[B] 1.31 Amyloidosis Flashcards
Etymology: “Amyloid”
Amylum = Starch
Give the two main groups of amyloidosis pathogenesis
- Immunmediated amyloidosis
- Non-immunmediated amyloidosis
Morphology of an amyloid protein
- Fibrils composed of protofilaments
- Fibre network (β-sheets) unique in:
- Staining
- Optical characteristics
Amyloid physical properties
- Formed by different proteins with abnormal structure
- Structure change is the consequence of different effects
- Insoluble in water & acids
- Soluble in bases
Amyloidosis staining properties
- HE: Pink, homogenous
- Congo red: Orange
- Polarised light: Golden shining
- PAS: Red
- Toluidine blue: Red
- Immunohistochemistry: IgG
- Macroscopic: Brown then blue
Other characteristics of amyloid
- Structurlly stable amyloid
- Trypsin resistant
- (Unless structurally unstable)
- 2 types of amyloidosis
- Primary (Local & atypical)
- Secondary (systemic & typical)
Immunmediated pathogenesis
- Background
- Monoclonal B-lymphocyte proliferation
- Plasma cell activation
- Immunoglobulin’s light chains
- Amyloid-light-protein
Result: Primary amyloidosis
Immunmediated pathogenesis
- Chronic inflammation
- Macrophage activation
- IL-1 & IL-6 production (cytokines)
- Abnormal protien production in hepatocytes
- SAA-protein (serum associated amyloid-protein) (soluble)
- AA-protein (insoluble)
Result: Secondary amyloidosis
Why is Secondary amyloidosis ‘secondary’
- Preceded by:
- Tissue necrosis
- Chronic inflammation
- Endotoxin production
- In vaccinated animals with bacterium vaccine
- In horses for hyperimmune serum production
Why is Secondary amyloidosis ‘typical’
Occurs on characteristic sites
Why is Secondary amyloidosis ‘systemic’
Observed in several organs
Recognition of amyloidosis
- Mostly by macroscopic investigation
- Local (predilection sites)
- Systemic (Certain organs - liver, spleen, kideny)
- Sometimes only by histopathology
Harmful effects of amyloid
- Intercellular deposition
- Blocks the normal transfer of materials
- Loss of function, regressive changes in tissues
The latter changes cause the problems, not the amyloid itself
Pathology of systemic amyloidosis: Liver
- Shape: Normal
- Size: Enlarged
- Colour: Pale, sometimes green in birds (biliverdin)
- Consistency: Dry cut surface, easy to tear
Amyloid is deposited on the basal membrane of sinusoids or in the walls of blood vessels
Pathology of systemic amyloidosis: Spleen
Deposition in the vessels of the vascular elements of the Malpighi-bodies
Pathology of systemic amyloidosis: Kidneys
Deposition:
- On the basal membrane of the glomerular capillaries and tubuli
- On/in the wall of blood vessels of the interstitium
Pathology of systemic amyloidosis: Adrenal gland
In the wall of the capillaries of the cortex
Pathology of systemic amyloidosis: Intestines
- On the basal membrane of the capillaries of the microvilli
- In the intestinal glands
Atypical, local amyloidosis
- Atypical: Because the cause is unknown
-
Local: Because:
- Occurs on the predilection sites of the body (“amyloid tumours”)
- In the skin or in the mucosa of the ansal cavity of horses, sometimes tumour-like swellings
- In the heart muscle of leptomeninx of aging animals
APUD-amyloidosis
Amine precursor uptake and decarboxylation-amyloidosis
- Production & decarboxylation of amine precursors
- Result: Secreted into the cell’s environment → Amyloid produced from excess protein
Cells of APUD-system
- Enterochromaffin cells of stomach & intestinal wall
- Parafollicular C-cells of thyroid gland
- α- and β-cells of Langerhans-islets
- ACTH-producing cells of adenohypophysis
