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391 Cards in this Set
- Front
- Back
|
driving force for diffusion of 02 into tissue
|
P02
|
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percent heme groups occupied by 02
|
SaO2
|
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decreased 02 saturation (Sa02)
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Cyanosis
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02 content equation
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1.34 x Hb x Sa02 + Pa02
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electron acceptor in oxidative pathway
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Oxygen
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inadequate 02 leads to ATP depletion
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Hypoxia
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decreased arterial (or venous) blood flow
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Ischemia
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PaO2 of respiratory acidosis
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retention of CO2 always decreases Pa02
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Ventilation defect
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impaired delivery of 02 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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02 cannot cross alveolar-capillary interface; interstitial lung disease (e.g., sarcoidosis)
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methemoglobin
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Sa02; heme iron +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 02; chocolate colored blood
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Carbon monoxide
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L Sa02; left-shift 02 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 mechanisms of toxicity
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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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house fires
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2,3 BPG, carbon monoxide, alkalosis, HbF, methemoglobin, hypothermia
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Right-shifted 02 curve
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T 2,3 BPG, high altitude, acidosis, fever
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Diffusion defect
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02 cannot cross alveolar-capillary interface; interstitial lung disease (e.g., sarcoidosis)
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methemoglobin
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Sa02; heme iron +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 02; chocolate colored blood
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Carbon monoxide
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L Sa02; left-shift 02 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 mechanisms of toxicity
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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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house fires
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2,3 BPG, carbon monoxide, alkalosis, HbF, methemoglobin, hypothermia
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Right-shifted 02 curve
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T 2,3 BPG, high altitude, acidosis, fever
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High altitude
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respiratory alkalosis enhances glycolysis; T 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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Anaerobic glycolysis
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ATP synthesis in hypoxia; lactate, dec intracellular pH, denatures proteins
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Decreased ATP
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impaired Na+/K+ ATPase pump (cellular swelling); reversible
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Irreversible injury hypoxia
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membrane/mitochondrial damage
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Mitochondrial damage causes release of:
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cytochrome c activates apoptosis
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Irreversible injury hypoxia leads to the cascade in which:
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inc 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 examples
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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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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 leads to:
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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); dec vitamin D
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cause of Chediak-Higashi
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microtubule polymerization defect resulting in decreased phagocytosis
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Chediak-Higashi details
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autosomal recessive, 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 MCC
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MCC alcohol (increase in NADH); DHAP--> G3P-> TG
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Fatty change in liver cellular appearance
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inc VLDL pushes nucleus to side
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Cause of fatty change in liver
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inc synthesis TG/FAs, dec beta-oxid FAs/synthesis apoproteins/release VLDL
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Fatty change in kwashiorkor
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dec 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: in Go phase
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(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
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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 or metaplasia are precursors for cancer
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Squamous dysplasia in cervix
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HPV
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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 inc 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 T cells
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Epithelioid cells
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y-interferon released by CD4 T cells activates macrophages
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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 in the healthy body
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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; T 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; inc 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; inc IgM
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Initial vessel events in inflammation
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transient vasoconstriction -> arteriolar vasodilation -> inc venular permeability
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Neutrophil rolling acute inflammation
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due to selectin
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Integrins
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neutrophil adhesion molecules; C5a and leukotriene B4 activate; neutrophil margination
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CD11/CD18
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markers for integrins
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Endothelial cell adhesion molecules activated by:
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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
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Leukocyte adhesion molecule defect clinical presentation
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failure of umbilical cord to separate; poor wound healing
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dec Activation neutrophil adhesion molecules by
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neutrophilic leukocytosis; corticosteroids
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inc Activation neutrophil adhesion molecules by
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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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02-dependent MPO system
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most potent microbicidal system; neutrophils, monocytes
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Production of superoxide from 02
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NADPH oxidase with NADPH cofactor; produces respiratory burst
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Nitroblue 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 (HOC1)
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genetic Microbicidal defects
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chronic granulomatous disease childhood (XR), myeloperoxidase deficiency (AR)
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Chronic granulomatous disease etiology
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absent NADPH oxidase; no respiratory burst
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Chronic granulomatous disease organism
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Staphylococcus aureus not killed (catalase positive)
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Chronic granulomatous disease, organisms NOT involved
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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; 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 produced:
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in conversion of factor XII to factor XI
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Bradykinin effects
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pain, vasodilator, inc 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 biochemical effect
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inhibits phospholipase A2, activation neutrophil adhesion molecules
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Corticosteroids peripheral blod smear effect:
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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; inc IgG; repair by fibrosis
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Granuloma
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cellular immunity; macrophages interact with THl 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
|
toxins from Corynebacterium diphtheriae, Clostridium d ffcile Cell cycle: key checkpoint Gt to S phase
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TP53 and RB suppressor genes
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arrests cell in G, 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 of a cell
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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 a chains
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Collagen
|
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 III collagen
|
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
|
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
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granulation tissue formation; fibronectin responsible
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Granulation tissue eventually...
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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 of wound healing
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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 primary intention
|
clean wound; appose wound margins with suture
|
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Healing secondary intention
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infected wound; leave wound open; myofibroblasts important
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Liver injury and repair
|
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 and repair
|
astrocyte and microglial cell repair cells; gliosis
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WBC alterations acute inflammation
|
neutrophilic leukocytosis, left shift, toxic granulation
|
|
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Erythrocyte sedimentation rate
|
increased fibrinogen enhances rouleau
|
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C-reactive protein
|
indicator acute inflammation and inflammatory atheromatous plaque
|
|
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Polyclonal gammopathy
|
diffuse elevation y-globulins; T IgG; chronic inflammation
|
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Total body water
|
ECF (plasma, interstitial fluid), ICF (cytosol)
|
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Osmosis
|
H2O 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
|
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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inc Hydrostatic pressure
|
pulmonary edema in LHF; pitting edema of legs in RHF; portal hypertension
|
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Renal retention sodium and water
|
inc hydrostatic pressure and dec oncotic pressure
|
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Causes renal retention sodium/water
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Dec cardiac output (activation RAA system), primary renal disease
|
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Dec Oncotic pressure (hypoalbuminemia):
|
kwashiorkor; nephrotic syndrome; cirrhosis
|
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Ascites in cirrhosis
|
dec oncotic pressure, inc hydrostatic pressure
|
|
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Exudate
|
protein and cell rich (pus); acute inflammation with inc 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
|
|
|
Systemic thromboembolism
|
majority from left heart
|
|
|
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
|
|
|
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
|
|
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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)
|
dec CO and LVEDP; inc PVR
|
|
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Cardiogenic shock
|
dec CO; inc LVEDP and PVR
|
|
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Septic shock
|
inc CO (inc venous return); dec PVR (vasodilation)
|
|
|
Kidneys and shock
|
most susceptible organ in shock; straight portion proximal tubule most susceptible
|
|
|
Shock complications
|
ischemic ATN, multiorgan failure, inc 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 location
|
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)
|
|
|
MC sarcoma in adults
|
Liposarcoma
|
|
|
MC sarcoma in children
|
Embryonal rhabdomyosarcoma
|
|
|
Teratoma appearance
|
ectoderm, endoderm, mesoderm derivatives; bone/teeth visible on x-ray
|
|
|
Hamartoma appearance
|
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 definition
|
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 have 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 metastasis
|
lymph node--> hematogenous
|
|
|
Vessel invading carcinomas
|
renal cell carcinoma (renal vein, vena cava), hepatocellular carcinoma
|
|
|
Sarcoma metastasis
|
hematogenous
|
|
|
Seedind of a tumor
|
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
|
|
|
EM neurosecretory granules and cancer
|
carcinoid tumors, small cell carcinoma, neuroblastoma
|
|
|
EM thin and thick myofilaments
|
rhabdomyosarcoma
|
|
|
EM Birbeck granules
|
histocytic neoplasms (Langerhan's histiocytosis)
|
|
|
Primary prevention of cancer
|
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 has resulted in
|
decreased incidence of cervical cancer; detects cervical dysplasia
|
|
|
Malignant melanoma
|
fastest increasing in world
|
|
|
cancer in person from Southeast China
|
nasopharyngeal carcinoma (EBV)
|
|
|
cancer in person from Southeast Asia
|
hepatocellular carcinoma (HBV + aflatoxin)
|
|
|
cancer in person from Japan
|
stomach cancer
|
|
|
cancer in person from 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) as a risk factor for
|
risk factor for adenocarcinoma
|
|
|
Endometrial hyperplasia as a risk factor for
|
risk factor for adenocarcinoma
|
|
|
Glandular (intestinal) metaplasia of stomach (Helicobacter) as a risk factor for
|
risk factor for adenocarcinoma
|
|
|
Chronic ulcerative colitis as a risk factor for
|
risk factor for adenocarcinoma
|
|
|
Villous adenoma of rectum as a risk factor for
|
risk factor for adenocarcinoma
|
|
|
Tubular adenoma of colon as a risk factor for
|
risk factor for adenocarcinoma
|
|
|
Scar tissue in lung as a risk factor for
|
risk factor for adenocarcinoma
|
|
|
Regenerative nodules in as a risk factor forcirrhosis
|
risk factor for hepatocellular carcinoma
|
|
|
Complete hydatidiform mole as a risk factor for
|
risk factor for choriocarcinoma
|
|
|
Dysplastic mole as a risk factor for
|
MC risk factor for malignant melanoma
|
|
|
UVB light as a risk factor for
|
MC risk factor for BCC, SCC, melanoma HHV-8: MC risk factor for Kaposi's sarcoma
|
|
|
EBV as a risk factor for
|
MC risk factor for nasopharyngeal carcinoma
|
|
|
Polycyclic hydrocarbons as a risk factor for
|
MC risk factor for larynx (SCC), lung cancers
|
|
|
Asbestos as a risk factor for
|
MC risk factor for mesothelioma
|
|
|
Polycyclic hydrocarbons as a risk factor for
|
MC risk factor for oral cavity, mid-esophagus SCC
|
|
|
Barrett's esophagus as a risk factor for
|
MC risk factor for distal esophagus adenocarcinoma
|
|
|
H. pylori as a risk factor for
|
MC risk factor for stomach adenocarcinoma and lymphoma
|
|
|
Tubular adenoma, villous adenoma as a risk factor for
|
MC risk factors for colon adenocarcinoma
|
|
|
HBV and HCV as a risk factor for
|
MC risk factors for hepatocellular carcinoma
|
|
|
Vinyl chloride as a risk factor for
|
MC risk factor for liver angiosarcoma
|
|
|
MC risk factor for gallbladder adenocarcinoma
|
Gallstones, porcelain gallbladder
|
|
|
MC risk factor for pancreas adenocarcinoma
|
Polycyclic hydrocarbons
|
|
|
MC risk factor for renal cell carcinoma
|
Polycyclic hydrocarbons
|
|
|
MC risk factor for urinary bladder
|
Polycyclic hydrocarbons
|
|
|
MC risk factor for penis SCC
|
HPV + lack of circumcision
|
|
|
MC risk factor for prostate adenocarcinoma
|
Age
|
|
|
MC risk factor for seminoma
|
Cryptorchid testis
|
|
|
MC risk factor for breast and endometrial carcinoma
|
Age > 50 with excess estrogen exposure
|
|
|
MC risk factor for vulva, vagina, cervix SCC
|
HPV 16/18
|
|
|
MC risk factor for vagina/cervix clear cell carcinoma
|
DES
|
|
|
MC risk factor for surface derived ovarian cancer
|
Nulliparity
|
|
|
MC risk factor for choriocarcinoma
|
Complete mole
|
|
|
MC risk factor for dysgerminoma of ovary
|
Turner syndrome (XO)
|
|
|
Turner syndrome (XO/XY) as a risk factor for
|
gonadoblastoma of ovary
|
|
|
MC risk factor for papillary cancer of thyroid
|
Ionizing radiation
|
|
|
MC risk factor for medullary carcinoma thyroid
|
Family history (MEN IIa/IIb)
|
|
|
MC risk factor for malignant lymphoma thyroid
|
Hashimoto's Thyroiditis
|
|
|
MC risk factor for osteogenic sarcoma
|
ionizing radiation
|
|
|
MC risk factor for primary CNS lymphoma in AIDS and Burkitt's lymphoma
|
EBV
|
|
|
MC risk factor for acute/chronic myelogenous leukemia
|
Ionizing radiation
|
|
|
MC risk factor for Burkitt's lymphoma
|
EBV
|
|
|
MC risk factor for T cell leukemia/lymphoma
|
HTLV-1
|
|
|
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, general types
|
protooncogenes, suppressor genes, anti-apoptosis genes
|
|
|
Types of mutations
|
point mutation MC, translocation, amplification (inc copies), overexpression (inc activity)
|
|
|
Burkitt's translocation
|
t(8;14)
|
|
|
CML translocation
|
t(9;22)
|
|
|
follicular lymphoma translocation
|
t(14;18)
|
|
|
APL leukemia translocation
|
t(15;17)
|
|
|
2 Key cancer genes:
|
TP53 suppressor gene, RAS protooncogene
|
|
|
Point mutation
|
inactivates suppressor genes (e.g., TP53), activates protooncogenes (e.g., RAS)
|
|
|
Amplification mutation
|
activates ERB-B2
|
|
|
Overexpression mutation
|
enhances activity of BCL-2
|
|
|
SIS Proto-oncogene
|
function- growth factor synthesis; mutation- overexpression
|
|
|
ERB-B2 Proto-oncogene
|
function- growth factor receptor; activation bad prognostic sign for breast carcinoma
|
|
|
RAS Proto-oncogene
|
function- GTP signal transduction; point mutation; 30% of all human cancer
|
|
|
ABL Proto-oncogene
|
function- non-receptor tyrosine kinase activity; translocation (9;22) causing CML
|
|
|
MYC Proto-oncogene
|
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 # 13
|
|
|
AD retinoblastoma
|
one hit theory; one already inactivated in germ cells
|
|
|
TP53 suppressor gene functions
|
G1-S phase inhibition, DNA repair, activation BAX apoptosis gene
|
|
|
Inactivation TP53 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
|
|
|
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
|
|
|
Xeroderma pigmentosum
|
AR; defect in DNA repair enzymes; inc risk for UVB light cancers
|
|
|
Hereditary non-polyposis syndrome
|
AD; inactivation DNA mismatch genes; colorectal cancer
|
|
|
Chromosome instability syndromes
|
AR; susceptibility to DNA damage; leukemias, lymphomas
|
|
|
Examples of chromosome instability
|
Bloom syndrome, ataxia telangiectasia, Wiskott-Aldrich syndrome
|
|
|
Carcinogens
|
chemicals (MC), viruses, radiation, H. pylori, physical (squamous cancer in burn scar)
|
|
|
Polycyclic hydrocarbons
|
key chemical carcinogen (cigarette smoke)
|
|
|
Aflatoxins
|
produced from Aspergillus; hepatocellular carcinoma
|
|
|
Asbestos
|
lung cancer, mesothelioma
|
|
|
Thorium dioxide causes
|
hepatocellular carcinoma, cholangiocarcinoma
|
|
|
Aniline dyes causes
|
transitional cell carcinoma
|
|
|
Vinyl chloride causes
|
angiosarcoma of liver
|
|
|
Benzene causes
|
leukemia
|
|
|
Cyclophosphamide causes (neoplasm)
|
transitional cell carcinoma of bladder
|
|
|
EBV causes which neoplasms:
|
Burkitt's; CNS lymphoma (AIDS); Hodgkins mixed cellularity; nasopharyngeal carcinoma
|
|
|
HBV and HCV cause which neoplasm
|
hepatocellular carcinoma
|
|
|
HPV causes which neoplasms
|
cervical, penis, and anorectal squamous cancers
|
|
|
HHV-8 causes which neoplasm
|
Kaposi sarcoma
|
|
|
UVB-cancers
|
basal cell carcinoma, squamous cell carcinoma, malignant melanoma
|
|
|
Key host defense to neoplasms
|
cytotoxic CD8 T cells (type N hypersensitivity)
|
|
|
cachexia in cancer
|
due to tumor necrosis factor-alpha
|
|
|
Most common anemia in cancer
|
anemia chronic disease
|
|
|
Most common coagulopathy in cancer
|
hypercoagulability
|
|
|
Most common COD in cancer
|
gram negative infection
|
|
|
Acanthosis nigricans, seborrheic keratoses and cancer
|
possible markers for gastric adenocarcinoma
|
|
|
clubbing and cancer
|
possible marker for lung cancer
|
|
|
Non-bacterial thrombotic endocarditis mitral valve and cancer
|
possible marker for pancreatic cancer
|
|
|
TNM staging
|
metastasis more important than nodal involvement
|
|
|
AFP found with
|
hepatocellular carcinoma, yolk sac tumors
|
|
|
PSA found with
|
prostate cancer
|
|
|
CEA found with
|
recurrence colorectal cancer
(any GI cancer) |
|
|
BJ protein found with
|
multiple myeloma
|
|
|
beta hCG found with
|
choriocarcinoma
|
|
|
Calcitonin elevated with
|
medullary carcinoma thyroid, hypocalcemia
|
|
|
Small cell carcinoma lung associated hormones
|
ADH (hyponatremia), ACTH (ectopic Cushing's)
|
|
|
Renal cell carcinoma associated hormones
|
EPO (polycythemia), PTH-related peptide (hypercalcemia)
|
|
|
Hepatocellular carcinoma associated hormones
|
EPO (polycythemia), insulin-like factor (hypoglycemia)
|
|
|
Medullary carcinoma of thyroid associated hormones
|
calcitonin (hypocalcemia), ACTH (ectopic Cushing's)
|
|
|
Squamous cell carcinoma of lung associated hormones
|
PTH-related peptide (hypercalcemia)
|
