What is the likely cause of a positive blood reagent strip reaction in a patient with red/brown urine, large blood on dipstick, and absence of significant red blood cells, following an adverse reaction during surgery?

Analysis of Urinalysis Results Following Surgical Adverse Reaction

The urinalysis findings indicate acute tubular necrosis with myoglobinuria, likely resulting from rhabdomyolysis that occurred during surgery.

Analysis of Specific Urinalysis Findings

a. Substance Causing Positive Blood Reaction

The positive blood reaction on the reagent strip is most likely caused by myoglobin rather than hemoglobin or intact red blood cells. This conclusion is supported by:

• Red/brown colored urine with "large" blood on dipstick but without significant intact RBCs on microscopic examination
• Presence of yellow-brown granules in renal tubular epithelial (RTE) cells
• Clinical context of an adverse reaction during surgery

Myoglobin is a heme-containing protein released from damaged muscle cells during rhabdomyolysis. It cross-reacts with the blood reagent on dipstick tests due to its peroxidase-like activity, similar to hemoglobin. The tetramethylbenzidine-based reagent in the dipstick reacts with the heme portion of myoglobin, producing a positive "blood" result even in the absence of intact RBCs.

b. Significance of Elevated Urobilinogen with Negative Bilirubin

The elevated urobilinogen (8.0 EU) with negative bilirubin suggests:

• Increased hemolysis or muscle breakdown releasing heme-containing proteins
• Normal liver function (able to conjugate bilirubin)
• Normal biliary excretion (no obstruction)

Urobilinogen is formed in the intestine by bacterial action on bilirubin and is partially reabsorbed and excreted in urine. The elevated level likely reflects increased heme protein breakdown from muscle injury rather than liver or biliary disease.

c. Significance of RTE Cells and Casts

The presence of RTE cells and various casts indicates acute tubular injury:

• RTE cells (6-10/hpf) with intracellular yellow/brown granules: Direct evidence of tubular epithelial damage with uptake of myoglobin
• RBC casts (3-4/lpf): Suggest glomerular injury or bleeding into tubules
• Dirty brown casts (1-2/lpf): Likely degenerating cellular casts containing myoglobin
• RTE cell casts (1-2/lpf): Confirm tubular epithelial injury and sloughing

This pattern is characteristic of acute tubular necrosis caused by myoglobinuria, which is toxic to renal tubules.

d. Composition of Yellow-Brown Granules

The yellow-brown granules are most likely myoglobin that has been phagocytosed by renal tubular epithelial cells. When myoglobin is filtered through the glomeruli, it can be reabsorbed by proximal tubular cells, appearing as yellow-brown granular inclusions within these cells. This represents the cellular response to clear myoglobin from the tubular lumen.

e. Confirmation of Granule Composition

The composition of these granules could be confirmed using:

• Prussian blue stain: Would be negative for myoglobin (positive only for hemosiderin)
• Immunohistochemical staining with anti-myoglobin antibodies: Would be positive if myoglobin is present
• Peroxidase staining: Would be positive due to the peroxidase-like activity of myoglobin

Clinical Implications and Management

This urinalysis pattern strongly suggests rhabdomyolysis with myoglobinuria causing acute tubular necrosis. Rhabdomyolysis can occur during surgery due to:

1. Prolonged immobilization causing muscle compression
2. Hypotension leading to muscle ischemia
3. Malignant hyperthermia
4. Medication reactions
5. Direct muscle trauma

Management Priorities:

1. Aggressive fluid resuscitation to maintain urine output >100 ml/hour
2. Monitor renal function closely with serial creatinine measurements
3. Maintain urine alkalinization (pH >6.5) to reduce myoglobin precipitation in tubules
4. Avoid nephrotoxic agents including aminoglycosides and NSAIDs
5. Monitor electrolytes closely, especially for hyperkalemia, hyperphosphatemia, and hypocalcemia
6. Consider renal replacement therapy if severe acute kidney injury develops

Monitoring Parameters:

• Serum creatinine and BUN
• Serum electrolytes, especially potassium
• Urine output
• Serum creatine kinase (CK) levels to confirm rhabdomyolysis
• Repeat urinalysis to monitor resolution

Conclusion

The urinalysis findings are consistent with myoglobinuria and acute tubular necrosis following rhabdomyolysis that occurred during surgery. This condition requires prompt recognition and management to prevent progression to severe acute kidney injury or renal failure.