Define chronic inflammation?
•Inflammation in which the cell population is especially
•Features tissue or organ damage, (necrosis), loss of function.
•Healing and repair
–scarring and fibrosis
•May follow from ongoing acute inflammation
•But also arises as primary pathology
•Tends to be long-term
How is chronic inflamtion represented Clinically?
•Often no specific “sore bit”
•Malaise and weight loss
–tuberculosis (lung, lymph node) – systemic effect
•Loss of function
–autoimmune thyroiditis (functional gland destruction) – hypothyroidism
When do we see chronic inflammation?
•Arising from acute inflammation
–follows on from acute
–inability to remove debris
–fails to resolve – ongoing acute insult
•Arising as a primary lesion
–only see chronic changes
What is the big picture of granulation in organisation as an outcome of acute inflammation?
•Granulation tissue is characteristic of organisation
•Results in healing and repair
•Leads to fibrosis and formation of a scar
What is the granulation tissue mechanism and function?
•Capillaries grow into inflammatory mass
•Macrophages from blood and tissue
•Fibroblasts lay down collagen to repair damaged tissue
•Collagen replaces inflammatory exudate
•patches tissue defects
•replaces dead or necrotic tissue
•contracts and pulls together
What are the products of granulation tissue?
•Fbrous tissue - scar
•Fibrosis as a problem
–adhesions between loops of bowel following peritonitis
•Can progress to chronic inflammation
What are the type of diseases which occur as a primary chronic inflammation?
–Autoantibodies directed against own cell and tissue components – autoantigens
–Damage or destroy organs, tissues, cells, cell components
–Thyroiditis, rheumatoid disease,
What are the main cells involved in primary chronic inflamation?
- Plasma cells
What are the causes of chronic inflamation?
1. Material resistant to digestion
2. Exogenous substances
3. Endogenous substances
–Cannot easily be phagocytosed
4.Granulomatous inflammation common
What are lymphocytes?
•Cells that are part of immune system
•Main types of lymphocyte
What is a Plasma cell?
Briefly describe B-cell mechanisms?
•Differentiate to plasma cells
•Facilitate immune response
•Act with macrophages
–antigen presenting capacity
Briefly describe T-cell mechanisms?
•T-cells produce cytokines
–Attract and hold macrophages
–Other cells eg lymphocytes
•Damage and kill (lyse) other cells and destroy antigen
–Chemical mechanisms - granule proteins
Briefly describe NK-cell mechanisms?
•NK cell destroy antigens and cells
–chemical mechanisms - granule proteins
what are Macrophages?
•Role in immune system - antigen presenting cell
•Monocyte, histiocyte, activated macrophage, epithelioid cell, giant cell
•Bone marrow, blood tissues
Briefly describe macrophage mechanisms?
•Motile phagocyte move from blood
•Take over from neutrophils
•Contain enzymes eg lysozyme
•Produce interferons and other chemicals
–destroy, influence process
What are fibroblasts and their function?
•Make and assemble structural proteins
Summary of outcome
•Ongoing tissue damage and destruction
•Insidious loss of function
•Cellular and stromal response
–granulation tissue, angiogenesis
•Scarring and fibrosis
•Characterised by presence of granulomas (granulomata) in tissues and organs
•Stimulated by indigestible antigen
–body cannot get rid of it
•Many serious infectious and idiopathic (= no known cause) diseases
•Aggregates of epithelioid macrophages in tissue
•May contain giant cells
•May surround dead material
•May be surrounded by lymphocytes
•Contain neutrophils, eosinophils
•Response to indigestible antigen
•Many are type IV hypersensitivity reactions
•Granulomas comprise epithelioid histioytes (macrophages)
•? fusion of macrophages to form larger cells
•Large cytoplasm; multiple nuclei
•Not always granuloma for giant cells to be present
Foreign body type
•Often associated with pyogenic granulation tissue
•eg pilonidal abscess
•Ruptured silicone implants
–usually but not always breast
–vacuoles contain leaked silicone
•Rarely see in measles
•Central cluster of nuclei
Infectious granulomatous diseases – examples relevant to global health
•Tuberculosis – Mycobacterium tuberculosis
•Leprosy – Mycobacterium leprae
•Syphilis – Treponema pallidum
Non-infective granulomas - examples
•Rheumatoid disease - tissue specific auto-immune disease, ? cause
•Sarcoidosis – classical clinical picture, ? cause
•Crohn’s disease – chronic inflammatory bowel disease, ? cause
•Process of repair of tissue damage
•Like any healing process after any injury
•Phase of acute inflammation
•Granulation tissue formation
•Local angiogenesis – new vessels grow
•Fibrosis and scar formation
Sequence of events
•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
Favouring wound healing
•Apposition of edges (no haematoma)
•Metabolic stability and normality
•Normal inflammatory and coagulation mechanisms
•Note local mediators
Impaired wound healing
•Dirty, gaping wound, large haematoma
•Poorly nourished, lack of vitamins C, A
•Abnormal CHO metabolism, diabetes, corticosteroid therapy
•Inhibition of angiogenesis