C12 Hepatobiliary Pathology I Flashcards
liver size vs overall body
Largest internal organ
o Adult carnivores ~3 % body weight
o Adult herbivores ~1 %
o Larger proportion in neonates
liver fetal origin
- Originates from endoderm (gut outpouch)
where does liver get its blood flow and oxygen?
- 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
how much lymph does liver produce? (% of thoracic duct flow)
Liver is the largest lymph producer
o 20-50 % of thoracic duct flow
liver functional unit
- Functional unit = lobule or acinus
> blood flow vs bile flow
liver lobule orientation
- Lobule: 6-sided arrangement around central vein
hepatocyte arrangement and mass
Hepatocytes arranged in monolayer plates
o 70-80 % of liver mass
o Exposed to blood on 2 sides
liver sinusoids are lines by what? where do they drain?
Sinusoids lined by fenestrated endothelium
o No basement membrane
o Drain into central vein
liver acinus is split into 3 zones based on what? what are the zone properties? which are prone to injury and what kind?
- Acinus split into 3 zones based on blood supply
<><><><> - 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…)
where do hepatocytes secrete bile? where does it go?
- 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!
what is included in a portal tract?
Portal tract = portal vein, bile duct, ≥ 1 arteriole, connective tissue, lymphatics, nerves
where do we find cholangiocytes? what is their commonality with hepatocytes?
- bile ductules lined by cholangiocytes
o Both hepatocytes and cholangiocytes arise from hepatic progenitor cells (liver stem cell)
Kupffer cells - what are they? where are they? what do they do?
- Attached to sinusoids
- Liver macrophages, poor APCs
- Remove bacteria from portal blood (last component of gut barrier)
- Phagocytosis without inflammation
Stellate (Ito) cells - function in liver?
- Store retinoids (ex. vitamin A): lipid
- Remodel extracellular matrix
- Important in fibrosis
hwo can we get a liver that is to small due to injury response? what will it look like? how will function be affected?
- 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
- Hepatocellular hypertrophy - when do we see this? what patterns are possible? can we reverse?
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
Hepatocytes can accumulate two major types of vacuole:
- Glycogenosis
- Steatosis/lipidosis
what causes glycogen vacuoles in the liver? what will it look like and how will function be affected?
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
what is liver steatosis/lipidosis? when do we see this? what does it indicate and why can it be problematic?
- 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
what is tension lipidosis? what animals?
Tension lipidosis: mostly in cattle, focal hypoxia due to pull of fibrous attachments
* localized liver lipidosis
Steatosis/lipidosis
- physiologic
> what animals? when/why?
- vs pathologic
> how does this happen?
> how can it result in lipogrulomas? significance?
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)
Lipidosis syndromes (4)
- 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
Ketosis/hepatic lipidosis in ruminants
> cause? effect?
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
Hyperlipemia in donkeys, miniature horses, and ponies
- what do we see in serum?
- results?
- risk factors?
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
Feline fatty liver syndrome
- risk factors, prognosis?
o Obese, nutritionally stressed cats, high mortality if untreated
o Pathogenesis unclear (probably multifactorial)
o Contribution of diabetes, pancreatitis, other diseases?
Primary idiopathic hyperlipidaemia
- associted with what other conditions
o May have glycogenosis and lipidosis, increased risk of gallbladder mucocele
Hepatic amyloidosis
- associated with? predisposes to / causes what?
o Usually associated with systemic amyloidosis
o Predisposes to rupture and bleeding, causes pressure atrophy of hepatocytes
liver apoptosis purpose? very high rates can cause?
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
liver necrosis
- stimulates what?
- what kinds and what do they look like?
Necrosis: stimulates inflammation
o Coagulative: intact, hypereosinophilic cells missing nuclei
o Lytic: disintegrating cells, often phagocytes (especially neutrophils)
coagulative necrosis in the liver is more common in what circumstance?
when do we usually see lytic?
- Coagulative: Common in acute toxicity
- Lytic: Later stages of necrosis
Focal/multifocal necrosis of liver
- is it common and obvious?
- causes?
- effects?
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
Lobular necrosis
- subdivided how? when do we see each?
- what gross pattern?
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
when do we see massive liver necrosis (death of entire lobule) and what does it look like? (think pigs)
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
liver regenerative capacity and redudnacy
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
Simply restoring cell mass is not enough to resolve injury to the liver
- what else must be restored? how?
o Must also restore the hepatic architecture
o Hepatocytes first form aggregates, then endothelium forms new channels
how fast can Acute centrilobular necrosis repair?
repair in 24-48 hours
Chronic or repetitive liver injury tends to produce what type of regeneration? mostly what species?
nodular regeneration (mostly dogs)
