Normal Ascitic Fluid Analysis
Defining Normal Ascitic Fluid in Cirrhosis
In uncomplicated cirrhotic ascites, the fluid is sterile, typically clear or straw-colored, contains ≤250 polymorphonuclear cells/mm³, has a serum-ascites albumin gradient (SAAG) ≥1.1 g/dL, and total protein concentration is usually <2.5 g/dL. 1, 2
Essential Initial Testing Parameters
When performing diagnostic paracentesis on new-onset ascites, the following constitute the mandatory screening tests:
Cell Count and Differential
- Total white blood cell count: Normal ascites contains 281 ± 25 leukocytes/mm³ (mean ± SEM) 2
- Polymorphonuclear (PMN) cells: Should be <250 cells/mm³; 27 ± 2% of total white cells are PMN in normal ascites 2
- PMN count ≥250 cells/mm³ indicates spontaneous bacterial peritonitis (SBP) and requires immediate empiric antibiotics 1
Serum-Ascites Albumin Gradient (SAAG)
- SAAG ≥1.1 g/dL indicates portal hypertension with 97% accuracy 1, 3
- Requires simultaneous measurement of serum and ascitic fluid albumin on the same day 1, 3
- High SAAG causes include cirrhosis, cardiac ascites, Budd-Chiari syndrome, and sinusoidal obstruction syndrome 1, 3
Total Protein Concentration
- Normal cirrhotic ascites typically has total protein <2.5 g/dL 1
- Protein <1.5 g/dL identifies patients at high risk for developing SBP 1, 3
- Cardiac ascites characteristically shows high SAAG with protein >2.5 g/dL, distinguishing it from cirrhotic ascites 3, 4
Gross Appearance Characteristics
The visual inspection provides immediate diagnostic clues:
- Clear/straw-colored: Normal uncomplicated cirrhotic ascites 2
- Turbid/cloudy: Suggests infection (SBP) or malignancy 1, 2
- White/milky: Indicates chylous ascites with triglycerides >200 mg/dL (often >1,000 mg/dL) 1
- Dark brown: Reflects high bilirubin from biliary tract disruption 1
- Black: May indicate pancreatic necrosis or metastatic melanoma 1
Conditional Testing Based on Clinical Suspicion
Additional tests should be ordered only when specific diagnoses are suspected:
When to Order Culture
- Culture at bedside in blood culture bottles if infection suspected 1, 3
- Culture-negative neutrocytic ascites (PMN >250 cells/mm³ with negative culture) requires identical treatment to culture-positive SBP due to similar mortality 1, 3
When to Order Additional Tests
- Cytology: For suspected malignancy (yield varies 0-96.7% depending on tumor site) 3
- Amylase: For suspected pancreatic ascites (typically >1,000 IU/L or >6 times serum amylase) 1, 3
- Adenosine deaminase: For suspected tuberculous peritonitis (levels <40 IU/L exclude TB with high accuracy) 1, 3
- Gram stain, LDH, glucose: When PMN ≥250 cells/mm³ to distinguish secondary bacterial peritonitis from SBP 1
Critical Diagnostic Thresholds for Secondary Peritonitis
When PMN count ≥250 cells/mm³, order Gram stain, culture, total protein, LDH, and glucose to detect secondary bacterial peritonitis requiring surgical intervention. 1
Secondary peritonitis is suggested by:
- Multiple organisms on Gram stain/culture 1
- At least 2 of 3 criteria: Total protein >1 g/dL, LDH greater than upper limit of normal for serum, glucose <50 mg/dL 1
- These criteria have 100% sensitivity but only 45% specificity for detecting perforation 1
Alternative criteria with 92% sensitivity and 88% specificity:
- Ascitic fluid CEA >5 ng/mL OR alkaline phosphatase >240 U/L 1
Common Pitfalls to Avoid
Do Not Rely on Outdated Parameters
- Specific gravity, protein concentration alone, and glucose level are NOT useful in differential diagnosis 2
- Traditional exudate-transudate classification is inferior to SAAG for determining etiology 5
Do Not Order CA-125
- CA-125 is elevated nonspecifically by ascites from any cause and has no diagnostic value 6, 3
- Ordering CA-125 leads to unnecessary gynecologic referrals and potentially fatal surgeries 6
Do Not Assume Single Etiology
- Approximately 5% of patients have mixed ascites with multiple contributing causes 6, 3
- Particularly important in cirrhotic patients who develop new ascites characteristics 6
Do Not Withhold Paracentesis for Coagulopathy
- Routine prophylactic transfusion of fresh frozen plasma or platelets before paracentesis is NOT recommended 1
- Hemorrhage occurs in only 0.2-2.2% of punctures with death rate of 0.02% 1
When to Perform Diagnostic Paracentesis
Diagnostic paracentesis is mandatory in:
- All patients with new-onset ascites 1, 3
- Hospitalized cirrhotic patients with any signs of infection 3
- Patients with gastrointestinal bleeding, hepatic encephalopathy, worsening renal/liver function 3
- Any patient with abdominal pain, fever, or clinical deterioration 1
Follow-Up Paracentesis
Repeat paracentesis is NOT routinely needed in typical SBP cases (advanced cirrhosis, typical symptoms, single organism, dramatic clinical response) 1
Repeat paracentesis IS indicated when: