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