What is inflammation
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I now have everything needed for a thorough, well-sourced answer. Here is the full explanation:
Inflammation
Definition
Inflammation is a protective response of vascularized tissues to harmful stimuli - including infections, dead cells, and tissue damage - designed to eliminate the cause of injury, clear out necrotic cells, and initiate tissue repair. It is fundamentally a double-edged process: while it protects and heals, it can also cause collateral tissue damage.
"Inflammation is a response designed to defend the host against infection and injury. However, inflammatory reactions can also cause damage to normal tissues and contribute to disease."
- Robbins, Cotran & Kumar Pathologic Basis of Disease
The Cardinal Signs (Latin Nomenclature)
| Latin | English | Cause |
|---|---|---|
| Rubor | Redness | Increased blood flow (vasodilation) |
| Calor | Heat | Increased blood flow |
| Tumor | Swelling | Edema from vascular leakage |
| Dolor | Pain | Prostaglandins, neuropeptides, cytokines |
| Functio laesa | Loss of function | Pain + tissue injury combined |
Types of Inflammation
1. Acute Inflammation
Acute inflammation is the rapid, early response to injury. It has three major components:
- Vascular dilation - small vessels (mainly postcapillary venules) dilate, increasing blood flow (causing redness and heat)
- Increased vascular permeability - plasma proteins leak into tissues, forming an exudate (causing swelling)
- Leukocyte emigration - neutrophils are recruited from blood to the injury site to destroy the offending agent
Vascular changes in sequence:
- Vasodilation (driven by histamine on vascular smooth muscle)
- Increased permeability with protein-rich fluid efflux
- Stasis - blood slows, leukocytes move to the vessel wall (margination)
- Neutrophils adhere to endothelium and migrate into tissues (diapedesis)
Exudate vs. Transudate:
- An exudate has high protein content and cellular debris - it signals inflammation with increased vascular permeability
- A transudate has low protein content and results from osmotic/hydrostatic imbalance without increased permeability (e.g., heart failure)
- Pus is a purulent exudate rich in neutrophils and dead cell debris
Leukocyte steps (CAPSID):
- Margination - leukocytes move to the periphery of blood flow
- Rolling - loose, selectin-mediated adhesion
- Adhesion - tight binding via integrins (ICAM-1, VCAM-1)
- Diapedesis - migration through the endothelium
- Chemotaxis - directed movement toward the injury site (driven by C5a, IL-8, LTB4)
- Phagocytosis - engulfment and killing of pathogens
Morphologic Patterns of Acute Inflammation
| Pattern | Description | Example |
|---|---|---|
| Serous | Watery, low-protein fluid | Blister from a burn |
| Fibrinous | Fibrin-rich exudate | Fibrinous pericarditis ("bread and butter" heart) |
| Purulent (suppurative) | Pus-forming, neutrophil-rich | Abscess, bacterial pneumonia |
| Ulcerative | Epithelial loss exposing deeper tissue | Peptic ulcer |
Outcomes of Acute Inflammation
Three possible outcomes exist:
- Complete resolution - offending agent eliminated, tissue regenerates (most common when injury is limited)
- Scarring (fibrosis) - when tissue destruction is extensive or when the tissue cannot regenerate
- Progression to chronic inflammation - when the acute response cannot resolve the injury
2. Chronic Inflammation
Chronic inflammation is a prolonged response (weeks to months) where inflammation, tissue injury, and attempted repair coexist simultaneously.
Causes:
- Persistent infections by microorganisms difficult to eradicate (mycobacteria, fungi, some viruses, parasites)
- Hypersensitivity/autoimmune diseases - self-perpetuating T and B lymphocyte reactions (rheumatoid arthritis, multiple sclerosis, IBD)
- Toxic substances - silica (silicosis), oxidized lipids (atherosclerosis)
Morphologic features (distinct from acute):
- Mononuclear cell infiltration: macrophages, lymphocytes, plasma cells (not neutrophils)
- Tissue destruction
- Attempted healing via angiogenesis and fibrosis
Key cells:
- Macrophages - the dominant cell; they phagocytose debris, present antigens, secrete cytokines (TNF, IL-1, IL-6, IL-12), reactive oxygen species, and growth factors that drive both injury and repair
- Lymphocytes (T cells) - activate macrophages via IFN-γ; B cells differentiate into plasma cells that produce antibodies
- Eosinophils - prominent in allergic and parasitic reactions
- Mast cells - release histamine, contribute to early vascular responses
Granulomatous inflammation is a special pattern of chronic inflammation - a distinctive collection of epithelioid macrophages (activated macrophages) surrounded by a rim of lymphocytes, sometimes with giant cells. It occurs when a T-cell/macrophage response is mounted against an agent that resists eradication (e.g., tuberculosis, sarcoidosis, Crohn's disease, fungal infections).
Mediators of Inflammation
The inflammatory response is orchestrated by a range of chemical mediators:
| Mediator | Source | Main Actions |
|---|---|---|
| Histamine | Mast cells, basophils, platelets | Vasodilation, increased permeability |
| Prostaglandins | Mast cells, leukocytes | Vasodilation, pain, fever |
| Leukotrienes | Mast cells, leukocytes | Increased permeability, chemotaxis |
| TNF, IL-1, IL-6 | Macrophages, endothelial cells | Endothelial activation; systemic: fever, shock |
| Chemokines | Leukocytes, macrophages | Chemotaxis and leukocyte activation |
| Complement (C3a, C5a) | Plasma (liver-derived) | Chemotaxis, mast cell activation, opsonization |
| Kinins (bradykinin) | Plasma (liver-derived) | Vascular permeability, pain, vasodilation |
| PAF | Leukocytes, mast cells | Vasodilation, permeability, leukocyte activation |
Mediators are either cell-derived (rapidly released from pre-formed granules, or synthesized de novo) or plasma-derived (inactive precursors activated by proteolytic cleavage - complement, kinins).
Systemic Effects of Inflammation (Acute Phase Response)
When inflammation is significant, systemic effects occur, driven mainly by cytokines (TNF, IL-1, IL-6):
- Fever - prostaglandin E2 acts on the hypothalamus
- Leukocytosis - release of neutrophils from bone marrow
- Acute phase proteins - liver produces CRP, fibrinogen, serum amyloid A
- Fatigue and malaise
- In severe cases: septic shock (hypotension, disseminated intravascular coagulation)
Clinical Relevance
Inflammation underpins a huge range of diseases:
- Beneficial (protective): bacterial pneumonia, wound healing, abscess
- Harmful (disease-causing): atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, asthma, multiple sclerosis, Alzheimer's disease, Type 2 diabetes (chronic low-grade inflammation)
Anti-inflammatory drugs target specific mediators:
- NSAIDs/Aspirin - inhibit COX enzymes → block prostaglandins
- Corticosteroids - broadly suppress cytokine production and leukocyte function
- Biologics (anti-TNF, anti-IL-6, anti-IL-1) - target specific cytokines in chronic inflammatory diseases
Source: Robbins, Cotran & Kumar - Pathologic Basis of Disease, Chapter 3 (Inflammation and Repair)
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