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ESA2 - Mechanisms Of Disease > Healing And Repair > Flashcards

Flashcards in Healing And Repair Deck (29):

Define regeneration

Growth of cells and tissues to replace lost structures following injury, provided the stem cells are still intact


What are labile cells? Give 3 examples

- Cells which are continuously proliferating throughout life to replace lost/damaged cells
- e.g. Surface epithelia of the epidermis, bone marrow, columnar epithelia of the gut mucosa and uterus


Can stable tissues undergo regeneration?

- Yes, cells remain in the quiescent G0 phase of the cell cycle and can re-enter in response to stimuli and undergo rapid division
- e.g. Parenchymal cells of the liver, kidney and pancreas, mesenchymal cells, fibroblasts, macrophages


Why can permanent tissues not regenerate?

- Cells leave the cell cycle permanently and cannot undergo mitotic division in postnatal life, as the tissues contain no stem cells that can replace damaged tissue
- e.g. cardiac myocytes cannot regenerate following infarction


Describe the replication pattern in stem cells

- Following mitosis, one of the daughter cells remains a stem cell and the other differentiates


Why can stem cells proliferate indefinitely without senescence? Are there any other cells which are capable of this?

- Stem cells produce TELOMERASE which maintains the length of the telomeres during continuous mitotic division (telomeres are shortened during each division until they become a critical length and cells undergo apoptosis)
- Cancer cells can also produce telomerase and can replicate indefinitely


What is the difference between totipotent, multipotent and unipotent cell types?

- Totipotent cells can differentiate into ANY cell type e.g. embryonic stem cells
- Multipotent cells can produce several different types of cells within the same lineage e.g. haematopoietic cells
- Unipotent cells can only differentiate into a SINGLE cell type e.g. epithelia


Give 2 instances where a fibrous scar may form

- If collagen framework of tissue is destroyed
- If there is ongoing chronic inflammation
(Cells cannot be replaced at an effective rate to exceed cell loss, resulting in formation of a fibrous scar)


Describe the process of fibrous repair (granulation tissue formation)

- Phagocytosis of necrotic debris
- Proliferation of endothelial cells, forming small capillaries (angiogenesis, stimulated by VEGF)
- Proliferation of fibroblasts/myofibroblasts which form granulation tissue (collagen and GAGs) and cause wound contraction
- Scar maturation (becomes less vascular and shrinks due to contraction)


Name 4 diseases which affect collagen synthesis

- Scurvy (vitamin C deficiency)
- Ehler's Danlos syndrome (lysyl oxidase deficiency)
- Osteogenesis imperfecta (type I collagen deficiency)
- Alport syndrome (type IV collagen deficiency)


Describe the symptoms of osteogenesis imperfecta

- Deficiency in type I collagen causes bones to be brittle and extremely fragile and prone to fractures
- Type 1 OI have blue sclerae, as the lack of collagen in the sclera makes them appear translucent


Describe the pathophysiology of Ehler's Danlos syndrome

- Deficiency in lysyl oxidase so collagen is unable to form stable cross links so lack tensile strength
- Skin is hyperextensible and joints are hypermobile as a result and wound healing is poor
- Rupture of colon, cornea and large arteries is not uncommon due to lack of tensile strength of collage


Why might patients with Alport syndrome present with haematuria?

- Deficiency in type IV collagen which affects the basement membrane in the glomerulus of the kidney (Bowman's capsule)
- Dysfunction of the membrane causes filtration of RBCs which would normally not enter filtrate and are therefore present in the urine
- This may progress to kidney failure


Give 3 examples of how cells can communicate via local mediators or hormones

- Autocrine (cell responds to signals that they themselves produce)
- Paracrine (cells respond to signals produces by adjacent cells within the local vicinity, often a different type)
- Endocrine (cells respond to hormones produced by endocrine organs which travel in the bloodstream to distant target cells)


What are growth factors?

- "Local polypeptide hormones" coded for by proto-oncogenes and act on cells via paracrine signalling over short distances
- Bind to specific receptors and stimulate/inhibit cell proliferation and angiogenesis


Give 4 examples of growth factors and their associated actions

- EGF (mitogenic for epithelia, hepatocytes and fibroblasts)
- VEGF (induces vasculogenesis, role in angiogenesis of tumours, chronic inflammation and wound healing)
- PDGF (migration and proliferation of fibroblasts, monocytes and smooth muscle cells)
- TNF (induces fibroblast migration and proliferation, secretion of collagenase)


What is contact inhibition? Name 2 important proteins involved in this

- Normal cells (when isolated) replicate until they are touching other cells and then stop
- Involves expression of adhesion molecules (cadherins which bind cell-cell, integrins which bind cell-stroma)
- Adhesion molecules are abnormally expressed in cancer cells, allowing them to invade surrounding tissues


When does healing by primary intention occur?

Incisional, closed, non-infected wounds with opposed edges and minimal loss of connective tissue scaffold


What are the 5 stages of healing by primary intention?

- Haemostasis (severed arteries contract and space fills with clotted blood)
- Inflammation (neutrophils and leucocytes invade to kill of any bacteria present)
- Migration of cells (macrophages migrate and remove neutrophils; release cytokines which attract fibroblasts and endothelial cells)
- Regeneration (epithelial cells proliferate and granulation tissue invades the space; angiogenesis progresses)
- Scarring and maturation (vascular channels regress, leaving an excess of fibrous tissue which matures)


When does healing by secondary intention occur?

Excisional or infected wounds with a large amount of tissue loss and unopposed edges


Describe the process of healing by secondary intention

- Inflammation (more intense response as infection is likely)
- Granulation tissue (abundant and fills open wound; grows in from the margins)
- Wound contraction (myofibroblasts contract into centre to close the wound)
- Scar formation (substantial but depends on the size of wound, no skin appendages present and skin is often thinner)


Explain the stages involved in fracture healing

- Haematoma formation and migration of macrophages
- Macrophages secrete cytokines which attract fibroblasts which secrete ECM of granulation tissue and osteoprogenitor cells
- Fibroblasts differentiate into chondroblasts which lay down hyaline cartilage, forming a fibrocartilaginous callus (procallus)
- Endochondral ossification of cartilage forming woven bone. Osteoblasts lay down new woven bone which forms lamellar bone
- Bone remodelling in response to mechanical stress and normal outline is restored


Name 5 local factors which may impair wound healing

- Blood supply
- Local infection
- Size, location and type of wound
- Denervation
- Presence of foreign bodies or necrotic tissue


Name 5 systemic factors that affect wound healing

- Age
- Diabetes/Obesity
- Malignancy due to cachexia
- Drugs e.g. Steroids
- Vitamin deficiency/malnutrition


What are the complications of fibrous repair?

- Formation of fibrous adhesions or replacement of parenchymal tissue with fibrous, which can compromise organ function
- Distortion of tissue architecture e.g. cirrhosis
- Keloid scar formation
- Wound dihisence
- Excessive scar contraction (cause strictures or fixed flextures)


Describe the process of healing following a myocardial infarction

- Cardiac myocytes are permanent cells which cannot proliferate and undergo regeneration
- Damaged myocardium undergoes fibrous repair and scar tissue is formed


Why is healing of cartilage poor?

Lacks blood supply, lymphatic drainage and innervation


Describe 2 instances where permanent cells may be replaced by supporting cells

- CNS - damaged neurones are replaced by glial cells via process of gliosis
- Skeletal muscle - damaged myocytes are reinforced by satellite cells which fuse with existing muscle fibres and cause hypertrophy


Describe the healing of a peripheral neve

- Severed axons undergo Wallerian degeneration
- Proximal stumps sprout and elongate and use Schwann cells from the distal stump to guide them back (grow 1-3mm/day)
- May require surgery if the axon ends are unopposed