Шига токсинімен байланысты гемолитикалық уремиялық синдром және оның салдары

Group of blood disorders related to bacterial infection
Later: Low platelets, low red blood cells, kidney failure
| prevention =
| treatment = Supportive care, dialysis, steroids, blood transfusions, plasmapheresis Kidney problems and low platelets then occur as the diarrhea progresses. Adults, especially the elderly, may present a more complicated presentation. The underlying mechanism typically involves the production of Shiga toxin by the bacteria. Treatment involves supportive care and may include dialysis, steroids, blood transfusions, or plasmapheresis.

After eating contaminated food, the first symptoms of infection can emerge anywhere from 1 to 10 days later, but usually after 3 to 4 days. These early symptoms can include diarrhea (which is often bloody), stomach cramps, mild fever, or vomiting that results in dehydration and reduced urine. People with HUS commonly exhibit the symptoms of thrombotic microangiopathy (TMA), which can include abdominal pain, low platelet count, elevated lactate dehydrogenase LDH, (an enzyme released from damaged cells, and which is therefore a marker of cellular damage) decreased haptoglobin (indicative of the breakdown of red blood cells) proteinuria (indicative of kidney injury), confusion, swelling, nausea/vomiting, and diarrhea. Additionally, patients with aHUS typically present with an abrupt onset of systemic signs and symptoms such as acute kidney failure, stroke, and coma. Failure of neurologic, cardiac, renal, and gastrointestinal (GI) organs, as well as death, can occur unpredictably at any time, either very quickly or following prolonged symptomatic or asymptomatic disease progression.

Shiga toxin producing E. coli (STEC) HUS occurs after ingestion of a strain of bacteria expressing Shiga toxin such as enterohemorrhagic Escherichia coli (EHEC), of which E. coli O157:H7 is the most common serotype.

Atypical HUS (aHUS) represents 5–10% of HUS cases Early signs of systemic complement mediated TMA include thrombocytopenia (platelet count below 150,000 or a decrease from baseline of at least 25%) and has not been proven effective in any controlled trials. People with aHUS and ESRD have also had to undergo lifelong dialysis, which has a 5 year survival rate of 34–38%.

HUS is caused by ingestion of bacteria that produce Shiga toxins, with Shiga toxin producing E. coli (STEC) being the most common type. Once ingested, the bacteria move to the intestines where they produce the Shiga toxins. The bacteria and toxins damage the mucosal lining of the intestines, and thus are able to gain entry into the circulation. Shiga toxin gains entry to the cell via Gb3 and endocytosis, it then is transported to the Golgi apparatus where furin cleaves the A subunit of the Shiga toxin. The presence of schistocytes is a key finding that helps to diagnose HUS. Shiga toxin directly activates the alternative complement pathway and also interferes with complement regulation by binding to complement factor H, an inhibitor of the complement cascade. Shiga toxin causes complement mediated platelet, leukocyte, and endothelial cell activation, resulting in systemic hemolysis, inflammation and thrombosis. Severe clinical complications of TMA have been reported in patients from 2 weeks to more than 44 days after presentation with STEC HUS, with improvements in clinical condition extending beyond this time frame, suggesting that complement activation persists beyond the acute clinical presentation and for at least 4 months. The consumption of platelets as they adhere to the thrombi lodged in the small vessels typically leads to mild or moderate thrombocytopenia with a platelet count of less than 60,000 per microliter. As in the related condition TTP, reduced blood flow through the narrowed blood vessels of the microvasculature leads to reduced blood flow to vital organs, and ischemia may develop. In contrast with typical disseminated intravascular coagulation seen with other causes of sepsis and occasionally with advanced cancer, coagulation factors are not consumed in HUS (or TTP) and the coagulation screen, fibrinogen level, and assays for fibrin degradation products such as "D Dimers", are generally normal despite the low platelet count (thrombocytopenia). Children and adolescents are commonly affected. One reason could be that children have more Gb3 receptors than adults which may be why children are more susceptible to HUS. Cattle, swine, deer, and other mammals do not have GB3 receptors, but can be asymptomatic carriers of Shiga toxin producing bacteria. Some humans can also be asymptomatic carriers. Once the bacteria colonizes, diarrhea followed by bloody diarrhea, hemorrhagic colitis, typically follows. Other serotypes of STEC also cause disease, inlduding HUS, as occurred with E. coli O104:H4, which triggered a 2011 epidemic of STEC HUS in Germany. Grossly, the kidneys may show patchy or diffuse renal cortical necrosis. Histologically, the glomeruli show thickened and sometimes split capillary walls due largely to endothelial swelling. Large deposits of fibrin related materials in the capillary lumens, subendothelially, and in the mesangium are also found along with mesangiolysis. Interlobular and afferent arterioles show fibrinoid necrosis and intimal hyperplasia and are often occluded by thrombi. ); and gastrointestinal (GI) symptoms (e. g., diarrhea, However, the absence of an identified complement regulatory gene mutation does not preclude aHUS as the cause of the TMA, as approximately 50% of patients with aHUS lack an identifiable mutation in complement regulatory genes.

The effect of antibiotics in shiga toxin producing E. coli is unclear.

Acute renal failure occurs in 55–70% of people with STEC HUS, although up to 70–85% recover renal function. With aggressive treatment, more than 90% of patients survive the acute phase of HUS, and only about 9% may develop ESRD. Roughly one third of persons with HUS have abnormal kidney function many years later, and a few require long term dialysis. Another 8% of persons with HUS have other lifelong complications, such as high blood pressure, seizures, blindness, paralysis, and the effects of having part of their colon removed. STEC HUS is associated with a 3% mortality rate among young children and a 20% mortality rate in middle age or older adults. Moschcowitz first described TTP as a distinct clinicopathologic condition that can mimic the clinical characteristics of Hemolytic–uremic syndrome (HUS). That was in a 16 year old girl who died 2 weeks after the abrupt onset and progression of petechial bleeding, pallor, fever, paralysis, hematuria and coma; and called "Moschcowitz disease". Moreover, Moschcowitz was among the first to work in psychosomatic medicine, and he presented a paper in 1935 on the psychological origins of physical disease. HUS was first described by Conrad Gasser in 1955, and the systemic character of HUS was subsequently defined. Bernard Kaplan identified several distinct entities that can manifest as HUS and emphasized that HUS was a syndrome with a common pathologic outcome. Kaplan is a Canadian professor and director of Pediatric Nephrology. He has an international reputation for his studies, over the past 34 years, on the hemolytic uremic syndromes. The discovery that endothelial cell injury underlies this broad spectrum of TMA disorders has come into focus during the last two decades. In the 1980s, Mohamed Karmali (1945 2016) was the first to make the association between Stx, diarrheal E. coli infection and the idiopathic hemolytic uremic syndrome of infancy and childhood. Karmali's work showed that the hemolytic uremic syndrome the children in Canada was caused by this particular bacteria. Karmali also developed the system of classifying strains of E. coli and determining which cause disease in humans. He defined the presence of microvascular injury in diarrhea associated HUS and the critical role of a verotoxin produced by specific strains of Escherichia coli. This verotoxin was subsequently found to be a member of a family of toxins first identified with Shigella and known as Shiga toxin (Stx). This relationship and the eventual link of TTP to abnormally high levels of ultra large Von Willebrand factor (vWF) multimers caused by congenital or acquired reductions in ADAMTS13 activity was established at approximately the same time. In 1924, a Finnish physician Erik Adolf von Willebrand (1870 1949) was consulted about a young girl with a bleeding disorder. Von Willebrand described this disorder in 1926, distinguishing it from hemophilia. The disorder was named after him, becoming known as von Willebrand disease. The cause of the disease was later discovered to be a deficiency of a protein, now known as von Willebrand factor, that enables hemostasis. Paul Warwicker is an English nephrologist, whilst in Newcastle in the mid 1990s his research in molecular genetics with Professors Tim and Judith Goodship led to the genetic mapping of the familial form of atypical HUS and the descriptions of the first HUS related mutations and polymorphisms in the factor H gene in both familial and sporadic HUS. He was awarded an MD in molecular genetics in 2000, and elected fellow of the Royal College of Physicians in the same year. Paul Warwicker confirmed the association of atypical HUS (aHUS) to defects in a region on chromosome 1 that contains the genes for several complement regulatory proteins. Later, mutations in complement factor H, complement factor I, membrane cofactor protein, factor B, C3, and thrombomodulin have now been found to cause many of the familial cases of aHUS. These discoveries have allowed a more comprehensive understanding of the pathogenesis, evaluation, and treatment of the entire spectrum of TMA disorders and provide a more rational and effective approach to the care of these children with complicated disease. Prior to the use of monoclonal antibodies patients with aHUS had an extremely poor prognosis. Eculizumab (Soliris®, Alexion Pharmaceuticals, Inc., Boston, MA, USA) is a humanized monoclonal complement inhibitor that is the first and only approved treatment for patients with aHUS by FDA in September 2011. Eculizumab binds with high affinity to C5, inhibiting C5 cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b 9, thus inhibiting complement mediated TMA. Eculizumab was proven to be effective in patients with aHUS in which it resolved and prevented complement mediated TMA, improving renal function and hematologic outcomes. Alexion head of R&D 'John Orloff, M. D. "The results met the high bar of complete TMA response, defined by hematologic normalization and improved kidney function," said Alexion R&D head John Orloff, M. D., who reckons the drug can become the "new standard of care for patients with aHUS." "We are preparing regulatory submissions for Ultomiris in aHUS in the U. S., European Union and Japan as quickly as possible," he added.

The country with the highest incidence of HUS is Argentina and it performs a key role in the research of this condition. In the United States, the overall incidence of HUS is estimated at 2.1 cases per 100,000 persons/year, with a peak incidence between six months and four years of age. In May 2011 an epidemic of bloody diarrhea caused by E. coli O104:H4 contaminated fenugreek seeds hit Germany. Tracing the epidemic revealed more than 3,800 cases, with HUS developing in more than 800 of the cases, including 36 fatal cases. Nearly 90% of the HUS cases were in adults.