Insights:

Concept of sepsis as an overwhelming infection where our body CANNOT mount a sufficient antibody response against it (usually in SPLEEN if bacteraemia). The course of damage occurs due to release of overwhelming amount of pro-inflammatory cytokines.

First it’s TNFalpha and IL-1b that kicks off sepsis. They cause pyrexia, they cause endothelial activation.

Anti-inflammatory cytokines are also released, that can cause paroxysmal immunosuppression (IL-10 and TGFbeta)

Endothelial activation releases the remaining pro-inflammatory cytokines (e.g. IL6, 12) that set in motion fluid loss and procoagulant states (thru increased TF, PAI, reduced TFPI and protein C thrombomodulin) that reduce tissue perfusion/cause infarction which results in lactic acidosis. Cytokines also directly increase gluconeogenesis and insulin resistance and kick adrenal cortex into gear.

As a side story, inflammatory cells are also recruited by other means: complement, thrombin and endothelial activation. Thrombin-mediated monocytes activation increases TF (procoagulant)

Late stage issues are directly linked to the systemic cytokines. DIC comes from the chronic procoagulant state from cytokines. Lactic acidosis comes from reduced tissue perfusion as mentioned. AKI from reduced tissue perfusion as mentioned. Freidrichson-Waterhouse syndrome of adrenal cortex from reduced perfusion as mentioned. ARDS specifically from increased permeability, mediated by cytokines acting on tight junctions.

References:

Abbas, A., Lichtman, A., Pillai, S., Baker, D. and Baker, A. (n.d.). Cellular and molecular immunology. 9th ed.

Kumar, V. (2017). Robbins basic pathology international edition. S.l. Elsevier - Health Science.