Multiple organ failure

For the first time, multiple organ failure was described in surgical patients; later it was isolated in a separate syndrome (Baue A., 1975, 1980). In the opinion of VA Gologorgsky and co-workers. (1985), AV Konycheva (1988), J. Zahringer et al. (1985), multi-organ failure can be considered as a breakdown of the organ adaptation reaction, and the non-specific nature of the changes that occur while this is manifested in the uniformity of the disturbances, regardless of the causative etiological factor and pathological process.

[1], [2], [3]

How does multi-organ failure develop?

Multiple organ failure is accompanied by significant metabolic disturbances.

The catabolism of muscle proteins (or "autocannibalism") is especially pronounced in the terminal stage of the disease. This is due to the disruption of the utilization of conventional energy substrates - carbohydrates and fats in patients in extremely serious condition with the formation of an irreplaceable energy deficit and the development of protein-dependent energy metabolism, which is based on the activation of proteolysis and the breakdown of structural proteins of vital organs, muscle tissue.

The substances released by activated microbial and viral toxins, macrophages, mastocytes, leukocytes (leukotrienes, lysosomal enzymes, oxygen radicals, various BAS) can themselves induce cell and tissue damage. A special place in the pathogenesis of polyorganic insufficiency is given to free radical oxidation, one of the universal mechanisms of cell damage.

The material on the leading role of immune system disorders and septic processes in multiorgan insufficiency has been accumulated. Gram-negative bacteria penetrating from the gastrointestinal tract of patients into the blood and organs are of primary importance, therefore it is suggested that the gastrointestinal tract is a kind of generator of multi-organ failure.

Features of the development of multiple organ failure

General features of patients in critical condition - infection, trauma, inflammation, tissue hypoperfusion and hypermetabolism. Summary - development of multi-organ failure.

Any trauma leads to the development of multifocal pathophysiological processes. Mediators occupy a leading place in the origin of cellular damage in organs and tissues. Their release depends on the severity of injury and shock, the activation of various mediator cascades during post-traumatic (post-operative) injuries. The degree of damage that occurs during the first 24 hours after trauma affects the outcome of multiple organ failure. Inflammatory mediators - indicators of organ damage - serve to refine this prognosis.

In the case of multiple organ failure, the main importance is:

• bacterial toxins,
• mediators of inflammation,
• damage to the endothelium,
• disturbance of homeostasis,
• damage to microcirculation.

As a result of hypoxia and reperfusion, neutrophil aggregation and adhesion occur, together with activation of the endothelium. Neutrophils use their mediators oxygen radicals, myeloperoxidase, hypochlorite, proteases. They all destroy the cell membrane in the organs and tissues and exacerbate tissue hypoxia.

In the initial phase of trauma and shock, the complement system, coagulation, fibrinolysis, kallikrein-kinin system is activated. Tissue trauma activates complement on an alternative pathway, and bacteria - according to the classical and alternative. Activated complement increases the production of pro-inflammatory cytokines [TNF, IL-1, platelet activating factor (PAF)] by macrophages. Membrane-attacking complement complex (C5b-C9) causes the production of secondary mediators of inflammation of PGE2, thromboxane and leukotrienes. The concentration of SZa and C5b-C9 on the first day after injury is higher in those patients who develop multiple organ failure. The release of free radicals, proteases, histamine, C5b-C9 complex, thrombin leads to an increase in P- and L-selectin expression and enhanced adhesion of neutrophils to the endothelium, which contributes to the further increase of tissue damage and aggravates the severity of multiple organ failure.

In the initial stage of severe trauma, a large number of cells are activated which synthesize neurotransmitters that act toxicly on tissues. The result of the action of the mediators is a systemic inflammatory reaction. In many cases, systemic inflammation leads to hypoxia and damage to organ function with the development of multiple organ failure. Hypoxia and reperfusion damage cause necrosis of enterocytes and increase the permeability of the intestinal wall. In the small and large intestine (already in the early stages of shock), there is a translocation of bacteria and their toxins from the lumen of the gut into the bloodstream. Hypoxia of the intestinal wall leads to the activation of lymphoid tissue associated with the intestine. A large number of inflammatory mediators (TNF, IL-1, IL-2, IL-4, IL-6, lysozyme, histamine, diphenesin), causing vascular insufficiency, enters the systemic bloodstream. Its main reason is considered nitrogen oxide (NO). The increase in NO production occurs with hypoxia due to the induction of NO synthase in the lungs, liver, spleen and intestines. An important place in the regulation of organ blood flow is occupied by the renin-angiotensin system. Angiotensin II is a mediator that increases the overall vascular resistance and decreases mesenteric blood flow. There is a positive correlation between the content of phospholipase A2 (PLA2), the development of ARDS and lethality. Ischemic damage to the intestinal mucosa in shock is accompanied by translocation of bacteria and increased PLA2. The intestinal mucosa contains a large amount of PLA2, which is hyperactivated by organ hypoperfusion. Under the action of PLA2, proinflammatory lipids are synthesized, lysifospholipids (precursors of PAF) and arachidonic acid (a substrate for the synthesis of eicosanoids). The result is the acceleration and enhancement of tissue damage processes.

Already in the early stages of the coagulation system involved in the pathogenesis of multiple organ failure. There is activation of external and internal formation of thrombin, which stimulates the expression of P-selectins on endothelial cells, converts fibrinogen into fibrin monomer and promotes the formation of thrombi. Fibrin deposition in the lumen of the alveoli, increased vascular permeability and transudation of plasma proteins into the interstitial space of lung tissue lead to development of ARDS. The activation of coagulation along the external pathway occurs with the participation of the tissue and VII clotting factors. The tissue factor is found in many tissues, including the brain, endothelium, macrophages, interstitial pulmonary alveoli. The deposition of fibrin, combined with inhibition of fibrinolytic activity (increase in the concentration of the inhibitor of the plasminogen activator), is considered the cause of atelectasis, violation of the ratio of ventilation (perfusion), morphological damage to the alveolar structure of the lungs. Hypercoagulation promotes the development of DIC syndrome, the deposition of fibrin in the microvascular channel reduces tissue blood flow and accelerates the development of multiple organ failure. High procoagulant activity is characteristic for patients with trauma and sepsis, which causes organ dysfunction in the chain of mediator damage, especially in the lungs, the PAF is a toxic mediator leading to the development of multiple organ failure due to increased vascular permeability.

Activation of the coagulation system and inhibition of fibrinolysis cause severe organ hypoperfusion. The negative aspects of this phenomenon are corrected with the help of activated protein C. It has an anti-inflammatory, anticoagulant and abribrinolytic effect. Activated protein C degrades Va and VIlla clotting factors, which leads to a reduction in thrombogenesis and inhibition of thrombin synthesis. As a result of inhibition of the plasminogen activator inhibitor, fibrinolysis is activated. The action of activated protein C leads to the preservation of endothelial functions due to a decrease in the interaction of leukocytes and selectins on the endothelium. The synthesis of cytokines (especially TNF) by monocytes decreases. The endothelium is protected from apoptosis. Activated protein C has an anti-inflammatory effect on neutrophils and endothelial cells.

In patients in critical condition (due to severe secondary immunodeficiency), an increased susceptibility to infection is noted. There is a correlation between the patient's severe condition and the development of generalized infectious complications. The critical state of the patient is always, for objective reasons, accompanied by a large number of infectious complications. Disturbances in the immunity system in critical conditions contribute simultaneously to the onset of infection and multiple organ failure.

At the moment, the question of inclusion in the multiorgan insufficiency of the immune system deficiency (secondary immunodeficiency) is being considered.

[4], [5], [6], [7], [8], [9], [10], [11]

Symptoms of multiple organ failure

Clinical symptoms of multiple organ failure and worsening of the disease prognosis are most often caused by combined cardiovascular, respiratory, kidney and liver disorders.

There are several stages of multi-organ failure - latent, explicit, decompensated and terminal. However, timely diagnosis of multiple organ failure is very difficult: only with a special study or a retrospective analysis it turns out that even in the early stages of the disease, patients had a hidden deficiency of many organs. The late diagnosis of multiple organ failure is due not only to the varying degree of damage to individual organs and systems, but also to the insufficient sensitivity of the techniques used to evaluate their functioning.

Is the syndrome of multiple organ failure in children with infectious diseases? It can be argued that it manifests itself in the most severe forms of diseases. In children with mild forms of infectious diseases, the clinical symptoms of damage to certain organs are usually not determined. However, with the help of laboratory and instrumental tests, it is often possible to find compensated or subcompensated multi-organ failure, which can be interpreted as a polyorganic insufficiency, a readiness for total disruption of the compensatory possibilities of the organism. Timely and detailed definition of the functional state of organs and systems in the presentation of multiple organ failure, as well as the availability of reserves for their compensation would allow us to choose the optimal range of therapeutic interventions and the mode of their implementation, preventing the development of clinically apparent multiple organ failure.

With the increase in the severity of the toxic syndrome, children develop hemodynamic disorders in the skin, kidneys, liver, up to occurrence of their ischemia, circulatory blockade, found in patients with the most severe forms of toxicosis in the terminal stage of the disease. In parallel with hemodynamic disorders in the blood of children accumulate various metabolites that have toxic properties, which indicates a violation of the excretory function of the kidneys, liver and gastrointestinal tract. The accumulation of ammonia in the blood of children with toxicoses also indicates the violation of biochemical processes of detoxification in the liver, since the reaction of the transfer of toxic ammonia to a relatively harmless urea is one of the most stable in phylogenetic terms. The same can be said about the accumulation in the blood of free phenol, which in the liver binds to glucuronic or sulfuric acid and should be excreted in this form with urine. Accumulation in the blood of medium-mass peptides (normally 90% of them is excreted through the kidneys) is evidence of kidney failure. In addition, we found that the binding capacity of albumin, which is the main circulating sorbent of toxins in the blood, also sharply decreases in proportion to the severity of the toxic syndrome, the degree of toxemia.

Consequently, the retention of metabolites in the blood of children at the height of clinical manifestations of toxicosis is due not only to mechanical causes associated with the deterioration of the delivery (delivery) of toxins to their excretory organs, but also to the violation of the entire detoxification complex, including the stage of the preliminary biochemical metabolites transformation and their removal from organism. At the same time, the starting point for the development of endotoxemia in children with toxicoses is the reaction of centralization of the systemic circulation, which is the main cause of circulatory hypoxia of the organs and tissues of the child's organism. Without a doubt, a number of organs that directly participate in the regulation of the adaptation syndrome described by G. Selye (1955) have a direct effect on the implementation and maintenance of centralization of hemodynamics. These include, in particular, the hormones of the renin-angiotensin system, the adrenal glands (catecholamines, GCS, aldosterone), the pituitary (vasopressin), and a number of BASs involved in the regulation of blood circulation and affecting the permeability of the vascular wall: histamine, serotonin, kinin, etc. ., released from the depot cells due to a stressful reaction in children with severe forms of infectious diseases.

Their long-term presence in the circulating blood predetermines the same long-term preservation of centralization of blood circulation, and hence, circulatory "stealing" of the organs and tissues of the body. Apparently, at an early age, the stressful (essentially protective) reaction of the body under certain circumstances (this includes the anatomical and physiological characteristics of children, and the characteristics of the infection - its virulence) is transformed into a distress-self-deepening pathological process, which is extremely dangerous for the child in the prognostic plan.

Normally, the utilization of most hormones, BAS and metabolites occurs in the liver. In conditions of infectious pathology, increased production of these substances, combined with inhibition of liver function, leads to their accumulation and long-term preservation of high concentrations in the blood. Their pathological effect in the body is intensified due to the fact that the development of toxic syndromes in children is the inactivation of their specific inhibitors and inactivators circulating in the blood.

Consequently, in the pathogenesis of polyorganism insufficiency, which naturally develops in children with toxicosis, infectious stress, violation of systemic circulation with development of ischemia of the majority of organs and tissues of the child's organism, increasing ischemia and progressive metabolic disturbance with accumulation of metabolic products, suppression of immunity and protective possibilities biological barriers for microflora and its toxic substances, increasing the concentration of all kinds of toxins in the blood, including the micros to and their toxins as well as hormones and bioactive substances. Moreover, the retention of toxic substances in the sick child's body is caused not only by the impairment of the delivery of toxins to the excretory organs, but also by the violation of the entire detoxifying complex, including the stages of their preliminary neutralization, biochemical transformation and elimination.

The third link in the pathogenesis of multiple organ failure is apparently the formation of multiple vicious circles, the mutual burdening of which leads to an inevitable fatal outcome. As a rule, the basis of vicious circles are adaptive reactions, which eventually turn into pathological ones. Decompensation of the cardiovascular system, kidneys and (or) the liver is also the cause of the strongest long-term stimulation of the vegetative centers of the brain and the pituitary-adrenal system. The depletion of this system was discovered by us in the study of the pathogenesis of acute adrenal insufficiency in children with severe forms of OCD and meningococcal infection. The relationship between the severity of toxic syndrome and intestinal paresis, as well as the level of toxic substances (eg, PSM, accumulating in toxicoses) and functional deficiency of kidneys and liver has been revealed. Hence, with the advent of functional decompensation of even one organ of the system of detoxification and elimination, a vicious circle of endotoxin formation and further deepening of the pathological process is formed. To a certain extent, the development of polyorganism deficiency resembles a snow avalanche, involving in its movement everything that is on its way. So in the child's body: a failure in the work of one organ in a serious infectious disease affects the work of others, like a collapse.

Treatment of multiple organ failure

Thus, multi-organ failure in children with toxicosis is a self-deepening process, a variant of a vicious circle, the starting point of which most often is acute cardiovascular and renal-hepatic insufficiency. With the occurrence of multiple organ failure, the likelihood of an unfavorable outcome of the disease increases significantly. However, timely diagnosis and the right treatment tactics can reduce the adverse effects of multiple organ failure and prevent the death of the patient.

Multiple organ failure in children with toxicosis requires immediate inclusion in the complex of treatment of methods of functional support of life support systems (IVL, pacemaker, cardiotonic drugs and vasopressors), extracorporeal elimination of toxic substances (plasmapheresis, dialysis, hemofiltration, hemosorption, etc.) detoxification and elimination, which will allow the body to maintain homeostasis on its own.