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
What is vascular grannulation tissue?
Network of newly formed capillaries, macrophages and support cells which replace the area of tissue damage.
1st step
What is fibrovascular granulation tissue?
Proliferating fibroblasts, capillaries and macrophages.
Second step
What is fibrous granulation tissue?
Fibroblasts synthesize collagen and align themselves so collagen is deposited in a uniform patter
Contraction frequently occurs, size of damaged area is reduced
Which of these is vascular and fibrous
Vascular Left
Fibrous R
What are the aims of wound healing?
To remove damaged tissue
To fill gap caused by tissue destruction
To restore structural continuity of injured part
What is secondary intention healing?
When there has been more extensive loss of cells and tissue
The reparative process is more complicated
Why does a large wound take alot longer to heal?
Inflammatory reaction is more intense to carry away the large amounts of necrotic debris and exudate
Much larger amounts of granulation tissue are formed
Greater amount of collagen synthesis to “fill in” damaged area
Wound contraction is more frequent
Scar tissue formation replacing normal tissue
What are local factors that influence wound healing?
Infection
Mechanical factors
Foreign bodies
Size, location, and type of wound
Vascular supply
Radiation
What are systemic factors that influence wound healing?
Nutrition - e.g. vitamin C and A, and protein deficiency inhibits collagen synthesis
Metabolic status: diabetes mellitus
Circulatory status : inadequate blood supply
Hormones: glucocorticoids have anti inflammatory effects
Immunosuppression
Age
What are the three phases of fracture healing?
Reactive
Repair
Remodeling
Discuss Haematoma/inflammation
Rupture of vessels
Haematoma formation
Inflammatory cell infiltrate
e.g macrophages, leukocytes, platelets
Bone cells die, mesenchymal cells differentiate into osteoblasts
Discuss the inflammatory phase and the time within this phase.
Granulation tissue/ soft callus
Connective tissue + cartilage = callus
Days - 2 weeks
What is the reparative phase and how long does it last?
Fourth Phase
Osteoclasts resorb dead bone
Soft callus —> bony callus
OB deposit woven bone
Bone deposited on ends of cortical bone (endochondral ossification)
Callus mineraltion: 4-16 weeks.
What is the remodelling phase and how long does it last?
Callus replaced with lamellar bone
Osteoclasts and osteoblasts active and in concert
Remodelling 1-4 years
May elminate any evidence of fracture
Give the overview of steps in a bone fracture
Fracture
Clot formation
Soft callus formation
Bony callus formation
Remodelling
Union
Myocardial infarction. Time taken to occur, what happens?
Myocardial infarction (12-24 hours) The nuclei fade (karyolysis) >disappear from the cells
- Neutrophils (black arrows- infiltrate the dead myocardium as an acute inflammatory
response. - Most of the myocytes in this field are dead (increased eosinophilia and lack of
nuclei (compare with the few viable cells still present).
- Contraction bands can be seen (green arrows) in the dead myocytes.
Myocardial infarction (48-72 hours) neutrophils infiltrating the dead myocardium
Myocardial infarction (one - several weeks).
Fibroblasts and endothelial cells start to migrate into the area of injury about 3 days after
the injury but it will take some days for granulation tissue to be readily seen.
Granulation tissue predominantly comprises macrophages, fibroblasts, newly formed
capillaries and lymphocytes.
Scar tissue (high power) in healed MI
- fibroblasts lay down more connective tissue
- inflammatory cells drain via lymphatics and capillaries degenerate leaving mature scar
that takes 6-8 weeks to form.
- collagen rich extracellular matrix with a few residual fibroblasts (e.g. green arrows) and
capillaries (green star). A few myocytes (black star) are present at the edge of the
scar.
