Effects of obstructive jaundice on the peripheral nerve: an ultrastructural study in rats

Obstructive jaundice (OJ) and hepatic disorders have been shown to be associated with peripheral neuropathy in several clinical studies. The study evaluated the effect of OJ on the ultrastructure of the rat sciatic nerve. In the OJ group, jaundice was created by ligation of common bile duct in Wistar-Albino rats. In the sham-operated control group the same procedure was performed without ligation of the bile duct. On day 7, all rats were re-operated and sciatic nerves were explored to harvest 2-cm-long nerve segments for quantitative and qualitative histopathological analysis by light and electron microscopy. Bilirubin was measured on serum samples. Bilirubin levels were significantly higher in jaundiced rats compared with that of controls (8.46 +/- 0.45 vs. 0.80 +/- 0.14 mmol/l, means +/- SD, p < 0.01). Control nerves did not show anything other than the normal histology. In the OJ group, degenerative changes such as irregularities, thinning, ruffling and invaginations, irregularshaped bodies, vacuolizations and focal segmental demyelination were observed in the myelin sheath. Myelin clusters were noted in the axoplasm. A varying degree of swelling was noted in the nucleus and cytoplasm of the Schwann cells. Morphometric analysis of specimens obtained from sciatic nerves showed that myelin injury (370.9 +/- 51.3 vs. 11.6 +/- 0.5 axons), axonal edema (142.1 +/- 24.2 vs. 10.6 +/- 0.5 edematous axons) and Schwann cell degeneration (50.3 +/- 11.6 vs. 3.2 +/- 0.2 Schwann cells) was significantly higher in the jaundiced rats than in the control group (p < 0.01). The ultrastructural alterations spotted in the rat peripheral nerve were attributed to hyperbilirubinemia and increased concentrations of several neurotoxic substances released from the Kupffer cells in OJ. Neuropathy in jaundiced patients seems to result from accompanying degenerative changes in the peripheral nervous system. However, the exact nature and initiating factors of this nerve injury remains to be unveiled.