Study Set Content:
toxicant-induced cholestasis can be
transient or chronic.
Damage to the intrahepatic bile ducts (which carry bile from the liver to the GI tract) is called
cholangiodestructive cholestasis
A useful biochemical index of bile duct damage is a sharp elevation in serum () activity. In addition, serum levels of () and() are elevate
alkaline phosphatase, bile salts, bilirubin
Initial lesions following a single dose of cholangiodestructive agents include swollen biliary(), debris damaged cells within lumens of the biliary tract, and inflammatory cell in filtration of portal tracts.
epithelium
Chronic administration of chemicals that cause bile duct destruction can lead to biliary proliferation and fibrosis resembling biliary ()
cirrhosis
A rare response is the loss of bile ducts, a condition known as () • reported in px receiving: antibiotics, anabolic steroids, contraceptive steroids, or the anticonvulsant carbamazepine
vanishing bile duct syndrome.
A specialized capillary with numerous fenestrae or high permeability; can be compromised by dilation or blockade of its lumen or by progressive destruction of its endothelial cell wall.
SINUSOIDAL DAMAGE
Dilation of the sinusoid will occur whenever efflux of hepatic blood is ()
impeded.
Blockade of lumen after large doses of () will occur when red blood cells become caught in the sinusoids (specialized capillary
APAP (acetaminophen)
A consequence of extensive sinusoidal blockade is that the liver becomes engorged with blood cells and the rest of the body goes into (). • Progressive destruction of the endothelial wall of the sinusoid will lead to gaps and then ruptures of its barrier integrity, with entrapment of red blood cells
shock
These disruptions of the sinusoid are considered the early structural features of the vascular disorder knownas (), which occurs after exposure to (), which may be found in some herbal teas and chemotherapeutic agents.
veno-occlusive disease, pyrrolizidine alkaloids
() from a mushroom and() from blue-green algae • disrupt the integrity of hepatocyte cytoskeleton by affecting proteins that are vital to its dynamic nature, preventing disassembly of actin filaments.
Phalloidin, microcystin
is defined biochemically as an appreciable increase in the hepatic lipid (mainly triglyceride) content, which is < 5 wt% in the normal human liver; can stem from disruptions in lipid metabolism. • The disruption in the lipid metabolism can change when there is build-up of lipids in the hepatocyte
FATTY LIVER (STEATOSIS)
Most common cause is () due to central obesity and sedentary lifestyle
insulin resistance
However, acute exposure to hepatotoxicants like () and some drugs can induce steatosis.
carbon tetrachloride
metabolic inhibitors ()()() cause at accumulation without causing death of cells • Chemical-induced steatosis is reversible and does not lead to death of hepatocytes
ethionine, puromycin, and cycloheximide
is by far the most relevant drug or chemical leading to steatosis in humans and in experimental animals.
Ethanol
is characterized by the accumulation of extensive amounts of collagen fibers, in response to direct injury or to inflammation With repeated chemical insults, destroyed hepatic cells are replaced by fibrotic scars. With continuing collagen deposition, the architecture of the liver is disrupted by interconnecting fibrous scars.
Hepatic fibrosis (scarring)
- When the fibrous scars subdivide the remaining liver mass into nodules of regenerating hepatocytes, fibrosis has progressed to cirrhosis and the liver has limited residual capacity to perform its essential functions.
Cirrhosis -
Primary cause of hepatic fibrosis/cirrhosis in humans worldwide is (). However, biliary obstruction and, in particular, alcoholic and NASH are of growing importance or the development of hepatic fibrosis. • () is not reversible, has a poor prognosis or survival, and is usually the result of repeated exposure to chemical toxicants (ethanol and heavy metals)
Cirrhosis, viral hepatitis
