Gen Path 20: Extracellular Accumulations, Mineralization, and Pigments

Hyaline

A variety of extracellular proteinaceous accumulations have a ___ appearance in histologic sections

Amyloidosis

Biochemically diverse group of disorders that have a common pathogenesis (protein misfolding) and generic morphologic appearance (highly organized fibrillar polypeptide chains rich in cross Beta-sheets)

Yellow, waxy

If visible macroscopically, amyloid appears as ___, ___, coalescing nodular or amorphous deposits

Iodine

Used as a gross technique to stain amyloid, even though amyloid deposits consist mainly of protein (typically associated with other molecules such as carbohydrate moieties)

Amyloid

At light microscopic level, ___ is homogeneous to indistinctly fibrillary and pale eosinophilic

Congo Red, congo

With ___ stain, amyloid takes a more orange-red hue (___philia)

Apple-green birefringence

Amyloid has characteristic ___ in polarized light, especially with Congo red stain

Anisotropic, birefringent

Amyloid is ___ because of its molecular periodicity; [same term] substances are ___

AL amyloid

1. Consists of immunoglobulin light chains derived from dyscrasic or neoplastic plasma cells; considered as primary

   1. Can be systemic (deposited almost anywhere in the body); but, in some extramedullary (e.g., cutaneous) plasmacytomas, amyloid deposition is limited (localized) to the stroma

   2. Localized deposits in nasal amyloidosis of horses also consist of this; conjunctiva, and skin also affected in some horses

   3. Retains its congophilia and apple-green birefringence after pretreatment with potassium permanganate

AA amyloid

1. Consists of amyloid A protein produced mainly by hepatocytes; associated with chronic inflammation; thus, classified as secondary

   1. Amyloid fibrils deposited in various tissues, particularly kidney (especially renal glomeruli), liver (especially space of Disse), and splenic white pulp

   2. Hereditary or familial forms are also recognized

   3. In Shar-Pei dogs and Abyssinian cats, these deposits are most abundant in renal medullary interstitium rather than in renal glomeruli

   4. Amyloid A is sensitive to potassium permanganate: congophilia and apple-green birefringence are lost after potassium permanganate treatment

AA, AL

__ amyloid is sensitive to potassium permanganate, while __ amyloid is tolerant to potassium permanganate.

AL, AA

__ amyloid is classified as primary, while __ amyloid is classified as secondary.

Systemic amyloidosis

1. More likely to be life-threatening; depending on organs involved and volume of amyloid deposits

   1. Diffuse and severe renal glomerular amyloidosis results in protein-losing nephropathy

Localized amyloidosis

Severity of disease depends more on biochemical nature of amyloid fibrils; precursor peptides or intermediate oligomers, rather than mature amyloid fibrils, are thought to be the injurious agent in some form

Fibrinoid change

1. Result of leakage of plasma proteins (e.g., immunoglobulin, complement or fibrin) into the wall of blood vessel

2. Observed in septic or immune-mediated vasculitis

Fibrosis

Excess in fibrous collagen, mainly type I collagen fibers, in interstitium

Granulation tissue

In many injured tissues, especially beneath ulcers or in wound healing, fibroblastic proliferation (fibrosis) is accompanied by endothelial proliferation (neovascularization) with formation of ___.

Fatty infiltration

Increase in number and/or volume of adipocytes in interstitium of organ or tissue (distinct from intracellular accumulation known as lipidosis or steatosis)

Obesity, cardiomyopathies, skeletal myopathies, atrophied

1. Increase in size and number of adipocytes in myocardial interstitium (especially near epicardium and skeletal muscle bundles): ___ and certain ___ or ___

2. Adipocytes also accumulate in ___ tissues (particularly skeletal muscle, thymus, and thyroid gland)

Gout

Deposition of sodium urate crystals (or urates) in tissue; occurs in primates, birds, and reptiles, but has not been reported in domestic animals

Tophi

Aggregates of urate crystals

May be visible grossly

Pathognomonic for gout

Acicular, birefringent

Microscopically, urate crystals are ___ (needle-shaped) and negatively ___ under polarized light

Articular (rare), visceral

What are the two forms of gout that birds and reptiles can be affected by?

Visceral gout

Characteristically affects visceral serosae (particularly parietal pericardium and kidneys)

Covered with a thin layer of gray granules

Gross appearance is diagnostic

Seen sporadically as the result of vitamin A deficiency, high-protein diets, and renal injury

Pseudogout

Deposits of calcium pyrophosphate crystals

Reported rarely in dogs

Pathogenesis is unknown

Grossly, chalky white deposits of crystalline material in joints

Cholesterol crystals

Dissolved out during histologic processing, leaving characteristic acicular (needle-shaped) clefts

Atherosclerosis, hyperthyroid

Cholesterol is present in atheromas (degenerated arterial intima plaques in ___); seen in ___ dogs

Cholesterol granulomas (cholesteatomas)

Choroid plexus of lateral or 4th ventricles in old horses; friable pale yellow nodules; often an incidental finding

Islet amyloid polypeptide (IAPP)

Amyloid deposited in pancreatic islets of cats and humans is derived from ___ secreted by beta cells

Can be associated with insulin-resistant type 2 diabetes mellitus

Beta-amyloid (Alpha-beta)

Accumulation of ___ in cerebral cortex of aged dogs with canine cognitive disorder and in humans with Alzheimer’s disease