patho study guide 2.docx

Hematology Hematopoiesis: process of blood cell production in adult bone marrow or in the liver/spleen of a fetus Bone marrow: also called myeloid tissue Stages include mitosis (proliferation) and maturation (differentiation) Factors that increase hematopoiesis Conversion of yellow bone marrow to re...

Hematology Hematopoiesis: process of blood cell production in adult bone marrow or in the liver/spleen of a fetus Bone marrow: also called myeloid tissue Stages include mitosis (proliferation) and maturation (differentiation) Factors that increase hematopoiesis Conversion of yellow bone marrow to red bone marrow by actions of erythropoietin Faster differentiation of progenitor cells Faster proliferation of stem cells into progenitor cells Erythropoiesis: development of red blood cells Maturation stimulated by erythropoietin which is excreted by the kidneys Erythropoietin: hormone released from the kidneys in response to low renal oxygenation Always present in the plasma Iron cycle Ferritin: major iron storage protein Apoferritin: ferritin without attached iron Transferrin: iron bound to apotransferrin and transports iron in the blood Transfers iron in circulation Iron for hemoglobin production is carried by transferrin to the bone marrow where it binds to transferrin receptors on erythroblasts TIBC: measure of available transferrin that is left unbound to iron Low transferrin that is actually saturated with iron = high TIBC = more capacity to bind Calcium is needed to activate clotting factors (factor 4) Blood clot sequence of events Injury induces formation of prothrombin activator Prothrombin activator changes prothrombin to thrombin Thrombin changes fibrinogen to fibrin Clot retraction Granulocytes: phagocytes Neutrophils, basophils, and eosinophils Mast cells Agranulocytes Monocytes and macrophages Lymphocytes Synthesis of blood clot Activation of prothrombin activator Prothrombin to be concerted to thrombin (need calcium) Thrombin converts fibrinogen to fibrin Control of clotting Fibrin in clot absorbs excess thrombin Antithrombin III inactivates excess thrombin Heparin: produced by mast cells and basophils Anemia classifications Etiologic factor or cause Size (-cytic) Hemoglobin content (-chromic) Microcytic hypochromic anemias: RBCs that are abnormally small and contain reduced amounts of hemoglobin Iron-deficiency anemia (IDA) Physiologic cause: menstruation or pregnancy For men or postmenopausal women: good indicator of malignancy Patho cause: GI bleed Ferritin LOW = saturated transferrin = HIGH TIBC Low reticulocyte count – initially Sideroblastic anemia: caused by defect in mitochondrial heme synthesis Altered mitochondrial metabolism causes ineffective iron uptake and results in dysfunctional hemoglobin synthesis Ringed sideroblasts in bone marrow to diagnosis Transferrin is HIGH so TIBC is LOW Thalassemia: abnormal formation of hemoglobin Mutation that causes loss or one or both of alpha globin chains or one or both beta globin chains Improper O2 transport or destruction of RBCs Diagnostic test is hemoglobin electrophoresis “target cells” may be seen Macrocytic normochromic anemias: DNA synthesis is defective due to deficiencies in vitamin B12 or folate Vitamin B12 is necessary in the formation of blood Involved in metabolism of every cell (especially DNA) Diagnostic: blood smear will show hypersegmented neutrophils Pernicious anemia: caused by B12 deficiency Lacks intrinsic factor from the gastric parietal cells which are required for B12 absorption May be congenital or autoimmune disorder related Neuro symptoms are likely to be present (paresthesia) Folate deficiency anemia Essential vitamin for RNA and DNA synthesis Manifestations: severe cheilosis, stomatitis, dysphagia (no neuro symptoms) Abnormally low serum folic acid Alcohol induced: macrocytic, megaloblastic Normocytic anemia: RBCs that are normal in size and hemoglobin content but insufficient in number Aplastic anemia Patho: hypocellular bone marrow that has been replaced with fat From autoimmune disease Pancytopenia: loss of all blood cells Posthemorrhagic anemia: acute blood loss Hemolytic anemia: accelerated destruction of RBCs Congenital vs acquired Intrinsic: in the cell Extrinsic: trauma, infection, drugs Autoimmune hemolytic anemia: based on the optimal temperature at which the antibody bind to the erythrocytes Drug induced hemolytic anemia: allergic reaction against foreign antigens Ex. Penicillin’s or cephalosporins G6PD deficiency: inability to produce NADPH in the pentose pathway Lack of NADPH leads to the cell anti-oxidant protection Hemolysis only with oxidative stress (infection or drug exposure) Normal between episodes: no exposure to triggers Diagnotisic: G6PD assay May be low but misleading at or directly after episode when the enzyme deficient group of cells has been removed Sickle cell anemia Homozygous for mutation: HbSS Heterozygous for mutation: HbAS HgBS is unstable and when exposed to acidosis or oxidative stress the cell sickles (permenant) Diagnostic: blood smear Will see sickled cells, target cells, and Howell-Jolly bodies Dx. Confirmed with hemoglobin electrophoresis Myeloproliferative RBC disorders Polycythemia: overproduction of RBCs RBC production occurs in the bone marrow under the stimulation of erythropoietin Polycythemia vera: overproduction of RBCs and increased WBCs and platelets Patho: acquired mutation in Janus Kinase 2 (JAK2) If RBCs are high: negative feedback on EPO which makes EPO level low in polycythemia Secondary polycythemia: elevated EPO Can occur as a normal response to needing more RBCs or from an overproduction (ex. Tumor) Clotting disorders Excessive bleeding: hypocoagulable state Platelets and coag factors are low = low ability to form a clot If platelets problems = PPP = petechiae, platelet dysfunction, low platelets Platelets are synthesized in the liver so need vitamin K Excessive clotting: hypercoagulable state Von Willebrand: decrease in or absence of VWF Decrease in ability of platelets to bind to vessel walls ITP: igG antibody that targets platelet glycoproteins Common in children after a viral infection TTP: platelets aggregate form microthrombi cause occlusion of arterioles and capillaries DIC: clotting and hemorrhage simultaneously occurs Factor V Leiden: autosomal dominant and is the mutation of factor V Causes factor V to be unable to be inactivated by protein C Clotting is encouraged Excessive clotting is almost always restricted to veins Protein C deficiency: loss of normal cleaving of factors Va and villa Protein S deficiency: leads to impaired function/activity of protein S and decreased degradation of these factors Increased risk of venous thrombosis Vitamin K dependent anticoagulant Hemophilia: X-linked genetic disease that leads to clotting factor deficiency A: deficiency of factor VIII B: deficiency of factor IX Immune B cells: produced in the bone marrow and migrate to lymph nodes Production, proliferation, and differentiation in bone marrow T cells: lymphocytes develop into mature T cells in the thymus Both T cells and B cells are immunocompetent before they have “seen” an antigen on the surface of an antigen presenting cell Granulocytes Neutrophils: defend against infection Serve as phagocytes in early inflammation Eosinophils: ingest antigen-antibody complexes and viruses Release cytokines and leukotrienes that augment the inflammatory response Increase in type 1 hypersensitivity allergic reactions and asthma Basophils: contain histamine Agranulocytes Lymphocytes Major cells of the immune system Are mature T, B, and plasma cells Natural killer cells: killer tumor cells and virally infected cells Found in peripheral blood and spleen Do not have to be induced by antigens Monocytes and macrophages: make up the mononuclear phagocyte system (MPS) Found in the tissue and lymphoid organ Provide the main line of defense against bacteria in the bloodstream Monocytes are the precursor to macrophages and dendritic cells Dendritic cells: are the “antigen processing” and “antigen presenting” cells that initiate immune response Antigens Antigenic determinant (epitope): precise recognition portion Antigenic binding site (paratope): matching portion Molecular size Haptens: antigens too small to induce immune response or with larger molecule that functions as carrier Innate immune system (1st line of defense) Physical barriers: skin, linings of GI tract, GU, and resp. tracts Mechanical cleansing: coughing, sneezing, vomiting, urination, sloughing off of cells Biochemical barriers: saliva, tears, earwax, sweat, and mucus Normal bacteria flora: spectrum of bacteria that covers many of the bodies surfaces Inflammation (2nd line of defense) Cardinal signs: redness, heat, swelling, pain, loss of function Neutrophils: predominate in early inflammation Monocytes and macrophages: predominate phagocyte in late inflammatory response Plasma protein synthesis: provides a biochemical barrier against invading pathogens Complement system, coagulation system, and Kinin system Interactions among all three are finely regulate to prevent injury to the host tissue and guarantee activation when needed Cellular mediators of inflammation Tissue close to the vessel contain mast cells Mast cells are the most important activator of inflammation Dendritic cells in the tissues Connect the innate and adaptive immune responses Biochemical Vascular changes (ex. Histamine) Interleukins: enhancement of acquired immune response Interferons: protect against viral infections by preventing them from infecting healthy cells Chemokines: attract leukocytes to site of inflammation Adaptive immune system (3rd line of defense) Lymphocytes (T and B cells) T: responsible for cell-mediated immunity B: responsible for humoral immunity that is mediated by circulating antibodies Immunoglobins: antibiodies, produced by plasma cells IgA: defends against pathogens on body surfaces IgD: located primarily on the surface of developing B lymphocytes IgE: mediator of many common allergic responses Defendor against parasites IgG: accounts for most of the protective activity against infections IgM: first antibody produced during the primary response to an antigen Primary response: primer of the individuals immune system IgM then IgG Secondary response: larger amounts of antibody are produced Rapidity is caused by the presence of memory cells that do not have to differentiate If more IgM present that they HAVE it If more IgG present than they HAD it Clonal diversity: antigen recognition Clonal selection: antigen processing and presentation Initiated when T and B cells interact with an antigen Antigen presentation MHC1: present foreign antigens to cytotoxic T cells (CD8) MHC2: present foreign antigens to T helper cells (CD4) Clinical presentation of infection Incubation: period from exposure to onset of symptoms Prodromal: mild symptoms Invasion: affects other tissues Convalescence: symptoms can decline or death if fatal Bacterial infections Exotoxins: enzymes released during growth Damage cell membranes and inhibit cell growth Endotoxins: contained in cell wall gram-negative bacteria and released during lysis of bacteria Stress Alarm stage: stressor triggers hypothalamic pituitary adrenal axis (HPA) which activates the sympathetic nervous system Resistance stage: beings with actions of adrenal hormones Ex. Cortisol, epinephrine, and norepinephrine Exhaustion stage: occurs if stress continues and resistance is not successful Inappropriate immune responses Autoimmunity: misdirected response against the hosts own cells Breakdown of tolerance during which the body’s immune system begins to recognize self antigens as foreign Alloimmunity: directed against beneficial foreign tissues (transplants or transfusions) Rh system: primarily expressed on erythrocytes + express the D antigen on the RhD protein - does not express the D antigen Rh negative gives birth to Rh positive: hyperbilli anemia (babys red blood cells are attacked by mother) Type 1 hypersensitivity IgE mediated Against environmental allergens IgE binds to crystialline fragment receptors on the surface of mast cells; cross linking causes the release of histamine from mast cell degranulation H1 and H2 receptors Manifestations from H1 Bronchial constriction Edema Vasodilation Manifestations from H2 Increase gastric secretions Decrease in the release of histamine from mast cells and basophils Type 2 hypersensitivity Tissue specific Mediated by IgG and IgM Ex. Graves disease Ex. Rheumatic fever: occurs after a group A beta strep throat infection Type 3 hypersensitivity Immune (antigen-antibody) complex mediated Bound in circulation and later deposited in vessel walls or extravascular occurs Not organ specific Clearance Large = macrophages Small = renal clearance Intermediate = deposited in tissues – cause problems Ex. Serum sickness (Raynauds) or arthus reaction Type 4 hypersensitivity Mediated by T lymphocytes (cell mediated) Destruction of the tissue is caused by direct killing by toxins from cytoxic T cells Ex. MS, TB skin test, DM1, Hashimoto, crohns Lupus: chronic multisystem inflammatory disease Type 3 hypersensitivity Common in females, blacks, and ages 20-40 Manifestations: arthritis, renal disease, rash, CV disease, anemia 11 findings are common, only need 4 findings for diagnosis Transfusion reaction: alloimmune and type 2 reaction ABO system: two major carb antigens (A and B) O: universal donor AB: universal recipient Antibodies are of the IgM class Graft rejection Need to match the human leukocyte antigen (HLA) DR locus is the most critical for graft/transplant acceptance Acute: cell mediated response against unmatched HLA antigens (type 4) Chronic: due to weak cell-mediated reaction against minor HLA antigens Leads to organ failure