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 biopsy. 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 Edited: Jul 26, 2007 1:51 PM
