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Development of ascites in cirrhosis according to the peripheral vasodilation and overfill theories 7 , 8
Increased production of locally-acting vasodilators by the endothelium
Liver cirrhosis
Portal hypertension
Vasodilation of splanchnic and peripheral arteries
Decreased cardiac and vascular sensitivity to endogenous vasoconstrictors
Sinusoidal hypertension
Decreased effective blood volume
Decreased cardiac output
Impaired lymphatic drainage
Activation of sympathetic nervous system and RAAS
Water and sodium retention
Renal vasoconstriction
Decreased glomerular filtration rate
rate of decompensated cirrhosis within one year can reach as high as 80 %. 1
Pathophysiology and clinical impact of ascites Ascites is one of the complications of portal hypertension related to cirrhosis and can manifest in decompensated cirrhosis ( stage 3 and stage 4 cirrhosis ). 2 Ascites can be classified further into three grades according to its severity . Refractory ascites is defined as an unpreventable early recurrence of ascites or ascites that cannot be resolved completely due to lack of adequate response towards sodium restriction and diuretic administration ( diuretic-resistant ascites ) or due to the occurrence of diuretic-induced complications , leading to inadequate dosing of diuretics ( diuretic-intractable ascites ) ( Table 1 ). 3 , 4
Most guidelines have reported little to no evidence about the natural progression of grade 1 ascites into grade 2 or 3 ascites , but previous evidence has shown that the presence of grade 1 ascites did not act as something that precedes grade 2 or 3 ascites in patients with liver cirrhosis . 5 By contrast , Tonon et al demonstrated a significantly higher probability of developing hepatic encephalopathy or acute-on-chronic liver failure within five years in patients with ascites grade 2 or 3 , compared with patients with ascites grade 1 . Nevertheless , no significant difference was observed between patients with ascites grade 2 or 3 and ascites grade 1 , in terms of 5-year survival rate . 6
Pathophysiology of ascites In general , there are several theories underlying the pathophysiology of ascites , including peripheral vasodilation , overfill theory , and systemic inflammatory response syndrome ( SIRS ). The primary mechanism of peripheral vasodilation theory is vascular-related , while the primary mechanism of the overfill theory is renal-related . 7 The most well-known theory is the hypothesis of splanchnic and systemic arterial vasodilation , accompanied by activated neurohormonal pathways ( see Figure 1 ). These events will eventually lead to retention of water and sodium , as well as a reduced glomerular filtration rate .
SIRS has also been considered as a critical factor in the development of ascites , even when bacterial infection does not occur . The translocation of viable pathogens ( particularly Gram-negative bacteria ) from the intestinal lumen to other organs , including mesenteric lymph nodes , has been contemplated as the possible mechanism .
Other complications Hepatorenal syndrome ( HRS ) Renal dysfunction is a common complication of liver cirrhosis . The dysfunction is mainly attributed to a disturbance in intra-renal circulation that later progresses to HRS . Not only circulatory dysfunction but also systemic inflammation have been proposed as the main driver of HRS . Activation of monocytes by pathogen-associated molecular patterns
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