Chronic Inflammation and Healing Flashcards
Define Chronic Inflammation
Inflammation of prolonged duration (weeks or months) in which active inflammation, tissue destruction and attempts at repair are proceeding simultaneously.
Develop from prolonged exposure to agent e.g. silica, wear particles from prothetic implants
Autoimmune disease states e.g. Rheumatoid arthritis, Crohns, Lupus
What are the causes of chronic inflammation?
Can develop from unresolved acture inflammation due to infection, injury e.g. gastritis, osteomyelitis
Develop from prolonged exposure to agent e.g. silica, wear particles from prosthetic implants
Autoimmune disease states e.g. SLE, RA
How long does chronic inflammation last?
Will persist until the damagin stimulus is eradicated
If damaging stimulus is eradicated —-> organisation and repair
Ongoing inflammation and tissue damage proceed at the same time as attempts at healing
List 4 (of 7) cells involved in chronic inflammation
Macrophages
Lymphocytes
Plasma cells
Mast cells
Fibroblasts
Endothelial cells
Eosinophils
Discuss the Maturation of macrophages.
Lifespan of blood monocyte - 1 day
Lifespan of tissue macrophages can be several months or years
Several growth factors, cytokines, adhesion molecules and cellular interactions regulate the conversion from bone marrow stem cell to tissue macrophage.
What is the role of macrophages?
Produce chemokines, cytokines and growth factors. These cause:
Cell influx
Fibroblast proliferation
Stimulate growth of blood vessels
Activation and recruitment of lymphocytes
Participate in bacterial and cell killing
Clear extracellular debris, fibrin and other foreign material
What are some advantages to the pagocytotic nature of Macrophages?
Increased lysosomal enzymes and ROS which is toxic to microbes
Production of cytokines, growth factors etc.
What are some disadvantages to the pagocytotic nature of Macrophages?
Cause dissolution of extracellular material or cells by producing some toxic products (e.g. NO metabolites or proteases)
T and B lymphocytes: Give time length, how they are activated?
Many long lived
Some present normally in certain tissues
Antigen activation
Release macrophage activating cytokines (+ve feedback until inflammatory stimulus removed)
What type of immunity are T cells primarily found?
Cell mediated immunity
What type of immunity are B cells primarily found?
In humoral mediated immunity
Differentiate into plasma cells which produce antibody
What do fibroblasts do?
Synthesises collagen (fibrosis) which leads to scar tissue
The process of forming new vessels via endothelial cells is called?
Angiogenesis
Eosinophils are primarily involved in what type of infection?
Parasitic
What is osteomyelitis?
Infection in the bone and marrow
Aetiology
Systemic or local infection
Mycobacteria and pyrogenic bacter common
Complications
Lose regions of bone,
Children - epiphyseal growth disturbance
Epidermoid carcinoma (longer term), septic arthritis
Treatment - antibiotic, surgical debridement
Granulomatous Inflammation: Persistent agent. Define.
E.g. peri-implant loosening
Clusters of T cell activated macrophages having engulfed foreign bodies
“Epithelioid” granulomas: resemble squamous cells
Picture before and after Foreign body granuloma
Osteoclast
Rheumatoid Arthritis: What is it? Where is it? What happens?
Local and systemic inflammation
Occurs in the joint
Due to chronic synovitis
Synovial cells hyperplasia and proliferation
Increased vascularity (angiogenesis)
Cell infiltrate: T cells, macrophages, plasma cells
Increased osteoclast number
Pannus invasion
Fibrosis and calcification
Crohns disease, name the type of inflammation circled and the cell.
What is regenerative healing?
Tissue replaced with parenchymal tissue. e.g. fracture healing, primary intension
What is non-regenerative healing?
Healing occurs by replacement with CT scar e.g. MI. Connective scar tissue - replaces dead tissue but not functioning parenchymal cells.
What is repair/healing?
If severe or chronic tissue injury resulting in both damage to parenchyma and the stromal framework.
Healing cannot be accomplished by regeneration (resolution)
Healing process is repair by deposition of collagen and other ECM components resulting in a scar.
Scar is formed by an intermediary tissue: granulation tissue.
What happens if a cell can’t regenerate and is injured? e.g. heart and muscle.
Extensive tissue and frameowkr destruction
Tissues cannot regenerate even if they can divide
In this case: Healing is not through resolution of the inflammatory exudate
Insead it is through organization and repair
What are the components of Granulation Tissue?
New blood vessels (angiogenesis)
Fibroblasts —> Collagen —-> scar
Macrophages and other mononuclear cells clear away dead tissue
