Pathology- Acute Liver Injury 1

Question 1

what are some common causes of hepatic injury?

Answer 1

VAS SPAT

Viral hepatitis, Antibiotics, Sepsis, Shock, Pregnancy, Alcohol, Tylenol

Question 2

Categories of disease?

Answer 2

vascular, infectious, toxic, autoimmune, metabolic, idiopathic, neoplastic, developmental

Question 3

where does portal vein come from and where does it go?

Answer 3

• 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

Question 4

What can cause liver to become ischemic?

Answer 4

• 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.

Question 5

budd chiari syndrome presentation?

Answer 5

• 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.

Question 6

what levels rise change with shock liver?

Answer 6

• 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.

Question 7

describe the open circulation of the hepatic sinusoids

Answer 7

• 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

Question 8

where are kupffer cells and what do they do?

Answer 8

• 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.

Question 9

what are ito cells and where are they located?

Question 10

what is the space of disse?

Answer 10

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

Question 11

what is the msot common tye of drugs to cause liver injury?

Answer 11

• antibiotics

Question 12

what are oval cells?

Answer 12

pluripotent cells (hepatic stem cells) that can differentiate into ductal cells and/or hepatocytes

Question 13

what is the difference between hepatocellular cholestasis and canalicular cholestasis?

Answer 13

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.

Question 14

how does pregnancy induce liver disease in some pregnancies?

Answer 14

1) HELLP syndrom- hemolysis, elevated liver enzymes, low platelets
2) acute fatty liver of pregnancy
3) intrahepatic cholestasis of pregnancy (most common)

Question 15

what causes intrahepatic cholestasis of pregnancy?

Question 16

what is tx for intrahepatic cholestasis?

Answer 16

• ursodeoxycholic acid

Question 17

what is the second most common pattern of drug induced liver injury? what levels are elevated?

Answer 17

-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

Question 18

which hepatocytes are often the first to be affected in many forms of hepatic injury? why?

Answer 18

• centrolobular hepatocytes becasue they receive blood w/ lower content of oxygen and metabolites than peri-portal hepatocytes.

Question 19

in many cases of severe hepatic injury, which hepatocytes are sometimes the only surviving ones and why?

Answer 19

• periportal hepatocytes bc they are the best supplied with blood rich in oxygen, nutrients and other goodies

Question 20

mechanism of tylenol hepatotoxicity

Answer 20

• 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

Question 21

what dose of tylenol cause toxicity and what are the manifestations?

Answer 21

• 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)

Question 22

what is the tx for tylenol overdose?

Answer 22

N-acetyl cysteine

Question 23

what zone of liver does acetaminophen affect?

Answer 23

central necrosis

Question 24

phosphoorus compounds affect which zone of liver?

Answer 24

• periportal hepatocytes

Question 25

yellow fever and some poisonous mushrooms injures which zone of liver?

Answer 25

• midzone

Question 26

what is focal necrosis?

Answer 26

• only few cells are affected with random distribution

Question 27

what is confluent necrosis?

Answer 27

affects large cell groups

Question 28

what is bridging necrosis?

Answer 28

• necrotic areas extend between lobules or parts of lobules like portal to portal or central to central

Question 29

what is massive necrosis?

Answer 29

when it affects 75% or more of the liver

Question 30

what does viral hepatitis also cause?

Answer 30

1) swollen pale hepatocytes
2) portal and lobular infiltration by lymphocytes, macrophages, and plasma cells
3) kupffer cell hypertrophy and hyperplasia
4) +/- cholestasis

Question 31

symptoms of viral hepatitis causing acute liver injury?

Answer 31

• malaise, anorexia, nausea, fatigue,

Question 32

how do you diagnose autoimmune hepatitis from virual hepatitis?

Answer 32

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

Question 33

what is the microscopic pathology of autoimmune hepatitis that is different from viral hepatitis and other hepatitis?

Answer 33

plasma cells are more prominent