FIGURE 3. Systemic Inflammatory Response Hypothesis.

Inflammatory mediators released from cirrhotic liver into systemic circulation reach remote organs including lung, liver and kidney causing endothelial damage and further organ injury. In addition, disruption of intercellular integrity of intestinal epithelial cells associated with cirrhosis causes bacterial invasion into circulation leading to substantial increase in circulating bacterial lipopolysaccharide (LPS). These additional inflammatory mediators elicit endothelial damages in multiple organs (worsening of cirrhosis, development of kidney and lung injury). Damaged organs release additional DAMPs leading to hemodynamic derangements which further exacerbate the systemic inflammatory response, leading to malicious aggregating cycle of inflammation, which ultimately leads to multi-organ failure. Abbreviations: DAMP, Damage Associated Molecular Pattern, IL-1, interleukin-1, TNF-α, Tumor Necrosis Factor-α, SIRS, Systemic Inflammatory Response Syndrome