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Flashcards in Regeneration and Repair Deck (22):

What is regeneration and what is repair?

Regeneration is defined as the replacement of dead or damaged cells by functional differentiated cells. Repair is to do with replacement with non-functional scar tissue.


Describe the cell cycle

To replicate the cell must go through the cell cycle. The G0 stage is called the quiescent stage and some cells like neurones will stay in this stage forever whilst other only for a short while. To pass onto the next stage the cell must successfully complete the previous stage and there are checkpoint for DNA integrity at G1-S and G2-M. If there is any damage detected the cell cycle is delayed and repair mechanisms are triggered, if this can’t be solved the cell will go through apoptosis.


What are the 3 classes of cell in term of regeneration capabilities?

• Labile cells – continuously proliferate such as in the skin and GI
• Stable cells of Quiescent cells – usually wait in the resting stage but regneration rates vary such as hepatocyts, osteoblasts and fibroblasts
• Permentant cells – never leave G0 such as neuroens and cardiac myocytes


How do growth actors affect regeneration, give examples of growth factors?

Growth Factors promote proliferation by binding to receptors and stimulating genes involved in the cell cycle, they can be autocrine, paracrine or endocrine. Examples of proteins include Epidermal Growth factor (EGF), Plaetlet Derived Growth factor (PDGF), Vascular endothelial growth factors (VEGF) and hormones such as: oestrogen, testosterone and growth Hormone.


How does cell contract affect regeneration?

Contact between basement membranes and adjacent cells – so if the cells are in contact this inhbits proliferation (called contact inhibtion), loosing contact cell to cell or to basement membrane promotes proliferation which can lead to cancer


When does fibrous repair take place?

For fibrous repair to take place the injury or inflammaton must either cause necrosis of permentant cells, or casue necrosis of labile/stable cells and also destroy the collagen framework.


What is the 1st stage of fibrous repair?

Inflammatory cells such as phagocytes and lymphocytes which digest unwanted tissue and debris. Endothelial cells are key due to the need for angiogenesis. And finally fibroblasts and Myofibroblasts which are important for the laying down of extracellular matrix such as inserting collagen.


What is the 2nd stage of fibrous repair?

Angiogenesis - developing some kind of blood supply is vital for wound healing and is initiated by an important growth factor called VEGF stimulating pre-existing blood vessels to sprout new blood vessels:
• Endothelial proteolysis of the basement membrane
• Migration of endothelial cells via chemotaxis (to the stimulus produced by the tissue requiring blood e.g. VEGF.
• Endothelial proliferation
• Endothelial maturation and tubular remodelling
• Recruitment of periendothelial cells e.g. pericytes and vascular smooth muscle cells


What is the 3rd stage of fibrous repair?

This is what supports and anchors the cells and keeps certain groups of cells in the correct compartments. It allows for communication between cells and facilitates cell migration. Collagen forms the extracellular framework in the matrix. There are two main groups of collagen the Fibrillar Collagens (long uninterrupted chains) I-III which are in the dermis and bones and cartilage etc. Then there is the Amorphous Collagen (interrupted and breaks so not very long like fibrillary and form sheets instead of fibrils) IV-VI such as the type IV in the basement membrane.


List 4 defects that can occur in collagen formation

1. Vitamin C – required in enzyme for hydroxylation of alpha chains
2. Ethlers Danlos Syndrome – defective type 3 (reticulin) causing overly stretchy skin
3. Osteogenesis imperfecta – type 1 collagen causing weak and brittle bones
4. Alport Syndrome – X linked (usually) leading to defect in type IV causing defected basement membrane (and collagen required in ear, eye and kidney)


What is the role of glycoprotein, proteoglycans and elastin in extrcellular matrix?

The Matrix glycoproteins organise and orientate cells whist also supporting migration. The proteoglycans organise the matrix, provide cell support and regulate the availability of growth factors. Finally elastin provides tissue elasticity.


Describe the healing process of skin

1. First a blood clot forms preventing further bleeding and infections. This dries out forming a scab
2. Acute inflammation then takes place with the movement in of neutrophils which use the clots as a frame work begin to digest the dead material and invading pathogens.
3. Then you get the migration of your chronic inflammatory cells such as lymphocytes and macrophages which digest the clot more and are activated by dead neutrophils. They then stimulate fibroblasts to arrive
4. Basal epidermal cells travel across the wound at about 0.5mm per days laying down basement membrane material underneath the scab
5. Fibroblasts and Myofibroblasts move in within a few days and begins to create the granulation tissue from glycoproteins that fills the wound. Angiogenesis is stimulated
6. Epidermal proliferation thicken this layer and then the scab falls off
7. Fibroblasts begin to lay down collagen forming an early scar, the epidermis normalises but without sweat glands or hair.
8. Blood vessels retreat and the scar becomes white


What is healing by primary intention?

This is when there is a clean uninfected surgical incision with apposed edges. There is minimal clot and few cells are killed so there is little to repair. The epidermis can re grow over the wound first whilst the slower dermis repairs underneath leading to a very thin scar. Only down side is that infection can be trapped inside the wound leading to abscess formation. In this process there is little need for contraction and the scars mature for about 2 years.


What is healing by secondary intention?

This can be due to infarct, ulcers abscesses or any large wound. The edges are unopposed, there is a large clot that dries into a scab. The epidermis regenerated from the bottom up and much more granulation tissue and collagen is produced leading to a large scar. Much more contraction takes place to bring the wound edges together and close the wound. However this can lead to deformities.


Describe the process of healing bone fractures

Large haematoma forms filling the fracture gap which provides a fibrin mesh which allow for the invasion of neutrophils, macrophages, endothelial cells, osteoblasts and fibroblasts. The necrotic tissue is removed and capillaries begin to develop. This large mixture of cell and clot forms a soft callus. Bone begins to be laid down in irregular patterns and the external callus provides a splint like support forming a hard callus. This is then slowly replaced by organised lamellar bone and the remodelling takes place in the direction of the mechanical stress for the bone.


What local factors influence wound healing?

• Sizes, type and location of wound
• Apposition of the edges of the wound
• Blood supply both arterial and venous
• Infection
• Foreign materials present
• Radiation Damage


What general factors influence wound healing?

• Age
• Drugs
• Dietary deficiencies
• General state of health i.e. diabetes
• CV status


What is wound dehiscence?

Inadequate granulation tissue or scar formation may lead to wound dehiscence where by the wound bulges out of the gap and is not contained, this commonly happens on the abdomen. Also if there isn’t adequate vascularisation then you may get ulceration.


What is keloidosis?

Keloidosis is when too much collagen is put down causing excessive fibrosis. This is when the scar bulges out of the wound itself and forms a prominent patch of scar tissue that grows outside of the original wound. This is usually caused by over activity of fibroblasts.


Describe regeneration of the liver

Cirrhosis of the liver appears as small regenerative nodules all over the liver due to the proliferation of hepatocytes inside a fibrous capsule. This is because although the hepatocytes can regenerate the liver architecture can’t.


What happens when repairing heart muscle of CNS neurons?

Cardiac Myocytes, cartilage and neurones in the CNS cannot regenerate. In the heart loss of cells is replaced with scar tissue whilst in the CNS it is replaces with Glial cells.


How do peripheral nerve regenerate?

Peripheral nerves can regenerate by Wallerian Regeneration. The side with the cell body will sprout and attempt to reconnect by following the left over Schwann cells. This occurs at 1-3mm per day. If there is a large gap where the nerve was severed this could lead to disorganised growth called a neuroma which may put pressure on other nerves and cause pain.