Healing: Regeneration and Repair Flashcards
Whatever the wound, what is the aim of the body?
To close the gap and repair it with a scar - the smaller the better.
Processes in wound healing:
- _____________ as all vessels are open.
- _____________ as the tissue is injured.
- _____________ (resolution and restitution) and/or repair (organisation), as structures have been injured or destroyed.
Haemostasis
Inflammation
Regeneration
What is regeneration?
Restitution with no, or minimal evidence of previous injury - healing by primary intention of a superficial abrasion.
What’s the difference between an abrasion and an ulcer?
In an abrasion, the top few layers of cells are lost (superficial scrape), but an ulcer is deeper - the injury goes into the submucosa.
In regeneration, new differentiated cells are mainly derived from what?
Stem cells (many terminally differentiated cells can’t divide).
Stem cells have prolonged ____________ activity and show asymmetric ___________ - they are part of the internal repair system to replace any lost/___________ cells in a tissue. The location of stem cells varies between tissues e.g. In the epidermis they are in the _______ layer adjacent to the ______ membrane, in the internal mucosa they’re at the bottom of the ________ and in the liver between the hepatocytes and the ______ ________.
Proliferative Replication Damaged Basal - basal Crypts Bile ducts
Describe the difference between unipotent, multipotent and totipotent stem cells.
Most adult stem cells are unipotent and only produce one type of differentiated cell (e.g. Epithelia). Multipotent SCs can produce several types of different cells e.g. Haematopoietic stem cells. Embryonic SCs are totipotent, which can produce any type of cell and so tissue in the body.
Not all tissues can regenerate, it depends on which of 3 types they are, name them.
Permanent tissues, labile tissues and stable tissues.
What are permanent tissues? Give examples.
Permanent tissues e.g. Neural tissue, skeletal and cardiac muscle, have mature cells that can’t undergo mitosis and few/no present stem cells.
What are labile tissues? Give examples.
Labile tissues e.g. Surface epithelia, haematopoietic tissue, contain short lived cells replaced by cells derived from stem cells.
What are stable tissues? Give examples.
Stable tissues e.g. Liver parenchyma, bone, fibrous tissue and endothelium, normally have a low level of replication, it can undergo rapid proliferation if necessary - both stem cells and mature cells proliferate.
Tissues are based into groups based on their proliferative activity, where are the different types of tissue in the cell cycle?
Labile cells are continually cycling, stable cells are in G0 and can reenter when necessary and permanent cells can’t reenter the cell cycle.
When is regeneration possible?
If damage occurs in labile/stable tissues and the tissue damage is not extensive - requires an intact connective tissue scaffold.
What is fibrous repair/organisation?
Healing with the formation of fibrous connective tissue/a scar. Specialised tissue lost and healing by secondary intention.
When does repair/organisation occur (instead of regeneration)?
When there is significant tissue loss/if permanent or significant tissue is injured.
What is the progression of scar formation over time?
Seconds-minutes: haemostasis, minutes to hours: acute inflammation, 1-2 days: chronic inflammation, 3 days: granulation tissue forms, 7-10 days: early scar, weeks-2 years: scar maturation.
Granulation tissue has a granular appearance and texture, what does it consist of and what is its function?
Consists of: developing capillaries, fibroblasts (and myofibroblasts) and chronic inflammatory cells.
Function: fills the gap, capillaries supply oxygen, nutrients and cells, it contracts and closes the hole.
What cells can be expected to be seen in a forming scar/granulation tissue?
Inflammatory neutrophils and macrophages for phagocytosis of debris and macrophages and lymphocytes for the production of chemical mediators, endothelial cells - the proliferation of which drives angiogenesis, fibroblasts and myofibroblasts to produce extracellular matrix proteins and responsible for wound contraction - fibrils within myofibroblasts.
Explain the colour and appearance of scars.
At first they are red, when there are a lot of blood vessels, then they eventually go white as melanocytes don’t regenerate. They also can’t lay down elastin, so the skin could be stretched - can’t replace deep, complex structures of sweat glands and hair follicles.
Collagen is the most ________ protein, it provides the ____________ framework and is composed of ________ helices of various polypeptide alpha chains. Fibrillation collagens ___, ___ and ____ are responsible for tissue strength. Amorphous collagens ___, ___ and ___ are integral in the basement membrane.
Abundant Extracellular Triple I, II and III IV, V and VI
Which type of collagen is the most common in hard and soft tissues (e.g. Bones and sclera) and which type in the basement membranes, secreted by epithelial cells?
Type I and Type IV.
Fibrillar collagen production takes ___ hours: polypeptide alpha chains are made in the __ of fibroblasts, enzymatic modification steps, including vitamin __ dependent hydroxylation take place. Alpha chains align and _____ ______ into procollagen triple helix, which is soluble and ________. Procollagen is cleaved to ________, which polymerises to form a myofibril then fibril, bundles of fibrils form _____. Cross linking between fibres produces ______ strength and there is slow _________ by collagenases.
1-2 ER C Cross link Secreted Tropocollagen Fibres Tensile Remodelling
Diseases from defective collagen are either inherited or acquired, describe an acquired defective collagen disease.
Scurvy is vitamin C deficiency, with inadequate hydroxylation of procollagen alpha chains, meaning reduced cross linking and so defective healing, as there is a lack of strength and the molecule is vulnerable to degradation. It particularly affects the collagen supporting blood vessels. Unable to heal wounds, tendency to bleed, tooth loss (periodontal ligament collagen has a short T1/2, so normal collagen’s replaced by defective), old scars reopen as fresh wounds (collagen turnover remains high).
Ehler’s-Danlos syndrome:
Heterogenous group of 11 __________ disorders involving defective cleaving of ___________ to tropocollagen. Collagen fibres lack adequate ________ _________, leading to poor would healing, hyperextensible _______, that is also thin, fragile and susceptible to ________ (can still ______ as the elastic fibres are normal). Joints are hypermobile and have a predisposition to ___________. In some forms there may be spontaneous rupture of the ______, large arteries or cornea, maybe with retinal ____________.
Inherited Procollagen Tensile strength Skin Injury Recoil Dislocate Colon Detachment
