Liver Pathology

Front 1

What are the components of the normal portal tract?

Back 1

hepatic a., portal v. , bile duct, lymphatics, nerves, CT (collagen type I)

limiting plate: border of hepatocytes that form outer boundary of portal tract

Front 2

What makes up the lobule model of the liver?

Back 2

hexagon bordered by 6 portal tracts w/ central vein in middle

3 areas: periportal, midzonal, centrilobular

Front 3

What are Kupffer cells?

Back 3

hepatic MPs that sit on endo cells of sinusoids & filter blood borne material

Front 4

What are stellate cells?

Back 4

= lipocytes, Ito cells

sinusoidal lining cells that store vitamin A, can synthesis collagen when activated

Front 5

What are 3 portal of entry to the liver resulting in injury?

Back 5

direct extension: penetrating trauma thru abd. wall or thru GI tract (ex. cattle w/ TRP)

hematogenous: localization w/in sinusoids, Kupffer cells, or capillary bed of GB

retrograde biliary transport: ascending bacterial or parasitic infections

Front 6

Describe a random pattern of hepatocellular degeneration & necrosis.

Back 6

single cell necrosis or MF aggregates of necrotic cells

typical of blood-borne infectious agents

inflammation: viral (little), bacterial (suppurative), Mycobacteria (granulomatous)

Front 7

Describe a centrilobular pattern of hepatocellular degeneration & necrosis.

Back 7

around central v. (most common type)

hypoxic injury occurs here 1st

most toxic drugs produce injury here

Front 8

What are 3 main causes of hyperbilirubinemia?

Back 8

1. overproduction thru hemolysis (hemolytic anemia, intestinal hemorrhage)
2. ↓ uptake by hepatocytes (hepatocellular dz, fasting horses)
3. ↓ outflow of bile (cholestasis: obstruction, hepatocellular dz)

Front 9

What are the 2 main patterns of cholestasis & what are the causes of each?

Back 9

1. extrahepatic
-intralumenal obstruction: choleliths, parasites, stricture, inspissated bile, GB mucocele
-extralumenal obstruction: neoplasm, abscess
-histology
*acute: distension of bile ducts, edema, mild portal inflammation
*chronic: circumferential bile duct fibrosis to biliary cirrhosis

2. intrahepatic: assoc. w/ hepatocyte disorders affecting ability to metabolize & excrete bile
-histology: canalicular stasis (bile plugs)

Front 10

What is the pathogenesis of liver fibrosis?

Back 10

hepatic injury --> stellate cells take on a myofibroblast form --> lose vitamin A storing function --> begin synthesis of collagen I

can lead to portal hypertension

Front 11

What is the significance of biliary hyperplasia?

Back 11

common nonspecific response to liver injury

Front 12

What is the pathogenesis of end-stage liver or cirrhosis?

Back 12

significant liver injury --> architecture of lobules lost & replaced by regenerative nodules surrounded by bands of fibrosis & often bile duct hyperplasia --> liver failure, portal hypertension, ascites

Front 13

What are some causes of end-stage liver or cirrhosis?

Back 13

chronic toxicity, chronic cholangitis &/or obstruction, chronic congestion (R heart failure), inherited disorders of metal metabolism (Cu, Fe), chronic hepatitis, idiopathic

Front 14

What metabolic distubrances are associated w/ liver injury?

Back 14

hypoglycemia
acidosis
sepsis
coag disorders
hypoalbuminemia

Front 15

What is hepatocutaneous syndrome?

Back 15

-crusting, erosions, ulceration of muzzle, face, footpads, & pressure points in some dogs w/ severe hepatic dz
-characteristic multinodular livers, often w/ little fibrosis b’twn nodules
-cause: unknown

= superficial necrolytic dermatitis

Front 16

What is the regeneration capacity of the liver?

Back 16

liver has extraordinary ability to regenerate

if injury is severe enough or repeated such that ECM is destroyed --> regeneration cannot reform into normal liver --> nodules replace missing mass (have abnormal blood supply, drainage, & disrupted biliary flow --> altered liver function)

Front 17

What is primary photosensitiziation?

Back 17

from eating plants w/ preformed photodynamic agents (ex. St. John’s Wort), or some drugs (NOT a result of hepatic dz)

Front 18

What is secondary photosensitization?

Back 18

hepatogenous: occurs in herbivores

-phylloerythrin: naturally occurring photodynamic pigment in plants that is normally cleared from portal blood by liver

-liver dz --> accumulation of phylloerythrin in blood & tissues --> tissue injury when exposed to UV light

Front 19

What is the main function of the exocrine pancreas & what is the most common sign of dysfunction?

Back 19

secretions conducted to duodenum via pancreatic ducts --> aid in digestion of protein, fat, carbs

maldigestion = dysfunction

Front 20

What are some development anomalies associated w/ the liver?

Back 20

congenital biliary cysts: common in cats (ddx: parasitic cysts, biliary adenomas); usually NGS

hepatic displacement: diaphragmatic hernias (congenital or traumatic)

Front 21

What are the consequences of inadequate hepatic blood flow?

Back 21

atrophy, telangiectasis, infarction

Front 22

What is the cause of passive congestion of the liver & what are the acute & chronic pathologic manifestions?

Back 22

R heart failure --> backup of blood in caudal vena cava & hepatic congestion

acute: congestion in centrilobular areas, atrophy of centrilobular hepatocytes, liver enlarged

chronic: centrilobular fibrosis, “nutmeg liver” (common in old dogs w/ endocardiosis)

Front 23

What is hepatic veno-occlusive dz?

Back 23

partial to complete occlusion of central vv. --> portal hypertension

Front 24

What are the 2 types of portosystemic shunts?

Back 24

1. extrahepatic: shunt occurs before portal v. enters liver
-usually a single vessel connecting portal v. w/ caudal vena cava, renal v., or azygous v.
-most commonly found in small breed dogs; also cats, other species

2. intrahepatic: usually result of a patent ductus venosus
-most commonly found in large breed dogs

Front 25

What are the hepatic, pre-hepatic, & post-hepatic causes of portal hypertension?

Back 25

hepatic: fibrosis along sinusoids --> collapse or stenosis, portal v. hypoplasia (young dogs & cats affected), intrahepatic arterior-venous fistula

pre-hepatic: thrombosis, tumor mets, parasites, abscesses --> restricted flow thru portal v.

post-hepatic: CHF --> inc. resistance to outflow of blood thru hepatic v.

Front 26

What are the consequences of portal hypertension?

Back 26

usually numerous shunt vessels, ascites (d/t ↑ pressure w/in portal v. & liver)

associated parenchymal disorders: hepatic fibrosis, cirrhosis (lobular dissecting hepatitis)

Front 27

lobular dissecting hepatitis

a. signalment
b. clinical signs
c. gross lesions
d. histo lesions

Back 27

a. young dogs
b. ascites, hypoalbuminemia, ↑ liver enzymes, ↑ bile acids (rapidly fatal)
c. small smooth livers, multiple portosystemic collaterals, portal hypertension
d. micronodules, diffuse disruption of hepatic architecture, diffuse infiltration of inflammatory cells

Front 28

What are 3 causes of hepatic lipidosis assoc. w/ increased inflow?

Back 28

1. excess dietary fat --> excess entry of FAs into liver
2. ↑ mobilization of TGs from adipose tissue d/t ↑ demand (lactation, starvation, endocrine abnormalities)
3. excess dietary carbs --> ↑ FA synthesis --> excessive TGs w/in hepatocytes

Front 29

What are 2 causes of hepatic lipidosis assoc. w/ abnormal metabolism?

Back 29

abnormal hepatocyte function (mitochondrial injury) --> ↓ energy for oxidation of FAs w/in hepatocytes --> accumulation of TGs w/in hepatocytes

↑ glucose & insulin levels --> ↑ esterification of FAs to TGs

Front 30

What are 2 causes of hepatic lipidosis assoc. w/ decreased excretion?

Back 30

↓ apoprotein synthesis --> ↓ production & export of lipoprotein from hepatocytes

hepatotoxins or drugs --> secretory defects --> impaired secretion of lipoprotein from liver

Front 31

What are the 3 broad categories of causes of hepatic lipidosis?

Back 31

increased inflow of fat

abnormal metabolism of fat

decreased excretion of fat

Front 32

What is steroid hepatopathy?

Back 32

glucocorticoid induced hepatocellular degeneration

excessive amts of endogenous or exogenous glucocorticoids --> marked swelling of hepatocytes d/t accumulation of glycogen

grossly, liver is yellowish, pale & enlarged (ddx: fatty liver)

Front 33

What is a cause of hepatic copper accumulation in dogs?

Back 33

hereditary disorders of copper metabolism occur in Bedlington terriers, Westies, Skye terriers, Dobermans, etc. --> chronic copper accumulation & liver dz --> chronic hepatitis & fibrosis

Front 34

What pigments may accumulate in the liver?

Back 34

bile: from cholestasis
hemosiderin: hemochromatosis: hepatic injury d/t excess iron accumulation
lipofuscin: residue of incompletely digested lipids (cell mems)
melanin: esp. in lower vertebrates, congenital in swine, sheep
fluke pigment: Fasciola most common

Front 35

infectious canine hepatitis

a. etiologic agent
b. histological lesions
c. gross lesions

Back 35

a. canine adenovirus I
b. centrilobular necrosis: unusual for viral infection, characteristic basophilic intranuclear inclusions in hepatocytes & endothelial cells
c. petechiae & ecchymoses on serosal surfaces d/t vascular necrosis, +/- blue eye

Front 36

herpes virus

a. associated hepatic lesions
b. etiologic agents

Back 36

a.MF random hepatic necrosis w/o inflammation, petechiae, ecchymoses

b. equine herpes virus 1, bovine rhinotracheitis, canine herpes, feline rhinotracheitis (neonates usually affected)

Front 37

What are 2 hepatic lesions associated w/ nematodes?

Back 37

larval migration thru liver is common --> focal fibrosis (“milk spotted liver”): ascarids, strongyles, Stephanurus dentatus

vena caval syndrome: Dirofilaria immitis adults collect in caudal vena cava --> severe intravascular hemolysis, DIC, acute hepatic failure

Front 38

What is the most common type of cholangitis & what is the most common cause?

Back 38

neutrophilic cholangitis: neutrophils in lumen or w/in epi cells of bile ducts

usually caused by ascending bacterial infection from GI tract

Front 39

lymphocytic cholangitis

a. species affected
b. histological lesions

Back 39

a. chronic idiopathic cholangitis of cats
b. moderate to dense lymphocytic & plasmacytic infiltrates of portal areas
+/- biliary proliferation & portal fibrosis

Front 40

What is the pattern of injury seen w/ toxic liver injury & why?

Back 40

centrilobular b/c enzymes involved in bioactivation are in highest concentrations there

Front 41

What are some causes of acute liver toxicity?

Back 41

blue green algae (preformed toxins)
plants
mycotoxins (aflatoxin B: Aspergillus flavus: acute in dogs, chronic in LA)
toxic mushrooms: Amanita spp
chemicals: phosphorous, carbon tetrachloride, cresols, metals
therapeutic drugs: acetaminophen, diazepam in cats; Trimethoprim-sulfa ABs, Carprofen

Front 42

Why are cats particularly susceptible to acetominophen toxicity?

Back 42

weak phase 2 enzyme activity (relatively deficient in glucuronyltransferase activity: forms conjugates b’twn bioactivated xenobiotics & glutathione)

Front 43

What are some causes of chronic hepatic toxicity?

Back 43

plants: pyrrolizidine alkaloids
therapeutic drugs: anticonvulsants in dogs

Front 44

Pyrrolizidine alkaloids

a. how they cause hepatic injury
b. characteristic lesion

Back 44

a. must be metabolized into alkylating agents to cause toxic injury

b. megalocytes: enlarged hepatocytes w/ very large dark staining nuclei

Front 45

hepatocellular nodular hyperplasia

a. cause
b. gross appearance

Back 45

a. normal, age related in dogs (starts at ~6 yrs)
b. solitary to multiple pale yellow to red-brown nodules in otherwise healthy liver, well circumscribed

Front 46

What are regenerative hepatic nodules?

Back 46

proliferative nodules in diseased, usually fibrotic livers

usually only a single portal tract w/in each nodule

Front 47

Describe the prevalence & gross appereance of:

a. hepatocellular adenoma
b. hepatocellular carcinoma

Back 47

a. uncommon benign, usually solitary mass (gross ddx in dog: nodular hyperplasia)
b. uncommon, friable, gray to yellow masses divided into lobules (mets uncommon)

Front 48

cholangiocellular adenoma

a. species most commonly affected
b. cystic variants

Back 48

a. cat
b. produce very large masses composed of fluid filled cysts

Front 49

cholangiocellular carcinoma

a. gross appearance
b. histologic appearance
c. biological behavior

Back 49

a. firm, umbilicated large single mass or multiple masses
b. ducts or acini lined by poorly differentiated cuboidal biliary epithelium
c. mets very common: aggressive tumor

Front 50

What are carcinoids?

Back 50

tumors in dogs & cats derived from neuroendocrine cells in biliary tree; highly metastatic

Front 51

ddx for nodular liver

Back 51

nodular hyperplasia
regenerative nodules
hepatocellular adenoma
hepatocellular carcinoma
biliary carcinoma
metastasis

Front 52

What are some causes of biliary obstruction?

Back 52

choleliths
parasites
stenosis d/t local tumors or abscesses

Front 53

cholecystitis

a. etiologies
b. acute
b. chronic

Back 53

a. canine adenovirus I, Rift Valley fever, Salmonella
b. characteristic edema & hemorrhage
c. usually accompanies prolonged bacterial infection or ongoing irritation by choleliths or parasites
-rarely GB can rupture --> severe peritonitis

Front 54

What is a gallbladder mucocele?

Back 54

distended gall bladder filled w/ a mucus plug (cause unkown)

Front 55

What is cystic mucinous hyperplasia of the gall bladder?

Back 55

hyperplastic lesion of gall bladder epi in old dogs (no clinical significance)

Front 56

pancreatic hypoplasia (juvenile pancreatic atrophy)

a. signalment
b. clinincal signs
c. lesion

Back 56

a. occurs in several dog breeds, esp. GSD & sporadically in calves
b. signs of EPI appear at 6-12 mos: thin despite voracious appetite, persistent diarrhea
c. exocrine pancreas dramatically diminished in size --> inadequate function

Front 57

What are Pacinian corpuscles?

Back 57

small pale nodules (clear spots) in cat pancreas that are pressure sensors (normal)

Front 58

What are some causes of pancreatic degeneration?

Back 58

prolonged anorexia or starvation
obstruction of pancreatic ducts (calculi, parasites, local neoplasms or abscesses)
chronic pancreatitis --> loss of zymogen granules

Front 59

What are some causes of acute pancreatitis/pancreatic necrosis?

Back 59

obstruction of pancreatic ducts by parasite migration or calculi
delivery of blood-borne toxins (uremic toxins) or therapeutic drugs (ex. Sulfonamides)
ischemia from a variety of causes --> direct injury to acinar cells
direct trauma to pancreas
aberrant transport of proenzymes w/in acinar cells --> inappropriate activation of enzymes w/in cells
consumption of high fat meal
hypercalcemic conditions (ex. hyperparathyroidism)

Front 60

What are some possible sequelae to acute pancreatitis?

Back 60

release of inflammatory mediators can cause widespread vascular injury, hemorrhage, DIC, shock, ARDS

Front 61

chronic pancreatitis

a. most common cause in dogs
b. lesions
c. possible sequelae

Back 61

a. series of mild episodes of acute pancreatitis
b. fibrosis & parenchymal atrophy, fibrous adhesions to adjacent organs, saponification of mesenteric fat
c. EPI, DM (horses) can occur if severe

Front 62

What is pancreatic nodular hyperplasia?

Back 62

age related change in old cats, dogs, cattle (no clinical significance)

raised smooth gray-white masses

Front 63

pancreatic carcinoma

a. species most commonly affected
b. gross appearance
b. biologic behavior

Back 63

a. dogs & cats
b. gray to yellow, invasive masses w/ abundant adhesions
c. mets common: aggressive tumor