Hemolytic-uremic syndrome

The Hemolytic-uremic syndrome (Gasser's disease) is one of few got diseases meeting usually in a children's age-grade. Possibly, given syndrome covers the whole spectrum of diseases, varying from the classical self-resolved form at children of thoracal age to more terrible and often fatal thrombocytopenic thromboembolitic the purpura (Moschcowitz'disease) observed at adults. For these diseases the general triad is characteristic: acute renal insufficiency with an oliguria, a hemolitic anaemia and a thrombocytopenia. However the diseases proceeding under shelter Gasser's disease, can have also this or that degree of an arterial angiopathy, a hypertensia and a lesion a CNS, an intestine or a liver.

Though the general denominator which would bind various forms of disease or served as basis for their classification or a treatment choice, is not found yet, some of recent basic scientific achievements help to inpour into a short of the given problem.

Aetiology and pathogenesis

Damage of endothelial cells plays the central role in a pathogenesis of renal lesions, a hemolysis and a thrombocytopenia. Endothelium damage can confine capillary membranes, but artery involving is not excluded also. Such differentiation can help with more detailed classifying and forecasting, and also an explanation of the nature of the big bunch of symptoms. The mechanism of damage of an endothelium is now object of disputes and scientific researches. 5 agents are identified at least, capable to have damaging an effect on endothelial cells at Gasser's disease: an endotoxin, a neuraminidase, an estrogen - keeping contraceptives, the true cytotoxin (verotoxin) produced by some strains of an intestinal rod, and the toxin developed Shigella dysenteriae. During epidemies of the Gemolitiko-uraemic syndrome some kinds of viruses, more often an adenovirus, but without accurate communication with disease have been secured. More convincing is development of the given syndrome in patients with the infection contaminations caused Shigella, a salmonella, a cytotoxic, intestinal rod or a pneumococcus. Now the attention of explorers is concentrated on verotoxin - producing E. Coli (VTEC O157:H7) and Shigella disenteriae type1. Gasser's disease it can be observed also at the women accepting hormonal contraceptive agents, containing an estrogen, or at pregnant women. Some researches note high frequency of occurrence of the Gemolitiko-uraemic syndrome at use of ampicillin for treatment of a dysentery caused Shigella disenteriae type1.

Damage of endothelial cells affects and puts in action variety of secondary processes: local intravascular coagulation of blood, coalescing of thrombocytes and aggregation of thrombocytes. At the majority of patients become perceptible appearance of decomposition products of fibrin in circulating blood and a thrombocytopenia. Presence of circulating monomers of fibrin (specifies in proceeding intravascular coagulation) is defined at minority of patients; it is supposed, that at the majority of patients by the reference moment behind medical aid intravascular coagulation stops. Actually in all cases fibrin deposit in pots of renal glomuluses that leads to narrowing or an obliteration of a lumen of capillars, depression of a glomerular filtration rate and reduction of perfusion of renal canaliculuses with their secondary dysfunction or a necrosis is observed. The majority of patients with Gasser's disease has a thrombocytopenia which is caused both the increased consumption of thrombocytes, and reduction of the season of their life. Moreover, thrombocytes circulating in blood are defective; in them there is less than serotonin, adenosinediphosphate, betathromboglobuline ability to aggregation that assumes their attrition also is lowered. Value of these factors and development of lesions of nephroses or a CNS is not established, however at occurrence at the patient of hemorrhagic complications of a thrombocytopenia it is necessary to remember the lowered function of thrombocytes.

Other surprising fact is obvious depression of production of a prostacyclin (PGJ2) endothelial cells at some patients with Gasser's disease and members of their monogynopaediums. The prostacyclin is an endogenous inhibitor of aggregation of thrombocytes. It assumes, that some humans have a genetical defect which the Gasser's if the etiological factor causes damage of pots can lead to disease. Such mechanism can cause disease in observed family cases.

Patients with the Gemolitiko-uraemic syndrome at depression of a hematocrit to 10-15 % quickly have a hemolitic anaemia. Coombs'test, as a rule, happens negative, and osmotic resistance and enzymes of erythrocytes are in norm limens. Thus, the anaemia at them is caused, possibly, the microangiopathy leading to damage of erythrocytes during their progression on the variated capillary network. The survival rate of the cells poured with blood also is lowered. The main cause of damage of erythrocytes is the mechanical trauma that promoted in some cases by the variated antioxidatic status of erythrocytes.

At last, as show the researches carried out for last decade, at disease Gasser's in process other organs, especially a liver and a brain, and also heart and lungs, probably, owing to all the same microangiopathy discussed above are involved also. Cramps, a stupor or a coma quite often happen complication of a gemolitiko-uremic syndrome, and they cannot be explained only a hypertensia caused by renal insufficiency, or disturbance of electrolytic balance. Nevertheless pathological changes in a brain of children who have died from Gasser's disease, were nonspecific (an edema, a necrosis of cells); microthrombuses (presumably owing to damage of pots) are found only in several cases.

Diagnostic researches

Prodromal disease usually for some days or weeks precedes Gasser's disease and more often shows a diarrhoeia and vomiting. The bloody chair becomes perceptible not always, but is frequent enough. Less often disease is preceded by an infection contamination of the top or inferior respiratory tracts or a virus infection contamination. Then, before the syndrome will start to show, the short season concerning a good condition can follow. Observable symptoms vary depending on gravity of disease and involving in process of various organs. Often at the first reference to the doctor, bound to complaints to pallor or slackness of the child, the anaemia and an uremia are found. The Hemolytic-uremic syndrome can show also the abdominal symptoms feigning an acute abdomen or an ulcerative colitis, with a bloody diarrhoeia and morbidity of an abdominal wall at pressing.

Disease symptoms widely vary both at out of renal, and at renal implications. Differences in gravity of disease are bound more likely to extrarenal implications, rather than with expression and duration of renal insufficiency. At not serious patients the anaemia, a thrombocytopenia and an azotemia, at more serious - an oliguria or an anuria and a hypertensia are observed. At the most serious patients persistent cramps, a coma, pulmonary insufficiency or myocarditis signs can become perceptible also.

Differential diagnosis Gasser's disease includes a hematosepsis and urgent abdominal surgical conditions with a concomitant prerenal oliguria or an acute tubular necrosis (a torsion of intestines with an infarct, impassability of an intestine, intestine punching, a diverticulum of an ileal intestine, a mucous colic). However in blood smears at Gasser's disease the hemolysis is usually defined, and abdominal signs, as a rule, find benign character. Factors of a serious vasculitis at renal insufficiency was rarely are taped at children's age (for example, a ljupus-nephrite) and usually do not cause a thrombocytopenia.

Laboratory assessment

Includes revealing of presence of thrombocytes in a smear and definition of number of leucocytes, a coagulative profile, the maintenance of electrolytes, liver functions, measurement of level of an urea nitrogen in bloods and a creatinine, and also cultural blood analysises and a feces. It is necessary to give the special attention to revealing of pathogenic strains of an intestinal rod, in particular 0157:H7 to which the leading part is attributed: in pathogenesis Gasser's disease. At children with appreciable disturbances of psychics, cramps or the pathological changes found at neurologic research, it is possible to effect a computer tomography of a skull and a lumbar puncture for a bleeding or meningitis exception. The routine biopsy of a nephros is not shown, it is spent only in atypical cases and in need of tool research.

Treatment

Now at Gasser's disease the bolstering treatment referred on conservation of a hematocrit) in comprehensible limens, on normalisation of the maintenance of electrolytes in Serum and water balance maintenance, and also on struggle against a hypertensia and cramps is carried out. Early carrying out of a peritoneal dialysis for correction of biochemical indicators of Serum and restoration of volume of blood reduces a mortality, seriously ill patients from 77 % to less than 10 %.

Routine continuous monitoring in intensive care unit includes the control over an electrocardiogram. For the control over intravascular volume and serial reception of blood samples for laboratory analysises establish expediently use of an endarterial catheter is central a venous catheter At patients with a labile (transitional) hypertensia. The catheter for urine deducing allows to carry out exact quantitative definition of a diuresis and a creatinine clearance. In case of an anuria this catheter delete in view of risk of a becoming infected.

Quantity of the fluids which are not containing sodium or a potassium, confine to the volume necessary for compensation of insensible losses of water (300 ml/m2 a day) plus its loss with urine and excrements. Other kinds of bolstering treatment, have the purpose the control over a hyperkalemia, a hypertensia and cramps if they arise. A hyperpotassemia if it is not an urgent condition, it is possible to treat by means of cation-exchange resins; the glucose, insulin and calcium Sodium chloridum are used at an emergency treatment. At not considerably expressed or moderate hypertensia treatment begin with a dialysis for reduction of intravascular volume; if symptoms remain, prescribe vasodilators. For the prevention of a tachycardia and rising of efficacyy of treatment it is possible to add beta-blocker, such as a propranolol. A serious hypertensia is better it is treated by means of continuous infusion of Sodium nitroprussidum at a constant BP - monitoring with use of an endarterial catheter. At conservation of a hypertensia after the terminal of an acute phase of disease it is possible to translate the patient on peroral reception of antihypertensives.

The daily control over a hematocrit and number of thrombocytes is carried out. If the hematocrit number is less than 20 %, to the patient pour erythrocyte mass. It is necessary to have near at hand a blood store on a case of subitaneous depression of hematocrit number as a result of a hemolysis or a bleeding. Transfusion of thrombocytes is effected at definition of their number below 20,0*109/l or in the presence of clinical signs of a bleeding.

Intercommunicated about application of anticoagulant therapy by a heparin or antithrombocyte with agents, and also fibrinolitic therapy by Streptokinasa, however the number of prospective controllable researches of their efficacyy while is insignificant. Anticoagulant therapy, does not give immediate antithrombotic effect, but is capable to render long beneficial effect on a hypertensia and a proteinuria in serious cases at the combined appointment of a heparin and Streptokinasa. However anticoagulant therapy is interfaced to a great risk of hemorrhagic complications; at the majority of children recover comes without its application.

Not numerous literary data do not allow to state a definitive assessment of efficacyy of a plasmapheresis at treatment Gasser's disease. It is described only two cases of such treatment; in one of them creatinine level in blood serum has started to decrease even to plasmapheresis carrying out for 14th day of disease. Efficacyy of a repeated plasma transfusion estimated also at treatment Gasser's disease at 10 children and 7 adults. Absence of data about carrying out of researches in control bunch complicates interpreting of the received results; as a whole the outcome of the disease was not better usually observed at standard treatment. At 2 sick (13 %,) as a result of transfusion the serumal hepatitis has educed. Risk degree in relation to efficacyy of a routine plasma transfusion, apparently, is too high, that does not allow to recommend repeated plasma transfusions to patients with not complicated Gasser's disease. The positive role of a plasmapheresis or plasma transfusion in treatment of specially culled patients with a relapsing gemolitiko-uremic syndrome or with obvious signs of disturbance of synthesis of a prostacyclin is more definitely established.

The forecast

On the basis of existing clinicopathologic correlations it is possible to secure subgroups of forms of a gemolitiko-uremic syndrome that helps the doctor with a choice of treatment and outcome forecasting. Classical form Gasser's disease, observed at small patients, shows mainly a lesion of renal glomuluses and has the good forecast (tab. 1).

Table 1. Forecast Hemolytic-uremic syndrome at different forms of disease.

At children of the senior age-grade and at adults the big expression of an arterial angiopathy, more serious hypertensia and involving of many organs become perceptible; on the average at them above a lethality and frequency of the remote consequences. Besides an age factor, unfavorable prognostic signs are absence of such harbinger, as a diarrhoeia, the recuring of disease and definition of its hereditary form. In other words, the forecast is worse when observable implications of disease disperse from its classical description. On the inverse extremity of a spectrum of forms of a gemolitiko-uremic syndrome there is a Moschcowitz'disease (thrombotic thrombocytopenic purpura), often fatal disease with more serious neurologic involving and less expressed disease of nephroses.

Though the serious lesion a CNS is a bad prognostic sign, at the patients who have persisted after an acute stage of disease, weakening of symptoms from the party a CNS can be observed. Has intercommunicated about 5 cases of recover of children after the long coma which have complicated flow Gasser's disease. As show the given autopsies, at the patients who have died after acute stage Gasser's disease, microemboluses are not found neither in a brain, nor in other organs, except nephroses; whereas at children who have died during an acute phase, presence of microthrombuses is usually defined in many organs. It assumes, that histological changes out of nephroses are resolved in due course.

The long-term forecast at Gasser's disease, apparently, the good. At an acute stage of disease 2 week term is critical. Necessity of carrying out of a dialysis within less than 2 weeks assumes the subsequent normalisation of function of nephroses. Necessity of continuation of a peritoneal dialysis more longly this term specifies in possible conservation

Particulate dysfunction of nephroses though irreversibility of renal insufficiency can be ascertained only in some months.