Liver 2 Flashcards
Name the cell type in the liver that deposits collagen in cases of hepatic fibrosis
Ito (hepatic stellate) cell
What is the role of Ito (hepatic stellate) cells in hepatic disease?
To deposit collagen (which can lead to hepatic fibrosis)
What is the alternative name for a hepatic Ito cell?
Hepatic stellate cell
What the alternative name for a hepatic stellate cell?
Ito cell
Ito (hepatic stellate) cells are responsible for collagen deposition in hepatic disease and fibrosis. What is their role in the non-diseased liver?
Storage of vitamin A and fat
Where, precisely, are hepatic Ito (stellate) cells found within the liver?
In the space of Disse
Explain why fibrosis within and around hepatic sinusoids is such a serious change.
The space of Disse becomes reduced or obliterated by collagen deposition. The ability of the liver to carry out its synthetic, catabolic and excretory roles is severely compromised by this reduced exposure of hepatocytes to plasma.
What does the term cirrhosis mean?
Diffuse hepatic fibrosis accompanied by regenerative nodule formation (end-stage liver is a better term than cirrhosis)
What is the term for diffuse hepatic fibrosis accompanied by regenerative nodule formation?
Cirrhosis (or end-stage liver)
Describe the appearance of an end-stage (cirrhotic) liver
The liver is small, firm, and irregular with nodules of regenerative parenchyma separated by tracts of fibrous connective tissue.
Name 3 causes of end-stage liver (cirrhosis). [The answer has 6 causes so if you can name even more than 3 that’s great]
- Chronic toxicity; 2. Chronic cholangitis or obstruction; 3. Chronic congestion (right-sided heart failure); 4. Inherited copper or iron storage disorders; 5. Chronic hepatitis; 6. Idiopathic
Explain why hepatotoxins commonly result in periportal, rather than centrilobular necrosis.
Hepatocytes in Zone 1 of theliver lobule (periportal; closest to portal areas) are the first to receive blood and, therefore, may be the first to be injured by circulating toxins -> PERIPORTAL NECROSIS
Which pattern of hepatic necrosis (centrilobular or periportal) is more likely in cases of hepatotoxicity and why?
Periportal. Hepatocytes in Zone 1 of theliver lobule (periportal; closest to portal areas) are the first to receive blood and, therefore, may be the first to be injured by circulating toxins -> PERIPORTAL NECROSIS
Which pattern of hepatic necrosis (centrilobular or periportal) is more likely in cases of anemia or hypoxia and why?
Centrilobular. Hepatocytes in Zone 3 of the lobule (centrilobular; closest to central veins) are the last to receive blood and, therefore, may be the first to be injured by ischemia -> CENTRILOBULAR NECROSIS
Name 3 routes in which bacteria can reach the liver via the bloodstream.
- The portal vein; 2. The umbilical veins from umbilical infections in newborn animals; 3. The hepatic artery, as part of a generalized bacteremia.
Name 3 NON-vascular routes by which bacteria may reach the liver.
- Ascending infection of the biliary system; 2. Parasitic migration; 3. Direct extension of an inflammatory process from tissues immediately adjacent to the liver, such as the reticulum.
What are the two main syndromes caused by Rhodococcus equi in foals?
Typically enterocolitis and/or bronchopneumonia
Which domestic species, and which specific subgroup in this species, is most commonly affected by disease due to Rhodococcus equi?
Horses; foals most commonly affected
You are performing a necropsy on a foal and find disseminated abscesses throughout the mesenteric lymph nodes, spleen, liver and large intestine. What is the most likely cause?
Rhodococcus equi
How is Rhodococcus equi spread among horses?
It is present in the soil and feces, and farms can be endemically infected. It may be ingested or inhaled to cause infection, but inhalation is believed to be the more common route.
You are performing a necropsy on a feedlot steer and find numerous foci of necrosis and abscess formation throughout the liver. What are the likely (a) cause and (b) pathogenesis?
(a) Fusobacterium necrophorum; (b) Damage to ruminal mucosa (rumenitis) -> bacteria enter portal circulation -> shower liver -> hepatic abscesses -> poor production
Explain why feedlot cattle with rumenitis may develop hepatic and even pulmonary abscesses.
Damage to ruminal mucosa (rumenitis) -> bacteria enter portal circulation -> shower liver -> hepatic (and possibly pulmonary) abscesses
Name the organism that causes Tyzzer’s disease.
Clostridium piliforme
Which hepatic disease is caused by Clostridium piliforme?
Tyzzer’s disease
Which animal types are most commonly affected by Tyzzer’s disease?
- Laboratory rodents; 2. Horses (foals and stressed weanlings)
How is Clostridium piliforme, the organism responsible for Tyzzer’s disease, spread among animals?
Fecal-oral transmission
What is the characteristic gross lesion of Tyzzer’s disease?
Numerous liver “dit-dots.” In an exam write: disseminated gray-white 1 to 3 mm diameter foci of necrosis surrounded by suppurative inflammation.
We think of leptospirosis primarily affecting the kidney. How, then, does it cause icterus? What is the pathogenesis?
Leptospirosis -> hemolysis -> ischemic injury to centrilobular hepatocytes -> centrilobular necrosis -> icterus
Each species has its own abortigenic herpesvirus strain. What strain causes abortion in: (a) horses; (b) cattle; (c) dogs; (d) cats?
(a) EHV-1; (b) BHV-1; (c) CHV-1; (d) FHV-1
Herpesviruses may cause abortion in adult animals. What fetal lesions are characteristic in a fetus aborted because of herpesviral infection?
Multifocal random pinpoint necrosis in multiple organs: liver, kidneys, lungs and spleen most commonly affected. These show up as randomly distributed white “dit-dots.”
You are examining the carcass of an aborted foal and notice randomly distributed white “dit-dots” through the liver, kidneys, lungs and spleen. What is the most likely cause of these?
Abortion due to infection with equine herpesvirus type 1 (EHV-1)
You are examining the carcass of an aborted calf and notice randomly distributed white “dit-dots” through the liver, kidneys, lungs and spleen. What is the most likely cause of these?
Abortion due to infection with bovine herpesvirus type 1 (BHV-1)
You are examining the carcass of a newborn puppy that failed to thrive and then died. You notice randomly distributed white “dit-dots” through the liver, kidneys, lungs and spleen. What is the most likely cause of these?
Infection with canine herpesvirus type 1 (CHV-1)
Herpesviruses may cause severe disease and death in fetal and neonatal animals. Give 4 possible routes of infection of a fetus/neonate with herpesviruses.
(1) Transplacental in utero; (2) During birth from birth canal; (3) After birth from infected littermates’ oronasal secretions; (4) After birth from dam’s oronasal secretions.
Dogs, especially in warmer climates, may develop “deep” (systemic) fungal infections that cause granulomatous inflammation in the lung and liver. Name one genus of fungus that is commonly involved.
(1) Histoplasma spp. ; (2) Blastomyces spp. (3) Coccidioides spp.
What is the cause of “milk spots” in the liver of pigs?
Migration of the nematode worm Ascaris suum through the liver
What gross lesion is characteristically seen in pigs infected with Ascaris suum?
Fibrous scars in the liver called “milk spots”
What organism causes heartworm disease in dogs?
The nematode worm Dirofilaria immitis
What organism causes vena caval (postcaval) syndrome in dogs?
The nematode worm Dirofilaria immitis
Explain the pathogenesis of vena caval (postcaval) syndrome in dogs.
The nematode worm Dirofilaria immitis (the cause of heartworm disease) normally lives in the pulmonary arteries. Heavy infestation can lead to worms also occupying the right heart and caudal vena cava –> acute hepatic failure -> rapid death
What lifecycle stage of the harmless Taenia tapeworms found in wild and domestic canids is found in intermediate hosts, and where in the intermediate host are these found??
The encysted intermediate stages of Taenia tapeworms are called Cysticercus. They are found in solid organs (often liver) of the intermediate hosts: horses, ruminants, pigs, rabbits, rodents etc.
You are examining the liver of a cow and find several encysted parasitic cysts, later identified as Cysticercus species. How was this cow infected? What is the lifecycle of this parasite?
From grazing on pasture contaminated by the feces of a canid infected with the tapeworm species Taenia. The lifecycle is completed when the canid eats the cyst in the intermediate host (i.e., the cow).
What organism causes hydatid cysts in sheep and aberrantly infected humans?
Echinococcus spp. These are tapeworms in canids that, when ingested in feces, cause formation of large cysts in the solid organs of the intermediate host. These cysts can be fatal in humans.
Why are humans so concerned about infection of pet dogs and wild canids (e.g., coyotes) with the relatively harmless tapeworms in the genus Echinococcus?
Echinococcus spp. are tapeworms in canids that, when ingested in feces, cause formation of large cysts in the solid organs of the intermediate host. These cysts can be fatal in humans.
What species of fluke infests the biliary ducts of ruminants?
Fasciola hepatica (and Fascioloides magna in wild ruminants)
You are examining the liver of a cow and find numerous linear and branching dark black tracts throughout the parenchyma that appear to follow vessels. What is the most likely cause?
These are migration tracts of liver flukes (Fasciola hepatica), which live in and migrate along biliary ductules
What is a serious sequela to hepatic fluke infestation in ruminants, and what is the pathogenesis?
Migrating flukes leave hemorrhagic and necrotic tracts in the liver before reaching the biliary ducts. These can cause hepatic disease by themselves but, more seriously, spores of Clostridium species can proliferate in necrotic hepatic tissue [C. haemolyticum –> bacillary hemoglobinuria (red water disease); C. novyi –> infectious necrotic hepatitis (black disease)]
Name two clostridial species that may proliferate in the necrotic debris left by migrating hepatic flukes in ruminants.
C. haemolyticum –> bacillary hemoglobinuria (red water disease); C. novyi –> infectious necrotic hepatitis (black disease)
Two clostridial species may proliferate in the necrotic debris left by migrating hepatic flukes in ruminants. Name them, and the disease caused by each.
C. haemolyticum –> bacillary hemoglobinuria (red water disease); C. novyi –> infectious necrotic hepatitis (black disease)
What predisposes cattle to development of infectious necrotic hepatitis, and what causes this disease?
Clostridium novyi causes infectious necrotic hepatitis (black disease). Migrating liver flukes (Fasciola hepatica) predispose to this disease by leaving hemorrhagic and necrotic tracts in the liver before reaching the biliary ducts. These can cause hepatic disease by themselves but, more seriously, spores of Clostridium species can proliferate in necrotic hepatic tissue.
What organism causes bacillary hemoglobinuria (red water disease) in ruminants?
Clostridium haemolyticum causes bacillary hemoglobinuria (red water disease). Migrating liver flukes (Fasciola hepatica) predispose to this disease by leaving hemorrhagic and necrotic tracts in the liver before reaching the biliary ducts. These can cause hepatic disease by themselves but, more seriously, spores of Clostridium species can proliferate in necrotic hepatic tissue.
On ultrasound examination you detect a smoothly-domed well-demarcated parenchymal mass in the liver of a dog. Assuming that it is not malignant, what are two likely diagnoses for this mass?
(1) Nodular hyperplasia; (2) Hepatocellular adenoma
In which type of domestic animal is hepatic nodular hyperplasia seen, and in which age group?
Dogs (middle-aged & older)
Compare and contrast the appearance and causes of (1) nodular hyperplasia and (b) nodular regeneration in the liver of dogs
(1) Nodular hyperplasia: usually solitary, well demarcated, smoothly domed and NOT associated with hepatic disease (neither causing nor resulting from it); (2) Nodular regeneration: the liver is small, firm and irregular with nodules of regenerative parenchyma separated by tracts of fibrous connective tissue. This disease is the result of prolonged insult to the liver, such as that caused by chronic anticonvulsant administration.
Describe the typical gross appearance of a liver with severe nodular regeneration (end-stage liver).
The liver is small, firm and irregular with nodules of regenerative parenchyma separated by tracts of fibrous connective tissue.
What is the name and appearance of a benign liver mass derived from hepatocytes?
Hepatocellular adenoma; Discrete, well circumscribed mass that may compress but does not invade adjacent liver parenchyma
What is the name and appearance of a malignant liver mass derived from hepatocytes?
Hepatocellular carcinoma; Poorly demarcated and multilobular mass that invades adjacent liver parenchyma. The centres of neoplastic lobules are frequently necrotic
What is the name and appearance of a benign liver mass derived from the cells that line biliary ductules?
Cholangiocellular adenoma (“biliary adenoma”). Variably sized cystic cavities in the liver lined by flattened biliary epithelium. These are difficult to distinguish from congenital biliary cysts.
In which domestic species is cholangicellular adenoma (“biliary adenoma”) most common?
Cats; rare in other species.
What is the name and appearance of a malignant liver mass derived from the cells that line biliary ductules?
Cholangiocellular carcinoma; Multiple, randomly distributed firm hepatic nodules, many with umbilicated centers
Many types of metastatic neoplasm can end up in the liver, where they usually appear as nodules with a characteristic “showering” distribution. One very common neoplasm doesn’t follow this rule, however, and can cause diffuse hepatic enlargement and an enhanced lobular pattern that can mimic various other hepatic diseases. What neoplasm is this?
Lymphoma
What is one characteristic (and “non-lumpy”) appearance of a liver with infiltrative / metastatic lymphoma? How does this appearance arise?
Diffuse hepatic enlargement, pale liver and an enhanced lobular pattern that can mimic various other hepatic diseases. The reason for this is that neoplastic lymphocytes typically aggregate in portal areas of each lobule, rather than forming discrete nodules (although the latter is possible and even common; lymphoma does not follow rules and should always be considered in a differential list).
What is another name for equine serum hepatitis?
Theiler’s disease
What is another name for Theiler’s disease in horses?
Equine serum hepatitis
What is the pathogenesis of Theiler’s disease in horses?
Horse receives an injection of a biologic that contains equine serum (e.g., tetanus antitoxin) –> After some time horse develops hepatic failure –> hepatic encephalopathy & icterus –> death. Cause / mechanism unknown
You are examining the liver of a horse that died of hepatic failure. The liver is small, flabby and limp (“dishrag” appearance). What is the most likely disease, and what aspect of this horse’s history should be investigated?
Theiler’s disease. You should investigate whether this horse has had a recent injection of a biologic that contains equine serum (e.g., tetanus antitoxin)
Theiler’s disease in horses results from (a) Clostridium piliforme infection or (b) recent injection of a biologic that contains equine serum (e.g., tetanus antitoxin). [Choose one answer]
(b) Recent injection of a biologic that contains equine serum (e.g., tetanus antitoxin)
Tyzzer’s disease in horses results from (a) Clostridium piliforme infection or (b) recent injection of a biologic that contains equine serum (e.g., tetanus antitoxin). [Choose one answer]
(a) Clostridium piliforme infection
Chronic copper toxicity occurs most often in sheep. What is its pathogenesis and how does it cause liver damage?
Dietary copper excess or molybdenum deficient soil -> Copper accumulates in liver -> [at later time] Animal ingests hepatotoxin (plant or mycotoxin) -> Hepatocyte injury -> Sudden release of copper -> Acute intravascular hemolysis -> Hepatocellular necrosis because of anemia. Note that the copper itself is not directly toxic to the liver
You are examining the liver of a young, rapidly growing pig that died of hepatic failure. The liver is swollen, necrotic and covered in fibrin. What disease should you be thinking of, and what is its cause?
Hepatosis dietetica. The cause is unknown, but it is vitamin E / selenium responsive and so may be due to a deficiency of these.
Which mineral must be supplemented in young, indoor-housed pet pigs?
Iron
Iron deficiency is a risk in which particular population of pigs?
Young, indoor-housed pet pigs
How does lack of iron supplementation result in liver disease in young, indoor-housed pet pigs?
Iron deficiency -> anemia -> ischemic injury to centrilobular hepatocytes -> centrilobular necrosis -> icterus
One cause of chronic hepatitis in dogs is copper accumulation. In one breed in particular there is a well-recognized genetic mutation that prevents copper excretion by hepatocytes. Name this breed.
Bedlington terrier
One cause of chronic hepatitis in dogs is copper accumulation in certain predisposed breeds. In the Bedlington terrier there is a well-recognized genetic mutation that prevents copper excretion by hepatocytes. In other breeds, however, it’s less clear whether copper accumulation is a cause for, or a result of the disease. Name one of these predisposed breeds.
Cocker spaniels; Doberman pinschers; Skye terriers; Standard poodles; West Highland white terriers
What agent causes infectious canine hepatitis?
Canine adenovirus type 1 (CAV-1)
True or false: infection with canine adenovirus-1 generally causes fulminant infection which is often fatal.
False; most infections are asymptomatic
Canine adenovirus type 1 (CAV-1), the cause of infectious canine hepatitis, has a tropism for which types of cells? Name three.
(1) Hepatocytes; (2) Endothelial cells; (3) Mesothelial cells, such as those lining the peritoneal, pleural and pericardial cavities
A thickened edematous gall bladder in a dog that died of systemic disease is characteristic of which disease, and what is the cause of this disease?
Infectious canine hepatitis, caused by canine adenovirus type 1 (CAV-1)
Canine adenovirus type 1 (CAV-1), the cause of infectious canine hepatitis, has a tropism for (1) hepatocytes; (2) endothelial cells; (3) mesothelial cells, such as those lining the peritoneal, pleural and pericardial cavities. Given this, what gross lesions would you expect, in addition to liver necrosis?
Widespread petechial hemorrhages because of the endothelial damage
How is canine adenovirus type 1 (CAV-1), the cause of infectious canine hepatitis, transmitted among dogs?
Urine-oral infection
Which canine disease is associated with development of “blue-eye”, in which the cornea becomes edematous and opaque?
Infectious canine hepatitis, caused by canine adenovirus type 1 (CAV-1). Infection or vaccination with CAV-1 can result in immune complex uveitis, a type III hypersensitivity reaction
Dogs recovering from or vaccinated against infectious canine hepatitis may develop ocular lesions. What are these ocular lesions and what is their pathogenesis?
Infectious canine hepatitis, caused by canine adenovirus type 1 (CAV-1) is associated with development of “blue-eye”, in which the cornea becomes edematous and opaque. Infection or vaccination with CAV-1 can result in immune complex uveitis, a type III hypersensitivity reaction
Lymphocytic cholangitis is a slowly progressive disease affecting which domestic species most commonly?
Cats
Lymphocytic cholangitis, a slowly progressive disease of cats, affects which age group?
Young to middle-aged cats
Lymphocytic cholangitis, a slowly progressive disease of cats, is caused by what?
No-one knows. It is presumed to be immune-mediated, but no definitive cause has been found
Gallstones are relatively uncommon in domestic animals. However, they are seen not infrequently in one species of domestic animal. Which one?
Cattle
What is the term for inflammation of the gall bladder?
Cholecystitis
What is the term for the condition of gallstones?
Cholelithiasis
Cholecystitis (gall bladder inflammation) is seen most commonly in dogs with which infectious disease?
Infectious canine hepatitis, caused by canine adenovirus type 1 (CAV-1)
Cholecystitis (gall bladder inflammation) is seen most commonly in calves with which infectious disease?
Enteric salmonellosis
Mucocele of the gall bladder is seen most frequently in which domestic species?
Dogs
Mucocele of the gall bladder does not cause clinical signs. True or false?
False. Mucocele of the gall bladder is often associated with signs of biliary obstruction and can occasionally lead to gallbladder rupture.
You perform a necropsy on a dog with biliary obstruction and note that the gall bladder is distended by mucus. What is this condition?
Gall bladder mucocele
You perform a necropsy on a dog with no clinical signs and note that the gall bladder has a “sponge-like” consistency. What is this condition?
Cystic mucinous hyperplasia
Describe the gross lesions of cystic mucinous hyperplasia of the gall bladder in dogs.
Sponge-like mucosal surface of the gall bladder caused by numerous 1-3 mm diameter cysts filled with mucus.
Both gall bladder mucocele and cystic mucinous hyperplasia of the gall bladder in dogs are associated with mucous distension of the gall bladder or its mucosa. However, one is typically associated with clinical signs, and sometimes even biliary obstruction or gall bladder rupture. Which one?
Gall bladder mucocele
What is the term for inflammation of the biliary ducts?
Cholangitis
What does the term cholangitis mean?
Inflammation of the biliary ducts
What is the most common reason for neutrophilic cholangitis?
Ascending bacterial infection from the intestine via the bile duct
In which domestic species is lymphocytic cholangitis most commonly seen?
Cats
What is the term for inflammation affecting both the biliary ducts and hepatic parenchyma?
Cholangiohepatitis
What does the term cholangiohepatitis mean?
Inflammation affecting both the biliary ducts and hepatic parenchyma
