The basic defect is unknown, even though pathologic and clinical features from diverse causes are somewhat similar. The biochemical basis may be a disturbance in the mitochondrial-oxidative pathway, depressing FFA oxidation and impairing apolipoprotein synthesis for VLDL assembly. Fatty liver may result from the accumulation of other neutral lipids. The fat vacuolization is small to medium. In Niemann-Pick disease, the phospholipid sphingomyelin accumulates in hepatocytes and Kupffer cells.
Cells appear foamy.
When lipid deposition is marked, the liver tends to be grossly enlarged, smooth, and pale. Microscopically, the general architecture can be normal. Triglyceride accumulations appear as large droplets that coalesce and displace the cell nucleus to the periphery. In microvesicular fatty liver, small droplets collect in the endoplasmic reticulum and in secondary lysosomes that do not fuse. Hepatocytes exhibit a foamy cytoplasm and a central nucleus.