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Urinalysis & Body Fluids

Chemical Testing

We have received our serous fluid specimen, properly handled and aliquoted. We now move to the chemistry department to analyze its molecular composition. Our entire chemical testing strategy is built around answering two fundamental questions in a specific order:

  1. First, what type of effusion is this?: Is it a transudate or an exudate? This is the great divide, the primary classification that dictates the entire clinical workup
  2. Second, if it is an exudate, what is the cause?: Is it infection, malignancy, pancreatitis, or something else?

To answer these questions, we employ a series of targeted chemical tests. And for the most important of these, a simultaneously drawn serum sample is not a luxury; it is a necessity. Without it, our most powerful diagnostic tools are useless

Primary Classification: Transudate vs. Exudate

This is the most critical determination we will make. We use two key analytes that reflect membrane integrity and cellular damage

Key Analytes: Protein & Lactate Dehydrogenase (LDH)

  • Total Protein
    • Physiology: The primary indicator of capillary permeability. A healthy serous membrane keeps large proteins like albumin in the blood. A damaged, inflamed membrane leaks them into the effusion
    • Significance: High protein suggests an exudate; low protein suggests a transudate
  • Lactate Dehydrogenase (LDH)
    • Physiology: A large intracellular enzyme found in all cells. Its presence in an effusion indicates cellular damage and lysis, either from inflammation or malignancy within the serous cavity. It is a more sensitive marker for inflammation than protein
    • Significance: High LDH strongly suggests an exudate; low LDH suggests a transudate

Gold Standard for Pleural Fluid: Light’s Criteria

  • This is the cornerstone of pleural fluid analysis.: Dr. Light’s research established a set of criteria that is nearly 98% sensitive for identifying exudates
  • Requirement: Paired fluid and serum samples are mandatory
  • The Rule: A pleural effusion is an EXUDATE if it meets AT LEAST ONE (1) of the following three criteria:
    1. Fluid Protein / Serum Protein Ratio > 0.5
      • Rationale: Compares the fluid protein to the systemic level. If the fluid is more than half as concentrated as the serum, it indicates significant leakage from the capillaries
    2. Fluid LDH / Serum LDH Ratio > 0.6
      • Rationale: Compares the fluid LDH to the systemic level. A high ratio indicates that the LDH in the fluid is not just from passive filtration but is being generated by an active inflammatory or malignant process locally
    3. Fluid LDH > 2/3 of the laboratory’s upper limit of normal for serum LDH
      • Rationale: This criterion acts as an independent measure of significant local inflammation, regardless of the patient’s serum LDH. (e.g., If the normal serum LDH range is 100-225 U/L, the cutoff would be 2/3 of 225, or >150 U/L)

Gold Standard for Peritoneal Fluid (Ascites): The SAAG

  • The Serum-Ascites Albumin Gradient (SAAG): has been shown to be more accurate than Light’s criteria for differentiating ascites. It is specifically designed to detect portal hypertension, the most common cause of ascites
  • The Calculation: SAAG = (Serum Albumin) – (Ascites Fluid Albumin)
  • Interpretation
    • SAAG ≥ 1.1 g/dL (“High Gradient”): Corresponds to a TRANSUDATE. This indicates the ascites is caused by portal hypertension (e.g., from cirrhosis), which creates a high hydrostatic pressure that forces a low-protein/low-albumin fluid into the peritoneum
    • SAAG < 1.1 g/dL (“Low Gradient”): Corresponds to an EXUDATE. This indicates the ascites is caused by a condition that increases membrane permeability (e.g., peritoneal carcinomatosis, TB peritonitis), allowing albumin to leak into the fluid and reducing the gradient

Investigating the Exudate: Secondary Chemical Tests

Once we have classified an effusion as an exudate, a panel of secondary tests can help pinpoint the specific cause

Glucose

  • Physiology: Glucose enters the serous fluid by diffusion from the plasma. Normally, its level is similar to the plasma level
  • Significance of LOW Glucose (<60 mg/dL or a fluid-to-serum ratio <0.5): A critically important finding. It indicates that glucose is being actively consumed within the serous cavity
  • Classic Causes of Low Fluid Glucose
    1. Infection (Empyema, Bacterial Peritonitis): Bacteria and the massive influx of neutrophils consume glucose through glycolysis
    2. Malignancy: Malignant cells have a high metabolic rate and consume glucose
    3. Rheumatoid Pleurisy: The intensely inflamed synovium-like membrane in the pleura has high metabolic activity

pH

  • This is a critical test, especially for pleural fluid.
  • CRITICAL HANDLING: Requires anaerobic collection (capped syringe) and transport on ice, exactly like a blood gas sample
  • Significance of LOW pH (<7.2)
    • In a parapneumonic effusion (an effusion next to a pneumonia), a pH <7.2 is the single strongest indicator of a complicated effusion or empyema. It signifies a high level of bacterial and neutrophilic metabolic activity
    • Clinical Implication: This result is a medical emergency that tells the clinician that the effusion is infected and requires immediate chest tube drainage to prevent permanent lung damage

Amylase & Lipase

  • Indication: Suspected pancreatitis
  • Physiology: In acute pancreatitis, digestive enzymes leak from the inflamed pancreas and can track into the peritoneal or pleural cavities
  • The Diagnostic Finding: A fluid amylase or lipase level that is significantly higher than the simultaneous serum level (often >1.5 times the upper limit of normal for serum) is diagnostic of a pancreatic effusion

Triglycerides

  • Indication: A milky white effusion
  • Physiology: This test is used to diagnose a chylothorax, which results from the leakage of chyle (lymphatic fluid from the intestines) due to a disruption of the thoracic duct. Chyle is rich in triglycerides from digested dietary fat
  • The Diagnostic Finding: A fluid triglyceride level > 110 mg/dL is diagnostic of a chylothorax. If the level is between 50-110 mg/dL, lipoprotein analysis should be performed to look for chylomicrons

Adenosine Deaminase (ADA)

  • Indication: Suspected tuberculous effusion
  • Physiology: ADA is an enzyme involved in purine metabolism that is found in high concentrations in activated T-lymphocytes. Tuberculous infections trigger a potent T-cell-mediated immune response
  • The Diagnostic Finding: A high ADA level (typically >40 U/L) is a highly sensitive and specific marker for tuberculous pleuritis or peritonitis, especially in high-prevalence areas

Conclusion

The chemical analysis of serous fluid is a logical, stepwise process. We begin with the global assessment - transudate or exudate? - using the powerful tools of Light’s Criteria and the SAAG. This initial classification sets the entire diagnostic path. Then, for exudates, we deploy a targeted arsenal of secondary tests. A low pH points to urgent drainage. High amylase points to the pancreas. High triglycerides point to a lymphatic leak. High ADA points to tuberculosis. By systematically applying these chemical tests, the laboratory provides a detailed molecular fingerprint of the disease process, giving the clinician a clear and actionable diagnostic roadmap