Inflammation & Healing
On this page 34 sections
INFLAMMATION
Overview
Inflammation is a protective response of vascularized tissue to infection, tissue injury or other harmful stimuli.
Its purpose is to eliminate the cause of injury, remove damaged tissue and initiate repair.
Cardinal signs
| Sign | Latin term | Mechanism |
|---|---|---|
| Redness | Rubor | Vasodilation |
| Heat | Calor | Increased blood flow |
| Swelling | Tumor | Increased vascular permeability and edema |
| Pain | Dolor | Chemical mediators and tissue pressure |
| Loss of function | Functio laesa | Tissue injury, pain and swelling |
Acute versus chronic inflammation
| Feature | Acute | Chronic |
|---|---|---|
| Onset | Rapid | Often gradual |
| Duration | Hours to days | Weeks to years |
| Main cells | Neutrophils | Macrophages, lymphocytes, plasma cells |
| Vascular changes | Prominent | Variable |
| Tissue destruction | Usually limited, but may be severe | Often persistent |
| Repair/fibrosis | May follow resolution | Commonly occurs simultaneously |
Acute Inflammation
Acute inflammation involves vascular changes and recruitment of leukocytes to the site of injury.
Vascular events
- Transient vasoconstriction may occur immediately after injury.
- Arteriolar vasodilation increases local blood flow.
- Vascular permeability increases.
- Protein-rich fluid enters the interstitial space.
- Blood flow slows, producing stasis.
- Leukocytes move toward the endothelial surface.
Exudate versus transudate
| Feature | Exudate | Transudate |
|---|---|---|
| Protein content | High | Low |
| Specific gravity | Usually higher | Usually lower |
| Mechanism | Increased vascular permeability | Hydrostatic or oncotic pressure imbalance |
| Typical setting | Inflammation | Heart failure, hypoalbuminemia |
MCQ tip: Exudate is associated with inflammation; transudate is associated with altered fluid pressures.
Leukocyte Recruitment
The sequence of leukocyte recruitment is one of the most frequently tested areas of general pathology.
Steps
Adhesion molecules
| Step | Molecules | Function |
|---|---|---|
| Rolling | E-selectin, P-selectin, L-selectin | Weak, transient leukocyte–endothelial interactions |
| Firm adhesion | Leukocyte integrins | Strong attachment to endothelium |
| Endothelial ligands | ICAM-1, VCAM-1 | Bind activated leukocyte integrins |
| Diapedesis | PECAM-1/CD31 | Helps leukocytes cross endothelial junctions |
| Chemotaxis | C5a, LTB4, IL-8 and bacterial products | Direct leukocytes toward inflammatory stimuli |
Remember: Selectins = rolling; integrins = adhesion; PECAM-1 = transmigration.
Cellular Response in Inflammation
Predominant inflammatory cells
| Cell | Main association |
|---|---|
| Neutrophils | Early acute inflammation and pyogenic bacterial infection |
| Monocytes/macrophages | Later acute inflammation and chronic inflammation |
| Lymphocytes | Viral infections and chronic immune responses |
| Eosinophils | Parasitic infections and allergic conditions |
| Mast cells | Histamine release and immediate hypersensitivity |
| Plasma cells | Antibody production |
Time course
- Neutrophils generally predominate during the first 6–24 hours.
- Monocytes/macrophages become more prominent after approximately 24–48 hours.
- Chronic inflammation often contains macrophages, lymphocytes and plasma cells.
These are typical patterns, not absolute rules.
Phagocytosis and Killing
Phagocytosis
- Recognition and attachment.
- Engulfment into a phagosome.
- Fusion with lysosomes.
- Intracellular killing and degradation.
Opsonization
Opsonins coat microorganisms and make them easier for phagocytes to recognize.
| Opsonin | Recognition |
|---|---|
| IgG | Fc receptors |
| C3b | Complement receptors |
| Collectins | Pattern-recognition pathways |
Oxygen-dependent killing
The respiratory burst generates reactive oxygen species.
NADPH oxidase converts oxygen into superoxide, which can form hydrogen peroxide.
Myeloperoxidase uses hydrogen peroxide and chloride to produce hypochlorous acid (HOCl), a potent antimicrobial agent.
Oxygen-independent killing
Includes:
- Lysozyme.
- Defensins.
- Lactoferrin.
- Proteolytic enzymes.
Clinical correlation: Chronic granulomatous disease
Defective NADPH oxidase impairs the respiratory burst and increases susceptibility to certain infections.
MCQ tip: Chronic granulomatous disease = defective NADPH oxidase.
Chemical Mediators of Inflammation
| Mediator | Main action |
|---|---|
| Histamine | Vasodilation and increased vascular permeability |
| Prostaglandins | Vasodilation, pain and fever |
| Leukotriene B4 | Neutrophil chemotaxis and activation |
| Leukotrienes C4, D4, E4 | Bronchoconstriction and increased vascular permeability |
| Bradykinin | Pain, vasodilation and permeability |
| C3a and C5a | Anaphylatoxin activity |
| C5a | Potent chemotactic activity |
| TNF and IL-1 | Endothelial activation, fever and systemic inflammatory responses |
| IL-6 | Promotes acute-phase protein synthesis |
| IL-8/CXCL8 | Neutrophil chemotaxis |
Arachidonic acid pathway
| Pathway | Enzyme | Products |
|---|---|---|
| Cyclooxygenase | COX-1/COX-2 | Prostaglandins and thromboxanes |
| Lipoxygenase | 5-lipoxygenase | Leukotrienes |
Important products
- PGE₂ contributes to pain and fever.
- PGI₂ promotes vasodilation and inhibits platelet aggregation.
- TXA₂ promotes platelet aggregation and vasoconstriction.
- LTB₄ is chemotactic for neutrophils.
- LTC₄, LTD₄ and LTE₄ contribute to bronchoconstriction.
Chronic Inflammation
Chronic inflammation is characterized by persistent inflammatory cell infiltration, tissue destruction and attempts at healing.
Major causes
- Persistent infections, including tuberculosis.
- Autoimmune diseases.
- Prolonged exposure to toxic substances.
- Foreign bodies.
- Persistent inflammatory stimuli.
Granulomatous inflammation
A granuloma is an organized collection of activated macrophages, often with surrounding lymphocytes.
Activated macrophages may develop an epithelioid appearance and fuse into multinucleated giant cells.
Types of granulomas
| Type | Mechanism | Examples |
|---|---|---|
| Immune granuloma | T-cell-mediated macrophage activation | Tuberculosis, sarcoidosis |
| Foreign-body granuloma | Reaction to material difficult to phagocytose | Sutures, foreign material |
Caseating versus noncaseating granulomas
| Feature | Caseating | Noncaseating |
|---|---|---|
| Central necrosis | Usually present | Usually absent |
| Classic association | Tuberculosis | Sarcoidosis |
| Giant cells | May be present | May be present |
Exam tip: Caseating granuloma strongly suggests tuberculosis in the appropriate context, but it is not exclusive to TB.
Giant cells
- Langhans giant cells may show peripheral, horseshoe-shaped nuclear arrangement.
- Foreign-body giant cells often show irregularly distributed nuclei.
Tissue Repair and Wound Healing
Tissue repair occurs through regeneration, scar formation or a combination of both.
Regeneration
Replacement of damaged cells by the same cell type, restoring normal structure and function when tissue architecture and proliferative capacity permit.
Fibrosis
Replacement of damaged tissue with connective tissue when regeneration is insufficient.
Granulation tissue
Granulation tissue contains:
- Newly formed capillaries.
- Fibroblasts.
- Inflammatory cells.
- Loose extracellular matrix.
It typically has a soft, pink-red granular appearance.
Primary versus secondary intention
| Feature | Primary intention | Secondary intention |
|---|---|---|
| Wound size | Small, clean edges | Large tissue defect |
| Tissue loss | Minimal | Significant |
| Granulation tissue | Relatively limited | More extensive |
| Wound contraction | Minimal | Prominent |
| Scar | Usually smaller | Usually larger |
| Example | Clean surgical incision | Large open wound |
Complications of wound healing
- Wound infection.
- Wound dehiscence.
- Excessive scar formation.
- Keloids.
- Hypertrophic scars.
- Contractures.
- Chronic nonhealing wounds.
Dental relevance: Extraction sockets and periodontal surgical wounds often heal through granulation tissue formation, remodeling and variable degrees of secondary intention.