Pathology chapters
Acute inflammation
What inflammation is for, the cardinal signs, the vascular changes and leakage that cause swelling, how neutrophils leave the vessels (margination, rolling, adhesion, transmigration, chemotaxis), how they kill microbes, exudate versus transudate, and the outcomes of acute inflammation.
- Acute inflammation is the rapid, short-lived response to injury or infection that delivers fluid, plasma proteins and neutrophils to the site; its signs are redness, heat, swelling, pain and loss of function.
- Vascular changes: brief vasoconstriction, then vasodilation (redness, heat) and increased permeability (protein-rich exudate: swelling).
- Neutrophils leave vessels by margination → rolling (selectins) → firm adhesion (integrins) → transmigration and move by chemotaxis (C5a, IL-8, LTB4), then phagocytose opsonised microbes and kill them with the respiratory burst.
On this page
Overview
Inflammation is the body's protective response to infection and tissue injury. It brings defence cells and molecules from the blood to the site, removes the cause, clears dead tissue, and starts repair.
Acute inflammation is fast (minutes to hours), short-lived (days), and dominated by fluid exudation and neutrophils. Chronic inflammation lasts longer and is dominated by lymphocytes and macrophages (see chronic inflammation).
Inflammation is protective, but it can also cause harm: anaphylaxis, rheumatoid arthritis, and scarring are examples of inflammation damaging the body.
Causes
Infections (the commonest), tissue necrosis (for example an infarct), foreign bodies, immune reactions (allergy, autoimmunity), trauma, burns, chemicals.
Cardinal signs
| Sign | Latin | Cause |
|---|---|---|
| Redness | Rubor | Vasodilation |
| Heat | Calor | Vasodilation, more blood flow |
| Swelling | Tumor | Exudate (oedema) |
| Pain | Dolor | Prostaglandins, bradykinin, swelling |
| Loss of function | Functio laesa | Pain and swelling |
The first four were described by Celsus; loss of function was added by Virchow.
Vascular changes
- Transient vasoconstriction (seconds).
- Vasodilation of arterioles (histamine, nitric oxide): increased blood flow → redness and heat.
- Increased vascular permeability: protein-rich fluid leaves the vessels → swelling (exudate).
- Stasis: blood becomes concentrated and slows, allowing leucocytes to marginate.
Mechanisms of increased permeability
- Endothelial cell contraction in post-capillary venules: the commonest mechanism; rapid and short-lived (immediate transient response), caused by histamine, bradykinin, leukotrienes.
- Direct endothelial injury (burns, toxins): immediate and sustained.
- Leucocyte-mediated injury.
- Increased transcytosis (VEGF).
- Leakage from new blood vessels (angiogenesis) during repair.
The commonest cause of increased permeability is endothelial contraction in venules, caused mainly by histamine.
Exudate vs transudate
| Feature | Exudate | Transudate |
|---|---|---|
| Cause | Inflammation (increased permeability) | Hydrostatic or oncotic imbalance (heart failure, low albumin) |
| Protein | High (more than about 3 g/dL) | Low (less than about 3 g/dL) |
| Specific gravity | Above 1.020 | Below 1.012 |
| Cells | Many (neutrophils, etc.) | Few |
| Appearance | Cloudy | Clear |
| Examples | Pneumonia effusion, peritonitis, TB effusion | Heart failure effusion, ascites in cirrhosis or nephrotic syndrome |
For pleural fluid, Light's criteria compare fluid and serum protein and LDH to identify an exudate.
Exudate = high protein, cells, inflammation. Transudate = low protein, pressure or oncotic imbalance.
Pus is a purulent exudate rich in neutrophils, dead cells and microbes.
Leucocyte recruitment
| Step | Molecules |
|---|---|
| Margination | Slow flow pushes white cells to the vessel wall |
| Rolling | Selectins (E-selectin and P-selectin on endothelium; L-selectin on leucocytes) bind loosely |
| Firm adhesion | Integrins on leucocytes (LFA-1, Mac-1) bind ICAM-1 and VCAM-1 on endothelium, activated by chemokines |
| Transmigration (diapedesis) | Leucocytes squeeze between endothelial cells, mainly in post-capillary venules, using PECAM-1 (CD31) |
| Chemotaxis | Movement towards the site along a chemical gradient |
Chemotactic agents: bacterial products, C5a, leukotriene B4 (LTB4), chemokines (IL-8).
Timing: neutrophils dominate in the first 6–24 hours; they are replaced by monocytes/macrophages after 24–48 hours. (In Pseudomonas infections neutrophils persist; in viral infections lymphocytes may come first; in allergy, eosinophils.)
Rolling = selectins. Firm adhesion = integrins (with ICAM-1). Transmigration = PECAM-1.
Phagocytosis
- Recognition and attachment: opsonins (IgG and complement C3b, and collectins) coat microbes; phagocytes bind them through Fc and complement receptors.
- Engulfment: pseudopods surround the microbe, forming a phagosome, which fuses with lysosomes to form a phagolysosome.
- Killing and degradation:
- Oxygen-dependent (most effective): NADPH oxidase produces superoxide (the respiratory burst); myeloperoxidase converts hydrogen peroxide and chloride to hypochlorous acid (HOCl), the most potent bactericidal system.
- Oxygen-independent: lysozyme, lactoferrin, defensins, major basic protein (eosinophils).
Neutrophils can also release neutrophil extracellular traps (NETs) that trap microbes.
Defects of leucocyte function
| Disorder | Defect | Features |
|---|---|---|
| Leucocyte adhesion deficiency type 1 | Integrin (CD18) defect | Recurrent infections, delayed separation of the umbilical cord, no pus |
| Chronic granulomatous disease | NADPH oxidase defect (no respiratory burst) | Recurrent infections with catalase-positive organisms (S. aureus, Aspergillus), granulomas; abnormal nitroblue tetrazolium or DHR test |
| Chédiak-Higashi syndrome | Defect in lysosome fusion (LYST gene) | Giant granules, recurrent infections, partial albinism, neuropathy |
| Myeloperoxidase deficiency | No HOCl | Usually mild; Candida infections |
Morphological patterns
- Serous: watery, low-cell fluid (skin blisters, effusions).
- Fibrinous: fibrin-rich exudate on serous surfaces (pericarditis: "bread and butter" appearance).
- Purulent (suppurative): pus; abscess is a localised collection of pus (staphylococci).
- Ulcer: loss of the surface epithelium with inflamed base (peptic ulcer).
Outcomes of acute inflammation
- Complete resolution: the usual outcome when injury is limited and tissue can regenerate.
- Healing by fibrosis (scarring): after extensive destruction or in tissues that cannot regenerate.
- Abscess formation.
- Progression to chronic inflammation.
Expect: cardinal signs, the sequence of vascular changes, the commonest mechanism of increased permeability, exudate vs transudate values, the steps of leucocyte recruitment with selectins, integrins and PECAM-1, chemotactic agents, opsonins, oxygen-dependent killing (NADPH oxidase, myeloperoxidase), leucocyte defects (LAD, CGD, Chédiak-Higashi), patterns and outcomes.
Quick revision
- Cardinal signs: rubor, calor, tumor, dolor, functio laesa.
- Vasodilation → redness, heat; permeability → exudate.
- Commonest permeability mechanism: venular endothelial contraction (histamine).
- Exudate: protein > 3 g/dL, SG > 1.020; transudate: low protein, SG < 1.012.
- Rolling (selectins) → adhesion (integrins/ICAM-1) → transmigration (PECAM-1) → chemotaxis (C5a, IL-8, LTB4).
- Neutrophils first 6–24 h; macrophages by 24–48 h.
- Opsonins: IgG, C3b. Killing: NADPH oxidase, myeloperoxidase (HOCl).
Written by The House Job from standard pathology references (Robbins and Cotran Pathologic Basis of Disease is the book named in the UHS PGET syllabus).
FAQ
What are the cardinal signs of inflammation?
Redness (rubor), heat (calor), swelling (tumor), pain (dolor) and loss of function (functio laesa).
What is the difference between an exudate and a transudate?
An exudate has a high protein content and many cells because of increased vascular permeability; a transudate has low protein and results from pressure or oncotic imbalance.
Which cells predominate in early acute inflammation?
Neutrophils, during the first 6–24 hours.
What is opsonisation?
Coating of microbes with molecules such as IgG and C3b that make them easier for phagocytes to recognise and engulf.