Figure 1: Current Understandings of the Pathophysiology of Hepato-Renal Syndrome
Development of hepato-renal syndrome are thought to occur through the following pathophysiological events: (1) Sinusoidal obstruction due to fibrin formation from stellate cells located in space of Disse following hepatocyte injury, (2) Development of portal hypertension and increased sheer stress to the portal vessel wall leading to increased production of nitric oxide, (3) Bacterial translocation from intestinal flora to the portal circulation activates innate immune system (eg. mononuclear cell), leading to massive production of cytokines (e.g., TNF-α and IL-6) and nitric oxide leading to (4) Splanchnic vasodilation, (5) These inflammatory mediators causes systemic inflammatory response which further aggregates splanchnic vasodilation and extra-organ damage, (6) Reduction in effective blood volume due to splanchnic dilatation, (7) Activation of systemic vasoconstricting system including sympathetic nervous system and renin-angiotensin-aldosterone system, (8) renal afferent artery vasoconstriction, reduction of glomerular filtration and (8) dramatic reduction in renal function.