Inflammation: Acute vs Chronic / Resolution and Healing

Question 1

What are the differences between Acute and Chronic Inflammation?

Answer 1

• Duration
• Characteristics of the inflammatory process
• Morphology
• Outcome

Question 2

What are the general features of Acute inflammation?

Answer 2

• Short time frame
  
  • Inflammatory stimulus is quickly resolved
• Cardinal signs are prominent
  
  • Redness (Hyperemia/ vasodilation)
  • Swelling (Increased vascular leakage)
  • Heat (Increased blood flow and mediator effects)
  • Pain (Mediators, swelling and tissue injury)
• Neutrophils and fibrin predominate
• Outcome:
  
  • Resolution with return to normal
  • Resolution with tissue fibrosis
  • Progression to chronic inflammation

Question 3

What are the general features of Chronic Inflammation?

Answer 3

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

Question 4

How does Chronic Inflammation develop?

Answer 4

• Major feature is the persistence of the agent/material that incited inflammation
  
  • Highly resistant agent/material
    
    • Mycobateria, 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 5

What vascular events are a feature of chronic inflammation?

Answer 5

• Mediators of acute vasculr changes (eg: histamine, kinins) are degraded
• Emigration shifts to monocytes and lyphocytes
  
  • Neutrophls are short-lied and migrate for a short period of time
  • Neutrophils are chemotactic for monocytes

Question 6

What cells are features of chronic inflammation?

Answer 6

• Monocytes / Macrophages
  
  • ​activated macrophages have various morphologic and functional features
  • Can proliferate locally
• Lymphocytes
  
  • ​many subsets involved
    
    • T-cells, B-cells, plama cells
    • Lymphokines help determine features of the response
• NK cells
• Fibroblasts
  
  • Proliferate in response to injury to produce collagen
• Endothelium
  
  • ​Neovascularization as part of the repair process

Question 7

What cells are derived from macrophages?

Answer 7

• Epithelioid macrophages
• Giant cells

Question 8

What is an Epithelioid macrophage?

Answer 8

• Activated macrophge that is larger, has abundant cytoplasm and a prominent secretory role

Question 9

What are Giant Cells?

Answer 9

• Multinucleated cells formed from the fusion of macrophages or epithelioid cells
• These have secretory and phagocytic properties
• 2 morphologic types are described:
  
  • Foreign body giant cells
  • Langhans giant cells

Question 10

What Mediators are features of Chronic inflammation?

Answer 10

• Cytokine microenvironment is more complex than for acute inflammation
  
  • Lymphokines
    
    • Drive T_H1 or T_H2 responses and mediate macrophage functions
  • Monokines
    
    • Directed towards removal of the inciting stimulus as well as healing / resolution responses

Question 11

What is the Ideal resolution of inflammation?

Answer 11

1. Inciting stimulus is removed
2. Pro-inflammatory mediators are removed and production stops
3. Vessels return to normal and leukocyte emigration stops
4. Inflammatory debris / exudate is removed
5. Normal cells repopulate the area
6. Tissue returns to normal (regeneration)
   
   • The tissue looks and functions the same as before the inflammatino event

Question 12

What is the non-ideal resolution of inflammation?

Answer 12

1. Inticing stimulus is not removed
   
   • chronic inflammation
2. Tissue does NOT return to normal
   
   • irreversible loss of structure and function

Question 13

What is healing and repair?

Answer 13

• 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 14

What are the mechanisms of healing?

Answer 14

• Regeneration:
  
  • ideal situation where teh tissue returns to it’s pre-injury structure and function
• Replacement:
  
  • occurs when tissue is irreversibly damaged and replaced by fibrous connective tissue

Question 15

What are the criteria for regeneration?

Answer 15

• Stomal integrity:
  
  • Basement membranes of epithelial surfaces and the extracellular matrx architecture of the tissue or organ must be intact
• Regenerative capacity of the injured cells
  
  • Injured cells must be capable of regeneration

Question 16

What cells can regenerate?

Answer 16

• Labile cells
  
  • Bone marrow cells and most mucosal surfaces
• Stable cells
  
  • Parenchymal cells such as hepatocytes and renal epithelium
  • Mesenchymal cells such as fibroblasts and endothelium

Question 17

What cells can NOT regenerate?

Answer 17

• Permanent cells
  
  • Neurons and cardiac myocytes

Question 18

What is Replacement?

Answer 18

• 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 19

What is granulation tissue?

Answer 19

• A transient fibrovascular tissue that grows into a site of irreversible damage
• Its purpose is to fill the damaged area to enhance wound contraction and replace the area with collagen
• Has 3 stages:
  
  • Inflammatory
  • Poliferative
  • Remodeling

Question 20

What is the stages of granulation tissue?

Answer 20

• Inflammatory
  
  • healing is initiated
  • debris is cleared from the area
• Proliferative
  
  • Endothelium and fibroblasts proliferate
• Remodeling
  
  • Macrophages leave and the wound contracts
  • Blood vessels and fibroblasts regress

Question 21

What are the morphological zones of granulation tissue?

Answer 21

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

Question 22

What is the function of Macrophagesin granulation tissue?

Answer 22

• Removal of inflammatory debris
• Production of a variety of monokines involved in healing
  
  • Platelet derived growth factor (PDGF)
  • Fibroblat growth factor (FGF)
  • Transforming growth factor-beta (TGF-B)

Question 23

What is the function of endothelium in granulation tissue?

Answer 23

• New vessels grow into the area in response to angiogenic factors (Neovascularization)
  
  • 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 24

What is the function of fibroblasts in granulation tissue?

Answer 24

• Production of collagen to fill in the damaged area
  
  • Collagen production is induced by TGF-B, FGF, Epidermal growth factor (EGF)
• Wound contraction
  
  • Myofibroblasts are specialized fibroblats that are induced by TGF-B
  • They contract to diminish the size of the wound

Question 26

What is wound healing?

Answer 26

• Wound healing occurs within 2 categories based on the extensiveness of the damage:
  
  • First intention healing
  • Second intention healing

Question 27

What is first intention healing?

Answer 27

• Best represented by incisional skin wounds
• The defect is small and healing occurs rapidly
• The resulting scar is usually minimal

Question 28

What is second intention healing?

Answer 28

• Best represented by exciional 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 29

What factors affect healing?

Answer 29

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