Conditions of occurrence and formation of the primary focus
The development of sepsis is impossible without a main predisposing factor — impaired immune reactivity of the host. This can include congenital defects or acquired conditions (chronic infections, alcoholism, oncology, cytostatic therapy).
The disease begins with microbial invasion through damaged integument, translocation from the gastrointestinal tract, or via iatrogenic routes (such as catheterization). In response to the invasion, innate immune cells (macrophages, T cells) recognize the pathogen via receptors and trigger a local inflammatory response. Normally, a purulent focus forms, maintaining a balance of pro-inflammatory and anti-inflammatory cytokines to localize the infection.
Barrier breakthrough and generalization
If the local inflammatory response is inadequate and the phagocytic system fails, the primary barrier is breached. A massive release of bacteria, their toxins, and cytokines enters the bloodstream.
Intensive microbial multiplication in the blood (bacteremia) and fibrin microthrombi begins, leading to hematogenous dissemination. Secondary septic-pyemic foci (e.g., purulent pleurisy, lung abscesses) form in various internal organs.
Systemic inflammatory response (SIRS) and shock
The key pathogenetic link is the mediator storm. Macrophages and endothelial cells overproduce pro-inflammatory cytokines (TNF, IL-6, IL-8), nitric oxide, histamine, and other mediators. Systemic inflammatory response syndrome (SIRS) develops.
This process leads to catastrophic hemodynamic consequences:
- Endothelial damage: triggers massive systemic vasodilation and increased capillary permeability.
- Circulatory disturbance: circulating blood volume (CBV) drops sharply, leading to hypotension and interstitial edema.
- Coagulopathy and hypoxia: the coagulation cascade is activated, leading to DIC. Tissues experience an acute oxygen shortage, switching to anaerobic metabolism.
Ultimately, tissue ischemia and the accumulation of toxic metabolic products (lactate, creatinine) lead to multiple organ dysfunction syndrome (MODS) and septic shock, which carry a high risk of mortality.
Development of immunoparalysis (CARS)
Approximately 48 hours after the onset of the massive pro-inflammatory mediator release, the body attempts to compensate. The compensatory anti-inflammatory response syndrome (CARS), mediated by IL-4, IL-10, and IL-13, is triggered.
If CARS is excessively pronounced, the stage of immunoparalysis ensues. The immune system completely loses its ability to resist bacterial aggression. Clinically, this manifests as chronic wound infection, a complete lack of tissue repair in purulent foci, and secondary nosocomial mixed infections.
Pathogenic features across different pathogens
Although the general pattern of sepsis development is universal, different groups of microorganisms exhibit distinct pathogenetic nuances:
- Gram-negative bacteria: initiate sepsis via the release of endotoxin (lipopolysaccharide) upon microbial death. The process starts very acutely, progresses aggressively, and is accompanied by early multiple organ dysfunction.
- Gram-positive bacteria: the cell wall (peptidoglycan) interacts with immune cell receptors, triggering the alternative complement pathway. Such sepsis develops more gradually, tends toward a progredient course, and frequently forms abscesses.
- Fungi: generalized fungal infections (e.g., Candida albicans, Cryptococcus neoformans) rarely present with a classic SIRS picture on their own, as most fungi do not secrete potent toxins. Severe clinical manifestations arise primarily upon the addition of secondary bacterial flora.
Briefly: answers to topical questions
What is the mechanism of DIC development in sepsis?
The mechanism of DIC in sepsis is associated with microcirculatory disorders and activation of the coagulation cascade. The acute form of the syndrome occurs upon the massive release of thromboplastic substances into the bloodstream. Pathogenetically, there is a rapid alternation of the initial stages of DIC without proper activation of protective and adaptive hemostatic mechanisms. First, the function of natural coagulation inhibitors, such as antithrombin III, α1-antitrypsin, and α2-macroglobulin, is impaired. Subsequently, due to the massive influx of tissue factors, hemodynamic shock develops, followed by massive bleeding and consumption coagulopathy.
What laboratory biomarkers are used to confirm bacterial sepsis?
Laboratory evaluation of suspected bacterial sepsis relies on markers of inflammation and infection:
- Procalcitonin: positive procalcitonin test — 10 ng/L or more; a criterion of plasma procalcitonin exceeding the norm by more than 2 standard deviations is also indicated.
- C-reactive protein (CRP): exceeding the norm by more than 2 standard deviations.
- Presepsis (P-SEP): indicated as a novel marker of the infectious process.
- Neutrophil CD64: indicated as a novel marker of the infectious process.
To memorize the stages of pathogenesis, use the logical chain: Focus $\rightarrow$ Breach $\rightarrow$ Storm $\rightarrow$ Shock $\rightarrow$ Paralysis. (Primary focus $\rightarrow$ bacterial entry into the blood $\rightarrow$ cytokine storm and SIRS $\rightarrow$ hypoperfusion and septic shock $\rightarrow$ compensatory immunoparalysis).
Class and exam questions
Why cannot sepsis resolve on its own?
Unlike cyclic infections, sepsis does not induce protective immunity. Due to immunoparalysis and the cascading nature of hemodynamic disorders, the body is incapable of self-healing.
Can viruses be an independent cause of sepsis?
No. Strict intracellular parasites (viruses) possess a strict tissue tropism and cause sepsis exclusively as part of a mixed infection when a bacterial agent is added.
What is the morphological specificity of sepsis?
Sepsis lacks a specific morphological substrate. The autopsy picture consists of non-specific signs of severe intoxication, tissue suppression, and multiple organ microthrombosis.
What else to study on this topic
- Mechanisms of bacterial biofilm formation and their role in resistance
- Generalized fungal infection: pathogenesis of candidal septicopyemia
- Nosocomial infections (HAIs) and multi-resistant hospital strains
- Particularly dangerous infections (plague, anthrax) presenting as sepsis
- Pathogenesis of anaerobic sepsis and the role of staphylococci in preparing the focus
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Other topics in the section "Infections of the Integumentary System and Sepsis"
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