The first important point to remember about AMYLOID is that it is a PROTEIN. It is an unusual protein ("beta folded") that is formed by cleavage from larger proteins and then deposited in EXTRACELLULAR areas of tissues.

As an extracellular deposit, it may cause ENLARGEMENT of affected organs.

The picture on the right shows a normal gerbil spleen (bottom) compared to an abnormal gerbil spleen with amyloidosis (top).

See how enlarged the spleen on the top is?

Could amyloid also cause dysfunction of affected organs?
Why? The amyloid fibrils are deposited in the Islets of Langerhans and compress the normal cells in the Islets. Thus the beta cells are destroyed and insulin is not produced. The result is the disease diabetes mellitus.

This is a photomicrograph of a thyroid gland.

Would amyloid deposits cause dysfunction in this organ?

So let's talk about some ways to diagnose amyloidosis. We can do so grossly as well as microscopically.

These are kidneys from an animal with amyloidosis. What is one way we can tell they have amyloid in them?

AMYLOID means "starch-like". This name was derived from the fact IODINE (a dye that stains starches) would also stain amyloid deposits.
The kidney on the left is a normal kidney and the one on the right is one stained with amyloid.

Note the red to black dots in the cortex corresponding to glomerular deposits of amyloid. There is a glycoprotein associated with the amyloid deposits which stains with iodine. There are also heavy deposits in the medulla.

However, iodine staining is a crude test and it is not accurate (there are many false negatives). Is there a more accurate method of diagnosis?

Tissue can be processed for histopathology and examined by light microscopy. Amyloid deposits are eosinophilic and hyaline (smooth & shiny). They are homogeneous and tend to be deposited in aggregates. Eventually the entire tissue may be filled with the deposits.

Amyloid is said to be a hyaline substance - notice it is homogeneous and eosinophilic (pink with H&E stain).

However other substances may have a similar appearance - thus special stains are needed.

Congo Red is a special stain used for amyloid. Congo Red is actually a dye used to stain fabric. It has been found to be a good stain for amyloid too. The amyloid deposits stain red. Congo Red will also stain connective tissue. How can we be certain the red material is amyloid?

Because Congo Red is not always definitive for diagnosis of AMYLOIDOSIS, other techniques have been used.

The most definitive diagnosis is by Electron Microscopy. The amyloid fibrils have a diagnostic appearance on electron micrographs (as you see here). The fibrils are non-branching, 7-10 nm in diameter, and are often arranged in crisscrossing bundles.

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