Hemolytic-uremic syndrome

‘Hemo’ refers to the blood, ‘lytic’ refers to breaking down, and ‘uremic’ refers to increased urea levels in the blood.

And this helps explain hemolytic uremic syndrome because the two main effects are destruction of red blood cells and the declining function of the kidney causing uremia - both of which result from tiny blood clots that form in tiny blood vessels - predominantly in the kidneys.

Classically, especially in children, hemolytic uremic syndrome is triggered by a bout of bloody diarrhea.

When that happens, it’s called diarrhea-positive or D positive hemolytic syndrome, sometimes shortened to HUS or simply typical HUS.

Escherichia coli or E. coli is usually the culprit, and children often pick it up through contaminated food or drink, like contaminated beef or unpasteurised milk from an infected cow.

The particular strain of E.coli responsible for hemolytic uremic syndrome is known as enterohemorrhagic E. coli or EHEC, serotype O157:H7.

These numbers and letters refer to the specific antigens on the surface of the bacteria.

‘157’ refers to the O-antigen present in the lipopolysaccharide cell wall and ‘7’ refers to the H-antigen located on the flagella of the bacteria.

Other strains of E. coli as well as other bacteria can also cause hemolytic uremic syndrome, but E. coli O157:H7 is the most common culprit.

After entering the digestive tract, E. coli O157:H7 attaches to the intestinal wall and secretes a toxin called Shiga-like toxin.

The toxin gets its name due to its structural similarity with shiga toxin produced by Shigella dysenteriae, another bacteria that causes bloody diarrhea and subsequent hemolytic uremic syndrome.

So that toxin gets absorbed by intestinal blood vessels and is then picked up by immune cells like eosinophils, basophils and neutrophils.

From there, the toxin is carried on the surface of these cells to the site of blood filtration - which is the glomerular capillaries of the kidney.

Endothelial cells lining these glomerular capillaries express a glycolipid receptor called globotriaosylceramide or Gb3-receptor that has an incredibly strong affinity for the shiga-like toxin - the receptor is like a little magnet that can simply snatch the toxin away from a white blood cell as it drifts by.

Once the toxin binds to the Gb3-receptor, it gets engulfed by the endothelial cell and once inside, it wreaks havoc on the cell.