Chronic Inflammation

Question 1

Acute Inflammation:
General Features

Answer 1

• Short Time Frame:
  
  • inflammatory stimulus is quickly resolved
• Cardinal Signs are prominent
  
  • redness
  • swelling
  • heat
  • pain
• neutrophils and fibrin predominate
• Outcome:
  
  • resolution with return to normal
  • Resolution with tissue fibrosis
  • Progression to chronic inflammation

Question 2

Chronic Inflammation:

General Features

Answer 2

• Long time Frame:
  
  • inflammatory stimulus is unresolved and persists
• Cardinal signs are not prominent
• Macrophages and lymphocytes predominates
• Cell-mediated immunity is an important component
• Outcome:
  
  • Ongoing without pregression/containment
  • Ongoing with progression/containment
  • Resolution with tissue damage and fibrosis

Question 3

Chronic Inflammation:
Development

Answer 3

• Major feature is persistence of the agent/material taht incited inflammation
  
  • highly resistant agent/material
    
    • mycobacteria, systemic fungi, foreign bodies, evasive agents
  • Low resistance of the host
    
    • inherited or acquired immunodeficiency, defects in the inflammatory response
• The acute response is unable to resolve the inflammatory stimulus

Question 4

Features of Chronic Inflammation:

Vascular Events

Answer 4

• Mediators of acute vascular changes are degraded
• Emigration shifts to monocytes and lymphocytes
  
  • neutrophils are short-lived and migrate for a short period of time
  • Neutrophils are chemotactic for monocytes

Question 5

Features of Chronic Inflammation:

Cells

Answer 5

• Monocytes/macrophages
  
  • activated macrophages have various morphologic and functional features
  • These can proliferate locally
• Lymphocytes
  
  • many subsets are involved
    
    • T-cells, B-cells, Plasma cells
    • Lymphokines help determine features fo the response
• NK cells
• Fibroblasts
  
  • proliferate in response to injury to produce collagen
• Endothelium
  
  • Meovascularization as part of the repair process

Question 6

Features of Chronic Inflammation:

Cells derived from macrophages

Answer 6

• Epithelioid macrophages
  
  • activated macrophages taht are larger, have abundant cytoplasm and a prominent secretory role
• Giant cells
  
  • multinucleated cells formed from the fusion of macrophages or epithelioid cells
  • These have secretory and pagocytic properties
  • Two morphologic types are described
    
    • Foreign body giant cells
    • Langhans giant cells

Question 7

Features of Chronic Inflammation:

Mediators

Answer 7

• The cytokine microenvironment is more complex than for acute inflammation
  
  • lymphokines
    
    • these drive Th1 or Th2 responses and mediate macrophage functions
  • Monokines
    
    • These are directed towards removal of the inciting stimulus as well as healing/resolution responses

Question 8

Resolution of Inflammation:

The Ideal

Answer 8

• The inciting stimulus is removed
• Pro-inflammatory mediators are removed and production stops
• Vessels return to normal and leukocyte emigration stops
• Inflammatory debris/exudate is removed
• Normal cells repopulate the area
• Tissue returns to normal
  
  • the tissue looks and functions the same as before the inflammation event

Question 9

Resolution of Inflammation:

Not so Idea

Answer 9

• The inciting stimulus is NOT removed
  
  • chronic inflammation
• Tissue does NOT return to normal
  
  • Irreversible loss of structure and function

Question 10

Healing and Repair

Answer 10

Healing is initiated at the time of injury and is promoted by factors produced during inflammation

Healing is the endpoint of injury and inflammation

Question 11

Mechanisms of Healing:

Regeneration

Answer 11

This is the ideal situation where the tissue returns to it’s pre-injury structure and function

Question 12

Mechanisms of Healing:

Replacement

Answer 12

This occurs when tissue is irreversibly damaged and replaced by fibrous connective tissue

Question 13

Criteria for Regeneration to Occur

Answer 13

• Stromal Integrity
  
  • basement membranes of epithelial surfaces and the exrtracellular matrix architecture of the tissue or organ must be intact
• Regenerative capacity of the injured cells
  
  • injured cells must be capable of regeneration

Question 14

Regeneration can occur with

Answer 14

• Labile cells
  
  • bone marrow cells and most mucosal surfaces
• Stable cells
  
  • parencymal cells such as hepatocytes and renal epithelium
  • mesenchymal cells such as fibroblasts and endothelium

Question 15

Regeneration can NOT occur with:

Answer 15

Permanent cells:

Neurons and cardiac myocytes

Question 16

Healing and Repari:

Replacement

Answer 16

• Damage which disrupts the stromal framework or involves permanent cells results in replacement with collagen
• Granulation tissue is the mechanism used to replace irreversibly damaged tissue

Question 17

Healing and Repair:

Replacement:

Granulation Tissue

Answer 17

• Transient fibrovascular tissue that grows into a site of irreversible damage
• It’s purpose is to fill the damaged area to enhance wound contraction and to replace the area with collagen

Question 18

Granulation Tissue

Answer 18

• Progresses through three main stages:
  
  • Inflammatory stage
    
    • Helaing is initiated and debris is cleared from the area
  • Proliferative stage
    
    • Endothelium and fibroblasts proliferate
  • Remodeling stage
    
    • Macrophages leave and the wound contracts
    • Blood vessels and fibroblasts regress

Question 19

Granulation Tissue:

Morphological Zones

Answer 19

• Zone of necrotic debris and inflammation
• Zone of capillary sprouts and arches
• Zone of capillary and fibroblast proliferation
• Zone of mature connective tissue

Question 20

Granulation Tissue:

Cell Functions:

Macrophages

Answer 20

• Removal of inflammatory debris
• Production of a variety of monokines involved in healing
  
  • platelet derived growth factor
  • Fibroblast growth factor
  • Transforming growth factor-beta

Question 21

Granulation Tissue:

Cell Functions:

Endothelium

Answer 21

• New vessels grow into the area in response to angiogenic factors
  
  • VEGF, TGF-b, angiopoetin
• Vessels provide nutrients to the healing area
• Vessels are highly permeable, and leak plasma and fluids into the area to support healing

Question 22

Granulation Tissue:

Cell Functions

Fibroblasts

Answer 22

• Production of collagen to fill in the damaged area
  
  • collagen production is induced by TGF-b, FGF, epidermal growth factor
• Wound contraction
  
  • myofibroblasts are specialized fibroblasts that are induced by TGF-b
  • They contract to diminsh the size of the wound

Question 23

Healing and Repair:

Wound Healing

Answer 23

• Wound healing occurs within two categories based on the extensiveness of the damage:
  
  • First intention healing
  • Second intention healing

Question 24

Wound Healing:

First Intention

Answer 24

• This is the best represented by incisional skin wounds
• The defect is small and healing occurs rapidly
• The resulting scar is usually mininal

Question 25

Wound Healing: Second Intention

Answer 25

* This is best represented by excisional skin wounds * The defect is large and healing can take a considerable period of time * The resulting scar can be extensive * Specialized tissues within the damaged area may be lost

Question 26

Healing and Repair: Factors affecting healing

Answer 26

* Nutritional status * Age * Presence of concurrent/systemic disease * Persistence of the damaging stimulus * Size and location of the damage