General Veterinary Pathology

AMYLOIDOSIS

Amyloid (G. Amylon; Amyl(o) - STARCH) means starch-like. Amyloid is a pathologic glycoprotein deposited in the extracellular spaces and forms fibrils on polymerization.

Histological characteristics

• Amyloid is specially stained with Congo Red. Under polarized light, green birefringence is noticed because of alignment of fibrils. Amyloid fibrils are 7.5 to 10 nm in diameter, rigid, non-branching hollow-cored tubules of unknown length. β-pleated sheet configuration is seen in X-ray diffraction.
• The P-component which is a glycosa-amino-glycan (GAG) facilitates polymerization of amyloid. The GAG makes the amyloid to stain with iodine. The amyloid is resistant to enzymatic digestion and progressively accumulate in tissues until the underlying disease process persists.

Types/Sources of amyloid

• Amyloid associated (AA): It occurs in chronic diseases and septic conditions. Precursor is serum amyloid associated protein (SAA).
• Amyloid light-chain (AL): It is produced in plasmacytoma and the precursor is immunoglobulin light-chain.
• The AI occurs in pulmonary arteries and derived from apolipoprotein AI.
• IAPP is associated with pancreatic islets and derived from islet amyloid polypeptide.

In the brain of aged animals, beta amyloid protein is produced from beta

Amyloidosis

• It is an immunological disorder in which homogeneous, translucent amyloid substance is deposited between capillary endothelium and adjacent cells.

Pathogenesis

• The main event occurring in amyloidosis is the deposition of amyloid fibrils due to abnormality of protein processing.
• The sources of amyloid may be acute phase proteins, immunoglobulins and endocrine secretes.
• The abnormal variant proteins are continuously incorporated to form fibrils. The preamyloid substances are soluble and synthesised in the cytoplasm and deposited in the extracellular spaces.
• The amyloid forms a β-pleated sheet despite their chemical heterogeneity. This makes the fibril resistant to digestion by macrophages and phagocytic cells and hence accumulates in tissues.
• The fibrils may disappear following the removal of cause. Splenic active macrophages remove the amyloid fibrils, but not in the kidneys.
• The amyloid, deposited around the blood vessels is more dangerous. Pressure atrophy of the adjacent cells and ischaemic anoxia results in degeneration and necrosis. Due to interference with gaseous exchange, supply of nutritents and removal of waste products and stenotic vessels, degeneration and necrosis of cells will occur amyloid precursor protein.

Types of amyloidosis

• Primary amyloidosis
• Secondary amyloidosis

Primary amyloidosis

• It results from antigen-antibody reaction and deposition of its precipitates. The condition is not associated with any diseases e.g. repeated exposure to antigens as in antisera and antitoxin production in horses and B cell dyscrasia (plasmacytoma) in humans in which immunoglobin light chain deposition occurs.
• The soluble immunoglobulin becomes insoluble with defective degradation.

Secondary amyloidosis

• The condition may be associated with chronic diseases like tuberculosis, septic conditions and neoplasia. The serum amyloid associated proteins increase (SAA) and converted to insoluble amyloid associated substances. This occurs in two phases. In the initial preamyloid phase, there is accumulation of reticular cells and macrophages in the spleen and other lymphoid tissue with consequent rise in plasma SAAs and globulins. Probably, the cytokines, interleukin-1and interleukin - 6 from macrophages stimulate the liver to synthesize SAAs.
• During the second phase, known as amyloid phase, PAS staining cells, amyloid deposition and fall in the SAAs level are found. Animals affected are dogs, cattle, horses and chickens. Spleen, liver, kidney, lymph node and adrenals are commonly affected.
• Grossly ,the amyloid deposition may be diffuse or focal. The amyloid is deposited around the central artery of splenic follicles and it forms sheet like deposits which is referred as bacon spleen and it may protrude resembling like a grain of sago known as sago spleen.
• The organ is waxy in consistency and the cut surface is grayish. Splenic corpuscles become large, gray and translucent. Liver is enlarged with rounded edges, doughy in consistency, pits on pressure and ruptures easily because of its friable nature.In renal amyloidosis, the organ is swollen, mottled, pale and yellow to orange in colour

Effects of amyloidosis

• Hypovolumic or haemorrhagic shock may occur following hepatic rupture. The deposition of amyloid is found between the endothelium of sinusoids and cords of hepatic cells. Hepatocellular atrophy occurs from pressure and nutritional deficiency. In renal amyloidosis, amyloid deposition occurs between capillary endothelium and epithelium of glomeruli interfering with glomerular filtration. The enlargement and ischaemic anoxia leads to tubular epithelial degeneration and necrosis, marked proteinuria, nephrotic syndrome, uremia and death
• In pancreatic amyloidosis, the deposition of amyloid is found between capillary and islet cells leading to islet cell destruction and development of Diabetes mellitus. Blindness may be encountered in horses in with conjuctival amyloid deposition.