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!
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).
‘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.
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.
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.
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…