Amyloidosis
Amyloidosis is a disease characterized by
the extracellular deposition of protein fibrils which have a specific configuration called
the beta-pleated sheet. This configuration leads to the staining properties and
insolubility of amyloid. The animal does not mount an inflammatory response to amyloid.
Amyloid can be deposited in any organ. Organ malfunction develops as normal tissue is
encroached upon by amyloid deposition.
Amyloidosis has a very similar presentation to immune complex GN but
amyloidosis occurs MUCH LESS frequently than does immune complex GN.
Forms of amyloid: There
are systemic and localized forms of
amyloidosis. Localized forms of amyloid can develop from hormone precursors including
proinsulin in the pancreas and precalcitonin in the thyroid gland. Localized deposition of
amyloid has been reported in humans in the following locations: cerebrum, skin,
myocardium, and respiratory tract. Localized amyloid is uncommon in dogs and cats with the
exception of pancreatic amyloid deposition in cats. There are 2 systemic forms of amyloid;
primary and secondary. Primary amyloid is derived from the light chains of
immunoglobulin in patients with plasma cell tumors, although not all patients with plasma
cell tumors develop amyloid. Primary amyloid is rare in dogs and cats.
Secondary amyloidosis is also called
reactive amyloidosis. Secondary amyloidosis usually occurs in patients which have a
chronic infectious, inflammatory, or neoplastic disease. Less than 10% of animals with
chronic inflammatory diseases develop amyloidosis. Serum amyloid A protein (SAA) is a
precursor of reactive amyloid and is increased 100 to 1000 times over normal in acute
inflammation. Chronic elevation of SAA alone is inadequate to produce amyloid. It is
possible that patients who develop reactive amyloid have impaired ability to degrade
SAA.
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The location
of amyloid deposition in the kidneys differs between dogs and cats and
results in different clinical signs in the two species. In the dog kidney, amyloid is
deposited adjacent to the glomerular basement membrane resulting in a disruption of the
filtration barrier and development of proteinuria.
The degree of proteinuria is usually great. Rapid deposition of amyloid may increase the
size of the kidneys. As amyloid encroaches on capillary lumen, RBF is decreased, leading
to a decrease in GFR and signs of renal failure.
In the cat kidney, amyloid is deposited
primarily in the renal medulla, capillary walls and interstitium leading to ischemia and
subsequent reduction of GFR and uremia. There is minimal glomerular involvement in
the cat so proteinuria is usually not present.
Signelment:
Amyloidosis can occur in any breed of dog or cat. Abyssinian cats and Sharpei dogs
develop a familial form of amyloidosis. There is no sex predisposition for the development
of amyloid. Most animals that develop amyloidosis are middle aged to geriatric.
Abyssinian cats and Sharpei dogs that develop amyloid can be young.
Diagnosis: The
laboratory findings and the
clinical picture of
amyloidosis in the dog are very similar to glomerulopathy. The clinical picture will also
reflect the underlying disease that precipitated amyloid deposition.
Biopsy:
Biopsy is needed to confirm amyloidosis. A wedge biopsy rather than a tru cut
biopsy is preferred in cats as amyloid is located in the renal medulla. Amyloid may be
diagnosed by fine needle aspiration of the kidney in dogs. The aspirate is stained with
congo red and viewed with polarized light. Rectal biopsy may demonstrate diffuse
deposition of amyloid although the use of rectal biopsy as a diagnostic tool instead of
renal biopsy has not been investigated in veterinary patients.
 |
the homogenous eosinophilic material is
amyloid
located in the glomeruli |
 |
Amyloid
is a homogenous eosinophilic material when viewed with a light microscope. When the tissue
is stained with Congo red and viewed with polarized light it appears birefringent and an
apple green color. Thioflavine T stain and viewing with ultraviolet light will
disclose amyloid in a biospy. Stain characteristics can be used to differentiate primary
from secondary amyloid. Following oxidation with permanganate, the secondary form of amyloid loses affinity for
Congo red stain. Other types retain affinity.
The appearance of amyloid viewed with
electron microscopy is a nonbranching random fibril of 100 angstrom diameter. |
| staining the gross kidney with iodine will identify amyloid in the glomeruli as black
dots in the renal cortex. |
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Treatment: There is no
proven specific treatment for amyloidosis. Treatment of the
underlying disease may result in regression of amyloid and associated signs.
Corticosteroids are contraindicated as they enhance the experimental production of amyloid
in lab animals. Melphalan may decrease the synthesis of amyloid in patients with
myeloma.
Other drugs which may mobilize amyloid or
slow the rate of deposition include: D-Penicillamine, colchicine, DMSO, and thymosin
although the response to treatment is usually poor. Supportive and symptomatic treatments
are the same as for glomerulopathy.
The prognosis
is usually poor. Some dogs can be managed up to 1 year. Some Abyssinian cats may be
asymptomatic.
Familial renal amyloidosis occurs in
the Abyssinian cat and the Sharpei dog. Amyloidosis has also been reported in young
Siamese and Oriental Shorthaired cats.
Affected Abyssinian cats usually present
between 1 to 5 years of age. Amyloid deposition is diffuse and includes: thyroid glands,
adrenal glands, spleen, gastrointestinal tract, liver, heart and pancreas. Symptomatology
is usually due to renal deposition. Siamese and Oriental Shorthaired cats have been
reported to develop fatal liver hemorrhage from amyloid deposition in the liver. Amyloid
deposition can be rapid and severe resulting in signs of renal failure or deposition can
be mild and only identified at necropsy. The mode of inheritance is not yet known.
Serum amyloid A protein has been identified suggesting amyloid in the Abyssinian is
reactive (secondary). Amyloid deposition occurs primarily in the renal medulla leading to
signs of renal failure including poor coat, weight loss, polyuria/polydipsia, and
anorexia. Physical examination findings are also those of CRF including dehydration,
stomatitis, pale membranes and small, irregular kidneys.
Laboratory findings include azotemia,
hyperphosphatemia, non regenerative anemia, acidosis and isosthenuria. Proteinuria is
usually mild or absent but occasionally can be severe.
Although treatment with DMSO or colchicine
may reduce the rate of amyloid deposition, experience is limited. Treatment is primarily
supportive treatment of chronic renal failure.
Familial renal amyloidosis in the Sharpei
dog is also called Sharpei fever or Sharpei hock syndrome as it begins with episodes of
fever and swollen hocks. The fever and joint swelling are self limiting but often reoccur.
Signs may develop in pups or adults. Renal and hepatic amyloid deposition leads to renal
or hepatic failure. Renal amyloid deposition may be medullary or glomerular.
last edit
October 08, 2002
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College of Veterinary Medicine
Washington State University
Pullman, WA 99164-7060
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