Hemolytic-uremic syndrome pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2], Anila Hussain, MD [3]


It is understood that hemolytic-uremic syndrome (HUS) is the result of microvascular endothelial cell damage characterized by thrombotic microangiopathy (TMA) in renal glomeruli, gastrointestinal tract, brain and pancreas in all of which the main lesion is the thickening of vessel wall (mainly in capillaries and arterioles), microthrombi in platelets and obstruction of vessel lumen ( partial or complete). Loss of physiological resistance to thrombus formation, complement consumption, leukocyte adhesion to damaged endothelium, the abnormal release of von Willibrand Factor (vWF) and fragmentation, and increased vascular shear stress lead to further amplification of microangiopathy. Typical/ Shiga-toxin-associated hemolytic uremic syndrome (HUS) is usually caused by E.Coli and serotype O157: H7 is most common while congenital predisposing conditions like complement factor abnormalities may play a role in recurrent and familial forms.




Mutations in the genes associated with atypical HUS can cause uncontrolled complement system activation which attacks endothelial cells leading to inflammation and thrombi formation and may lead to kidney injury and renal failure. Examples include:[12][13][14]

Other genetic conditions predisposing to atypical HUS include:

Associated Conditions

Conditions associated with HUS include:

Gross Pathology

On gross pathology, [feature2], and [feature3] are characteristic findings of HUS.

Microscopic Pathology

On microscopic histopathological analysis finding of HUS.

  • Granular (muddy brown) casts
  • Characteristic fibrin thrombi in glomerular and interstitial capillaries
  • Slough into tubular lumen
High magnification microscopy of HUS Source:By Nephron [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], from Wikimedia Commons


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  2. Malyukova I, Murray KF, Zhu C, Boedeker E, Kane A, Patterson K; et al. (2009). "Macropinocytosis in Shiga toxin 1 uptake by human intestinal epithelial cells and transcellular transcytosis". Am J Physiol Gastrointest Liver Physiol. 296 (1): G78–92. doi:10.1152/ajpgi.90347.2008. PMC 2636932. PMID 18974311.
  3. Pacheco AR, Sperandio V (2009). "Inter-kingdom signaling: chemical language between bacteria and host". Curr Opin Microbiol. 12 (2): 192–8. doi:10.1016/j.mib.2009.01.006. PMC 4852728. PMID 19318290.
  4. Walker WA. Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management. 4th ed. Hamilton, Ont.: BC Decker, 2004
  5. Hughes DT, Clarke MB, Yamamoto K, Rasko DA, Sperandio V (2009). "The QseC adrenergic signaling cascade in Enterohemorrhagic E. coli (EHEC)". PLoS Pathog. 5 (8): e1000553. doi:10.1371/journal.ppat.1000553. PMC 2726761. PMID 19696934.
  6. Ståhl AL, Sartz L, Nelsson A, Békássy ZD, Karpman D (2009). "Shiga toxin and lipopolysaccharide induce platelet-leukocyte aggregates and tissue factor release, a thrombotic mechanism in hemolytic uremic syndrome". PLoS One. 4 (9): e6990. doi:10.1371/journal.pone.0006990. PMC 2735777. PMID 19750223.
  7. Ståhl AL, Svensson M, Mörgelin M, Svanborg C, Tarr PI, Mooney JC; et al. (2006). "Lipopolysaccharide from enterohemorrhagic Escherichia coli binds to platelets through TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome". Blood. 108 (1): 167–76. doi:10.1182/blood-2005-08-3219. PMC 1895830. PMID 16514062.
  8. Cherla RP, Lee SY, Tesh VL (2003). "Shiga toxins and apoptosis". FEMS Microbiol Lett. 228 (2): 159–66. PMID 14638419.
  9. Brigotti M, Carnicelli D, Ravanelli E, Barbieri S, Ricci F, Bontadini A; et al. (2008). "Interactions between Shiga toxins and human polymorphonuclear leukocytes". J Leukoc Biol. 84 (4): 1019–27. doi:10.1189/jlb.0308157. PMID 18625912.
  10. Pijpers AH, van Setten PA, van den Heuvel LP, et al. Verocytotoxin-induced apoptosis of human microvascular endothelial cells. J Am Soc Nephrol 2001;12:767- 778
  11. Hughes AK, Stricklett PK, Schmid D, Kohan DE (2000). "Cytotoxic effect of Shiga toxin-1 on human glomerular epithelial cells". Kidney Int. 57 (6): 2350–9. doi:10.1046/j.1523-1755.2000.00095.x. PMID 10844605.
  12. Frémeaux-Bacchi V (2013). "[Pathophysiology of atypical hemolytic uremic syndrome. Ten years of progress, from laboratory to patient]". Biol Aujourdhui. 207 (4): 231–40. doi:10.1051/jbio/2013027. PMID 24594571.
  13. Loirat C, Noris M, Fremeaux-Bacchi V (2008). "Complement and the atypical hemolytic uremic syndrome in children". Pediatr Nephrol. 23 (11): 1957–72. doi:10.1007/s00467-008-0872-4. PMID 18594873.
  14. Jessica Caprioli, Marina Noris, Simona Brioschi, Gaia Pianetti, Federica Castelletti, Paola Bettinaglio, Caterina Mele, Elena Bresin, Linda Cassis, Sara Gamba, Francesca Porrati, Sara Bucchioni, Giuseppe Monteferrante, Celia J. Fang, M. K. Liszewski, David Kavanagh, John P. Atkinson & Giuseppe Remuzzi (2006). "Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome". Blood. 108 (4): 1267–1279. doi:10.1182/blood-2005-10-007252. PMID 16621965. Unknown parameter |month= ignored (help)
  15. Adrovic A, Canpolat N, Caliskan S, Sever L, Kıykım E, Agbas A; et al. (2016). "Cobalamin C defect-hemolytic uremic syndrome caused by new mutation in MMACHC". Pediatr Int. 58 (8): 763–5. doi:10.1111/ped.12953. PMID 27324188.
  16. Feng S, Eyler SJ, Zhang Y, Maga T, Nester CM, Kroll MH; et al. (2013). "Partial ADAMTS13 deficiency in atypical hemolytic uremic syndrome". Blood. 122 (8): 1487–93. doi:10.1182/blood-2013-03-492421. PMC 3750341. PMID 23847193.

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