Ascites due to cirrhosis

Runyon BA. American Association for the Study of Liver Diseases (AASLD) Practice Guideline Management of adult patients with ascites due to cirrhosis. Hepatology 2004 39 841-856. 

Of 12 patients with ascites due to cirrhosis of the liver, who received subcutaneous octreotide 300 micrograms bd for 11 days, 11 had increased renal plasma flow and 10 had a reduced GFR (44). Creatinine concentrations did not change. The effects of octreotide on the kidneys have been variably reported in previous studies. In patients with cirrhosis the effects are likely to be affected by the activated renin-angiotensin-aldosterone system. 

Applefeld, J.J., Kasmer, R.J., Hak, L.J., Dukes, G.E., Wermeling, D.P., McClain, C.J. A dose-response study of orally administered torasem-ide in patients with ascites due to cirrhosis. Ahment. Pharm. Therap. 1994 8 397-402... 

Indications 1) Suspended rheum and 2) replete water. Tuberculous exudative pleurisy, rheumatic pleurisy, ascites due to cirrhosis, schistosomiasis, nephritis, or uremia from systemic lupus erythematosus. 

It has been used effeetively in the treatment of oedema and ascites in cardiac failure and also in ascites due to cirrhosis of the liver. The procaine component helps in reducing the discomfort of local irritation which may he caused hy the mercurial compound when injected into tissues. 

Mersalyl is used to increase the output ofoedemafluid in such typical conditions as renal disease, heart failure etc. It is also employed in the treatment of nephrotic oedema and in ascites due to cirrhosis of the liver. 

Ethacrynic acid is normally used in the treatment of fluid retensive conditions due to congestive heart failure, cirrhosis of the liver, renal disease, and the nephrotic syndrome. It is invariably employed for the control and management of ascites due to lymphoedema, idiopathic oedema and malignancy. It is also recommended through i.v in an emergency situation of acute pulmonary oedema. 

In another study in 7 patients with ascites due to liver cirrhosis, pre-treatment with two doses of aspirin 900 mg reduced the natriuretic effect of spironolactone 300 mg daily by 33%. However, there was no significant change in urinary output. ... 

Prevention of infection caused by hematogenous dissemination of endogenous flora due to the underlying immune status of patients, e.g. prolonged neutropenia, (functional) splenectomy, cirrhosis of the liver with ascites. 

Portal hypertension most commonly occurs as a consequence of chronic liver disease. Portal hypertension Is caused by Increased blood flow within the portal venous system and increased resistance to portal flow within the liver. Splanchnic blood flow is increased in patients with cirrhosis due to low arteriolar resistance that is mediated by increased circulating vasodilators and decreased vascular sensitivity to vasoconstrictors. Intrahepatic vascular resistance is increased in cirrhosis due to fixed fibrosis within the spaces of Disse and hepatic veins as well as reversible vasoconstriction of hepatic sinusoids and venules. Among the consequences of portal hypertension are ascites, hepatic encephalopathy, and the development of portosystemic collaterals—especially gastric or esophageal varices. Varices can rupture, leading to massive upper gastrointestinal bleeding. 

It is difficult to obtain an accurate measure of renal function in patients with cirrhosis. A number of studies have shown that they tend to have low serum creatinine levels. This has been explained by a reduced muscle mass in cirrhotic patients and a reduced conversion of creatine to creatinine [10]. The calculation of creatinine clearance using the Cockcroft and Gault formula is also inaccurate in predicting GFR in these patients because it uses the serum creatinine level (which may be falsely low) and body weight in the calculation, which is likely to be inflated due to the presence of ascites [12]. The measured creatinine clearance, based on urinary excretion of creatinine, should theoretically be more accurate, even in patients with reduced muscle mass or impaired creatinine synthesis. However, it has been shown that this also overestimates the GFR because of an increased fractional tubular secretion of creatinine in cirrhotic patients, particularly those with reduced GFR [10]. 

About 50% of patients with cirrhosis develop ascites within 10 years of diagnosis and 50% of these will die within 2 years. The process by which ascites forms in cirrhosis is not fully understood but appears to involve the accumulation of vasodilator substances, activation of the renin-angiotensin-aldosterone system (causing renal retention of sodium and water), and the production of antidiuretic hormone (causing hyponatraemia due to dilution, not deficiency, of plasma sodium). 

Fig. 6.6 Liver cirrhosis with ascites (longitudinal section) the left lobe of liver is rounded and pluinp intrahepatic vessels are reduced. Irregular and inhomogeneous structure. Clear undulatory limitation (arrow) on the underside due to nodular transformation. Wide hypoechoic fringe due to ascites...

Reduction in colloidosmotic pressure The colloidosmotic pressure in the plasma is lower in hver cirrhosis patients. This results from (1.) restriction in the synthesis of albumin (which is, however, only clinicaUy manifest after 3 or 4 weeks due to the half-life of plasma albumin), (2.) greater loss of protein-rich fluid in the abdominal cavity, and (3.) dilution of the vascular volume. A critical concentration of albumin in the plasma is deemed to be about 3 g/100 ml (ca. 435 pmol/1). Below this albumin value, there is a clear correlation between portal hypertension and the formation of ascites. The coexistence of portal hypertension and hypalbuminaemia (critical concentration 2.5—3.0 gldl) is an important prerequisite for the formation of ascites. 

An increase in the retention of sodium occurs in the early stages of severe liver disease, particularly in liver cirrhosis, without any disruption of the water balance. This early tendency towards sodium retention can be detected using the NaCl-tolerance test. The retention of sodium reduces the sodium excretion rate in the urine to < 10 mval/day (normal rate 120 to 220 mval/day). Diuresis is not primarily restricted patients with ascites and oedema react to an excessive intake of water with an adequate excretion of diluted urine, albeit in the virtual absence of sodium excretion. The limited sodium excretion derives from increased, mainly proximal tubular reabsorption of sodium and not from diminished glomerular filtration. Overall maintenance of the liver architecture is usually accompanied by undisturbed sodium excretion, despite existing portal hypertension (such as in primary biliary cirrhosis). Marked sodium retention is, however, usually found in alcoholic-toxic cirrhosis. For this reason, such patients are not only the ones most frequently affected by ascites and oedema, but as a rule they display the most serious forms. This is probably also due to additional biochemical and hormonal factors which are present to a greater degree in patients with alcohol-related liver disease. 

Spironolactone has been used as a potassium-sparing diuretic in cardiac failure and in the management of ascites and edema associated with hepatic cirrhosis with secondary hyperaldosteronism. It is also used to treat hyperaldosteronism due to adrenal tumors or adrenal hyperplasia. It has a weak positive inotropic effect and a modest antihypertensive effect, in keeping with its natriuretic action. 

Triamterene blocks dihydrofolate reductase and can cause folate deficiency with megaloblastic anemia and pancytopenia, particularly in patients with hepatic cirrhosis, who have reduced clearance of the drug (SED-11, 431). When this has been reported, all patients were taking doses of 150-600 mg/day for ascites and all had hepatic cirrhosis, often due to alcohol abuse (SEDA-17, 269). It is advisable to use spironolactone rather than triamterene in patients with cirrhosis. 

The hepatorenal syndrome is characterized by acute renal failure in the setting of advanced cirrhosis, sometimes with ascites. The diminution in renal function is felt to be due to marked vasoconstriction without any structural abnormality. A variety of vasoconstrictor substances have been implicated,... 

Three symptoms dominate the clinicopathological picture of hemochromatosis cirrhosis, diabetes, and skin pigmentation. Cirrhosis is severe and is followed by its classical complications, portal hypertension and hepatic insufficiency. The portal hypertension leads to ascites, esophageal varices, and gastrointestinal hemorrhage. The destruction of the islet is responsible for diabetes, which is sometimes severe enough to lead to death in coma if insulin therapy is not instituted. The skin acquires a marked tan, sometimes reminiscent of the color of bister. The skin discoloration is due to melanin formation rather than iron accumulation. 

Indications for transplantation include poor synthetic function, refractory ascites, subacute bacterial peritonitis, chronic encephalopathy, recurrent variceal bleeding, unacceptable quality of life, hepa-to-pulmonary syndrome, and a life expectancy of less than 18 months due to liver disease. The most common clinical conditions associated with cirrhosis requiring transplantation are chronic viral... 

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