What is perivenular?

What is Perivenular?

Perivenular refers to the anatomical region immediately surrounding the central vein (also called the terminal hepatic venule) in the liver lobule, corresponding to Rappaport zone 3 or the centrilobular area.

Anatomical Definition

• The perivenular region represents the area of hepatocytes and sinusoids that are located adjacent to and surrounding the central vein, which drains blood from the liver lobule into the hepatic venous system 1
• This zone is also referred to as the "centrilobular area" or "zone 3" in the Rappaport classification of liver acinar zones 1, 2
• The central vein itself is lined by endothelial cells and serves as the primary drainage point for blood that has perfused through the liver sinusoids from the portal triads 3

Physiological Characteristics

• Perivenular hepatocytes are exposed to blood with the lowest oxygen tension and nutrient concentration within the liver lobule, as blood flows from the portal areas through the sinusoids toward the central vein 2, 3
• These hepatocytes express distinct metabolic enzymes, including glutamine synthetase and cytochrome P4502E1, which serve as biomarkers of perivenous hepatocytes 3
• The Wnt/β-catenin signaling pathway, activated by Wnt2, Wnt9b, and R-spondin3 secreted from the central vein endothelium, regulates perivenular gene expression and hepatic metabolic zonation 3

Clinical Significance in Liver Pathology

Toxic and Metabolic Injury

• Perivenular hepatocytes are the first cells to display signs of toxicity following long-term alcohol use, as P450IIE1 (which oxidizes ethanol and generates toxic metabolites) is predominantly localized in this zone 2
• Pericentral (zone 3) necrosis is a characteristic pattern of acute toxic injury and can occur in autoimmune hepatitis with acute onset, closely resembling drug-induced hepatitis 1

Vascular Disorders

• In Budd-Chiari syndrome and hepatic venous outflow obstruction, the hallmark histological findings include congestion, liver cell loss, and fibrosis in the perivenular/centrilobular area 1
• Perivenular fibrosis without congestion can occur in patients with longstanding suprahepatic IVC obstruction 1
• The absence of congestion in the centrilobular area is a strong argument against the diagnosis of hepatic vein thrombosis 1

Autoimmune Hepatitis

• Central perivenulitis (inflammation around the central vein) is an additional histological feature that can be seen in cases of acute liver failure due to autoimmune hepatitis, along with portal lymphoid follicles and plasma cell-enriched infiltrates 1
• The perivenular pattern of injury may represent an early histological manifestation of autoimmune hepatitis that transitions to interface hepatitis in sequential biopsies 1

Transplant Pathology

• Central perivenulitis in liver transplantation encompasses dropout of zone 3 hepatocytes, red blood cell extravasation, and perivenular mononuclear inflammation 4
• When associated with portal-based acute cellular rejection, central perivenulitis carries significant risk for development of zone 3 fibrosis and potential progression to ductopenic chronic rejection 4

Diagnostic Imaging Context

• In multiple sclerosis imaging, "perivenular" refers to white matter lesions that form around small intraparenchymal veins in the brain, which can be visualized on high-field MRI and help distinguish MS lesions from other conditions 1
• The presence of a central vein within brain lesions (visible in at least 2 perpendicular planes) is a distinctive feature of MS that aids in differential diagnosis 1