Target Organ Toxicity Flashcards
why is the liver so susceptible to toxicity arising from xenobiotic exposure?
lots of metabolism; lots of perfusion; enterohepatic cycling; first pass effect; binding proteins; active transport pumps; high rates of cell mitosis;
what is BUN?
blood urea nitrogen– increased urea in blood indicates reduced GFR
what is GFR?
glomerular filtration rate
3 regions of the respiratory system
nasal passages; conducting airways (trachea and bronchi); gas exchange region (alveoli)
sources of lung damage
oxidative stress (ozone–from motor vehicle exhaust); gases and vapours; particles and aerosols
what is PM2.5
particulate matter less than 2.5 um – associate with human respiratory tract toxicity– including death
What are the toxic responses of the liver?
steatosis; necrosis; cholestasis; cirrhosis; carcinogenesis
what is steatosis?
fatty liver; >5% fat accumulation in liver; can be due to chronic or acute exposure; reversible; –>e.g ethanol (binge drinking or chronic drinking); c
what is the clinical marker of steatosis?
serum triglycerides (storage form of lipids);
what is necrosis?
focal (central, midzone, or peripheral) or massive (throughout the river); usually acute exposure; irreversible; involves decreased ATP or altered Ca regulation;
what are some examples of liver necrosis-causing agents?
acetominophen (Tylenol); produces active quinonamine– produces ROS; CCl4 (carbon tetrachloride); liquid at R; disinfectant
what is a biomarker for liver necrosis?
gamma glutamyl transpeptidase; GGT in blood plasma
what is cholestasis of the liver?
canicular cholestasis–decreased bile formation and biliary secretion;
symptoms of liver cholestasis?
jaundice–>due to excess bilirubin in blood
examples of xenobiotics that cause liver cholestasis?
ethanol, certain metals, steroids, certain drug
clinical marker of liver cholestasis?
GGT and plasma bilirubin
what is liver cirrhosis?
extensive fibrosis throughout the liver;
what causes cirrhosis of the liver?
chronic alcohol consumption; ethanol–>mitochondrial damage–> steatosis; necrosis–>fibrosis
what is the clinical marker of liver cirrhosis?
plasma GGT
what is carcinogenesis of the liver/
common form of cancer–> most common;
what can cause liver cancer
improper storage of grains–> creates aflotoxins; alfotoxins + common disease hepatitis= cancer of the liver
can produce all 5 stages of liver toxicity very easily in lab animals–> better to use a fish than a dog; also many xenos cause all 5 stages
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major function of the kidney?
excretion of metabolic (nitrogenous) waste; regulation of EC fluid volume (bp regulation); electrolyte homeostasis; acid-base balance; blood pressure regulation; metabolizes vit D to active form
what are nephrotoxicants?
affect the nephrons in the kidney
examples of nephrotoxicants
certain heavy metals (Cadmium); organochlorines; (halogenated hydrocarbons); and drugs–especially antibiotics and analgesics
why are PCT cells the most susceptible to nephrotoxicants?
tubular transport of many xenos occur in PCT cells–>can result in accumulation; have the greatest CYP activity among kidney cells; high metabolic activity (lots of mito)
–glomerular cells also susceptible
how can one test kidney function?
urinalysis; blood analysis;
what tests does urinalysis involve?
proteinuria; glycosuria; functional enzyme tests;
what does proteinuria test for?
increased levels of small proteins indicates loss of PCT reabsorption, indicating toxicity to PCT cells; increased amounts of large proteins indicates damage to glomerular cells;
what does glycosuria measure?
increased glucose in urine–>indicates tubular dysfunction (in absence of hyperglycemia)
what does functional enzyme tests measure?
amount of GGT in urine–>indicates cells are dying (like with liver)
what does blood analysis measure?
blood uria nitrogen; creatine clearance;
what is creatine clearance?
presence of creatine in the blood indicates impaired kidney function
what are the acute effects of resp toxicity?
can be reversible or irreversible; airway reactivity; pulmonary edema;
what is airway reactivity?
usually bronchial sm muscle is targeted–> effect is usually muscle contraction; a major concern for asthmatics when there is a lot of air pollution (gases and fine particles) in hot, urban areas
what is pulmonary edema and what can cause it?
fluid accumulation in the lungs–> reduces O2/CO2 exchange; Cl2; NH3; gas
what are chronic effects of resp toxicity?
usually irreversible; fibrosis; emphysema; asthma; neoplasia
what is fibrosis of the lungs?
increased ECM protein (collagen) production by fibroblasts, builds up in alveoli–> lungs become smaller and stiffer
what is emphasyma of the lungs?
kind of opposite to fibrosis– lungs become more stretchy and larger–> due to break down of elastin; results in impaired alveolar gas exchange
what can cause neoplasia of the lungs?
tobacco smoke; metallic dusts; and fumes (As, Cd, Ni, Cr); asbestos, radon gas
