Cases, What's this?

What’s this? #5 Amyloidosis

Last week we asked “what’s this?”. Alicia D got it right with renal glomerular amyloidosis, and paleomanuel also correctly spotted some swelling! To understand what’s going wrong in this kidney, we first need to understand the problem with proteins.

When proteins go wrong, all sorts of chaos can occur in the body. One particularly interesting abnormality is when the proteins fold incorrectly when being made, and stick together in clumpy plaques (called proteinopathies = protein + pathology).

You are nothing without your proteins. They act out the instructions written in your DNA – making and holding us together (connective proteins), allowing us to grow and move (contractile and cell division proteins), giving us energy (metabolic and oxygen transport proteins), defending us (immune proteins), giving us colour (pigmentary proteins), and so on and so on and so on!

File:Main protein structure levels en.svg

All proteins are built up from long chains of smaller molecules called ‘amino acids’ (a protein’s primary structure; the lego blocks of life).  These chains fold into different shapes (secondary structure).  Sometimes these fold further – tertiary structure.  And some proteins are made up of multiple folded chains – quaternary structure (super complicated lego mansion).

The accummulation of protein gives the kidney a yellow colour

The accummulation of protein gives the kidney a yellow colour

‘Amyloidosis’ is actually a group of diseases caused by a build up of sticky protein plaques.  Some types of amyloidosis are inherited, like ‘Shar-Pei Fever’ (not to be confused with Sharpie Fever) in Shar-Pei dogs.

Shar-pei dogs, which can actually become airborne in strong winds

Shar-pei dogs can actually use their skin folds to become airborne in strong winds…maybe

In affected dogs, the liver over-produces a protein called serum amyloid A (SAA) involved in inflammation. Some of the SAA proteins fold incorrectly, making sheets that stick together.

Congo red (x100) stains the amyloid fibrils orange-red within the glomeruli

Congo red (x100) stains the amyloid fibrils orange-red within the glomeruli

The sticky sheets of protein float around in the blood, and get lodged in the kidney’s blood filtering machinery (the glomerulus). They stick together and clog up the filter, making the kidneys appear swollen and discoloured with proteinaceous gunk. The delicate blood vessels in the glomerulus are a bit like coffee filter paper: they are easily torn and damaged by trying to push past the protein clogs and keep filtering the blood clean. Once damaged, normal molecules are lost rather than filtered (like coffee granules leaking past the filter paper in to your cup). Once the kidneys lose their ability to filter, we call it kidney failure. Because the whole thing is triggered by repeated episodes of inflammation and SAA release, it is often associated with fever in Shar-pei dogs.

Iodine stains the amyloid deposits in the glomeruli black

Iodine staining the amyloid deposits in the glomeruli dark brown

Amyloid reacts with iodine and forms big brown blobs, so we can see the clumpy SAA plaques in the kidney with the naked eye. We can also stain it with Congo Red under the microscope, which stains the proteins red.  In fact, the Congo Red dye binds in a very regular pattern, almost crystal like, so that when polarised light is shone through it, it becomes apple green…

Polarised light reveals the Congo Red dye as apple green, when bound to amyloid fibrils

Polarised light reveals the Congo Red dye as apple green, when bound to amyloid fibrils

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One thought on “What’s this? #5 Amyloidosis

  1. Pingback: Foodie Friday: Beefy Buns | Veterinary Forensic Pathology

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