4. Lipid accumulations in parenchymal and stromal cells. Lipid phagocytosis.

Lipid accumulation in parenchymal and stromal cells. Lipid phagocytosis.

A reminder:

• Parenchymal cells = functional parts of an organ in the body
• Stroma = structural tissue of organs (i.e. CT)

There are four pathways for abnormal intracellular accumulations:

1. 1. Inadequate removal of a normal substance due to packaging or transport defects
2. 2. Defects in folding, packaging, transport or secretion of abnormal endogenous substance
3. 3. Failure to degrade due to inherited enzymopathy
4. 4. Deposition and accumulation of abnormal exogenous substance as we don’t have the correct machinery to degrade, transport or store

Lipid accumulation, also known as Steatosis, is the abnormal retention of lipids in a cell. It is the product of the first of the above four methods, inadequate removal of a normal substance. Steatosis is commonly seen in the liver, the major organ involved in fat metabolism, but can also be seen in the heart, skeletal muscle, kidney and other organs.

Excess lipid accumulates in vesicles that displace in the cytoplasm, it can be divided into two categories:

• Macrovesicular steatosis - where the fat vacuoles displace the nucleus
• Microvesicular steatosis - where the fat vacuoles do not displace the nucleus

Remember: On routine H&E the fat vacuoles look empty, because alcohol and xylene dissolve the lipid during processing. To prove that they contain fat, stain frozen sections with Sudan III/IV or Oil Red O, which colour the droplets orange-red.

Lipid accumulation is most common in the liver and can be the product of:

• Excessive entry of lipids
• Enhanced FA synthesis by hepatocytes
• Increased esterification of FA into TAGs
• Decreased apoprotein synthesis (remember lipids leave the liver as lipoproteins, which need apoproteins)
• Decreased oxidation of FA by mitochondria
• Impaired lipoprotein excretion

Example: The commonest causes of fatty liver are alcohol abuse and non-alcoholic fatty liver disease (obesity, type 2 diabetes); others are protein malnutrition (kwashiorkor), hepatotoxins such as carbon tetrachloride, and hypoxia. Grossly the liver is enlarged, yellow and greasy.

Other lipid accumulations include:

• Cholesterol and cholesteryl ester accumulation
• In atherosclerosis
• In hereditary hyperlipidemia (formation of xanthomas, fat tumours)

Lipid phagocytosis occurs in atherosclerosis when lipids are forced into intimal wall of the vessels causing foam cells.