4 Healing & repair Flashcards
1
Q
Whatever the wound, basic ‘plan’ is the same, what is this basic ‘plan’ ? Involving …. Gap, repair it with …. / ….. and the smaller the scar the ….
A
- close the gap
- repair it with normal tissue
- repair it with a scar
- the smaller the scar the better
2
Q
5 steps involved in wound healing ?
A
- haemostasis - blood vessels are bleeding
- inflammation - been tissue injury
- proliferation of injured tissues
- regernation / resolution / restitution and / or repair (organisation) of structures that have been injured or destroyed
- re-modelling: the return, if possible, to original form
3
Q
Haemostasis happens within (time frame of injury)?
A
first few minutes of injury
4
Q
What happens during haemostasis ?
A
- Platelets adhere to each other and to the injured site.
- They change into an amorphous shape, more suitable for clotting, and they release chemical signals to promote clotting.
- Activation and formation of a fibrin clot binding everything together to stop blood loss
- Vasoconstriction of arterioles and arteries
5
Q
Inflammation increases local blood flow bringing …. to site of injury
A
- oxygen
- nutrients
- immune cells
6
Q
In inflammation what is removed by phagocytosis ?
A
- damaged and dead cells
- bacteria and debris
7
Q
Proliferation: growth of new tissue involves what ?
A
- regeneration of damaged tissues
- granulation tissue formation
- angiogenesis
- myofibroblasts close the gap
- cells die by apoptosis when process complete
8
Q
Granulation tissue formation means what ?
A
fibroblasts grow and form/ repair a new, provisional matrix/scaffold
9
Q
what is angiogenesis ?
A
new vessel formation
10
Q
How do myofibroblasts close/decrease the gap ?
A
gripping the wound edge and contracting
11
Q
In proliferation what do the original cells in a skin lesion do ? [aleter Q!]
A
multiply and grow across the wound bed
12
Q
What is granulation tissue NOT ?
A
granuloma
13
Q
What does granulation tissue have ?
A
granular appearance and texture
14
Q
granulation tissue consists of ?
A
- Developing capillaries
- Fibroblasts and myofibroblasts
- Chronic inflammatory cells
15
Q
Functions of granulation tissue ?
A
- Fills the gap
- Capillaries supply oxygen, nutrients and cells * Contracts and closes the hole
16
Q
What is involved in the step regeneration/ resolution/ restitution ?
A
- proliferation, if possible, of the original cells e.g. epithelial cells
- other cells of tissue/organ to return the tissue/organ to a near normal and funcitonal state
17
Q
If possible , what happens during re-modelling stage ?
A
return to original structure
18
Q
What happens to collagen or bone during re-modelling stage ?
A
re-aligned along the original structure, for instance in the skin along the “tension lines”
or bone returns to its pre-existing form and strength
19
Q
How are cells that are no longer needed removed ?
A
apoptosis
20
Q
Timescales of healing of haemostasis
A
seconds - minutes
21
Q
Timescales of healing of acute inflammation
A
minutes - hours
22
Q
Timescales of healing of chronic inflammation
A
1-2 days
23
Q
Timescales of healing of granulation tissue forms
A
3 days
24
Q
Timescales of healing of early scar
A
7 - 10 days
25
Timescales of healing of scar maturation
weeks - 2 years
26
What may insults be ? give examples
anything that causes tissue damage:
* infection
* burn
* insult due to toxins e.g. paracetamol etc.
27
Regeneration invovles either .... or ... insults
minor or more severe
28
Minor insult :
Restitution with ..1.. evidence that there was a ...2... injury
A ..3.. injury with ..4... edges: Wound healing by ..5.. intention
1. no, or minimal,
2. previous
3. superficial
4. closely aligned
5. primary
29
More severe insults involve .... injury , other ...., edged ..... ?
wound healing by .... intention ?
* more severe injury
* other insult
* where edges are not closely aligned
* secondary intention
30
In regeneration of more severe insults:
1. tissue does not ....
2. gap is filled in ...
1. return to original structure
2. by scar formation
31
Which cells are mainly derived from stem cells ?
new differentiated cells
32
Whic cells cannot divide ? [change answer]
Once terminally differentiated most terminally differentiated cells can't divide
33
Stem cells:
1. activity ?
2. replicaiton shown ?
3. what system to do what ?
1. ongoing/prolonged proliferative
2. asymmetric replication
3. 'Internal repair system' to replace lost or damaged cells in tissues
34
Stem cells vary between which tissues ? found where ?
LIE !!
Liver - between hepatocytes & bile ducts
Intestinal mucosa - bottom of crypts
Epidermis - basal layer adjacent to the basement membrane
35
Unipotent stem cells:
1. most .... cells
2. only produce ....e.g.
1. adult stem
2. one type of differentiated cell e.g. epithelia
36
multipotent
1. produce..
2. e.g.
1. several types of differentiated cell
2. haematopoietic stem cells
37
Pluripotent stem cells:
1. .... stem cells
2. can produce....
1. embryonic
2. any type of cell & therefore any tissues of the body
38
Totipotent stem cells:
1. what cells ?
2. can produce what ?
1. embryonic stem cells & extra-embryonic including placental cells
2. any type of cell and therefore any tissue of the body and placenta
39
1. Can all tissues regenerate ?
2. what does it depend on if all tissues regenerate ?
1. no
2. whether tissues are labile, stable, permanent
40
Tissues of the body are divided into 3 groups on the basis of their proliferative activity , what are these 3 groups ?
* labile
* stable
* permanent
41
What are labile tissues ?
* continuously dividing tissues
* proliderate throughout life replacing cells that are destroyed
42
Examples of labile tissues
* surface epithelia
* lining mucousa of secretory ducts of glands of the body
* columnar epithelia of GI tract and uterus
* transitional epithelium of urinary tract
* cells of bone marrow and haemotopoietic tissues
43
what are stable tissues ?
normally have what ?
* quiescent tissues
* normally have a low level of replication but cells in these tissues can undergo rapid division in response to stiumli and can reconstruct tissue of origin
44
examples of stable tissues ?
* parenchymal cells of liver , kidneys, pancreas
* mesenchymal cells e.g. fibroblasts, smooth muscle cells
* vascular endothelial cells
* resting lymphocytes
* other white blood cells
45
what are permanent tissues ?
* non-dividing tissues
* contain cells that have left the cellcycle and can't undergo mitotic division in postnatal life
* have no or only a few stem cells that can be recruited to replace cells
46
examples of permanent tissues
* neural tissue
* skeletal and cardiac muscle cells
47
Although quiescent cells are typically non-dividing cells that are in a state of dormancy or temporary inactivity, however what do certain quiescent cells have the capacity to do?
to re-enter the cell cycle and resume proliferation when necessary
48
In what circumstances can regeneration take place ?
* little/no interference i.e. absence of recurrent / unresolved insults
* if tissue damage not extensive
* regeneration requires an intact connective tissue scaffold - upon which regenerating tissue can build itself
* if damage occurs in lable or stable tissue
49
in fibrous repair tissue does not...
fully return to original state
50
What healing results in a scar ?
healing with formation of fibrous connective tissue
51
Formation scar seen when :
* specialised tissue is...
* seen in healing by...
* lost
* secondary intention
52
Formation of scar occurs with what ?
* signigican tissue loss
* if permanent or complex tissue is injured
53
Pathway of injury and inflammation to regeneration ?
1. Injury and inflammation
2. necrosis of labile / stable tissues
3. collagen framework intact
4. Regeneration
54
Fibrous repair pathway involved when collagen framework destroyed ?
1. injury and inflammation
2. necrosis of labile / stable tissues
3. collagen framework destroyed
4. fibrous repair (scar)
55
Fibrous repair pathway involved when on-going chronic inflammation ?
1. injury and inflammation
2. necrosis of labile or stable tissues
3. on-going chronic inflammation
4. fibrous repair (scar)
56
Fibrous repair pathway involved with necrosis of permanent tissues ?
1. injury and inflammation
2. necrosis of permanent tissues
3. fibrous repair (scar)
57
6 steps of fibrous repair
1. blood clots
2. neutrophils infiltrate and digest clot
3. macrophages and lymphocytes are recruited
4. vessels sprout, myofibroblasts make glycoproteins
5. vascular network, collagen synthesised macrophages reduced
6. maturity, cells much reduced, collagen matures, contracts and remodels
58
Which cells are invoved in fibrous repair ?
* inflammatory cells
* endothelial cells
* fibroblasts and myofibroblasts
59
Function of inflammatory cells in fibrous repair ?
–Phagocytosis of debris – neutrophils, macrophages
–Production of chemical mediators – lymphocytes, macrophages
60
Function of endothelial cells in fibrous repair ?
–Proliferation results in angiogenesis
61
Function of fibroblasts and myofibroblasts in fibrous repair ?
–Produce extracellular matrix proteins, e.g. collagen
– Responsible for wound contraction - contraction of fibrils within myofibroblasts
62
Where may scarring occur ?
* any tissue
* any organ
63
What is an ulcer ?
* A breach in the continuity of the skin/epithelium.
* Depth of the lesion such in bowel.
* Something is hindering the healing process or ongoing injury.
64
The control mechanisms in regeneration and fibrous repair are ....
poorly understood
65
Although the control mechanisms in regeneration and fibrous repair are poorly understood, what is known ?
cells communicate with each other to produce a fibroproliferative response
66
Cell to cell communication can be via what ?
* local mediators (e.g. growth factors)
* by hormones
* by direct cell-cell or cell-stroma contact
67
Considering local mediators and hormones, cell communication can be ?
* autocrine
* paracrine
* endocrine
68
Autocrine cell communication is where cells ...
respond to the signalling molecules that they themselves produce
69
Paracrine cell communication is where cells ...
* produces the signalling molecule that act on adjacent cells
* responding cells are close to the secreting cell and are often of a different type
70
Endocrine cell communication is where ...
hormones are synthesised by cells in an endocrine organ, they are then conveyed
in the blood stream to target cells to effect physiological activity
71
Growth factors:
* Important in ..1...
* they are ..2.. that act on cell ...3..
* coded by ..4....
* can be considered as ' ....5...'
1. wound healing
2. polypeptides
3. cell surface receptors
4. proto-oncogenes
5. local hormones
72
why can growth factors be considered as local hormones ?
they act only over a short distance or even on the secreting cell itself
73
Growth factors bind to specific receptors and do what ?
stimulate transcription of genes that regulate entry of cell into cell cycle and the cell's passage through it
74
List 9 effects that growth factors may have
* proliferation
* mitogenesis
* DNA synthesis
* angiogenesis
* movement of cells
* differentiation
* tissue remodelling
* chemotaxis
* growth
75
4 examples of growth factors
* epidermal growth factor
* vascular endothelial growth factor
* platelet derived growth factor
* tumour necrosis factor
76
Growth factors are produced by cells such as ....
* platelets
* macrophages
* endothelial cells
77
Epidermal growth factor:
1. mitogenic for ....
2. produced by ...
3. binds to ...
1. epithelial cells, hepatocytes, fibroblasts
2. keratinocytes, macrophages, inflammatory cells
3. epidermal grwoth factor receptor (EGFR)
78
Vascular endothelial growth factor:
1. potent inducer of ...
2. important in ...
1. blood vessel development (vasculogenesis)
2. growth of new blood vessels (angiogenesis) in tumours, chronic inflammation, wound healing
79
platelet-derived growth factor:
1. stored in ...
2. released on...
3. also produced by ....
4. causes migration and proliferation of ...
1. platelet alpha granules
2. platelet activation
3. macrophages, endothelial cells, smooth muscle cells, tumour cells
4. fibroblasts, smooth muscle cells, monocytes
80
Tumour necrosis factor induces ...?
* fibroblast migration
* fibroblast proliferation
* collagenase secretion
81
what does contact inhibition involve ? [understand and rewrite!]
* signalling through adhesion molecules
* inhibits proliferation in intact tissue, promotes proliferation in damaged tissues
* altered in malignant cells
82
Cadherins bind...
cells to each other
83
Integrins bind...
cells to the extracellular matrix
84
Primary and secondary intention refers to descriptions of wound healing related to
* size of the wound
* amount of loss tissue
85
Wounds healed by primary intention ?
* incised
* closed
* non-infected
* sutured
86
Wounds healed by primary intention involves
..1... of basement membrane continuity but death of only ..2.. number of ..3.. and ..4.. tissue cells
1. Disruption
2. small
3. epithelial
4. connective
87
There is minimal what in healing by primary intention ?
clot & granulation tissue
88
In healing by primary intention:
1. .... regenerated
2. .... undergoes fibrous repair
3. sutures out at about .... days
4. minimal .... & ...., good strength
1. epidermis
2. dermis
3. 10
4. contraction & scarring
89
Healing by secondary intention involves what wound ?
* excisional
* wounds with tissue loss, separated edges
* infected
* infarcts, ulcers, abscesses
90
Healing by secondary intention happens in open wound filled by ..1.. tissue - grows in from wound ...2..
1. abundant granulation
2. margins
91
Differences in process of healing by secondary intention to healing by primary intention .?
* considerable wound contraction must take place to close wound
* substantial scar formation, new epidermis often thinner than usual
* takes longer than healing by primary intention
92
In healing by secondary intention, considerable wound contraction must take place to close wound:
1. Intially occurs as scab...
2. after 1 week .... appear and ....
3. contract to draw the .... towards the centre - final shape of scar depends on ..... of wound
1. contract when it dries and shrinks
2. myofibroblasts, contract
3. margins , original shape
93
6 steps involved in how bone heal?
1. haematoma formation
2. granulation tissue forms
3. soft callus
4. hard callus
5. lamellar bone formation
6. remodelling
94
In the second stage of healing bone fractures where a fibrin mesh then granulation tissue is formed:
A . ...1.... release ...2..
B. which activate ...3... cells to ..4... and ..5... activity
C these areas of bone resorption may be visible on an ....6...
1. platelets and inflammatory cells
2. cytokines
3. osteoprogenetic
4. osteoclastic
5. osteoblastic
6. X-ray
95
soft callus is also called .... callus or....
fibrocartilagenous callous or procallus
96
Local factors that can influence wound healing ?
1. Type, size, location of wound
2. Mechanical stress - can pull apart delicate tissue
3. Blood supply
4. Local infection - produces persistent tissue injury and inflammation
5. Oedema
6. Necrosis - needs clearing during process of repair
7. Foreign bodies - prouce persistent inflammation and favour infection
8. Repeated/ongoing injury
97
general/systemic factors that can influence wound healing ?
1. Age - children heal quickly, elderly people more slowly
2. Anaemia, hypoxia and hypovolaemia - poorer oxygen delivery to healing tissue
3. Obesity - increased tension on wounds & wound dehiscence
4. Diabetes
5. Genetic disorders - e.g. Ehlers-Danlos syndrome
6. Drugs such as steroids
7. Vitamin deficiency - vitamin C defieicny inhibits collagen synthesis
8. Immunodeficiency
9. Malnutrition - impact protein synthesis
98
Complications of fibrous repair ?
* Insufficient fibrosis
* formation of adhesions
* loss of function
* Disruption of complex tissue relationships within an organ
* Overproduction of fibrous scar tissue
* Excessive scar contraction
99
How to predict the type of healing that will occur depends on what ?
* type of tissue
* extent of injury
* complicating factors such as infection
* the patient
100
What does insufficient fibrosis include ?
* Wound dehiscence, hernia, ulceration
* For example obesity, elderly, malnutrition, diabetes, steroids.
101
why is Formation of adhesions a complication of fibrous repair ? give example
* Compromising organ function or blocking tubes, e.g., intestinal obstruction following abdominal surgery
102
Why is loss of function a complication of fibrous repair ? include example
Due to replacement of specialised functional parenchymal cells by scar tissue
, e.g., healed myocardial infarction with non-contracting area of myocardium
103
why is Disruption of complex tissue relationships within an organ a complication of fibrous repair ?
give example
Distortion of architecture interfering with normal function, e.g., liver cirrhosis
104
EXAMPLE OF
Overproduction of fibrous scar tissue as a complication of fibrous repair ?
keloid scar
105
1. Keloid scar = ...
2. due to ...
3. they don't...
4. they are more common in people like...
1. overgrowth of fibrous tissue
2. overproduction of collagen which exceeds borders of the scar
3. regress and excision just creates another one
4. afro-caribbean
106
why is Excessive scar contraction complication of fibrous repair ?
1. can cause...
2. disfiguring scars following...
* Can cause stenosis, narrowing of lumen of tubes, such as the GI or urinary tracts
* Disfiguring scars following burns or joint contractures resulting in fixed flexures.
