Week 2 Pathology - Inflammation, Healing and Repair Flashcards
What are the major features of acute inflammation?
1) Alterations in vascular calibre, leading to increased blood flow
2) Structural changes in microvasculature to permit plasma proteins and leukocytes to leave the circulation
3) Emigration of leukocytes from microcirculation to accumulate at focus of injury and eliminate offending agent
What are typical stimuli for acute inflammation?
Infection, necrosis, foreign bodies, immune reactions
What is an exudate?
Extravascular fluid high in protein concentration, with cellular debris and high specific gravity
What is a transudate?
Extravascular fluid low in protein concentration, with little specific gravity
What is oedema?
Excess fluid in the interstitial space, either can be exudative or transudative in origin
What inflammatory mediators induce vasodilation?
Nitrous Oxide
Histamine
What inflammatory mediators are responsible for increased vascular permeability ?
How long does this occur for?
Histamine, leukotrienes, bradykinin, neuropeptide P
15-30 mins
How does inflammation lead to slower blood flow in microvasculature?
Slower blood flow occurs due to loss of fluid, concentration of RBCs in small vessels, and accumulation of leukocytes along endothelium (due to expression of adhesion molecules which facilitate migration into the interstitial fluid)
What cells are responsible for the release of cytokines, predominantly TNF, IL-1?
Macrophages
Endothelial cells
Mast Cells
What cells are responsible for the release of vasodilatory and permeability mediators prostaglandins, histamine, leukotrienes, platelet activating factor?
Mast cells
Leukocytes
**Basophils also secrete histamine
What are the outcomes of acute inflammation?
1) Complete resolution: removal of cellular debris by macrophages and reabsorption of oedema by lymphatics
2) Healing by connective tissue replacement (more substantial tissue destruction) - cells incapable of regeneration
3) Progression to chronic inflammation –> acute inflammatory response cannot be resolved either by persistence of injurious agent or interference with normal healing process
What are the key features of chronic inflammation?
1) Infiltration with mononuclear cells (macrophages, lymphocytes, plasma cells)
2) Tissue destruction caused by persistent offending agent
3) Fibrosis and angiogenesis
What is the predominant cell type in chronic inflammation?
Monocytes, differentiating into macrophages
What are the two key roles of macrophages?
Eliminate injurious agents
Initiate process of repair
What other cell types are present in chronic inflammation?
Lymophocytes
Plasma cells
Eosinophils
Mast cells
What is the immediate response to a wound?
Rapid activation of coagulation pathways and formation of blood clot on wound surface, forms a scaffold for migrating cells which will participate in repair
What occurs within 24 hours of wound?
Neutrophil invasion of incision margin, migrates to fibrin clot
What occurs 24-48 hours of wound?
Epithelial cells from both edges begun to proliferate along dermis, and meet in the midline underneath surface scab, forming epithelial layer which bridges the wound
What type of collagen is deposited first, and what is it replaced by?
Initially, Type III - but replaced later by type I collagen
What occurs by day 3?
Neutrophils largely replaced by macrophages, epithelial cells continuing to proliferate and form a covering nearing thickness of epidermis
What occurs by day 5?
Neovascularisation reaches its peak, granulation tissue fills the incisional space, with leaky vessels allowing plasma proteins and fluid into extravascular space. Fibroblasts drawn into wound
What occurs in week 2 of a wound?
Continued collagen accumulation and fibroblast proliferation, but reduction in leukocytes, oedema, and vascularity
Contrast primary and secondary intention?
Primary = involving epithelial layer, principle mechanism is epithelial regeneration
Secondary = more extensive tissue loss, combination of regeneration and scarring - with greater amount of granulation tissue required, with associated wound contracture of scar to reduce surface area of wound
What types of cells are known as ‘labile’ or continuously dividing tissues?
Haematopoetic cells in bone marrow
Stratified squamous epithelia
Cuboid epithelia of endocrine organ ducts
Columnar epithelium of GIT, uterus, fallopian tubes
Transitional epithelium of urinary tract
Readily regenerate as long as pool of stem cells preserved
What cells are known as ‘stable tissues’ and have limited capacity to regenerate?
Solid parenchymal organs, ie kidney, liver, pancreas
What cells are permanent tissues?
Brain, heart
What are the 5 steps to bone healing?
- Haematoma (hours)
- Influx of inflammatory cells, fibroblasts, and new blood vessels (24 hours)
- Procallus formation
- Ossification (2-3 weeks)
- Remodelling (6 weeks + )
What factors affect wound healing?
Infection
Nutrition (protein and vitamin deficiency)
Glucocorticoids
Mechanical factors
Poor perfusion
Foreign body
Diabetes
What are key features on assessment of a fracture?
1) Open vs closed
2) Intra vs extra-articular
3) Neurovascular status
4) Swelling/skin condition