JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
September 2021
D-M13

 

Signalment (JPC #2458719):  12-week-old male Golden Retriever

 

HISTORY:  This dog presented for acute onset of ataxia, disorientation, vomiting, drooling, collapse, and apparent blindness.

 

HISTOPATHOLOGIC DESCRIPTION:  Liver:  There is diffuse lobular hypoplasia characterized by small lobules with closely apposed portal triads.  Hepatocytes are diffusely small (atrophy).  Central veins are often indistinct.  Diffusely, portal triads contain multiple tortuous arterioles (arteriolar hyperplasia), minimally increased numbers of bile ducts (bile duct hyperplasia), and inapparent portal veins (portal vein hypoplasia).  There is rare individualization of brightly eosinophilic hepatocytes (single cell death) admixed with karyorrhectic debris. Multifocally there are few aggregates of hemosiderin- and lipid-laden macrophages (lipogranulomas).  There are rare, random aggregates of few neutrophils, lymphocytes, and macrophages.  Sinusoids at the periphery of the section are mildly congested.

 

MORPHOLOGIC DIAGNOSIS: 

1. Liver:  Lobular hypoplasia, diffuse, severe, with hepatocellular atrophy, portal venous hypoplasia, and arteriolar hyperplasia, Golden Retriever, canine.

2. Liver: Hepatitis, neutrophilic and histiocytic, multifocal, random, minimal.

 

CONDITION:  Congenital portosystemic shunt (PSS)

 

GENERAL:

• Portosystemic shunt is an anomalous vessel(s) that directly connects the portal vein to systemic venous circulation, bypassing the liver
  • Occurs in dogs and cats, rarely pigs, foals, goats, calves
  • Two categories: Intrahepatic or Extrahepatic
• Inherited basis suspected in Irish wolfhound, Yorkshire terrier, Cairn terrier, and Australian cattle dog
• Histopathological changes are nonspecific; differentiation from other congenital vascular anomalies and other vascular anomalies in the liver often requires clinical and imaging data
• Does not cause portal hypertension (thus, no ascites) while all other vascular anomalies do cause portal hypertension

 

PATHOGENESIS:

• Two categories:
  • Intrahepatic shunt (large breed dogs): most commonly a persistent patent ductus venosus in the left hepatic division
  • Extrahepatic shunt (small breed dogs and cats): most commonly are a direct shunt from portal vein or tributaries (gastric vein, splenic vein) to the caudal vena cava (portocaval shunt) or azygous vein (portoazygous shunt)
• Hepatic hypoplasia due to diversion of hepatotrophic factors (e.g. insulin, glucagon, growth factors, and amino acids)
• Hepatic encephalopathy: Blood bypasses hepatic circulation à diversion of waste products (ammonia, bile acids) and nutrients from GI tract à hepatic hypoplasia, arteriole hypertrophy/hyperplasia, hyperammonemia and elevated serum bile acids à accumulation of toxic substances (especially ammonia) à neurotoxicity (hepatic encephalopathy)

 

TYPICAL CLINICAL FINDINGS:

• Adolescent, stunted growth, failure to thrive
• Hepatic encephalopathy: Signs are variable and exacerbated by high protein diet
  • Dogs/Cats: Depression, incoordination, coma and seizures, vomiting
  • Large animals: Dull, central blindness, aggression (calves), frenzy (foals)
• Clinical pathology consistent with decreased hepatic function: Elevated serum bile acids, hypoalbuminemia, hyperammonemia with formation of ammonium biurate crystals in alkaline urine, hypoglobulinemia, hypoglycemia, decreased BUN, hypocholesterolemia, +/- mild to moderate microcytic, normochromic, nonregenerative anemia

 

TYPICAL GROSS FINDINGS:

• Microhepatica; liver may otherwise be smooth with normal color and texture; may be diffuse or regional depending on the shunt location
• Single large-caliber anomalous vessel between the portal venous and systemic venous circulation; portal vein may be hypoplastic distal to shunt
• +/- renal, cystic, or urethral ammonium biurate calculi

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Portal veins small or absent, reduplication of arterioles, lobular atrophy
  • Lobular atrophy characterized by close irregular spacing of portal triads
  • Portal veins inapparent, collapsed, empty; small veins may be absent
  • Hepatic arterioles are prominent, increased in numbers, and tortuous (compensatory change)
• Microvesicular steatosis (lipidosis) and lipogranulomas (Kupffer cells and macrophages with cytoplasmic lipid vacuoles and brown pigment – hemosiderin, lipofuscin, and ceroid)
• In some cases: bile duct proliferation (ductular reaction), edema (dilated portal lymphatics, lymphatics in centrilobular connective tissue), increased fibrous connective tissue around portal triads and hepatic vein
• Histologic severity cannot be used to predict long-term outcome of surgery

 

DIFFERENTIAL DIAGNOSIS:  The following have similar microscopic changes, but differ from congenital PSS in that they can cause portal hypertension:

• Acquired PSS: Other congenital abnormalities (arteriovenous malformations, hypoplasia/dysplasia of portal veins) and any chronic liver disease that causes sufficient fibrosis and atrophy, significantly restricting portal blood flow and resulting in portal hypertension may result in acquired PSS (opening of fetal, vestigial blood vessels); ascites always present
  • Locations: between the portal vein or its tributaries and the caudal vena cava, renal vein, or azygos vein.
  • Gross: multiple small, tortuous, thin-walled vessels
• Congenital intrahepatic arteriovenous (arterioportal) fistulae (anastamoses): Arterioportal fistulae between branches of hepatic artery and portal vein > blood goes from high to low pressure > retrograde flow and arterialization of portal circulation > portal hypertension > acquired extrahepatic shunts > hepatic atrophy; may also be acquired secondary to trauma or severe cirrhosis; dilated tortuous portal vein in liver lobe
• Primary hypoplasia of portal vein (PVH): Dogs (Cairn terriers, Yorkshire terriers) and occasionally cats; affects extra- and/or intrahepatic portal vein; intrahepatic PVH considered underlying cause of hepatoportal fibrosis and idiopathic noncirrhotic portal hypertension in some young dogs; causes portal hypertension, ascites, and acquired PSS
• Hepatoportal microvascular dysplasia (HMD): Dogs (Cairn terriers, Yorkshire terriers, Maltese, other small and toy breed dogs); have elevated serum bile acids but lack identifiable intra- or extrahepatic shunts; histologic changes typical of other congenital vascular anomalies; do develop portal hypertension and ascites; may be part of the disease spectrum of portal vein hypoplasia

 

COMPARATIVE PATHOLOGY:

• Dogs and cats are most often affected; rare in goats, pigs, foals, calves, and other species

 

REFERENCES:

1. Brown DL, Van Wettere AJV, Cullen JM. Hepatobiliary system and exocrine pancreas. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:430,436-438.
2. Cullen JM, Stalker MJ.  Liver and biliary system.  In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier Ltd; 2016:266-267,289-292

Click the slide to view.

---