Patho Exam 1 Study Guide PDF

Lecture 1: Bone Marrow Primary Lymphoid Organs - Bone marrow - All cells originate from hematopoietic stem cells in bone marrow - Thymus - site of T cell differentiation - T cells screened for positive selection - MHC responsible for recogn...

Lecture 1: Bone Marrow Primary Lymphoid Organs - Bone marrow - All cells originate from hematopoietic stem cells in bone marrow - Thymus - site of T cell differentiation - T cells screened for positive selection - MHC responsible for recognition of self vs non-self Secondary Lymphoid Organs- all divided into T and B cell separate storage components - Lymph nodes - Spleen - Responsible for clearance of old, damaged or abn RBC - Highly vascular - Splenectomy reasons: abdominal trauma, splenic infarct - After splenectomy → decreased RBCs & platelets, poor immune response especially gram + cocci - Gut Associated Lymphoid Tissue (GALT) Fluids Plasma- fluid portion of blood - Plasma - clot = serum - Highly proteinaceous (most of these proteins are produced in the liver) - Help maintain oncotic pressure Lymph- fluid in lymphatic system - Lower protein content - 75% is drained from thoracic lymphatic duct into left subclavian vein, 25% is drained from the right lymphatic duct into the right subclavian vein Immunoglobulins (secreted form of antigen binding receptors**) - Require activation by helper T cells - Helper T cells → activate B cells → B cells differentiate into memory B cells & plasma cells → plasma cells secrete immunoglobulins Name Properties Structure In circulation IgA Found in mucus, saliva, tears, Dimer breast milk Protects against pathogens IgD Part of B cell receptor Monomer Activates basophils & mast cells IgE Protects against parasitic worms Monomer Allergic reactions  IgG MOST ABUNDANT Monomer Able to cross placenta IgM Responsible for early stages of Pentamer immunity Erythrocytes - Stimulated by EPO → EPO is produced in the kidneys - In order for a mature RBC to be released into circulation it has to lose its organelles & nucleus so it is pliable - Life cycle of RBC 120 days - 1% of circulating RBCs are reticulocytes (immature RBC that lasts 3 days in marrow, 1 day in blood) - RBC composed of: membrane, hgb (requires iron), metabolic enzymes for glycolysis, & LDH - Iron important = maintains globin structure/porphyrin ring Non-Erythrocytes - Granulocytes (most common) - Lymphocytes (T and B cells) - Monocytes/Macrophages - Platelets Blood Disorders RBC - Too much: - Polycythemia vera - Kidney tumors (due to over production of EPO) - Too little: anemia - MOST common cause of anemia is iron deficiency, caused by - Excessive blood loss - Low iron intake - Lead poisoning - Microcytic: low raw materials (low iron) - Macrocytic: vitamin deficiency (low B12/ folate) - Large cells, few in number - Normocytic: blood loss or systemic disease - Normal size, low number or hgb  - Wrong: GENETIC - Sickle cell - Mutation in beta chain of hgb, not shaped correctly - Thalassemia - Mutation of one or both alpha or beta chains in hgb - Spherocytosis - Enzyme deficiencies - Being destroyed: - Hypersplenism - Hemolysis - Intravascular trauma (prosthetic heart valve) - WHEn RBC are destroyed they release: - Bilirubin - Hgb - Lactose dehydrogenase (LDH) - Increased reticulocytes - Schistocytes WBC - Too much: - Leukemia: WBCs proliferate in the bone marrow - Lymphoma: WBCs proliferate in the lymphatic tissue (lymph nodes, spleen) - Hodgkins: unknown precursor cell - Non-Hodgkin's: T and B cell proliferation - Multiple Myeloma: expansion of terminal B cell in bone - Presentation for these diseases: fatigue, poor immune response, enlarged lymph nodes, bone pain or fracture - Hypersensitivity Type 1 (allergic reaction) Type 4 IgE mediated T-cell mediated Onset within 1 hr Onset days to weeks anaphylaxis Rash, sjs - Too little: - Myelodysplastic syndrome (faulty manufacture of multiple cell lines because of bone marrow failure) - Wrong: GENEtIC DISORDERS  - Severe combined Immunodeficiency disease (SCID) - Being destroyed: - Sepsis - Drug induced (steroids) - Immune based (lupus, felty syndrome, hypersplenism) Coagulation system: coagulation factors must be activated by enzymes in circulation - Main role: hemostasis (control bleeding, confine activity to site of blood loss) - Balance between prothrombotic and antithrombotic factors - When activated fibrin plug forms - Primary hemostasis: vasoconstriction & platelet adhesion/ activation - Secondary hemostasis: fibrin formation - Initiation - Amplification - Propagation Platelets: fragments of megakaryocytes - Megakaryocytes are stimulated by thrombopoietin - Thrombopoietin is produced in the liver and kidneys - FEEDBACK: if platelet level is low, more thrombopoietin in system to stimulate megakaryocytes - Von Willebrand factor allows platelets to attach to endothelial cells - Platelets live about 10 days in circulation Thrombophilia: - Caused by platelet or coagulation factor dysfunction Platelet Disorders: (can be quantitative or qualitative) - Virchow's triad of factors contributing to thrombosis - Hypercoagulability - Stasis - Endothelial injury - Making it wrong: - Von Willebrand disease (platelets cannot attach to endothelial wall) Coagulation Factor Dysfunctions: (are quantitative/ genetic) - Coagulation factor deficiencies are genetic - 8 is derived from endothelial cells and 13 is derived from platelets - Balanced by anticoagulation factors - Protein C and S - Plasmin - Antithrombin Lecture 2 - Immunity & Inflammation Immunity:  #1 normal function = protect from foreign organisms/threats Determine self from nonself 2 Branches ○ Innate Immunity 1st line of defense, triggers the acquired system Always active ○ Acquired Immunity Action of T & B Lymphocytes (aka b cells & t cells) ○ Both immune systems share these components Monocytes & macrophages Lymphocytes Granulocytes Innate Immunity: Includes ○ endothelial cells/barriers - release cytokines ○ Mucociliary clearance ○ Phagocytes ○ Dendritic cells ○ Natural Killer Cells ○ Mast Cells ○ Complement proteins Release cytokines, interleukins, & travel to lymph tissue to present antigen to lymphocytes Nonspecific and always ready/ever present, response is immediate Mononuclear Phagocytes: aka Macrophages Perform antigen processing Abundant near MUCOSAL surfaces Phagocytose microorganisms & debris Travel to secondary lymphoid organs to present the antigen that T cells recognize → lymph nodes & spleen Dendritic Cells: Antigen presenting cells at EPITHELIAL surfaces Same function as phagocytes Dendritic cells = lymph nodes & spleen Langerhans cells = skin Kupffer cells = liver endothelial cells Granulocytes: Neutrophils ○ The most abundant granulocyte  ○ Phagocytose & destroy foreign antigens ○ Attracted to inflammatory sites by chemokines & granules released from cytoplasm destroy microbe/foreign substance ○ Release neutralizing enzymes ○ Associated with bacterial disease states Eosinophils ○ Triggered by parasitic infections ○ Stimulated by IL-5 ○ Less effective at phagocytosis than neutrophils ○ Major Basic Protein (MBP) destroys parasites ○ Triggers histamine release from mast cells & basophils ○ Release antiparasitic granules Basophils ○ Granules mediate immediate & late phase allergic responses ○ Interact with IgE antibodies ○ Release histamine to induce inflammation and vasodilation Mast Cells ○ Basophils that interface directly with the environment ○ Interacts with IgE antibodies BUT can ALSO be activated WITHOUT IgE ○ Release histamine ○ Promote angiogenesis & fibrinogenesis Complement Proteins: Are manufactured in the LIVER Activates series of reactions to enhance immune reaction 3 different pathways ○ Classical ○ Alternative ○ MB Lectin Most important convergence point of the 3 pathways is @ C3 ○ C3 cleaved into C3B - produces more profound opsonization reaction C3A - produces small, weak inflammatory reaction Acquired Immunity: Takes longer in response time than innate Lymphocytes ○ Bind to specific antigens ○ 70-80% circulating are T Cells Cellular immunity ○ 10-15% are B Cells  Humoral immunity - produce antigen specific antibodies ○ Remainder are Natural Killer Cells (considered a T cell but is apart of innate immunity) No antigen specific T cell receptors, injects perforin and facilitates apoptosis T Lymphocytes (thymus) ○ Receptor on surface remains cell bound ○ T cells activate B cells B Lymphocytes (bone marrow) ○ Once activated (by helper T cells) - clone expansion & release antibodies/immunoglobulins ○ B cells differentiate into plasma cells (which secrete antibodies/immunoglobulins) and memory B cells Once threat neutralized T & B cells contract ○ Small % remain as memory cells ○ Repeat attack results in a faster & more magnified response Inflammation: A normal response to immune system activation Eliminates initial threat, removes abnormal tissue, begins tissue repair 4 CARDINAL SIGNS OF INFLAMMATION - especially near skin sites ○ Redness ○ Swelling ○ Heat ○ Pain ○ Also loss of function if severe ○ Dilation of arterioles & more permeable capillaries causes the cardinal S&S Day 6 = maximum inflammation Inflammatory response in absence of foreign trigger → autoimmunity Classification of Inflammation: Acute = days to weeks Subacute = weeks to months Chronic = months to years ○ Periods of remission & exacerbations Acute Inflammation: Initiated by innate immune cells, which release cytokines & interleukins that cause arterial dilation → S&S of inflammation Recognize threat by Pattern Recognition Receptors (PRRs) ○ PAMP = pathogen associated molecular patterns ○ DAMP = damage associated molecular patterns Proceeds to exudative inflammatory rxn Exudative Inflammatory Reaction: Brief arteriole vasoconstriction prevents spread of agent Vasodilation of arterioles/capillaries → exudation of blood serum causing swelling and pain (flush agent from tissue) Know that there are vascular changes in permeability to induce an exudative inflammatory response Mediators of Inflammation: Autocrines ○ Signals that act back on initial cell Paracrines ○ Influence nearby cells (par = near) Hormones/endocrine ○ Act on distant cells, downstream effects ○ Circulate in blood to stimulate more leukocyte production Exocrine ○ Package product released 1. Cell Derived Mediators Name Source Effect Histamine Basophils & Mast Cells Vasodilation Serotonin Basophils & Mast Cells Vasodilation Nitric Oxide Gas released by damaged Vasodilation endothelial cells Some bactericidal activity Arachidonic Acid Derivatives Damaged cell membranes Vasodilation Mediate pain & fever Cytokines Tissues, cells Chemotaxis (attracks WBC) & systemic effects  2. Plasma Derived Mediators Name Source Effect Factor XII - Hageman Factor Produced by Liver Activitates - Kinin system - Coagulation system - Fibrinolysis system Bradykinin (Kinin System) Tissue necrosis vasodilation , pain Thrombin Coagulation System Cleaves fibrinogen into fibrin for clots Triggers production of nitrous oxide & chemokines Plasmin Fibrinolysis System Breaks down fibrin clots C-Reactive Protein (CRP) Produced by Liver Activates complement system Acute phase reactant ( binds damaged tissue) Complement System Comprised of proteins made by Stimulate histamine release liver Opsonization MAC Patterns of Inflammation Serous Inflammation: - Lacks fibrin - Large amounts of clear, watery fluid → from mesothelial cells of serous membranes - Usually precedes other forms of inflammation - Ex’s = inflammation of serous membranes, edema in glottis/larynx, skin blisters Granulomatous Inflammation: (TB) - Aggregate of macrophages which fuse together form a mass of granulation tissue - Appears as small nodules Fibrinous Inflammation: (C. diff) - Excessive fibrinogen which forms a temporary barrier against additional inflammation - Pseudomembranous sheets - Pseudo colitis Purulent Inflammation: - Thick exudate (pus)  - Associated with pyogenic bacteria - Types depend on what location it is in: abscess, empyema, phlegmon - Abscess: localized, enclosed, surrounded by wall of capsule - Empyema: inflammation in body cavity - Phlegmon: inflammation that spreads in loose fibrous connective tissue without borders - Erysipelas: phlegmon of the skin Ulcerative Inflammation: - Occurs near epithelial surface - Necrosis of superficial layers exposes deeper tissues → ulcer Catarrhal Inflammation: - Watery exudate of serum & mucus - Mucus membranes of respiratory & GI tracts - Mucosa appears erythematous & swollen - Ex. → acute rhinitis - Caused by - Hypersensitivity, bacterial, viral, physical, or chemical tissue injury Outcomes of Acute Inflammation: - Favorable - Absorption - Tissue repair - Organization (scar) - Unfavorable - Acute organ insufficiency - Abscess formation - Chronic inflammation Chronic Inflammation: lasts months to decades - Alternating phases of recovery and exacerbations OR chronic exposure to agent - Persistent infections (TB), prolonged exposure to the agent, autoimmunity - Outcomes - Chronic organ insufficiency - Fibrosis - Cirrhosis Types of Chronic Inflammation: - Silicosis - Silica particles trapped in lung tissue triggers immune response - Scar tissue formed - Asbestosis - Asbestos trapped in lung - Leads to mesothelioma  - Chronic Cholecystitis - Stones form in GB & blocks normal bile duct transport - GB wall thickens & becomes fibrotic Anti-Inflammatory Process: - Acute inflammation & coagulation have tightly controlled counter mechanisms - If controls lost → may be life threatening - Autoimmunity - Excessive coagulopathy - Systemic Inflammatory Response Syndrome (SIRS) - 2 or more of the following: - Fever >38 or < 36 C - Tachycardia - Tachypnea - WBC >12,000 or 6.5% Type 1 DM: Destruction of beta cells - majority due to autoimmune destruction by T lymphocytes Hallmark is LACK of insulin ○ Increased ketone formation ○ Diabetic ketoacidosis can be 1st presentation Strong environmental role - viral exposure or vit d def. Maturity Onset Diabetes of the Young: MODY Mutation in glucokinase (the glucose sensor for beta cells) (cannot phosphorylate glucose) Results in insufficient release of insulin Gestational Diabetes: Placental hormones induce insulin resistance Increased risk of developing T2DM later in life for mother Type 2 DM: POOR utilization of insulin 2 metabolic effects ○ Insulin resistance by target tissues ○ Inadequate release of insulin by beta cells Stronger genetic component & strongly associated w/obesity Insulin Resistance: Nutritional excess increases free fatty acids & converted to triglycerides in adipose tissue → when subcutaneous fat can no longer expand, excess lipids stored in VISCERAL adipose tissue Visceral adipose tissue (central obesity) most closely linked to insulin resistance Patient Presentation: acute At glucose > 200 mg/dL the kidneys cannot reabsorb glucose  ○ Glycosuria causes osmotic diuresis (water follows) → polyuria/nocturia ○ This causes dehydration → polydipsia ○ Calories lost by glucose in urine → increased hunger or polyphagia ○ Dehydration + calorie loss = weight loss Diabetic Ketoacidosis: is more common in T1DM Increased plasma osmolality causes fluid to shift to extracellular space = cellular dehydration occurs Increased serum glucose + lack of insulin = ketone body formation (ketogenesis) Treatment = slow introduction of insulin + hydration + electrolytes (sodium and potassium) Hyperosmolar Coma: is more common in T2DM Severe hyperosmolar state WITHOUT ketogenesis No ketones, insulin still produced so no ketone bodies Hypoglycemia: Symptoms = shaking, palpitations, anxiety, sweating, hunger (as severe as confusion or coma) Treatment = oral glucose or IM glucagon Chronic Complications: largely due to vascular effects of hyperglycemia Microvascular complications - ○ Overproduction of reactive oxygen species results in increased protein deposition in vessel walls → endothelial cell dysfunction, loss of endothelial cells & occlusion Macrovascular Complications - atherosclerosis (75% of DM deaths) ○ Coronary artery disease ○ Peripheral artery disease Diabetic Foot ulcers - due to neuropathy & vascular disease Diabetic Therapies: Replace Insulin - human recombinant most common form ○ Modified to enhance monomer formation = rapid acting ○ Modified to reduce solubility & clearance = long acting Stimulate receptors on beta cells to release insulin = sulfonylureas ○ Regardless of glucose levels - risk of hypoglycemia ○ Glipizide or glyburide GLP-1 agonists = incretin (enhances glucose stimulated insulin release) → hella GLP1 ○ Stimulate beta cell proliferation to release insulin & decrease gastric emptying (slow motility) ○ GLP-1 analogs → drugs that inhibit the enzyme that breaks down GLP-1 (because the body needs the extra insulin the medications will stop the enzyme that breaks down GLP1) ○ Exanatide  Inhibit gluconeogenesis = Metformin Drugs that increase glucose excretion by the kidney (instead of being absorbed into the blood, & goes to kidney=it is urinated out)(block glucose reabsorption) = SGLT2 inhibitors Decrease glucose absorption in the gut = acarbose (prevents the breakdown of starches into sugar) Decrease glucagon release = DPP-4 inhibitors Decrease insulin resistance = thiazolidinediones (pioglitazone) Lecture 5- Endocrine: Pituitary Gland Endocrine - Bodywide homeostasis (responsible for different aspects of homeostasis - Tightly integrated with nervous system (sympathetic and parasympathetic) - Endocrine disorders - hypersecretion/hyposecretion of hormones - Hyporesponsiveness (lack of response) of receptors - Inflammation of glands - Gland tumors Glands of the endocrine sys: Hypothalamus- integrative center of endocrine and nervous systems ○ Controls emotions, behavior and multiple body system homeostasis ○ Responds to deviations from normal: temperature, volume, osmolality, satiety, body fat content ○ Stimulates hormones that are made in anterior pituitary ○ Stimulates release of hormones that are made by hypothalamus and stored in posterior pituitary Pituitary Gland- anterior and posterior ○ Tight feedback between target gland, hypothalamus, and pituitary ○ Anterior pituitary ○ Posterior pituitary Store hypothalamic hormones and release on demand Target glands ○ Thyroid gland- metabolism and calcium homeostasis ○ Parathyroid gland- calcium homeostasis ○ Adrenal gland- volume, glucose, sexual homeostasis ○ Gonads General H-P (hypothalamic-pituitary) hormone characteristics  Hormone release is pulsatile (half lives are short lived: minutes) ○ Difficult to measure levels ○ Challenge test done based on feedback properties of axes Anterior pituitary hormones: made by ant. pituitary Go Look For The Adenoma Pussy Hypothalamus Ant. Pituitary Target Organ Inhibited by: Key features (stimulates) CRH ACTH Adrenal Glands Stimulated in response (corticotropin to metabolic, physical releasing hormone) (Adrenocorticotropin (release mental stressors Hormone) corticosteroids & Processed from adrenal prohormone POMC androgens) POMC → Growth of adrenal tissue Termed HPA axis TRH Thyroid Stimulating Thyroid Gland & Somatostatin Responsible for (thyrotropin releasing hormone (TSH) synthesis of T4 & metabolism in every hormone) T3 cell of body important for normal growth & development Fetal hyposecretion = severe mental  retardation Hyposecretion in children = short Overstimulation due to iodine imbalance or tumor GnRH LH (luteinizing Acts on the GnRH, LH, & FSH = (gonadotropin hormone) gonads to secrete pulsatile, burstlike releasing hormone) gonadotropins pattern & (men testosterone LH & FSH FSH (follicle & women responsible for stimulating hormone) estrogen) steroidogenesis in ovaries & testes (stimulate ovarian follicles, menstrual cycle, breast growth, spermatogenesis) GHRH Growth hormone Promotes tissue Somatostatin Stimulates cartilage (growth hormone growth growth releasing hormone) throughout body Acts via insulin-growth-factor I Prolactin Stimulates breast Dopamine from development & the hypothalamus milk synthesis Posterior Pituitary hormones: made by hypothalamus & stored in the post. Pituitary Hormone Stimulated Receptors Key features (responsible for:) Vasopressin (ADH) - Increases in serum V1A- smooth muscle Increased osmolality→ increased osmolality (amt of (causes thirst & water conservation water in blood vasoconstriction) decreases and amt of V1B- increase in ACTH solutes increased) release (thirst is triggered)V2- distal nephrons of kidneys (conserves -large decreases in water in renal collecting intravascular volume cells) (blood loss) Oxytocin -smooth muscle contraction -regulation of behavior: trust  formation and interpersonal bonding (breast feeding) Diabetes Insipidus: polyuria & polydipsia Lack of ADH or action (cannot concentrate urine = polyuria, persists even if urine output is decreased) Causes ○ CNS/ central diabetes insipidus: poor synthesis or secretion of ADH Common causes: head injury, brain tumor, post craniotomy ○ Nephrogenic: kidneys cant respond to ADH ○ Pregnancy: increased metabolic clearance of ADH (bc placenta enzymes degrades vasopressin) Inappropriate ADH Syndrome: excess ADH without hyperosmolality Clinical presentation: hyponatremia without edema (severe = coma) Causes: increased ADH release/ interfere with feedback mechanism ○ Vasopressin-secreting tumor: small-cell lung carcinoma ○ CNS disorders: infection, tumor, CVA, aged-related atrophy, trauma, DTs, psychosis, demyelinating disease, inflammatory diseases (Guillain Barre) ○ Pulmonary disorders: TB, pneumonia, abscess, cavitation, resp failure, PPV (positive pressure ventilation) ○ Drugs: desmopressin Caution with quick correction of sodium: central pontine myelinolysis Pituitary Adenoma: Common & usually benign Pituitary enclosed in tight bony space → cannot accommodate expansion Arise from secretory or nonsecretory cells Macroadenomas (>10 mm) ○ LESS likely to secretory ○ Symptoms due to expansion = headache, visual field defects, hydrocephalus, pituitary failure CN II, III, IV, V & VI Microadenomas (