Pathology- Acute Liver Injury 1 Flashcards
what are some common causes of hepatic injury?
VAS SPAT
Viral hepatitis, Antibiotics, Sepsis, Shock, Pregnancy, Alcohol, Tylenol
Categories of disease?
vascular, infectious, toxic, autoimmune, metabolic, idiopathic, neoplastic, developmental
where does portal vein come from and where does it go?
- brings blood from intestines and spleen to the liver
- portal ven carries most of teh blood and the hepatic artery carries the rest to the liver
What can cause liver to become ischemic?
- shock aka total body hypoperfusion can cause ischemic hepatitis esp if d/t long term heart failure
- dual hepatic blood supply makes it less vilnerable to ischemia.
- portal vein thrombosis can cause ischemia limited to liver.
budd chiari syndrome presentation?
- tender hepatomegaly, abd pain and ascites commonly d/t hypergoagulable state esp with a myeloproliferative disorder.
budd chiari syndrome is caused by hepatic vein thrombosis –> ischemic hepatitis.
what levels rise change with shock liver?
- rapid rise in transaminase in 1-3 days and then steady decline to normal in 7-10 days
- bilirubin rise only as transaminase falling and rarely goes above 4x ULN
- alk phosphate rarely goes above 2x ULN.
describe the open circulation of the hepatic sinusoids
- sinusoids lined by fenestrated endothelial cells that have entiehr tight junctions nor a basement membrane
- this means that there is no continous diffusion barrier between plasma and hepatocytes’ cell surface
where are kupffer cells and what do they do?
- kupffer cells are in between endotehlial cells and form part of the sinusoidal lining
- kupffer cells phagocytize things like bacteria and their products –> cause them to release IL1, TNF, IL6, IL8, IL12, TGFbeta, interferon, PGD2, PGE2, thromboxane, complement –> sepsis.
what are ito cells and where are they located?
what is the space of disse?
it is between the sinusoidal lining cells and the hepatocyte cell membrane
- hepatic interstitium
- space of disse contain ECM glycoproteins and occasional collagen fibrils normally
what is the msot common tye of drugs to cause liver injury?
- antibiotics
what are oval cells?
pluripotent cells (hepatic stem cells) that can differentiate into ductal cells and/or hepatocytes
what is the difference between hepatocellular cholestasis and canalicular cholestasis?
hepatocellular cholestasis- secreteion of bile into canaliculi is impeded so bile is accumulated in the hepatocytes
- canalicular cholestasis means bile canaliculiis affected interfering with the motility and resulting in cnalicular bile plugs.
how does pregnancy induce liver disease in some pregnancies?
1) HELLP syndrom- hemolysis, elevated liver enzymes, low platelets
2) acute fatty liver of pregnancy
3) intrahepatic cholestasis of pregnancy (most common)
what causes intrahepatic cholestasis of pregnancy?
what is tx for intrahepatic cholestasis?
- ursodeoxycholic acid
what is the second most common pattern of drug induced liver injury? what levels are elevated?
-cholestatitc with severely elevated bilirubin and alk phosphate and moderately elevated transaminases
*psychoactive meds are the 2nd most comon types of drugs to cause liver injury in a hepatocellular or cholestatitc pattern
which hepatocytes are often the first to be affected in many forms of hepatic injury? why?
- centrolobular hepatocytes becasue they receive blood w/ lower content of oxygen and metabolites than peri-portal hepatocytes.
in many cases of severe hepatic injury, which hepatocytes are sometimes the only surviving ones and why?
- periportal hepatocytes bc they are the best supplied with blood rich in oxygen, nutrients and other goodies
mechanism of tylenol hepatotoxicity
- tylenol –> NAPQI which is conjugated w/ glutathione to a nontoxic compound
- when hepatocytes run out of glutathione, NAPQI build up and injures them esp the centrolobular hepatocytes
what dose of tylenol cause toxicity and what are the manifestations?
- less than 10grams/day is probabs unlikley but >12g is likley and >16g is lilkey severe
- first 24 hrs the initial maniefestations of toxicity is nausea, vomiting, sweating, pallor, lethargy, ang malaise
- between 24 and 72 hours, the patient feels fine but between 72-96 hours, the manifestations reappear along with jaundice, confusion (or worse encephalopathy) and bleeding)
what is the tx for tylenol overdose?
N-acetyl cysteine
what zone of liver does acetaminophen affect?
central necrosis
phosphoorus compounds affect which zone of liver?
- periportal hepatocytes
yellow fever and some poisonous mushrooms injures which zone of liver?
- midzone
what is focal necrosis?
- only few cells are affected with random distribution
what is confluent necrosis?
affects large cell groups
what is bridging necrosis?
- necrotic areas extend between lobules or parts of lobules like portal to portal or central to central
what is massive necrosis?
when it affects 75% or more of the liver
what does viral hepatitis also cause?
1) swollen pale hepatocytes
2) portal and lobular infiltration by lymphocytes, macrophages, and plasma cells
3) kupffer cell hypertrophy and hyperplasia
4) +/- cholestasis
symptoms of viral hepatitis causing acute liver injury?
- malaise, anorexia, nausea, fatigue,
how do you diagnose autoimmune hepatitis from virual hepatitis?
autoimmune hepatitis is not a common cause of acute liver injury but the tx is different.
- clinical presentation is similar to viral heptiaits but there are diagnostic antibodies like anti-nuclear and anti-smooth muscle
what is the microscopic pathology of autoimmune hepatitis that is different from viral hepatitis and other hepatitis?
plasma cells are more prominent
