Chronic Inflammation And Wound Healing Flashcards
What are the 3 phases of wound healing?
- inflammatory (substrate, lag phase), 1-3/7d
- proliferate (repair phase, lag phase) 3/5-14d
- Maturation (remodelling phase) 14d+
What is the decline of the inflammatory phase?
Loss of stimulus, altered cellular signals
- as inflammation dies down, fewer inflammatory factors are secreted, existing ones removed and macrophages and neutrophils reduced at the wound site
What is the role of macrophages in the decline of the inflammatory phase?
- secrete growth factors and cytokines that attract cells involved in proliferation stage of healing to the tissue
- respond to low oxygen content of their surroundings to produce factors that induce angiogenesis
- recruit cells that re-epithelialise the wound and lay down a new extracellular matrix
What is angiogenesis?
Formation of capillary buds to produce new blood vessels - pre-existing blood vessels send out capillary buds to make new vessels
How is the process of angiogenesis performed?
- Migration of endothelial cells towards angiogenic stimulus
- Remodelling of endothelial cells into capillary tubes
- Recruitment of peri-endothelial cells, smooth muscle cells
- Stimulated by TGF𝛃 (transforming growth factor 𝛃), FGF (Fibroblast growth factor), PGDF (platelet derived growth factor)
- tumours can also stimulate angiogenesis
How is tissue repair conducted?
Fibroblasts (activated) and fibrocytes (maintenance) are two states of the same cell
Repair = migration and proliferation of fibroblasts triggered by growth factors - mainly macrophage derived
1. The fibroblast synthesises extracellular matrix and collagen
2. Fibrosis is the formation of excess fibrous connective tissues in an organ
What is scarring?
Confluent fibrosis that obliterates the architecture of the underlying organ or tissue
What is the effect of scarring?
Altered composition of new tissue affects the function of that organ or tissue
- e.g. heart after myocardial infarction, coal miners lung, cirrhosis of the liver, spinal infuris (prevents the neurons reconnecting).
What are the outcomes of chronic inflammation?
Start with acute inflammation then if:
- excessive exudate = suppuration → repair and organisation or the discharge of pus → fibrosis
- excessive necrosis = repair and organisation → fibrosis
- persistant causal agent = chronic inflammation →fibrosis
What is purulent or suppurative inflammation?
Persistant or excessive necrosis and cellular exudate - exudate dominated by neutrophils (pus)
- normally induced by bacteria (pyogenic bacteria)
What is apoptosis?
Programmed cell death with limited activation of the immune system
What is necrosis?
Premature death of cell/tissue caused by factors external to the cell - can cause an abscess leading to granuloma formation
What are causes of necrosis?
Injury, infection (flesh-eating bacteria), infarction/stroke (hypoxia), reduced blood flow (gangrene), poisons (snake bite/ spider venoms)
What is early phase necrosis?
Massive neutrophil accumulation in tissue cavity in response to necrosis
What is late phase necrosis?
Granulation tissue develops around abscess including macrophages and lymphocytes - and an outer layer of fibroblasts and connective tissue
What cells are involved in chronic inflammation?
Macrophage, monocytes in the blood are of bone marrow origin, move into tissue (macrophage) 30-60 day life span in tissue
- efficient digestion of particulates, degenerate neutrophils and microorganisms
- produce mediators which regulate inflammation
What is the specific type of macrophage present in chronic inflammation?
Epithelioid macrophages (activated macrophages that resemble epithelial cells) - less phagocytic, different markers
What are multi-nucleated giant cells?
Formed by fusion of epithelioid macrophages around a chronic stimulus
What role do T cell lymphocytes play in chronic inflammation?
Produce inflammatory mediators - regulate chronic inflammation
What role do plasma cells play in chronic inflammation?
Differentiated B cells produce antibodies
Both T and B cells are attracted by chemokines to site of chronic inflammation
Fibroblasts produce an extra layer of connective tissue - “walls off” area
How does a granuloma form?
An organised collection of giant epithelioid macrophages
- Macrophages clustered around agent or or area of necrosis or accumulation of neutrophils, surrounded by collar of T lymphocytes as parts of the normal adaptive immune response, surrounded by layer of fibroblasts and connective tissue
What are the different types of granuloma?
Foreign body granuloma - too big to be phagocytosed
Immune granuloma - prototype is mycobacteria - hard to kill bacteria or parasites
Abscess - surrounds an area of extensive necrosis
How would you describe the structure of a granuloma?
Caseous necrosis surrounded by activated macrophages with giant cells clustered throughout. This area is surrounded by lymphocytes which are encased in fibroblast
What are consequences of chronic inflammation?
Granulomatous enteritis (cow) - (mycobacterium allium), Johne's disease - loss of function - interferes with water and nutrient uptake
