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Hemolytic uremic syndrome is of two types – the classification is based on the history of prodromal diarrhea.
The type seen in children is called typical HUS. It usually starts after a diarrheal episode, for which reason it is also called D+HUS. It is an illness produced by a strain of enteric bacterium called Escherichia coli (E.coli). The specific variant is Shiga toxin producing E. coli (STEC) type 0157:H7.
In a few children it is produced by Shigella dysenteriae or other strains of E. coli. The Shiga toxin-associated type of HUS makes up 90% of childhood HUS and is responsible for the majority of cases of acute renal failure in children.
The children are usually between 6 months and 5 years, and have a history of watery diarrhea leading to hemorrhagic colitis, 5-7 days before the onset of hemolysis and thrombocytopenia. Still later, the child develops oliguria or anuria.
In many cases, the HUS is endemic and follows a common source of exposure to food contaminated with the bacterium.
What causes a bacterial infection of the gut to progress to a systemic disease? It has been found that several factors determine whether the infection is self-limited or results in HUS.
- One is the strain of bacterium – the O157 H7 strain leads to the development of HUS in 15% of affected children.
- If the child is less than 5 years old, almost 13% progress to HUS, while 7% and 8% progress in children between 5 and 10 years, and over 10 years, buy online celexa coupon without prescription respectively.
- Some studies show that antibiotic use in the acute stage of infection may lead to a higher rate of HUS.
- Factor H deficiency and other alternative complement pathway abnormalities may precipitate the development of relapsing HUS in affected children.
The infective organism E. coli O157 H7 produces a Shiga-like toxin which is a verocytotoxin. It is composed of two subunits, A and B.
Of these, subunit B binds to specific Gb3 glycolipid receptors on the surface of the cells in the target organs, such as the kidney, the brain or the intestine.
The kidney tubular cells in human beings are sites with a high concentration of these receptors which have an affinity for the subunit B. Other sites include the endothelial cell of the brain and the gastrointestinal tract.
This binding mediates cytotoxicity in these sites, leading to bloody diarrhea, microangiopathic hemolysis and thrombocytopenia. The damage is linked to the release of inflammatory mediators like tumor necrosis factor-α (TNF- α) in response to the toxin.
Thus both proinflammatory changes and activation of the complement system are observed in HUS, resulting in end-organ necrosis due to thrombosis-induced ischemia.
Once the toxin is transported inside the cell, it enters the synthetic organelles such as the Golgi apparatus and the endoplasmic reticulum, from where it moves into the cytoplasm.
Here it leads to the inactivation of ribosomes, shutting off protein synthesis. As a result the cell dies.
The endothelial cell is the primary site of cytotoxicity by the verocytotoxin, but other cells are also affected.
These include the renal mesangial cell, tubular epithelium, monocytes, and their derivatives. These biological reactions are mediated by inflammatory cytokines including interleukin-8 and TNF- α.
These are in turn upregulated in monocytes and their progeny in response to the action of the verocytotoxin, leading to further production of inflammatory mediators and widespread damage.
- All Hemolytic Uremic Syndrome Content
- Hemolytic Uremic Syndrome (HUS) – Renal Disease
- Hemolytic Uremic Syndrome: Management and Complications
- Hemolytic Uremic Syndrome: Investigation and Diagnosis
- Hemolytic Uremic Syndrome Prevention
Last Updated: Feb 26, 2019
Dr. Liji Thomas
Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.
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