Learning Objective
Differentiate positive and negative acute-phase reactants, understand their regulation during inflammation, and recognize their clinical significance.
Acute-Phase Reactants
Acute-phase reactants are plasma proteins whose serum concentrations change in response to acute or chronic inflammation.
- Produced primarily by the liver
- Induced mainly by IL-6 (with contributions from IL-1 and TNF-α)
They are classified as positive (upregulated) or negative (downregulated) reactants.
Activity
Positive Acute-Phase Reactants (↑ during inflammation)
C-reactive protein (CRP)
-
- Acts as an opsonin
- Fixes complement and enhances phagocytosis
- Used clinically as a nonspecific marker of inflammation
Ferritin
-
- Sequesters iron, limiting availability to microbes
- Contributes to anemia of chronic disease
Fibrinogen
-
- Coagulation factor involved in endothelial repair
- Increased levels correlate with elevated ESR
Haptoglobin
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- Binds free hemoglobin
- Prevents hemoglobin-mediated oxidative injury
Hepcidin
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- Decreases intestinal iron absorption by degrading ferroportin
- Decreases iron release from macrophages
- Key mediator of anemia of chronic disease
Procalcitonin
-
- Preferentially elevated in bacterial infections
- Useful in distinguishing bacterial from viral inflammation
Serum amyloid A (SAA)
-
- Persistent elevation may result in secondary (AA) amyloidosis
Activity
Negative Acute-Phase Reactants (↓ during inflammation)
Albumin
-
- Decreased to conserve amino acids for the synthesis of positive reactants
Transferrin
-
- Reduced and internalized by macrophages to limit circulating iron
Transthyretin (Prealbumin)
-
- Decreased to redirect amino acids toward acute-phase protein production
High-Yield USMLE Step 1 Summary
- IL-6 → acute-phase reactants
- CRP & ESR = markers of inflammation
- Hepcidin ↑ → anemia of chronic disease
- Serum amyloid A ↑ chronically → AA amyloidosis
- Albumin, transferrin, and prealbumin ↓ during inflammation
