Morphology and diagnostic methods
Intravital recognition of the pathology is possible exclusively through the examination of biopsy specimens. Previously, this disease was classified among stromal-vascular protein dystrophies.
- Light microscopy: with traditional stains, deposits appear as an amorphous, eosinophilic, hyaline-like intercellular substance.
- Histochemical methods: for differential diagnosis with fibrin and collagen, Congo red (Congo red) staining is used.
- Polarization microscopy: stained structures exhibit birefringence (anisotropy) and glow with a characteristic greenish color.
Physicochemical nature of amyloid
Despite biochemical heterogeneity, the physical structure is identical for all types of the disease. It is studied using electron microscopy, crystallography, and infrared spectroscopy.
The substance consists of two fractions:
- F-component (fibrillar): accounts for about 95% of the mass. It is represented by unbranched fibrils 7.5–10 nm wide. The fibril sheath has a characteristic folded structure, which determines the birefringence effect.
- P-component (glycoprotein): accounts for about 5%. It has a pentagonal structure. It shares structural homology with C-reactive protein (CRP), has a high affinity for fibrils, and is critically important for the formation of tissue deposits.
Main biochemical types
About 15 biochemical variants are known, but two main types are distinguished:
- AL amyloid (Amyloid Light chain). Synthesized by plasma cells (immunocytes) during monoclonal proliferation of B-cells. It consists of immunoglobulin light chains (more frequently type VI λ-chains, less frequently κ-chains), or more specifically, their NH₂-terminal fragments.
- AA amyloid (Amyloid Associated). A unique non-immunoglobulin protein (molecular weight 8,500, consisting of 76 amino acid residues). It forms in secondary amyloidosis. Its precursor is the SAA protein (serum amyloid A), which is synthesized in the liver and circulates in the blood bound to the HDL3 lipoprotein subclass.
Specific forms and pathogenesis
In addition to AL and AA, other specific precursor proteins are encountered:
- Transthyretin (TTR): a serum protein that normally transports thyroxine and retinol. Upon genetic mutations (substitution of a single amino acid), it undergoes abnormal aggregation and proteolysis, forming ATTR amyloid. This leads to familial amyloid polyneuropathy.
- β₂-amyloid: forms the core of senile plaques in Alzheimer's disease. It is formed from a large transmembrane glycoprotein APP (Amyloid Precursor Protein).
- Other precursors: keratin, hormones (e.g., procalcitonin).
The very process of conversion of precursor proteins into fibrils occurs with the participation of effector cells. Although the mechanism is not fully understood, macrophages are considered the main candidates for this role. Based on the spread of the process, classification distinguishes systemic (generalized, affecting multiple systems) and local (deposits in a single organ) amyloidosis.
Briefly: answers to topical questions
What do organs look like macroscopically in pronounced amyloidosis?
The macroscopic picture in amyloidosis depends on the affected organ:
- Kidneys — dense, with a greasy sheen on the cut surface; in the end stage, an amyloid shrunken kidney develops.
- Spleen — amyloid may deposit along the follicles ("sago spleen") or diffusely throughout the pulp ("lardaceous spleen").
The appearance of organs may also correspond to the underlying disease against which the dystrophy developed.
In which chronic diseases does secondary AA amyloidosis most frequently develop?
Secondary AA amyloidosis (reactive systemic) most frequently develops against the background of chronic inflammation with tissue destruction.
- Autoimmune diseases — rheumatoid arthritis (the most common cause), ankylosing spondylitis.
- Chronic infections — tuberculosis, syphilis, leprosy.
- Suppurative-inflammatory processes — chronic osteomyelitis, bronchiectasis, pulmonary abscesses, prolonged infective endocarditis.
- Inflammatory bowel diseases — ulcerative colitis, regional enteritis (Crohn's disease).
- Tumor processes — certain types of tumors.
What is the complete clinical classification of amyloidosis?
The clinical classification of amyloidosis is based on the dissemination of the process, etiopathogenesis, and clinical syndromes.
According to dissemination, the following are distinguished:
- Systemic amyloidosis — involvement of multiple organ systems.
- Local amyloidosis — deposits are found in only one organ (including localized tumor-like forms).
According to etiology and pathogenesis, systemic amyloidosis is divided into:
- Primary amyloidosis (idiopathic, associated with immunocyte dyscrasia).
- Secondary amyloidosis (acquired, a complication of chronic inflammation).
- Congenital amyloidosis (hereditary, familial).
- Senile amyloidosis.
- Amyloidosis in hemoblastoses (in multiple myeloma and Waldenström macroglobulinemia).
The name of the pathology comes from the Latin amylum — starch. To distinguish this "animal starch" from collagen, Congo red staining is used. It is easy to remember: Congo Red Colors Starch. In polarized light, it produces a greenish glow and birefringence.
Class and exam questions
Where exactly is amyloid deposited in tissues?
Deposits form exclusively outside cells: in the interstitial tissue and in the walls of blood vessels.
Which protein is the precursor in secondary amyloidosis?
This is the SAA protein (serum amyloid A), which is synthesized in the liver and circulates together with lipoproteins. AA amyloid is formed from it.
Which cells synthesize AL amyloid?
It is formed by plasma cells (immunocytes) during monoclonal proliferation of B-lymphocytes and consists of immunoglobulin light chains.
What is the characteristic feature of the amyloid P-component?
It accounts for only 5% of the mass, has a pentagonal structure, and is structurally similar to C-reactive protein (CRP). Without its participation, the formation of deposits in tissues is impossible.
What else to study on this topic
- The role of macrophages in the conversion of precursor proteins into fibrils
- Association of SAA protein with the HDL3 lipoprotein subclass
- Transthyretin (TTR) mutations and the development of familial amyloid polyneuropathy
- Mechanisms of β₂-amyloid formation from APP in Alzheimer's disease
- Clinical syndromes in systemic and local amyloidosis
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