Pathology Synopsis

PATHOLOGY SYNOPSIS Abbreviations used at end of notes Cell injury PO₂: driving force for diffusion of O₂ into tissue Sao: percent heme groups occupied by O₂ Cyanosis: decreased O₂ saturation (SaO2) O, content: 1.34 x Hb x SaO2 + PaO2 Oxygen: electron acceptor in oxidative pathway Hypoxia: inadequate O₂ leads to ATP depletion Ischemia: decreased arterial (or venous) blood flow Respiratory acidosis: retention of CO, always decreases PaO2 Ventilation defect: impaired delivery of O₂ to alveoli; intrapulmonary shunting of blood (c.g., RDS) Perfusion defect: absent blood flow to alveoli; increased alveolar dead space (e.g., pulmonary embolus) Diffusion defect: O₂ cannot cross alveolar-capillary interface; interstitial lung disease (e.g., sarcoidosis) Methemoglobin: SaO2; heme iron +3; oxidizing agents (sulfur/nitro drugs); Rx with IV methylene blue Clinical methemoglobinemia: cyanosis not corrected by O₂; chocolate colored blood Carbon monoxide: SaO2; left-shift O₂ binding curve; inhibits cytochrome oxidase Causes carbon monoxide poisoning: car exhaust, space heaters, smoke inhalation S/S carbon monoxide poisoning: headache; cherry red color skin Cyanide: inhibits cytochrome oxidase; systemic asphyxiant Carbon monoxide + cyanide poisoning: house fires Left-shifted O, curve: 2,3 BPG, carbon monoxide, alkalosis, HbF, methemoglobin, hypothermia Right-shifted O₂ curve: ↑2,3 BPG, high altitude, acidosis, fever High altitude: respiratory alkalosis enhances glycolysis; ↑ synthesis 2,3 BPG Mitochondrial poisons: damages membrane and drains off protons; alcohol, salicylates Uncoupling agents in mitochondria: drain off protons; dinitrophenol, thermogenin (brown fat) Complication mitochondrial poisons/uncoupling agents: hyperthermia Decreased ATP: impaired Na/K ATPase pump (cellular swelling); reversible Anaerobic glycolysis: ATP synthesis in hypoxia; lactate intracellular pH, denatures proteins Irreversible injury hypoxia: membrane/mitochondrial damage Mitochondrial damage: release cytochrome c activates apoptosis Irreversible injury hypoxia:↑ cytosolic Ca² activates phospholipase, proteases, endonuclease Free radicals: unpaired electron in outer orbit; damage cell membranes and DNA Free radicals: superoxide, hydroxyl, peroxide, drugs (acetaminophen) Superoxide dismutase: neutralizes superoxide Glutathione: neutralizes peroxide, drug FRs Catalase: neutralizes peroxide Lipofuscin: indigestible lipid of lipid peroxidation; brown pigment increased in atrophy and FR damage Reperfusion injury in heart: superoxide FRs + calcium Mitochondrial injury: cytochrome c in cytosol initiates apoptosis SER hyperplasia: alcohol, barbiturates, phenytoin Complications SER hyperplasia: increases drug metabolism (e.g., oral contraceptives); vitamin D Chediak-Higashi: membrane protein defect in transferring lysosomal enzymes to phagocytic vacuoles Chediak-Higashi: AR; giant lysosomes I cell disease: absent enzyme marker in Golgi apparatus (mannose 6-phosphate); empty lysosomes Rigor mortis: stiff muscles after death due to ATP depletion Fatty change in liver: MCC alcohol (increase in NADH); DHAP G3PTG Fatty change in liver:↑ VLDL pushes nucleus to side Causes fatty change: ↑ synthesis TG/FAs, B-oxid FAs/synthesis apoproteins/release VLDL Fatty change in kwashiorkor: synthesis of apoproteins Ferritin: primary iron storage protein; soluble in blood; serum level reflects marrow storage iron Hemosiderin: insoluble ferritin degradation product visible with Prussian blue stain Atrophy: reduction in cell/tissue mass by either loss or cell shrinkage Brain atrophy: ischemia; Alzheimer's Exocrine gland atrophy in CF: duct obstruction by thick secretions Labile cells: stem cells (skin, marrow, GI tract) Stable cells: in Go phase (smooth muscle, hepatocytes); can enter cell cycle (growth factors, hormones) Permanent cells: cannot replicate; cardiac/striated muscle; neurons Hypertrophy: increase in cell size (structural components, DNA) LVH: increased preload (valve regurgitation), increased afterload (hypertension, aortic stenosis) RVH: pulmonary hypertension Bladder smooth muscle hypertrophy: prostate hyperplasia constricts urethra Removal of kidney: hypertrophy of remaining kidney Hyperplasia: increase in number of cells Endometrial hyperplasia: unopposed estrogen (obesity, taking estrogen) RBC hyperplasia: increased EPO (blood loss, ectopic secretion, high altitude) Prostate hyperplasia: increased dihydrotestosterone Gynecomastia: hyperplasia male breast tissue; normal in newborn, adolescent, elderly Metaplasia: one adult cell type replaces another cell type Squamous metaplasia in bronchus: smoking Intestinal metaplasia in stomach: Paneth cells, goblet cells; H. pylori chronic atrophic gastritis Squamous metaplasia bladder: Schistosoma hematobium infection Barrett's esophagus: glandular metaplasia of distal esophagus; due to GERD Dysplasia: atypical hyperplasia or metaplasia are precursors for cancer Squamous dysplasia in cervix: human papilloma virus Squamous dysplasia in bronchus: smoking Necrosis: death of groups of cells Coagulation necrosis: preservation of structural outline (due to lactic acid) Infarction: pale (e.g., heart, kidney); hemorrhagic (e.g., lung, small bowel); dry gangrene Liquefactive necrosis: brain infarct, bacterial infections; wet gangrene Caseous necrosis: variant coagulation necrosis; granulomas due to TB/systemic fungi Granulomas: activated macrophages (epithelioid cells); multinucleated giant cells; CD4 T cells Epithelioid cells: y-interferon released by CD4 T cells activates macrophages Multinucleated giant cells: fusion of epithelioid cells Granulomas: type IV hypersensitivity Enzymatic fat necrosis: associated with pancreatitis; soap formation (Ca²+ fatty acids) Fibrinoid necrosis: necrosis of immune reactions (immune vasculitis/endocarditis) Postmortem necrosis: autolysis; no inflammatory reaction Dystrophic calcification: calcification of damaged tissue; normal serum calcium Dystrophic calcification: pancreatitis; atherosclerotic plaque Metastatic calcification: calcification of normal tissue; increased serum calcium or phosphorus Nephrocalcinosis: metastatic calcification of collecting tubule basement membranes S/S nephrocalcinosis: polyuria due to nephrogenic diabetes insipidus; renal failure Apoptosis: gene regulated individual cell death Signals activating apoptosis: mullerian inhibitory factor, tumor necrosis factor, hormone withdrawal 2 Corticosteroids: lymphopenia, cosinopenia, neutrophilia Chronic MPD: neoplastic stem cell disorder, splenomegaly; marrow fibrosis; risk for leukernia Examples of MPD: polycythemia vera, myelofibrosis and myeloid metaplasia Relative polycythemia: plasma volume; ↑ RBC count, normal RBC mass Absolute polycythemia: ↑ RBC count and RBC mass Appropriate polycythemia: hypoxic stimulus for EPO to generate RBCs Causes of appropriate absolute polycythemia: lung disease, cyanotic heart disease, high altitude Appropriate absolute polycythemia: normal plasma volume; ↑ RBC mass; SaO;↑ EPO Inappropriate absolute polycythemia: no hypoxic stimulus for EPO Causes of inappropriate polycythemia: ectopic secretion EPO, polycythemia vera Polycythemia vera: ↑ plasma volume and RBC mass; normal SaO2; + EPO Ectopic EPO (renal cell carcinoma): normal plasma volume; ↑ RBC mass; normal SaO2; ↑ ΕΡΟ Myelofibrosis myeloid metaplasia: marrow fibrosis; extramedullary hematopoiesis; splenomegaly Lab findings in myelofibrosis: tear drop RBCs; dry bone marrow aspirate (marrow fibrosis) Essential thrombocythemia: MPD with increase in abnormal appearing platelets Myelodysplastic syndrome: severe anemia in elderly: 30% develop leukemia; ringed sideroblasts Benzene: aplastic anemia; acute leukemia Leukemia by age: ALL: newborn-14; AML: 15-60; CML: 40-60; CLL: > 60 Acute vs chronic leukemia: acute: blasts > 30% in bone marrow; chronic: blasts <10% in bone marrow AML: Auer rods in myeloblasts Acute promyelocytic leukemia: t(15;17); defect in retinoic acid; Rx retinoic acid (↑ maturation); DIC Acute monocytic leukemia: gum infiltration CML: t(9;22) of ABL POC; Philadelphia chromosome 22; leukocyte alkaline phosphatase score ALL: early pre-B (80%); CALLA (CD10) and TdT positive; CNS and testicle involvement ALL: t(12:21) offers good prognosis CLL: B cell neoplasm; y-globulins; MCC generalized lymphadenopathy patients > 60-yrs-old Adult T cell leukemia: HTLV-1; CD, T cells; skin infiltration; lytic bone lesions with hypercalcemia Hairy cell leukemia: positive TRAP stain; splenomegaly; Rx with purine nucleosides Nodal sites: germinal follicles: B cells; paracortex: T cells; sinuses: histiocytes Testicular cancer: metastasizes to para-aortic nodes Stomach cancer: metastasizes to left supraclavicular nodes (Virchow node) Phenytoin: atypical lymphocytosis Cat scratch disease: Bartonella henselae; granulomatous microabscesses Follicular B-cell lymphoma: t(14:18); overexpression of BCL-2 anti-apoptosis gene Burkitt lymphoma: t(8;14); EBV association; common childhood NHL.; "starry sky" appearance Extranodal lymphomas: risk factors- H. pylori (stomach); Sjogren's syndrome Mycosis fungoides: CD, T neoplasm; skin lesions with Pautrier's microabscesses Sezary syndrome: leukemic phase of mycosis fungoides Polyclonal gammopathy: sign of chronic inflammation Monoclonal gammopathy: M component (spike); sign of plasma cell disorder Confirmatory tests: serum and urine immunoelectrophoresis, bone marrow aspirate Bence Jones protein: light chains in urine; predictive of a malignant plasma cell disorder Multiple myeloma: M spike; lytic bone lesions; pathologic fractures; hypercalcemia; renal failure MGUS: MC monoclonal gammopathy; may progress to myeloma Findings in MGUS: elderly patient; no BJ protein; no malignant plasma cells Waldenstrom's macroglobulinemia: lymphoplasmacytic lymphoma; IgM M spike; hyperviscosity Hodgkin's lymphoma: neoplastic component Reed Sternberg (RS) cell; CD15 CD30 positive Lymphocyte predominant Hodgkin's: infrequent classic RS cells Nodular sclerosing Hodgkin's: female dominant, supraclavicular nodes + anterior mediastinal nodes Mixed cellularity Hodgkin's: male dominant; numerous RS cells; EBV association 11