October 20, 2010

Q&A: Concerning Amyloidosis

Amyloidosis is the general term used to refer to the extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins, many of which circulate as constituents of plasma. These deposits may result in a wide range of clinical manifestations depending upon their type, location, and the amount of deposition.

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In this article:
Overview of Amyloidosis
MCQ: clinical scenario
MCQ: answer
MCQ: explanation

Overview of Amyloidosis

The subunit proteins forming amyloid deposits are derived from soluble precursors which have undergone conformational changes that lead to the adoption of a predominantly antiparallel beta-pleated sheet configuration. Multiple different human protein precursors of amyloid fibrils are known. Amyloid has a characteristic gross pathologic and microscopic appearance, demonstrating apple-green birefringence with polarized light microscopy of Congo red stained tissue.

There are several major forms of amyloidosis. The principal types of amyloidosis seen in tertiary referral centers and inpatient medical services are the AL (primary) and AA (secondary) types, although other types of amyloid (eg, ATTR) are clinically important, some of which are common and others rare.

The prevalence of the most common types of amyloidosis varies between different parts of the world. In developed countries, AL is the most common type of systemic amyloidosis, while, in developing countries, AA amyloid is more frequent. This is a likely result of a higher burden of chronic infectious diseases such as tuberculosis, leprosy, and osteomyelitis in the latter. In the two most common forms of systemic amyloidosis, primary (AL) and secondary (AA) amyloidosis, the major sites of clinically important amyloid deposition are in the kidneys, heart, and liver. In some disorders, clinically important amyloid deposition is limited to one organ.

The type of precursor protein, the tissue distribution, and the amount of amyloid deposition largely determine clinical manifestations. Some clinical and laboratory features that suggest amyloidosis include waxy skin and easy bruising, enlarged muscles (eg, tongue, deltoids), symptoms and signs of heart failure and cardiac conduction abnormalities, hepatomegaly, evidence of heavy proteinuria or the nephrotic syndrome, peripheral and/or autonomic neuropathy, and impaired coagulation.

The definitive method for diagnosis of amyloidosis is tissue biopsy, although the presence of amyloidosis may be suggested by the history and clinical manifestations (eg, nephrotic syndrome in a patient with multiple myeloma or long-standing, active rheumatoid arthritis). In some patients, the presence of amyloid is demonstrated by findings on imaging.

MCQ: clinical scenario

A patient with systemic amyloidosis becomes progressively jaundiced over three months. On examination he is found to have hepato-splenomegaly, a markedly raised serum alkaline phosphatase.

This patient is most likely to have amyloidosis involvement of the:

a) anterior pararenal space
b) space of Disse
c) vestibule space
d) epidural space
e) sub-arachnoid space

MCQ questions & answers on medicalnotes.info

MCQ: answer

The correct answer is B

MCQ: explanation

The peri-sinusoidal space in the livers are known as spaces of Disse and serve as a major site of amyloid involvement. Hepatocytes are separated from the sinusoids by this plasma-filled space. In the liver, as in other organs, amyloidosis gives rise to amorphous, hyaline extracellular deposits in the walls of arteries and arterioles, with lesser involvement of portal or hepatic veins

Hepatic involvement is common in patients with systemic amyloidosis. Localized disease in the liver is rare but has been reported. Features of hepatic amyloidosis include hepatomegaly and increased serum alkaline phosphatase, each of which are found in 60% of patients with biopsy-proven liver involvement; clinical liver disease, however, is rarely encountered. A small number of patients with hepatic amyloidosis develop severe intrahepatic cholestasis with jaundice. This syndrome portends a poor prognosis, although death results from extrahepatic (primarily renal) disease.

Liver biopsy is not required to confirm hepatic involvement in patients with known systemic amyloidosis. If the diagnosis is uncertain, liver biopsy may be useful and can be performed safely if clotting parameters are normal and any history of a bleeding disorder is excluded.

1). UpToDate: Overview of amyloidosis. Available online: https://www.uptodate.com/contents/overview-of-amyloidosis

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