What fluid studies are important for ascites fluid and what do they reveal?

Essential Ascitic Fluid Studies and Their Diagnostic Significance

All patients with new-onset ascites or clinical deterioration require immediate diagnostic paracentesis with mandatory testing of cell count with differential, ascitic fluid albumin, and total protein—these three tests, combined with simultaneous serum albumin, provide the foundation for accurate diagnosis and risk stratification. 1, 2

Mandatory First-Line Studies

Cell Count with Differential

• Absolute neutrophil (PMN) count >250 cells/mm³ diagnoses spontaneous bacterial peritonitis (SBP), requiring immediate antibiotic therapy regardless of culture results 2, 3
• PMN count >500 cells/μL provides 96% diagnostic accuracy for SBP, making it the single most reliable infection marker 4
• Total white blood cell count >1,000 cells/μL increases likelihood of SBP with a likelihood ratio of 9.1 3
• Culture-negative neutrocytic ascites (PMN >250 with negative culture) carries identical morbidity and mortality to culture-positive SBP and requires the same treatment 2

Serum-Ascites Albumin Gradient (SAAG)

• SAAG ≥1.1 g/dL confirms portal hypertension with 97% accuracy, distinguishing it from all other causes 2, 4, 5
• SAAG <1.1 g/dL (likelihood ratio 0.06) effectively excludes portal hypertension and indicates peritoneal causes: malignancy, tuberculosis, pancreatic ascites, or nephrotic syndrome 2, 3
• Requires simultaneous serum and ascitic fluid albumin measurement for accurate calculation 2
• This single test replaced outdated exudate/transudate classification and should guide all subsequent management decisions 5

Ascitic Fluid Total Protein

• Protein <1.5 g/dL (15 g/L) identifies patients at highest risk for developing SBP, warranting consideration for prophylactic antibiotics 1, 2
• Protein >2.5 g/dL combined with high SAAG specifically indicates cardiac ascites rather than cirrhotic ascites 2, 6
• Helps distinguish between different portal hypertension etiologies: cirrhosis typically shows low protein, while cardiac and Budd-Chiari show elevated protein 1, 2

Bacterial Culture

• Inoculate ascitic fluid directly into aerobic and anaerobic blood culture bottles at the bedside, which increases culture yield from 77% to 100% compared to delayed laboratory inoculation 1, 2, 3
• Perform in all patients with suspected infection, hospitalized patients, or those with clinical deterioration 1, 2

Conditional Studies Based on Clinical Suspicion

Cytology for Malignancy

• Order when SAAG <1.1 g/dL or clinical suspicion for peritoneal carcinomatosis exists 2
• Diagnostic yield varies widely (0-96.7%) depending on tumor type and peritoneal involvement 2
• Sensitivity improves with larger fluid volumes submitted 7

Amylase

• Measure when pancreatic ascites is suspected; levels typically exceed 1,000 IU/L or >6 times serum amylase 1, 2
• Elevated amylase definitively establishes pancreatic origin (pancreatitis, pseudocyst rupture, or pancreatic duct disruption) 1

Adenosine Deaminase (ADA)

• ADA <40 IU/L excludes tuberculous peritonitis with high accuracy in endemic areas or high-risk patients 2
• Particularly valuable in developing countries where tuberculosis remains a common ascites etiology 7

Creatinine and Urea

• Significantly elevated fluid creatinine and urea levels definitively distinguish urinary ascites from true ascites following bladder or ureteral injury 1, 8
• This is the most reliable test when trauma or iatrogenic injury raises concern for urine leakage 8
• Fluid appearance alone is unreliable, as both ascites and urine can appear clear or cloudy 2, 8

Additional Biochemical Markers

• Ascitic fluid pH <7.35 or blood-ascitic fluid pH gradient ≥0.10 increases SBP likelihood (likelihood ratio 9.0 and 11.3 respectively), though PMN count remains superior 3
• Lactate dehydrogenase (LDH) >885 U/L suggests non-portal hypertension causes but adds limited value beyond SAAG 9, 7
• Glucose levels have minimal diagnostic utility in routine practice 7
• Triglycerides should be measured if fluid appears milky to diagnose chylous ascites 7

Critical Diagnostic Algorithm

Step 1: Perform paracentesis and send for cell count with differential, albumin, and total protein; draw simultaneous serum albumin 1, 2

Step 2: Calculate SAAG immediately:

• SAAG ≥1.1 g/dL = Portal hypertension (cirrhosis, cardiac ascites, Budd-Chiari, sinusoidal obstruction) 2, 5
• SAAG <1.1 g/dL = Peritoneal process (malignancy, tuberculosis, pancreatic, nephrotic) 2, 5

Step 3: Assess infection risk:

• PMN >250 cells/mm³ = Start empiric antibiotics immediately for SBP 2, 3
• Protein <1.5 g/dL = High SBP risk, consider prophylaxis 2

Step 4: Refine diagnosis with protein level:

• High SAAG + high protein (>2.5 g/dL) = Cardiac ascites, evaluate for heart failure 2, 6
• High SAAG + low protein (<2.5 g/dL) = Cirrhotic ascites 2

Step 5: Add conditional tests based on clinical context:

• Suspected malignancy → cytology 2
• Suspected pancreatic disease → amylase 1, 2
• Suspected tuberculosis → ADA 2
• Suspected urine leak → creatinine/urea 1, 8

Critical Pitfalls to Avoid

• Never rely on CA125 levels—they are elevated by ascites from any cause due to mesothelial cell pressure and have zero diagnostic value 1, 2
• Never skip simultaneous serum albumin—SAAG cannot be accurately calculated without it 2
• Never delay bedside culture inoculation—laboratory transport reduces culture sensitivity by 23% 3
• Recognize mixed ascites in 5% of patients who have multiple contributing causes (e.g., cirrhosis plus heart failure plus diabetic nephropathy) 1, 2
• Never use fluid appearance alone to distinguish ascites from urine—creatinine level is definitive 2, 8
• Never withhold paracentesis for coagulopathy or thrombocytopenia—the procedure is safe even with abnormal coagulation parameters 3