Amyloidosis

Dr Menaka Sethi
Assistant professor
 Amyloidosis (Beta cells of pancreas also release amylin)

 Amyloidosis is deposition of amyloid (variety of proteinaceous materials) in the

interstitial tissues in a wide variety of clinical disorders
 It is deposited between cells in various tissues and organs of the body, usually
between the capillary endothelium and the adjacent cells
 With H&E stains, Amyloid appears as an amorphous (shapeless), eosinophilic,
hyaline (homogeneous and transluscent) extracellular substance
 It is deposited between cells in various tissues and organs of the body, usually
between the capillary endothelium and the adjacent cells
 Amyloid mass has an irregular border, contains few nuclei, and does not contain
any connective tissue fibres
 Amyloid resembles starch in some of its chemical reactions
Occurrence

 Amyloidosis is most common in humans, but it also occurs in all species of

domestic animals
 It is common in the dog, cattle, horse, and chicken
 Amyloidosis may affect any tissue
 Most common sites are spleen, liver and kidneys
 Amyloidosis is a prominent lesions in the spleens of chickens having
tuberculosis
 Aetiology

❑ Primary amyloidosis: Detectable any underlying disease

 Amyloidosis is also associated with various neoplasm, especially multiple
myeloma (a malignant neoplasm of plasma cells) and lymphoma.
(Cancer of plasma cell) (Cancer of lymphatics)

❑ Secondary amyloidosis
 Associated with chronic inflammatory diseases such as tuberculosis (chicken)
and osteomyelitis.
 It is also seen in chronic infections caused by autoimmune diseases (e.g.
rheumatoid arthritis)
Microscopic morphology of amyloidosis

 Light microscope: Amorphous, hyaline deposition that has apple-

green birefringence upon polarization after Congo red staining
 Electron microscope: Most forms of amyloid are 7.5 to 10
nanometer fibrils in a β-pleated sheet configuration
Types of amyloid
 Based on the biochemical analysis, its composed of 2 main types of complex proteins
❑ Fibril proteins: Comprise about 95% of amyloid
❖ AL (amyloid light chain) protein: Derived from plasma cells and contains
immunoglobulin light chains and its deposition is associated with some form of
monoclonal B cell proliferation
• AL protein is made up of either complete immunoglobulin light chains, or their
fragments, or both
❖ AA (amyloid associated) protein:AA(amyloid associated): Is a non immunoglobulin
protein synthesized the liver and typically deposited during chronic inflammatory
diseases. They are derived from a larger serum precursor protein synthesized in the liver
called SAA (serum amyloid associated protein)
➢ Both these proteins are antigenically distinct, and are deposited in different clinical
conditions
❑ Non fibrillar components: which include p component predominantly; constitute the
remaining 5% of amyloid
 In humans primary amyloidosis is associated with multiple myeloma, a malignant
neoplasm of plasma cells.
 There is production of abnormal amounts of a single specific immunoglobulin
(monoclonal gammopathy), producing an M (myeloma) protein and also secret only
lamda or kappa light chains. This two light chains are known as Bence jones proteins
 Due to small molecular size, they can excreted in the urine
 These are also present in the serum of patients with multiple myeloma
 In animals also, patients of multiple myeloma show Bence jones proteins in the serum
 An extramedullary plasmacytoma ( a plasma cell neoplasm) in a cat has been found
associated with monoclonal gammopathy and with systemic AL amyloidosis
 In secondary amyloidosis ( also known as reactive systemic amyloidosis) the amyloid
deposits are also systemic in distribution which is found in case of chronic
inflammatory disease conditions like tuberculosis, bronchiectasis, and chronic
osteomyelitis
Pathogenesis of amyloidosis
Amyloidosis of liver
 The amyloid in liver is deposited between
the endothelium of the sinusoids and cells
of the hepatic cords. With progressive
accumulation, the blood flow is hindered,
hepatic cells are compressed and undergo
pressure and nutritional atrophy. Fatty
Microscopic changes occurs from hypoxia and
inadequate nutrition. This gives the organ its
cyanotic-yellow color. Death is due to
rupture and massive hemorrhage into the
peritoneal cavity

Amyloid deposition in liver

IMPORTANT
Amyloidosis of kidney
Amyloidosis, kidney, cross section, dog: The blue black foci, which are glomeruli
containing amyloid stained by Lugol’s iodine
The amyloid deposits are seen as pinkish colour mass deposited
mainly in the glomerular capillary tuft. The deposits are also
present in peritubular connective tissue producing atrophic
tubules and amyloid casts in the tubular lumina, and in the
arterial wall producing luminal narrowing
Methyl violet, methyl green, crystal violet and thionin stain amyloid red and the surrounding tissue blue or green.
These dyes are aniline dyes and their reaction is called metachromatic staining reaction.

Congo red is rapidly absorbed by amyloid, and gives it a red colour

Congo red staining is not absolute specific and transmission electron microscope to identify 7.5 to 10nm filaments
may be necessary

Congo red stain: The amyloid deposits are seen mainly in the glomerular capillary tuft stained red pink
When the tissue sections are viewed with polarized light they exhibit a apple green birefringence. This
feature of amyloid can be used to identify it in tissue sections
 Amyloidosis of spleen
 Amyloidosis of the spleen has two different anatomical patterns
 Most commonly, the amyloid deposits around the central artery of the splenic
follicle and progressive accumulation of the amyloid appears as protruding,
waxy, grey focus which resembles a grain of sago (sago spleen) resulting in
moderately enlarged spleen , so called sago spleen.
 Alternatively, the amyloid deposits may affect principally the splenic artery and
extends into the surrounding splenic pulp, forming large, sheet-like deposits,
producing a large, firm spleen mottled with pale, gray, waxy discolorations
(Lardaceous spleen)
 When the amyloidosis is diffuse, the spleen is swollen, firm in consistency, has a
greyish colour, and the cut surface has a waxy appearance.
Significance
 Amyloid deposition is a permanent change and persists for the life of the
individual
 It is especially serious in the kidney(uraemia), pancreas (diabetes) and liver
(hepatic rupture)
 Causes pressure atrophy of adjacent cells
 The deposited amyloid is quite impervious (impenetrable) to fluids and gases,
as a result exchange of gases, nutrients and waste materials between blood
vessels and adjacent cells cannot occur, results in degeneration and necrosis of
the surrounding cells
 Further, as the mass of amyloid enlarges, it presses upon the vessel and causes
stenosis (narrowing) of the blood vessels, which restricts the flow of blood
through the vessel and causes ischaemia in a portion of the involved organ