Chronic inflammation Flashcards
What are responsible for coordinating the inflammatory response?
Numerous inflammatory mediators
How does the predominant inflammatory cell type differ between acute and chronic inflammation?
Acute= neutrophils Chronic= macrophages, lymphocytes and plasma cells
What are the different gross characteristics of acute vs chronic inflammation?
Acute: involes lots of exudate, plasma proteins and leukocytes
Chronic: fibrosis, tissue destruction and repair
What are the causes of chronic inflammation?
- Persistant infections (e.g. tough microbes such as mycobacteria)
- Prolonged exposure to toxic agents (e.g. chronic hepatitis due to barbituates)
- Some foreign materials are indestructible e.g. some suture materials)
- Immune mediated inflammatory diseases (autoimmune or immunodeficient)
- Unidentified mechanisms
What are the different morphological changes between acute and chronic inflammation?
In acute it is mainly oedema, vascular changes and neutrophilic inflammation. In chronic it is:
- tissue destruction (caused by the persistant stimulus)
- Attempts of healing (replace damage with CT- fibrosis and angiogenesis- and tissue proliferation)
- Infiltration of mononuclear cells (macrophages,lymphocytes and plasma cells)
Where do kupffer cells exist?
Liver
Where do sinus histiocytes exist?
Lymph nodes and spleen
Where no monocytes exist?
In the blood
Which mediators help activate macrophage migration?
- Exogenous factors: Microbial products and foreign bodies: often engage with TLRs
- Endogenous factors: cytokines (IFN-y) produced by T lymphocytes
What is the role of an activated macrophage?
- Phagocytosis
- Increase lysosomal enzymes, increase ROS, Increase nitrogen species, increase proteases
- Increase cytokines (TNF, IL-1) and increase growth factors (VEGF, FGF)
**VEGF= vascular endothelial growth factor FGF= fibroblast growth factor
What is the role of lymphocytes in chronic inflammation?
Lymphocytes and macrophages interact, recruiting and activating each other. Can lead to very chronic/ severe reactions.
What is the role of plasma proteins in chronic inflammation?
Activated by B lymphocytes the produce antibodies directed against persistent foreign/ self antigens.
Why do nodular lesions form in some cases of chronic inflammation?
If the respnse is unable to remove the inciting agent then it is a mechanism to isolate/ sequester the lesion.
e.g. granulomas and abscesses
What is the definition of an abscess?
A collection of pus surrounded by a fibrous capsule that is visible grossly
Most commonly caused by bacteria.
What is the definition of a granuloma?
A nodular aggregation of macrophages which are usually surrounded by a collar of mononucelar leukocytes. It is a cellular attempt to contain an agent that is difficult to eradicate
List some of the cells you’d usually find in a granuloma
- Epitheloid macrophages
- Giant multinucleated cells
- Fibroblasts
- Lymphocytes
- Macrophages
What is a caseating granuloma?
A granuloma with a centre of necrotic debris
Which agents often result in a granuloma?
- Many fungi, parasites, algae
- Foreign body material
- Few bacteria (mycobacteria)
- A few viruses
What is the difference between regeneration and repair by connective tissue deposition?
- Regeneration is the proliferation of cells/ tissues to replace lost tissue. Results in the complete resolution of lost structures.
- Connective tissue deposition is the replacement of injured cells with connective tissue - collagen deposition and scar formation (fibrosis) or a combination of regeneration and scar tissue.
What happens in stage one of wound healing?
- First 24 hours
- Activation of coagulatioin pathway
- Blood clot formation
- Neutrophils appear
What happens in stage two of wound healing?
- Last 2-7 days
- Macrophages replace neutrophils (by 2-4 days)
- Proliferation of epithelial cells
- Epithelial cells and fibroblasts proliferate to form granulation tissue
- Fibroblasts develop parallel to the wound surface and perpendicular to the new capillaries (angiogenesis)
What happens in stage three of wound healing?
- Lasts weeks
- Remodelling and maturation
- Leucocytes and increased vascularuty dissapear in the second week.
- granulation tissue is converted to a palce, avascular scar (made of fibroblasts and dense collagen)
- Wound contraction occurs in larger wounds.
