Goljan HY General Pathology
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| PO2 | driving force for diffusion of O2 into tissue
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| SaO2 | percent heme groups occupied by O2
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| Cyanosis | decreased O2 saturation (SaO2); O2 content
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| Oxygen | electron acceptor in oxidative pathway
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| Hypoxia | inadequate O2 leads to ATP depletion
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| Ischemia | decreased arterial (or venous) blood flow
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| Respiratory acidosis | retention of CO, always decreases PaO2
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| Ventilation defect | impaired delivery of O2 to alveoli; intrapulmonary shunting of blood (e.g., RDS)
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| Perfusion defect | absent blood flow to alveoli; increased alveolar dead space (e.g., pulmonary embolus)
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| Diffusion defect | O2 cannot cross alveolar-capillary interface; interstitial lung disease (e.g., sarcoidosis)
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| Methemoglobin | ↓ SaO2; heme Fe+3; oxidizing agents (sulfur/nitro drugs); Rx with IV methylene blue
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| Clinical methemoglobinemia | cyanosis not corrected by O2; chocolate colored blood
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| Carbon monoxide | ↓ SaO2; left-shift O2 binding curve; inhibits cytochrome oxidase
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| Causes carbon monoxide poisoning | car exhaust, space heaters, smoke inhalation
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| S/S carbon monoxide poisoning | headache; cherry red color skin
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| Cyanide | inhibits cytochrome oxidase; systemic asphyxiant
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| Carbon monoxide + cyanide poisoning | house fires
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| Left-shifted O2 curve | ↓ 2, 3 BPG, carbon monoxide, alkalosis, HbF, methemoglobin, hypothermia
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| Right-shifted O2 curve | ↑ 2, 3 BPG, high altitude, acidosis, fever
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| High altitude | respiratory alkalosis enhances glycolysis; ↑ synthesis 2,3 BPG
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| Mitochondrial poisons | damages membrane and drains off protons; alcohol, salicylates
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| Uncoupling agents in mitochondria | drain off protons; dinitrophenol, thermogenin (brown fat)
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| Complication mitochondrial poisons/uncoupling agents | hyperthermia
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| Decreased ATP | impaired Na+/K+ ATPase pump (cellular swelling); reversible
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| Anaerobic glycolysis | ATP synthesis in hypoxia; lactate ↓ intracellular pH, denatures proteins
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| Irreversible injury hypoxia | membrane/mitochondrial damage
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| Mitochondrial damage | release cytochrome c activates apoptosis
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| Irreversible injury hypoxia | ↑ cytosolic Ca2+ activates phospholipase, proteases, endonuclease
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| Free radicals | unpaired electron in outer orbit; damage cell membranes and DNA
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| Free radicals | superoxide, hydroxyl, peroxide, drugs (acetaminophen)
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| Superoxide dismutase | neutralizes superoxide
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| Glutathione | neutralizes peroxide, drug FRs
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| Catalase | neutralizes peroxide
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| Lipofuscin | indigestible lipid of lipid peroxidation; brown pigment increased in atrophy and FR damage
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| Reperfusion injury in heart | superoxide FRs + calcium
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| Mitochondrial injury | cytochrome c in cytosol initiates apoptosis
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| SER hyperplasia | alcohol, barbiturates, phenytoin
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| Complications SER hyperplasia | increases drug metabolism (e.g., oral contraceptives); low vitamin D
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| Chediak-Higashi | membrane protein defect in transferring lysosomal enzymes to phagocytic vacuoles
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| Chediak-Higashi | AR; giant lysosomes
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| I cell disease | absent enzyme marker in Golgi apparatus (mannose 6-phosphate); empty lysosomes
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| Rigor mortis | stiff muscles after death due to ATP depletion
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| Fatty change in liver | MCC alcohol (increase in NADH); DHAP → G3P → TG
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| Fatty change in liver | VLDL pushes nucleus to side
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| Causes fatty change | ↑ synthesis TG/FAs, beta-oxidation of FAs, synthesis apoproteins/release VLDL
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| Fatty change in kwashiorkor | ↓ synthesis of apoproteins
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| Ferritin | primary iron storage protein; soluble in blood; serum level reflects marrow storage iron
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| Hemosiderin | insoluble ferritin degradation product visible with Prussian blue stain
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| Atrophy | reduction in cell/tissue mass by either loss or cell shrinkage
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| Brain atrophy | ischemia; Alzheimer’s
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| Exocrine gland atrophy in CF | duct obstruction by thick secretions
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| Labile cells | stem cells (skin, marrow, GI tract) →←→⇦
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| Stable cells | in G0 phase (smooth muscle, hepatocytes); can enter cell cycle (growth factors, hormones)
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| Permanent cells | cannot replicate; cardiac/striated muscle; neurons
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| Hypertrophy | increase in cell size (structural components, DNA)
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| LVH | increased preload (valve regurgitation), increased afterload (hypertension, aortic stenosis)
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| RVH | pulmonary hypertension
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| Bladder smooth muscle hypertrophy | prostate hyperplasia constricts urethra
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| Removal of kidney | hypertrophy of remaining kidney
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| Hyperplasia | increase in number of cells
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| Endometrial hyperplasia | unopposed estrogen (obesity, taking estrogen)
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| RBC hyperplasia | increased EPO (blood loss, ectopic secretion, high altitude)
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| Prostate hyperplasia | increased dihydrotestosterone (DHEA)
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| Gynecomastia | hyperplasia male breast tissue; normal in newborn, adolescent, elderly
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| Metaplasia | one adult cell type replaces another cell type
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| Squamous metaplasia in bronchus | smoking
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| Intestinal metaplasia in stomach | Paneth cells, goblet cells; H pylori chronic atrophic gastritis
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| Squamous metaplasia bladder | Schistosoma hematobium infection
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| Barrett’s esophagus | glandular metaplasia of distal esophagus; due to GERD
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| Dysplasia | atypical hyperplasia and metaplasia are precursors for cancer
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| Squamous dysplasia in cervix | human papilloma virus
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| Squamous dysplasia in bronchus | smoking
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| Necrosis | death of groups of cells
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| Coagulation necrosis | preservation of structural outline (due to ↑ lactic acid)
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| Infarction | pale (e.g., heart, kidney); hemorrhagic (e.g., lung, small bowel); dry gangrene
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| Liquefactive necrosis | brain infarct, bacterial infections; wet gangrene
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| Caseous necrosis | variant coagulation necrosis; granulomas due to TB/systemic fungi
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| Granulomas | activated macrophages (epithelioid cells); multinucleated giant cells; CD4 TH1 cells
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| Epithelioid cells | γ-interferon released by CD4 T cells activates macrophages
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| Multinucleated giant cells | fusion of epithelioid cells
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| Granulomas | type IV hypersensitivity
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| Enzymatic fat necrosis | associated with pancreatitis; soap formation (Ca2+ + fatty acids)
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| Fibrinoid necrosis | necrosis of immune reactions (immune vasculitis/endocarditis)
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| Postmortem necrosis | autolysis; no inflammatory reaction
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| Dystrophic calcification | calcification of damaged tissue; normal serum calcium
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| Dystrophic calcification | pancreatitis; atherosclerotic plaque
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| Metastatic calcification | calcification of normal tissue; increased serum calcium or phosphorus
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| Nephrocalcinosis | metastatic calcification of collecting tubule basement membranes
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| S/S nephrocalcinosis | polyuria due to nephrogenic diabetes insipidus; renal failure
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| Apoptosis | gene regulated individual cell death
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| Signals activating apoptosis | mullerian inhibitory factor, tumor necrosis factor, hormone withdrawal
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| Signal modulators of apoptosis | TP53 suppressor gene, BCL-2 genes
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| BCL-2 genes | anti-apoptosis gene; prevents cytochrome c from leaving mitochondria
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| Caspases | responsible for enzymatic cell death in apoptosis; proteases and endonucleases
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| Markers of apoptosis | eosinophilic cytoplasm, pyknotic (ink dot) nucleus
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| Apoptosis | loss Mullerian epithelium in male fetus; thymus involution; killing cancer cells
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| Histamine | key chemical in acute inflammation; mast cell; arteriole vasodilation; ↑ venular permeability
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| Rubor acute inflammation | redness; arteriole vasodilation (histamine)
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| Calor acute inflammation | heat; arteriole vasodilation (histamine)
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| Tumor acute inflammation | swelling; ↑ vessel permeability (histamine)
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| Dolor acute inflammation | pain; bradykinin, PGE
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| Acute inflammation | neutrophil dominant; ↑ IgM
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| Initial vessel events | transient vasoconstriction → arteriolar vasodilation → ↑ venular permeability
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| Neutrophil rolling acute inflammation | due to selectins
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| Integrins | neutrophil adhesion molecules; C5a and leukotriene B, activate; neutrophil margination
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| CD11/CD18 | markers for integrins
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| Endothelial cell adhesion molecules | activated by IL-1 and TNF
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| ICAM | intercellular adhesion molecule
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| VCAM | vascular cell adhesion molecule Leukocyte adhesion molecule defect
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| Activation neutrophil adhesion molecules | neutrophilic leukocytosis; corticosteroids
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| Activation neutrophil adhesion molecules | neutropenia; endotoxins
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| Chemotaxis | directed movement; C5a and LTB4
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| Opsonizing agents | IgG, C3b; enhance phagocytosis
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| Neutrophils, monocytes, macrophages | receptors for IgG, C3b
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| O2-dependent MPO system | most potent microbicidal system; neutrophils, monocytes
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| ProductionofsuperoxidefromO2 | NADPH oxidase with NADPH cofactor; produces respiratory burst
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| Nitro blue tetrazolium (NBT) | test for respiratory burst
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| Superoxide dismutase | converts superoxide to peroxide
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| Myeloperoxidase | lysosomal enzyme that combines peroxide + Cl to form bleach (HOCl)
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| Microbicidal defects | chronic granulomatous disease childhood (XR), myeloperoxidase deficiency (AR)
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| Chronic granulomatous disease | absent NADPH oxidase; no respiratory burst
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| Chronic granulomatous disease | Staphylococcus aureus not killed (catalase positive)
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| Chronic granulomatous disease | Streptococcus killed (catalase negative)
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| Myeloperoxidase deficiency | AR; respiratory burst present; no bleach produced
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| Opsonization defect | Bruton’s agammaglobulinemia (XR, decreased IgG)
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| Phagocytosis defect | Chediak-Higashi (see cell injury); also has defect in microtubule polymerization
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| COX inhibitors | non-steroidals (non-selective), selective COX-2 inhibitors
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| PGE2 | vasodilation, fever
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| PGI2 | vasodilator; prevent platelet aggregation
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| Nitric oxide | vasodilator; FR gas from conversion arginine to citrulline
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| IL-1 and TNF | fever, synthesis acute phase reactants in liver, leukocytosis
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| IL-6 | stimulated by IL-1; stimulates synthesis of acute phase reactants
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| Acute phase reactants | fibrinogen, ferritin, C-reactive protein
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| Bradykinin | kinin produced in conversion of factor XII to factor XI
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| Bradykinin | pain, vasodilator, vessel permeability; cough/angioedema, ACE inhibitors
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| Anaphylatoxins | C3a and C5a; directly stimulate mast cell release of histamine
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| Prostaglandin I2 | synthesized by endothelial cells; vasodilator, inhibits platelet aggregation
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| Lipoxygenase | hydroxylation of arachidonic acid
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| Zileuton | inhibits lipoxygenase
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| Zafirlukast, montelukast | block lipoxygenase receptor
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| LTC4, -D4, -E4 | bronchoconstrictors
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| TXA2 | synthesized by platelets; platelet aggregation, vasoconstriction, bronchoconstriction
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| Dipyridamole | inhibits thromboxane synthase
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| Corticosteroids | inhibits phospholipase A2, activation neutrophil adhesion molecules
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| Corticosteroids | neutrophilic leukocytosis, lymphopenia, eosinopenia
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| Fever | right shift OBC; hostile to bacterial/viral replication
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| Chronic inflammation | monocyte/macrophage; ↑ IgG; repair by fibrosis
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| Granuloma | cellular immunity; macrophages interact with TH1 class cells (memory cells)
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| Positive PPD | Langerhan’s cells process PPD and interact with TH1 class cells
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| Suppurative inflammation | abscess; Staphylococcus aureus (coagulase)
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| Cellulitis | subcutaneous inflammation; Streptococcus pyogenes (hyaluronidase)
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| Pseudomembranous inflammation | toxins from Corynebacterium diphtheriae, Clostridium difficile
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| Cell cycle | key checkpoint G1 to S phase
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| TP53 and RB suppressor genes | arrests cell in G1 phase for DNA repair or apoptosis
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| BAX gene | stimulates apoptosis; activated by TP53 suppressor gene if too much DNA damage
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| Extracellular matrix | basement membrane, interstitial matrix
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| Complete restoration | cell must be capable of duplication, no damage to basement membrane
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| Scar tissue | end-product of repair by connective tissue
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| Collagen | triple helix of cross-linked α chains
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| Collagen | cross-links at points of hydroxylation (lysyl oxidase) increase tensile strength
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| Type I collagen | bones, tendons
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| Type II collagen | early wound repair
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| Type IV collagen | basement membrane
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| Type X collagen | epiphyseal plate
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| Laminin | key basement membrane glycoprotein
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| Fibronectin | key interstitial matrix glycoprotein
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| Angiogenesis in repair | basic fibroblast growth factor, vascular endothelial growth factor
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| Key event in wound repair | granulation tissue formation; fibronectin responsible
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| Granulation tissue | becomes scar tissue
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| Collagenases | zinc cofactor (metalloprotease); type III collagen replaced by type I collagen
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| Tensile strength of healed wound | 80% original strength
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| Inhibition wound healing | infection (MCC S. aureus), zinc deficiency, DM
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| Ehlers-Danlos syndrome | defects in collagen synthesis and structure; hyperelasticity
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| Scurvy | ↓ collagen tensile strength by decreasing cross-links at points of hydroxylation
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| Keloid | excessive type III collagen; common in blacks
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| Pyogenic granuloma | exuberant granulation tissue; bleeds when touched
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| Healing by primary intention | clean wound; appose wound margins with suture
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| Healing by secondary intention | infected wound; leave wound open; myofibroblasts important
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| Liver injury | regenerative nodules; abnormal cytoarchitecture
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| Lung injury | type II pneumocyte repair cell
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| CNS injury | astrocyte and microglial cell repair cells; gliosis
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| WBC alterations in acute inflammation | neutrophilic leukocytosis, left shift, toxic granulation
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| Erythrocyte sedimentation rate | increased fibrinogen enhances rouleaux
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| C-reactive protein | indicator of acute inflammation and inflammatory atheromatous plaque
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| Polyclonal gammopathy | diffuse ↑ of γ-globulins; ↑ IgG; chronic inflammation
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| Total body water | ECF (plasma, interstitial fluid) + ICF (cytosol)
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| Osmosis | H20 shift between ECF and ICF; controlled by serum Na+ and glucose
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| Edema | increased fluid in interstitial space or body cavities; transudate, exudate, lymph
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| Transudate | protein and cell-poor fluid in interstitial space/body cavity; alteration Starling’s forces
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| Starling’s forces | oncotic pressure (albumin) keeps fluid in vessels, hydrostatic pressure pushes fluid out
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| Pitting edema | decreased oncotic pressure and/or increased hydrostatic pressure
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| ↑ Hydrostatic pressure | pulmonary edema in LHF; pitting edema of legs in RHF; portal hypertension
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| Renal retention sodium and water | ↑ hydrostatic pressure and ↓ oncotic pressure
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| Causes of renal retention of sodium/water | ↓ cardiac output (activation RAA system), primary renal disease
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| ↓ Oncotic pressure (hypoalbuminemia) | kwashiorkor; nephrotic syndrome; cirrhosis
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| Ascites in cirrhosis | ↓ oncotic pressure, ↑ hydrostatic pressure
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| Exudate | protein and cell rich (pus); acute inflammation with ↑ vessel permeability
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| Lymphedema | radical mastectomy; filariasis; inflammatory carcinoma (lymphatics plugged by tumor)
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| Thrombus | endothelial injury, stasis, hypercoagulability
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| Venous thrombus | fibrin clot with entrapped RBCs, WBCs, platelets; deep veins below knee (stasis)
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| Heparin/warfarin | anticoagulants that prevent venous clot formation
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| Arterial thrombus | endothelial injury; platelets held together by fibrin
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| Aspirin | prevents platelet thrombus in arteries
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| Pulmonary thromboembolism | femoral vein site of origin
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| Systemic thromboembolism | majority from left heart
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| Fat embolus | long bone fractures; delayed symptoms (48 hrs); thrombocytopenia, hypoxemia
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| Amniotic fluid embolism | DIC; lanugo hair in maternal pulmonary arteries
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| Diving | 1 atmosphere pressure increase with 33 foot descent into water; N2 gas dissolved in tissue
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| Decompression sickness | release of N2 gas from tissue with rapid ascent; ischemic damage
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| Dyspnea, chest pain underwater | pulmonary embolus
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| Dyspnea, chest pain rising to surface | spontaneous pneumothorax
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| Hypovolemic shock (blood loss) | ↓ CO and LVEDP; ↑ PVR
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| Cardiogenic shock | ↓ CO; ↑ LVEDP and PVR
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| Septic shock | ↑ CO (↑ venous return); ↓ PVR (vasodilation)
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| Kidneys | most susceptible organ in shock; straight portion proximal tubule most susceptible
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| Shock complications | ischemic ATN, multiorgan failure, ↑ AG metabolic acidosis
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| Tumors | parenchyma neoplastic component
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| Benign tumors | epithelial (e.g., adenoma) or connective tissue (e.g., lipoma, leiomyoma)
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| Carcinoma | epithelial origin; squamous cell carcinoma, adenocarcinoma, transitional cell carcinoma
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| Basal cell carcinoma | invades but does not metastasize
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| Squamous cell carcinoma | lower lip, oral pharynx, larynx, lung, esophagus, skin, cervix
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| Adenocarcinoma | distal esophagus → colon, kidney, liver, pancreas, prostate, breast, lung, endometrium
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| Transitional cell carcinoma | renal pelvis, ureter, bladder
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| Sarcoma | malignancy of connective tissue origin; e.g., osteogenic sarcoma (bone)
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| Liposarcoma | MC sarcoma in adults
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| Embryonal rhabdomyosarcoma | MC sarcoma in children
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| Teratoma | ectoderm, endoderm, mesoderm derivatives; bone/teeth visible on x-ray
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| Hamartoma | normal tissue, normal site; bronchial hamartoma, Peutz Jeghers polyp
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| Choristoma | normal tissue aberrant tissue location; pancreatic tissue stomach wall
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| Mixed tumor | different morphologic patterns, same germ cell layer; pleomorphic adenoma parotid
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| Leukemia | malignancy of stem cells in bone marrow
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| Lymphoma | malignancy of lymph nodes
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| Extranodal lymphoma sites | stomach (MC), Peyer’s patches
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| Malignant tumors | invade and metastasize; benign tumors do not
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| Upregulate telomerase | increases telomere length; found in all neoplastic cells
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| Monoclonality | key finding in neoplastic vs. normal cells
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| E-Cadherin | intercellular adhesion; lose adhesion in malignant cells
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| Malignant cells | receptors for laminin (basement membrane), fibronectin (ECM)
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| Invasion enzyme | type IV collagenase (basement membrane)
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| Angiogenesis | basic fibroblast growth factor, vascular endothelium growth factor
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| Metastasis | lymphatic, hematogenous, seeding; often more common than primary cancer
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| Carcinoma | lymph node -> hematogenous
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| Vessel invading carcinomas | renal cell carcinoma (renal vein, vena cava), hepatocellular carcinoma
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| Sarcoma | hematogenous
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| Seeding | ovarian cancer, periphery lung, CNS via spinal fluid
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| Sites where metastasis more common primary cancer | lung, bone, brain, liver, adrenal
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| Sites where primary cancer more common than metastasis | GI tract, kidney, urogenital
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| Bone metastasis | osteoblastic (radiodense); osteolytic (radiolucent)
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| Bone sites metastasis | vertebra MC (Batson venous plexus)
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| Osteoblastic metastasis | prostate cancer; increased serum AP, hypercalcemia
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| Osteolytic metastasis | breast cancer
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| EM neurosecretory granules | carcinoid tumors, small cell carcinoma, neuroblastoma
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| EM thin and thick myofilaments | rhabdomyosarcoma
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| EM Birbeck granules | histocytic neoplasms (Langerhan’s histiocytosis)
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| Primary prevention | stop smoking; sun screen; high fiber diet
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| Cancers in children | leukemia (MC), CNS tumors, Burkitt’s, Ewing’s, neuroblastoma
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| Cancer vaccine | hepatitis B vaccine; prevents hepatocellular carcinoma
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| Cancer incidence men | prostate → lung → colorectal
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| Cancer incidence women | breast → lung → colorectal
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| Cancer mortality men | lung → prostate → colorectal
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| Cancer mortality women | lung → breast → colorectal
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| Gynecologic cancers | endometrium → ovary → cervix
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| Cervical Pap smear | decreased incidence of cervical cancer; detects cervical dysplasia
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| Malignant melanoma | fastest increasing in world
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| Southeast China | nasopharyngeal carcinoma (EBV)
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| Southeast Asia | hepatocellular carcinoma (HBV + aflatoxin)
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| Japan | stomach cancer
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| Africa | Burkitt’s lymphoma, Kaposi sarcoma (HHV-8)
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| Squamous dysplasia oropharynx, larynx, bronchus, cervix | risk for squamous cell carcinoma (SCC)
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| Chronic irritation sinus orifices, third degree burn scars | risk for SCC
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|
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| Actinic (solar) keratosis | risk factor for SCC
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|
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| Glandular metaplasia of esophagus (Barrett’s) | risk factor for adenocarcinoma
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| Endometrial hyperplasia | risk factor for adenocarcinoma
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|
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| Glandular (intestinal) metaplasia of stomach (Helicobacter) | risk factor for adenocarcinoma
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| Chronic ulcerative colitis | risk factor for adenocarcinoma
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|
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| Villous adenoma of rectum | risk factor for adenocarcinoma
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| Tubular adenoma of colon | risk factor for adenocarcinoma
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| Scar tissue in lung | risk factor for adenocarcinoma
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|
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| Regenerative nodules in cirrhosis | risk factor for hepatocellular carcinoma
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| Complete hydatidiform mole | risk factor for choriocarcinoma
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| Dysplastic mole | MC risk factor for malignant melanoma
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| UVB light | MC risk factor for BCC, SCC, melanoma
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| HHV-8 | MC risk factor for Kaposi’s sarcoma
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| EBV | MC risk factor for nasopharyngeal carcinoma
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| Polycyclic hydrocarbons | MC risk factor for larynx (SCC), lung cancers
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| Asbestos | MC risk factor for mesothelioma
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|
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| Polycyclic hydrocarbons | MC risk factor for oral cavity, mid-esophagus SCC
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|
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| Barrett’s esophagus | MC risk factor for distal esophagus adenocarcinoma
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| H. pylori | MC risk factor for stomach adenocarcinoma and lymphoma
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| Tubular adenoma, villous adenoma | MC risk factors for colon adenocarcinoma
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|
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| HBV and HCV | MC risk factors for hepatocellular carcinoma
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|
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| Vinyl chloride | MC risk factor for liver angiosarcoma
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|
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| Gallstones, porcelain gallbladder | MC risk factor for gallbladder adenocarcinoma
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|
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| Polycyclic hydrocarbons | MC risk factor for pancreas adenocarcinoma
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|
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| Polycyclic hydrocarbons | MC risk factor for renal cell carcinoma
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|
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| Polycyclic hydrocarbons | MC risk factor for urinary bladder
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|
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| HPV + lack of circumcision | MC risk factor for penis SCC
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|
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| Age | MC risk factor for prostate adenocarcinoma
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|
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| Cryptorchid testis | MC risk factor for seminoma
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|
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| Age >50 with excess estrogen exposure | MC risk factor for breast and endometrial carcinoma
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|
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| HPV 16/18 | MC risk factor for vulva, vagina, cervix SCC
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|
||||
| DES | MC risk factor for vagina/cervix clear cell carcinoma
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|
||||
| Nulliparity | MC risk factor for surface derived ovarian cancer
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|
||||
| Complete mole | MC risk factor for choriocarcinoma
🗑
|
||||
| Turner syndrome (XO) | MC risk factor for dysgerminoma of ovary
🗑
|
||||
| Turner syndrome (XO/XY) | gonadoblastoma of ovary
🗑
|
||||
| Ionizing radiation | MC risk factor for papillary cancer of thyroid
🗑
|
||||
| Family history (MEN IIa/IIb) | MC risk factor for medullary carcinoma thyroid
🗑
|
||||
| Hashimoto’s thyroiditis | MC risk factor for malignant lymphoma thyroid
🗑
|
||||
| Ionizing radiation | MC risk factor for osteogenic sarcoma
🗑
|
||||
| EBV | MC risk factor for primary CNS lymphoma in AIDS and Burkitt’s lymphoma
🗑
|
||||
| Ionizing radiation | MC risk factor for acute/chronic myelogenous leukemia
🗑
|
||||
| EBV | MC risk factor for Burkitt’s lymphoma
🗑
|
||||
| HTLV-1 | MC risk factor for T cell leukemia/lymphoma
🗑
|
||||
| Bacterial causes of cancer | H. pylori (stomach adenocarcinoma and lymphoma)
🗑
|
||||
| Parasitic causes of cancer | S. hematobium (SCC bladder), C. sinensis (cholangiocarcinoma)
🗑
|
||||
| Carcinogenesis | mutations involving regulatory genes
🗑
|
||||
| Regulatory genes | proto-oncogenes, suppressor genes, anti-apoptosis genes
🗑
|
||||
| Types mutations | point mutation MC, translocation, amplification (↑ copies), overexpression (↑ activity)
🗑
|
||||
| Translocations | Burkitt’s t(8;14); CML t(9;22); follicular lymphoma t( 14;18); APL leukemia t( 15;17)
🗑
|
||||
| Key cancer genes | TP53 suppressor gene, RAS protooncogene
🗑
|
||||
| Point mutation | inactivates suppressor genes (e.g., TP53), activates proto-oncogenes (e.g., RAS)
🗑
|
||||
| Amplification | activates ERB-B2
🗑
|
||||
| Overexpression | enhances activity of BCL-2
🗑
|
||||
| S/S POC | function-growth factor synthesis; mutation-overexpression
🗑
|
||||
| ERB-B2 POC | function growth factor receptor; activation bad prognostic sign for breast carcinoma
🗑
|
||||
| RAS POC | function-GTP signal transduction; point mutation; 30% of all human cancer
🗑
|
||||
| ABL POC | function-non-receptor tyrosine kinase activity; translocation (9;22) causing CML
🗑
|
||||
| MYC POC | function nuclear transcription; translocation (8; 14) causing Burkitt’s lymphoma
🗑
|
||||
| Inactivation suppressor genes | majority are point mutations; loss of suppression
🗑
|
||||
| Sporadic retinoblastoma | two hit theory; two separate point mutations of RB suppressor gene on
🗑
|
||||
| AD retinoblastoma | one hit theory; one already inactivated in germ cells
🗑
|
||||
| TP53 suppressor gene functions | G,-S phase inhibition, DNA repair, activation BAX apoptosis gene
🗑
|
||||
| Inactivation TP 53 suppressor gene | inactivation causes majority of human cancers
🗑
|
||||
| RB suppressor gene function | G1-S phase inhibition
🗑
|
||||
| Inactivation RB suppressor gene | retinoblastoma, osteogenic sarcoma
🗑
|
||||
| APC suppressor gene function | prevents nuclear transcription by catenin
🗑
|
||||
| Inactivation APC suppressor gene | familial polyposis (FAP)
🗑
|
||||
| BRCA1/2 suppressor genes function | DNA repair Inactivation
🗑
|
||||
| BRCA 1/2 suppressor genes | breast, ovarian cancers
🗑
|
||||
| BCL-2 function | anti apoptosis gene (keeps cytochrome c in mitochondria)
🗑
|
||||
| BCL-2 gene | t(14;18) translocation of heavy chain causes overexpression; follicular B cell lymphoma [think t(14;18) = t(l4;lB) for foLLicular B]
🗑
|
||||
| Xeroderma pigmentosum | AR; defect in DNA repair enzymes; ↑ risk for UVB light cancers
🗑
|
||||
| Hereditary non-polyposis syndrome (HNPCC) | AD; inactivation DNA mismatch genes; colorectal cancer
🗑
|
||||
| Chromosome instability syndromes | AR; susceptibility to DNA damage; leukemias, lymphomas
🗑
|
||||
| Examples chromosome instability | Bloom syndrome, ataxia telangiectasia, Wiskott-Aldrich syndrome
🗑
|
||||
| Carcinogens | chemicals (MC), viruses, radiation, H. pylori, physical (squamous cancer in bum scar)
🗑
|
||||
| Polycyclic hydrocarbons | key chemical carcinogen (cigarette smoke)
🗑
|
||||
| Aflatoxins | produced from Aspergillus; hepatocellular carcinoma
🗑
|
||||
| Asbestos | lung cancer, mesothelioma
🗑
|
||||
| Thorium dioxide | hepatocellular carcinoma, cholangiocarcinoma
🗑
|
||||
| Aniline dyes | transitional cell carcinoma
🗑
|
||||
| Vinyl chloride | angiosarcoma of liver
🗑
|
||||
| Benzene | leukemia
🗑
|
||||
| Cyclophosphamide | transitional cell carcinoma of bladder
🗑
|
||||
| EBV | Burkitt’s; CNS lymphoma (AIDS); Hodgkin’s mixed cellularity; nasopharyngeal carcinoma
🗑
|
||||
| HBV and HCV | hepatocellular carcinoma
🗑
|
||||
| HPV | cervical, penis, and anorectal squamous cancers
🗑
|
||||
| HHV-8 | Kaposi sarcoma
🗑
|
||||
| UVB cancers | basal cell carcinoma, squamous cell carcinoma, malignant melanoma
🗑
|
||||
| Key host defense | cytotoxic CD8 T cells (type IV hypersensitivity)
🗑
|
||||
| Cachexia | due to tumor necrosis factor-α
🗑
|
||||
| Most common anemia | anemia chronic disease
🗑
|
||||
| Most common coagulopathy | hypercoagulability
🗑
|
||||
| Most common COD in cancer | gram negative infection
🗑
|
||||
| Acanthosis nigricans, seborrheic keratoses; possible markers for gastric adenocarcinoma |
🗑
|
||||
| Clubbing | possible marker for lung cancer
🗑
|
||||
| Non-bacterial thrombotic endocarditis mitral valve | possible marker for pancreatic cancer
🗑
|
||||
| TNM staging | metastasis more important than nodal involvement
🗑
|
||||
| AFP | hepatocellular carcinoma, yolk sac tumors
🗑
|
||||
| PSA | prostate cancer
🗑
|
||||
| CEA | recurrence colorectal cancer
🗑
|
||||
| BJ (Bence-Jones) protein | multiple myeloma
🗑
|
||||
| β-human chorionic gonadotropin | choriocarcinoma
🗑
|
||||
| Calcitonin | medullary carcinoma thyroid; hypocalcemia
🗑
|
||||
| Small cell carcinoma lung | ADH (hyponatremia), ACTH (ectopic Cushing’s)
🗑
|
||||
| Renal cell carcinoma | EPO (polycythemia), PTH-related peptide (hypercalcemia)
🗑
|
||||
| Hepatocellular carcinoma | EPO (polycythemia), insulin-like factor (hypoglycemia)
🗑
|
||||
| Medullary carcinoma of thyroid | calcitonin (hypocalcemia), ACTH (ectopic Cushing’s)
🗑
|
||||
| Squamous cell carcinoma of lung | PTH-related peptide (hypercalcemia)
🗑
|
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