FIGURE 1
Development of ascites in cirrhosis according to the peripheral vasodilation and overfill theories 7 , 8
SIRS
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
Ascites
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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