Overview Of Amyloidosis, Its Various Types, Clinical Features, And Treatment

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Overview

Amyloidosis is defined as a group of diseases, in which deposits of an abnormal protein called amyloid, form in tissues and organs throughout the body. Proteins are important molecules involved in almost each and every structure and function within our cells. They are made up of chains of smaller units called amino acids, which fold themselves into three-dimensional structures. This folding allows the protein to work properly and interact with other molecules. In amyloidosis, the proteins are made in the normal way, but when they are released from the cell they open up again. These abnormally folded proteins collect together in long chains or fibril, and the deposits they form are called amyloid.

Historical Aspect Of The Disease
“Amylin” a Latin word means “starch”. Matthias Schneider, a German Botanist was the first to use the term “amyloid” in botany, for starch, referring to “starch-like”. German pathologist Rudolf Virchow (1804 - 1881) applied it in the medical literature in 1854. Used the word “Amyloid” to describe some deposits in nervous system which showed the same color reaction with iodine and sulfuric acid, i.e. a change from brown to blue, typical to starch in the later years it was found that the chemical nature was unrelated to starch but proteins! Yet... The name “amyloid” still remains Probably because of Virchow was considered as one of the most valued scientists of his time In the later years it was found that the chemical nature was unrelated to starch but proteins! 

Properties Of Amyloid Proteins 
Amyloid is not a single entity More than 20 different proteins can aggregate to form fibrils. The mechanisms of formation are different. Therefore amyloidosis should not be considered as a single disease… rather, a group of diseases with deposition of similar appearing proteins. Thats mean Physically they all look similar, but chemically they altered. their properties are categorized into;
Physical nature: On Electron Microscopy, all amyloid proteins are similar. All types of amyloid are continuous non branching fibrils. While on x-ray crystallography, "Cross Beta Pleated sheet" Confirmation. And Under Infrared Spectroscopy, It is responsible for Distinctive Congo Red Staining and apple-green Birefrengence 
Chemical Nature: Chemically 95% of these Amyloid proteins are Fibrillary and remaining 5% are made up of substance P which could be Proteoglycans, Glucosaminoglycane and Serum Amyloid P etc.

a. congo red stain.  

b. Apple Green Birefrenges

Biochemical Form Of Amyloid Proteins

1. Major  a). AL protein   b).AA protein   c). Beta amyloid protein

2. Minor a). TTR    b). B2 microglobulin   c). Serum Amyloid P

Amyloid Light Chain (AL)

Amyloid fibrils are difficult to break down and as they accumulate in various tissues and interstitium they start to cause damage. Eventually the build-up of amyloid fibrils stops the affected tissue from working properly. AL amyloidosis also known as Primary Amyloidosis, is caused by a bone marrow disorder. The bone marrow produces blood cells including plasma cells (a type of white blood cell that forms part of the immune system). Plasma cells make antibodies to help fight infection. Each antibody is made up of four protein chains, two heavy chains and two light chains, which attach to each other to form the complete antibody. In AL amyloidosis the abnormal protein that builds up and causes problems is the antibody light chain, hence the name AL amyloidosis. Instead of attaching to heavy chains, the abnormal light chains open up and bind to other abnormal light chains to form amyloid fibrils. These gradually build up over time amyloid light-chain fibril can occur almost anywhere in the body, but the organs most commonly affected include, the kidneys, the heart, liver, spleen, nerves and the digestive system.

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Clinical Features

Amyloidosis comes with a wide variety of symptoms. It mainly depends on the organ or system where amyloid fibrils get deposited. The common common of all include but not limited to;
1. Renal involvement: Nephrotic range proteinurea is most common and feared complication. Renal involvemet is the example of Secondary Amyloidosis in which B2 microglobulin gets deposits in the glomeruli and interstitium of kidney, leading to ischemia of glomeruli and renal tubules and patient eventually develop Chronic Renal Failure. 
2. Hepatic Involvement: Liver Involved in most of the Systemic complications of Amyloidosis. Abnormal protein get deposited in space of Disse, leading to compression of cord of hepatocytes and eventually shrinkage and atrophy of hepatocytes occur.
3. Spleen: Grossly two pattern may seen , Sago or nodular pattern and Lardaceous or Diffuse pattern of Spleen.
4. Cardiac Involvement: Commonly associated with systemic Amyloidosis but rarely localized type or Senile Cardiac Amyloidosis may also seen. It may result into heart failure and arrythmias.
 
Treatment

Treatment for AL amyloidosis involves chemotherapy, steroids (high-dose therapy) and stem cell transplant. And other drugs treatment is aimed at reducing the plasma cells to stop further amyloid light chains being made, that would otherwise build up in tissues and organs. It also gives the body a chance to break down existing deposits naturally. However on its own, this process can take many months or years. New treatments which break down the amyloid deposits more quickly are currently being tested in AL amyloidosis. The hope is that they can reduce symptoms and restore function quickly and in doing so improve quality of life for patients.