List the different outcomes of acute inflammation
- Resolution
- Abscess
- Organisation and repair (granulation of tissue = scarring)
- Chronic inflammation (organisation with continued inflammation and tissue-based immune response)
Describe resolution
- Acute inflammation exudate eliminates damaging agents
- Macrophages remove dead cells and exudate
- Local cells regrow
- Tissue structure and function returns to normal
- Not a common outcome following tissue damage and acute inflammation
e. g. where resolution occurred after acute inflammatino following:
- Pneumonia
- Tubular necrosis kidney
- Sunburn
What must happen for resolution to occur?
- There must be minimal damage to the architecture
- Allows normal sturcture and function to be restores
best e.g. is lobar pneumonia
- no damage to alveolar wall architecture
- exudate forms in alveolar air dacs
- Liquefied exudate is reabsorbed
- Alveolar lining cells regrow
What is an abscess?
- An abscess is a large accumulation of liquid purulent exudate (pus) in an area where the tissue damage has led to extensive necrosis
- It becomes ‘walled-off in an attempt to limit the spread of inflammation
- It is especially caused by bacteria e.g. staphylococcus
e.g. abscess in the lung
Describe organistation and repair
- Remove debris
- Grow new vessels and support cells
- Lay down collagen
- Collagen matures
- Granulation tissue matures to scar:
>Vascular, fibrovascular, and collagenous
Describe the organisation of exudate stage of organisation and reapir
- Capillaries grow into damaged area
- Fibroblasts migrate into area and mutliply
- Fibroblasts synthesise collagen
- New capillaries regress
- Fibroblasts regress
Describe the macrophage clearing debris stage
Macrophage phagocytose solid debris, and enzymes liquefy the rest of it
Describe the vascular granulation stage
- Capillaries grow into damageed area by budding from nearby vessels
- Capillary netwrok is fromed
- Some fibroblasts move in
> Angiogenesis is driven by specific growth factors and receptors. The myofibroblast cells have ability to secrete collagen as well as contractile smooth-muscle like ability
Describe the histology of vascular granulation tissue
- New capillaries dominate hisotlohy
- Residual inflammatory cells remain
Describe the fromation of fibrovascular granulation tissue
- Fibroblasts proliferate and excrete collagen fibers
- Capillary network still present but less prominent
> Many of the cells are myofibroblasts - also can contract
Describe the histology of fibro-vascular granulation tissue
- Mixture of capillaries and fibroblasts
Describe the formation of fibrous granulation tissue and scar (fibrous repair)
- Most new capillaries regress
- Fibroblasts align and secrete large amounts of collagen fibre
> Myofibroblast contraction reduces the volume of tissue and causes contraction of the damaged area
Describe the histology of fibrous granulation tissue and scar
- Few capillaries remain
- Histology dominated by newly formed collagen and fibroblasts
Describe the process of healing by repair
- The formation of scar following tissue damage is an example of healing by repair
- In contrast to resolution, restoration of normal structure and function of damaged tissue does not occur
Describe chronic inflammation
When a damaging stimulus persists, complete healing cannot occur, and chronic inflammation ensues
- Damage, organisation, and repair occur concurrently
- Tissue is infiltrated by specific immune effector cells
- Always heals by scarring
Describe the mechanism of chronic inflammation
- Macrophage is the main effector cell
- It is activated by gamma-interferon (y-INF)
- Has a phagocytic role
- Has a secretory role
> Mediators of inflammation, oxygen metabolites, proteases, and hydrolases
> Cytokines (IL-1, TNF-a)
> Growth factors (PDGF, EGF, FGF)
Give an example of chronic inflammation
Chronic peptic ulcer of the stomach
- Stomach contains acid (very low pH)
- Protective mucosa is damaged, exposing sensitive tissues underneath to gastric acid
- Tissue necrosis is followed by acute inflammation with exudate formation
- Exudate organises into granulation tissue, but in meantime, more damage has been caused on the surface by more gastric acid
So long as gastric acid continues to cause damage, the lesion cannot complete the process of healing with scar
State the two general properties of chronic inflammation
- Chronic inflammation occurs when the damaging stimulus cannot be eradicated
- In persisting chronic inflammation there is a stalemate between continuing damage and continuing attempts to repair by fibrous scar formation
Describe the scenarios of chronic inflammation that occur when it is not a stalemate (better/worse)
- Things get BETTER if the damaging stimulus is removed or neutralized. Healing process gains upper hand + scarring completes
- Things get WORSE if damaging stimulus increases or if healing is impaired
Describe the events of the chronic peptic ulcer getting better
- Gastric acid is removed or neutralized
- Damage is stopped
- Ulcer heals with scar formation
Describe the events of the chronic peptic ulcer getting worse
- Gastric acid increases or repair process is impaired
- Damage overwhelms repair
- Ulcer perforates (bleeding into the stomach)
List some causes of chronic inflammation
- Damaging stimulus is not amenable to eradication or neutralization e.g. gastric acid
- Bacteria persist because they are distanced from neutrophils, antibiotics, etc
- Bacteria persist because they are resistant to neutrophil phagocytosis e.g. TB
Describe granulomatous inflammation
A special form of chronic inflammation in which neutrophils are ineffective, so macrophages are involved early as part of an immune
- Macrophages aggregate around the damaging agent (with lymphocytes and fibroblasts) forming a ‘granuloma’
- Macrophages can fuse together to form a giant cell
List come causes of granulomatous inflammation
- Low pathogenicity organisms which excite a type IV immune response
- Organic or inorganic foreign material
- Some fungi
- Metabolic condition - sarcoidosis, Crohn’s disease
