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 the acute inflammatory response.

What is Inflammation?

• Inflammation is a protective response.
• Key signs of inflammation (itis):
  • Appendicitis: Inflammation of the appendix
  • Gastritis: Inflammation of the stomach
  • Arthritis: Inflammation of joints

Inflammation: Overview

• Inflammation's primary goals:
  • Remove the initial cause of cell injury (e.g., microbes, toxins).
  • Remove the consequences of cell injury (e.g., necrotic cells and tissues).
  • Initiate the process of repair.
• Without inflammation:
  • Infections could not be controlled.
  • Wounds would not heal.
  • Injured tissue would become persistent sores.

Cardinal Signs of Inflammation

• Calor (Heat): Increased blood flow due to vasodilation. Mediators include histamine, prostaglandins, and bradykinin
• Rubor (Redness): Increased blood flow due to vasodilation — also histamine, prostaglandins, and bradykinin.
• Tumor (Swelling/Edema): Accumulation of fluid due to increased vascular permeability, and tissue damage. Histamine is responsible
• Dolor (Pain): Release of chemicals that stimulate nerve endings (e.g., bradykinin and PGE2). Nerve endings are stimulated through increased pain/swelling.
• Functio Laesa (Loss of Function): Increased pain/swelling, which causes loss of function.

Causes and Types of Inflammation

• Causes:
  • Infections (bacterial, viral, fungal, parasitic)
  • Tissue necrosis (ischemia, physical/chemical injury, trauma)
  • Foreign bodies (sutures, splinters, dirt)
  • Immune reactions (hypersensitivity, autoimmune diseases)
• Types:
  • Acute inflammation
  • Chronic inflammation
  • Granulomatous inflammation

The Steps of Inflammatory Response

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

Acute Inflammation

• 4 Key Events:
  • Vascular changes (vasodilation)
  • Microvascular changes (increased vascular permeability)
  • 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

• Phagocytes, dendritic cells, and epithelial cells have pattern recognition receptors that detect infectious agents.
• Examples: Toll-like receptors (TLRs), inflammasomes, Fc receptors, and complement system (lectin) recognize and bind to these substances.

I. Vascular Changes: Alteration in Vascular Flow and Caliber

• Vasodilation is the earliest manifestation of inflammation—caused by histamine and nitric oxide.
• Vasodilation increases blood flow to the site, leading to redness and warmth.
• Increased hydrostatic pressure contributes to swelling (edema).

II. Microvascular Changes: Increased Permeability of Microvasculature

• Increased permeability of blood vessels is a hallmark of acute inflammation.
• Histamine, kinins, and other mediators cause gaps between endothelial cells, allowing plasma proteins and leukocytes to escape into the interstitial space.
• Fluid leakage results in edema.

What is Edema?

• Edema is the accumulation of excess fluid in interstitial tissues or body cavities. Two major types of edema are transudate and exudate, differentiated by protein content and inflammatory cell involvement

Differences between Transudate and Exudate

• Transudate: Low protein content, low specific gravity (<1.020), results from hydrostatic imbalances, light straw color.
• Exudate: High protein content, high specific gravity (>1.020), results from inflammation and injury, yellowish-white appearance.

III. Cellular Events: WBC Extravasation and Phagocytosis

• Extravasation: Leukocytes migrate from blood vessels to the site of injury/infection. This involves several steps: margination, rolling, adhesion, transmigration, and chemotaxis.
• Phagocytosis: Phagocytic cells (neutrophils, macrophages) engulf and destroy pathogens, necrotic cells, or foreign material. This process involves recognition and attachment, engulfment, and killing/degradation.

Step 5: Chemotaxis and WBC Activation

• Transmigrated leukocytes move to the site of injury, guided by chemotactic agents.
• Chemotactic agents can be exogenous (e.g., bacterial products) or endogenous (e.g., from the complement system or cytokines).
• Different types of leukocytes will respond, depending on the type of stimulus (ex: neutrophils first, macrophages later).

Leukocyte Activation

• Activation of leukocytes by various stimuli leads to production of arachidonic acid metabolites, secretion of lysosomal enzymes, degranulation, cytokine secretion, and modulation of cell adhesion molecules (CAMs).

Phagocytosis

• This is the "process of engulfment".

• Phagocytic cells (Neutrophils, Macrophages) engulf and degrade material/pathogens. Steps include recognition/attachment, engulfment, killing/degradation.

• Oxygen-dependent killing uses NADPH oxidase complexes and other methods.

• Oxygen-independent methods include lysozyme, lactoferrin, and other proteins.

This quiz explores the fundamental concepts of inflammation, including its definition and the acute inflammatory response. Students will learn about the signs of inflammation, its primary goals, and the importance of the inflammatory process in healing and disease management.