Week 2 (2) Chronic Inflammation and Healing Flashcards
Define CHRONIC INFLAMMATION
“Inflammation of prolonged duration (weeks or months) in which atice inflammation, tissue destriction and attempts of repair are proceeding simultaneously”
What CAUSES Chronic Inflammation?
- Can develop from UNRESOLVED ACUTE INFLAMMATION due to infection (e.g. gastritis, osteomyelitis)
- Can develop from _exposed exposur_e to agent (e.g. silica, prosthetic implants)
- autoimmune diseases (RA)
List the main cell types involved in Chronic Inflammtion
*Mast Cells
*Macrophages
*Fibroblasts
*Endothelial Cells
*Lymphocytes
* Plasma Cells
*Eosinophils
Explain the maturation of macrophages
Stem cell changes to a monoblast ( in the bone marrow)
Monocyte (in the blood)
Macrophage ( in tissue) -> **then DIFFERENTIATION ** into microglia (CNS), Kupffer cells (liver), Alveolar macrophages (lungs) and osteoclasts (bones) OR ACTIVATION –> giant cells, epithelioid cells, macrophages
Role of MACROPHAGES in Chronic Inflammation
They are active compounds that produce chemokines, cytokines and growth factors (which causes fibroblast proliferation, blood vessel growth, activation and recruitment of lymphocytes)
Participate in bacterial and cell killing
Clear debris, fibrin and other foreign material
Macrophages and Phagocytosis - Pros and Cons
Pros:
increased lysosomal enzymes and ROS (toxic to mocrobes)
production of cytokines, growth factors
Cons
cause dissolution of extracellular material or cells by producing toxic products (nitric oxide metabolites of proteases)
Lymphocytes in Chronic Inflammation
TWO TYPES:
T and B lymphocytes
- long lived, some present normally in certain tissues
- Antigen activated
- release macrophage activating cytokines
Difference between T Cells and B Cells
T Cells - in cell mediated immunity
B Cells - in humoral mediated immunity, differentiate into plasma cells which produce antibody
Chronic Inflammation - HISTOPATHOLOGY
Plasma Cells: Terminally differentiated B cells, produces antibodies
Fibroblasts: synthesises collagen (fibrosis) scar tissue
Endothelial cells: forms new vessels
Eosinophils: paracitic infection
Osteomyelitis
(An infection that can arise from acute UNRESOLVED inflammation)
Infection in the bone and marrow
Complications - loss of bone, growth disturbance in children, epidermoid carcinoma
Treatment - antibiotic or surgical debeidement
Granulomatous Inflammation:
(Persistent agent causing chronic inflammation)
Clusters of T cells activated macrophages having engulfed foreign bodies
- epitheloioid granulomas: resemble squamous cells
Rheumatoid Arthritis
(Example of Autoimmune disease causing Chronic Inflammation)
Local and systemic inflammation:
Joint - chronic synovitis, synovial cells hyperplasia and proliferation
Increased Vascularity
Cells come along - t cells, macrophages, plasma cells
Increased osteoclasts
Crohn’s Disease
(Example of autoimmune disease causing chronic inflamamtion)
Understand the diagrams (red surfaces and giant multinucleated cell)
What are the NORMAL phases of healing?
- REACTIVE - inflammation (days)
- REPAIR - granulation tissue (months)
- Maturation/Remodellign - collagen (weeks)
SCARS
What are they and when do they form?
Severe or chronic tissue injury may mean that healing cannot be accomplished.
Healing process is now repairing the area using COLLAGEN.
A scar is formed by an intermediary tissue called…. GRANULATION TISSUE
What is GRANULATION TISSUE?
made of:
- new blood vessels (growth factors)
- fibroblasts –> collagen –. scars
- macrophages clear away dead tissue.
WHY: some cells are uable to regenerate, or there may be extensive tissue destriction. Healing is NOT through the inflammatory exudate response but by ORGANISATION AND REPAIR
Granulation tissue will undergo THREE sequential changes
1. Vascular Granulation Tissue
- newly formed capillaries, macrophages and support cells.
2. Fibrovascular granulation tissue
- proliferatine fibroblasts, capilliaries and macrophages
3. Fibrous Granulation Tissue
- fibroblasts synthesize collagen adn align themselves so that collagen is deposited in a uniform manner.
Aims of Wound Healing:
- remove damamged tissue
- fill gap caused by destruction
Why would a bigger woud take longer to heal?
- needs to carry away more necrotic debris and excudate
- much larger amounts of granulation tissue are formed
- greater amount of collagen synthesis needed to fill damaged areas
- scar tissue formation replaces normal tissue
List both LOCAL and SYSTEMIC factors that influence wound healing
LOCAL
- infection
- mechanical factors
- foreign bodies
- size, location and type of wound
- vascular supply
SYSTEMIC
NUTRITION: --vitamin C and A, protein deficiency inhibits collagen synthesis.
METABOLIC STATUS - diabetes
CIRCULATORY STATUS - no blood
HORMONES - glucocotricoids have anti-inflammatory response
IMMUNOSUPPRESSION
AGE
Regenerative HEALING
EG - A BROKEN BONE
LIST THE STAGES, will need to refer to diagrams in lecture slides
1. Early Fracture:
Haematoma/Inflammation: rupture of cessels, inflammatory cell infiltrate (macrophages, leukocytes, platelets), bone cells die
Inflammation Stage - granulation tissue/soft callus (callus is CT and cartilage)
2. Reparative Phase
Osteoclasts resorb dead bone, bone deposited on the end of cortical bone, soft callus develops
3. Remodelling Phase
- callus replaced with lamellar bone, osteoclasts and blasts still active
NON REGENERATIVE REPAIR E.G Myocardial Infacrtion
Please list the stage of _non-regenative repai_r in a myocardial infarction from 6 hours to several weeks
-
6-12 Hours
- no macroscopi changes, increased eosinophilia of dead cells -
12-24 Hours
- Nuclei fade (karyolysis)
- neutrophils infiltrate the dead myocardium as acute inflammatory response.
- Most monocytes are dead -
48-72 Hours
- many neutriphils infiltrate the dead myocardium. -
Several Weeks
- fibroblasts and endothelial cells migrate into the area of injury.
- granulation tissue develops - comprises of macrophages, fibroblasts, capilliaries and lymphocytes.
5. Scar Tissue
- fibroblasts lay down more CT
- scar takes 6-8 weeks to form
