Intestinal amyloidosis: causes and pathogenesis
Last reviewed: 23.04.2024
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The cause of amyloidosis, including the intestine, is not clear. The mechanism of amyloid formation can be considered open only with AA- and AL-amyloidosis, that is, those forms of generalized amyloidosis, in which the intestine is most often affected.
With AA-amyloidosis, amyloid fibrils are formed from the amyloid-fibrillar protein SAA, which is synthesized in the liver intensively, into the amyloidoblast macrophage, the plasma precursor . The enhanced synthesis of SAA by hepatocytes stimulates the macrophage mediator interleukin-1, which leads to a sharp increase in the content of SAA in the blood (presamyloid stage). Under these conditions, macrophages are unable to completely degrade SAA, and amyloid fibrils are assembled from its fragments in the intargins of the amyloidoblast plasma membrane. Stimulates this assembly amyloid - stimulating factor (ASF), which is found in the tissues (spleen, liver) in the pre-damoidal stage. Thus, the macrophage system plays the leading role in the pathogenesis of AA-amyloidosis - it stimulates the enhanced synthesis of the precursor protein - SAA by the liver, it also participates in the formation of amyloid fibrils from the degrading fragments of this protein.
In AL-amyloidosis, the serum precursor of the protein of amyloid fibrils is the L chain of immunoglobulins. It is believed that there are probably two mechanisms for the formation of AL-amyloid fibrils:
- degradation of monoclonal light chain degradation 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, primarily the lymphoid system is involved in the pathogenesis of AL-amyloidosis; with its perverse function associated with the emergence of "amyloidogenic" light chains of immunoglobulins - the precursor of amyloid fibrils. The role of the macrophage system is secondary, subordinate.
Pathomorphology of amyloidosis of the intestine. 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. The masses of the amyloid substance fall along the course of the reticular stroma of the mucosa, in the walls of the vessels of both the mucous membrane and the submucosal layer between the muscle fibers, along the nerve trunks and ganglia, which sometimes leads
To atrophy of the mucous membrane and its ulceration. The predominant deposition of amyloid was 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. At the first type of amyloid deposits, there is a syndrome of impaired absorption, with the second - a disorder of the motor function of the intestine.
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