Exam #2 Study Guide (1).docx

MODULE 3 Hematology Understand basic physiology of hematopoiesis, erythropoiesis, and what erythropoietin is and what it does. Hematopoiesis: Process of blood cell production in adult bone marrow or in the liver and/or spleen of the fetus. Two stages of hematopoiesis: mitosis (proliferation)—the cel...

MODULE 3 Hematology Understand basic physiology of hematopoiesis, erythropoiesis, and what erythropoietin is and what it does. Hematopoiesis: Process of blood cell production in adult bone marrow or in the liver and/or spleen of the fetus. Two stages of hematopoiesis: mitosis (proliferation)—the cells beginning to divide maturation (differentiation)—mature hematological cells Bone marrow (aka myeloid tissue)-in cavity of bones (pelvic bones, vertebrae, cranium/mandible, sternum, ribs, humerus, femur). Primary site of residence of hematopoietic stem cells. Red bone marrow—produces RBCs Yellow bone marrow—does not produce RBCs Increasing hematopoiesis: Erythropoietin converts yellow marrow to hematopoietic red marrow. Faster differentiation of progenitor cells. Faster proliferation of stem cells into progenitor cells. Erythropoiesis: Development of RBCs. Erythrocytes derived from erythroblasts, maturation by erythropoietin. Blast=committed to becoming that cell line. Erythropoietin. Reticulocytes: Last mature form of erythroblast. Contains polyribosomes (-globin synthesis) and mitochondria (-heme synthesis). Reticulocyte count indicates whether new RBCs being produced. Good indicator of erythropoiesis. Erythropoietin: Hormone secreted by kidney in peritubular interstitial cells (and a little from liver). Kidney senses decreased delivery of O2 = stim of erythropoietin. Stimulates stem cells to form proerythroblasts, which are committed to producing erythroid cells and promotes release of reticulocytes. In each step, # of hgb increases and nucleus decreases in size. RBC production increases in 24 hrs, life span is 4-12 hrs (short half life), increase in red cell number in 5 days, always present in plasma. Hemoglobin: Oxygen carrying protein of erythrocyte. Each hgb molecule has 4 hemes which carry 4 molecules of O2. Lack mitochondria—depends on glycolysis for energy. Know different anemia’s basic patho and how they classified Microcytic-hypochromic anemias: Iron deficiency anemia Most common type of anemia. Cognitive impairment in children. Causes: diet, excessive blood loss, parasite infestation, metabolic/functional iron deficiency, menorrhagia (most common physiologic cause). For men and postmenopausal women, a good indicator of malignancy. GI bleed—most common pathophysiologic cause. Also lead poisoning, intravascular hemolysis, pregnancy (nonpathologic, take supplement). Low MCV, low MCH, high RDW, low initial retic count and elevated after tx, ferritin low, low serum iron, TIBC high (transferrin saturation decreased). Cardiac sx, stomatitis, glossitis, pallor, koilonychia (spoon nails), pica. In elderly, lethargy and confusion. Sideroblastic anemia Caused by defect in mitochondrial heme synthesis=dysfunctional hgb synthesis. Ringed sideroblasts (erythroblasts contain iron granules that have not been synthesized into hemoglobin) in bone marrow. MCV usually normal but can be up/down, serum iron elevated, transferrin saturation high, TIBC low. Iron overload/hemochromatosis, enlarged liver and spleen. Thalassemia AUTOSOMAL RECESSIVE. Dx test is hgb electrophoresis. Abnormal formation of hgb. Mutation causes loss of one or both alpha globin chains or one or both of beta globin chains=improper O2 transport and destruction of RBCs=anemia. e“Target cells” may be seen. MCV low, MCH low, ferritin/serum iron normal to high, TIBC normal to borderline. Macrocytic-Normochromic anemias: Megaloblastic anemias Folate/B12 deficiency, poisons, some antiviral drugs, some chemo agents DNA synthesis defective r/t deficiencies in B12/folate. RBCs do not form sufficiently and released prematurely. Vitamin B12 (cobalamin) deficiency: Stored in liver. Keeps nervous system functioning (myelination of nerves). Necessary for formation of blood. Important in DNA synthesis/regulation. Lab findings: mod to severe anemia, MCV very high, MHC normal, hypersegmented neutrophils on smear, pancytopenia (decrease in all blood cells) if severe, elevated LDH and slight increase in indirect bili r/t intramedullary destruction. Folate deficiency: Essential for RNA/DNA synthesis. Absorption in upper small intestine and not dependent on any facilitation. Associated with neural tube defects of fetus. Most common cause of deficiency=diet. Severe cheilosis, stomatitis, painful ulcers in buccal mucosa/tongue, dysphagia, neuro sx usually not seen. Lab findings: Mod to severe anemia, MCV very high, MHC normal, hypersegments neutrophils on smear, megaloblastic RBCs, pancytopenia if severe, abnormally low serum folic acid, B12 normal. Pernicious anemia Most common macrocytic anemia caused by Vitamin B12 deficiency. Lacks intrinsic factor from gastric parietal cells required for B12 absorption. May be congenital or autoimmune (autoantibodies against intrinsic factor released from parietal cells in fundus of stomach). Stomach acid important to pull B12 from food. Weak, fatigue, paresthesias, atrophic glossitis, lemon yellow/sallow skin, neuro sx r/t nerve demyelination sometimes not reversible. Schilling test can determine lack of intrinsic factor or problem in absorption center ileum/small intestines from Crohn’s. Macrocytic Anemias: Alcohol induced Macrocytic, megaloblastic. Anemia from: Interferes with absorption of folic acid (megaloblastic). Interferes with hemoglobin synthesis (sideroblastic). Interferes with erythropoiesis (macrocytosis). Can be reversed with abstinence within weeks. Normocytic-Normochromic Anemias: Aplastic anemia Pancytopenia. Autoimmune disorders and some due to chemical exposures (benzene, arsenic, chemo drugs). Pure RBC aplasia (only RBCs affected). Fanconi anemia – rare genetic anemia from defects in DNA repair. Hypocellular bone marrow replaced with fat. Hypoxic, pallor, weakness, fever, dyspnea. Eval with bone marrow bx. Posthemorrhagic anemia Acute blood loss. Sx depends on severity of blood loss. Hemolytic anemia Accelerated destruction of RBCs. Congenital vs acquired. Intrinsic/hereditary – autoimmune hemolytic anemias RBC bursts. Warm reactive type, cold agglutinin type, cold hemolysin type. Extrinsic/drug induced – immune, infx, drugs, hyperactive spleen, trauma, drug-induced. Allergic reaction against foreign antigens. Called hapten model. PCN, cephalosporins. May be asymptomatic, jaundice, splenomegaly. G6PD deficiency. X linked recessive. Lack of NADPH leads to cells antioxidant protection loss. Shortened life span of RBC, episodic hemolytic anemia with oxidative stresses. Heinz bodies – when hgb is oxidized it denatures and forms this precipitant. Triggers – fava beans, infection, drugs. No tx, only avoid triggers. Test with G6PD assay. Sickle cell: See below. Anemia of chronic disease Most common in elderly. Mild to mod anemia. Begins as normocytic and then progresses to microcytic when advanced. Likely r/t chronic inflammatory response. Release of cytokines and interleukin, stimulates hepcidin release from liver, which regulates entry of iron into circulation=iron trapped in macrophages and liver cells and decreased gut absorption. Decreased erythropoiesis (ineffective marrow response to erythropoietin, altered iron metabolism). TIBC down and ferritin up. MCV normal. Transferrin very low (not good indicator). RBC morph nondiagnostic. Bone marrow can distinguish between IDA and ACD. S/s r/t causative disease (AIDS, malaria, RA, lupus, hepatitis, renal failure, malignancies). Iron basics – transferrin and ferritin 67% total body iron bound (stored) to heme in erythrocytes (hgb) and muscle cells (myoglobin). 30% stored mononuclear phagocytes (macrophages). Rest lost in urine, seat, bile, minor bleeding. 25mg iron required daily for erythropoiesis; 1-2 mg dietary and rest is from iron recycling. Ferritin major iron storage protein. Apoferritin (secreted by liver): ferritin w/o attached iron (precursor), binds w/free iron and becomes transferrin. Hemosiderin: ferritin micelles, normal in small amounts in spleen, liver, bone marrow is normal. Excess iron that collects in cells (insoluble form of iron). Transferrin: iron bound to apotransferrin (precursor). Transfers iron in circulation. Iron for hgb production carried by transferrin to bone marrow where it binds to transferrin receptors on erythroblasts (essential for mature RBC to carry O2). Binds w/ receptors in intestinal epithelial cells->released into blood capillaries (plasma transferrin). Iron cycle Transferrin-iron complex binds to transferrin receptor on erythroblasts plasma membrane->complex moves into cell by endocytosis->iron released (dissociated) from transferrin->dissociated transferrin returned to bloodstream for reuse. 
 Iron metabolism Duodenum and upper jejunum site of absorption. Enhanced by meat, poultry, fish. Inhibited by carbonates, tannate (tea), oxalate (spinach, rhubarb), phosphates (vegetables), clay. HCl promotes absorption. Roles of fibrin, thrombin Thrombin changes fibrinogen to thrombin. Fibrin in the clot absorbs excess thrombin. 
 TTP, ET, ITP, DIC basic patho 
 Thrombotic thrombocytopenic purpura (TTP): Genetic mutation of ADAMTS13 gene. Thrombotic microangiopathy (damage to microvasculature). Platelets aggregate, form microthrombi and cause occlusion of arterioles and capillaries. Acquired form due to triggers that cause antibodies that block activity of ADAMTS13 enzyme. HUS (hemolytic uremic syndrome) same general pathophys as TTP. R/t syndrome that occurs after diarrheal illness (E. coli, shigella) and more common in children. Manifestations: Fever, purpura, altered mental status, neuro signs, renal dysfunction, thrombocytopenia, hemolytic anemia, widespread ischemia. Labs: Thrombocytopenia, hemolytic anemia (increased RBC, retic, schistocytes on smear, elevated LDH. PT and PTT normal. Plasmapheresis must be initiated immediately. Essential thrombocythemia (ET): Increased platelets greater than 600,000. Myeloproliferative disorder of platelet precursor cells. Megakaryocytes in marrow produced in excess. Microvascular thrombus. Asymptomatic. Often in tandem with inflammatory dx, can occur w/ polycythemia vera. Immune thrombocytopenic purpura (ITP): IgG antibody targets platelet glycoproteins. Autoimmune attack on platelets. Antibody covered platelets sequestered and removed from circulation. Phagocyzed by macrophages in spleen. Acute form of ITP after viral infx most common childhood bleeding disorder. Manifestations: Petechia and purpura, progressing to major hemorrhage. Disseminated intravascular coagulation (DIC): Clotting and hemorrhage occur together. Caused by infx, massive trauma, neoplastic dx, chronic inflammatory dx, complication of childbirth. Increased protease activity in blood caused by unregulated release of thrombin w/ subsequent fibrin formation and accelerated fibrinolysis. Widespread thromboses cause ischemia, infarction, organ hypoprofusion. Clotting factors then depleted=excessive bleeding. Significant endothelial damage, critically ill pts. FDP and D-dimer increase. S/S: Bleeding from venipuncture sites and art lines, purpura/petechiae/hematomas, symmetric cyanosis of fingers/toes. Sickle cell patho Autosomal recessive. Homozygous for mutation have sickle cell anemia. Heterozygous for mutation have sickle cell trait. HbgS unstable and when exposed to acidosis or oxidative stress (hypoxia) cell sickles. Sickled cells survive between 10-20 days. Shortnes RBC lifespan and occludes small vessels=tissue ischemia. Lab test is hgb electrophoresis to confirm dx. Sickled cells/target cells/Howell-Jolly (remnant of DNA left in RBC) bodies on smear. Nucleated RBC, WBC elevated. Usually spleen will remove Howell-Jolly but in dysfunctional spleen, remain in circulation. S/S: Painful attacks from infx, dehydration, hypoxia. Jaundice from hemolysis. Pigment gallstones, splenomegaly/infarcted spleen, poor healing ulcers, severe anemia, hemolytic/aplastic crisis. Episodes hours to days. Vaso-occlusion, painful, sickled cells clump and block. Organ damage, osteonecrosis, renal tubular concentrating defect, retinopathy, pulmonary hypertension, acute chest crisis, splenic sequestration crisis (sudden pooling blood, hypovolemia/hard bloated abdomen, circulatory collapse=surgical emergency). 
 Calcium and platelet function 
 Calcium is required in multiple steps in the process to activate clotting factors (factor IV). Platelets: Thrombocytes develop from megakaryocyte progenitor cells. Actin and myosin allow platelet to contract and retain clot/close damaged vessels. Thromboxane activates other platelets to become sticky. Fibrin stabilization factor is the meshwork and strengths clot. Cell membrane key role in hemostasis. Glycoproteins on surface repulse adherence to “normal” endothelium AND promote adherence to injured endothelium (repels normal and promotes adherence to injured). Contain phospholipids to activate several stages in clotting cascade. Live 8-10 days. Eliminated by tissue macrophage system. Functions: Vasoconstriction, initiate platelet-platelet interactions to form platelet plug, activate coagulation or clotting cascade, initiate repair including clot retraction/dissolution. Life cycles of erythrocytes and platelets 
 Erythrocytes: Most abundant cell in blood. Responsible for tissue oxygenation. Contain hemoglobin (no mitotic division). 120 life cycle. Replaced by spleen. Platelets: Incapable of mitotic division. Not technically cells. No nucleus/DNA. Live 5-9 days and removed by spleen. Produced in bone marrow and stored in spleen. Activated by ADP. Basics of clotting cascade; don’t need to memorize all the steps just 
understand the basics of what does what Vascular injury leads to vasoconstriction. Formation of platelet plug. Tissue factor activates coagulation cascade. Formation of a blood clot (secondary hemostasis). Clot retraction and clot dissolution (fibrinolysis). 
 Intrinsic pathway: damage INSIDE vessel (when inside vessel or cells come in contact w/ foreign surface), more factors and takes more time to clot. Needs activation of prothrombin factor. Extrinsic pathway: Most dominant. Tissue injury outside, clot in 15 secs/quick. Activated when tissue factor is released by damaged endothelial cells. Needs activation of prothrombin factor. Chemical mediators associated with clotting Injury to vessel induces formation of prothrombin activator Prothrombin activator changes prothrombin to thrombin (dependent on adequate calcium). Prothrombin attaches to platelets adherent to injured area. Thrombin changes fibrinogen to fibrin. Fibrin meshes w/ blood cells/platelets/plasma to form clot. Fibrin whole goal of process. Fibrinogen is most abundant clotting factor. Clot retraction, assisted by platelets, expresses serum Endothelium prevents formation of spontaneous clots in normal vessels. Nitric oxide and prostacyclin, thrombin inhibitors (antithrombin III), tissue factor inhibitors, and degrading activated clotting factors (thrombomodulin-protein C)
 Von Willebrand factor, protein C, protein S, Factor V Leiden 
 VonWillebrand factor: Activates platelet plug formation. Acts as bridging molecule (anchor) at sites of vascular injury for normal platelet adhesion. Carries factor VIII into circulation. Factor VIII is required during intrinsic pathway. Von Willebrand’s disease: decrease or absence of vWF=decrease in ability for platelets to bind to vessel wall. Decrease in factor VIII=missing or defective vWB. Protein C: Degrades activated clotting factors. Part of protector to keep body from excessively clotting. Protein C deficiency: Congenital or acquired. Thrombophilia. Increased risk of venous thromboembolism. Purpura fulminans in newborns. Skin necrosis and DIC possible. Protein S: Vitamin K dependent anticoagulant that normally activates protein C in degradation of factor Va and Factor Vllla. Deficiency leads to impaired function/activity of protein S and decreased degradation of these factors. Increased risk of VENOUS thrombosis. 3 hereditary types. Can be acquired through Vit K deficiency, tx w/ warfarin, sex hormone therapy, pregnancy, liver dx, chronic infx like HIV. Factor V Leiden: Mutation of factor V. Autosomal dominant disorder. Can have incomplete penetrance. Common in European Caucasians. Causes factor V to be unable to be inactivated by protein C. Excessive clotting in veins (DVTs). Myeloproliferative RBC disorders Polycythemia vera: Overproduction of RBCs. Splenomegaly. More likely to develop gouty arthritis. Burning hands/feet, bluish discoloration of skin. Acquire mutation of JAK2. Allows EPO receptor to be stuck in on position. Dx can convert to acute myeloid leukemia. If RBC is inappropriately high, then EPO level is low. Secondary polycythemia: High altitude living=hypoxia=compensatory increase in RBC. Tumor can also be source of elevated EPO. MODULE 4 Immune System, Inflammation, Alterations of the Immune System, and Stress 
 Understands the basic of the physiology of the innate and adaptive immune system; as well as cell types: B and T cells 1) Innate: Natural/native. First line of defense. Physical barriers incl skin, linings of GI/GU/resp tracts, mechanical cleansing (sloughing/mucus and cilia/coughing and sneezing/flushing/vomiting/pee). 2) Second line of defense is inflammation. Red/heat/swelling. Vascular response=vessel dilation, increased vascular permeability and leakage, WBC adhere to inner walls of vessels. Leakage of plasma causes swelling and blood thickens r/t loss of plasma. 3) Adaptive: Acquired immunity. More sophisticated and less primal, just antibodies. Slower acting, specific and long lived. Includes immunoglobulins (antibodies), lymphocytes (B cells and T cells). Clonal diversity: Recognize specific antigens. Mostly in fetus. Primary lymphoid organs (thymus, marrow). Results in immature but immunocompetent T and B cells, getting ready for invader. B cell development w/ production, proliferation, differentiation in marrow. Each cell responds to one specific antigen. T cells in thymus. Development of antigen-specific T cell receptors. Sit and wait to see antigen in secondary lymphoid tissues. Clonal selection: Antigen processing and presentation. Initiated when T and B cells interact with antigen. B and T cells naive until seen first antigen on surface of an APC. Immune response initiated if antigen is appropriate type and presented appropriately. 4) B cells: Adaptive immunity. Responsible for humoral immunity that is mediated by circulating antibodies. Produced in bone marrow. 5) T cells: Responsible for cell mediated immunity. Cells kill targets directly or attracts another cell to kill. Thymus site of T cell maturation. 
 Understand the basics of the physiology of inflammation including the cell types and which ones activate and come later 
 Inflammation is process in vascular tissues. Kinin causes dilation of blood vessels, pain, smooth muscle contraction, vascular permeability, and leukocyte chemotaxis. Tissue close to the vessel contain mast cells, which are important activator in inflammation. Dendritic cells in the tissue connect innate and adaptive immune responses. Cellular mediators: mast cells, granulocytes, monocytes/macrophages, NK cells, cellular fragments (platelets). Biochemical mediators: cause vascular changes. Incl histamine, chemotactic factors, leukotrienes, prostaglandins and platelet-activating factor. Inflammatory response initiated when tissue injury occurs or when PAMPs are recognized by PRRs on cells of innate immune system. Mast cells: Contain histamine and chemotaxic factors. Central cell of inflammation. Important in sx of allergy. Activated by physical injury, chemicals/toxins, immunologic factors/anaphylaxis, and toll-like receptors activated by bacterial and viruses. Chemical release by degranulation and synthesis of lipid-derived chemical mediators, which is important contribution to inflammatory response. Mast cell synthesis of mediators: Leukotrienes: slower than histamine. Similar effects to histamine in later stages. Smooth muscle contraction/increased vascular permeability. Prostaglandins: Similar to leukotrienes but also induce pain. Aspirin and some NSAIDs block prostaglandins. Platelet activating factor: Endothelial cell retraction to increase vascular permeability, leukocyte adhesion to endothelial cells and platelet activation. Mast cell degranulation: Histamine: vasoactive amine causes temporary, rapid construction of lg blood vessels and dilation of postcapillary venules. Causes edema. H1 receptor-proinflammatory-in smooth muscle cells of bronchi and causes bronchoconstriction when stimulated. H2 receptor-antiinflammatory-induces secretion of gastric acid in parietal cells of stomach mucosa. Neutrophils: EARLY INFLAMMTORY RESPONSE. Short lived. Attracted to site by chemicals that call them there. Breakdown of neutrophils=purulent exudate. Monocytes/macrophages: LATE ARRIVING. Longer living. Produced in bone marrow. Predominant phagocyte in late inflammatory response. Activation of adaptive immunity. Involved in wound repair. Cellular products: chemokines or cytokines regulate innate or adaptive resistance by affecting other neighboring cells. Proflammatory or anti-inflammatory. Incl: Interleukins: Produced by macrophages and lymphocytes in response to pathogen. Regulates inflammation. Enhances acquired immune system. Interferons: Protects against VIRAL infx. Does not directly kill viruses but prevents them from infecting addl healthy cells. Tumor necrosis factor: Secreted by macrophages in response to PAMP. Induces fever, causes cachexia, probable responsibility for fatalities from gram neg bacterial septal shock. Chemokines: Attract leukocytes to site of inflammation. Granulocytes vs agranulocytes 
 Granulocytes: Granules contain enzymes capable of destroying microorganisms. Diapedesis helps to migrate through vessel wall and then to sites where action needed. BEN last night GRANULOCYTE (basophil, eosinophil, neutrophil) Neutrophils: Most numerous. Phagocytes in early inflammation. Eosinophils: Ingest antigen-antibody complexes and viruses. Release cytokines and leukotrienes for inflammatory response. Increase in type 1 hypersensitivity allergic reactions and asthma. Increase and attack parasitic infections. Basophils: Least abundant. Contain histamine. Increase at sites of allergic inflammatory reactions, parasitic infections, esp exoparasites (ticks). Local inflammatory response. Mast cells: Important in wound healing. In tissues. Similar to basophils. Central cells in inflammation. Also contain IgE receptors. Contain histamine and heparin. Agranulocytes: Lymphocytes: Major cells of immune system. Mature T, B and plasma cells. Long life span. NK cells: Kill tumor cells and virally infected cells. Do not have to be induced by antigens. Must enter cell to replicate. Important against VIRAL infections. Recognize infected cells—viral or tumor. Monocytes/Macrophages: Main line of defense against bacteria. Macrophages are precursor to macrophage and dendritic cells. Macrophages major antigen-processing and antigen-presenting cells that initiate immune response. Initiate wound healing. Dendritic cells: Antigen process and antigen presenting. Initiate immune responses. Present antigen to antibody. Primary vs. Secondary responses 
 Primary: B-cell differentiation. IgM first->IgG against specific antigen on first exposure. Prime of immune system. Secondary: Rapid. Larger amounts of antibody produced. Creates cells to remember. Rapidity is caused by present of memory cells that do not have to differentiate. IgM in similar quantities but IgG in greater numbers in 2nd response. Ex: vaccines. Know basics of patho of infection; bacterial and viral Bacterial: Gram neg vs gram pos. Can lead to bacteremia or sepsis. Produce toxins and extracellular enzymes to destroy phagocytic cells. Prevents complement system from being activated. Become resistant when surface molecules altered that express antigens=antibodies created in body can’t fight resistant bacteria. Exotoxins: enzymes released during growth. Damages cell membranes, activates second messengers and inhibits protein synthesis. Endotoxins: contained in cells walls of gram-neg bacteria and released during lysis of bacterial. Called pyrogenic bacteria=fever. Endotoxins inside gram negative bacteria. 2) Viral: Virion. Common in humans. Life cycle completely intracellular. Attaches/binds to host cell via protein receptors, penetrates host cell by endocytosis, releases genetic material into host cytoplasm. Bypasses immune defenses—rapid division, IC survival, coats w/ self proteins, antigenic variation, neutralization, complement invasion, immune suppression. 
 Basic patho of HIV and cell types involved 
 Final phase of HIV is when sufficient numbers of CD4 cells are destroyed and when production of new CD4 cells can’t match destruction. Pt has fatigue/fever/wt loss, atypical or opportunistic infections or cancer (Kaposi sarcoma/histoplasmosis). AIDS is CD4 or Tcells <200. With HIV, killer T cells (CD8) attack and kill infected cells. Understand difference in hypersensitivity reactions; and patho behind 
disease processes discussed 
 Type I: IgE mediated. Environmental allergens. Release of histamine from mast cell degradation. Histamine binds to H1 (bronchial constriction, edema, vasodilation) and H2 receptors (increased gastric secretion, decreases release of histamine from mast cells and basophils). Increase chemotactic activity. Examples: allergic rhinitis, anaphylaxis, anaphylactic reaction (release of chemical mediators, mast cells release more histamine, vasodilation->respiratory distress->deterioration->failure of compensatory mechanisms). Type II: Tissue specific. Mediated by IgG and IgM. Cell destroyed by antibodies and complement, cell destruction w/ phagocytosis, neutrophils release granules, antibody dependent cell mediated toxicity present, causes target cell malfunction. Example: Graves disease-receptors turned on and increased thyroid hormone permanently, autoimmune hemolytic anemia, rheumatic fever. Type III: Immune (antigen-antibody) complex mediated. Not organ specific. Complexes formed in circulation and deposited later in vessel walls or extravascular tissues. Ex: Vasculitis, nephritis, arthritis. Immune complex dx: Serum sickness (affects blood vessels, joints, kidneys), ex Raynaud’s AND arthritis reaction w/ swelling. Type IV: Mediated by T lymphocytes or is cell mediated. Destruction of tissue caused by direct killing of toxins from cytotoxic T cells. Don’t involve antibody. Cell mediated takes hours or days. Ex: MS, TB skin test, DM1, Crohn’s, Hashimoto disease, graft rejection, poison ivy, metal allergy. Understand role of the immunoglobulins and their role 
 Immunoglobins: aka antibodies. Produced by plasma cells, which come from B lymphocytes. Classes characterized by antigenic, structural, and functional differences. Direct protection(activation of antibody alone) or indirect (activation of other components needed-needs help). IgA (areola-through breast milk, secretions) : Body secretions. Defects against pathogens on body surface (resp and GI). J chain attaches to mucosal epithelial cells to protect IgA from being damaged. IgD (director-regulate cell activity): Limited info, low concentration, primary in plasma. B cells. IgE (emergency-immediate responses, initiates inflammatory reaction): Mediator of common allergic responses. Causes immediate hypersensitivity reaction. Causes mast cell degradation=histamine release and heparin. Defender against PARASITES. Initiates anti-inflammatory response to attract eosinophils (phagocytes). IgG (gestation-passive immunity, primary antibody in immune response): Most abundant. Most protective activity against infections. Present in all body fluids. Antibacterial and antiviral antibody. IgM (major-largest): Largest size. First antibody produced during primary response to antigen. Doesn’t cros membrane barriers-found vascularly. Autoimmunity vs. alloimmunity and patho of diseases discussed 
 Autoimmunity: Breakdown of tolerance where body’s immune system recognizes self antigens as foreign. Familial association. Ex: Systemic lupus erythematosus: type III hypersensitivity. Autoantibodies against self produced. Damage at tissue level. Mostly females. Blacks>whites. Kidney damage-high affinity. Deposition of circulating immune complexes containing antibody against host’s DNA. S/S: Arthralgias/arthritis, vasculitis/rash, renal dx, anemia, CV dx—at least 4 findings indicates SLE. No cure. Alloimmunity: Immune system reacts against antigens on tissues of other members of same species. Ex: Transient neonatal alloimmunity (Rh factor—fetus expressing parental antigens not found in mother), transplant rejection, transfusion reaction (type II reaction, IgM class antibodies, O blood type universal donor, AB universal recipient). Physiology of the stress response; including the substances involved and their effect on the body 
 1) Selye’s General adaptation syndrome (GAS): -Alarm stage (fight or flight): Stressor triggers hypothalamic-pituitary-adrenal axis, activates SNS. -Resistance or adaptation (mobilization that contributes to fight or flight): Begins with actions of adrenal hormones (cortisol, epi, norepi). -Stage of exhaustion (breakdown of compensatory mechanisms, may lead to onset of dx): Occurs only if stress continues and adaptation is not successful. 2) Stress response: Initiated by CNS and endocrine system. Corticotropin-releasing hormone released from hypothalamus and also peripherally at inflammatory sites. Stressor can be perceived or real. 3) Neuroendocrine regulation: SNS aroused and causes adrenal gland medulla to release catecholamines (mimic sympathetic stim, released from chromaffin cells of adrenal medulla-large amts of epi {affects CV}, small amts of norepi {constricts vessels, blood to core, increased mental awareness}—fight or flight). Hypothalamic CRH stims pituitary gland to release prolactin, endorphins, growth hormone, adrenocorticotropic hormones that stim adrenal gland cortex to release cortisol. Cortisol: Activated by ACTH, stims gluconeogenesis, elevates glucose, powerful anti-inflammatory and immunosuppressive agent (poor wound healing and prone to infx). 4) Immune-related conditions and dx associated w/ stress. Stress=increased level sof pro-inflammatory cytokines=possible link between stress/immune fcn/dx, stress induced immune changes affect immune cell fcn (causes decreased NK cells and T cell cytotoxicity and impaired B cell function). Infections; clinical manifestations and microorganisms responsible for diseases Viral (virons enter cells): Erythema infectiosum (Fifth’s disease/slapped cheek syndrome) Parvovirus B19, droplet Erythematous and macular rash 1st on cheeks/ears, rash and joint sx. If pregnant in 1st trimester can cause defects/miscarriage. IgG (had it and gone), IgM (have it and miserable). Herpangina Acute viral illness, enterovirus, Coxsackie A & B Fever, ulcerative mouth lesions, cough, coryza, pharyngitis. Fecal-oral and oral-oral route. High fever, sore throat, malaise, h/a, backache, anorexia, drooling, vomiting, diarrhea. R/o strep pharyngitis. Infectious mononucleosis (kissing dx) Infectious, widespread. Epstein-Barr Virus. Via saliva. Fever, fatigue, pharyngitis, adenopathy. Rare splenic rupture. Monospot screening test. Influenza High infectious. Orthomyxovirus in antigenic types A and B. Virons attach to respiratory epithelial cells and enter by endocytosis. Antigenic drift (mutating), antigenic shift (recombination into 2 viruses) Cold like sx, fever, chills, malaise, h/a, nausea, muscle aches, nasal stuffy. Measles (Rubeola) Measles virus. Acute viral dx. Fever higher than 101, erythematous maculopapular rash, cough, coryza, conjunctivitis. Rash on face->rest of body after 3-5 days. Characteristic rash of oral mucous membranes known as Koplik spots. Direct contact w/ infectious droplets, highly contagious. Mumps (parotitis) Mumps virus. Transmitted via respiratory. Highly contagious. Affects salivary glands, primarily parotid gland. Tender, swollen parotid glands typically covering angle of jaw, fever up to 104. Positive IgG titers or mumps IgM antibodies. Roseola (6th disease) Herpesvirus HHV-6, HHV-7, roseolovirus. Droplet or fecal-oral route. Viral dx of infants and children under 2 Sig fever up to 106 for 7-10 days, when resolved then faint, erythematous maculopapular rash lasting hours to days. Rubella (German measles) Rubella virus. Direct or droplet contact w/ nasopharyngeal secretions. Maculopapular rash beginning on face and spreading. Joint pain in adults. Detected on nasal smear. Varicella Varicella zoster virus (herpes family). Mild acute viral illness, highly contagious. Fever and generalized, pruritic, vesicular rash. Detected in vesicular scrapings during first 3-4 days. West Nile Virus Flavivirdae arbovirus family. Fever, h/a, fatigue, muscle pain, malaise, nausea, anorexia, vomiting, rash, lymphadenopathy, meningoencephalitis. CSF w/ IgM antibody for WNV is confirmative. CSF w/ pleocytosis (increased # lymphocytes in CSF). Cytomegalovirus DNA virus, herpesvirus. Direct person-person contact. Mono like sx, fever, overwhelming fatigue, pharyngitis, ulcerative lesions in mouth, loss of vision. Causes retinitis. Humans and monkeys natural hosts. Transplant pts worrisome, remains for life—can be latent for years. Bacterial infections: Lyme disease. Tick born infx via deer tick. Caused by spirochete Borrelia burgdorferi Erythema migrans at bite site, fever, h/a, lethargy. ELISA and then western blot assay to detect both IgM and IgG. Stage 1: Early localized dx-flu like sx, erythema migrans rash Stage 2: Early disseminated dx-Fatigue, arthralgia, CN palsies, multiple erythema migrans lesions but smaller. Stage 3: Late disease-months to years later. Arthritis affecting large joints, CNS and PNS affected, subacute encephalopathy, distal paresthesias, memory/mood/sleep problems, cardiac involvement Pertussis (100 day cough, whooping cough) URI caused by Bordetella pertussis. Respiratory transmission. Catarrhal stage: Mild URI sx w/ cough and conjunctival injection (contagious), like common cold. Paroxysmal stage: Severe burst of cough w/ inspiratory whoop followed by vomiting, no fever or low grade, child unable to breathe w/ coughing attacks. Nasopharyngeal cultures or IgA testing to confirm. Rocky Mountain Spotted Fever Infected tick, Rickettsia rickettsii. Triad of sx: fever, rash, hx of tick bite. Petechial rash 6th day or later to palms and soles. Fever sudden, severe h/a, myalgia, n/v, abd pain, lymphadenopathy, cough, confusion. Titers Scarlet fever Acute infx dx a/w streptococcal pharyngitis, vascular response to bacterial endotoxin produced by group A hemolytic streptococcus=increased vascular response. Large droplets. Prodrome of 1-2 days of fever, sore throat, h/a, and maybe abd pain and vomiting, possible paranoia and halluicinations. Rash in 1-5 days—blanchable, starts on chest, armpits and behind ears, concentrated in skin folds. Skin peels, face first, then palms, then axillary/groin. Strawberry tongue. Fungal infections Candida albicans: most common. Skin, GI tract, mouth, vagina. If immune system compromised, can become systemic. Tinea (ringworm) Parasitic and protozoan infections Benefit at expense of host. Parasitic worms Intestinal and tissue nematodes (hookworm/roundworm). Hookworms bad in pregnancy—cognitive/growth issues, low birth weight. Flukes (liver, lung fluke). Parasitic, feed on blood. Tapeworms Transmitted mainly through vectors Malaria by mosquitos. Trypanosomes by tsetse fly Leishmania spp by sand fleas Others in contaminated water or food, ex giardia Malaria Most common infx worldwide. Enters blood, survives in liver and invades parenchymal cells. Sx fever, fatigue, vomiting, h/a, jaundice 10-15 days after bite Toxoplasmosis Caused by intracellular parasite toxoplasma gondii. Cats primary host. Once infected, lies dormant in muscle tissue. Feline feces, raw or undercooked meat (pork), eating soil contaminated fruit/veggies. Flu like sx, neuro sx, a/w ADHD and OCD. Increased risk in pregnant and immunocompromised. Plasma cell disorders Multiple myeloma Neoplastic proliferation of single plasma cell line Leads to many copies of 1 specific immunoglobulin (normally IgG or IgA) Leads to bone marrow elements being replaced by malignant plasma cells. Bone pain, fx, anemia, renal failure, recurrent infx (most common cause of death). Anemia, leukopenia, thrombocytopenia in advanced dx. More in African American pop. Hodgkin’s lymphoma Cancer of lymph system. Lymphadenopathy first finding. Most common sx painless lymphadenopathy, fever, weight loss, night sweats. Non-Hodgkin’s lymphoma Solid tumor w/ malignant transformation and growth of B or T cell lymphocytes or precursors. Commonly B cell. 2x more common as Hodgkin’s. Starts in nodes and can spread to blood/bone marrow. Lymphadenopathy, HSM/abd pain/fullness, recurrent infx. Leukemias Acute: AML, ALL AML: Neoplasm of myelogenous progenitor cells, mostly adults, response to therapy NOT favorable ALL: Neoplasm of early lymphocytic precursors. Common in children under 15. Very responsive to therapy. CNS involvement w/ B cell phenotype, increased LDH, rapid leukemic cell proliferation. Both manifest: Anemia, neutropenia, recurrent infx, TCP, splenomegaly, hepatomegaly, lymphadenopathy, bone/joint pain, thymus mass. Chronic: CLL, CML CLL: Common after age 50. Monoclonal proliferation of lymphocytes that are morphologically mature but functionally defective. Least aggressive type. Normally asymptomatic, discovered on routine CBC, generalized painless lymphadenopathy, splenomegaly, frequent URI. Advanced: fatigue, wt loss, pallor, rashes, easy bruising, bone tenderness and pain CML: Neoplastic clonal proliferation of myeloid stem cells. Normally older than 40. Chronic course for yrs until transforming to acute leukemia. End point acute phase or blast crisis (accelerated phase of blast and promyelocyte production/immature cells). Philadelphia syndrome—those w/ this chromosome have shorter survival and do not respond to tx. May be asymptomatic, constitutional sx, recurrent infx, easy bruising/bleeding, anemia, splenomegaly/HSM, lymphadenopathy.