Inflammation & Tissue Repair

What are the three lines of defense?

Physical/chemical defense

Inflammatory response

Immune response

What is innate immunity?

Immediate (minutes–hours), nonspecific (any pathogen), no memory.

Inflammation

Cellular response of the body to tissue damage & injury; caused by allergy, injury or infection

Three stages of acute inflammation.

Vascular → cellular → opsonization

Vascular Stage of Inflammation

Brief vasoconstriction → vasodilation → ↑ capillary blood flow (meaning redness, and heat increased). Protein/fluid exudates enter extravascular spaces → increasing amount of fluid in tissue spaces = swelling, pain, ↓ mobility.

Cellular Stage of Inflammation

Invasion of leukocytes (mainly neutrophils). Blood flow slows, delivery & action of leukocytes through: 1) Adhesion & margination 2) Transmigration 3) Chemotaxis.

Why is there a higher risk of clots during inflammation?

Because blood flow slows & RBCs are pushed aside as WBCs move to the vessel wall.

What is Chemotaxis in the cellular stage of inflammation?

Movement in response to a chemical gradient

What is margination in the cellular stage of inflammation?

Adhesion of the leukocytes to the wall of the blood vessel, preparing to exit into tissue

What is transmigration in the cellular stage of inflammation?

Movement of the WBCs from the vascular space to the extravascular spaces or tissues.

Which WBCs are the first responders and most numerous?

Neutrophils

What is Exudate?

Fluid that has left the vascular space in response to an inflammatory condition

Types of Inflammatory Exudates

Serous: watery

Fibrinous: thick, clotted

Purulent: pus

Abscess: walled-off pus

Hemorrhagic: bloody

Opsonization Stage of Inflammation

Coats foreign antigens → triggers inflammation → makes them easier for macrophages & WBCs to phagocytize. Key opsonins: C3b and antibodies.

What is an opsonin?

A molecule that marks pathogens or debris for phagocytosis.

How do neutrophils recognize opsonized invaders?

Neutrophil receptors bind the tags, activating the cell to start phagocytosis.

What are pseudopods?

Extensions of the neutrophil that wrap around the invader during phagocytosis.

What is a phagosome?

A bubble inside the neutrophil that encloses the invader after it is engulfed.

What is a phagolysosome?

A phagosome fused with a lysosome, where enzymes and oxygen radicals destroy the invader.

What is the goal of inflammation?

Increase blood flow to the site, increase healing cells at the site, & prepare for tissue repair.

What are some systemic manifestations of inflammation? Recall and explain each.

Fever, leukocytosis (↑ WBCs), ↑ circulating plasma proteins

Hallmarks of Inflammation

Pain, redness, swelling, heat, loss of function

What causes pain during inflammation?

Prostaglandins sensitize pain nerve endings so that mediators like bradykinin, histamine, and leukotrienes trigger stronger pain signals

How does fever occur in inflammation?

Pyrogens raise the hypothalamic set point, causing the body to generate and retain heat.

What are pyrogens?

Fever producing agents

Define Prostaglandins

Chemical mediators that regulate cell functions and participate in the inflammatory response.

How are prostaglandins formed?

Cell injury or immune activation → Phospholipids → arachidonic acid (via phospholipase A₂)

Arachidonic acid → prostaglandins (via COX-1 or COX-2)

Act locally to cause pain, inflammation, and fever

Examples of Antiprostaglandins

Aspirin, acetaminophen, NSAIDs (block prostaglandin activity to reduce pain, fever, and inflammation).

COX-1 – Functions and locations

• Where it’s found: Stomach, kidneys, blood vessels, platelets, and most tissues.

• What it does:

  • Stomach: Decreases acid, increases mucus, regulates blood flow → protects stomach lining.

  • Kidneys: Maintains adequate blood flow and kidney function.

  • Cardiovascular system: Regulates blood vessel tone (vasoconstriction & vasodilation) and platelet function.

• Overall: Always active (“housekeeping” enzyme). Blocking COX-1 with NSAIDs → can cause stomach irritation, ulcers, bleeding.

COX-2 – What it does and where it’s found

• Where it’s found: Brain, bone, kidneys, GI tract, female reproductive system.

• What it does:

  • Usually inactive or low until pain or inflammation occurs.

  • Activated by inflammatory signals (interleukin-1, TNF-alpha), injury, or H. pylori infection.

  • Produces prostaglandins that cause pain, swelling, and other signs of inflammation.

• Drug effects:

  • COX-2 inhibitors (selective NSAIDs) reduce pain and inflammation.

  • Usually cause less stomach damage than non-selective NSAIDs, but long-term use can affect GI, kidney, and heart function.

Bradykinin

Inactive in plasma/mast cells; vasodilator that causes pain; broken down by ACE angiotensin converting enzyme

Complement

Cascade of 20+ proteins that destroy antigens; triggers mast cells to release histamine

Histamine

Released by mast cells; causes vasodilation, muscle constriction, tissue swelling, and itching

Leukotrienes

Released by mast cells; contributes to asthma and allergy symptoms

Prostaglandins

In most tissues; released by mast cells; increase capillary permeability, attract WBCs to site of inflammation, cause pain, and reduce fever

What are the two types of chronic inflammation?

Nonspecific or Granulomatous chronic inflammation

Nonspecific chronic inflammation

macrophages and lymphocytes accumulate at the site of tissue damage, leading to scar tissue formation from fibroblast proliferation.

Granulomatous chronic inflammation

Macrophages surround substances the body can’t remove, forming small granulomas (1–2 mm) that are encircled by lymphocytes.

What does osteoarthritis do?

Produces inflammation and degeneration of joints; “wear and tear” arthritis.

What tissues are affected in osteoarthritis?

Cartilage, bone, and synovium are degraded; inflammation develops in the synovial fluid.

Osteoarthritis – common symptoms

Joint pain, morning stiffness, instability, limited mobility

What is Gout?

An arthritic condition caused by overproduction of uric acid or inability to excrete uric acid, leading to hyperuricemia.

3 stages of gout

Acute gouty arthritis → Intercritical gout → Chronic tophaceous gout

Acute gouty arthritis

Hyperuricemia, pain & swelling of one joint (usually great toe), pain often starts at night, lasts 10 days.

Intercritical gout

Symptom-free periods of several years, followed by recurrence of gout attacks.

Chronic tophaceous gout

Solid urate crystal deposits (tophi) in joints and other tissues; can lead to joint deformity and kidney damage.

What is arachidonic acid?

A fatty acid in cell membranes that produces prostaglandins, thromboxanes, and leukotrienes involved in inflammation and immune responses.