Table of Contents · 6 sections
Inflammation is one of the fundamental processes in medicine. Without understanding its pathophysiology, it is impossible to comprehend the mechanisms of action of NSAIDs, glucocorticoids, antibiotics, and the pathogenesis of most diseases. This topic accounts for up to 15–20% of exam questions in pathophysiology. This article provides a comprehensive breakdown of the phases, mediators, clinical manifestations, and systemic responses.
Definition and cardinal signs
Inflammation is a standard pathological process evolutionarily formed as a protective response to tissue injury. Its purpose is to limit and destroy the damaging agent and restore the tissue.
The five cardinal signs were described by Celsus and Galen:
| Sign | Latin | Mechanism |
|---|---|---|
| Redness | Rubor | Arterial hyperemia → vasodilation |
| Swelling (edema) | Tumor | Exudation — leakage of plasma into tissue |
| Heat (elevated temperature) | Calor | Increased blood flow + pyrogens (IL-1, IL-6, TNF-α) |
| Pain | Dolor | Receptor irritation by bradykinin, prostaglandins, and exudate pressure |
| Loss of function | Functio laesa | Combination of all the above + tissue destruction |
Phases of inflammation
1. Alteration (injury)
Primary alteration is the direct tissue damage caused by an etiological factor (bacteria, trauma, burn). Secondary alteration is damage caused by released lysosomal enzymes and free radicals. Damaged cells release:
- Lysosomal enzymes (proteases, lipases, glycosidases)
- K⁺ ions (depolarization → pain)
- Phospholipase A₂ → arachidonic acid → cascade activation
2. Exudation (vascular phase)
Sequence of vascular reactions:
- Transient arteriolar spasm (seconds) — a reflex response to injury
- Arterial hyperemia — arteriolar dilation induced by histamine, bradykinin, NO. Increased blood flow → redness and heat
- Venous hyperemia — slowed outflow due to compression of veins by exudate, leukocyte margination, microthrombosis
- Stasis — complete cessation of blood flow in microvessels
Exudation — leakage of fluid and plasma proteins through the microvessel wall. Mechanisms: endothelial cell contraction (histamine, leukotrienes) and direct endothelial injury.
Types of exudate: serous, fibrinous, purulent, hemorrhagic, mixed.
3. Leukocyte emigration
Sequence: margination (peripheral orientation) → rolling (rolling along the endothelium, selectins) → adhesion (firm attachment, integrins) → diapedesis (migration through the wall) → chemotaxis (directed movement toward the focus).
Chemotactic factors: C5a (complement), LTB₄ (leukotriene), IL-8, bacterial peptides (f-Met-Leu-Phe).
4. Proliferation (repair)
The final phase — cell multiplication for tissue restoration. Key processes: angiogenesis (formation of new vessels), granulation tissue formation, epithelialization, remodeling.
Inflammatory mediators
Cellular mediators
| Mediator | Source | Effect |
|---|---|---|
| Histamine | Mast cells, basophils | Vasodilation, increased permeability, pruritus |
| Serotonin | Platelets | Increased permeability |
| Prostaglandins (PGE₂, PGI₂) | All cells (via COX-2) | Pain, fever, vasodilation. NSAID target |
| Leukotrienes (LTB₄, LTC₄) | Leukocytes (via 5-LOX) | Chemotaxis (LTB₄), bronchospasm (LTC₄/D₄) |
| Cytokines (IL-1, IL-6, TNF-α) | Macrophages | Fever, acute-phase proteins, endothelial activation |
| Nitric oxide (NO) | Endothelium, macrophages | Vasodilation, bactericidal action |
Plasma mediators
- Complement system: C3a, C5a — anaphylatoxins (mast cell degranulation, chemotaxis); C3b — opsonization; C5b-C9 — membrane attack complex (lysis)
- Kinin system: bradykinin — pain, vasodilation, increased permeability
- Coagulation system: fibrin limits the focus of inflammation, thrombin activates the endothelium
Systemic inflammatory response syndrome (SIRS) and sepsis
When inflammation spreads beyond the local focus, a systemic reaction develops. SIRS criteria (≥2 of 4):
- Temperature > 38 °C or < 36 °C
- Heart rate > 90/min
- Respiratory rate > 20/min or PaCO₂ < 32 mmHg
- Leukocytes > 12×10⁹/L or < 4×10⁹/L or > 10% immature forms
Sepsis (per Sepsis-3, 2016) is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Criterion: SOFA ≥ 2. Screening: qSOFA ≥ 2 (systolic BP ≤ 100, RR ≥ 22, altered mental status). Calculator: qSOFA online, SOFA online.
Acute and chronic inflammation
| Sign | Acute | Chronic |
|---|---|---|
| Duration | Minutes to days | Weeks to years |
| Main cells | Neutrophils | Macrophages, lymphocytes |
| Exudation | Pronounced | Minimal |
| Outcome | Resolution, suppuration, chronization | Fibrosis, atrophy, amyloidosis |
| Examples | Appendicitis, pneumonia, abscess | Rheumatoid arthritis, tuberculosis, atherosclerosis |
Frequently asked questions
Is inflammation good or bad?
Inflammation is a defense reaction: without it, the body cannot cope with infection or repair tissue. However, excessive or chronic inflammation destroys tissues and underlies many diseases (atherosclerosis, rheumatoid arthritis, Crohn's disease).
How do NSAIDs suppress inflammation?
NSAIDs block cyclooxygenase (COX) → reduce prostaglandin synthesis → decrease pain, edema, and fever. Read more: NSAIDs: Mechanism and Classification.
What is the difference between exudate and transudate?
Exudate is inflammatory fluid: high protein content (>30 g/L), cellular, turbid. Transudate is non-inflammatory fluid due to congestion: protein <30 g/L, clear. Distinguishing between them determines management tactics.
Study pathophysiology through interactive lessons. Related topics: NSAIDs, immunoglobulins, necrosis and apoptosis.