**3. Pathophysiology of ascites in cirrhosis**

Ascites is one of the cardinal complications in liver cirrhosis in most patients [8]. Onset of ascites naturally connotes decompensated underlying liver cirrhosis which also signifies poor prognosis with short life expectancy [10, 17, 18]. Several factors contribute to the development of cirrhosis. The heart, for instance, plays an important role through a complex mechanism in the development of liver disease. The mechanism through which the heart and liver affect each other in the development of ascites is yet to be fully elucidated [14]. Several circulatory abnormalities observed in cirrhotic patients promulgated the peripheral arterial vasodilation hypothesis proposed in the last century [19]. The circulatory abnormalities manifest as increased cardiac output, portal hypertension, peripheral vascular resistance, arterial hypotension and splanchnic vasodilation [6, 20]. Circulatory abnormalities from cardiac disease affect circulatory volume with a resultant decrease in tissue perfusion affecting majorly the kidney functionality [21]. Earlier in the disease, renal dysfunction is less expressed; however, with disease advancement the patient may experience difficulty in sodium excretion and consequent sodium and water retention [22]. Cirrhotic ascites basically develop from failure in renal excretion of sodium [22]. Different mechanisms also play a role in ascites in cirrhosis. Intrinsic factors including arterial vasodilation affect the blood pressure hormones such as the renin-angiotensin-aldosterone system (RAAS) which stimulates sodium reabsorption from the distal nephron [22]. The sympathetic nervous system (SNS) induces renal constriction and sodium reabsorption from the tubules with ascites [23, 24]. The heart, SNS and RAAS play a synergistic role in sodium retention and development of ascites in cirrhosis.

#### **3.1 Pathogenesis of portal hypertension in ascites**

The portal vein is a major vein comprising of a group of veins which supply the visceral organs including the abdomen, pancreas, intestine, etc. These veins bifurcate into smaller vessels in the hepatic tissue. Intrinsic factors and disease conditions such as cirrhosis result in blockage of these tiny veins in the hepatic tissue increasing the blood pressure in the veins with resultant portal hypertension. Other causes of portal hypotension include portal vein thrombosis, schistosomosis, idiopathy, etc. Ascites develops in portal hypertension when the post-sinusoidal gradient is above 12 mmHg [25]. Portal hypertension elevates the hydrostatic pressure within the hepatic sinusoids permitting seepage of transudate into the peritoneal cavity [26, 27]. The extent of ascites' development is dependent on the level of hydrostatic pressure [28] and less on oncotic plasma albumin pressure [26, 29]. Signs and symptoms of portal hypertension include haematuria, dysentery, bloody vomitus due to spontaneous rupture and haemorrhage from varices, encephalopathy due to abnormal liver function and thrombocytopaenia. Factors such as abnormal increase in nitric oxide production and circulation of endogenous vasoconstriction such as catecholamines, leukotrienes and angiotensin II enhance hepatic vascular resistance and portal hypertension [30, 31].

#### *3.1.1 Pathogenesis of hepatorenal syndrome in ascites*

One of the complications of activation of RAAS and SNS in cirrhosis is the resultant renal vasoconstriction leading to decrease in renal perfusion and glomerular filtrate rate which progresses to renal impairment [21, 22, 32, 33]. In hepatorenal syndrome, there are no significant morphological changes in renal histology, while the patients largely retain normal tubular function [5, 21]. The kidney analyte and serum creatinine concentration does not increase until the glomerular filtration rate becomes markedly reduced below 40 ml/min [22]. Most patients with cirrhosis have their creatinine level below 1.2 mg/dl, and diagnosis of HRS is only made when the creatinine concentration

#### *Review on Ascites in Pets DOI: http://dx.doi.org/10.5772/intechopen.84767*

is higher than 1.5 mg/dl in the absence of other complicating aetiologies [22]. Hepatorenal syndrome manifests in two different types in cirrhotic patients. Type I HRS is a fulminating form of the disease rapidly progressing to acute renal failure often precipitated by variceal bleeding, septic infection and spontaneous bacteria peritonitis with poor prognosis of days to weeks [22]. Type 2 is a more chronic form of HRS. Most patients with this form of disease have a more stable creatinine concentration with only signs of refractory ascites due to unresponsive diuretics [34, 35].

With advancement in cirrhosis, there is also progressive increase in sodium and water reabsorption and decrease in renal blood flow and glomerular filtration [36]. Approximately 20% of cirrhotic patients with refractory ascites progress to HRS which results from severe liver and systemic circulatory dysfunction [28]. Hepatorenal syndrome results from marked overactivity of RAAS, SNS, AND and other endogenous vasoconstrictor factors which exceeds renal production of vasodilatory substances [PGE2, prostacyclin, nitric oxide]. The imbalance from renal vasodilatory mechanism and the intrinsic vasoconstrictor enhances vasoconstriction and hypoperfusion and decreases GFR with ultimate result of renal failure [22].
