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Intrahepatic circulation in liver disease.

P M Huet, G Pomier-Layrargues, J P Villeneuve

Seminars in Liver Disease

|November 1, 1986

Summary

Cirrhosis alters liver microcirculation, creating shunts that bypass sinusoids. Despite changes, diffusion of small molecules like water and lidocaine remains unaffected in cirrhotic livers.

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Area of Science:

Hepatology
Vascular Biology
Pharmacokinetics

Background:

Cirrhosis significantly alters liver structure and function, impacting microvascular dynamics.
Understanding microvascular changes is crucial for predicting drug disposition and liver function in cirrhosis.

Purpose of the Study:

To characterize microvascular events in experimental and human cirrhosis using the multiple indicator dilution technique.
To investigate the impact of intrahepatic shunts and sinusoidal changes on substance diffusion and elimination in cirrhosis.

Main Methods:

Multiple indicator dilution studies in experimental animals and human cirrhotic patients.
Characterization of intrahepatic shunts, portohepatic anastomoses, and sinusoidal morphology.
Assessment of diffusion of various molecules (albumin, sucrose, water, lidocaine) across the liver microvasculature.

Main Results:

Intrahepatic shunts bypassing sinusoids were observed in approximately one-third of cirrhotic patients with portal hypertension, primarily between portal and hepatic veins.
Portohepatic anastomoses in cirrhotics were often large (>20 microns).
Sinusoidal changes (collagenization, capillary-like transformation) reduced extravascular space for albumin but did not limit diffusion of water, sucrose, or lipophilic substances like lidocaine.

Conclusions:

Cirrhosis induces significant intrahepatic shunting and alters sinusoidal architecture, impacting microvascular function.
Despite structural changes, the diffusion of small and lipophilic molecules is preserved, suggesting preserved hepatocellular access for certain substances.
Differential perfusion of cirrhotic nodules via portal and hepatic arteries influences substance elimination, highlighting complex alterations in liver hemodynamics.

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