Exudate with ascites

Synonyms

Proteinaceous ascites; proteinaceous peritoneal effusion;

First author

Richard W. Licht et al. were the first to publish the diagnostic distinction between transudate and exudate by the so-called Light criteria in 1972 (Licht 1972).

Hepatorenal syndrome (HRS), a complication of ascites, was first described by Frerichs in 1861 and Flint 2 years later as a coincidence of liver and kidney failure (Wolf 2000).

Ascites is said to occur when a serous fluid accumulates in the free peritoneal cavity (Herold 2022), the quantity of which exceeds the 50-75 ml normally present in the peritoneal cavity (Rudralingram 2017).

Ascites may be an exudate or a transudate. Differentiation between the two is important as they are caused by different diseases. This can be assessed by biochemical tests (see Laboratory) and other criteria (see Diagnostics). However, it is not always possible to clearly differentiate between the two (Herold 2022).

Ascites is differentiated between exudate and transudate (Rudralingam 2016).

It is also differentiated by the "International Ascites Club" (Riemann 2008) - depending on the severity of ascites - between:

• Stage I / Grade 1:

In this case, the amount of ascites is small (Buchta 2004) and can be detected exclusively by imaging such as sonography (Riemann 2008).

• Stage II / Grade 2:

This is moderate ascites, but already leads to symmetrical distention of the abdomen (Riemann 2008).

• Stage III / Grade 3:

Here, a pronounced ascites is found, which leads to a clear distension of the abdomen (Riemann 2008).

The most frequently affected by ascites are patients with liver cirrhosis with approx. 80 %, followed by malignancies with approx. 10 % (Wiest 2006).

Infected ascites develops in 10 - 20 % of patients with ascites (Wiest 2006).

• Exudate:

In exudate, the peritoneum itself is diseased (Braun 2018). Ascites is formed secondarily in e.g.:

- infections

- hemorrhages

- Neoplasms (12%)

(Rudralingam 2017 / Hirner 2004)

- pancreatogenic ascites in e.g. pancreatitis 1 %, pancreatic fistulas, pancreatic pseudocysts (Riemann 2008)

- Other causes such as nephrotic syndrome, collagenoses, hypothyroidism, peritoneal tuberculosis, benign ovarian tumor (Hirner 2004).

• Transsudate:

In transudate, the peritoneum is intact. Ascites forms due to increased hydrostatic pressure or decreased colloid osmotic pressure (Braun 2018) in e.g.:

- portal hypertension in hepatic parenchymal disease (the most common cause at 78%)

- cardiac causes such as heart failure (5%), pericarditis constrictiva, tricuspid reg urgitation (Riemann 2008)

- nephrotic syndrome (Rudralingam 2017 / Hirner 2004)

- occasionally also due to metastatic remodeling of the liver and secondary ascites (Baltzer 2000)

• Exudate:

An exudate consists of fluid and corpuscular components that leak from the vessels of the terminal stroma by secretion (Riede 2009).

• Transsudate:

Transsudate, on the other hand, results from increased capillary permeability due to a decrease in colloid osmotic pressure accompanied by an increase in hydrostatic pressure (Baltzer 2000). In this process, increased ultrafiltration takes place (Hallbach 2006).

• Ascites in malignant disease:

Here, the tumor cells lining the peritoneum produce a protein-rich fluid. This contributes to the development of ascites, as does fluid that is aspirated into the peritoneum from the extracellular space (Kasper 2015).

• Spontaneous bacterial peritonitis (SBP):

Several mechanisms are pathophysiologically significant in the development of SBP:

- Disruption of the mucosal barrier with concomitant increase in intestinal permeability.

- bacterial overgrowth of the intestine with gram-negative germs

- reduced complement-mediated and humoral defense against infections (Wiest 2006)

Ascites typically accumulates in the dependent parts of the abdominal cavity. In the supine position, these are the Morison's pit (hepato-renal fossa), the Douglas space (excavatio vesicouterina and the excavatio rectouterina [Meckler 2004]).

(Rudralingram 2017)

Patients usually first notice ascites by an increase in abdominal girth and weight gain. Patients usually report that they had previously experienced meteorism (before the rain comes the wind).

Depending on the severity of the ascites, dyspnea may occur due to diaphragmatic elevation. If abdominal wall weaknesses have previously existed, hernias filled with ascites may develop (Braun 2018). Patients also frequently complain of rapid fatigability (Riemann 2008).

Worsening renal function and the appearance of hepatic encephalopathy may be indicative of "spontaneous bacterial peritonitis (SBP)" (see also "Complications") (Hirner 2004). SBP is also associated with pain, fever, and jaundice (Wiest 2006).

• Exudate in ascites:

This must definitely be further clarified as it indicates malignancy or inflammation such as tuberculous peritonitis, sarcoidosis, bacterial peritonitis, Kaposi syndrome (Riemann 2008), nephrotic syndrome, pancreatitis, etc (Baars 2011).

• Transsudate in ascites:

Transsudate primarily indicates portal hypertension or chronic right heart failure. Therefore, diagnostic measures should first be directed in this direction (Baars 2011).

Ascites should be punctured diagnostically at:

- any hospitalization

- deterioration of renal function

- Occurrence of encephalopathy (Herold 2022).

Worsening renal function and the appearance of encephalopathy may indicate spontaneous bacterial peritonitis (SBP) (see also "Complications").

The following tests may be used to diagnose ascites:

• Ballottement:

Also referred to as a fluctuant wave. This is caused by a rocking around a solid body triggered during a shock (Rudralingram 2017).

• Sonography
• ARAER- criteria (Ascites- to- Rectus Abdominis muscle Echogenicity Ratio).
• Peritoneoscopy (see "Imaging").

Differentiation exudate / transudate is possible with determination of:

• Echogenicity ratio of ascites to rectus abdominis muscle = ARAER (Ascites-to-Rectus Abdominis muscle Echogenicity Ratio) s. Imaging: Sonography
• SAAG- value
• the Light- criteria (see "Laboratory")

• Sonography

Abdominal sonography can detect ascites from a volume of approximately 50 ml at predilection sites (Herold 2022). Using transvaginal ultrasound, amounts as small as 0.8 ml can be visualized (Rudralingram 2017).

The echogenicity ratio of ascites to rectus abdominis muscle = ARAER (Ascites-to-Rectus Abdominis muscle Echogenicity Ratio) is suitable for sonographic differentiation of whether it is an exudate or transsudate. In exudate, the ARAER is significantly higher than in transsudate. The sensitivity is 87.5% and the specificity is 79.2% (Cekic 2017).

• Peritoneoscopy

One can use peritoneoscopy to identify the causes of exudative (and transsudative) ascites. The success rate was 100% in a study by Abayli (2019), and the overall diagnostic accuracy was also 100%.

• Computed tomography

Traditionally, CT was used to detect ascites. It is now possible to image even small volumes sonographically. In the qualitative assessment of ascites, sonography is even superior to CT. Therefore, CT no longer plays a role in the detection of ascites (Rudralingram 2017).

- Biochemical evaluation of the punctate:

• An exudate is characterized by:

- turbid, cell-rich fluid (Baltzer 2000)

- specific gravity > 1.016 g / l

- protein content > 2.5 g / dl (Herold 2022)

- Serum ascites albumin gradient = SAAG ≤ 11 g / l (Chub 2018) or 1.1 g / dl (Herold 2022).

• A transudate is characterized by:

- clear, cell-poor fluid (2000)

- specific gravity < 1,016 g / l

- protein content < 2.5 g / dl (Herold 2022)

- Serum ascites albumin gradient = SAAG ≥ 11 g / l (Chub 2018) or 1.1 g / dl (Herold 2022).

The sensitivity of the SAAG- value regarding the presence of portal hypertension is 96.7%, while for the liquid protein concentration, the distinction exudate / transudate was correct only in 55.6% of cases (Chub 2018).

Light- criteria:

The modified Light- criteria can also be used to determine whether ascites is an exudate or a transudate. The sensitivity is 97.9% and the specificity is 74.3% (Chub 2018).

- 1. fluid: plasma protein- ratio > 0.5

- 2. fluid: plasma LDH ratio > 0.6

- 3. LDH in ascites > 2/3 x upper reference limit for plasma LDL (Chub 2018).

If any of these 3 criteria are met, it is an exudate. In the original publication, sensitivity was 99% and specificity was 98% (Chub 2018).

In a study by Getnet et al (2019), the cause of ascites in transudate was shown to be more benign disease, whereas in exudate, malignancy was predominant.

• Spontaneous bacterial peritonitis (SBP):

Every punctate should always be examined for SBP. In SBP, the number of PMN (polymorphonuclear) - leukocytes is ≥ 500 x 106 / l (Kopcinovic 2014).

- Leukocyte-esterase strip test:

To enable a more rapid diagnosis of spontaneous bacterial peritonitis, a leukocyte esterase strip test should be performed in addition to microbiological tests. This is easy to perform and shows a high sensitivity between 64.7-100% and specificity between 99 -100% (Kopcinovic 2014). According to the 2018 guideline, the test strip was used to diagnose SBP in 1,041 patients in a recent multicenter study. This showed a significantly lower sensitivity of 45.3%, while the specificity was 99.2%. Hence, it is recommended to use the test strips only as a supplement to the usual diagnostic tests if no clinical chemistry laboratory is immediately available (Gerbes 2018).

• Inflammatory ascites

In inflammatory ascites, granulocytes are additionally elevated and culture is positive (Wiest 2006).

• Pancreatogenic ascites

Pancreatogenic ascites is characterized by an elevation of lipase (Herold 2022).

• Malignant ascites:

- is usually hemorrhagic

- contains cholesterol (Herold 2022) > 45 mg / dl (sensitivity approx. 80 %, specificity approx. 70 % [Wiest 2006])

- CEA in the predominant cases > 2.5 ng / ml (Braun 2018) (sensitivity about 45 %, specificity about 100 % [Wiest 2006])

- Ascites- total protein > 2.5 g / dl (sensitivity approx. 75 %, specificity approx. 70 %)

- Ascites / serum LDH > 1.0 (sensitivity approx. 60 %, specificity approx. 75 %)

- Cytology positive (sensitivity approx. 80 %, specificity approx. 100 %)

(Wiest 2006)

• Chylous ascites

In chylous ascites, triglycerides are elevated to > 1,000 mg / dl (Braun 2018).

• Transsudate in ascites

An exudate in ascites must always be differentiated from a transudate in terms of differential diagnosis.

• Hepatorenal syndrome:

In this case, acute kidney failure occurs in the context of chronic, usually already advanced liver diseases (Wolf 2000). It occurs mainly in spontaneous bacterial peritonitis and after ingestion of nonsteroidal anti-inflammatory drugs (Wiest 2006).

• Leg edema:

In the supine position, ascites can lead to compression of the vena cava. The compression causes an increase in hydrostatic pressure with subsequent leg edema (Hirner 2004).

• Umbilical hernias:

The abdominal pressure increase can result in sometimes monstrous umbilical hernias (Hirner 2004).

• Spontaneous bacterial peritonitis (SBP):

This is found in approximately 15% of patients with ascites and liver cirrhosis (Hirner 2004). Occasionally it also occurs in association with ascites caused by heart failure, acute hepatitis, nephrotic syndrome, acute liver failure (Kasper 2015).

In this case, the intestine is the source of infection. The bacteria enter the ascites via mesenteric lymph nodes (Hirner 2004).

- Stage I:

In case of minimal ascites, no specific therapy is required. However, sodium restriction, control examinations and follow-up are already recommended (Wiest 2006).

- Stage II:

From stage II onward,:

- saline intake should be limited to < 3 g / d

- fluid intake to 1 - 1.5 l / d

- Therapy with diuretics:

- Aldosterone antagonists such as spironolactone 100 - 400 mg / d

- Loop diuretics such as furosemide 40 - 160 mg / d (Hirner 2004). Buchta (2004), on the other hand, advises against loop diuretics because they can promote the development of encephalopathy

In about 85% of cases, these measures can achieve flushing out ascites (Hirner 2004).

- Stage III:

In case of very large amounts of ascites, a puncture is necessary. In this case, a so-called paracentesis treatment is recommended, i.e., approx. 5 l of ascites fluid should be removed with parallel use of 8 - 10 g albumin / l i. v. (Hirner 2004).

• Spontaneous bacterial peritonitis:

All patients with a v. a. spontaneous bacterial peritonitis should be treated with antibiotics immediately - even before obtaining the microbiological tests (Kopcinovic 2014). Kasper (2015) recommends against gram-positive and gram-negative aerobes IV- cefotaxime for 5 days.

If there is no improvement of the ascites under the above measures, thus a so-called therapy-refractory ascites is present, interconventional or surgical measures are necessary. These include:

- Transjugular intrahepatic portosystemic shunt (TIPS):

This is a connection between the hepatic vein and a branch of the portal vein (Hill 2020), a functional side-to-side shunt. By inserting a TIPS, compression of the portal vein system is achieved. This method is used when stable liver function is still present without evidence of hepatic encephalopathy with a bilirubin level < 3 mg / dl (Hirner 2004).

• Perito- neovenous ascites valve:

This is a collector located in the abdominal cavity, a venous catheter in the internal jugular vein and a check valve with a pumping chamber above the costal arch. After insertion of the valve, also known as the Denver valve, the shunt system closes in approximately 50% of patients within the first year (Hirner 2004).

• Liver transplantation:

If the patient has signs of terminal decompensated cirrhosis, the indication for transplantation should be reviewed (Hirner 2004).

• Exudate in ascites:

Prognosis depends on the cause of the disease.

• Transsudate in ascites:

In the most common cause of ascites, liver cirrhosis, 50% of patients die within the following year despite therapy, except for those who have undergone transplantation (Hirner 2004).

• Spontaneous bacterial peritonitis (SBP):

Despite antibiotic therapy, up to 70% of patients die (Hirner 2004).

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