FATTY CHANGE
In this program, we will review fatty change.
Which cells are most susceptible to fatty change?
This figure depicts normal lipid metabolism in the hepatocyte.

Lipid is delivered to the hepatocyte from dietary sources or body fat stores in the form of free fatty acids (FFAs).

A small amount of FFAs are also synthesized in the hepatocyte itself from acetate.

Some of the FFAs are utilized for the synthesis of cholesterol and phospholipids, and some may be oxidized to ketone bodies (1). Most of the intracellular FFAs are esterified to triglycerides (2). Once triglycerides are produced, they must be complexed to a lipid acceptor protein (or apoprotein) prior to export from the cell (3) as lipoproteins.

Triglycerides may accumulate if the balance between the synthesis of triglycerides and their utilization or mobilization is upset. When intracellular triglycerides accumulate, a fatty liver results.

Let's look at some specific examples of fatty change in the liver and explore the pathogenesis of the lesion in each case.
Fatty livers are enlarged, pale, greasy, friable. See the gross appearance of a fatty liver.
You may have noticed that the fatty liver had fracture lines on the surface. The liver readily fractures because it is so friable. This increased fragility of the liver is not just a postmortem change, though the fragmentation we just saw did occur during the necropsy examination.
In this view there is hemorrhage along the fracture of a very fatty liver. What consequences would these fractures have to the animal?
Starvation causes increased mobilization of FFA from fat stores ---> increased synthesis of TG plus decreased export of TG ---> fatty liver
What is the pathogenesis of fatty liver in starvation. Think about it then click here for a review...
In what other disease does fatty liver result from increased mobilization of body fat?
Protein is needed for movement of TG out of hepatocyte. Inhibition of protein synthesis ---> fatty liver

This liver is from a pig that was being fed moldy feed containing aflatoxins.

The toxic metabolites of aflatoxin bind to nucleic acids and nucleoproteins, effectively inhibiting protein synthesis.

 

The pathogenesis of the fatty change is shown diagrammatically in the figure (left).

Other toxins, such as carbon tetrachloride, phosphorus, and methionine, also inhibit protein synthesis, leading to fatty liver by a similar mechanism.

Anemia leads to hepatocyte hypoxia, which is another cause of triglyceride accumulation.

Now that you know hypoxia is responsible for this change, can you explain the distribution of fat in the hepatocytes around the central vein? Answer »

Hypoxia - inhibits utilization of FFA and export of lipid from cell.

Hypoxia directly interferes with mitochondrial function and inhibits the utilization of FFA for phospholipid and cholesterol production and the oxidation of FFA to CO2 and ketones (1). This leads to an increase in the amount of FFA available for TG synthesis.

In addition to increasing the amount of TG produced, hypoxia also inhibits the export of lipid from the cell by inhibiting lipoprotein synthesis and transport (2).
Now that we have a good understanding of the pathogenesis and gross appearance of fatty change, let's look at a fatty liver histologically.
Note that the large crisp vacuoles which often displace the nucleus and give the hepatocytes the appearance of adipocytes. See a high power view of this area »

This is a feline kidney. How would you describe it?
The histologic section of the same kidney reveals clear vacuoles in the renal tubular epithelial cells. What is the significance of this finding?
The heart is rarely involved with fatty change. In this heart from a dog note the pale myocardium.

A histologic section reveals myocardial cells filled with variably sized vacuoles.

These vacuoles could contain either water or fat. Oil Red O or Sudan IV staining of this section would prove the vacuoles contain fat.

So, in general, what is the significance of fatty change?
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