Welcome back to another episode of Angry Pathology!
Amyloidosis, also known as What Killed The Captive Cheetah and Foie Gras, is a disorder of the immune system in which misfolded proteins like to gather in certain places where they may/may not interfere with normal tissue function. Sound familiar? Trust me, it’s not as bad as prions, although the two are related.
*pause so I can have a gin and tonic because I am not dealing with immunopathology while sober* Great let’s go!
Despite the numerous different origins of these proteins, they all have beta-pleated sheets and accumulate in fibrils. They are deposited extracellulary (outside of cells) where they then push these cells into a corner and demand their lunch money (increased pressure on cells is Not Good). Once these scoundrels settle in, they are extremely hard to get rid of. The deposits of cell-bullies do not evoke an inflammatory response from the body, kinda like how high school disciplinary procedures ignore repeat offenders.
Localised/organ-specific amyloidosis
This form is uncommon in domestic animals, but amyloid deposition in the islets of Langerhans is a common cause of type II diabetes in cats. Old dogs often have deposits in the arteries of the brain, but this is incidental.
Systemic amyloidosis
Being more common than localised amyloidosis, this form is also largely incidental. This can be further split into:
Primary amyloidosis (immunoglobulin-associated)
This is very rare in animals as the conditions that bring it to fruition are also rare, such as multiple myelomas. The major protein in this type are whole or partial immunoglobulin light chains, as seen here:
Immunoglobulins (antibodies) are usually made by plasma cells in response to a foreign thing in the body (antigens). Antibodies bind antigens and mark them for disposal by the macrophages. This is a very simple explanation of part of an immune response, but you get the point.
A monoclonal (one clone=one parent cell so all baby cells are the same) plasma cell tumor secretes excessive amounts of wacky light chains, which are called Bence-Jones proteins. Because they are so small, they can often slip through the kidneys into the urine. Macrophages, in accordance with their job description, try to eat these proteins but don’t get very far. The result is a partially digested mess of tough-to-perish proteins settling in between cells of various tissues. This is referenced as AL-type amyloidosis (L for light chains) Only a small subset of patients with myeloma patients will develop amyloidosis though.
Secondary amyloidosis (reactive)
(this is where the fun is) This is the most common form of amyloidosis, known as AA-type amyloid. It occurs secondarily to chronic infections, chronic inflammation as well as some tumors (especially those of endocrine origin). All of these pathways cause chronic stimulation of macrophages, which in turn chronically demand that the liver produce serum amyloid protein (SAA) in response to the chronic tissue injury. SAA is a normal acute phase inflammation protein, but being overproduced and then partway eaten leads to it depositing wherever. Here, I drew a diagram:
Something like tuberculosis can cause this, but the example I really want to get to is that of cheetahs. I’m sure you have heard that cheetahs in captivity are so stressed that they need service dogs. Another symptom of this stress is chronic stomach ulcers which leads to amyloid deposition in the renal medullary interstitium and renal failure.
Familial amyloid is another form is AA-amyloid, which affect the kidneys (medullary intersititium) and liver of Shar Peis, the kidneys (glomeruli) of Abyssinians and the livers of Siamese cats. This form is hereditary.
Some target organs of AA-amyloid:
Spleen-red and white pulp
Liver-space of Disse
Kidney-glomeruli or medulla as seen mostly in cats
Amyloid deposition in the glomerulus can cause nephrotic syndrome, where damage to the filtration membrane causes serum proteins to leak into the urine. The liver is usually not as severely affected, although it is more prone to rupture. Amyloid deposits may also be found in the GIT, lymph nodes, skin...basically anywhere.
I hope this explanation is helpful in understanding an incredibly rare and usually incidental finding. Hey, not everything has to be useful to be interesting. Have a lovely amyloid-free day!
Image sources:
http://myplace.frontier.com/~dffix/medmicro/igs.htm
https://vetpath.wordpress.com/2009/07/16/amyloidosis-and-diabetes-in-a-dog/
