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PA3.1-2 | Acute Inflammation — Vascular & Cellular Events, Mediators — SDL Guide

Learning Objectives

Define acute inflammation and describe its biological purpose.
Identify the five cardinal signs of acute inflammation and explain their cellular and vascular basis.
Outline the sequence of vascular events: vasoconstriction, vasodilation, increased permeability, stasis, and exudate formation.
Describe the leucocyte recruitment cascade — margination, rolling, adhesion, transmigration, and chemotaxis.
Explain the mechanisms of phagocytosis including opsonisation, engulfment, and microbicidal killing (oxygen-dependent and -independent).
Identify the major chemical mediators of acute inflammation and link each to its source and primary action.
Classify the morphological patterns of acute inflammation (serous, fibrinous, suppurative, ulcerative) with clinical examples.
List the possible outcomes of acute inflammation.

INSTRUCTIONS

Inflammation is the body's first line of defence — understanding it explains fever, wound healing, pus formation, and the mechanism of virtually every anti-inflammatory drug. This module builds a mechanistic map of acute inflammation from the first vascular twitch to the fate of the exudate. By the end, the cardinal signs, leucocyte trafficking cascade, and mediator pharmacology will form an integrated picture you can apply to any inflammatory condition.

References

Robbins & Kumar: Basic Pathology, 11th ed., Ch 2 (Acute and Chronic Inflammation) (textbook)
Harsh Mohan: Textbook of Pathology, 8th ed., Ch 5 (textbook)

Version 2.0 | NMC CBUC 2024

CLINICAL SCENARIO

You stub your toe. Within seconds the area turns red, swells, feels hot, throbs with pain, and you limp. Five ancient Latin words capture this perfectly. What is the molecular storm behind those five seconds — and why does your body trigger it at all?

WHY THIS MATTERS

Acute inflammation underpins the pathogenesis of infections, surgical wounds, myocardial infarction, appendicitis, and allergic reactions. NSAIDs, corticosteroids, and antihistamines — the most-prescribed drug classes in clinical practice — all target mediators you will map in this module. Understanding this cascade lets you reason about drug mechanisms, predict complications like abscess or chronic inflammation, and interpret histopathology reports.

RECALL

Before proceeding, recall from Year-1:
• Cells of the innate immune system (neutrophils, macrophages, mast cells, eosinophils).
• Basic structure of blood vessels (endothelium, basement membrane).
• Complement system: classical vs. alternative pathway, and the terminal membrane-attack complex.
• Arachidonic acid as a membrane phospholipid precursor.
This module builds directly on those foundations.

Definition and Purpose of Inflammation

Diagram explaining inflammation as a protective vascular and cellular response, distinguishing infection from sterile triggers and comparing acute and chronic inflammation. — **Panel A:** Living vascularised tissue, injury stimulus, blood vessel, endothelial lining, vasodilation, increased vascular permeability, protein-rich exudate, neutrophil migration, dead cell clearance, repair initiation. **Panel B:** Infective trigger, bacteria in wound, sterile triggers, bone fracture, myocardial infarct, gout crystal, shared pathway to inflammation. **Panel C:** Timeline from seconds to days to weeks/months, acute inflammation, vascular changes, neutrophilic exudation, chronic inflammation, mononuclear cells, fibroblasts, collagen deposition, tissue remodelling, '-itis' suffix examples.

Inflammation is a protective vascular and cellular response of living vascularised tissue to injury, infection, or abnormal stimuli, aimed at eliminating the causative agent, clearing dead cells, and initiating repair.

It is not synonymous with infection — sterile injury (e.g., a bone fracture, myocardial infarct, gout crystals) triggers identical mechanisms. The suffix -itis denotes inflammation of the named structure (appendicitis, meningitis, hepatitis).

Acute inflammation is rapid in onset (seconds to days), characterised by vascular changes and neutrophilic exudation. Chronic inflammation is slower, dominated by mononuclear cells and tissue remodelling — covered in a subsequent module (PA3.1, chronic portion).

> Clinical pearl link: Recognising that inflammation can be sterile is essential when reading postoperative or post-infarction histology reports that describe 'inflammation' without implying infection.

The Five Cardinal Signs and Their Basis

Celsus (1st century CE) described four signs; Virchow added a fifth:

Latin term	English	Mechanism
Rubor	Redness	Vasodilation → ↑blood flow → congestion
Tumor	Swelling	↑Vascular permeability → protein-rich exudate in interstitium
Calor	Heat	↑Blood flow (systemic temp. blood to periphery) + local metabolic activity
Dolor	Pain	Bradykinin, prostaglandin E₂, and substance P sensitise nociceptors
Functio laesa	Loss of function	Combined effect of pain, swelling, and tissue disruption

Each sign maps to a specific vascular or mediator event explored in the blocks below.

A labeled infographic maps the five cardinal signs of inflammation to their vascular and mediator mechanisms in an inflamed skin wound. — **Panel A:** Inflamed skin wound overview showing epidermis, dermis, dilated capillaries, congestion, protein-rich exudate, sensory nerve endings, tissue disruption, redness, swelling, and local heat.. **Panel B:** Rubor / Redness: vasodilation leading to increased blood flow and vascular congestion.. **Panel C:** Tumor / Swelling: increased vascular permeability with endothelial gaps and protein-rich exudate entering the interstitium.. **Panel D:** Calor / Heat: increased peripheral blood flow and increased local metabolic activity.. **Panel E:** Dolor / Pain: nociceptor sensitisation by bradykinin, prostaglandin E2, and substance P.. **Panel F:** Functio laesa / Loss of function: reduced movement due to combined pain, swelling, and tissue disruption..

SELF-CHECK

Which cardinal sign of acute inflammation is PRIMARILY explained by increased vascular permeability rather than vasodilation?

A. Rubor (redness)

B. Calor (heat)

C. Tumor (swelling)

D. Dolor (pain)

Reveal Answer

Answer: C. Tumor (swelling)

Tumor (swelling) results from protein-rich fluid (exudate) leaking into the interstitium due to increased vascular permeability. Rubor and calor are primarily due to vasodilation increasing blood flow. Dolor involves sensitisation of nociceptors by prostaglandins and bradykinin.

Vascular Events: The Haemodynamic Response

The vascular response unfolds in a precise sequence following injury:

1. Transient vasoconstriction (seconds): neurogenic reflex via axon reflex; very brief and clinically imperceptible.

2. Vasodilation (lasting): arterioles dilate first, then capillary bed opens. Mediators: histamine, nitric oxide (NO), and prostaglandins. Result: ↑blood flow → rubor + calor.

3. Increased vascular permeability: allows protein-rich fluid (>3 g/dL protein) to leak — forming exudate. Mechanisms:
• Endothelial cell contraction (most common) — histamine and leukotrienes cause cytoskeletal contraction, widening inter-endothelial gaps. Affects venules. Immediate, transient or delayed/prolonged.
• Direct endothelial injury — e.g., burns, caustic agents. Affects venules and capillaries. Immediate and sustained.
• Transcytosis — VEGF-stimulated vesicular transport through endothelial cytoplasm (important in tumours and chronic states).
• Leucocyte-mediated injury — ROS and proteases from adherent neutrophils damage endothelium.

4. Stasis: as fluid leaves the vessel, blood becomes viscous; flow slows. Leucocytes move to the vessel periphery (margination).

Exudate vs. transudate distinction (tested frequently):

	Exudate	Transudate
Protein	>3 g/dL	<2 g/dL
Specific gravity	>1.020	<1.012
Mechanism	Active inflammation (↑permeability)	Hydrostatic/oncotic imbalance
Example	Pleural empyema	Cardiac failure effusion

A three-panel medical diagram showing the sequence of vascular changes after injury, mechanisms of increased permeability, and the exudate versus transudate distinction. — **Panel A:** Sequential vascular response after injury: transient vasoconstriction, vasodilation, increased vascular permeability, stasis, leucocyte margination, rubor, calor, histamine, nitric oxide, prostaglandins, exudate.. **Panel B:** Mechanisms of increased vascular permeability: endothelial cell contraction in venules, direct endothelial injury in venules and capillaries, VEGF-mediated transcytosis, leucocyte-mediated endothelial injury by ROS and proteases.. **Panel C:** Exudate versus transudate comparison: protein concentration, inflammatory permeability mechanism, hydrostatic or oncotic imbalance, darker protein-rich exudate and pale low-protein transudate..