Path-Liver Dz

Question 1

when the liver regenerates, how does the anatomy, histo, and function change?

Answer 1

it doesn’t, it returns to normal

Question 2

what is the most common cause of acute liver failure?

Answer 2

drugs (and toxins)

Question 3

what drugs usually cause liver failure?

Answer 3

acetaminophen, and then new drugs on the market

Question 4

this can cause acute liver failure, but usually causes chronic liver failure

Answer 4

viral hepatitis

Question 5

what actually happens in drug-induced liver injury (DILI)? (3 possibilities)

Answer 5

1) toxic rxn to drug or more commonly drug metabolite, 2) inflamm immune rxn to drug, 3) drug hepatitis

Question 6

what are the two classes of hepatotoxic drugs?

Answer 6

1) intrinsic, 2) idiosyncratic

Question 7

what is an intrinsic drug injury?

Answer 7

injury is predictable and dose dependent (example: acetaminophen, other toxic metabolites)

Question 8

what is an ideosyncratic drug injury?

Answer 8

injury not predictable or dose-dependent (ABX, herbal)

Question 9

which two pathways of tylenol metabolism result in non-toxic, water-soluble metabolites?

Answer 9

glucuronidation & sulfation

Question 10

metabolism of tylenol by the ____ system produces an alkylating metabolite, _____, that is directly toxic to the liver

Answer 10

cytochrome P-450; NAPQI

Question 11

under non-toxic levels of tylenol administration, what happens to the minute fraction of NAPQI that is formed?

Answer 11

immediately and irreversibly conjugated with sulfhydryl groups of glutathione and rendered nontoxic (excreted by kidneys)

Question 12

when the amount of unconjugated NAPQI depletes glutathione stores, what happens to the excess?

Answer 12

covalently binds to and inactivates hepatocyte proteins, causing cell death

Question 13

how do you treat an acetaminophen overdose?

Answer 13

N-acetylcysteine replenishes depleted glutathione

Question 14

how does chronic alcoholism affect the metabolism of tylenol?

Answer 14

it induces cytochrome P-450, thus increasing the amount of toxic metabolite formed (toxicity at a lower dose!)

Question 15

which zone of hepatocytes are most sensitive to hepatotoxic injury?

Answer 15

zone 3/perivenular (closest to central vein, farthest from portal area and thus hypoxic and malnourished)

Question 16

moderate tylenol overdose leads to (reversible/irreversible) hepatocyte injury to zone ___ hepatocytes

Answer 16

reversible; zone 3 only

Question 17

severe tylenol overdose leads to (reversible/irreversible) hepatocyte injury to zone ___ hepatocytes

Answer 17

irreversible; all zones (need transplant)

Question 18

when hepatocytes die from tylenol overdose, histology shows?

Answer 18

centri-lobular coagulative necrosis (pink ghost cells)

Question 19

a week after injury, what happens to the dead hepatocytes?

Answer 19

macrophages chew them up & the liver becomes shrunken and much less heavy

Question 20

years to decades of chronic liver injury with attempted repair lead first to ______, which is _____ reversible

Answer 20

liver fibrosis; partially

Question 21

When liver injury continues long after fibrosis has developed, _____ will result. This is ____ reversible.

Answer 21

cirrhosis; not

Question 22

what is the most common cause of chronic liver failure?

Answer 22

cirrhosis

Question 23

what two anatomic alterations arise as a consequence of longstanding, repetitive injury?

Answer 23

1) thick fibrous bands/scars/septa, 2) anatomically abnormal nodules of regenerated tissue that lack portal areas

Question 24

what are the two major consequences of the anatomic alterations seen in cirrhosis?

Answer 24

1) reduced functional liver tissue & 2) altered vascular:parenchymal relationships

Question 25

three clinical changes seen as a result of cirrhosis

Answer 25

1) decreased hepatic synthetic function, 2) decreased hepatic detox, and 3) portal HTN from increased resistance

Question 26

decreased hepatic detox results in?

Answer 26

encephalopathy

Question 27

portal HTN results in?

Answer 27

splenic enlargement (back pressure) & variceal bleeding

Question 28

a cirrhosed liver is (small/large) with a (smooth/bumpy) surface

Answer 28

small, bumpy

Question 29

in cirrhosis, rounded regenerative nodules are encased in?

Answer 29

dense fibrous connective tissue

Question 30

the repetitive injury and repair that occurs in cirrhosis leads to risk of?

Answer 30

hepatocellular carcinoma

Question 31

nodules of hepatocellular carcinoma are (smaller,larger) and of a different ____

Answer 31

larger, color (darker, lighter, more bile-stained, etc)

Question 32

a trichrome stain emphasizes?

Answer 32

fibrous connective tissue

Question 33

rapid exchange of nutrients and metabolic waste products is facilitated in the liver by what two anatomical features (which are reversed in cirrhosis)?

Answer 33

1) fenestrations in endothelial cytoplasm (lost), 2) absence of a subendothelial BM (develops in cirrhosis)

Question 34

in the setting of chronic, persistent, inflammation, cytokines and growth factors stimulate _____ cells to deposit _____ in the space of _____

Answer 34

stellate cells; collagen; Disse

Question 35

varices are dilated, thin-walled ___ within the esophageal _____ developing as a consequences of ____ in cirrhosis

Answer 35

veins; submucosa; portal HTN

Question 36

why are patients with cirrhosis at particular risk for massive hematemesis from rupture of esophageal varices?

Answer 36

decreased coagulation factors due to liver dz

Question 37

isolated portal HTN (with healthy liver) results from?

Answer 37

thrombotic occlusion of the hepatic portal vein

Question 38

thrombotic occlusion of the hepatic vein (post-hepatic) causes what syndome?

Answer 38

Budd-Chiari syndrome

Question 39

initially, Budd-Chiari syndrome causes the liver to become?

Answer 39

swollen and congested

Question 40

name two causes of hepatic venous obstruction other than a thrombus

Answer 40

constrictive pericarditis, severe right heart failure

Question 41

when CHF results in hepatic venous obstruction it is known as ____ and if it progresses to cirrhosis it is called ____

Answer 41

congestive hepatopathy; cardiac cirrhosis

Question 42

portal vein entry is located at the ____ of the hepatic lobule, while central vein exit is located at the ____

Answer 42

apices; center

Question 43

"red blood cell-trabecular lesions" are found in what region of the hepatic lobule?

Answer 43

the center because this is where the backflow of blood occurs (RBCs replace centrilobular hepatocytes in the plates)

Question 44

hepatic vein obstruction leads to ______ of the caudate lobe due to _____

Answer 44

hypertrophy; bypass of blood through small caliber veins that directly enter IVC from caudate lobe

Question 45

congestive hepatopathy from acute-onset heart failure causes?

Answer 45

hepatomegaly and centrilobular fibrosis

Question 46

amyloidosis cause liver size to (increase/decrease) and appears as homogenous eosinophilic material (inside/outside) the hepatocyte

Answer 46

increase; outside (fills and expands space of Disse, crowding out sinusoids and leading to atrophy of hepatocytes)