Chronic Inflammation Flashcards
Acute Inflammation:
General Features
- 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
Chronic Inflammation:
General Features
- 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
Chronic Inflammation:
Development
- 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
- highly resistant agent/material
- The acute response is unable to resolve the inflammatory stimulus
Features of Chronic Inflammation:
Vascular Events
- 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
Features of Chronic Inflammation:
Cells
- 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
- many subsets are involved
- NK cells
- Fibroblasts
- proliferate in response to injury to produce collagen
- Endothelium
- Meovascularization as part of the repair process
Features of Chronic Inflammation:
Cells derived from macrophages
- 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
Features of Chronic Inflammation:
Mediators
- 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
- lymphokines
Resolution of Inflammation:
The Ideal
- 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
Resolution of Inflammation:
Not so Idea
- The inciting stimulus is NOT removed
- chronic inflammation
- Tissue does NOT return to normal
- Irreversible loss of structure and function
Healing and Repair
Healing is initiated at the time of injury and is promoted by factors produced during inflammation
Healing is the endpoint of injury and inflammation
Mechanisms of Healing:
Regeneration
This is the ideal situation where the tissue returns to it’s pre-injury structure and function
Mechanisms of Healing:
Replacement
This occurs when tissue is irreversibly damaged and replaced by fibrous connective tissue
Criteria for Regeneration to Occur
- 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
Regeneration can occur with
- 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
Regeneration can NOT occur with:
Permanent cells:
Neurons and cardiac myocytes
Healing and Repari:
Replacement
- 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
Healing and Repair:
Replacement:
Granulation Tissue
- 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
Granulation Tissue
- 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
- Inflammatory stage
Granulation Tissue:
Morphological Zones
- Zone of necrotic debris and inflammation
- Zone of capillary sprouts and arches
- Zone of capillary and fibroblast proliferation
- Zone of mature connective tissue
Granulation Tissue:
Cell Functions:
Macrophages
- Removal of inflammatory debris
- Production of a variety of monokines involved in healing
- platelet derived growth factor
- Fibroblast growth factor
- Transforming growth factor-beta
Granulation Tissue:
Cell Functions:
Endothelium
- 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
Granulation Tissue:
Cell Functions
Fibroblasts
- 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
Healing and Repair:
Wound Healing
- Wound healing occurs within two categories based on the extensiveness of the damage:
- First intention healing
- Second intention healing
Wound Healing:
First Intention
- This is the best represented by incisional skin wounds
- The defect is small and healing occurs rapidly
- The resulting scar is usually mininal
Wound Healing:
Second Intention
- 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
Healing and Repair:
Factors affecting healing
- Nutritional status
- Age
- Presence of concurrent/systemic disease
- Persistence of the damaging stimulus
- Size and location of the damage
