Path-Liver Dz Flashcards
when the liver regenerates, how does the anatomy, histo, and function change?
it doesn’t, it returns to normal
what is the most common cause of acute liver failure?
drugs (and toxins)
what drugs usually cause liver failure?
acetaminophen, and then new drugs on the market
this can cause acute liver failure, but usually causes chronic liver failure
viral hepatitis
what actually happens in drug-induced liver injury (DILI)? (3 possibilities)
1) toxic rxn to drug or more commonly drug metabolite, 2) inflamm immune rxn to drug, 3) drug hepatitis
what are the two classes of hepatotoxic drugs?
1) intrinsic, 2) idiosyncratic
what is an intrinsic drug injury?
injury is predictable and dose dependent (example: acetaminophen, other toxic metabolites)
what is an ideosyncratic drug injury?
injury not predictable or dose-dependent (ABX, herbal)
which two pathways of tylenol metabolism result in non-toxic, water-soluble metabolites?
glucuronidation & sulfation
metabolism of tylenol by the ____ system produces an alkylating metabolite, _____, that is directly toxic to the liver
cytochrome P-450; NAPQI
under non-toxic levels of tylenol administration, what happens to the minute fraction of NAPQI that is formed?
immediately and irreversibly conjugated with sulfhydryl groups of glutathione and rendered nontoxic (excreted by kidneys)
when the amount of unconjugated NAPQI depletes glutathione stores, what happens to the excess?
covalently binds to and inactivates hepatocyte proteins, causing cell death
how do you treat an acetaminophen overdose?
N-acetylcysteine replenishes depleted glutathione
how does chronic alcoholism affect the metabolism of tylenol?
it induces cytochrome P-450, thus increasing the amount of toxic metabolite formed (toxicity at a lower dose!)
which zone of hepatocytes are most sensitive to hepatotoxic injury?
zone 3/perivenular (closest to central vein, farthest from portal area and thus hypoxic and malnourished)
moderate tylenol overdose leads to (reversible/irreversible) hepatocyte injury to zone ___ hepatocytes
reversible; zone 3 only
severe tylenol overdose leads to (reversible/irreversible) hepatocyte injury to zone ___ hepatocytes
irreversible; all zones (need transplant)
when hepatocytes die from tylenol overdose, histology shows?
centri-lobular coagulative necrosis (pink ghost cells)
a week after injury, what happens to the dead hepatocytes?
macrophages chew them up & the liver becomes shrunken and much less heavy
years to decades of chronic liver injury with attempted repair lead first to ______, which is _____ reversible
liver fibrosis; partially
When liver injury continues long after fibrosis has developed, _____ will result. This is ____ reversible.
cirrhosis; not
what is the most common cause of chronic liver failure?
cirrhosis
what two anatomic alterations arise as a consequence of longstanding, repetitive injury?
1) thick fibrous bands/scars/septa, 2) anatomically abnormal nodules of regenerated tissue that lack portal areas
what are the two major consequences of the anatomic alterations seen in cirrhosis?
1) reduced functional liver tissue & 2) altered vascular:parenchymal relationships
three clinical changes seen as a result of cirrhosis
1) decreased hepatic synthetic function, 2) decreased hepatic detox, and 3) portal HTN from increased resistance
decreased hepatic detox results in?
encephalopathy
portal HTN results in?
splenic enlargement (back pressure) & variceal bleeding
a cirrhosed liver is (small/large) with a (smooth/bumpy) surface
small, bumpy
in cirrhosis, rounded regenerative nodules are encased in?
dense fibrous connective tissue
the repetitive injury and repair that occurs in cirrhosis leads to risk of?
hepatocellular carcinoma
nodules of hepatocellular carcinoma are (smaller,larger) and of a different ____
larger, color (darker, lighter, more bile-stained, etc)
a trichrome stain emphasizes?
fibrous connective tissue
rapid exchange of nutrients and metabolic waste products is facilitated in the liver by what two anatomical features (which are reversed in cirrhosis)?
1) fenestrations in endothelial cytoplasm (lost), 2) absence of a subendothelial BM (develops in cirrhosis)
in the setting of chronic, persistent, inflammation, cytokines and growth factors stimulate _____ cells to deposit _____ in the space of _____
stellate cells; collagen; Disse
varices are dilated, thin-walled ___ within the esophageal _____ developing as a consequences of ____ in cirrhosis
veins; submucosa; portal HTN
why are patients with cirrhosis at particular risk for massive hematemesis from rupture of esophageal varices?
decreased coagulation factors due to liver dz
isolated portal HTN (with healthy liver) results from?
thrombotic occlusion of the hepatic portal vein
thrombotic occlusion of the hepatic vein (post-hepatic) causes what syndome?
Budd-Chiari syndrome
initially, Budd-Chiari syndrome causes the liver to become?
swollen and congested
name two causes of hepatic venous obstruction other than a thrombus
constrictive pericarditis, severe right heart failure
when CHF results in hepatic venous obstruction it is known as ____ and if it progresses to cirrhosis it is called ____
congestive hepatopathy; cardiac cirrhosis
portal vein entry is located at the ____ of the hepatic lobule, while central vein exit is located at the ____
apices; center
“red blood cell-trabecular lesions” are found in what region of the hepatic lobule?
the center because this is where the backflow of blood occurs (RBCs replace centrilobular hepatocytes in the plates)
hepatic vein obstruction leads to ______ of the caudate lobe due to _____
hypertrophy; bypass of blood through small caliber veins that directly enter IVC from caudate lobe
congestive hepatopathy from acute-onset heart failure causes?
hepatomegaly and centrilobular fibrosis
amyloidosis cause liver size to (increase/decrease) and appears as homogenous eosinophilic material (inside/outside) the hepatocyte
increase; outside (fills and expands space of Disse, crowding out sinusoids and leading to atrophy of hepatocytes)
