Page 98 - Textbook of Pathology, 6th Edition

82 II. Non-fibrillar components which include P-component
AMYLOIDOSIS
predominantly; there are several different proteins which
Amyloidosis is the term used for a group of diseases charac- together constitute the remaining 5% of amyloid.
terised by extracellular deposition of fibrillar proteinaceous
substance called amyloid having common morphological I. Fibril Proteins
appearance, staining properties and physical structure but
with variable protein (or biochemical) composition. By electron microscopy, it became apparent that major
First described by Rokitansky in 1842, the substance was component of all forms of amyloid (about 95%) consists of
subsequently named by Virchow as ‘amyloid’ under the meshwork of fibril proteins. The fibrils are delicate, randomly
SECTION I
mistaken belief that the material was starch-like (amylon = dispersed, non-branching, each measuring 7.5-10 nm in
starch). This property was demonstrable grossly on the cut diameter and having indefinite length. Each fibril is further
surface of an organ containing amyloid which stained brown composed of double helix of two pleated sheets in the form
with iodine and turned violet on addition of dilute sulfuric of twin filaments separated by a clear space. By X-ray
acid. By H&E staining under light microscopy, amyloid crystallography and infra-red spectroscopy, the fibrils are
appears as extracellular, homogeneous, structureless and shown to have cross-β-pleated sheet configuration which
eosinophilic hyaline material; it stains positive with Congo red produces 1000 A° periodicity that gives the characteristic
staining properties of amyloid with Congo red and
staining and shows apple-green birefringence on polarising birefringence under polarising microscopy. Based on these
microscopy.
The nomenclature of different forms of amyloid is done features amyloid is also referred to as β-fibrillosis.
by putting the alphabet A (A for amyloid), followed by the Chemical analysis of fibril proteins of amyloid reveals
suffix derived from the name of specific protein constituting heterogeneous nature of amyloid. Chemically two major
amyloid of that type e.g. AL (A for amyloid, L for light chain- forms of amyloid fibril proteins were first identified in 1970s
derived), AA, ATTR etc. while currently 20 biochemically different proteins are
known to form amyloid fibrils in humans in different
PHYSICAL AND CHEMICAL NATURE OF AMYLOID clinicopathologic settings. Thus these proteins can be
categorised as under:
Ultrastructural examination and chemical analysis reveal the i) AL (amyloid light chain) protein
complex nature of amyloid. It emerges that on the basis of ii) AA (amyloid associated) protein
morphology and physical characteristics, all forms of amyloid are iii) Other proteins
similar in appearance, but they are chemically heterogeneous.
Based on these analysis, amyloid is composed of 2 main types AL PROTEIN. AL amyloid fibril protein is derived from
General Pathology and Basic Techniques
of complex proteins (Fig. 4.9): immunoglobulin light chain, which in most cases includes
I. Fibril proteins comprise about 95% of amyloid. amino-terminal segment of the immunoglobulin light chain

Figure 4.9 Diagrammatic representation of the ultrastructure of amyloid. A, Electron microscopy shows major part consisting of amyloid fibrils
(95%) randomly oriented, while the minor part is essentially P-component (5%) B, Each fibril is further composed of double helix of two pleated
sheets in the form of twin filaments separated by a clear space. P-component has a pentagonal or doughnut profile. C, X-ray crystallography and
infra-red spectroscopy shows fibrils having cross-β-pleated sheet configuration which produces periodicity that gives the characteristic staining
properties of amyloid with Congo red and birefringence under polarising microscopy.