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Systemic inflammatory response syndrome and sepsis

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Systemic Inflammatory Response Syndrome (CERD), or simply sepsis, is a terrible and life-threatening disease (or condition) known as blood poisoning. CVD begins as mild sepsis, but the immune response caused by an infection - most often bacteria, but sometimes viruses, parasites or fungi - can build up very quickly. [

Definition: in case of sepsis, the immune system begins to intensively fight the infection, resulting in an extensive inflammatory process throughout the body that stimulates the formation of microscopic blood clots. Microscopic blood clots begin to block small blood vessels called capillaries, weakening the flow of blood and oxygen and causing malfunctioning of vital organs (resulting in tissue death), for example: brain, heart and kidney tissues, as well as tissues of the hands, feet, fingers arms and legs. Sepsis occurs when the body's own chemicals enter the bloodstream to fight infection and initiate inflammation in the immune system throughout the body. Mild sepsis can sometimes quickly lead to another condition called “shock” or “septic shock”, causing blood pressure to drop so low that it can lead to death.

Inflammation can kill a person, not just dangerous microbes. Inflammation is the body’s natural defense against disease, necessary to fight germs, however, if the reaction is excessive, it can also lead to [your] death!

Mild sepsis begins as a “complication” of seemingly less serious infections - it develops while the body is struggling with the initial infection.

What are these simple words?

Sepsis is a general infection of the body in which the infection spreads with the blood stream. With sepsis, not a single organ is inflamed, but the whole organism.

In 70% of patients, sepsis is a complication of local inflammation: abscess, phlegmon, boils, meningitis, pneumonia, pleurisy, lymphadenitis, etc., as well as the wound process: trauma, surgery, etc. It is important to emphasize that sepsis develops when the body's defenses are depleted (immunity) as a result of a protracted primary inflammatory process. As a rule, this is due to delayed or improper treatment of the primary inflammatory process.

The causative agents of sepsis are various bacteria (staphylococci, streptococci, meningococci, pneumococci, enterococci, Escherichia coli, Salmonella, etc.) and fungi (Candida, Aspergillus, etc.).

Classification

Forms of sepsis are classified depending on the location of the primary infectious focus. Based on this feature, primary (cryptogenic, essential, idiopathic) and secondary sepsis are distinguished. In primary sepsis, the entrance gates cannot be detected. The secondary septic process is divided into:

  • pleuro-pulmonary - develops against a background of purulent lung diseases (abscessed pneumonia, pleural empyema, etc.)
  • odontogenic - due to diseases of the dentofacial system (caries, root granulomas, apical periodontitis, periostitis, periandibular phlegmon, jaw osteomyelitis)
  • tonsillogenic - occurs against the background of severe tonsillitis caused by streptococci or staphylococci
  • surgical - develops when the infection enters the bloodstream from a postoperative wound
  • obstetric and gynecological - occurs after complicated abortions and childbirth
  • urosepsis - characterized by the presence of an entrance gate in the genitourinary system (pyelonephritis, cystitis, prostatitis)
  • cutaneous - a source of infection are purulent skin diseases and damaged skin (boils, abscesses, burns, infected wounds, etc.)
  • peritoneal (including biliary, intestinal) - with localization of primary foci in the abdominal cavity
  • rhinogenic - develops due to the spread of infection from the nasal cavity and paranasal sinuses, usually with sinusitis
  • otogenic - associated with inflammatory diseases of the ear, often purulent otitis media.
  • umbilical - occurs with omphalitis in newborns

By the time of occurrence, sepsis is divided into early (occurs within 2 weeks from the appearance of the primary septic focus) and late (occurs later than a two-week period). In terms of the rate of development, sepsis can be lightning fast (with the rapid development of septic shock and the onset of death within 1-2 days), acute (lasting 4 weeks), subacute (3-4 months), recurring (lasting up to 6 months with alternating decay and exacerbations) and chronic (lasting more than a year).

Sepsis in its development passes through three phases: toxemia, septicemia and septicopyemia. The toxemia phase is characterized by the development of a systemic inflammatory response due to the onset of the spread of microbial exotoxins from the primary focus of infection, in this phase bacteremia is absent. Septicemia is marked by the dissemination of pathogens, the development of multiple secondary septic foci in the form of microthrombi in the microvasculature, and persistent bacteremia is observed. The septicopyemia phase is characterized by the formation of secondary metastatic purulent foci in the organs and bone system.

Causes of sepsis

For the development of sepsis, it is necessary that pathogenic bacteria - pathogens of infection (bacteria, viruses, fungi) enter the body. As a result of mass infection with putrefactive products of the destruction of pathogenic microorganisms and toxins, an inflammatory process occurs.

The inflammatory reaction of the body that occurs in response to the introduction of infectious agents is associated not so much with the pathogens themselves as with the state of the human immune forces. The decrease in protective forces leads to the fact that the body cannot timely localize pathogenic organisms and prevent their spread into various organs.

The following can contribute to the development of sepsis:

  • Violation of the rules of antiseptics and asepsis in the treatment of purulent wounds, as well as during surgical interventions.
  • Wrong selection of antibacterial agents in the treatment of internal inflammatory processes.
  • Immune System Disorders.

The highest likelihood of developing sepsis in people with long-term chronic diseases, in which immunity is observed against this background.

What diseases can be complicated by sepsis:

  • Osteomyelitis,
  • Burns, extensive injuries,
  • Infectious and inflammatory diseases
  • Wounds and ulcers on the skin,
  • Pneumonia, purulent formations in the lungs,
  • Severe tonsillitis,
  • Infectious and inflammatory complications after surgery,
  • Purulent otitis media
  • Peritonitis,
  • Carbuncle, boil,
  • Congenital pathologies of the immune system,
  • Infection after childbirth, miscarriage, abortion,
  • HIV infection
  • Oncological diseases.

This list is rather conditional, because sepsis can complicate any infectious and inflammatory process in the body.

For the development of sepsis, certain conditions must be met:

  1. The presence of a primary focus (source of infection) from which pathogens enter the bloodstream.
  2. The spread of pathogens with the bloodstream throughout the body.
  3. The formation of secondary foci, of which in the future pathogens will also spread throughout the body.
  4. The response of a protective system that responds to the penetration of pathogens by the inflammatory process.
  5. The inability of the body to build the necessary immune defense and respond in a timely manner to the introduction of pathogens.

To successfully treat a patient, it is first necessary to determine the “gateway” through which sepsis has entered the body, and only then activate the body’s defenses to neutralize harmful pathogens.

First signs

Patients' complaints are very diverse, but the main symptoms should be given to the following symptoms of sepsis:

  • severe chills
  • fever
  • a change in the patient’s mental state (euphoria or, on the contrary, apathy),
  • tired, blank stare
  • pallor of the skin,
  • hollow cheeks
  • hyperemia of the face,
  • profuse sweating,
  • petechial hemorrhages in the form of stripes and spots on the surface of the forearms and legs.

In addition, sepsis can occur with herpes on the lips, bleeding of the mucous membranes of the oral cavity, shortness of breath, the appearance of seals and pustules on the skin.

Symptoms of sepsis in adults

The clinical course of sepsis can be lightning fast (rapid development of manifestations within 1-2 days), acute (up to 5-7 days), subacute and chronic.

Often there are atypicality or "attrition" of its symptoms (for example, and at the height of the disease there may not be a high temperature), which is associated with a significant change in the pathogenic properties of pathogens as a result of the massive use of antibiotics. Sepsis can occur with the formation of local abscesses in various organs and tissues (infection from the primary focus) - the so-called. septicopyemia, in which the course of sepsis depends on the location of ulcers (for example, an abscess in the brain with corresponding neurological disorders), and without metastatic ulcers - the so-called. septicemia, often with a more rapid course, pronounced general symptoms.

When diagnosing, they distinguish:

  • Syndrome of a systemic inflammatory reaction. It is characterized by a change in body temperature (both upward, more than 38 ° C, and downward, below 36 ° C), heart palpitations (more than 90 beats per minute) and breathing (more than 20 breaths per minute), a change in the number of leukocytes in blood (less than 4 × 109 or more than 12 × 109 cells per liter of blood).
  • Sepsis. With the same symptoms as in the case of a systemic inflammatory syndrome, one of the known pathogens is found in one of the normally sterile tissues (blood, cerebrospinal fluid, urine ...), signs of peritonitis, pneumonia, purpura and other local inflammatory processes are detected.
  • Severe sepsis. It is characterized in the same way as usual sepsis, but with hypotension, hypoperfusion or dysfunction of individual organs.
  • Septic shock. The most serious condition, after which every second patient due to a violation of the blood supply to organs and tissues, death occurs. It is determined by the same symptoms as sepsis, when intensive resuscitation measures do not lead to normalization of blood flow and blood pressure. Other signs of septic shock include slower urine production and confusion.

In February 2016, the concepts and diagnostic criteria for sepsis were revised. The concept of a systemic inflammatory response syndrome and severe sepsis is considered irrelevant, the concepts of sepsis and septic shock are given new definitions.

For the detection and diagnosis of sepsis, the use of SOFA and qSOFA scales is recommended.

Neonatal sepsis

With the development of sepsis in newborns (the source is a purulent process in the tissues and vessels of the umbilical cord - umbilical sepsis), vomiting, diarrhea, complete abandonment of the baby from the chest, rapid weight loss, dehydration, skin lose their elasticity, become dry, sometimes earthy in color, often local suppuration in the navel, deep phlegmon and abscesses of various localization.

The sepsis factors in newborns include:

  • Infectious and inflammatory diseases in a pregnant woman (pyelonephritis, adnexitis, colpitis),
  • Signs of amnion infection (dirty water, placenta overlay),
  • Community-assisted birth
  • Infections in the puerperas (endometritis, mastitis),
  • Anhydrous period in childbirth> 6 hours.

Septic shock

The most severe complication of sepsis. The work of all organs, metabolism, blood flow is disrupted.
The highest risk of developing septic shock in elderly people with immunocompromised patients. Up to half of all patients with this complication die.

Symptoms of septic shock:

  • an increase in body temperature over 39 ° C,
  • or a decrease in body temperature below 36 ° C,
  • heart rate more than 90 beats per minute,
  • frequent breathing, shortness of breath,
  • nausea, vomiting, diarrhea,
  • urine reduction
  • significant deterioration of the patient’s condition,
  • impaired consciousness: at first the patient becomes agitated, claims that everything is in order with him, and then lethargy, lethargy,
  • thirst,
  • drop in blood pressure
  • dryness and pallor of the skin,
  • then a cold, sticky sweat occurs
  • skin hemorrhages,
  • cyanosis of the tips of the fingers, nose, lips, earlobes.

If a patient in a state of septic shock does not immediately receive medical attention, he will die.

Pulmonary embolism

Most often it is a complication of thrombophlebitis. With thromboembolism, a piece of a thrombus comes off, enters with a blood stream into the heart, and then into the pulmonary vessels. Reaching a sufficiently small vessel, a blood clot blocks it.

  • dyspnea,
  • the skin becomes pale, acquires an ash gray hue,
  • cyanosis of the tips of the fingers, nose, lips, earlobes,
  • shortness of breath, wheezing
  • a cough during which blood can flow out with sputum,
  • pain in the half of the chest,
  • drop in blood pressure
  • an increase in heart rate to 100 beats per minute,
  • severe pain behind the sternum,
  • heart rhythm disturbance,
  • dizziness, tinnitus,
  • loss of consciousness, fainting,
  • coma,
  • pain under the right rib
  • belching, nausea, vomiting.

The course of pulmonary embolism may be different. Sometimes it is not accompanied by practically no symptoms, and sometimes quickly leads to the death of the patient.

Cerebral thromboembolism

It is usually a complication of thrombophlebitis. Often occurs at night.

  • impaired consciousness, a state of stupor,
  • increased drowsiness
  • disorientation in time and space,
  • headaches, symptoms resembling meningitis,
  • disturbances in movements and sensitivity, reflexes, depending on which vessel the blood clot is stuck in, and which part of the brain was therefore deprived of oxygen.

Diagnostics

Diagnosis of sepsis is carried out using laboratory and clinical methods:

  • a general blood test allows you to identify the inflammatory picture as a whole,
  • blood culture For an accurate diagnosis, it is recommended to do multiple seeding, which allows you to take into account the life cycle of the pathogen at different stages of therapy. Blood is taken from the patient’s vein and subjected to laboratory analysis,
  • Bakseeding contained in the purulent focus,
  • biochemical blood test (taken from a vein, the analysis is performed on an empty stomach),
  • PCR method allows you to isolate the DNA of the pathogen,
  • X-ray, ultrasound, computed tomography, MRI are used to search for primary foci.

All these methods allow you to diagnose blood poisoning, including cryptogenic sepsis, and determine how to treat it.

Sepsis treatment

Sepsis is treated only in an infectious or therapeutic hospital, in the intensive care unit and intensive care. The principles of treatment are similar to the treatment of other foci of infection, but the general serious condition and risk of death are taken into account.

For the treatment of sepsis in adults, apply:

  • antibiotics at maximum doses given sensitivity, intravenously.
  • conduct an active fight against toxicosis,
  • activate their own immune system, correct disturbed vital processes.

It is necessary to create peace and isolation, a special diet is prescribed, in case of a serious condition - artificial intravenous nutrition.

It is important to remove the infection from the primary focus, the use of two or more antibiotics, sometimes in combination with hormones.

If necessary, patients receive an infusion of blood plasma, gamma globulin and glucose.

When forming secondary purulent foci, their surgical treatment is necessary - opening abscesses, removing pus and washing the wounds, excising the affected areas.

Prevention

Prevention of sepsis is based on the correct and timely treatment of local purulent processes and compliance with aseptic conditions during operations and other medical procedures.

The prevention of sepsis can also include the competent use of antibacterial agents. It should be understood that any bacteria and fungi can develop resistance to drugs. The stronger antibiotics we use, the stronger and “smarter” our opponents become. The use of antibiotics of the latest generations without appropriate indications deprives us of the means of struggle in really serious situations when these drugs could save lives. Any antibiotics should be used strictly as prescribed by your doctor.

The main content of modern concepts of inflammation

Inflammation has an adaptive character, due to the reaction of the body's defense mechanisms to local damage. The classic signs of local inflammation - hyperemia, local temperature increase, edema, pain - are associated with:

  • morphological and functional rearrangement of endotheliocytes of postcapillary venules,
  • coagulation of blood in postcapillary venules,
  • adhesion and transendothelial migration of leukocytes,
  • complement activation,
  • kininogenesis
  • expansion of arterioles,
  • degranulation of mast cells.

Особое место среди медиаторов воспаления занимает цитокиновая сеть, контролирующая процессы реализации иммунной и воспалительной реактивности Главные продуценты цитокинов - Т-клетки и активированные макрофаги, а также, в той или иной степени, другие виды лейкоцитов, эндотелиоциты посткапиллярных венул, тромбоциты и различные типы стромальных клеток. Cytokines act primarily in the focus of inflammation and in the reacting lymphoid organs, eventually performing a number of protective functions.

Mediators in small quantities are able to activate macrophages and platelets, stimulate the release of adhesion molecules from the endothelium and the production of growth hormone. The developing acute phase reaction is controlled by the pro-inflammatory mediators IL-1, IL-6, IL-8, TNF, as well as their endogenous antagonists, such as IL-4, IL-10, IL-13, soluble TNF receptors, called anti-inflammatory mediators . Under normal conditions, by maintaining a balance of relationships between pro- and anti-inflammatory mediators, prerequisites are created for healing wounds, destroying pathogenic microorganisms, and maintaining homeostasis. Systemic adaptive changes in acute inflammation include:

  • stress reactivity of the neuroendocrine system,
  • fever
  • the release of neutrophils into the circulatory bed from the vascular and bone marrow depot,
  • increased leukocytopoiesis in the bone marrow,
  • hyperproduction of acute phase proteins in the liver,
  • development of generalized forms of the immune response.

The normal concentration of key pro-inflammatory cytokines in the blood usually does not exceed 5-10 pkg / ml. With pronounced local inflammation or the failure of the mechanisms that limit its course, some of the cytokines — TNF-a, IL-1, IL-6, IL-10, TCP-beta, γ-INF — can enter the systemic circulation, exerting long-distance effects for the limits of the primary focus. In these cases, their blood content can be tens or even hundreds of times higher than normal values. With the inability of regulatory systems to maintain homeostasis, the destructive effects of cytokines and other mediators begin to dominate, which leads to impaired permeability and capillary endothelial function, triggering of DIC, the formation of distant foci of systemic inflammation, and the development of organ dysfunction. Secondary humoral factors of systemic inflammation include almost all known endogenous biologically active substances, enzymes, hormones, products and metabolic regulators (more than 200 biologically active substances in total).

The total effects provided by mediators form a systemic inflammatory response syndrome (SVR).

In its development began to distinguish three main stages

Stage 1. Local production of cytokines in response to infection

A special place among inflammatory mediators is occupied by the cytokine network, which controls the processes of realization of immune and inflammatory reactivity. The main producers of cytokines are T-cells and activated macrophages, as well as to some extent other types of leukocytes, postcapillary venule endotheliocytes (PCV), platelets and various types of stromal cells. Cytokines act priority in the focus of inflammation and on the territory of the reacting lymphoid organs, ultimately performing a number of protective functions, participating in the healing processes of wounds and protecting body cells from pathogenic microorganisms.

Stage 2. The release of a small amount of cytokines into the systemic circulation

Small numbers of mediators are able to activate macrophages, platelets, the release of adhesion molecules from the endothelium, and the production of growth hormone. The developing acute phase reaction is controlled by pro-inflammatory mediators (IL-1, IL-6, IL-8, tumor necrosis factor (TNF), etc.) and their endogenous antagonists, such as IL-4, IL-10, IL-13, soluble receptors to TNF and others, called anti-inflammatory mediators. By maintaining balance and a controlled relationship between pro- and anti-inflammatory mediators under normal conditions, prerequisites are created for healing wounds, destroying pathogenic microorganisms, and maintaining homeostasis. Systemic adaptive changes in acute inflammation include stress reactivity of the neuroendocrine system, fever, release of neutrophils into the circulation from the vascular and bone marrow depot, increased leukocytopoiesis in the bone marrow, overproduction of acute phase proteins in the liver, development of generalized forms of the immune response.

Stage 3. Generalization of the inflammatory reaction

With severe inflammation or its systemic failure, some types of cytokines TNF-a, IL-1, IL-6, IL-10, transforming growth factor ß, IFN-y (for viral infections) can penetrate into the systemic circulation, accumulate there in quantities sufficient to realize their long-distance effects. In the case of the inability of the regulatory systems to maintain homeostasis, the destructive effects of cytokines and other mediators begin to dominate, which leads to impaired permeability and function of the capillary endothelium, triggering of DIC, the formation of distant foci of systemic inflammation, and the development of mono- and multi-organ dysfunction. Apparently, any disturbances in homeostasis that can be perceived by the immune system as damaging or potentially damaging can also act as factors of systemic damage.

At this stage of SVR syndrome, from the perspective of the interaction of pro- and anti-inflammatory mediators, it is possible to conditionally separate two periods.

The first, initial - period of hyperinflammation, characterized by the release of ultra-high concentrations of pro-inflammatory cytokines, nitric oxide, which is accompanied by the development of shock and early formation of multiple organ failure syndrome (PON). However, already at the moment there is a compensatory release of anti-inflammatory cytokines, the rate of their secretion, concentration in the blood and tissues is gradually increasing with a parallel decrease in the content of inflammatory mediators. A compensatory anti-inflammatory response develops, combined with a decrease in the functional activity of immunocompetent cells — the period of “immune paralysis”. In some patients, the formation of a stable anti-inflammatory reaction is immediately recorded due to genetic determination or reactivity altered by environmental factors.

The fundamental differences between systemic inflammation and “classic” are expressed in the development of a systemic reaction to primary alteration. In this case, the pro-inflammatory mechanisms lose their protective function of localizing damage factors and themselves become the main driving force of the pathological process.

The accumulation of pro-inflammatory mediators in the blood and the resulting clinical changes are considered as SSVR. The formalization of the nature of inflammation in the form of SSVR was somewhat random, the concept of sepsis syndrome was introduced when trying to more accurately determine the group of patients with sepsis during clinical trials. The next step was decisive - working on the task of determining sepsis, the 1991 conciliation conference of the American College of Chest Physicians / Society Critical Care Medicine, starting from basic research in the field of inflammation, formulated the concept of SSVR, emphasizing its non-specificity.

Pathogenesis of sepsis

A figurative definition of the pathogenesis of sepsis was formulated by I. V. Davydovsky in the 30s of the XX century “Infectious disease is a kind of reflection of bilateral activity, it has nothing to do with either banal intoxication or the attack of an“ aggressor ”that uses poisonous substances.

The causes of infection must be sought in the physiology of the body, and not in the physiology of the microbe. ”

In the XXI century (2001), this definition was reflected in the concept of PIRO (PIRO), which involves 4 pathogenesis of sepsis. Predisposition, including various genetic factors (genetic polymorphism of Tall-like receptors, polymorphism of gene coding IL-1, TNF, CD14, etc.), the presence of concomitant diseases, immunosuppression, age factor, Infection, pathogenicity factors, localization focus, the Response of the body to the infection - CBP syndrome and Organ dysfunction.

Age, genetic factors, concomitant diseases, immunosuppressive treatment, etc.

Localization of the foci of infection

Clinical manifestations of an infectious process (such as body temperature, heart rate, leukocytosis, concentration of procalcitonin C-reactive protein)

Organ dysfunction

To assess the degree of organ dysfunction, the S0FA scale is used.

Experimental studies of the pathophysiological mechanisms of the development of sepsis at the end of the 20th century led to the conclusion that multiple organ dysfunction in sepsis is a consequence of the early and excessive production of pro-inflammatory cytokines (“excess SSVR”) in response to infection, but the failure of anticytokine therapy has cast doubt on this concept.

The “new” pathophysiological concept (“chaos theory”, J Marshall, 2000) suggests a variety of interacting pro- and anti-inflammatory mechanisms “The basis of a systemic inflammatory response is not only and not so much the action of pro- and anti-inflammatory mediators, but oscillatory multisystem interactions, a systemic inflammatory response syndrome in sepsis, it’s not a monotonous reaction, but a chaos symphony ”, but“ the determinant of sepsis severity is an imbalance in immunity and depression of all endogenous anti-infection defense mechanisms ”.

Activation of systemic inflammation in sepsis begins with the activation of macrophages. The mediator between the macrophage and the microorganism (infect) is the so-called Toll-like receptors (TLRs), each of which subtypes interacts with pathogenicity factors of a certain group of pathogens (for example, type 2 TLRs interact with peptidoglycan, lipoteichoic acid, fungal cell wall, and t d, TLR type 4 - with a lipopolysaccharide of gram-negative bacteria).

The most well-studied pathogenesis of gram-negative sepsis. The lipopolysaccharide (LPS) of the cell wall of gram-negative bacteria, when it enters the systemic circulation, binds a lipopolysaccharide-binding protein (LPS-SB), which transfers LPS to macrophage CD14 receptors, increasing the response of macrophages to LPS by 1000 times. The CD14 receptor in a complex with TLR4 and MD2 protein through a number of intermediaries activates the synthesis of nuclear factor kappa B (NFKB), which enhances the transcription of genes responsible for the synthesis of pro-inflammatory cytokines - TNF and IL-1.

Moreover, with a large amount of lipopolysaccharide in the bloodstream, “proinflammatory” mediators between LPS and macrophages play an anti-inflammatory role, modulating the immune response (“chaos theory”). Thus, LPS-SB binds excess LPS in the bloodstream, decreasing the transmission of information to macrophages, and the soluble CD14 receptor enhances the transfer of LPS bound to monocytes to lipoproteins, reducing the inflammatory response.

The ways of modulating systemic inflammation in sepsis are diverse and practically unexplored, but each of the “pro-inflammatory” units in certain situations becomes the “anti-inflammatory” unit of this “chaos”.

A non-specific factor of anti-infection protection is the activation of the complement system, in addition to the classic and alternative pathway of complement activation, a lectin pathway has been identified in recent years in which a mannose-binding lectin (MBL) binds to a microbial cell in combination with serine proteases (MBL / MASP), directly splitting SZ, non-specifically activates the complement system.

An increase in the concentration of TNF and IL-1 in the bloodstream becomes a starting point, triggering a cascade of the main links in the pathogenesis of sepsis, the activation of inducible NO synthase with an increase in nitric oxide (II) synthesis, activation of the coagulation cascade and inhibition of fibrinolysis, damage to the collagen matrix of the lungs, an increase in permeability of the endothelium and t .d.

An increase in the blood concentration of IL-1, TNF activates inducible NO synthase, which leads to an increase in the synthesis of nitric oxide (II). It is responsible for the development of organ dysfunction in sepsis due to the following effects: an increase in the release of free radicals, an increase in permeability and shunt, and a change in enzyme activity , inhibition of mitochondrial function, increased apoptosis, inhibition of leukocyte adhesion, platelet adhesion and aggregation.

TNF and IL-1, as well as the presence of chemoattractants in the lesion, lead to the migration of leukocytes to the inflammatory lesion, their synthesis of adhesion factors (integrins, selectins), secretion of proteases, free radicals, leukotrienes, endothelin, eicosanoids. This leads to damage to the endothelium, inflammation, hypercoagulation, and these effects, in turn, increase the migration of leukocytes, their adhesion and degranulation, closing the vicious circle.

For violations of the lymphocytic blood germ in SSVR, lymphopenia, "differentiation" of pro-inflammatory T-helpers 1 into anti-inflammatory T-helpers 2, and increased apoptosis are characteristic.

Violations of the hemostatic system in sepsis are also triggered by an increase in the concentration of TNF, IL-1.6 in the blood, damage to the endothelium of the capillaries with an increase in tissue factor IL-6 and tissue factor activate the external coagulation mechanism by activating factor VII, TNF inhibits natural anticoagulants (protein C, antithrombin III, etc.) and disrupts fibrinolysis [(for example, due to the activation of an inhibitor of plasminogen activator-1 (PAI-1)].

Thus, in the pathogenesis of sepsis, 3 key components of microcirculatory disorders are distinguished: an inflammatory response to infection (neutrophil adhesion to capillary endothelium, capillary leakage, endothelial damage), activation of the coagulation cascade and inhibition of fibrinolysis.

Systemic inflammatory response and organ dysfunction

Local inflammation, sepsis, severe sepsis and PON are the links of the same chain in the body's reaction to inflammation due to bacterial, viral or fungal infections. Severe sepsis and septic shock constitute a significant part of the body's SSR on infection and develop due to the progression of systemic inflammation with impaired function of organs and their systems.

In general, from the standpoint of modern knowledge, the pathogenesis of organ dysfunction includes 10 consecutive steps.

Activation of systemic inflammation

SSVR is formed against a background of bacterial, viral or fungal invasion, shock of any nature, the phenomenon of ischemia / reperfusion, massive tissue damage, and translocation of bacteria from the intestine.

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Changes in the microcirculation system

Vasodilation and increased vascular permeability. With local inflammation, the purpose of these changes is to facilitate the penetration of phagocytes to the site of damage. In the case of CB activation, a decrease in systemic vascular tone and vascular endothelial damage at a distance from the primary focus are observed.

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Reactivation of factors initiating inflammation

Tissue necrosis resulting from SV, in turn, stimulate its re-activation. The process becomes autocatalytic, self-supporting, even in conditions of radical rehabilitation of the infectious focus, or stopping bleeding, or eliminating another primary damaging factor.

Septic shock occurs as a result of excessive vasodilation, increased vascular permeability and myocardial dysfunction due to inhibition of the activity of beta and alpha myocardial adrenoreceptors (limitation of the inotropic and chronotropic reactions), depressive effect of NO on cardiomyocytes, increase in the concentration of endogenous catecholamines, but decrease in their effectiveness due to superoxidation , a decrease in the density of beta-adrenoreceptors, impaired Ca2 + transport, a decrease in the sensitivity of myofibrils to Ca2 +, progress When septic, septic shock leads to hypoperfusion of organs and tissues, PON and death.

An imbalance of the mediator cascade in sepsis leads to endothelial damage and significant hemodynamic disorders:

  • increased cardiac output
  • decrease in OPSS,
  • redistribution of organ blood flow,
  • decrease in myocardial contractility.

Septic shock occurs as a result of excessive vasodilation, increased vascular permeability and severe hypotension, progressing, it leads to hypoperfusion of organs and tissues, PON and death.

There are currently no single generally accepted criteria for organ-system dysfunction. For routine clinical practice, criteria A are most appropriate Baue et al. and SOFA.

Criteria for organ dysfunction in sepsis (2000)

FactorCharacteristic

Clinical and laboratory criteria
Systolic blood pressure 5 0 meq / l
plasma lactate content is 1 5 times higher than normal

Less than 15 points on the Glasgow scale

The SOFA (Sepsis organ failure assessment) scale allows you to quantify the severity of organ-system disorders. A zero value on the SOFA scale indicates the absence of organ dysfunction. Today, the informational significance of the SOFA scale with a minimum of component parameters has the most complete scientific confirmation, which makes it possible to use it in most domestic medical institutions.

Risk factors for the occurrence of organ systemic dysfunction:

  • elderly age,
  • severe concomitant pathology,
  • chronic alcoholism,
  • the index of severity of the general condition of APACHE-II is above 15 points,
  • genetic predisposition to rapid generalization of systemic inflammation.

Орган, стоящий в самом начале цепи патологических повреждений при сепсисе, как правило, - легкие. При тяжелом сепсисе на фоне перитонита ОПЛ возникает в среднем в 40-60% случаев, а его наиболее тяжелую форму - ОРДС - диагностируют в 25-42% случаев. Функциональная несостоятельность других органов/ систем в 83,7% случаев реализуется на фоне ОПЛ. In this regard, the most vulnerable organ, the kidney, renal dysfunction (OPD) acts as a component of PON in 94.8% of patients with severe abdominal sepsis. If oliguria is easily eliminated within 1-3 days, impaired renal excretory function of the kidney persists for a longer time.

Acute hepatic dysfunction syndrome is recorded in one third of patients with abdominal sepsis, less often in other clinical forms of sepsis. Signs of hepatic insufficiency almost always develop against the background of already existing functional insufficiency of other organs, most often joining the following combinations of multiple organ syndromes of OPL + OPD or shock + OPL + OPD.

Consciousness disorder - encephalopathy syndrome - occurs on average by the second day of sepsis and is more common in elderly and elderly patients under the existing PON syndrome. A significant role in the development of encephalopathy is played by the severity of functional organ and homeostatic disorders, the cumulative effects of arterial hypotension and hypoxemia. Unlike ARDS, the duration of consciousness disorders does not exceed 5-6 days.

In the most common form, the sequence of PON formation is as follows OPL ± SHOCK - "SPD -" Encephalopathy - "Syndrome of acute hepatic dysfunction.

The main feature of organ dysfunction in abdominal sepsis, unlike other localizations of the primary focus, is the severity of the multiple-organ syndrome and the involvement of more systems in its structure. Risk factors for septic shock:

  • elderly age,
  • severe concomitant pathology of the cardiovascular system,
  • chronic liver disease
  • ARACNE-I index> 17 points,
  • bacteremia caused by a gram-negative microorganism.

Refractory septic shock and progressive PON are the main causes of death of patients with sepsis in the acute period of the disease. An increase in the number of organs involved in the PON process increases the risk of death of the disease, and the infection process plays a leading role in the development of organ dysfunction. The development of organ dysfunction, in addition to the original one, increases the risk of death by 15-20%. The average mortality rate in sepsis deficiency in the two systems is 30-40%.

Bacteremia and sepsis

Bacteremia - the presence of a bacterial infectious agent in the systemic circulation is one of the possible, but not necessary manifestations of sepsis. In the presence of the criteria for sepsis indicated above, the absence of bacteremia should not affect the diagnosis. Even with the most scrupulous observance of the technique of blood sampling and the use of modern technologies for the detection of microorganisms in the most severe patients, the frequency of registration of bacteremia, as a rule, does not exceed 45%. The detection of microorganisms in the bloodstream in the absence of clinical and laboratory evidence of systemic inflammation syndrome in the patient should be regarded as transient bacteremia.

The clinical relevance of recording bacteremia may include:

  • confirmation of the diagnosis and determination of the etiology of the infectious process,
  • evidence of a mechanism for the development of sepsis (e.g., catheter-related infection),
  • assessment of the severity of the pathological process (for some situations, for example, in the identification of K pneumoniae, P aeruginosa),
  • substantiation of the choice of antibiotic treatment regimen,
  • evaluation of the effectiveness of treatment.

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Clio-laboratory criteria for systemic inflammation

Clinical and laboratory signs of SSVR are nonspecific, its manifestations are characterized by fairly simple diagnostic parameters:

  • body hyper or hypothermia,
  • tachypnea
  • tachycardia,
  • a change in the number of white blood cells in the blood.

The diagnosis of SSVR is based on the registration of at least two of the four clinical and laboratory parameters listed in the table.

Criteria for the diagnosis of sepsis and septic shock

System, organClinical and laboratory indicators

SSVR - the systemic reaction of the body to the effects of various strong irritants (infection trauma surgery, etc.)

Characterized by two or more of the following symptoms
body temperature> 38 C or 90 / min
respiratory rate> 20 / min or hyperventilation (PaCO2 12x10 9 / ml, or 9 / ml or immature forms> 10%

Sepsis - SSVR on the invasion of microorganisms

The presence of a focus of infection and 2 or more signs of a systemic inflammatory response syndrome

Sepsis, combined with organ dysfunction, hypotension, impaired tissue perfusion. Manifestations of the latter, in particular, increased concentration of lactate, oliguria, acute impairment of consciousness.

Severe sepsis with signs of tissue and organ hypoperfusion, arterial hypotension, which cannot be eliminated with the help of infusion therapy

Multiple organ dysfunction / insufficiency syndrome (PON)

Dysfunction in 2 or more systems

Refractory septic shock

Arterial hypotension persisting, despite adequate infusion, the use of inotropic and vasopressor support

Despite the imperfection of the SSVR criteria (low specificity), their sensitivity reaches 100%. Therefore, the main practical meaning of the diagnosis of SSVR syndrome is to identify a group of patients who are anxious for the clinician, which requires a rethinking of the treatment tactics and the proper diagnostic search necessary for timely and adequate therapy.

From a general biological standpoint, sepsis is one of the clinical forms of SSVR, where a microorganism acts as a factor initiating damage. Thus, sepsis is a pathological process, which is based on the reaction of the body in the form of generalized (systemic) inflammation to an infection of various nature (bacterial, viral, fungal).

The clinical interpretation of this view of the pathogenesis of sepsis resulted in the classification and diagnostic criteria proposed by the conciliation conference of the American College of Pulmonologists and the Society of Specialists in Critical Medicine (ASSR / BSSM).

The low specificity of the SSVR criteria has led to the development of approaches for differential diagnosis of the syndrome of infectious and non-infectious genesis. To date, the best diagnostic test for this purpose is to determine the content of procalcitonin in the blood using direct measurement or a semi-quantitative rapid test. The concentration of procalcitonin in the blood increases with the bacterial or fungal nature of sepsis

Diagnostic metrics requirements

  • be available in practice
  • objectively reflect the state of various parts of the immune system,
  • dynamically respond to changes in the clinical condition of the patient during treatment.

Laboratory tests recommended for detecting immunodeficiency in critically ill patients:

  • determination of the absolute number of lymphocytes, HLA-DR monocytes and apoptotic lymphocytes,
  • the content of immunoglobulins M, C, A in the blood,
  • phagocytic activity of neutrophils.

Criteria for the diagnosis of immunodeficiency ^

  • the absolute number of lymphocytes in the peripheral blood is less than 1.4x10 9 / l,
  • the number of HLA-DR-positive monocytes less than 20%, apoptotic lymphocytes - more than 10%,
  • a decrease in blood content of more than 1.5 times the norm (0.7-2.1 g / l) and - below the norm (9-15 g / l), the phagocytic index of neutrophils in the early stages of phagocytosis (PH 5 min - below 10%).

The calculation of the absolute number of lymphocytes in a general blood test is available in each clinic and is very informative. A decrease in lymphocytes below 1.0x10 9 / l indicates immunodeficiency. The determination of HLA-DR-positive monocytes and apoptotic lymphocytes (CD 95) is also informative, however, the method is less accessible because it is carried out using flow cytofluorimetry. The determination of the content of immunoglobulins in the blood (using test systems) and the phagocytic activity of neutrophils (latex test, microscopy) is considered quite simple. Thus, secondary immunodeficiency in the composition of PON can be diagnosed on the basis of three criteria out of five available. A significant decrease in lymphocytes (less than 1.0 × 10 9 / L) and immunoglobulins (IgM 1.5 times lower than normal and IgG lower than normal) is highly likely to indicate secondary immunodeficiency.

Determination of the concentration of cytokines in serum is not widespread in clinical practice, since none of the known mediators can be considered universal. Numerous studies show that the release of pro-inflammatory mediators is differentiated. The content of TNF-a, IL-1, 6, 8 in the blood of healthy donors is on average from 0 to 100 pkg / ml. Lethal is considered a concentration of 3000-4000 PCG / ml. The content of TNF-a is associated with early events (shock), IL-8 - with later clinical manifestations (DIC, severe hypoxia, death). A high concentration of IL-6 is characteristic of the fulminant development of septic shock and correlates with mortality. Patients with septic shock are not considered a homogeneous group by the content of cytokines. There are reports of a relationship between a stably high concentration of TNF, IL-1, interferon-a, and mortality. There may be no correlation between high cytokines and shock. With gram-negative and fungal infection, the content of granulocyte colony-stimulating factor in the blood increases. Its high concentrations are found in patients with neutropenia, and they correlate with the degree of temperature increase.

The content of acute phase proteins (procalcitonin and C-reactive protein) is associated with the degree of inflammatory response and serves to monitor during treatment. The concentration of C-reactive protein (more than 50 mg / l) with a sensitivity of 98.5% and a specificity of 45% indicates the development of sepsis. The content of procalcitonin 1.5 ng / ml or more allows you to identify sepsis, with a sensitivity of 100% and a specificity of 72%. In patients with malignant neoplasm of the esophagus, 1-3 days after esophagectomy, an increase in the concentration of C-reactive protein is noted (10-20 times,

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Pathological processClinical and laboratory characteristics