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Urinalysis & Body Fluids

Disease Correlation

We have spent the last several lectures meticulously taking apart the analysis of cerebrospinal fluid. We’ve learned the what and the how. Today, we learn the why. This is the synthesis. We will take the classic patterns of laboratory results and correlate them directly with the major pathologies of the central nervous system

Your value as a laboratory scientist is not just in your ability to generate a correct number, but in your ability to recognize a pattern of results and understand its clinical implication. When you see a CSF with 5,000 neutrophils, rock-bottom glucose, and sky-high protein, you shouldn’t just see numbers; you should see a patient with acute bacterial meningitis whose life is in immediate danger. This lecture is about learning to see the patient through the data

Infectious Meningitides: The Classic Triad

Meningitis, the inflammation of the meninges, is the most common and critical diagnosis made from CSF. Differentiating the cause is an absolute emergency

Acute Bacterial Meningitis: A Neurological Emergency

  • Pathophysiology: Bacteria enter the subarachpečknoid space, multiply rapidly, and trigger a massive, purulent inflammatory response. This inflammation leads to increased intracranial pressure, cerebral edema, and vasculitis, which can cause stroke and permanent neurological damage
  • The Classic CSF Profile
    • Appearance: Turbid to frankly purulent (looks like pus)
    • Opening Pressure: Markedly elevated
    • WBC Count: Markedly elevated (>1,000/µL, often many thousands)
    • Differential: >80% Neutrophils. This is the hallmark. You may see toxic granulation and vacuolization in the neutrophils
    • Protein: Markedly elevated (>100 mg/dL) due to profound BBB breakdown
    • Glucose: Markedly decreased (<40 mg/dL or <40% of plasma). This is due to consumption by both the bacteria and the massive number of neutrophils
    • Lactate: Markedly elevated (>35 mg/dL)
    • Gram Stain: Often positive, providing a rapid presumptive ID of the causative agent (S. pneumoniae, N. meningitidis, L. monocytogenes, etc.)
  • Clinical Bottom Line: This pattern is a “panic” result. The lab must phone the clinician immediately. Treatment with broad-spectrum antibiotics cannot wait for culture results

Aseptic (Viral) Meningitis: The Common Imposter

  • Pathophysiology: A virus (e.g., enterovirus, herpes simplex virus) infects the meninges. The resulting inflammation is typically less intense and is mediated by a different arm of the immune system. The disease is usually self-limiting
  • The Classic CSF Profile
    • Appearance: Clear to slightly hazy
    • Opening Pressure: Normal to slightly elevated
    • WBC Count: Moderately elevated (typically 50-1,000/µL)
    • Differential: Predominantly Lymphocytes. There may be an initial neutrophilic response in the first 24-48 hours, but it quickly shifts to a lymphocytic pleocytosis
    • Protein: Normal to moderately elevated (e.g., 50-100 mg/dL). The BBB is not as severely damaged
    • Glucose: Normal. This is the key differentiating feature from bacterial meningitis
    • Lactate: Normal
    • Microbiology: All bacterial stains and cultures will be negative. Diagnosis is often confirmed with PCR for specific viral DNA/RNA
  • Clinical Bottom Line: This profile allows clinicians to confidently withhold or stop antibiotics and provide supportive care

Chronic (Fungal/Tuberculous) Meningitis: The Insidious Invader

  • Pathophysiology: An insidious, slow-growing infection, often seen in immunocompromised patients (Cryptococcus) or as a result of disseminated TB. The inflammation develops over weeks to months
  • The Classic CSF Profile
    • Appearance: Hazy, viscous. A classic finding in TB meningitis is the formation of a delicate, web-like clot (“pellicle”) after the fluid sits overnight
    • WBC Count: Moderately elevated (100-500/µL)
    • Differential: A mix of Lymphocytes and Monocytes. Neutrophils are typically low
    • Protein: Markedly elevated, often higher than in bacterial meningitis, due to the chronic inflammation
    • Glucose: Decreased. Both fungi and mycobacteria consume glucose
    • Microbiology
      • Fungal: India Ink may reveal encapsulated Cryptococcus. Fungal culture or antigen tests are key
      • Tuberculous: Acid-fast stains have low sensitivity but are diagnostic if positive. Culture or molecular amplification (PCR) is required
  • Clinical Bottom Line: The diagnosis can be challenging and is often delayed. The combination of lymphocytic pleocytosis with low glucose should raise strong suspicion

Non-Infectious CNS Pathologies

Subarachnoid Hemorrhage (SAH)

  • Pathophysiology: Bleeding into the subarachnoid space, most commonly from a ruptured cerebral aneurysm. The blood acts as a chemical irritant to the meninges
  • The Classic CSF Profile (after differentiating from a traumatic tap)
    • Appearance: Visibly bloody initially, with xanthochromic supernatant after centrifugation. This is the diagnostic finding
    • Opening Pressure: Markedly elevated
    • RBC Count: Very high and consistent across all tubes
    • WBC Count: Will be elevated in proportion to the blood present, but also due to a secondary chemical meningitis caused by the blood
    • Microscopic: After 12-24 hours, look for erythrophages and hemosiderin-laden macrophages, which are definitive proof of in-vivo bleeding
  • Clinical Bottom Line: The lab’s confirmation of xanthochromia differentiates a true bleed from a procedural complication, directing the patient toward urgent neurosurgical intervention

Multiple Sclerosis (MS)

  • Pathophysiology: A chronic autoimmune disease where the body’s own immune system attacks the myelin sheaths of CNS neurons. This leads to localized inflammation and the production of immunoglobulins within the CNS
  • The Classic CSF Profile
    • Appearance: Clear and colorless
    • WBC Count: Normal to slightly elevated (<50/µL)
    • Differential: Predominantly lymphocytes and plasma cells (activated B-cells)
    • Protein: Normal to slightly elevated
    • Glucose: Normal
    • The Key Diagnostic Test: Oligoclonal Bands.
      • CSF protein electrophoresis is performed alongside a serum sample from the same patient
      • In >90% of MS patients, the CSF will show two or more discrete gamma globulin bands that are NOT: present in the serum
      • This pattern signifies intrathecal (within the CNS) synthesis of IgG, the hallmark of MS
  • Clinical Bottom Line: Lab findings support a clinical diagnosis of MS, ruling out other mimics

Guillain-Barré Syndrome

  • Pathophysiology: An autoimmune disease typically affecting the peripheral nervous system (nerve roots), often triggered by a preceding infection. It causes demyelination of peripheral nerves
  • The Classic CSF Profile
    • Appearance: Clear, may be xanthochromic if protein is very high
    • Key Finding: Albuminocytologic Dissociation.
      • Protein: Markedly elevated. This is due to increased permeability of the nerve root vessels near the CSF space
      • WBC Count: Normal or only very slightly elevated.
    • This “dissociation” between a very high protein level and a normal cell count is the classic finding
  • Clinical Bottom Line: This distinctive pattern strongly supports the diagnosis of Guillain-Barré syndrome

CNS Malignancy

  • Pathophysiology: Cancer cells seed the meninges (carcinomatous meningitis) or arise from primary CNS tumors. Leukemia and lymphoma can also infiltrate the CNS
  • The Classic CSF Profile
    • Appearance: Can be clear or cloudy, depending on cell count
    • WBC Count: Varies from normal to markedly elevated
    • Differential: A mixed pleocytosis is common
    • Protein: Often elevated
    • Glucose: Can be decreased as tumor cells have high metabolic rates
    • The Key Diagnostic Test: Cytology.
      • A cytospin slide is examined for malignant cells. Look for classic features: cellular clustering/molding, high N:C ratio, irregular nuclear membranes, prominent nucleoli
  • Clinical Bottom Line: The unequivocal identification of malignant cells in the CSF is diagnostic of CNS metastasis or primary malignancy and has profound implications for the patient’s prognosis and treatment plan

Conclusion

As we’ve seen, a small set of laboratory tests on CSF can differentiate between a wide and dramatic range of pathologies. The power lies not in any single result, but in the pattern. By learning to recognize these classic diagnostic profiles, you transition from a laboratory scientistwho generates data to a scientist who provides diagnostic insight. This is the ultimate expression of our profession’s importance in patient care