Lecture 7: Inflammation Overview

Lecture 7: Inflammation: Introduction & Acute Inflammation

• Learning Outcomes: Students will be able to define inflammation and discuss the events and components of an acute inflammatory response.

What is Inflammation?

• Inflammation is an inflammatory response to tissue injury.
• Types of inflammation resulting in inflammation include: appendicitis (appendix inflammation), gastritis (stomach inflammation), and arthritis (joint inflammation).

Inflammation: Overview

• Inflammation is a protective response.
• Its goals are to eliminate the initial cause of injury (e.g., bacteria, toxins), the consequences of cell injury (e.g., necrotic cells), and initiate the repair process.
• Without inflammation, infections would not be controlled, wounds would never heal, and injured tissue would remain open sores.

Cardinal Signs of Inflammation

• Calor (Heat): Due to vasodilation (increased blood flow) from histamine, prostaglandins, and bradykinin.
• Rubor (Redness): Increased blood flow.
• Tumor (Swelling/Edema): Fluid accumulation due to increased permeability and tissue damage, especially from histamine, tissue damage.
• Dolor (Pain): Release of chemicals (e.g., bradykinin and PGE2) which stimulate nerve endings.
• Functio Laesa (Loss of Function): Increased pain and swelling.

Causes and Types of Inflammation

• Infections: Bacterial, viral, fungal, parasitic.
• Tissue Necrosis: Ischemia (lack of blood supply), physical/chemical injury, trauma.
• Foreign Bodies: Sutures, splinters, dirt.
• Immune Reactions: Hypersensitivity, autoimmune diseases.
• Types:
  • Acute inflammation (initial response)
  • Chronic inflammation (long-term response)
  • Granulomatous inflammation (a type of chronic inflammation)

The Steps of Inflammatory Response

• Recognition: Host cells recognize the offending agent.
• Recruitment: Leukocytes and plasma proteins move to the site of injury.
• Removal: Activated leukocytes eliminate the offending agent.
• Regulation: Termination of the response.
• Repair: Damaged tissue is repaired.

Acute Inflammation

• Vascular Changes: Vasodilation (increased blood flow).
• Microvascular Changes: Increased vascular permeability (plasma proteins and white blood cell leakage).
• Cellular Events: WBC emigration, accumulation, and activation at the site of injury.
• Chemical Mediators: Derived from plasma proteins and cells.

Recognition of Microbes, Necrotic Cells, and Foreign Substances

• Danger signals are triggered from microbes and dead cells.
• Phagocytes, dendritic cells, and epithelial cells express pattern recognition receptors that recognize infectious agents.
  • Examples include: toll-like receptors (TLRs), inflammasomes, Fc receptors, and the complement system (lectin).

I. Vascular Changes: Alteration in Vascular Flow and Caliber

• Earliest manifestation is vasodilation, which is induced by histamine and nitric oxide.
• Vasodilation leads to increased blood flow resulting in redness (rubor) and heat (color).

II. Microvascular Changes: Increased Permeability of Microvasculature

• A hallmark of acute inflammation.
• Caused by histamine, kinins, and other mediators.
• Increased gaps between endothelial cells lead to increased vascular permeability, allowing plasma proteins and leukocytes to escape and enter sites of infection/injury.
• Fluid leak results in edema (swelling).

What is Edema?

• Edema is the accumulation of excess fluid in interstitial tissues or serous cavities.
  • It's classified into transudate (low protein) and exudate (high protein).

Differences between Transudate and Exudate

• Transudate: Low protein content, low specific gravity (<1.020), result from hydrostatic imbalance, light straw color.
• Exudate: High protein content, high specific gravity (>1.020), result from inflammation/injury, yellowish-white colored.

III. Cellular Events: WBC Extravasation and Phagocytosis

• WBCs migrate to the site of injury and exit blood vessels, a process called extravasation.
• Extravasation steps include margination, rolling, adhesion, transmigration, and chemotaxis.

Step 5: Chemotaxis and WBC Activation

• Transmigrated leukocytes migrate to sites of injury along chemotactic gradients.
• Chemotactic agents can be exogenous or endogenous.
• Examples include soluble bacterial products, components of the complement system (e.g. C5a), and cytokines (e.g IL-8, leukotrienes).
• Leukocyte type varies depending on the stimulus and age of the inflammatory response (e.g., neutrophils in early stages, macrophages later).

Leukocyte Activation

• Activated by microbes, necrotic cells, antigen-antibody complexes, and chemotactic factors.
• Activation results in production of arachidonic acid metabolites, secretion of lysosomal enzymes, degranulation, cytokine secretion, and modulation of cell adhesion molecules (CAMs).

Phagocytosis

• Process of engulfing and eliminating solid particles (e.g., bacteria, necrotic tissue, foreign material) by phagocytic cells (e.g., neutrophils, macrophages).
• Three stages: Recognition/attachment, engulfment (phagosome formation), killing/degradation (phagolysosome formation).
  • Killing/degradation uses both oxygen-dependent and oxygen-independent mechanisms.

References

• Robbins and Cotran Pathologic Basis of Disease, 10th ed. (2021)
• Harsh Mohan Textbook of Pathology, 7th ed.