Inflammation and Repair
Inflammation is the body's protective response to tissue injury, involving vascular and cellular events. Repair occurs through regeneration or fibrosis depending on tissue capacity.
Key Facts
The five cardinal signs of inflammation are rubor (redness), calor (heat), tumor (swelling), dolor (pain), and functio laesa (loss of function) Acute inflammation is mediated by neutrophils and lasts hours to days; chronic inflammation involves macrophages and lymphocytes Histamine from mast cells causes immediate vasodilation and increased vascular permeability Granulomatous inflammation is characterised by epithelioid macrophages — seen in TB, sarcoidosis, Crohn's disease Labile cells (e.g., epithelial, haematopoietic) continuously divide; permanent cells (e.g., neurones, cardiac myocytes) cannot regenerate TGF-beta is the key cytokine driving fibrosis via fibroblast activation and collagen deposition Type III collagen is laid down initially in wound healing, replaced by type I collagen during remodelling Wound tensile strength reaches approximately 80% of normal by 3 months
Overview
Key Facts
Inflammation is a complex biological response to harmful stimuli such as pathogens, damaged cells, or irritants. It is a protective mechanism that aims to eliminate the cause of injury, clear necrotic debris, and initiate repair.
Epidemiology
Inflammation underlies virtually all pathological processes. Chronic inflammatory diseases (e.g., rheumatoid arthritis, atherosclerosis, inflammatory bowel disease) account for a significant proportion of disease burden in the UK, with an estimated 50% of all deaths attributable to inflammation-related diseases.
Aetiology
Causes of inflammation include:
- Infections: Bacterial, viral, fungal, parasitic
- Physical agents: Trauma, radiation, heat, cold
- Chemical agents: Toxins, venoms, caustic substances
- Immune reactions: Hypersensitivity, autoimmunity
- Tissue necrosis: Ischaemia, infarction
Pathophysiology
Acute inflammation follows a stereotyped sequence:
- Vascular changes: Transient arteriolar vasoconstriction → vasodilation (histamine, prostaglandins) → increased permeability → exudate formation
- Cellular events: Margination → rolling (selectins) → adhesion (integrins, ICAM-1) → transmigration (diapedesis) → chemotaxis → phagocytosis
- Chemical mediators: Histamine, bradykinin, complement (C3a, C5a), prostaglandins, leukotrienes, cytokines (IL-1, TNF-alpha, IL-6)
Outcomes of acute inflammation: Resolution, abscess formation, chronic inflammation, or fibrosis
Chronic inflammation is characterised by simultaneous inflammation, tissue destruction, and repair. Key cells include macrophages, lymphocytes, and plasma cells.
Clinical Presentation
Acute Inflammation
- Local: Redness, heat, swelling, pain, loss of function
- Systemic: Fever, leucocytosis, raised CRP/ESR, acute phase response
- Severe: SIRS, sepsis, organ dysfunction
Chronic Inflammation
- Granulomatous: Caseating (TB) vs non-caseating (sarcoidosis)
- Non-specific chronic: Lymphocyte and macrophage infiltration, fibrosis
- Autoimmune: Tissue-specific or systemic destruction
Wound Healing
- Primary intention: Clean, apposed wound edges — minimal scarring
- Secondary intention: Open wound, granulation tissue fills defect — more scarring
- Tertiary intention: Delayed primary closure after initial open management
Red Flags
- Signs of systemic inflammatory response (SIRS): HR >90, RR >20, temp >38°C or <36°C, WCC >12 or <4 ×10⁹/L
- Non-healing wounds: consider malignancy, vasculitis, pyoderma gangrenosum
- Unexplained granulomatous inflammation: exclude TB, fungal infection before diagnosing sarcoidosis
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Acute bacterial infection | Neutrophilia, fever, purulent exudate | Blood cultures, CRP, procalcitonin |
| Viral infection | Lymphocytosis, mild inflammation | Viral PCR, serology |
| Autoimmune inflammation | Chronic, multisystem, autoantibodies | ANA, dsDNA, ANCA, RF |
| Granulomatous disease | Epithelioid cells, giant cells | Biopsy, AFB stain, ACE level |
| Malignancy | Chronic inflammation, weight loss, mass | Biopsy, CT staging |
| Foreign body reaction | Giant cell reaction around material | Histology with polarised light |
Diagnosis / Investigation
Bedside
- Temperature: Fever indicates systemic inflammatory response
- Wound inspection: Signs of infection, healing stage assessment
Bloods
- CRP: Rises within 6 hours, peaks at 48 hours — useful for monitoring acute inflammation
- ESR: Slower to rise and fall — better for chronic inflammation monitoring
- Procalcitonin: More specific for bacterial infection than CRP
- FBC: Neutrophilia (bacterial), lymphocytosis (viral), eosinophilia (parasitic/allergic)
- Serum amyloid A, ferritin, fibrinogen: Additional acute phase reactants
Imaging
- Ultrasound/CT/MRI: Identify abscess collections, inflammatory masses
- PET-CT: Detect occult inflammation, vasculitis, malignancy
Special Tests
- Histology/biopsy: Gold standard for characterising inflammation type
- Immunohistochemistry: Identify cell populations in tissue
- Flow cytometry: Lymphocyte subsets in blood/tissue
Management
Non-pharmacological
- Wound care: debridement, appropriate dressings, offloading pressure
- Nutritional optimisation (vitamin C, zinc, protein for wound healing)
- Smoking cessation — impairs wound healing and promotes chronic inflammation
Pharmacological
- NSAIDs: Inhibit COX-1/COX-2, reducing prostaglandin synthesis — ibuprofen 400mg TDS
- Corticosteroids: Broad anti-inflammatory — inhibit phospholipase A2, NF-κB; prednisolone 5-60mg OD
- DMARDs: Methotrexate 7.5-25mg weekly for chronic autoimmune inflammation
- Biological agents: Anti-TNF (adalimumab, infliximab), anti-IL-6 (tocilizumab) for refractory inflammation
- Antibiotics: When infection is the inflammatory trigger — guided by culture and sensitivity
Surgical
- Incision and drainage: For abscess cavities
- Debridement: Removal of necrotic tissue to promote healing
- Skin grafting: For large wounds unable to heal by secondary intention
Referral Criteria
- Non-healing wounds >6 weeks — consider tissue viability or dermatology referral
- Unexplained chronic inflammation — rheumatology or immunology
- Granulomatous inflammation of unknown cause — respiratory or infectious diseases
Prognosis
- Acute inflammation: typically resolves within days to weeks if cause eliminated
- Chronic inflammation: may persist indefinitely — leads to tissue damage and fibrosis
- Wound healing: tensile strength reaches 80% of original by 3 months; never reaches 100%
- Keloid/hypertrophic scarring: more common in Afro-Caribbean populations, young adults, sternal/deltoid sites
- Chronic non-healing wounds affect approximately 2% of the UK population, costing the NHS an estimated £5 billion annually
Other Relevant Information
Key Chemical Mediators
| Mediator | Source | Action |
|---|---|---|
| Histamine | Mast cells, basophils | Vasodilation, increased permeability |
| Bradykinin | Plasma (kinin system) | Pain, vasodilation, permeability |
| PGE2, PGI2 | COX pathway | Vasodilation, pain, fever |
| LTB4 | LOX pathway | Neutrophil chemotaxis |
| C3a, C5a | Complement | Chemotaxis, opsonisation, mast cell degranulation |
| IL-1, TNF-α | Macrophages | Fever, acute phase response, adhesion molecules |
| IL-6 | Macrophages, T cells | CRP production, fever |
Phases of Wound Healing
| Phase | Timing | Key Events |
|---|---|---|
| Haemostasis | Minutes | Platelet plug, fibrin clot |
| Inflammation | Hours–days | Neutrophils then macrophages |
| Proliferation | Days–weeks | Granulation tissue, angiogenesis, epithelialisation |
| Remodelling | Weeks–months | Collagen cross-linking (type III → type I) |