JPC SYSTEMIC PATHOLOGY
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, small hepatocytes, and numerous closely opposed portal triads. 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 admixed with karyorrhectic debris (single cell necrosis). Multifocally there are few aggregates of hemosiderin and lipid laden macrophages (lipogranulomas). There are random aggregates of few neutrophils, lymphocytes and macrophages in portal areas. Peripheral sinusoids are mildly congested.
- Liver: Lobular hypoplasia, diffuse, severe, with hepatocellular atrophy, venous hypoplasia, and arteriolar hyperplasia, Golden Retriever, canine.
- Liver: Hepatitis, neutrophilic and histiocytic, multifocal, random, minimal.
CONDITION: Congenital portosystemic shunt (PSS)
- Anomalous vessels that directly connect portal venous to systemic venous circulation, bypassing the liver
- Occurs in dogs and cats, rarely pigs, foals, goats, calves
- Two categories: Intrahepatic and extrahepatic
- Inherited basis suspected in Irish wolfhound, Yorkshire terrier, Cairn terrier, Maltese, Australian cattle dog, old English sheepdog, golden retriever, Labrador retriever, Persian cats; and Himalayan cats
- Resulting histopathological changes are nonspecific; differentiation from other congenital vascular anomalies often requires clinical and imaging data
- Does not cause portal hypertension while all other vascular anomalies do cause portal hypertension
- Intrahepatic shunt (large breed dogs): Most commonly results from persistent patent ductus venosus in the left hepatic division
- Extrahepatic shunt (small breed dogs and cats): Most common types are direct shunt from portal vein, gastric vein, or splenic vein to the caudal vena cava (portocaval shunt) or azygous vein (portoazygous shunt)
- Diversion of hepatotrophic factors (e.g. insulin, glucagon, and amino acids) leads to hepatic hypoplasia
- Bypassing hepatic circulation > diversion of ammonia and bile acids from gastrointestinal tract > leads to hyperammonemia and elevated serum bile acids
- Hepatic encephalopathy results from hyperammonemia due to both direct shunting and hepatic hypoplasia
TYPICAL CLINICAL FINDINGS:
- Stunted growth, failure to thrive
- Hepatic encephalopathy: Depression, incoordination, coma and seizures,+/- polydipsia/polyuria (dogs); signs exacerbated by a high protein diet
- Clinical pathology: 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 and of normal color and texture
- Hepatic hypoplasia may be regional or diffuse, depending on shunt location
- Single relatively large anomalous vessel between the portal venous and systemic venous circulation
- +/- renal, cystic, or urethral ammonium biurate calculi
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Histologic changes represent hypoperfusion
- Lobular atrophy (close spacing of portal triads); small acini and hepatocytes
- Small or absent small portal veins
- Empty large portal veins
- Reduplication of hepatic arterioles
- Bile duct proliferation
- Dilated lymphatics in portal triads and centrilobular connective tissue
- Lipogranulomas with hemosiderin throughout the liver
- Ito and Kupffer cell hypertrophy
- Histologic severity cannot be used to predict long-term outcome in dogs undergoing surgical correction of PSS
ADDITIONAL DIAGNOSTIC TESTS:
- Ammonia tolerance test (not diagnostic in Irish wolfhounds because of unassociated transient metabolic hyperammonemia)
- Immunohistochemistry: Perisinusoidal hepatic stellate cells express increased alpha-smooth muscle actin and desmin in congenital PSS livers, in contrast to normal livers, interpreted as cellular proliferation and myofibroblast differentiation
DIFFERENTIAL DIAGNOSIS: The following have similar microscopic changes, but differ from congenital PSS in that they can cause portal hypertension:
- 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: Dogs and occasionally cats; affects extra- and/or intrahepatic portal vein; underlying cause of hepatoportal fibrosis and idiopathic noncirrhotic portal hypertension (about half of cases develop portal fibrosis and biliary hyperplasia); causes portal hypertension, ascites, and acquired PSS
- Hepatoportal microvascular dysplasia (HMD): 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
- Acquired PSS: Arises from chronic liver disease secondary to chronic passive congestion, or primary liver disease (e.g. hepatitis, therefore often has inflammation), leading to portal hypertension and opening of fetal, vestigial blood vessels; ascites always present
- Locations: mesenteric veins and caudal vena cava, right renal vein, or gonadal veins
- Gross: network of tortuous thin-walled vessels
- Dogs and cats most affected; rare in goats, pigs, foals, calves, and other species
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