Portal blood flow

Portal venous-systemic venous shunting of blood impairs delivery of portal substances to the liver. Shunting of this sort can occur as a result of congenital vascular anomalies (portosystemic shunts or portosystemic vascular anomalies, microvascular dysplasia), congenital defects in ductal plate formation (resulting in acquired shunts [Pilai et al 2016]) or secondary to acquired defects, such as chronic inflammatory disease with associated fibrosis. The decreased availability of normal hepatotrophic factors in portal blood can lead to hepatic atrophy. These abnormalities in hepatic blood flow are mostly diagnosed in dogs (Toulza et al 2006) and are infrequent in other species, including cats (Ruland et al 2009), horses (Fortier et al 1996), ruminants (Fortier et al 1996, Marçal et al 2008, Kinde et al 2014) and camelids (Ivany et al 2002). On histologic examination, features of shunts are hepatic atrophy, arteriolar duplication with smooth muscle hypertrophy, and small or absent portal veins. Other features may be seen as well, depending on whether the shunt is congenital or acquired (Pilai et al 2016).

The clinicopathologic findings in these conditions results from:

• Delivery of substances normally absorbed by the intestine and removed efficiently by hepatocytes after delivery from portal blood or normally filtered by the liver are now delivered directly to or stay in the systemic circulation.
• Decreased hepatic functional mass resulting from reduced blood flow and decreased delivery of hepatotrophic factors (e.g. insulin, glucagon, epidermal growth factor).
• Abnormalities in iron homeostasis resulting in functional iron deficiency.

 Laboratory detection of altered hepatic portal blood flow

Note that clinical pathologic findings in animals with altered hepatic portal blood flow are variable and some animals may show few or none of these abnormalities.

• Increased concentrations of substances normally filtered by the liver directly to the systemic circulation.
  • Increased ammonia concentration, with decreased urea production and resulting ammonium urate crystalluria
  • Increased bile acids are seen in dogs with shunts (congenital, acquired) and microvascular dysplasia (Toulza et al 2006).
  • In one study in dogs and cats, measurement of fasting bile acids and ammonia was sensitive and specific for the diagnosis of shunts in dogs and cats. In dogs, high ammonia (>59 μmol/L) were slightly less sensitive than bile acids (>20 μmol/L) (86 versus 93%) but more specific (86 vs 67%).  In cats, high ammonia was less sensitive than bile acids (76 versus 100%) but slightly more specific (76 versus 71%) (Ruland et al 2010). Note, that measurement of post-prandial bile acid concentrations may have improved sensitivity at the expense of specificity (particularly in dogs).
• Decreased hepatic functional mass resulting from reduced blood flow and decreased delivery of hepatotrophic factors (e.g. insulin, glucagon, epidermal growth factor).
  • Decreased protein synthesis: Albumin, protein C, antithrombin, fibrinogen.
    • Protein C: Studies have shown that protein C can act a biomarker of hepatic function and hepatoportal perfusion. This is because protein C concentrations appear to be governed by hepatic portal flow and are not only influenced by synthetic capability of the liver. Measurement of protein C activity can assist clinicians in:
      • Recognition of portosystemic shunts: 88% of dogs with shunts in one study had low protein C activity, i.e. <70% (reference interval 75-135%) (Toulza et al 2006). Note that the lowest protein C activity in this study was seen in dogs diagnosed with hepatic failure.
      • Differentiating shunts from microvascular dysplasia, since portal blood flow is abnormal in the former and normal in the latter. In the above study, 30 of 35 dogs with microvascular dysplasia had protein C activity ≥ 70%.
      • Monitoring response to ligation of portosystemic vascular anomalies: In the above study, protein C activity increased to >70% in 10 of 15 dogs after shunt ligation (and all but 1 dog showed an increase in protein C activity) whereas serum bile acid concentrations remained increased in most of the dogs (Toulza et al 2006).
  • Hypocholesterolemia
• Iron homeostasis defects which result in a “functional” iron deficiency (cause unknown). Dogs are not truly iron deficient, unless they are young with low iron stores or have concurrent variceal bleeding from the esophagus (Jensen et al 1983), resulting in chronic blood loss. Many dogs with shunts have increased iron stores in the liver, indicating a defect in iron metabolism versus deficiency per se.
  • Microcytic hypochromic RBCs on a hemogram, possible siderocytes (iron-containing inclusions in RBCs).
  • Low iron and % saturation of transferrin on a chemistry panel.
• Other abnormalities:
  • RBC shape changes: Some dogs with shunts can have schistocytes in blood smears, presumably due to turbulent blood flow through the portal system.
  • Altered liver enzymes: Many dogs with congenital shunts and microvascular dysplasia can have mildly increased liver enzymes (ALT, AST, and ALP most commonly). Bilirubin concentrations are usually normal in dogs with these two disorders. Animals with acquired shunts, secondary to chronic liver disease, can have increases in all liver enzymes and bilirubin (Toulza et al 2006). Boxer dogs with ductal plate malformations are typically not hyperbilirubinemic but have increased liver enzyme activities (ALT, AST, ALP mostly, with mild increases in GGT activity in fewer dogs) and bile acid concentrations (Pilai et al 2016).
  • Ascites: Animals with acquired defects in hepatic portal flow, e.g. those with fibrosis secondary to chronic active hepatitis, can develop a transudative effusion (low or high protein, but typically a low protein transudate).