Clinical Applications: CSF and Urine Proteins – Lecture #3

A comprehensive set of Q&A flashcards covering protein levels in body fluids, blood-brain barrier assessment, CSF and urine protein analysis methods, electrophoretic findings, diseases such as bacterial meningitis and multiple sclerosis, urine proteinuria patterns, and detection of Bence Jones proteins.

What is the typical protein concentration of serum or plasma?

High—approximately ≥3 g/dL.

What protein level defines an exudate?

≥3 g/dL of protein in the fluid.

How much protein is normally present in cerebrospinal fluid (CSF)?

15–45 mg/dL (~0.4 % of plasma level).

What is the usual 24-hour urinary protein excretion in a healthy adult?

50–100 mg/24 hr (trace amounts).

How do CSF protein and glucose levels typically change in bacterial meningitis?

CSF protein greatly increases while CSF glucose decreases (due to bacterial/WBC use).

What barrier controls passage of proteins between blood and CSF?

The blood-brain barrier (blood-CSF barrier).

Why is albumin the preferred analyte for assessing blood-CSF barrier integrity?

Albumin is neither synthesized nor metabolised in the CNS; any CSF albumin must have crossed the barrier.

State the CSF/serum albumin index value that indicates an intact barrier.

< 9.

Give the CSF/serum albumin index ranges for mild, moderate, severe, and complete barrier impairment.

9–14 = slight; 14–30 = moderate; 30–100 = severe; > 100 = complete breakdown.

Which immunoglobulin is quantitatively most abundant in CSF and used to evaluate intrathecal synthesis?

IgG.

Name two laboratory indicators of increased intrathecal IgG synthesis.

Elevated CSF IgG Index and presence of oligoclonal IgG bands.

What electrophoretic technique most sensitively detects oligoclonal bands?

High-resolution agarose or polyacrylamide isoelectric focusing with immunofixation.

Multiple sclerosis (MS) usually shows elevated CSF gamma globulins. What is typically seen in the paired serum?

Serum gamma globulins are usually normal (not elevated).

List four CNS diseases (other than MS) that may elevate the CSF gamma region.

Encephalitis, meningitis, tertiary syphilis (neurosyphilis), arachnoiditis, and intracranial tumors.

What daily volume of CSF is produced in adults?

Approximately 500–700 mL (CSF is renewed about four times daily).

How is CSF obtained for laboratory testing?

By lumbar puncture (spinal tap).

Why can’t the biuret reaction be used to measure CSF total protein?

CSF protein concentrations are too low for the biuret method’s sensitivity.

Name the two acids most commonly used in turbidimetric assays for CSF and urine proteins.

3 % sulfosalicylic acid (SSA) and 3 % trichloroacetic acid (TCA).

Explain how turbidimetry measures CSF protein.

Protein is precipitated; resulting turbidity is proportional to protein concentration and read spectrophotometrically.

What specimen characteristic, caused by CNS hemorrhage, can falsely elevate turbidimetric CSF protein?

Xanthochromia (yellow discoloration from xanthematin).

Which CSF protein fraction migrates anodal to albumin and is normally present?

Pre-albumin (2–7 % of total CSF protein).

Give the normal CSF electrophoresis percentage range for albumin.

50–70 %.

What are the normal gamma-globulin and beta-globulin percentage ranges in CSF electrophoresis?

Gamma = 3–13 %; Beta = 7–23 %.

Describe the hallmark electrophoretic finding in MS.

Oligoclonal IgG bands in CSF without corresponding bands in serum.

Which laboratory assay provides a direct index of active demyelination in MS?

Myelin basic protein assay (radioimmunoassay).

What is the initial screening method for detecting urinary protein in routine urinalysis?

Semi-quantitative dipstick test.

State the four preparatory steps before performing urine protein electrophoresis.

1) Microscopic exam, 2) Filtration/centrifugation, 3) SSA or TCA turbidity quantitation, 4) Concentration of urine.

Why is the biuret method unsuitable for total urine protein measurement?

Low normal protein plus ammonia interference hamper accuracy and sensitivity.

Which dyes are commonly used in dye-binding assays for urine protein?

Coomassie brilliant blue and Ponceau S.

How is 24-hour urine total protein (mg/24 hr) calculated?

(Protein mg/dL) × (Urine volume mL) ÷ 100.

In selective glomerular proteinuria, which proteins dominate the urine electrophoretic pattern?

Albumin (≥80 %) and transferrin.

Which electrophoretic pattern shows reduced albumin but elevated α1, α2, β, and γ globulins, indicating tubular damage?

Tubular proteinuria pattern.

What are Bence Jones proteins?

Free immunoglobulin light chains (kappa or lambda) of ≈25 kDa excreted in urine.

List the two main mechanisms causing Bence Jones proteinuria.

1) Overload proteinuria (excess light chains saturate reabsorption); 2) Tubular defect/toxicity induced by the light chains.

Describe the Bradshaw screening test for Bence Jones proteins.

Layer urine over concentrated HCl; a white precipitate at the interface indicates excess globulins (positive in ~95 % of BJ cases).

Summarize the classic heat test behavior of Bence Jones proteins.

Soluble at room temp; precipitate at 65 °C (15 min); re-dissolve at 100 °C (3 min).

Why might very high Bence Jones concentrations yield a false-negative in the heat test?

Excess protein may fail to re-dissolve at 100 °C.

Which light-chain type appears about twice as often in dysglobulinemia-related proteinuria?

Kappa light chains.