Pathophysiology concepts and miscellaneous Flashcards
Amyloidosis
What is it?
What are the three most common subtypes and how do they come about?
A condition a/w a number of inherited and inflammatory disorders in whicih extracellular deposits of fibrillar proteins are responsible for tissue damage and functional compromise.
These abnormal fibrils are produced by the aggregation of misfolded proteins (which are soluble in their normal folded configuration).
The fibrillar deposits can bind a wide variety of substrates, including serum amyloid P.
Amyloid is deposited in the extracellular space. CAn encroache on and produce pressure atrophy of adjacent cells.
Amyloid is not a single chemical entity.
The three major biochemical forms are:
1. Amyloid light chain (AL) protein - complete immunoglobulin light chains, the amino-terminal fragments of light chains, or both. Most are lambda. Normally produced from fre Ig light chains secreted by a monoclonal population of plasma cells.
2. Amyloid-associated (AA) protein. derived from proteolysis of serum amyloid-associated protein that is synthesized in the liver and circulates in the blood. SAA production is increased in inflammatory states and therefore a/w chronic inflammation (secondary amyloidosis)
3. B-amyloid (AB) protein - cerebral plaques found in AD and deposited in walls of cerebral blood vessels. The ABeta protein is derived by proteolysis from a much larger transmembrane glycoprotein called amyloid precurosr protein.
systemic mastocytosis
diagnostic criteria
2017 WHO classification diagnostic criteria for systemic mastocytosis; must demonstrate major criterion and at least 1 minor criterion or ≥ 3 minor criteria
ICC diagnostic criteria are very similar to the WHO 5th edition criteria; variation from WHO 5th edition are noted
Major criterion
Multifocal dense mast cell infiltrates detected in sections of bone marrow or extracutaneous organs; infiltrate is defined as ≥ 15 mast cells in aggregate (ICC specifies that the mast cells must express tryptase or CD117)
Minor criteria
> 25% of mast cells in bone marrow biopsy are spindled, have abnormal morphology of bone marrow aspirate / tissue infiltrate mast cells are immature or atypical
Detection of KIT mutation in blood, bone marrow or other nonskin tissue (activating point mutation at codon 816 or any KIT mutation conferring ligand independent activation (Leukemia 2022;36:1703)
Expression of one or more of the following antigens in the mast cell population in addition to normal mast cell markers (by flow cytometry or IHC): CD25, CD2, CD30 (Leukemia 2022;36:1703)
Persistent serum total tryptase > 20 ng/mL (except in context of associated myeloid neoplasm)
What is GMS and what is it used for?
What specifically does it stain?
How does it work?
Grocott-Gomori methenamine silver (GMS) is a special stain to detect fungi
Outlines fungal organisms by staining polysaccharides in cell walls
Aldehyde groups form on polysaccharides (1,2-glycols) via oxidation by chromic acid (Suvarna: Bancroft’s Theory and Practice of Histological Techniques, 8th Edition, 2019, IHC World: A Common Mistake When Staining for Fungi [Accessed 31 March 2021])
Aldehyde groups are further oxidized over time
Fungal cell walls (high polysaccharide density) retain more aldehyde groups
Background structures, such as basement membranes, collagen and reticulin (lower polysaccharide density) retain fewer aldehyde groups
Aldehyde groups reduce silver nitrate (or Schiff molecules) to create a metallic silver precipitate which appears gray to black
What is amyloid?
an abnormal protein with a beta pleated structure composed of haphazardly arranged nonbranching fibrils measuring 8 - 10 nm in diameter
