Pathology of Acute and Chronic Liver Failure and Cirrhosis (Quiz 3) Flashcards
what’s the most common cause of acute liver failure
- Tylenol (acetaminophen) overdose
cirrhotic causes of chronic liver failure
- alcohol
- viral hepatitis
- steatohepatitis
- autoimmune/bilary
- genetic/metabolic
two types of hepatotoxic drugs
- intrinsic (acetaminophen)
- idiosyncratic
how can acetaminophen be toxic
- metabolism by cyto P450 produces NAPQI (toxic)
- generally conjugated with glutathione but in high doses will deplete glutathione stores and cause cell death in the hepatocyte
how to treat Tylenol overdose
MOA
- N-acetylcysteine (NAC)
- replenishes depleted glutathione stores
effect on chronic alcoholism with taking tylenol
- induces cytochrome P450
- creates more toxic metabolite
- chronic alcoholics suffer liver injury at a lower toxic dose
the hepatocytes nearest the ______ are perfused by blood having the highest level of oxygen and nutrients
- nearest the portal area
- Zone 1
which zone of hepatocytes are relatively hypoxic and malnourished and more sensitive to hepatotoxic injury
- zone 3
which zone of hepatocytes are damaged during moderate acetaminophen overdose
what about with severe acetaminophen toxicity
- zone 3
- all zones
why could PT/INR be high when albumin is normal
- albumin has a much longer half life than coagulation factors
what do dead hepatocytes due to acetaminophen toxicity look like
- bright pink (eosinophilic)
threshold for acetominophen toxicity in adults is how much
10-15 g
pathologic findings for cirrhosis
- thick fibrous bands
- regenerative nodules
why might you have splenomegaly with cirrhosis
- increased portal venous back pressure transmitted to splenic veins
what size is the liver with cirrhosis
- smaller
what helps facilitate rapid exchange of nutrients between hepatocytes and sinusoids
- pores in endothelial cytoplasm of sinusoid
- absence of sub endothelial basement membrane
what happens to the hepatocytes and sinusoids during cirrhosis
- loss of pores in sinusoid endothelium
- sub endothelial basement membrane develops
- stellate cells develop myofibroblastic phenotype that forms collagen in space of Disse
why do varices form
- shunt from the obstructed portal circulation to the systemic circulation
prehepatic non-cirrhotic causes of chronic liver failure
- portal vein thrombosis
- blockage in an inflow vein
what symptoms of portal vein thrombosis do you see
- signs of portal hypertension
- esophageal varices
- splenomegaly
what else can cause portal vein thrombosis
- sluggish blood flow in a patient with cirrhosis
intrahepatic non-cirrhotic causes of chronic liver failure
- amyloidosis
what do you see on histology with amyloidosis
best way to check for amyloidosis
- amyloid proteins
- atrophic hepatocytes
- stain with Congo red
splenic enlargement in amyloidosis is caused by
- protein deposition
post hepatic non-cirrhotic causes of chronic liver failure
- hepatic vein/IVC thrombosis (Budd-Chiari)
- constrictive pericarditis
- right heart failure
what is Budd-Chiari
what happens
- thrombotic occlusion of hepatic vein or IVC
- blocked exit of blood from liver
- back pressure of blood damages the liver
difference between hepatic vein thrombosis and hepatic portal vein thrombosis
- hepatic vein thrombosis causes liver injury
how can constrictive pericarditis and right heart failure causes posthepatic portal hypertension
- heart can’t handle blood returning form the liver
- increase in hepatic venous back pressure
what do you see histologically with Budd-Chiari syndrome
- centrilobular congestion with red blood cell lesions
what effect on the liver size does Budd-Chiari have
what about the spleen
- hypertrophy of the caudate lobe
- splenomegaly from portal hypertension
another name for right sided heart failure causing portal hypertension
- congestive hepatopathy
what do you see on gross findings with congestive hepatopathy
- nutmeg liver
