Etiology and risk groups
Inflammation by its very nature is always a systemic response of the body to the action of a damaging (phlogistic) agent, but it is specifically in SIRS that this principle manifests to the maximum extent. The syndrome rarely occurs in isolation; most often, it becomes a complication of severe pathological conditions.
The high-risk group includes patients with the following diagnoses:
- Sepsis.
- Diffuse peritonitis.
- Intestinal obstruction.
- Renal or hepatic failure.
- Conditions following post-ischemic organ reperfusion or large tissue masses.
Pathogenesis and mechanisms of intoxication
SIRS is underpinned by acute and severe endotoxemia. The initiating link in the pathogenesis is the failure of natural detoxification systems (liver, kidneys, lungs, skin, gastrointestinal tract) and the immunobiological surveillance system (ISS). An additional source of intoxication is toxic substances from the gastrointestinal tract (skatole, indole, phenol) that massively enter the bloodstream due to increased permeability of the intestinal wall.
Biologically active substances (BAS) rapidly accumulate in the body fluids. By origin, they are divided into four groups:
- Inflammatory mediators: cytokines, biogenic amines, lipid peroxides, prostaglandins, leukotrienes, acute-phase proteins, and enzymes.
- Normal metabolic products: urea, creatinine, bilirubin glucuronide. They accumulate due to impaired excretion against the background of renal and hepatic failure.
- Products of abnormal metabolism: ammonia (in liver failure) or ketone bodies (in concomitant diabetes mellitus).
- Tissue destruction products: compounds formed during the breakdown of cells directly in the primary site of inflammation.
An excess of these substances impacts microcirculation, provokes DIC syndrome (disseminated intravascular coagulation with widespread microthrombosis), and leads to multiple organ dysfunction syndrome (MODS). In addition, many BAS possess antigenic activity, causing allergic reactions, immunodeficiencies, pathological tolerance, and immune autoaggression reactions.
Stages of SIRS development
The process of inflammation generalization proceeds in three successive stages:
- Compensation (adaptation) stage. The body attempts to cope with the avalanche of toxins from the inflammatory focus by maximally activating detoxification systems. Concurrently, CARS (Compensatory Anti-inflammatory Response Syndrome) is initiated.
- Generalization stage. The body's reserves are depleted, and adaptation mechanisms are operating at their utmost limit.
- Decompensation (maladaptation) stage. Cleansing mechanisms finally fail. Multiple organ dysfunction syndrome rapidly progresses. While the failure of 1–2 organs is still amenable to medical correction, the failure of three vital organs turns the condition into a critical one requiring specialized life-support procedures.
Diagnostic criteria
A diagnosis of SIRS is valid if a patient exhibits at least two of the four clinical and laboratory signs:
- Body temperature: fever above 38 °C or hypothermia below 36 °C (the latter is typical for the decompensation stage).
- Tachycardia: heart rate exceeds 90 beats per minute.
- Tachypnea: respiratory rate greater than 20 breaths per minute, accompanied by hypocapnia (PaCO₂ dropping below 32 mmHg).
- Changes in the complete blood count (leukocyte formula): marked leukocytosis (> 12×10⁹/L), leukopenia (< 4×10⁹/L at the decompensation stage), or a shift to the left (band neutrophil percentage exceeds 10%).
Principles of treatment
Therapy for the systemic inflammatory response is built upon three basic principles:
- Etiotropic principle: aimed at eliminating or reducing the strength of the phlogistic factor's impact. A classic example is the use of antibiotics or sulfonamides to destroy infectious agents.
- Pathogenetic principle: the goal is to break the key links in the mechanism of inflammation development. The action is aimed at blocking the processes of alteration (damage) and exudation (e.g., using antihistamines). Simultaneously, general and local mechanisms of adaptation are stimulated: compensation, regeneration, tissue protection and restoration.
- Symptomatic therapy: necessary to prevent or eliminate distressing symptoms that exacerbate the patient's condition. Pain relievers, tranquilizers, anti-stress drugs, and substances helping to normalize the functions of physiological systems are used.
Briefly: answers to topical questions
Which specific cytokines initiate SIRS?
Sources indicate that for SIRS, the main triggering mechanism is an acute and significant increase in the concentration of inflammatory mediators, including cytokines. In the description of the systemic reaction cascade in sepsis, the following cytokines are named among the mediators secreted by macrophages:
- Tumor necrosis factor-alpha (TNFα).
- Gamma-interferon (γ-interferon).
- Interleukin-1 (IL-1).
- Interleukin-6 (IL-6).
An excess of TNFα and IL-1 disrupts thermoregulation and autonomic control, causing fever, tachycardia, and tachypnea. High concentrations of IL-6 exert a direct damaging, depressive effect on the myocardium.
What markers are used for early laboratory diagnosis of sepsis and SIRS (aside from basic criteria)?
The cited sources explicitly name the following for the laboratory diagnosis of sepsis:
- Procalcitonin — an elevation of this marker is a sign of bacterial flora accession; a level > 0.5 µg/L indicates a high risk and probable bacterial coinfection, which is important for the diagnosis and prognosis of sepsis.
- Blood culture — performed three times at the peak of fever; indicated as a test for diagnosing infective endocarditis/sepsis.
For SIRS, diagnostic criteria are provided in the sources, but separate additional early laboratory markers of SIRS, aside from these criteria, are not specified.
What is the mechanism of DIC syndrome development in SIRS?
The development of DIC syndrome in SIRS is caused by endothelial dysfunction and generalized activation of the hemostasis system. The mechanism includes the following main links:
- Endothelial injury — inflammatory mediators (PAF, prostaglandin E2, NO) damage capillary endothelium, triggering intravascular coagulation.
- Activation of procoagulants — occurs simultaneously via the extrinsic and intrinsic pathways.
- Activation of the cellular link — a reaction releasing procoagulants and proaggregants.
As a result, progressive consumption of hemostatic factors occurs (consumption coagulopathy), systemic hypercoagulation develops with the formation of excess fibrin monomer and microthrombi.
The four "T" rule for SIRS criteria: Temperature (fever/chills), Tachycardia (pulse >90), Tachypnea (shortness of breath >20), and Tissue of white cells (leukocytes up/down or a shift).
Class and exam questions
How does SIRS differ from regular inflammation?
Conventional inflammation proceeds predominantly as a local process. SIRS occurs when inflammatory mediators and toxins break into the systemic circulation in huge quantities, causing a generalized reaction of the entire body.
Why might SIRS present with hypothermia instead of fever?
A drop in temperature below 36 °C, as well as a sharp decrease in leukocyte levels (leukopenia), is characteristic of the terminal stage of decompensation. This indicates that the body's adaptive reserves are completely depleted.
What is CARS and when does it occur?
This is the Compensatory Anti-inflammatory Response Syndrome (CARS). It is initiated at the first stage of SIRS as the body's attempt to contain systemic inflammation and protect its own tissues from damage.
What else to study on this topic
- Mechanisms of DIC syndrome development in systemic inflammation.
- Pathogenesis of multiple organ dysfunction syndrome (MODS) and prognostic scales.
- The role of the immunobiological surveillance system (ISS) in the body's detoxification.
- Immunopathological reactions in SIRS: from allergy to autoaggression.
- Impact of intestinal wall permeability on the level of endotoxemia.
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