Chronic inflammation Flashcards

1
Q

Why does chronic inflammation occur?

A

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

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2
Q

What cells are involved in chronic inflammation?

A

Macrophages

Lymphocytes

Plasma cells

Eosinophils

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3
Q

Name 5 possible outcomes of chronic inflammation

A

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)

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4
Q

Name 4 things that cause macrophage activation

A

Cytokines (particularly IFNg)

Bacterial endotoxins (via TLRs)

Chemical mediators of inflammation (e.g. ILs)

proteins on the extracellular matrix

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5
Q

What are the effects that activation has on macrophages?

A

Increased size and epitheliod cell type

Increased lysosomal activity

Increased metabolic rate

Increased phagocytic activity

Increased ability to kill microbes

Increased ROS RNS

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6
Q

In what situations is chronic inflammation seen?

A

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)

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7
Q

How is chronic inflammation defined?

A

Inflammation lasting over 24-48hrs to years

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8
Q

What are the three components of chronic inflammation?

A

Ongoing inflammation (lymphocytes, macrophages, eosinophils, plasma cells)

Ongoing tissue repair (angiogenesis and fibrosis)

Ongoing tissue destruction (necrosis)

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9
Q

Gastric ulcers are a result of chronic inflammation

Name two factors favouring ulceration and two factors affecting healing

A

Favours ulceration:
H. pylori
Alcohol
NSAIDs
Stress
Zollinger-Ellinson

Favours healing:
Immune response
PPIs
Antibiotics
Good blood supply

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10
Q

What are the morphological features of peptic ulcers?

A

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.

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11
Q

Name 3 functions of macrophages

A

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

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12
Q

Name 4 types of tissue macrophages and where they are found

A

Kupffer cells: liver
Microglia: neural tissue
Epithelioid cells: granulomas
Osteoclasts: bone
Alveolar macrophages: lung

Activated macrophages
Histiocytes/Giant cells: Connective Tissue

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13
Q

How do chronic peptic ulcers arise?

A

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.

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14
Q

What are the possibel outcomes of a peptic ulcer?

A

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.

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15
Q

How do granulamatous inflammatory reactions occur?

A

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)

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16
Q

Name 5 products secreted by macrophages and state their effects

A

Remove damaged tissue from site of injury
Proteases
Hydrolytic enzymes

Bacterial and cell killing
ROS

Stimulate fibroblast proliferation and collagen synthesis
IL-1, cytokines, TNFa

Angiogenesis and fibroblast migration
VEGF, FGF, PDGF

Pro-inflammatroy mediators
PAF, prostaglandins