Pathology
Inflammation
Acute vs chronic — the cardinal signs, mediators, and when healing turns harmful
Inflammation is the body's coordinated response to tissue injury or infection — protective when controlled, destructive when sustained. Acute inflammation: minutes to days; cardinal signs (Celsus, ~30 AD) rubor (redness), calor (heat), tumor (swelling), dolor (pain), functio laesa (loss of function). Vasodilation and increased vascular permeability deliver neutrophils and plasma proteins. Mediators: histamine (mast cells), prostaglandins (COX-1/2 from arachidonic acid), leukotrienes, bradykinin, cytokines (TNF-α, IL-1, IL-6), complement (C3a, C5a). Chronic inflammation: weeks to years; macrophages and lymphocytes dominate, fibrosis, granulomas (TB, sarcoidosis). Drives atherosclerosis, type 2 diabetes, Alzheimer disease, cancer. Anti-inflammatory drugs (NSAIDs, corticosteroids, biologics) are among the most prescribed worldwide.
- Five cardinal signsRubor, calor, tumor, dolor, functio laesa
- Acute timescaleMinutes to days
- Chronic timescaleWeeks to years
- Key cytokinesTNF-α, IL-1β, IL-6
- NSAIDs targetCOX-1 and/or COX-2 (prostaglandins)
- TNF-α blockersInfliximab, adalimumab, etanercept
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Why inflammation matters
- Infection control. Recruits cells and complement to clear pathogens.
- Wound healing. Necessary first phase before repair.
- Vaccine response. Adjuvants induce inflammation to boost adaptive memory.
- Chronic disease. Underlies atherosclerosis, diabetes, cancer, Alzheimer.
- Autoimmunity. Misdirected inflammation against self tissues.
- Sepsis. Life-threatening systemic dysregulation.
- Drug targets. NSAIDs, steroids, biologics — among most prescribed therapies.
Common misconceptions
- Inflammation is always bad. Required for healing and infection control.
- Steroids are first-line for everything. Powerful but cause Cushing, osteoporosis, infection — taper carefully.
- Cold suppresses inflammation universally. Ice reduces edema/pain locally but doesn't affect systemic disease.
- NSAIDs are safe over-the-counter. ~16,500 US deaths/yr from GI bleeds; renal and CV risks real.
- Chronic inflammation has obvious symptoms. Often silent — atherosclerosis develops decades before MI.
- Anti-inflammatory diet cures disease. Diet helps modestly; doesn't replace pharmacotherapy in RA, IBD.
Frequently asked questions
What triggers acute inflammation?
PAMPs (pathogen-associated molecular patterns — LPS, flagellin, viral RNA) recognized by TLRs and NLRs. DAMPs (damage-associated — ATP, HMGB1, mitochondrial DNA released by injured cells). Triggers mast cell degranulation (histamine), complement activation, and macrophage activation. Sequence: vasodilation (heat, redness), increased permeability (swelling from plasma exudate), neutrophil margination and emigration (along ICAM-1/selectin gradients), phagocytosis of pathogens.
What's the difference between acute and chronic inflammation?
Acute: short, neutrophil-dominant, exudative (fluid and cells leak from vessels), resolves with healing. Chronic: prolonged (>2 wk), macrophage and lymphocyte dominant, often coexists with tissue destruction and repair (fibrosis, scarring). Causes of chronic include persistent infection (TB, hepatitis B/C), foreign bodies (silica, asbestos, sutures), autoimmunity (RA, IBD), and metabolic stress (obesity, atherosclerosis).
How do NSAIDs work?
Inhibit cyclooxygenase (COX) enzymes that convert arachidonic acid to prostaglandins. Aspirin: irreversibly acetylates COX-1 and COX-2 (low dose 81 mg blocks platelet TXA2 for life of platelet ~10 days). Ibuprofen, naproxen: reversible, non-selective. Celecoxib: COX-2 selective (less GI bleeding but increased CV risk — rofecoxib withdrawn 2004). Side effects: gastric ulcers (COX-1 protects mucosa), kidney injury, hypertension, increased CV events.
What's a granuloma?
Organized aggregate of activated macrophages (epithelioid cells), often with multinucleated giant cells (Langhans, foreign body) and surrounding lymphocytes. Forms when macrophages can't eliminate pathogen — wall it off. Caseating granulomas (central necrosis): TB, some fungi. Non-caseating: sarcoidosis, Crohn disease, foreign body. Diagnostic on biopsy. Acid-fast stain (Ziehl-Neelsen) for mycobacteria.
What is sepsis?
Life-threatening organ dysfunction caused by dysregulated host response to infection (Sepsis-3, 2016). Cytokine storm — TNF-α, IL-1, IL-6 systemic. Hypotension (refractory to fluids = septic shock), DIC, ARDS, AKI. Mortality 20-40%. Treatment: early broad-spectrum antibiotics (within 1 hr — every hour of delay increases mortality ~7%), IV fluids 30 mL/kg, vasopressors (norepinephrine first-line), source control. Surviving Sepsis Campaign protocols globally adopted.
How does chronic inflammation cause disease?
Atherosclerosis: oxidized LDL drives macrophage foam cell formation; plaque rupture causes MI. Type 2 diabetes: adipose macrophages secrete TNF-α causing insulin resistance. Cancer: chronic inflammation (HCV→HCC, H. pylori→gastric cancer, IBD→colorectal) creates mutagenic environment via ROS. Alzheimer: microglial activation contributes to neurodegeneration. Rheumatoid arthritis: synovial T cell, macrophage, fibroblast cross-talk destroys joint.
What are biologics for inflammation?
Monoclonal antibodies or fusion proteins targeting specific cytokines. TNF-α blockers (infliximab, adalimumab, etanercept) — RA, psoriasis, Crohn, UC, ankylosing spondylitis. IL-6 (tocilizumab) — RA, giant cell arteritis, CRS, COVID-19. IL-17 (secukinumab) — psoriasis. IL-23 (ustekinumab, risankizumab) — psoriasis, Crohn. JAK inhibitors (tofacitinib, baricitinib) — oral, broader effect. Side effect: increased infection risk (TB reactivation), screen with IGRA before starting.