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. STEC-HUS is usually preceded by a prodrome of diarrhea, which is often bloody, and is caused by Shiga-like toxin-producing bacteria such as enterohemorrhagic Escherichia coli (EHEC), of which E. coli O157:H7 is the most common serotype. Other serotypes also cause disease and can emerge as new causes of STEC-HUS, as occurred with E. coli O104:H4, which triggered a 2011 epidemic of STEC-HUS in Germany.The typical pathophysiology of HUS involves the binding of Shiga-toxin to the globotriaosylceramide (Gb3; also called ceramide trihexoside which accumulates in Fabry disease) receptor on the surface of the glomerular endothelium. This action includes a cascade of signaling events leading to apoptosis and binding of leukocytes to endothelial cells. The Shiga-toxin-activated endothelial cells then become thrombogenic (clot-producing) by a mechanism that is not fully understood, though they have been shown to induce the release of cytokines and chemokines that are implicated in platelet activation. Additionally, the binding action of Shiga-toxin inactivates a metalloproteinase called ADAMTS13, the deficiency of which causes the closely related TTP. Once ADAMTS13 is disabled, multimers of von Willebrand Factor (vWF) form and initiate platelet activation, causing microthrombus formation. The activation of platelets resulting from inhibition of ADAMTS13 is due to the hyperactivity of large multimers of uncleaved vWF.
These early symptoms can include diarrhea (which is often bloody), stomach cramps, mild fever, or vomiting that results in dehydration and reduced urine. HUS typically develops about 5–10 days after the first symptoms, but can take up to 3 weeks to manifest, and occurs at a time when the diarrhea is improving. Related symptoms and signs include lethargy, decreased urine output, blood in the urine, kidney failure, low platelets, (which are needed for blood clotting), and destruction of red blood cells (microangiopathic hemolytic anemia). High blood pressure, jaundice (a yellow tinge in skin and the whites of the eyes), seizures, and bleeding into the skin can also occur. In some cases, there are prominent neurologic changes.People with HUS commonly exhibit the symptoms of thrombotic microangiopathy (TMA), which can include abdominal pain, low platelet count, elevated lactate dehydrogenase LDH, (a chemical released from damaged cells, and which is therefore a marker of cellular damage) decreased haptoglobin (indicative of the breakdown of red blood cells) anemia (low red blood cell count), schistocytes (damaged red blood cells), elevated creatinine (a protein waste product generated by muscle metabolism and eliminated renally), proteinuria (indicative of kidney injury), confusion, fatigue, 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, hypertension (high blood pressure), myocardial infarction (heart attack), stroke, lung complications, pancreatitis (inflammation of the pancreas), liver necrosis (death of liver cells or tissue), encephalopathy (brain dysfunction), seizure, and coma.