Steatosis

Micrograph demonstrating marked (macrovesicular) steatosis in non-alcoholic fatty liver disease. Masson's trichrome stain.

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Histological section of a mouse's liver showing severe steatosis. The clear vacuoles contained lipid in life; however, histological fixation caused it to be dissolved and hence only empty/clear spaces are seen.

In cellular pathology, steatosis (also called fatty change, fatty degeneration or adipose degeneration) is the process describing the abnormal retention of lipids within a cell. It reflects an impairment of the normal processes of synthesis and elimination of triglyceride fat. Excess lipid accumulates in vesicles that displace the cytoplasm. When the vesicles are large enough to distort the nucleus, the condition is known as macrovesicular steatosis; otherwise, the condition is known as microvesicular steatosis. While not particularly detrimental to the cell in mild cases, large accumulations can disrupt cell constituents, and in severe cases the cell may even burst.

The risk factors associated with steatosis are varied, and include diabetes mellitus, protein malnutrition, hypertension cell toxins, obesity, anoxia and sleep apnea. As the liver is the primary organ of lipid metabolism it is most often associated with steatosis; however, it may occur in any organ, commonly the kidneys, heart, and muscle.

Pathogenesis

No single mechanism leading to steatosis exists, rather a varied multitude of pathologies disrupt normal lipid movement through the cell and cause accumulation. These mechanisms can be separated on whether they ultimately cause an oversupply of lipid which can not be removed quickly enough (too much in), or whether they cause a failure in lipid breakdown (not enough used).

Macrovesicular is the more common form of fatty degeneration, and may be caused by oversupply of lipids due to obesity, obstructive sleep apnea (OSA), insulin resistance, or alcoholism. Nutrient malnutrition may also cause the mobilisation of fat from adipocytes and create a local oversupply in the liver where lipid metabolism occurs. Excess alcohol over a long period of time can induce steatosis. The breakdown of large amounts of ethanol in alcoholic drinks produces large amounts of chemical energy, in the form of NADH, signalling to the cell to inhibit the breakdown of fatty acids (which also produces energy) and simultaneously increase the synthesis of fatty acids. This "false sense of energy" results in more lipid being created than is needed.

Microvesicular fatty degeneration is characterized by small intracytoplasmic fat vacuoles (liposomes) which accumulate in the cell. Common causes are tetracyclines, acute fatty liver of pregnancy, Reye's syndrome, and hepatitis C.

Failure of lipid metabolism can also lead to the mechanisms which would normally utilise or remove lipids becoming impaired, resulting in the accumulation of unused lipids in the cell. Certain toxins, such as alcohols, carbon tetrachloride, aspirin, and diphtheria toxin, interfere with cellular machinery involved in lipid metabolism. In those with Gaucher's disease, the lysosomes fail to degrade lipids and steatosis arises from the accumulation of glycolipids. Protein malnutrition, such as that seen in kwashiorkor, results in a lack of precursor apoproteins within the cell, therefore unused lipids which would normally participate in lipoprotein synthesis begin to accumulate.

Histology

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Micrograph of fatty liver showing lipid steatosis. H&E stain.

Histologically, steatosis is physically apparent as lipid within membrane bound liposomes of parenchymal cells. When this tissue is fixed and stained to be better viewed under a microscope, the lipid is usually dissolved by the solvents used to prepare the sample. As such, samples prepared this way will appear to have empty holes within the cells where the lipid has been cleared. Special lipid stains, such as Sudan stains and osmium tetroxide are able to retain and show up lipid droplets, hence more conclusively indicating the presence of lipids. Other intracellular accumulations, such as water or glycogen, can also appear as clear vacuoles, therefore it becomes necessary to use stains to better decide what is accumulating.

Grossly, steatosis causes organ enlargement and lightening in colour. This is due to the high lipid content increasing the organ's volume and becoming visible to the unaided eye. In severe cases, the organ may become vastly enlarged, greasy, and yellow in appearance.

Radiography

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Liver steatosis (fatty liver disease) as seen on CT

On X-ray computed tomography (CT), the increased fat component will decrease the density of the liver tissue, making the image less bright. Typically the density of the spleen and liver are roughly equivalent. In steatosis, there is a difference between the density and brightness of the two organs, with the liver appearing darker. On ultrasound, fat is more echogenic (capable of reflecting sound waves). The combination of liver steatosis being dark on CT and bright on ultrasound is sometimes known as the flip flop sign.

See also

• Fatty liver
• Lipid metabolism
• Non-alcoholic fatty liver disease
• Visceral fat
• Fat globules