Toxicology Exam 3

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Functions of the liver
- production of bile which is stored in the gall bladder
- storage of glucose in the form of glycogen
- metabolism of protein and fats
- storage of A, D, K, B12 and Folate
- synthesis of clotting factors
- detoxification
Fatty liver
- deposits of fat cause liver enlargement
- still functional
- reversible
liver fibrosis

scar tissue forms
liver cirrhosis
- growth of connective tissue destroys liver cells
- 20-25 yrs of heavy drinking
- non reversible
most succeptible zone for damage
- zone 1
- highest blood flow
Toxic responses of the renal system
- afferent arteriolar constriction
- obstruction
- back leak
Afferent arteriolar constriction to the glomerulus results in

decreased glomerular pressure
Toxins to the lungs may be

particualates or gases
Size of particles effecting the alveolar region

1 micrometer
consequence of impaired nutrient homeostasis in the liver
- hypoglycemia
- confusion
- hypercholesterolemia
consequence of impaired filtration of particulates in the liver

endotoxemia
Consequences of impaired protein synthesis in the liver
- excess bleeding
- hypoalbuminemia
- ascites
- fatty liver
consequences of impaired bioactivation and detoxification in the liver
- jaundice
- hyperammonemia => coma
- Loss of secondary male sex characteristics
- diminished drug metabolism
- inadequate detoxification
consequences of limpaired formation of bile and biliary secretion in the liver
- fatty diarrhea
- malnutrition
- vitamin E deficiency
- jaundice
- gallstones
- hypercholesterolemia
- Manganese induced neurotoxicity
- delayed drug clearance
Toxins that may cause fatty liver
- CCL4
- ethanol
- fialuridine
- valproic acid
toxins that may cause hepatocyte death
- apap
- Cu
- dimethylformamide
- ethanol
- ecstasy
toxins that may cause immune mediated response in the liver
- declofenac
- ethanol
- halothane
- tienilic acid
toxins that may cause canalicular cholestasis
- chlorpromazine
- cyclosporin A
- 1,1-dichlorethylene
- estrogens
- Mn
- phalloidin
toxins that may cause bile duct damage
- amoxicillin
- ANIT
- methylene dianiline
- sporidosmin
toxins that may cause sinusoidal disorders
- anabolic steroids
- cyclophosphamide
- microcystin
- pyrrolidine alkaloids
toxins that may cause fibrosis and cirrhosis of the liver
- arsenic
- ethanol
- vitamin A
- vinyl chloride
toxins that may cause tumors in the liver
- aflatoxin
- androgens
- thorium dioxide
- vinyl chloride
Zone 1 hepatotoxins
- Fe overload
- allyl alcohol
Zone 3 hepatotoxins
- CCL4
- APAP
- Ethanol
Bile duct toxins
- methylene dianiline
- sporidesmin
sinusoidal toxins
- cyclophosphamide
- monocrotaline
kupffer cell toxins
- endotoxin
- GdCL3
Ito cell toxin
- Vitamin A
- Ethanol (chronic)
Reasons for zone 1 toxicity
- preferntial uptake area
- high oxygen levels
Reasons for zone 3 toxicity
- more P450 enzymes
- less GSH for detoxification
Reason for bile duct toxicity

high concentrations of reactive metabolites in the bile
reasons for sinusoidal toxicity
- greater vulnerability to toxic metabolites
- less ability to maintain glutathione levels
reason for toxicity in kupffer cells

preferential uptake and activation
reason for toxicity in Ito cells
- preferential site for vitamin A storage
- activation and transformation to collagen synthesizing cells in response to ethanol

Author

Rx2013

78850

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Toxicology Exam 3

Description

Toxic Responses of the hepatic, renal and respiratory systems

Updated

2011-04-11T16:41:05Z

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