Pathophysiology of the Hematopoietic System PDF

CHAPTER 11 : Hematopoietic System coat (leuk-plates) ( < 1 % ) blood components > plasm...

CHAPTER 11 : Hematopoietic System coat (leuk-plates) ( < 1 % ) blood components > plasma (55 % ) buffy erythrocytes (48 %) - , , 9) bone marrow makes all the blood cells erythrocytes (RBC's) transport = O2 via hemoglobin leukocytes (WBC's) = inflammation + immunity thrombocytes= platelets clotting , the complete blood count (CBC) : provides info regarding the # of blood cells + their structural - functional characteristic it tells you : , WBC differentiation count +% of all WBC -> - types RBC > MCV (mean corpuscular volume) = indicates size hemoglobin (hbg) + MCH) mean corpuscular hemoglobin) amt in each RBC hematocrit (het) platelets+ MPV (mean platelet volume) = indicates size red blood Cells (RBC'slerythrocytes) : maturation= the period from stem cell in circulation - reticulocyte = about 1 week reticulocyte > - mature erythrocyte = 24-48 hrs : mature lifespan = 120 days -> end of life - spleen hbg erythropoietin hormone secreted the their maturation by Kidneys stimulates bone marrow to make RBC's = + , differentiation. + proliferation conditions that trigger erythropolitin production > hemorrhage ↑ altitude > - , anemia. COPD. + iron + hemoglobin hbg-protein = in RBCs that carries O2 to organs(tissues , the rate at which hbg is synth depends. on iron availability , lack of iron - low amts Of. hbg in RBC's body stores iron as feratin (serum ferritin levels) : iron deficiency anemia - take iron supplements there are 4 hemoglobin molecules on RBC + in the center of each one = iron every spOz ( measures amt O2 bound to. hemoglobin) spleen breaks & old RBC's > - degradation products = iron + amino acids -> recycled E the home molecule - bilirubin + transported - liver + get rid of it in bile bilirubin : insoluble in plasma t attaches to plasma proteins for transport (unconjugated) removed from blood by liver + conjugated wh glucuronide to be H20 soluble ( conjugated + jaundice) excess bilirubin = underlying liver / galbladder : adult jaundices 20. · normal =.O 2 thrombocytes (platelets) = function to form platelet plug to control bleeding , 8-9 days in circulation anemia = abnormally low # of circulating RBC's or hbg levels or problems wh the size of RBC's results in diminished Oxygen carrying capacity , caused by : excessive loss destruction of RBC's or deficient RBC production blc of a lack of nutritional elements or bone marrow failure < symptoms fatigue low 4 rate shortness of breath headaches dizziness : + energy. , , , types of anemias : Vitamin C ! hbg synth blo low iron (norm : 14-16) iron deficiency anemia : most common d Hbg F : 12-14 M dark stools = : ,. megaloblastic anemias : cobalamin def (B1). + folic acid def anemias. aplastic anemia : rare but sus blood disorder when marrow can't make enough blood cells + platelets ↑ risk of infection) issues/ bleeding issues , stem cell transplantation = only cure : 4 expos to chemicals. EGPD deficiency hereditary deficiency = of glucose-6-phosphate dehydrogenase > oxidative denaturation - of hbg+ red blood cell injury + lysis; happens after exposure to oxidative drugs (aspirin sulfonamides , &ava beans , or infection > - RBC pop sickle cell anemia = inherited disorder where an abnormal Hbg chronic hemolysis pain , organ failure , thalassemias = group of inherited disorders of Hbg synth - decreased synth. of a or B-globin HbA chains Vitamin B12) cobalamin deficiency - caused by lack of B12 in the diet , hard to absorb orally - IM intra dose oral supplements ordered loss nasal sprays or very ↑ : can cause neuro symptoms like memory intrinsic factor (IF) made by stomach parietal cells - transport t help absorb vitamin B12 pernicious autoimmune condition that occurs when the immune attacks stomach anemia = system parietal cells that make If -> can't absorb vitamin BR2 folic acid (Bal deficiency anemia-caused by dietary deficiency (usually absorption issues) , seen wh chronic alcoholics blc alcohol supresses folate absorption : pregnant women need to take 0 4. my folic acid daily to prevent neural tube defects Polycythemia vera = too many RBC's. RBC mass is increased + hematocrit > 54 % men + >47 % women causes : loss of vascular fluid (hemoconcentration) + hypoxia (d 02) like chronic long disease too many RBC's - risk of clump t form thrombus more RBC's + increased blood volume to compensate for low oxygen splenomegaly depletion of, iron , hypertension. I cerebral blood flow venous stasis , , thromboembolism transfusion therapy provides - replacement RBCs + other blood components (whole blood not done too often) packed RBCs (most common) platelets fresh frozen plasma. , (clotting factors) , cyroprecipitate ( super form of plasmal 4 ABO blood are determined the presence absence of 2 RBC A and B major types by or antigens : the presence of a Dantigen determines the Rh + type , absence : Rh-type 5 stages of hemostasis (stopping bleeding) : 1.. vessel spasm 2. ) formation of the platelet plug. ) blood 3 coagulation) development of an insoluble fibrin clot 4) clot retraction 5) clot dissolution thrombosis = the inappropriate formation of clots within the vascular system bleeding : failure of blood to clot in response to appropriate stimulus requirements for blood clotting : presence of platelets produced in the bone marrow + platelet activation von Willebrand factor (vWfl = not a clotting factor , located in the blood vessel walls that aids in activating clotting factors clotting factors (1-12) synthesized in the liver extrinsic (outside the vessell + intrinsic (inside the vessel) come together to form common pathway plasminogen (enzyme) in clot + waits to break t clot needs to be activated by tissue plasminogen activator aka. pa Slow release of +pa from injured tissue converts plasminogen - plasmin which digests fibrin give +pa-stroke patients d dimer = protein released when clot breaks↓ can test for it in blood , nonspecific test that if there has been to breakd says a clot starting somewhere in the body hypercoagulable states : increased risk of developing clots in arterial or venous circulations arterial thrombi- conditions that produce turbulent blood flow + platelet adherance venous thrombi- conditions that cause stasis of blood flow wI4 #s of coagulation factors conditions that cause I venous thrombi risk : DVT-Rside of heart > - PE pregnancy (lots of pressure + pooling in lower extremities) use of oval contraceptives post-surgical state immobility malignant diseases (cancer conditions that cause I arterial thrombi risk : is chemic stroke or MI Atherosclerosis diabetes mellitus smoking ↑ blood lipid + cholesterol levels ↑ platelet levels (lifestyle ways) plaque built up + platelets stick to it virchows triad : 3 things that significantly increase risks of clots forming hypercoagubility vascular damage circulatory stasis platelet defects : norm = 150 000 300 000 - , , impaired platelet function thrombocytopenia : results from ad platelet prod increased sequestration of platelets in spleen. Or decreased platelet survival 3 types of thrombocytopenia drug induced idiopathic : , and thrombotic thrombocytopenic purpura ' bleeding : from small vessels in nose mouth EI tract, uterine , , cavity & petechiae pinpoint purplish : red spots (almost exclusive to platelet deficiency) usually on upper trunk-neck > purpura : purple areas of bruising , more blobby + bruised looking immune thrombocytopenic purpura (ITP) platelet antibody formation destruction of platelets , autoimmune : + in nature. causes : bleeding gums , epistaxis (nosebleeds). bruising , + petechiae : severe thrombocytopenia - 20 , 000 without a cause , treatment > - high dose steroids or IVIG (intravenous immunoglobulin) heparin-induced thrombocytopenia (HIT) : 10 % of ppl treated wh heparin develop thrombocytopenia within 5 days 1% 5 % of ppl develop life-threatening thromboembolic events (weeks after the -. initial start of heparin blo of an immune uxn : platelets drop by 50 % - must stop heparin Vitamink = essential cofactor for activation of clotting factors fat soluble , , synthesized by GI bacteria necessary for activating many of the 12 clotting factors , liver makes clotting factors but needs vitamink to activate : Vitamin 1) deficiency > lots of inactivated clot. factors - abnormal bleeding - coagulation disorders can be caused by : defective synthesis , inherited disease or a , consumption clot factors. von Wildebrand disease : most common hereditary bleeding disorder deficiency in vWf I not a clotting factor protein made by vessel endothelium to assist factors , causes : spontaneous bleeding prolonged bleeding time + disseminated intravascular coagulation (DIC) : abnormal bleeding clotting + at the same time very serious disorder where the cascade overturned itself is usually caused by something else + (pregnancy retained placental fragments) big clots form in blood t use all the clotting factors so then bleeding in other places conditions associated wI DIC : obstetric conditions , cancers. Infections/sepsis) , shock , traumalsurgery hematologic , conditions treatment : figure out underlying cause while also providing clotting factors +anticoagulants > heparin. Fresh frozen plasma platelets , , cryoprecipitate thrombus = clot embolus = clot that has travelled somewhere , DVTIVTE-embolus in leg vein , pulmonary emboli = embolus in pulmonary circulation M1 embolus in Coronary artery stroke)CVA-embolus obstructs brain vessel = , , CHAPTER 9 : Drug Therapy for Coagulation Disorders family of anticoagulants : 4 classes - blood thinners heparins Vitamin K antagonist direct thrombin inhibitors factor Xa inhibitors anticoagulants : Do NOT dissolve existing clots , given to prevent new clot formation , given for prevention of thromboembolic disorders or management , main adverse effect - bleeding heparin-high alert medication , requires double sign off for IV - can be life-threatening if X dose we use lab values to measure how long blood takes to clot - partial thromboplastin time (PTT) normal PTT = 25-35 sees. , want heparin pt. to be = 45-70 secs (1 Xs control value) , PTT only done for I not SQ. PTT drawn every 6 hus , another test : anti-Xa- shows effectiveness of heparin antidote = protamine sulfate low molecular weight heparin enoxaparin (LMWH) : synthetic heparin , inactivates clotting factor Xa via antithrombin , SQ injection wh prefilled syringe wh bubble (leave the bubble + inject) always has to go in the abdomen (no PTT blo SQ) prevents + manages DVT + PE - antidote : protamine sulfate warfarin : effectiveness measured by prothrombin time (PT) and international normalized ratio (INR) Show blood can clot) normal INR (if dr too thin) quickly = I , warfarin pt INR. = goal is 2-3 > 3- notify. antidote : Vitamin 1 (K-Central , have to get INR labs weekly until therapeutic INR- once a month remember - Im not ready (INR) to go to war (warfarin) for 2-3 yrs (therapeutic range) direct thrombin inhibitors = no lab monitoring direct Xa inhibitors = replacing warfarin blo d risk no labs , , cheaper clotting cascade sequence : Xa > - prothrombin - thrombin - fibrinogent fibrin class : antiplatelet agents inhibit platelet activation + adhesion + aggregation (sticking to each other) 2 classes : App receptor antagonists+ thromboxane Az inhibitors thrombolytic drugs erythropoeisis stimulating agents granulocyte colony stimulating agents #APTER 35 : Vitamins Affecting the Hematological System Vitamin K : blood clotting , activates precursor proteins in the liver - clotting factors deficiency in vitamin 1 abnormal bleeding vitamin K green leafy vegetables = = , only give to warfarin pts. as antidote Vitamin Biz : cobalamin essential for normal metabolism of all body cells RBCs nerve cells. , , growth t metab. of carbs , protein , fats deficiency -> pernicious anemia thrombocytopenia , dysrhythmias. , + neuro symptoms in meat , eggs , fish , cheese B12 injections to treat pernicious anemia blo they can't absorb it Vitamin Ba : folic acid folic acid/folate = a B complex vitamin essential for normal metabolism of all cells RBCs. , + growth deficiency > megaloblastic anemia children impaired growth , a glossitis - , in liver. Kidney beans fresh , green vegetables , fortified grain products can buy OTC supplement Vitamin C : ascorbic acid essential for formation of skin , ligaments cartilage ,. Done , + teeth required for wound healing. metabolism of iron + folic acid , preservation of blood vessel integrity deficiency -> irritability. malaise 4. tendency to bleed , scurry , disturbances of bone growth, death. of teeth coma , loosening in fruits + veggies - citrus improves the absorption of iron iron supplementation ferrous sulfate : Po tablet or liquid form , doesn't matter what time to take it , take wh meal if GI upset in red meat liver fish dried peas lentils beans fortified cereals + breads , , , poultry , , , , can cause : constipation , dark green black stool take wl citrus or orange juice + drink thru a straw to avoid stained teeth a cute iron overdose -> result of too many multivitamins antidote : deferoxamine (Desferal) = removes excess ferritin + combines it to be water soluble so it can be excreted from the Kidneys CHAPTER 12 : Immunizations immunity : the body's ability to defend against pathogens t foreign substances that cause disease > innate (natural) = the natural resistance with which a person is born with kicks in , immediately > adaptive immunity : the 2nd line of defense , responding less rapidly but more effectively 96 his after Central lymphoid organs : bone marrow -> makes all the blood cells (RBCs WBCs ,. platelets T cells mature in the B cells mature in the bone marrow thymus. spleen - can live who it but isn't ideal important to immune function. makes , lymphocytes , Stores RBCs + platelets + filters blood If spleen removed - have to give a ton of vaccines to help build up immunity peripheral lymphoid organs : lymph nodes : where T + B cells hangout after they mature + wait for something to happen cells of the immune system : < innate immunity (1st line of defense granulocytes = neutrophils basophils eosinophils (allergic , , rxns + parasitic infections) macrophages , dendritic cells , natural Killer (NK) cells , mast cells s adaptive immunity (what we acquire) lymphocytes = T Cells + B cells all immune cells made from bone marrow - stem cells > - differentiate into myeloid or lymphoid > myeloid innate immunity RBC's platelets : , , < lymphoid adaptive immunity =. NK cells , B cells T cells , humoral immunity = Blymphocytes produces antigen-specific , antibodies (if you humorous you B funny) cell-mediated immunity = T lymphocytes , no memory - no antigen-antibody response : CD4 Cells + CDs cells CD4 cells affected by HIV (type of T cell) Blymphocytes (B cells) = following an immune response B cells differentiate into : Plasma cells : ones that make antibodies (immunoglobulins) > memory B cells : do rapid + enhanced response the 2nd time around , 1st time they sit back t observe 5 kinds of plasma B cells (immunoglobulins) : GAMED IgG ( titer antibodies , mom-baby) IgA , (colostrum) , IgM (active infection). IgE , IgD 4) types of T cells : CD8 (cytotoxic) CD4(helper) memory T , , cells , regulatory or TREGS innate immunity : how the body protects itself from birth physical barriers : skin wl bacteria that live there chemical barriers : put of stomach cellular defenses : cilia in upper respiratory tract adaptive immunity : active or passive active can get immunity by vaccination or getting the disease making antibodies t memory B cells : + passive passing immunity who their body doing any work baby (encourage moms to get : , mome Vaccines in utero-breastfeed during cold season) , artificial immunity giving immunoglobulins : to a particular disease ex. ) rogam and rabies : doesn't last forever blo body didn't make it itself the complement system : ennances (complements) the ability of antibodies + phagocytic cells to clear microbes + damaged Cells from an organism promote , inflammation , I attack the pathogen's cell membranes attracts more macrophages + phagocytic cells to site of infection (innate adaptivel + antigens foreign : substances that stimulate an immune response antibodies : recognize antigens (receptors on immune cells + secreted proteins) types of antigens - bacteria , fungi , viruses protozoa ,. parasites , nonmicrobial agents major histocombatibility complex molecules (MHC) = antigens present on all body cells that label it "me" > in humans : human leukocyte antigens (HLA) if there is a problem wl HLA- autoimmune disorders ↑ cells cannot recognize antigens - they need to be presented wh the antigen antigen-presenting cells : macrophages + dendritic cells , present to CD4 helper T cells 7 goes over to T cells -> look this isn't supposed to be here > - T cells take over + kill the right ones otherwise T cells would kill all of our cells fetus : develops an immune system at 5-6 wKs , secondary lymphoid organs well developed at birth (lymph nodes , spleen tonsils) ,. IgA IgM shortly after + birth , reach adult levels by tyr of age elderly : n ability to adapt to environmental stresses , thymus atrophies so decreased # of T cells blc they can't mature , everything slows down + doesn't react as fast anymore hypersensitivity disorders : "ACID" type I IgE mediated allergic type Il cytotoxic antibody-mediated type III IgGlIgM : mediated : : , , type IV delayed or cell mediated : type 1 : allergic cause : IgE antibodies bind to mast cells + basophilse release histamine + other inflammatory mediators ex. ) anaphylaxis , asthma , urticara (hives). food allergies allergic , rhinitus (hay fever) type 11 : cytotoxic cause : antibodies bind to antigens on cell surfaces leading to cell destruction ex. ) autoimmune hemolytic anemia , transfusion uxns , drug rxns type 111 : immune complex cause : antigen-antibody complexes form deposit in tissues -> inflammation - ex. ) serum sickness , glomerulonephritis type IV : delayed cause : T cells + macrophages are activated - delayed immune response ex. ) contact dermatitis , Pneumonitis vaccines = microorganisms that have been killed I weakened (attenuated) , given by exposure to the pathogen , live vaccines can rarely produce disease in some ppl don't pregnant ppl wl active malignant disease HIV I dose steroids give live vaccines to : women , , , systemic common live vaccines : influenza nasal mist varicella , , measles mumps rubella (MMR) common (not live) = influenza IM , hemophilus influenzae type B (HiBl , hep A + B meningococcal , toxoids = bacterial toxins , immunity not permanent require boosters , > ex. ) diphtheria , tetanus , acellular pertussis (DTaP) immunoglobulins (IG) = made from serum of ppl wh high concentrations of the specific antibody required > BBW : increased risk of thrombosis > hep B , rabies , cho-gham , varicella-zoster IVIE. intravenous immunoglobulin E CIVIC) = pooled antibody made from donated plasmat blood , treats : autoimmune diseases + systemic lupus erythematosus (SLE + Vasculitis inflammatory - infectious conditions , immunodeficiency states , < goal : normalize compromised immune system vaccines adverse effects : soreness , erythema pain , at injection site , low grade fever malaise , CHAPTER 13 + 14 : Drug Therapy to Decrease Immunity + for Cancer Treatment indications : autoimmune disorders > Ulcerative colitis - , Crohn's disease , rheumatoid arthritis , psoriasis organ transplantation prevention of rejection immunosuppressive agents after organ transplant : > cytotoxic immunosuppressants : prototype-mycophenolate mofetil (cell-cept) , also methotrexate used for prophylaxis of organ rejection after cardiac , hepatic Kidney transplant , , cancer chemotherapy damage or kill dividing cells : conventional antirejection agents fungal : metabolites that inhibit T cells cyclosporine (BBW : HiN + nephrotoxicity) , sirolimus tacrolimus , adjuvant meds to suppress immune function : > corticosteroids : potent anti-inflammatory agents that suppress the immune response > monoclonal antibodies "imab + umab" : originate from a single B cell source , suppress specific components of the immune system that cause tissue damage in particular disorders lab produced proteins that mimic the immune system's ability to fight off diseases "Umab" - fully human monodonal antibodies , "mab" - chimeric , human animal Jusually mouse transplant pts. need to take immunosuppressants for life > include : antirejection meds , monoclonal antibodies , + corticosteroids all immunosuppressants greatly I risk of infection + other serious illnesses like cancer antineoplastic drugs (anti-cancer) : damage) kill cancer cells (cytotoxic to cure cause remission , , or Palliation of symptoms , sometimes used for non-malignant conditions classes of cytotoxic drugs : alkylating agents - cyclophosphamide (Cytoxan) " > antimetabolites -> methotrexate = plant alkaloids > vincristine - > antibiotics -> bleomycin biologic antineoplastic drugs : > monoclonal antibodies = specific to that type of cancer. less adverse effects than cytotoxic drugs growth factor inhibitors factor these meds block these receptors growth receptors on CA cell mems. , > = = hormone inhibitors = block production of tumors that use estrogens + androgens to grow-tamoxifen for breast cancer chemotherapeutic agents cause : suppresses the immune system Unable to differentiate btwn "normal" Cells + CA cells - alopecia thrombocytopenia neutropenia myelosupp. , , , GI effects > nausea - , vomiting , diharrea , anorexia mucositisl stomatitis fatigue administering chemotherapeutic agents : do not administer if > - WBC < 2 000 , , Neutrophils 1500. Platelets < 50 000 , use a large vein) portl catheter to avoid extravasation (med in surrounding tissue not bloodstream avoid direct contact wh solutions for injection + when handling pt. room (wear : gloves , face shield , gown dispose of contaminated materials in biohazard containers