Aetiology and Pathophysiology of Ascites
Ascites is identified by the peritoneal fluid accumulation in a patient affected with the pattern of decompensated liver cirrhosis (1). The multifactorial causes of ascites include the portal hypertension, dysregulation of hormones (i.e. cytokine imbalance) as well as volume dysregulation. The development of negative intrathoracic and hemostatic pressures as well as diaphragmatic defects increases the predisposition of the patient towards acquiring ascites and associated clinical complications (1). The development of hepato-hydrothorax facilitates the drainage of ascites fluid through the peritoneal cavity. Cirrhotic patients experience the symptoms of cough and shortness of breath and the abnormal accumulation of fluid predisposes them towards acquiring the pattern of empyema, pneumonia, atelectasis and hypoxemia (1). Ascites develop gradually in the cirrhotic patients. This condition might appear painless and followed by abdominal discomfort emanating from the mechanical distension. Other causes of ascites include the pancreatic disorders, nephrosis, congestive heart failure, pyogenic peritonitis, tuberculous peritonitis and neoplasm (2). Ascites might also develop under the influence of pancreatic, gastric, colonic, breast, endometrial and ovarian carcinomas. This condition could also manifest from the pattern of constructive pericarditis that remains undiagnosed for a longer duration (2). The pattern of chronic ascites develops due to sustained impairment in the pattern of sodium excretion that leads to the abnormal accumulation of sodium ions thereby facilitating elevation in the volume of the extracellular fluid. The pathogenesis of ascites is based on the factors attributing to neurohumoral activation, peripheral arterial vasodilation and portal hypertension (3). The pattern of portal hypertension assists in elevating the hydrostatic pressure inside the hepatic sinusoids that results in the accumulation of transudates inside the peritoneal cavity. Therefore, the measurement of hydrostatic pressure indicates the quantity of ascites fluid in the affected patient. Portal hypertension develops in response to the structural alterations in the liver cells that occur in its cirrhotic state. The intensity of portal hypertension is based on the vascular resistance of the hepatic cells as well as inflow inside the portal veins. This pattern of dynamic alterations in liver cells, nodular development and hepatic fibrosis is indicative of the development of hepatic vascular resistance. The abnormal contraction of myofibroblasts and hepatic stellate cells impairs the hepatic portal pressure that is measured by the defected sinusoidal tone. Hepatic vascular resistance in the ascites patient might aggravate further under the influence of elevated concentrations of the vasoconstrictors like leukotrienes, catecholamines, angiotensin II and endothelin I (3). Cirrhotic ascites manifests with the development of hyponatremia that emanates because of arterial underfilling and systemic vasodilation (4). The reduction in mean arterial pressure and systemic vascular resistance and an elevated cardiac output lead to the development of hyperdynamic circulation in patients affected with cirrhotic ascites. The splanchnic vasodilation in ascites occurs due to an abnormal elevation in the circulating vasodilators attributing to prostacyclins, prostaglandins, platelet activating factor, substance-P, intestinal peptide, glucagon and nitric oxide (4). The multifactorial induction of nitric oxide synthase inside the endothelial cells assists in the development of portal hypertension as well as advanced cirrhosis. This induction occurs because of mechanical activation from several factors attributing to bacterial DNA, endotoxins, tumour necrosis factor – α, growth factor as well as shear stress (4). The pattern of steatohepatitis proves to be the exogenous attribute that elevates the predisposition of the affected patient in terms of developing cirrhotic ascites (5). Furthermore, the genetic risk of acquiring cirrhotic ascites exists in patients with a family history of the disease. The pattern of abnormal hepatocellular regeneration, collagen deposition, necrosis as well as inflammation leads to the transformation of the liver in terms of an elevated resistance system manifested with smooth muscle abnormality and fibrotic spectrum (5). Elevated portal pressure when exceeds above 8mmHg, leads to the formation of ascites in the cirrhotic patient. Cirrhotic patients experience an elevated risk of developing variceal haemorrhage that might lead to the establishment of hepatorenal syndrome, hepato-hydrothorax, bacterial peritonitis and hepatic encephalopathy (5). The splanchnic hypoperfusion leads to the activation of RAAS (renin-angiotensin-aldosterone system) that results in the retention of peritoneal fluid. The abnormal induction of the SNS (sympathetic nervous system), alteration in the concentration of serum sodium and vascular pressure leads to the abnormal secretion of renin near proximal nephrons that facilitates the formation of angiotensin II (from angiotensin I) in liver under the influence of ACE (angiotensin converting enzyme) (5). Angiotensin II induces the release of vasopressin and aldosterone that concomitantly increases the thirst drive as well as abnormal retention of fluid in the liver cells. The elevated volume of fluid (i.e. blood) passes through the mesenteries as well as the surface of the liver under the influence of elevated hydrostatics, hypoalbuminemia, permeability of the vascular wall as well as reduced osmotic fluid. This leads to the sustained increase in the process of fluid reabsorption through the lymphatic channels as well as the peritoneal surface. The peritoneal cavity that assimilates 25-50 ml serous fluid experiences 5-10mmHg pressure in the state of decompression (5). Retention of peritoneal fluid decreases the pattern of resistance and friction between the bowel parts that evidentially leads to serosal surface hydration. In conclusion, the sustained defects in the peritoneal surface and lymphatic system properties (under the influence of fibrotic defects and infectious as well as inflammatory manifestations) profoundly disrupt the reabsorption mechanisms in human body that evidentially leads to the development of cirrhotic ascites and associated co-morbidities (5).
Laboratory analysis of the ascites fluid is necessarily required for the systematic configuration of differential diagnoses (6). The total protein analysis is required with the objective of measuring the generation of exudate or transudate across hepatocytes as well as the peritoneal cavity. The diagnostic modality attributing to serum-ascites albumin gradient warrants administration with the objective determining the occurrence of portal hypertension (6). Tumour markers including VEGF (vascular endothelial growth factor) and LDH (lactate dehydrogenase) assist in identifying development of benign as well as malignant co-morbid conditions (6). The development of tuberculosis manifestation along with cirrhotic hepatitis requires tracking with the utilization of diagnostic modalities including adenosine deaminase and blood glucose levels (6). However, the precision of the diagnosis is based on the appropriateness of clinical correlation between the laboratory findings and patient’s symptomatology. The most significant measure warranted in evaluating the pattern of ascites attributes to abdominal paracentesis (7). This diagnostic tool is considered as a safest modality with less than 1% complication rate. Evidence-based clinical literature reveals the minimum risk of haemorrhagic manifestations in relation to the administration of paracentesis modality (7). Therefore, this intervention does not require the evaluation of platelet count and fresh frozen plasma sampling of the selected patients. The ascitic fluid assessment is based on the laboratory analysis of neutrophil count as well as the total serum protein. The ascitic fluid requires inoculation in the blood culture containers with the objective of evaluating the presence of bacterial infection of the fluid of interest (7). The protein content of the ascites fluid requires assessment for calculating the predisposition of the affected patient in terms of developing SBP (spontaneous bacterial peritonitis). The protein quantity of less than 1.5 g/dL elevates the risk of acquiring SBP and associated clinical complications (7). Patients with elevated ascitic neutrophil count (i.e. > 0.25 g/L) are diagnosed with SBP (7). Large volume abdominal paracentesis allows the withdrawal of 5 litres of peritoneal fluid in the absence of PPCI (postparacentesis colloid infusion) (8). However, the extraction and retrieval of more than five litres of ascitic fluids requires the utilization of albumin for evidentially reducing the risk of developing circulatory system complications. On an average, the patients can tolerate each abdominal paracentesis intervention for a tenure of fourteen days; however, the frequency of administration is based on several variables attributing to the tolerability of the intervention, symptomatology as well as frequency of occurrence of ascites (8). Paracentesis is a diagnostic intervention that does not promise to treat the pattern of ascites in the affected patients. However, the physician might recommend the concomitant administration of diuretic and salt-restriction approaches for challenging the recurrent accumulation of ascitic fluid inside the peritoneal cavity (8). The pattern of haemorrhagic ascites is categorized in accordance with the RBC (red blood cell) count intervention (9). Patients with exceeding RBC counts (i.e. > 50,000/μl) experience elevated risk of developing the pattern of spontaneous, hepatocellular carcinoma based, iatrogenic and traumatic ascites (9). The SAAG (Serum-Ascites Albumin Gradient) intervention assists in identifying the pattern of ascites emanating from portal hypertension (10). The SAAG value of greater than or equal to 11g/L is confirmative of the aetiology of portal hypertension. Values less than 11g/L indicate that the development of ascitic fluid is unrelated to the pattern of portal hypertension in the affected patient (10). The assessment of ascitic cytology through the laboratory evaluation of ascitic amylase, mycobacterium and PCR modalities assists in diagnosis the ascitic co-morbid states attributing to tuberculosis and pancreatitis (11). Ascitic cytological evaluation also assists in ruling out the development of cancer complications in the suspected patients (12). The evaluation of urinary sodium in ascitic patients is required in the context of evaluating the state of their diuretic responsiveness (13). The reduction in urinary sodium in patients with cirrhotic ascites reciprocally decreases their life expectancy and survival rate. Patients with reported reduction in the quantity of urinary sodium appear to exhibit a sustained decrease in their serum albumin level and elevation in the Child-Pugh score (13). These signs are indicative of the development of advanced hepatic disease in the ascitic patients. Accordingly, the physicians also require assessing the ADH (antidiuretic hormone) level of the ascites patients with the objective of identifying the frequency of their neurohormonal dysfunction that might lead to the increased renal tubular reabsorption of sodium and associated elevation in diuretic resistance (13). The elevation in ADH level hampers the physiology of excretion of free water that eventually results in the development of dilutional hyponatremia in the ascites patients. The physicians require evaluating BUN (Blood Urea Nitrogen) levels of the ascitic patients with the objective of assessing their predisposition towards acquiring the pattern of renal dysfunction (13). The BUN evaluation assists in predicting the glomerular filtration rate in ascitic patients affected with hepatic cirrhosis. The glomerular filtration rate of less than 20 ml/min is indicative of neurohormonal induction in hepatic ascites that predisposes the patient towards acquiring heopatorenal syndrome and associated adverse clinical manifestations (13). This confirms the significance of BUN assessment in terms of calculating the pattern of renal vasoconstriction and risk of developing hepatic and renal system complications in the ascitic patient (13). Abdominal ultrasonogram is a recommended diagnostic modality requiring administration in the context of confirming the pattern of cirrhotic ascites while ruling concomitantly out the development of malignant ascites (14). Ultrasound intervention assists in evaluating the thickness of the gallbladder for determining the cirrhotic aetiology of the ascites patient. The sustained increase in the gall bladder thickness is indicative of the development of portal hypertension and reduction in peripheral vascular resistance under the influence of cirrhotic ascites (14). Ultrasnography intervention evaluates the gall bladder density in cirrhotic patients with 93% accuracy (14). The physicians therefore, attain the opportunity of clinically correlating the elevation in patient’s gall bladder density with concomitant reduction in serum albumin under the influence of hepatic dysfunction that eventually leads to the development of gall bladder edema and reduction in oncotic pressure (14). CT abdominal intervention assists in evaluating the density of abdominopelvic peritoneum in the ascites patient (15). CT modality also facilitates the evaluation of bowel and gastric walls thickening with the objective of identifying any GI pathology that might co-exist with cirrhotic ascites. The assessment of serosal calcification and fibrosis on the posterior peritoneal wall, spleen and liver in the setting of gastrointestinal disorders leads to the acquisition of the diagnosis of EPS (encapsulating peritoneal sclerosis) in the ascites patients (15). CT abdominal intervention is a significant tool that facilitates the evaluation of biliary peritonitis, tuberculous peritonitis, eosinophilic peritonitis as well as vernix caseosa peritonitis in the ascites patient (15).
The pattern of malignant ascites requires administering PleurX drain as a first-line intervention for draining the ascites fluid (16). Evidence-based research literature advocates the requirement of administering 2-gm sodium on a daily basis along with oral diuretics in the context of facilitating the pattern of sodium excretion (17). Furosemide and spironolactone require administration in dosages of 20-40mg and 100-200mg per day. However, the highest allowable dosages of furosemide and spironolactone attribute to 160mg and 400mg per day (17). The patients affected with cirrhotic ascites with peripheral edema also require losing 300-500 grams of weight on a daily basis (17). The treatment modalities for refractory ascites attribute to liver transplantation, peritoneovenous shunting as well as therapeutic paracentesis (17). The treatment of SBP in cirrhotic ascites requires administering cephalosporins in the prescribed dosages. Patient’s susceptibility to antibiotics requires assessment with the objective of analysing the level of patient’s resistance against the recommended antibiotic. The preferable dose of cefotaxime in the ascites patient is 2grams-twice daily, warranting administration through intravenous route. Continuous cefotaxime therapy for a tenure of five days proves helpful in challenging the pattern of bacterial infection in the ascites patient. The therapeutic intervention for treating the hepatorenal failure in the ascites patient focuses on the enhancement of the renal and hepatic blood circulation, reduction in central hypovolemia as well as splanchnic vasodilatation. Accordingly, the vasoconstrictor medication (including Telipressin) needs intravenous administration for effectively normalizing the hepatorenal function. The recommended dosage of IV Terlipressin attributes to 1mg, requiring administration in 6-hourly intervals (3). Terlipressin needs administration in a dosage of 2mg in 4-hourly interval in case the initial intervention fails to effectively decrease the abnormal elevation in the serum creatinine level (3). Ascitic subjects of liver transplantation require the systematic administration of hemodialysis intervention in concordance with terlipressin therapy for effectively controlling the pattern of electrolyte imbalance and azotemia complications (3). The administration of aquaretics in ascitic patients is warranted with the objective of enhancing the renal circulation without disturbing the electrolytic balance (18). These drugs act as diuretics and reduce the risk of re-accumulation of fluids in the ascitic patient. The administration of human albumin proves to be the safest treatment modality because of its efficacy in terms of expanding the plasma volume and controlling the plasmatic oncotic pressure (19). Indeed human albumin reduces the predisposition of ascitic patient in terms of developing circulatory system abnormalities after experiencing kidney failure and paracentesis (19). Ascites complicated by alcoholic liver disease requires the systematic administration of glucocorticosteroids for treating the pattern of hepatic encephalopathy (20). Steroids effectively stabilize the functionality of polymorphonuclear neutrophils and reduce the production of NF-κB (nuclear factor-κB) and AP (activator protein)-1 factors (20). They effectively reduce the concentration of serum bilirubin in the ascitic patients after seven days of their consistent administration. Pentoxifylline effectively down regulates TNF-α while elevating the intracellular levels of 3′,5′ cGMP and 3′,5′ cAMP because of its phosphodiesterase inhibition property (20). This drug actively interferes with the expressions of procollagen I and profibrogenic cytokine, thereby challenging the progression of hepatorenal fibrosis in the ascites patient (20). The administration of antioxidants to the ascites patients decreases the pattern of oxidative stress, thereby generating the hepatoprotective outcomes (20).
Management Strategies (Medication, alternative treatment, counselling)
Alternative treatment interventions for cirrhotic ascites advocate the requirement of administering piper longum, purgation as well as oral lipids for the systematic acquisition of the goal-oriented therapeutic outcomes (21). The systematic administration of 60 ml of decoction of Melia azadirachta, 5 grams of Zingiber officinale and Piper longum and 15 grams of Terminalia chebula along with dietary regimen proves to reduce the pattern of peripheral edema and ascites in cirrhotic patients (21). Dietary approaches require the administration of medicated gruel, green gram soup, Solanum indicum and medicated water for achieving the therapeutic benefits (21). The concomitant administration of low sodium diet with diuretic intervention is the preliminary treatment of choice for the ascitic patients (22). The pattern of hepatic encephalopathy in ascitic patients requires administering non-absorbable disaccharides in the context of the fact that they evidentially reduce the colonic pH, thereby inducing the transformation of ammonium from ammonia (23). They also induce positive alterations in the colonic microbes in terms of facilitating the production of urease generating bacteria. Lactulose intervention facilitates the pattern of bowel management in the ascitic patients; however, it remains ineffective in generating therapeutic outcomes in the hyponatremic state (11). The enhancement of the dietary intake of the ascites patients in necessarily required for reducing the risk of developing hepatic decompensation (24). The ascitic patients affected with obesity require stabilizing their insulin resistance with the objective of reducing their predisposition towards acquiring hepatic carcinomatosis (24). Patients affected with the pattern of cirrhotic hepatitis require administering meals in short intervals for effectively stabilizing their energy metabolism as well as basal metabolic rate (24). Evidence-based research literature advocates the requirement of practising exercise approaches with the objective of improving the hepatic function of the ascitic patients (24). In the presented clinical scenario, the exercise intervention would effectively elevate patient’s peak oxygen consumption and enhance his muscle strength and volume (24). Resultantly, the patient will gain improvement in the pattern of his muscle wasting to the desirable extent. The exercise intervention will also reduce the risk of LP in terms of developing the pattern of sarcopenia with age advancement (24). In conclusion, the pattern of ascites that remains clinically undiagnosed/undetectable requires no treatment for the affected patients. However, the pattern of known ascites requires the concomitant administration of aldosterone antagonists and loop diuretics along with dietary management approaches in the context of reducing the progression and intensity of hepatic, renal and peritoneal manifestations (25). The treating physicians as well as nurse professionals require interdisciplinary collaboration with the objective of streamlining the ascites management approaches in the hospital environment (26). The reduction in risk of treatment errors warrants the systematic enhancement of the clinical knowledge of physicians, pharmacists and nurse professionals in the context of undertaking medical-decision making for the ascitic patients. Healthcare professionals also require understanding the need of administering person-centred, holistic and community based treatment interventions for the ascitic patients in the context of improving treatment outcomes. The enhancement of patients’ compliance with the treatment regimen is necessarily required to reduce the probability of occurrence of adverse disease outcomes in the population of interest. A blend of calculated therapeutic and lifestyle interventions require configuration by the medical experts for effectively reducing the burden of cirrhotic ascites in the community environment.
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