Inflammation (MOD)

What are the clinical (cardinals) signs of acute inflammation?

Sign	Medical Term	Cause
Redness	Rubor	Vasodilation
Heat	Calor	Increased blood flow
Swelling	Tumor	Fluid leakage into tissues
Pain	Dolor	Bradykinin & prostaglandins
Loss of function	Functio laesa	Tissue damage/swelling

What is Inflammation?

A protective response of the body to eliminate the cause of cell injury, remove damaged tissue, and begin healing.

What are the two types of inflammation?

Acute and Chronic

What is acute inflammation?

Acute Inflammation

• Rapid onset (minutes to days)

• Short duration

• Main cell: Neutrophils

Examples:

• Cut on your finger

• Bacterial infection

• Sprained ankle

Acute inflammation is a rapid, short-duration response characterized by fluid exudation and neutrophil migration that aims to eliminate the cause of injury and initiate tissue repair, ending in resolution, scar formation, abscess, ulcer, fistula, or chronic inflammation.

What is chronic inflammation?

Chronic Inflammation

• Lasts weeks, months, or years

• Main cells:

  • Macrophages

  • Lymphocytes

  • Plasma cells

Examples:

• Rheumatoid arthritis

• Tuberculosis

• Chronic hepatitis

What are the common causes of acute inflammation?

Acute inflammation can be triggered by infection, trauma, physical or chemical injury, necrosis, foreign bodies, or immune-mediated reactions, all of which cause tissue damage and activate the inflammatory response.

What happens in the vascular phase of Acute inflammation?

The vascular phase is the first stage of acute inflammation and involves changes in blood vessels.

1. Brief vasoconstriction occurs immediately after injury.

2. Vasodilation follows, caused by histamine, prostacyclin, and nitric oxide, increasing blood flow to the area.

3. Increased blood flow raises hydrostatic pressure, causing redness (rubor) and heat (calor).

4. Blood vessels become more permeable (leaky), allowing fluid and proteins to enter tissues.

5. This leakage causes edema (swelling/tumor).

6. As fluid leaves the vessels, neutrophils move toward the vessel wall (margination), preparing for migration into the injured tissue.

What are the the 5 different types of mechanism of increased vascular permeability:

endothelial contraction

endothelial retraction

direct endothelial injury

delayed prolonged response

leukocyte mediated damage

What is vascular permeability?

Vascular permeability means blood vessels become "leaky," allowing fluid and proteins to move from the bloodstream into tissues.

Normal vessel

[Cell][Cell][Cell]

After histamine

[Cell] [Cell] [Cell]

↑ gaps

What are the steps of cellular Phase in Acute Inflammation?

What is rolling in cellular Phase

Rolling is the first step of leukocyte (WBC) movement from the blood vessel to the site of injury.

Rolling is the first step of leukocyte recruitment in acute inflammation, where selectins on endothelial cells form weak bonds with Sialyl-Lewis X on leukocytes, causing the WBC to slow down and roll along the vessel wall.

Cellular Phase: Adhesion

After rolling, the WBC needs to stop completely so it can leave the blood vessel and enter the tissue.

Adhesion is the second step of leukocyte recruitment, where activated integrins on WBCs bind tightly to ICAM-1 and VCAM-1 on endothelial cells, causing the leukocyte to stop and prepare to exit the bloodstream.

Cellular Phase: Transmigration (Diapedesis)

This is the third step of leukocyte recruitment.

After the WBC has:

1. Rolled (selectins)

2. Adhered (integrins)

Transmigration (diapedesis) is the movement of leukocytes through the endothelial layer into tissues, mediated primarily by PECAM-1 (CD31) on both leukocytes and endothelial cells.

Cellular Phase: Chemotaxis

Chemotaxis is the directed movement of leukocytes toward a site of infection or injury, guided by chemical attractants such as C5a, IL-8, LTB₄, and bacterial products.

Step	Main Molecule
Rolling	Selectins
Adhesion	Integrins
Transmigration	PECAM-1 (CD31)
Chemotaxis	C5a, IL-8, LTB₄

What are the mediators of Chemotaxis?

Endogenous (Made by the Body)

1. C5a (Complement)

   • Powerful chemoattractant

2. LTB₄ (Leukotriene B4)

   • Attracts neutrophils

3. interleukin IL-8

   • Cytokine that recruits neutrophils

Exogenous (From Bacteria)

4. Bacterial products

   • Especially bacterial peptides and polysaccharides

example of Phagocytotic cells

○Neutrophils (early in acute inflammatory response)

○Monocytes and macrophages

○Dendritic cells

Outcomes of Acute Inflammation

Resolution

Resolution = Complete healing and return to normal tissue.

For resolution to occur:

✅ The inciting agent (bacteria, virus, toxin, injury) must be removed.

✅ The tissue must be able to regenerate (replace damaged cells).

✅ Inflammatory cells (especially neutrophils) and debris must be cleared away.

✅ Normal tissue structure and function are restored.

A localized collection of pus surrounded by a wall of inflammatory tissue.

Abscess

Impaired host defenses, obstruction, foreign body, trauma.

pain, fever, rupture, and swelling

What's in the pus?

🟢 Neutrophils (dead and alive)
🟢 Bacteria (if infection is present)
🟢 Necrotic tissue debris
🟢 Fluid

●Requirements for abscess formation: The body cannot rid itself of the inciting agent, or the process of repair and scarring is occurring more rapidly in the tissue around the site of the abscess.

loss of the surface lining (epithelium/mucosa) and deeper underlying tissue.

Ulcer

Mucosal defect

seen in GI tract

pain, hemorrhage, perforation

●If only the mucosa is lost, the correct term is an erosion.

●Microscopic morphology of an ulcer: The ulcer has four layers, which recapitulate steps from acute inflammation to repair. The layers, from superficial to deep, are fibrin, neutrophils, granulation tissue, and fibrosis.

●Complications of an ulcer: Pain; hemorrhage, if the ulcer involves a vessel; and perforation, resulting in hemorrhage within a cavity or the lumen of the gastrointestinal tract, or seeding of the peritoneal cavity with the contents of the gastrointestinal tract, causing peritonitis.

An abnormal passage (tunnel) connecting two organs or an organ to the skin.

Fistula

trauma, surgery, infection, inflammation.

enterocutaneous fistula (skin to colon, occurring in colon cancer or inflammatory bowel disease)

Infection or hemorrhage

Scar formation

Replacement of lost parenchyma with disorganized connective tissue (i.e. collagen).

Loss of function.

●Influenced by depth of injury, location, genetics, nutrition, etc.

●Requirements for scar formation: Loss of tissue in an organ not capable of regeneration or loss of basement membrane or other framework required for successful regeneration.

What are the causes of chronic inflammation?

Viral infection, persistent microbial infection, prolonged exposure to a toxin, and autoimmune dysfunction/disease

What are the cells involved in chronic inflammation?

Macrophages and Lymphocytes

What is the process of granulomatous inflammation (specific type of chronic inflammation?

collections of activated macrophages i.e. epithelioid histiocytes), can have multinucleated giant cells.

●Immune response designed to wall off irritant, infection, foreign body, or autoimmune conditions

●Associated conditions:

○Tuberculosis, sarcoidosis, silicosis, Crohn’s disease, foreign body granuloma (i.e. splinter, glass, suture), fungal infections (i.e. Histoplasmosis, Cryptococcosis)

Acute vs Chronic inflammation