hemolytic uremic syndrome
Introduction
Introduction to hemolytic uremic syndrome Hemlyticuremic syndrome (HUS): a syndrome characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Mainly found in infants and young children, only dozens of domestic reports, more common in school-age children. This disease is one of the common causes of acute renal failure in children. It has had a small epidemic in Agenyan, North America, and South America. There is no special treatment for this disease, and the mortality rate has reached 77%. In recent years, because of comprehensive therapy, especially In the early application of peritoneal dialysis, the mortality rate has dropped to 4.5%. basic knowledge The proportion of illness: the incidence rate is about 0.004%-0.005% Susceptible people: mainly found in infants and young children Mode of infection: non-infectious Complications: acute renal failure, congestive heart failure, pulmonary edema, hypertensive encephalopathy, hyperkalemia, metabolic acidosis, chronic renal insufficiency, mental retardation, epilepsy
Cause
Cause of hemolytic uremic syndrome
The disease is divided into three major categories: primary, secondary and recurrent.
1, the primary has no clear cause.
2, secondary can be divided into the following types:
(1) Infection: At present, it is relatively clear that E. coli O157:H7, O26O111O113O145, which produces veracytotoxin, Shigella dysenteriae type I can also produce this toxin, and the neuroproximal enzyme produced by Pneumococci, Can cause glomerular and vascular endothelium damage, others are still seen in typhoid, Campylobacter jejuni, Yessinia, Pseudotuberculosis, Pseudomonas, Bacteroides infection and some viral infections such as mucinous virus Coxsackie virus , Echo virus, influenza virus, Epstein-Barr virus and rickettsia infection.
(2) secondary to certain immunodeficiency diseases such as agammaglobulinemia and congenital thymic hypoplasia.
(3) Family hereditary: The disease is autosomal recessive or dominant inheritance, occurring in the same family or siblings. There have been reports of the incidence of three siblings in the country.
(4) drugs: such as cyclosporine, mitomycin and contraceptives.
(5) Others: such as those combined with pregnancy, organ transplantation, glomerular disease and cancer.
3, recurrent episodes are mainly seen in the genetic predisposition, children after transplantation, can also see scattered cases.
Recent studies have shown that the pathogenesis of this disease is mainly due to various reasons caused by endothelial cell damage, especially the endothelial cell damage caused by the spiral cytotoxin produced by Escherichia coli and Shigella dysenteriae type I, such as Endothelial damage can be caused by nerve aminoases, circulating antibodies and drugs produced by viruses and bacteria. Human vascular endothelial cells have a glycoprotein receptor (GB3) that accepts spiral cytotoxin, which can bind toxins with high affinity. Inhibition of eukaryotic cell synthesis of protein, resulting in cell death, glomerular endothelial cell injury and death can cause endothelial cells and glomerular basement membrane to separate into the subendothelial space and stimulate local intravascular coagulation, cellulose heparin deposition, thereby reducing Filtration area and altered permeability of the filter membrane result in decreased glomerular filtration rate and acute renal failure.
Endothelial cell damage, collagen exposure can activate platelet adhesion and coagulation, red blood cells can be mechanically deformed and dissolved by deposition of cellulose, on the other hand, a glycoprotein von Willebrand present in platelets and endothelial cells Factor (VWF) release after cell injury can also accelerate platelet adhesion and coagulation. Vascular endothelial injury can reduce the synthesis of anti-platelet aggregation prostacyclin (PGI2), and thrombocytosis-producing thrombus released after platelet aggregation A2 (TXA2), in contrast to PGI2, also causes vasoconstriction, which promotes thrombosis, which causes hemolytic anemia and thrombocytopenia.
Elastase and other proteolytic enzymes released by neutrophil infiltration can increase the damage of endothelial cells and glomerular basement membrane, and promote the cleavage of VWF, inhibit the growth of PGI2, promote thrombosis, and, in addition, the microorganisms The presence of lipoproteins and monocyte-derived cytokines such as interleukin I and tumor necrosis factor can aggravate the action of cytotoxins, increase damage to endothelial cells, and promote blood coagulation.
The main lesion is in the kidney; thrombosis and cellulose necrosis have been reported in the brain, adrenal gland, liver, spleen, heart muscle and intestine in recent years.
Under light microscopy, glomerular capillary wall thickening, stenosis, thrombosis and hyperemia were observed, and cellulose-like matrix was stained with Schiff's periodic acid (PAS) and periodic acid hexamethylenetetramine silver (PASM). Small material basement membrane (GBM) with different proliferation or light weight, mesangial hyperplasia and occasional crescent formation. Acute arterial injury can be manifested as thrombosis and fibrinoid necrosis. Membrane fibrosis proliferative occlusion, middle fibrosis, similar to hypertensive vascular disease, may have mild to severe tubulointerstitial lesions.
Immunofluoroscopy revealed fibrinogen, clotting factor VIII and platelet membrane antigen deposition in the glomerular capillaries and vascular wall, as well as IgM and C3 deposition.
Electron microscopy is typical of endothelial cell hyperplasia, swelling and formation of subendothelial space between endothelial cells and GBM, including cellulose-like substances and lipids, epithelial cell foot processes fusion, capillary wall thickening, luminal stenosis, lumen Red blood cell debris or shrunken red blood cells can be seen, and GBM divides due to endothelial cell formation of the basement membrane or occasional mesangial insertion.
These changes can be focal, and in a more severe case, extensive glomerular and vascular thrombosis with bilateral cortical necrosis can be seen. These lesions can also be seen in adult HUS and thrombotic thrombocytopenic purpura (TTP), so Less scholars believe that HUS and TTP are different manifestations of the same disease, and the latter is open to the public and has a poor prognosis.
Prevention
Hemolytic uremic syndrome prevention
According to the Japanese Medical Forum, February 8, 2001: The Japanese Medical Association survey showed that early administration of fosfomycin can prevent hemolytic uremic syndrome (HUS) caused by intestinal hemorrhagic E. coli infection.
19 9 8 ~ 19 9 In 9 years, 556 medical institutions reported 1048 cases of intestinal hemorrhagic E. coli infection. Of the 1033 cases that were effective, 655 were symptomatic enteric hemorrhagic E. coli infections. Symptoms, a total of 601 antibiotics, of which the most phosphorus (60. 2%), in addition to norfloxacin (5. 5%), kanamycin (2.0%), the use of other antibacterial The drug is 27.6%.
Of the 655 cases, 31 cases of HUS occurred, 5 of which died. The diagnosis of HUS was according to the Japanese Society for Pediatric Nephrology HU S standard: 1 with hemolytic anemia (H b 10g / dl), 2 with thrombocytopenia (100,000 / l or less) 3, the acute renal dysfunction (serum creatinine concentration is more than 1.5 times the normal value of each age group).
In patients with intestinal hemorrhagic Escherichia coli infection without fosfomycin, the incidence of HUS was 11.11%, and in the group of fosfomycin (362 cases), 11 cases of HUS (incidence rate 3. 04%), the ratio of the two The ratio was 0. 251, a significant difference, the study also found that on the third day, the incidence of HUS was 2. 17%, after 4 days, the incidence rate of the drug was 4.55%, so it should be administered as soon as possible. Prevent HUS from occurring.
Complication
Complications of hemolytic uremic syndrome Complications acute renal failure congestive heart failure pulmonary edema hypertensive encephalopathy hyperkalemia metabolic acidosis chronic renal insufficiency mental retardation epilepsy
Acute complications of acute renal failure such as congestive heart failure, pulmonary edema, hypertensive encephalopathy, hyperkalemia, metabolic acidosis, etc., chronic renal insufficiency, neurological damage sequelae Such as mental retardation, limb paralysis, mental behavior abnormalities and seizures.
Symptom
Symptoms of hemolytic uremic syndrome Common symptoms No urinary oliguria, hematuria, diarrhea, repeated vomiting, abdominal pain, high blood pressure, intermittent hematuria, lethargy
The disease is mainly found in infants and young children, South America and South Africa, the average age is <18 months, North America <3 years old, India about 60% <2 years old, domestic report 1 group 38 cases, 19 cases 7-13 years old, gender is male Lord, there is no significant difference with foreign countries.
Prodromal symptoms are mostly gastroenteritis, manifested as abdominal pain, vomiting and diarrhea, may be bloody diarrhea, very similar to ulcerative colitis, there are reports of acute abdomen, a few prodromal symptoms of respiratory infection, accounting for about 10% ~ 15%, the prodromal period lasted about 3 to 16 days (average 7 days), and the mortality rate of patients without gastroenteritis prodromal symptoms was significantly higher.
After the prodromal period, after a few days or weeks of intermittent, immediately acute onset, there are serious manifestations within a few hours including hemolytic anemia, acute renal failure and bleeding tendency, the most common complaints are melena, hematemesis, no urine , oliguria or hematuria, children with pale, weak, high blood pressure accounted for 30% to 60%, nearly 25% of patients with congestive heart failure and edema, 30% to 50% of patients with hepatosplenomegaly, about 1/3 of patients have Skin ecchymosis and subcutaneous hematoma, 15% to 30% of children with jaundice.
Some symptoms vary from region to region. For example, in India, the disease often occurs after dysentery, and 60% have fever. In Argentina and Australia, central nervous system symptoms are more common in 28% to 52%, which is characterized by lethargy and abnormal personality. Convulsions, coma, hemiplegia, ataxia, etc.
According to the symptoms of suddenness and sudden appearance of hemolytic anemia, thrombocytopenia and acute renal failure are not difficult to diagnose, but should be caused by other causes of acute renal failure, glomerulonephritis, thrombocytopenia and hemolytic anemia. Identification.
The main prognosis is the degree of kidney damage, 86% to 100% have oliguria, 30% have no urine (for 4 days to several weeks), and some infants have only transient oliguria and urinary abnormalities, most patients Renal function can be completely restored, and some patients with chronic renal insufficiency and hypertension can have recurrence. The prognosis of patients with recurrence is poor.
Examine
Examination of hemolytic uremic syndrome
1, hematological changes due to acute hemolysis, hemoglobin decreased significantly, can be reduced to 30 ~ 50g / L, network red blood cells increased significantly, serum bilirubin increased, the surrounding blood picture is characterized by red blood cell morphology abnormalities, the performance of varying sizes, Polychromatic, triangular, thorn-shaped and red blood cell debris, white blood cell elevation can be seen in 85% of patients, 90% of cases have thrombocytopenia at the beginning of the disease, the average is 75 × 109 / L, mostly return to normal within 2 weeks .
2. The results of clotting factor examination are closely related to the disease stage. In the early stage, prothrombin time is prolonged, fibrinogen is decreased, fibrin degradation products are increased, and blood coagulation II, VIII, IX and X factors are reduced, but return to normal after several days. .
3, urine routine can be seen in different degrees of hematuria, red blood cell debris, 10% have gross hematuria, severe hemolysis may have hemoglobinuria, in addition, there are varying degrees of proteinuria, white blood cells and casts, renal function tests can be seen to varying degrees Metabolic acidosis, hyperkalemia and azotemia.
Diagnosis
Diagnosis and diagnosis of hemolytic uremic syndrome
Diagnosis can be based on medical history, clinical symptoms, and laboratory findings.
Hemolytic uremic syndrome should be differentiated from thrombotic thrombocytopenic purpura. Hemolytic uremic syndrome with fever and central nervous system symptoms is not easy to differentiate from thrombotic thrombocytopenic purpura. The latter central nervous system damage is more complicated than hemolytic uremic syndrome. Symptoms are more common and heavier, and kidney damage is lighter than hemolytic uremic syndrome. In addition, thrombotic thrombocytopenic purpura is mainly seen in adults, while hemolytic uremic syndrome is mainly found in children, especially infants.
In addition, it is also necessary to differentiate from immune hemolytic anemia, idiopathic thrombocytopenia, sepsis, paroxysmal nocturnal hemoglobinuria, acute glomerulonephritis, acute renal failure caused by various causes.
