Identification of Factors Contributing to Hepatomegaly in Severely Burned Children

Abstract

Hepatomegaly is a common postmortem observation in severely burned children, with the liver often tripling in size when compared with normal livers for age, weight, and sex. Lesions identified at autopsy include deposition of large and small fat droplets in the hepatocyte, congestion, centrilobular necrosis, and cholestasis. The present study was designed to identify the primary causes of hepatomegaly in severely burned children postmortem. For this purpose, 41 autopsies were reviewed and, when available, blood and tissue samples were studied. Histopathologic findings showed that large intrahepatocytic fat droplets within hepatocytes and cholestasis were important contributors to hepatomegaly. Liver density and wet/dry weight ratios significantly decreased with increasing liver size. Hepatocyte volume increased with increasing liver size (P < 0.001) as did total fat content (P < 0.001). The liver enzymes, alanine aminotransferase and aspartate aminotransferase, remained normal except within 5 to 10 days of injury and 5 to 10 days of death. Triglycerides made up 4% to 70% of the total fat, with the percentage of triglycerides increasing with the severity of hepatomegaly. Saturated fatty acids represented about 85% of the total fatty acids in normal-sized livers, whereas in the largest livers (400% of predicted), only 25% of the fatty acids were saturated. This study provides evidence that 85% to 90% of the hepatomegaly observed in severely burned children postmortem is associated with hepatocyte enlargement, which includes up to 19% intracellular fat. Increases in extracellular protein, intracellular glycogen, and fluid accumulation may make a minor contribution to postburn hepatomegaly.

Alternative Mechanism for White Adipose Tissue Lipolysis after Thermal Injury

“…Using this model, we observed increased fatty infiltration in liver tissue. This is consistent with the clinical findings that significant hepatic fatty infiltration and hepatomegaly are associated with increased incidence of sepsis and mortality in severely burned patients (8,9); however, the mechanisms underlying the abnormal deposition of lipid in the liver are unclear. Due to the increased appreciation of metabolic cross-talk between liver and WAT in the context of IR and hypermetabolism (10), we hypothesized that increased lipolysis in WAT after severe burn injury and sepsis contributed to hyperlipidemia and hepatic lipid infiltration that led to detrimental outcomes.…”

Burn and smoke inhalation injury in sheep depletes vitamin E: Kinetic studies using deuterated tocopherols

“…Following combined burn and smoke inhalation injury in sheep, markers of liver damage progressively increased, reaching statistical significance by 12 h for serum aspartate aminotransferase (AST, p<0.05) and by 18 h for serum alanine aminotransferase (ALT) (Traber, et al unpublished observations). It should be noted that many burn patients have fatty liver (42), a metabolic consequence that has been suggested to be a result of oxidative stress in the liver (43,44), but this is phenomenon is usually observed after a longer period of time subsequent to the injury. At least up to 48 h, the liver appears to be able to maintain export of α-tocopherol to the plasma.…”

“Systemic apoptotic response” after thermal burns

“…Most of the hepatomegaly (85-90%) derived from the hepatocyte enlargement due to the increase in intracellular fat. Increases in extracellular protein, intracellular glycogen, and fluid accumulation made a minor contribution [77,78].…”