Pathophysiology of HUS

Related Information: HUS Pathophysiology, hemolytic uremic syndrome pathophysiology

HUS frequently is preceded by an infectious disease, mostly diarrhea (90%) and an upper respiratory disease less frequently (10%). Use of anti-motility drugs increases the chances of developing HUS. HUS is especially caused by a toxin which is secreted by Escherichia coli O157:H7. The other agents are Shigella, Yersinia, Salmonella, and Campylobacter species.

Shiga and similar toxins produced by different strains of S. dysenteriae and also E. coli O157:H7. Almost 70% of the HUS cases are due to these toxins in children. Owing to their cytotoxic activity on vero cells, the toxins are known as verotoxins. It is normally transmitted through contaminated food like ground beef, undercooked cattle products, unpasteurized dairy products, etc. The contaminated food does not give any indications like smell, taste or look.

Even contact between persons or water supply contamination also helps in transmission. E. coli bacterium is normal flora which is found in gastrointestinal tracts of many cattle (healthy ones). Transmission into children can easily occur from a cow while petting it.

Sometimes HUS is linked to viruses like echovirus, varicella, coxsackie A, or B, infectious agents like Clostridium difficile and Streptococcus pneumoniae, AIDS, cancer, chemotherapeutic agents like Mitomycin C, gastric, prostatic and pancreatic malignancies. There are assumptions like immune complexes mediate HUS or HUS are genetically derived or HLA-type.

HUS is sub-classified into two forms namely D+ and D- HUS, based on the infection of diarrhea in the patient. D- HUS accounting for 10% of the cases is otherwise called atypical HUS. D- HUS is characterized by thrombocytopenia, acute renal failure and microangiopathic hemolytic anemia.

Hemolytic Uremic Syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are opposite ends of the same disease. The primary injury occurs in the endothelial cells. This damage activates a chain of events leading to microvascular lesions along with platelet-fibrin hyaline microthrombi occluding capillaries and arterioles, finally resulting in consumptive thrombocytopenia.

Epithelial damage is mainly due to the bacterial or viral toxins. In TTP, hyaline microthrombi are caused all over the microcirculation and microvascular thromboses are found in skin, brain, intestines, pancreas, adrenals, skeletal muscle, spleen and heart. But in contrast, microthrombi are limited only to the kidneys in HUS. The agents and drugs involved in both prove toxic to vascular endothelium.

Though vascular lesions are similar in both, CNS participation predominates in TTP. In HUS, DIC is absent and the pathology is confined to kidneys. Hyaline thrombi are found in glomerular capillaries and afferent arterioles and not found in vessels. Neurologic symptoms, except for those that are linked with uremia are not common. So HUS is defined by the feature of renal involvement especially. When cross examined, the kidneys will be found swollen and pale along with many flea bite hemorrhages on the surface of the kidney. Generally vasculitis is absent.

But in recent times, attention is focused on the levels of ADAMTS13 which are normally found in HUS but is depressed in TTP. ADAMTS13 is in fact Von Willebrand factor-cleaving protease. Later, enzyme assay will be used in differentiating TTP and HUS. HUS can also be reported to recur at times and even a 30% mortality rate is noted.