Chronic inflammation Flashcards
Why does chronic inflammation occur?
Persistence of a damaging stimulus (chronic insult)
Complete healing after resolution of acute inflammation cannot occur
Chronic inflammation is the body’s response to continued tissue necrosis and organisation
What cells are involved in chronic inflammation?
Macrophages
Lymphocytes
Plasma cells
Eosinophils
Name 5 possible outcomes of chronic inflammation
Continued chronic inflammation
Change in tissue function (atrophy, metaplasia)
Resolution (healing one stimulus is removed)
Scarring with dysfunction (e.g. cirrhosis)
Catastrophe (tissue insult worsens)
Name 4 things that cause macrophage activation
Cytokines (particularly IFNg)
Bacterial endotoxins (via TLRs)
Chemical mediators of inflammation (e.g. ILs)
proteins on the extracellular matrix
What are the effects that activation has on macrophages?
Increased size and epitheliod cell type
Increased lysosomal activity
Increased metabolic rate
Increased phagocytic activity
Increased ability to kill microbes
Increased ROS RNS
In what situations is chronic inflammation seen?
Persisting infection (H. pylori, TB)
Chronic or autoimmune diseases (bronchitis, Chron’s, Rheumatoid arthritis)
Foreign material (sutures, silica)
Immunosuppression (HIV)
Inadequate blood supply or persisting insult (ulcers, bed sores)
How is chronic inflammation defined?
Inflammation lasting over 24-48hrs to years
What are the three components of chronic inflammation?
Ongoing inflammation (lymphocytes, macrophages, eosinophils, plasma cells)
Ongoing tissue repair (angiogenesis and fibrosis)
Ongoing tissue destruction (necrosis)
Gastric ulcers are a result of chronic inflammation
Name two factors favouring ulceration and two factors affecting healing
Favours ulceration:
H. pylori
Alcohol
NSAIDs
Stress
Zollinger-Ellinson
Favours healing:
Immune response
PPIs
Antibiotics
Good blood supply
What are the morphological features of peptic ulcers?
The base of peptic ulcers is smooth and clean as a result of peptic digestion of exudate, and blood vessels may be evident.
In active ulcers the base may have a neutrophilic inflammatory infiltrate.
Beneath this, active granulation tissue infiltrated with mononuclear leukocytes and a fibrous or collagenous scar forms the ulcer base.
Vessel walls within the scarred area are typically thickened and are occasionally thrombosed. Scarring may involve the entire thickness of the wall and gather the surrounding mucosa into folds that radiate outward.
Name 3 functions of macrophages
Phagocytosis and destruction of bacteria and debris
Control of other inflammatory cells by secreting cytokines
Process and present antigen to T cells
Secrete factors involved in tissue destruction and repair
Name 4 types of tissue macrophages and where they are found
Kupffer cells: liver
Microglia: neural tissue
Epithelioid cells: granulomas
Osteoclasts: bone
Alveolar macrophages: lung
Activated macrophages
Histiocytes/Giant cells: Connective Tissue
How do chronic peptic ulcers arise?
The lining of the stomach is usually protected from acid and proteolytic enzymes by a thick alkaline mucus layer on the surface of the epithelium.
If this is degraded then the acid and enzymes destroy the epithelium and supporting stroma, causing ulceration.
Tissue damage stimulates an acute inflammatory reaction with the formation of exudate near the surface of the ulcer, granulation tissue forms to promote healing and repair. Id the healing response cannot overcome the persistent damage caused by gastric acid then a chronic gastric ulcer results that may persist for years.
What are the possibel outcomes of a peptic ulcer?
Healing: damaging stimulus overcome by healing process
Perforation: healing and repair mechanisms overwhelmed by continued damage from gastric acid, ulceration continues, penetrating the thickness of the stomach wall
Chronic ulcer: damage caused by acid is counterbalanced by healing process, results in a persistent ulcer.
How do granulamatous inflammatory reactions occur?
These reactions occue when neutrophil phagocytosis is inadequate to neutralise the causative agent.
Chronic inflammatory response where neutrophils are replaced by lymphocytes and macrophages which form clusters (granulomas)
