Transcripts
DR. BRANDT:
We heard about thrombotic microangiopathy earlier today. This is the pathologic lesion of HUS; it's also seen in TTP. If you do a renal biopsy, this is what tells you that you have hemolytic uremic syndrome. We often don't need a biopsy to tell us this, but this is what's occurring in the body that gives us the clinical picture of HUS.
Now, we heard this morning a great deal about Shiga toxin and Gb3 from Dr. Lingwood. And this is my version of what goes on. E. coli O157 releases shiga-toxin into the gut of the infected child. HUS, in turn, is due to the action of shiga-toxin on blood vessels, and blood vessels are made up of endoethelial cells. When the shiga-toxin is absorbed into the child's blood stream, two events occur in endothelial cells. First, the endothelial cells swell, which narrows the vessel lumen where red blood travel, carrying oxygen to the body. Second, platelet and fibrin clots form in the blood vessel, blocking further blood flow downstream.
So in addition to direct damage to endothelial cells from the toxin, which can produce a toxin-programmed cell-death, we also have damage from poor blood flow, leading to low oxygen levels in tissue; this is called hypoxia.
Hypoxia causes cell dysfunction which can lead to cell death, in essence suffocation of the cells.
