Hemolytic uremic syndrome

Pathogenesis and development of the syndrome

Hemolytic uremic syndrome belongs to a heterogeneous group of thrombotic microangiopathies (TMAs). Despite different etiologies, all disorders in this group share a similar clinical and morphological phenotype based on generalized thrombus formation in the microvasculature.

Pathophysiological cascade in HUS:

1. Activation of the complement system occurs (uncontrolled).
2. Thrombi composed of platelets and fibrin form in small blood vessels (capillaries and arterioles).
3. Active thrombus formation consumes blood platelets, resulting in consumption thrombocytopenia.
4. Red blood cells passing through narrowed and partially occluded microvessels are physically destroyed. Microangiopathic hemolytic anemia develops.
5. Thrombosis leads to tissue ischemia. Vital organs—primarily the kidneys and the central nervous system—suffer first.

Histologically, acute TMA reveals swelling (edema) and detachment of the endothelium from the basement membrane. Amorphous material accumulates beneath the endothelium, and the vascular lumen is often completely obstructed by thrombotic masses.

Infection-mediated (typical) HUS

The classic scenario of HUS development is associated with bacterial intestinal infections. The main culprits are microorganisms that produce Shiga toxin.

• Shigella dysenteriae type 1: Characterized by extremely high virulence. The infectious dose is as low as up to 200 cells. The bacterium secretes an exotoxin (Shiga toxin) that acts as an entero- and neurotoxin. It irreversibly blocks ribosomes and protein synthesis in the intestinal epithelium, damages capillary endothelium, and causes local ischemia. When the toxin enters the systemic circulation, TMA and HUS develop. Other Shigella species secrete less active Shiga-like toxins.
• Enterohemorrhagic Escherichia coli (EHEC): Most commonly the E. coli O157:H7 serotype. The infection manifests with watery diarrhea and abdominal pain, transitioning into hemorrhagic colitis on days 2–3 (fever may be absent). HUS acts as a severe complication affecting primarily young children 5–10 days after the onset of diarrhea.

Atypical hemolytic uremic syndrome (aHUS)

Unlike typical HUS, the atypical variant is a systemic disease not directly linked to bacterial toxins. It is characterized by a progressive course and a poor prognosis.

aHUS is based on a genetic or acquired defect leading to constant, uncontrolled hyperactivation of the alternative pathway of the complement system. This causes damage to the body's own endothelium and triggers generalized thrombus formation in the microcirculatory vessels.

Class and exam questions

What else to study on this topic

• Clinical manifestations and diagnostic criteria of enterohemorrhagic Escherichia coli infection (E. coli O157:H7)
• Morphological differences between TMA and disseminated intravascular coagulation (DIC) syndrome
• Peculiarities of the course of intestinal infections caused by enterotoxigenic (ETEC) and enteroinvasive (EIEC) Escherichia
• The mechanism of cellular damage by Shiga toxin at the molecular level

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.