Clinical meaning
Sepsis pathogenesis involves a dual-phase immune response. The initial hyperinflammatory phase features activation of pattern recognition receptors (TLRs, NOD-like receptors) by PAMPs, triggering NF-κB-mediated cytokine release (TNF-alpha, IL-1β, IL-6). This cascade activates the complement system, coagulation cascade (tissue factor pathway), and endothelial dysfunction. Nitric oxide overproduction causes refractory vasodilation. Glycocalyx degradation increases capillary permeability. Subsequently, an immunosuppressive phase (immune paralysis) develops with lymphocyte apoptosis, monocyte deactivation, and increased susceptibility to secondary infections. Organ dysfunction is quantified by the SOFA score: a ≥2-point increase identifies sepsis. Septic shock is sepsis with vasopressor requirement to maintain MAP ≥65 and lactate >2 despite adequate fluid resuscitation. The clinician orders the initial resuscitation protocol, prescribes empiric antimicrobials, initiates vasopressor therapy, identifies and controls the infectious source, and manages multi-organ support.
Diagnosis & workup
Diagnostics & workup: - Order sepsis panel: CBC/diff, CMP, lactate, procalcitonin, blood cultures x2, coagulation studies - Order organ-specific biomarkers: troponin (myocardial dysfunction), lipase, hepatic panel - Calculate SOFA score: PaO2/FiO2 ratio, platelet count, bilirubin, MAP/vasopressors, GCS, creatinine/UOP - Order source-directed imaging: CT abdomen/pelvis with contrast, chest X-ray, ultrasound - Obtain procalcitonin trending: >0.5 strongly suggests bacterial infection; useful for antibiotic de-escalation - Order DIC panel if coagulopathy suspected: fibrinogen, D-dimer, PT/INR, peripheral smear for schistocytes - Consider echocardiogram to assess for sepsis-induced cardiomyopathy (new LV dysfunction) - Calculate predicted fluid responsiveness: pulse pressure variation, IVC ultrasound, passive leg raise