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Intrahepatic circulation in liver disease
Insights
Cirrhosis alters liver microcirculation, creating shunts that bypass sinusoids. Despite changes, diffusion of small molecules like water and lidocaine remains unaffected in cirrhotic livers.
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.
Abstract:
Using the multiple indicator dilution approach, events occurring in the microvascular bed can be characterized in experimental animals with different types of cirrhosis and in man. Intrahepatic shunts can be found shunting blood away from sinusoids in both cirrhotic patients and cirrhotic animals. Such shunts were present in about one-third of cirrhotic patients with portal hypertension, and occurred mainly between the portal vein and hepatic veins. In cirrhotics, portohepatic anastomoses are usually large in diameter (more than 20 micron in diameter). Collagenization of the space of Disse and the progressive transformation of sinusoids into capillary-like channels decrease the extravascular space accessible to albumin and probably to other large molecules and protein-bound substances. However, unlike findings obtained in well-capillarized organs, these sinusoidal changes do not appear to limit the diffusion of sucrose, water, and lipophilic substances, such as lidocaine in the extravascular and intracellular spaces. The pattern observed for labeled sucrose curves following hepatic artery injection in cirrhotic patients could be secondary to the passage through the dense peribiliary capillary plexus originating from the enlarged arterial bed in cirrhosis. The difference in the perfusion of cirrhotic nodules with regard to the portal venous and hepatic artery routes introduces important new concepts in the overall mechanism of the elimination of endogenous and exogenous substances by the cirrhotic liver: blood entering the liver by the two afferent vessels will not flow through the same vascular bed before reaching the efferent hepatic veins.