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Intestinal amyloidosis - Causes and pathogenesis
Last reviewed: 04.07.2025
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The cause of amyloidosis, including that of the intestine, is not clear. The mechanism of amyloid formation can be considered disclosed only in AA and AL amyloidosis, i.e. those forms of generalized amyloidosis in which the intestine is most often affected.
In AA amyloidosis, amyloid fibrils are formed from the plasma precursor of the amyloid fibrillar protein, the SAA protein, entering the macrophage - amyloidoblast, which is intensively synthesized in the liver. Enhanced synthesis of SAA by hepatocytes stimulates the macrophage mediator interleukin-1, which leads to a sharp increase in the SAA content in the blood (pre-amyloid stage). Under these conditions, macrophages are unable to completely degrade SAA, and amyloid fibrils are assembled from its fragments in the invaginates of the plasma membrane of the amylodoblast. This assembly is stimulated by the amyloid-stimulating factor (ASF), which is found in tissues (spleen, liver) in the pre-amyloid stage. Thus, the macrophage system plays a leading role in the pathogenesis of AA amyloidosis - it stimulates increased synthesis of the precursor protein - SAA by the liver, and it also participates in the formation of amyloid fibrils from degrading fragments of this protein.
In AL amyloidosis, the serum precursor of the amyloid fibril protein is the L-chains of immunoglobulins. It is believed that there are 2 possible mechanisms for the formation of AL amyloid fibrils:
- disruption of the degradation of monoclonal light chains with the formation of fragments capable of aggregation into amyloid fibrils;
- the appearance of L-chains with special secondary and tertiary structures with amino acid substitutions. Synthesis of amyloid fibrils from L-chains of immunoglobulins can occur not only in macrophages, but also in plasma and myeloma cells synthesizing paraproteins.
Thus, the pathogenesis of AL amyloidosis primarily involves the lymphoid system; its perverted function is associated with the appearance of "amyloidogenic" light chains of immunoglobulins - the precursor of amyloid fibrils. The role of the macrophage system is secondary, subordinate.
Pathomorphology of intestinal amyloidosis. Despite the fact that amyloidosis affects essentially all parts of the digestive tract, the intensity of amyloidosis is more pronounced in the small intestine, especially in the vessels of its submucosal layer due to its significant vascularization. Masses of amyloid substance fall out along the reticular stroma of the mucous membrane, in the walls of the vessels of both the mucous membrane and the submucosal layer between muscle fibers, along the nerve trunks and ganglia, which sometimes leads to
To atrophy of the mucous membrane and its ulceration. Predominant deposition of amyloid has been found either in the "inner layer" of the vascular wall (intima and media) or in the "outer layer" (media and adventitia), which largely determines the clinical manifestations of the disease. With the first type of amyloid deposition, a syndrome of impaired absorption occurs, with the second - a disorder of the intestinal motility.
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