soluble Vit. K IV. Hemophilia Factor VIII (hemophilia A 1/10,000), 85% of cases Factor IX (hemophilia B 1/100,000) chromosome X V. Thrombocytopenia – lack of platelets usu. below 50,000/ul bleeding small capillaries and blood vessels mucosal, skin low number of platelets ITP- autoimmune (common) - idiopathic thrombocytopenia VI. Disseminated Intravascular Clotting - DIC abnormal bleeding and clot formation critically ill patients coagulation and clot lysis in uncontrolled manner due to massive tissue damage & depletion of clotting factors |
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Defective Coagulation
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Thromboembolic conditions
clots from: 1. roughened vasc surfaces or 2. slow moving blood - stasis venous thrombosis, pulmonary embolism (rt) clots in the arts (lft) to brain, kidneys artificial heart valves, by-pass surgery long-term bed immobilization |
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Treatment for coag
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HEPARIN — immediate anticoagulation
Lasts 1.5 – 4 hours COUMARINS — compete with Vitamin K, 2-4 days to act Blocks formation of VII, IX and X reverse with Vitamin K |
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Collection tube anticoagulation
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SILICONIZE the tube
HEPARIN - promotes anti thrombin in the blood used in hemodialysis heart-lung machine CALCIUM CHELATORS “bind” calcium which is required for clotting oxalates - chelate Ca++ out of blood citrates – deionize Ca++ - so it no longer works in the cascade |
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Blood Coagulation Tests
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Platelet count
150,000-300,000/ µl is normal thrombocytopenia - aplastic anemia, autoimmune platelet function - myeloproliferative, uremia, drugs (aspirin, antibiotics), von Willebrand Disease Bleeding Time time for skin wound to stop bleeding |