Session 4 Flashcards
What are the three processes of wound healing?
Haemostasis
Inflammation
Regeneration and repair
What is needed for regeneration to take place?
An intact connective tissue scaffold
What are the different types of tissues according to their proliferative capacity (and examples)?
Labile tissues proliferate throughout life -e.g. Surface epithelial cells, cells of bone marrow and haematopoietic tissues
Stable tissues normally have low levels of proliferation but can undergo rapid division in response to stimuli - e.g. Cells in liver, kidney and pancreas and mesenchymal cells such as fibroblasts and smooth muscle cells
Permanent tissues contain cells that have left the cell cycle - e.g. Neurones and muscle cells
What are the processes involved in fibrous repair?
Phagocytosis of necrotic tissue debris
Proliferation of endothelial cells resulting in small capillaries growing into the area (angiogenesis)
Proliferation of fibroblasts and myofibroblasts - repair tissue at this stage is called granulation tissue
The granulation tissue becomes less vascular and matures into a fibrous scar
Scar matures and shrinks due to contraction of myofibroblasts
Name some diseases that result from collagen synthesis defects
Scurvy - vitamin C deficiency. Hydroxylation of pro collagen is absent
Ehlers-danlos syndrome - collagen fibres lack tensile strength. Skin is hyper flexible & fragile and joints are hyper mobile. Would healing is poor, joint dislocations are common and large arteries may be ruptured
Osteogenesis imperfecta - too little bone tissue hence skeletal fragility
Give some examples of important growth factors that regulate the entry and passage of cells through the cell cycle.
- epidermal growth factor - mitogenic for epithelial cells, hepatocytes and fibroblasts. Produced by inflammatory cells they bind to epidermal growth factor receptors.
- vascular endothelial growth factor (VEGF) - proangiogenic in chronic inflammation, wound healing and tumours.
- platlet derived growth factor - released on platlet activation to cause migration and proliferation of fibroblasts, smooth muscle cells and monocytes
- tumour necrosis factor - induces fibroblast migration and proliferation
- granulocyte colony stimulating factor (G-CSF) (granulocytes are neutrophils, eosinophils and basophils)
What is contact inhibition?
When normal cells become isolated they will replicate until they form a mono layer of cells around them. This occurs in wound healing but is altered in malignant cells. Signalling is through adhesion molecules
When does healing by primary and secondary intention occur?
Primary - incisional, closed, non-infected and/or sutured sounds with opposed edges.
Secondary - excisional or infected wounds with tissue loss and separated edges.
Outline the process of healing by primary intention
Haemostasis - severed arteries contract, the narrow surface is filled with clotted blood, there is dehydration of the surface clot and a scab is formed, preventing bacteria from entering.
Inflammation - neutrophils appear at the margins of the incision, warding off bacteria
Migration of cells - macrophages start to appear and scavenge dead neutrophils and secrete cytokines that attract fibroblasts and endothelial cells. Epidermal cells fuse below the scab, depositing basement membrane as they go.
Regeneration - granulation tissue invades the space. Epidermal cells undermine the scab which falls off. Fibroblasts produce collagen and angiogenesis progresses.
Early scarring - collagen forms a scar, epidermis normalises.
Scar maturation - scar has collagen and elastin with little cells. Old scars appear white as capillaries disappear.
Outline the process of healing by secondary intention
The open wound is filled with granulation tissue which grows in from the wound margins. The inflammatory response is more intense because there is more necrotic debris and a larger clot. Considerable wound contraction occurs.
Substantial scar tissue is seen, the new epidermis is often thin and healing is delayed if infection is present.
Outline the process of healing of bone fractures
A fracture results in a haemotoma which fills the gap and surrounds the bone injury.
A fibrin mesh and then the granulation tissue is formed. Platlets and inflammatory cells release cytokines that activate osteoprogenitor cells.
Soft callus forms after ~1 week resulting in a budge around the fracture. It consisting of fibrous tissue and cartilage within which woven bone begins to form
Hard callus appears after several weeks. It is laid down by osteoblasts which initially form woven bone before forming lamellar bone.
Remodelling of the bone occurs in response to mechanical stresses placed on it.
What are local factors that influence healing and repair?
Size location and type of wound Blood supply Local infection Foreign material Mechanical stress Presence of necrosic tissue
What are systemic factors that influence healing and repair?
Age
Drugs
Diet - eg vitamin c and essential amino acids
General state of health - eg diabetes
What are possible complications of fibrous repair?
Formation of fibrous adhesions
Loss of function due to replacement of parenchymal cells (eg MI)
Distortion of architecture (eg liver cirrhosis)
Overproduction of scar tissue (keloid)
Extensive scar contraction leading to obstructed tubes, disfiguring scars (burns) or joint contractures.
Describe healing and repair in the heart, liver, peripheral nerves, CNS and cartilage
Heart - fibrosis
Liver - some regenerative capacity
Peripheral nerve - proximal stumps sprout and regenerate (~1mm/day)
CNS - replaced by glial cells
Cartilage - lacks blood supply and innervation so poor healing
