Systemic Effects of Inflammation

Fever - Body's Burning Defense

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Acute Phase Response - Protein Power‑Up

• Systemic inflammation response; liver boosts Acute Phase Protein (APP) synthesis.
• Major Inducers: IL-6, TNF-α, IL-1.

  ⭐ IL-6 is the principal cytokine stimulating hepatic synthesis of most acute phase proteins.

• Positive APPs (↑ levels):
  • C-Reactive Protein (CRP): Opsonin, complement activation. Rapid.
  • Serum Amyloid A (SAA): Recruits cells; AA amyloidosis risk.
  • Fibrinogen: Clotting; ↑ ESR.
  • Hepcidin: ↓ iron (absorption/release).
  • Haptoglobin: Binds free Hb.
  • Ceruloplasmin: Cu transport, antioxidant.
  • Alpha-1 Antitrypsin: Protease inhibitor.
  • 📌 Mnemonic (Key +ve APPs): Can He See Real Fine Art? (CRP, Hepcidin, SAA, Fibrinogen, Alpha-1 Antitrypsin). Also: Haptoglobin, Ceruloplasmin.
• Negative APPs (↓ levels):
  • Albumin: ↓ synthesis, dilution.
  • Transferrin: ↓ to sequester iron.

Leukocytosis - White Cell Warriors

• Increased WBC count, typically > 11,000/µL.
• Neutrophilia: Most common; bacterial infections, acute inflammation. Accelerated release from marrow (CSFs, IL-1, TNF), often with "left shift" (immature forms).
• Lymphocytosis: Viral infections (e.g., infectious mononucleosis).
• Eosinophilia: Allergic reactions, parasitic infections (IL-5 driven).
• Leukemoid Reaction: Extreme elevation, WBC > 50,000/µL.
  • Caused by severe infections, inflammation, or paraneoplastic.
  • Toxic changes in neutrophils: Toxic granulations, Döhle bodies, cytoplasmic vacuoles.

  ⭐ Leukocyte Alkaline Phosphatase (LAP) score is typically high in leukemoid reactions and low in Chronic Myeloid Leukemia (CML).

Systemic Syndromes - Inflammation's Wide Reach

• SIRS (Systemic Inflammatory Response Syndrome): Widespread inflammatory state. Requires ≥2 criteria (📌 Mnemonic: "TEMPered Hounds Retch White BAIT"):

  • Temperature: >38°C or <36°C
  • Heart Rate: >90/min
  • Respiratory Rate: >20/min or PaCO₂ <32mmHg
  • WBC Count: >12,000/µL, <4,000/µL, or >10% immature band forms.

• Sepsis Spectrum & Key Mediators:

• Other Systemic Effects:

  • Anemia of Chronic Disease: ↑Hepcidin blocks iron release/absorption, leading to ↓RBC production.
  • Cachexia: Profound weight loss and muscle wasting; mediated by TNF-α, IL-1, IL-6.
  • Acute Phase Response: Fever, leukocytosis, ↑plasma acute-phase proteins (e.g., CRP, fibrinogen).

⭐ TNF-α is a major mediator of cachexia (muscle wasting) and the profound hypotension seen in septic shock.

Lab Markers - Tracking Inflammation

• Erythrocyte Sedimentation Rate (ESR): Indirect measure; influenced by fibrinogen, immunoglobulins. Rises/falls slowly.
• C-Reactive Protein (CRP): Acute-phase reactant. Rises/falls rapidly (6-8 hrs peak). More sensitive for acute inflammation.
• Procalcitonin (PCT): Specific for bacterial infections; differentiates from viral/non-infectious causes.
• Leukocytosis: ↑ WBC count, especially neutrophils (neutrophilia); left shift.

⭐ CRP levels rise and fall more rapidly than ESR in response to inflammation, making it a better indicator of acute changes and treatment response.

High‑Yield Points - ⚡ Biggest Takeaways

• Fever: Mediated by PGE2 in hypothalamus, induced by IL-1, TNF.
• Acute Phase Proteins (APPs): CRP, SAA, fibrinogen synthesized in liver; ESR ↑.
• Leukocytosis: Neutrophilia (bacterial), lymphocytosis (viral), eosinophilia (parasitic/allergy).
• Sepsis: Life-threatening organ dysfunction from dysregulated host response to infection; TNF, IL-1, IL-6 are key.
• Anemia of Chronic Disease: ↑ Hepcidin blocks iron release.
• Cachexia: Weight loss and muscle wasting, often TNF-α mediated.