Extracellular accumulations: amyloidosis. Types of amyloidosis, pathogenesis, microscopic & gross organ pathomorphology. Histochemical staining methods
This is, in effect, the continuation of the above, except amyloidosis is a more common and significant accumulation.
Amyloid is an abnormal protein substance which can be deposited among the cells in various tissues in a condition known as amyloidosis.
Amyloidosis is a product of protein misfolding, leading to insoluble, aggregated proteins. It is heterogenous, although always visually the same, with nonbranching fibrils in a beta-sheet formation.
There are four main types of amyloidosis, based on the particular protein that has been misfolded (although there are actually 30 types in total)
- AL- amyloid (Amyloid light chain)
- Derived from light chains
- AA-amyloid (Amyloid-associated)
- Derived from serum amyloid A (SAA), an acute phase reactant
- Beta Amyloid
- Derived from amyloid precursor protein
- Endocrine amyloid
Examples: the classic disease behind each type:
- AL – multiple myeloma and other plasma cell dyscrasias.
- AA – long-standing inflammation: rheumatoid arthritis, tuberculosis, bronchiectasis, chronic osteomyelitis, familial Mediterranean fever.
- Aβ – Alzheimer disease (plaques, vessel walls).
- Endocrine – calcitonin in medullary thyroid carcinoma, amylin in the islets in type 2 diabetes.
- ATTR (transthyretin) – senile cardiac and familial amyloidosis.
We are also able to divide amyloidosis based on the pathology itself, we split this based on location of amyloids:
- Generalized systemic amyloidosis
- Amyloids deposited throughout the body
- Primary (AL amyloid), secondary (reactive, result of inflammation; AA amyloid), or hereditary (mostly transthyretin amyloid)
- Localized
- Amyloids found in a single organ
Pathogenesis: Amyloidosis is the product of the following chain
- Excessive production of proteins that are prone to misfolding
- Mutations that produce proteins that cannot fold properly clump together
- Defective or incomplete degradation of these proteins
- They are then deposited in the extracellular tissues
Morphology
Kidney (NOTE SLIDE):
- Gross appearance may be unchanged or large, pale, gray and firm
- Microscopically, deposits are found in glomeruli, the interstitial peritubular tissue and in the walls of blood vessels
Spleen (NOTE SLIDE):
- Gross appearance shows enlargement, firm in consistency with pale gray, waxy deposits inside
- Microscopically, 2 patterns, in the folliculi we see tapioca like granules while in the sinuses and pulp there are large sheetlike deposits of amyloids
Liver
- Gross appearance shows massive enlargement, very pale, grayish and waxy
- Microscopically, deposits found in the space of Disse
Heart
- Gross appearance may be unchanged, or may be minimal enlargement with gray-pink subendocardial elevations
- Microscopically, deposits found throughout the myocardium between myocardial fibers