C12 Hepatobiliary Pathology I

Question 1

liver size vs overall body

Answer 1

Largest internal organ
o Adult carnivores ~3 % body weight
o Adult herbivores ~1 %
o Larger proportion in neonates

Question 2

liver fetal origin

Answer 2

• Originates from endoderm (gut outpouch)

Question 3

where does liver get its blood flow and oxygen?

Answer 3

• 70-80% of blood flow and 80% of oxygen is from portal vein
  o Portal flow critical for flushing through nutrients, toxins, etc
• However, 25% of cardiac output goes to liver via hepatic artery

Question 4

how much lymph does liver produce? (% of thoracic duct flow)

Answer 4

Liver is the largest lymph producer
o 20-50 % of thoracic duct flow

Question 5

liver functional unit

Answer 5

• Functional unit = lobule or acinus
  > blood flow vs bile flow

Question 6

liver lobule orientation

Answer 6

• Lobule: 6-sided arrangement around central vein

Question 7

hepatocyte arrangement and mass

Answer 7

Hepatocytes arranged in monolayer plates
o 70-80 % of liver mass
o Exposed to blood on 2 sides

Question 8

liver sinusoids are lines by what? where do they drain?

Answer 8

Sinusoids lined by fenestrated endothelium
o No basement membrane
o Drain into central vein

Question 9

liver acinus is split into 3 zones based on what? what are the zone properties? which are prone to injury and what kind?

Answer 9

• Acinus split into 3 zones based on blood supply
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• Zone 1 (periportal)
  o Most prone to direct toxic injury
• Zone 2 (midzonal)
• Zone 3 (periacinar/centrilobular)
  o Most active in detoxification
  o Lowest oxygen
  o Most prone to toxic AND hypoxic injury

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* Basis of zonal pattern (more on this later…)

Question 10

where do hepatocytes secrete bile? where does it go?

Answer 10

• Hepatocytes secrete bile into canaliculi between them
  o Drains into bile ductules lined by cholangiocytes
• Bile stored in gallbladder (except horses, rats)
  o Empties into duodenum
  o May join pancreatic duct in some species (ex. cats) – implications of pancreatitis!

Question 11

what is included in a portal tract?

Answer 11

Portal tract = portal vein, bile duct, ≥ 1 arteriole, connective tissue, lymphatics, nerves

Question 12

where do we find cholangiocytes? what is their commonality with hepatocytes?

Answer 12

• bile ductules lined by cholangiocytes
  o Both hepatocytes and cholangiocytes arise from hepatic progenitor cells (liver stem cell)

Question 13

Kupffer cells - what are they? where are they? what do they do?

Answer 13

• Attached to sinusoids
• Liver macrophages, poor APCs
• Remove bacteria from portal blood (last component of gut barrier)
• Phagocytosis without inflammation

Question 14

Stellate (Ito) cells - function in liver?

Answer 14

• Store retinoids (ex. vitamin A): lipid
• Remodel extracellular matrix
• Important in fibrosis

Question 15

hwo can we get a liver that is to small due to injury response? what will it look like? how will function be affected?

Answer 15

• Reduced demand (illness, starvation) produces hepatocellular atrophy
  o Loss of cytoplasmic mass, some apoptosis in chronic starvation
  o Smaller, darker, and firmer (reduced cell:connective tissue ratio)
  o Can be marked without impairing function

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• Hepatic atrophy
  o Overall organ is too small
• Regional hepatic atrophy
  o Can be due to pressure (ex. from a tumour) or locally impaired blood flow
  o Right lobe atrophy in horses: compression by chronically distended cecum and/or
  right dorsal colon

Question 16

• Hepatocellular hypertrophy - when do we see this? what patterns are possible? can we reverse?

Answer 16

o Increased cytoplasmic volume, can result from anything stimulating smooth ER
o Can be centrilobular (recall this is the primary site of detoxification) or diffuse
o Always tends to enlarge the entire liver, reversible if trigger is removed
o Classic example: chronic phenobarbital administration in epilepsy

Question 17

Hepatocytes can accumulate two major types of vacuole:

Answer 17

• Glycogenosis
• Steatosis/lipidosis

Question 18

what causes glycogen vacuoles in the liver? what will it look like and how will function be affected?

Answer 18

Glycogenosis: buildup of glycogen-filled vacuoles but function remains NORMAL
o Liver will be enlarged and tan to bronze coloured
o Common causes include steroid treatment, hyperadrenocorticism

Question 19

what is liver steatosis/lipidosis? when do we see this? what does it indicate and why can it be problematic?

Answer 19

• Steatosis/lipidosis: cytoplasmic fat globules
  o Seen anytime lipid uptake exceeds excretion
  o Not directly harmful, indicates other damage
  o Usually reversible but makes liver more prone to other damage

Question 20

what is tension lipidosis? what animals?

Answer 20

Tension lipidosis: mostly in cattle, focal hypoxia due to pull of fibrous attachments
* localized liver lipidosis

Question 21

Steatosis/lipidosis
- physiologic
> what animals? when/why?

• vs pathologic
  > how does this happen?
  > how can it result in lipogrulomas? significance?

Answer 21

Physiologic
o Neonates: due to high fat content in milk
o Adults: increased triglyceride mobilization in late
pregnancy/lactation
o If dietary intake is not sufficient to prevent excess
accumulation, can tip into pathologic lipidosis

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o Pathologic: injured/hypoxic hepatocytes (can’t metabolize fat efficiently)
o If fatty hepatocytes rupture, can form lipogranulomas as Kupffer cells clean up
(increase with age, not clinically significant)

Question 22

Lipidosis syndromes (4)

Answer 22

• Ketosis/hepatic lipidosis in ruminants
• Hyperlipemia in donkeys, miniature horses, and ponies
• Feline fatty liver syndrome
• Primary idiopathic hyperlipidaemia
• Lipidosis in toy breed dogs after stress, fasting

Question 23

Ketosis/hepatic lipidosis in ruminants
> cause? effect?

Answer 23

o Dietary insufficiency and/or abomasal displacement in high producing dairy cows
o Nutrient deficient pregnant/lactating ewes with pregnancy toxemia
o Cows more tolerant of ketosis than ewes, which tend to die quickly

Question 24

Hyperlipemia in donkeys, miniature horses, and ponies
- what do we see in serum?
- results?
- risk factors?

Answer 24

o Increased serum very low density lipoproteins (VLDL)
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o Rapidly fatal in older, overweight, pregnant or lactating mares
o Severe hepatic lipidosis and lipid in heart and skeletal muscle
o Often also develop disseminated intravascular coagulation
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o Reduced feed intake or increased stress (negative energy balance), insulin resistance may play a role

Question 25

Feline fatty liver syndrome
- risk factors, prognosis?

Answer 25

o Obese, nutritionally stressed cats, high mortality if untreated
o Pathogenesis unclear (probably multifactorial)
o Contribution of diabetes, pancreatitis, other diseases?

Question 26

Primary idiopathic hyperlipidaemia
- associted with what other conditions

Answer 26

o May have glycogenosis and lipidosis, increased risk of gallbladder mucocele

Question 27

Hepatic amyloidosis
- associated with? predisposes to / causes what?

Answer 27

o Usually associated with systemic amyloidosis
o Predisposes to rupture and bleeding, causes pressure atrophy of hepatocytes

Question 28

liver apoptosis purpose? very high rates can cause?

Answer 28

Apoptosis: used to remove old/damaged cells and remodel
o Apoptotic bodies rapidly phagocytosed by other hepatocytes or Kupffer cells
o Very high rates of apoptosis can stimulate stellate cells to cause fibrosis

Question 29

liver necrosis
- stimulates what?
- what kinds and what do they look like?

Answer 29

Necrosis: stimulates inflammation
o Coagulative: intact, hypereosinophilic cells missing nuclei
o Lytic: disintegrating cells, often phagocytes (especially neutrophils)

Question 30

coagulative necrosis in the liver is more common in what circumstance?

when do we usually see lytic?

Answer 30

• Coagulative: Common in acute toxicity
• Lytic: Later stages of necrosis

Question 31

Focal/multifocal necrosis of liver
- is it common and obvious?
- causes?
- effects?

Answer 31

Focal/multifocal necrosis: common, often not grossly visible
o Nonspecific: any bacteria causing septicaemia, viruses, parasitic migration, biliary obstruction…
o Often found in cattle at slaughter, little functional effect

Question 32

Lobular necrosis
- subdivided how? when do we see each?
- what gross pattern?

Answer 32

Lobular necrosis: subdivided by zone affected
o All produce zonal pattern grossly (surviving hepatocytes pale and fatty, dead areas red and collapsed), but zonal patterns do not always mean necrosis
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o Centrilobular/zone 3: most common, seen in hypoxia, toxicity, acute heart failure, viruses, slow (agonal) death

o Midzonal/zone 2: least common, some toxins

o Portal/zone 1: uncommon, direct acting toxins

o Paracentral: form of coagulative necrosis usually due to infarction, a wedge- shaped portion of the lobule dies

Question 33

when do we see massive liver necrosis (death of entire lobule) and what does it look like? (think pigs)

Answer 33

o All of the cells are dead so the lobule collapses and will scar if the matrix is damaged
o Hepatosis dietetica in rapidly growing pigs on low protein grain diets
o Due to a combination of vitamin E, sulphur, and selenium deficiency
o Affected pigs die suddenly in good body condition

Question 34

liver regenerative capacity and redudnacy

Answer 34

o Can replicate to repair damage (reduces with age)
o Can remove 70% of mass without functional significance and will return to normal mass within a few weeks
o If connective tissue framework is undamaged, can completely restore damage

Question 35

Simply restoring cell mass is not enough to resolve injury to the liver
- what else must be restored? how?

Answer 35

o Must also restore the hepatic architecture
o Hepatocytes first form aggregates, then endothelium forms new channels

Question 36

how fast can Acute centrilobular necrosis repair?

Answer 36

repair in 24-48 hours

Question 37

Chronic or repetitive liver injury tends to produce what type of regeneration? mostly what species?

Answer 37

nodular regeneration (mostly dogs)