What is chronic inflammation?
Chronic inflammation is inflammation in which the cell populations are predominantly lymphocytes, plasma cells and macrophages.
What is the predominant cell population composed of during chronic inflammation?
Lymphocytes
Plasma cells
Macrophages
What does chronic inflammation feature?
Tissue damage/death (necrosis)
Healing/repair (granulation tissue, fibrosis and scarring`).
Can chronic inflammation be developed from an acute inflammatory episode?
Yes.
Can chronic inflammation arise as a primary pathology?
Yes.
What does the clinical presentation of chronic inflammation usually feature?
No clear ‘sore bit’
Malaise
Weight loss
Name 3 examples of chronic inflammation.
Autoimmune thyroiditis (functional glandular destruction) Crohn's disease (ulceration/fibrosis of GI tract) Leprosy (cutaneous nerve destruction)
What is organisation?
An outcome of acute inflammation involving granulation tissue, angiogenesis, fibrosis and scar formation.
What does organisation result in?
Formation of granulation tissue
Angiogenesis
Fibrosis and formation of scar
What is a angiogenesis?
Formation of new blood vessels.
What are the 4 steps of angiogenesis?
New vessels form from capillary buds.
VESF (vascular endothelial stimulating factor) released by hypoxic cells which stimulates proliferation.
Enzyme secretion aids the process.
Blood supply is enabled to enter the tissue.
What factor is released by hypoxic cells to stimulate proliferation during angiogenesis?
VESF- Vascular Endothelial Stimulating Factor
What does granulation tissue involve?
Angiogenesis, fibroblasts/collagen, macrophages
What is the acute/chronic interface built on?
Acute inflammation developing into chronic inflammation.
What does acute-on-chronic inflammation feature?
Exudate/neutrophils alongside lymphocytes/fibroblasts/fibrosis
What type of tissue will acute-on-chronic inflammation feature?
Pyogenic tissue (pus).
What are the products of granulation tissue?
- Fibrous tissue- scar (skin blemish)
- Fibrosis as a problem
- Chronic inflammation
What is primary chronic inflammation developed from?
Autoimmune disease.
How does primary chronic inflammation occur?
Autoantibodies are directed against the body’s own cell and tissue components (autoantigens). This leads to the damage and destruction of organs, tissues, cellular components and cells.
What do lymphocytes do?
Part of immune system, many subtypes/functions, T-cells and B-cells, main functions in immune response and memory.
What do plasma cells do?
Differentiated B-cells, involved in antibody production, intermediate size.
What are the B-cell mechanisms?
Differentiate to plasma cells, facilitate immune response, act with macrophages (antigen presenting capacity) , immune memory.
What are the T-cell mechanisms?
Produce cytokines (attract and hold macrophages, activate them, permeability), produce interferons (antiviral effects; attract/stimulate other cells, damage and kill other cells and destroy antigens.
What do NK cells do?
Destroy antigens and cells (chemical mechanisms; innate immunity).
What do macrophages do?
Destroy debris, antigen presenting cell, bone marrow production. (Long lived, motile phagocytes move from blood, contains enzymes such as lysosome, produces interferons and other chemicals)
What do fibroblasts do?
Motile cells, metabolically active, make and assemble structural proteins such as collagens.
What is granulomatous inflammation?
Inflammation characterised by the presence of granulomas in the tissues and organs.
What is granulamatous inflammation stimulated by?
An indigestible antigen that the body can’t get rid of.
In what diseases is granulomatous inflammation often seen?
Serious and idiopathic (unknown causes).
What are granulomas?
Granulomas are aggregates of epithelioid macrophages in tissue. May surround dead tissue.
What may granulomas contain?
Giant cells
Neutrophils / eosinophils
What are granulomas surrounded by?
Lymphocytes.
What are giant cells?
Cells with a large cytoplasm/large nuclei- granulomas are not required for their formation.
Name 4 types of giant cell.
Langhan’s type
Foreign body type
Silcione-associated
Warthen-Finkeldy
Name 3 diseases of granulamatomous tissue that are relevant to global healthcare?
Tuberculosis
Syphilis
Leprosy
Do non-infective granulomas exist?
Yes- seen in Rheumatoid arthritis, sarcoidosis and Crohn’s disease.
What is wound healing?
A repair process of tissue damage.
What does wound healing involve?
Acute inflammation
Granulation tissue formation
Angiogenesis
Fibrosis and scar formation
What are surgical wounds an example of?
Healing by PRIMARY intention.
Requires a minimal gap for the blood to clot. A small amount of granulation tissue will form and a linear scar will usually be made.
What are other injuries an example of?
Healing by SECONDARY intention.
Involves the loss of granulation tissue ingrowth. This features contraction and scarring.
What does the sequence of events involve in healing by secondary intention?
- injury, blood clot, acute inflammation, fibrin
- many growth factors and cytokines involved
- granulation tissue growth - angiogenesis
- phagocytosis of fibrin
- myofibroblasts move in and lay down collagen
- contraction of scar
- re-epithelialisation
What factors favour wound healing?
Cleanliness Apposition of edges Sound nutrition Metabolic stability Normal inflammatory/coagulatory mechanisms
What can impaired wound healing involve?
Dirty wound, large haematoma, poor nourishment, lack of vitamins (A/C), abnormal CHO metabolism, diabetes, corticosteroid therapy, angiogenetic inhibition.
How does fracture healing differ from regular wound healing?
The bony structure must be repaired as well as the tissue.
What is the pre-callus process of fracture repair?
- Trauma, fracture, haematoma
- Bits of dead bone and soft tissue
- Acute inflammation, organisation, granulation tissue, macrophages remove debris
- Granulation tissue includes osteoblasts as well as fibroblasts
What does the granulation tissue include in fracture healing?
Osteoblasts as well as fibroblasts.
What is the callus-forming process of fracture repair?
The osteoblasts lay down woven bone. There are nodules of cartilage present which is followed by the remodelling of the bone- osteoclasts remove the dead bone, there is progressive replacement of woven bone by lamellar bone, and an eventual reformation of cortical and trabecular bone.
What lays down woven bone in fracture repair?
Osteoblasts.
What removes dead bone in fracture repair?
Osteoclasts.
What does progressive replacement of woven bone by lamlelar bone result in within fracture repair?
Eventual reformation of cortical and trabecular bone.
