Wound Healing Flashcards
1
Q
Purpose of wound healing
A
To restore normal tissue function
2
Q
What is the biggest factor that delays wound healing
A
Infection
3
Q
Healing begins during
A
The acute inflammatory response
Often within 24 hours of injury
Very fast in young healthy people
4
Q
Healing is promoted by
A
-Clean wound
-Growth factors
-Good nutrition status (water, protein, vit c, copper, zinc, selenium)
-Good apposition of wound edges
-Good blood supply and lymphatic drainage
-Healthy immune system
-Survival of stromal and parenchymal cells for regeneration ( minimal loss of function )
5
Q
Healing is Delayed by
A
-Chronic inflammation due to continued presence/repeat exposure to causative agent or large area of necrotic tissue
-Growth inhibitors
-Poor nutritional status (dehydration, lack of nutrients
-Poor apposition of wound edges
-Poor blood supply and or poor lymphatic drainage (elderly, CV, resp or lymphatic disorders, tissue hypoxia)
-Immunosuppression (radiation, chemotherapy, drugs; steroids, NSAIDS) diabetes, elderly
-Loss of stromal and parenchymal cells (noticeable loss of function; scarring)
6
Q
Apposition
A
- = approximation
-I.e wound edges are close together; may require stitches or casting
7
Q
“Repair”
A
Implies healing with scarring
Should use term resolved or healed with client
8
Q
Debridement
A
- Process of cleaning up the wound site
- Includes removal of dead cells, necrotic tissue, and foreign material using physical, surgical, cellular, or chemical means
- Essential to wound healing
9
Q
Innate Immune Mechanisms Involved in Debridement
A
-Macrophages (M2)
-Flushing Mechanisms
-Enzymes
10
Q
Macrophages and Debridement
A
-Macrophages: M2 Macrophages clean up cellular debris/microbes using phagocytosis
11
Q
Flushing Mechanisms Debridement
A
-Such as tears, urination, stool, mucous, saliva
-Dilute and wash pathogen out/away
-Use copious amounts of fluid to help cleanse mucosal surfaces
12
Q
Enzymes Mechanisms Debridement
A
-Proteolytic
-Such as lysozyme (tears, saliva)
-Help disrupt pathogens normal protein structure including changing shape and or removing amino acids
-When protein is changed, protein cannot function properly so bacterial/virus protein can’t make you sick
13
Q
Term used to describe removal of pus laden tissue from wound
A
Aspiration
14
Q
If wound is not cleaned of debris or is infected …
A
It will not heal properly
Causes chronic inflammation, delayed healing, and probably scarring
15
Q
Would healing: Resolution
A
-Complete restoration of injured tissues to the original structure and function
-Damaged cells recover
-BEST OUTCOME
-No permanent deficits
-May take as long as 2 years
16
Q
Examples of Resolution
A
-Mild sunburn (did it blister? = second degree burn)
-Uterus post partum (why doctors suggest waiting 2 years)
17
Q
Wound Healing: Regeneration
A
-Production of new, healthy stromal and parenchymal body cells to replace those damaged by the injury
-Replacement occurs by mitotic cell division (mitosis)
18
Q
Regenerative Potential
A
-Based on cells ability to replicate by mitosis
-Varies on specific cell type
-Is that cell capable of mitosis
19
Q
3 Levels of Regenerative Potential
A
-Labile Cells
-Stable Cells
-Permanent Cells
20
Q
Parenchymal cells
A
-Functional cells of the organ
-Their survival or ability to reproduce if injured is vital to the ability of the injured tissue to return to normal function
21
Q
2 Types of cells that do not divide to replace
A
-Neurons
-Cardiac muscle cells
22
Q
Labile Cells
A
-Capable of mitosis
-Constantly regenerating for normal tissue maintenance and to repair small wounds
-Cause most aggressive cancers (epithelial cancers, blood cell cancers)
23
Q
Examples Labile Cells
A
-Epithelium
-Areas of wear and tear; epidermis, linings of digestive tracts, resp, urinary, reproductive
-Red bone marrow (all blood cells)
24
Q
Stable Cells
A
-Do not normally divide but capable of mitosis if stimulated to do so by injury
-Also have ability to undergo cancer
25
Stable Cell Examples
-Endocrine and exocrine glands
-Liver (Hepatocytes)
-Kidney (Glomeruli and Nephron tubules)
-Smooth muscle
-Fibroblasts
-Osteoblasts
-Chrondroblasts
-Vascular endothelium
-Lung alveolar cells
-Neuroglia
26
Permanent Cells
-Have no regenerative potential
-Cannot under mitosis (after very early childhood)
-Even if tissue is injured and cells need replacing
-replaced by SCAR TISSUE
27
Examples permanent cells
-Neurons
-Cardiac Muscle cells
-Skeletal muscle (2+ years of age)
28
4 Primary Types of Tissue
Epithelium, Connective, Muscle, Nervous
29
Epithelium
-Cover surfaces
-Line structures
-Form glandular tissues
-Endocrine glands
-Exocrine glands
-Mucous secreting goblet cells
-Lacrimal glands
-GI glands
-Depending on specific location epithelial cells may be LABILE (at surfaces with lots of wear and tear) or STABLE cells (other areas)
30
Connective Tissue
-Binds (Connects) structures
-Dermis, Adipose, Bones, Cartilage, Tendons, Ligaments, Blood
-Most secrete collagen
-In general CT considered STROMAL TISSUE
-STABLE CELLS
31
Connective tissue Fibroblasts
-Usually considered stromal cells
-In Tendons and Ligaments which are essentially collagen fibroblasts considered parenchymal
-Extremely hardy and survive most tissue injuries
32
Fibroblasts are responsible for
-All collagen secretion including subtypes made during normal wound healing and scar tissue formation
33
Muscle Tissue
-Contracts to provide motility to the organ
-Skeletal, cardiac, smooth
-Skeletal muscle has some limited regenerative potential = considered STABLE until 2 years old then PERMANENT
-Smooth muscle = STABLE
-Cardiac muscle = PERMANENT
34
Nervous Tissue
-Neurons and supportive cells called neuroglia
-In CNS areas of neural atrophy replaced by excess CSF instead of scar tissue
-Decrease in brain tissue noticeable with medical imaging
-Neurons are PERMANENT
-Neuroglial cells are STABLE
35
Which categories of regenerative potential include stromal cells
Labile, Stable, Permanent
36
Wound Healing: Repair
-Replacement of destroyed tissue with SCAR tissue
37
Scar tissue formation is called
Fibrosis
-Made by a subtype of COLLAGEN that is produced by FIBROBLASTS during prolonged wound healing
38
Functions of Scar Tissue
-Weaker “filler” protein within a large wound or area of chronic inflammation
-Replaces dead parenchymal cells but does not restore normal tissue function —> deficits occur
39
Scar tissue provides damaged tissue with up to __ or original strength
80%
40
Fibrosis
-Dual purpose Term
-Used to describe normal collagen production AND scar tissue production
41
Collagen
Major fibre type in all connective tissues except blood
42
Fibroblasts
-Most common type of stromal cell
-Found in all types of connective tissue except blood
-Very hardy/resilient survive in situations that kill parenchymal cells like hypoxia
-
43
During Wound Healing Fibroblasts Will Become..
-Myofibroblasts
-Use their motility to infiltrate the wound site and fill in the site with secreted matrix = proteins and extra cellular fluid
-May simply be framework for new parenchymal cells to repopulate area or remodel to become permanent scar tissue (dependent on specifics of the situation)
44
Fibrosis: Collagen Production
-Production of collagen by CT cells called fibroblasts
-2 meanings depending on its location
-Fibrosis can mean normal collagen production during CT development, maintenance and normal wound healing
-Fibrosis can also mean excessive collagen production that results in scar/fibrotic tissue formation during wound repair
45
Fibroblasts are
Stromal
46
Fibroblasts can secrete
Several types of connective tissue protein fibers
-Main fibre is COLLAGEN
47
If parenchymal cells are permanently lost..
Fibroblasts will fill in the wound with scar tissue (collagen)
48
Collagen
-Most abundant CT fibre type
-Production regulated by gene expression within the fibroblasts (can change with circumstances)
-Normal collagen is healthy tissue and scar collagen are NOT the exact same proteins structurally or functionally
49
Normal Collagen Vs Scar Collagen
-Normal collagen is long, strong, and flexible, providing tensile strength, helps form a framework for parenchymal cells as they reproduce to return damaged tissues to full function
-Scar collagen is short, weak, and has minimal flexibility, very minimal strength to healing tissue, essentially “filler” to replace lost parenchymal cells
50
Amount of scar tissue and location..
Will determine whether normal or close to normal physiological activity is possible
-Cannot take over the normal parenchymal cell job
51
Other function of collagen..
When collagen comes into contact with platelets, it triggers the coagulation cascades =important to keep collagen out of blood stream to prevent intravascular thromboxane
52
Another name for a scar
Cicatrix
53
Fibrosis means
Production of collagen by fibroblasts
-Normal in creation and maintenance of healthy stromal tissues and is required in wound healing
54
Excessive fibrosis
Is scar tissue formation
55
Dense CT
-Collagen is arranged in regular rows, allowing strength and flexibility in the direction of orientation of the fibres (normal tendon)
56
Dense Irregular CT
Collagen arranger in a random pattern, allowing for some strength and flexibility in all directions (pericardium, dermis, sclera)
57
In scar tissue the subtype of collagen that replaces the normal collagen is..
Short, weak and randomly arranged
58
Dense and Irregular CT
Are a vascular
59
Achilles Tendon
Collagen is regularly arranged in long strong flexible bands with a few fibroblasts that produce and secrete collagen
-allows for strength of the tendon along a specific direction
-injury happens when outside forces cause over stretching of the collagen fibers and they break
60
2 Major Cell Types Involved in Wound Healing
1. Macrophages
2. Myofibroblasts
61
Macrophages
-Phagocytic “clean up” cells
-Typically M2 subtype but M1 tissue residing may still be alive and helping
-Early: Cell debridement
-Promote healing by secreting chemical mediators
-Secrete angiogenic factors and fibroblast growth factor
-Later: Blood clot dissolution
62
Myofibroblasts
Early: change gene expression to produce actin —> Myofibroblasts infiltrate damage site and secrete collagen fibers —> form framework for parenchymal cells to re establish in the site
-Later: Wound contraction to shrink size of wound
63
Angiogenic Factor
Chemicals that stimulate the production of new arterioles, capillaries, venules, and lymphatic capillaries during wound healing
64
Fibroblast Growth Factor
Stimulate the mitotic division of fibroblasts within the wound site
65
What are Myofibroblasts
-Fibroblasts in which gene to make protein actin has been turned on
-Called Myofibroblasts due to their ability to migrate into the wound site
-Contract around wound site to reduce edges of wound
-Pulling sensation is Myofibroblasts working
-Can also cause itchy feeling at the irritate nerve endings
-Following wound healing actin secretion ends and cells return to normal tissue fibroblasts
-Parenchymal cells will repopulate the wound using the collagen framework
66
What happens if you scratch a scab off?
Restarts at healing stage one if it bleeds
67
Blood Clot Dissolution
-Destruction of blood clot happens once the endothelial lining of the vessel has healed
68
Blood Clot Dissolution and Plasmin
-Plasmin is made in the liver and circulates in the blood plasma as the inactive precursor plasminogen
-Used to enzymatically digest the fibrin threads =fibrinolysis
69
Fibrinolysis
-Process of Plasmin phagocytizing fibrin threads
70
Blood Clot Dissolution Macrophages
Will phagocytize any degenerating RBCs or platelets that are trapped in the tissue space
Ie. part of any bruising of the injured tissue
71
What cell makes collagen?
Fibroblasts
72
Fibroblasts are part of which basic tissue type
Connective tissue (stromal)
73
What determines extent of scar tissue formation within a wound?
1) extent of tissue damage
2) complicated healing
3) non regenerative parenchymal cells
74
Does all fibrosis cause permanent scarring,
No
75
The ability of a damaged tissue to return to normal physiological activity depends on the relative balance between ____ and ____ function
Stromal/fibroblast
Parenchymal
76
The Healing Process Overlapping Phases
1) Fill in the wound
2) Seal the wound
3) shrink the wound
Phase 1
Phase 2
Phase 3
77
Healing Process Phase 1
-Inflammation
-Begins immediately and lasts 2-3 days
-Epithelialization may continue into phase 2 depending on severity of damage
78
The Healing Process: Fill in the Wound
-With inflammatory exudate created during the acute inflammatory response; Debridement occurs; blood clot formed if necessary
79
The Healing Process: Phase 2
-Proliferation and Reconstruction (new tissue formation)
-From day 3-14
80
Healing Process: Seal the Wound
-Via re-epithelialization at wound surface by myoepithelial cells
81
Healing Process: Phase 3
-Remodelling and Maturation
-From several weeks to up to 2 years
82
Overlap in Healing Phases
-Overlap in phase 1 and 2 and 2 and 3
-Exact length of each phase depends on severity and location of the wound
-Good blood flow and lymphatic drainage are required, if compromised healing will take longer
-Length of time required for tissue to complete phase 3 is also dependent on the specific tissue type including regenerative potential of each cell type injured
83
3 Types of Wound Healing
1) Primary (first) intention healing
2) Secondary (second) intention healing
3) Tertiary (third) intention healing
84
Comorbidities
-Individual has more than one risk factor of already has a specific disorder that places individual at higher risk for serious illness
85
Primary Intention Healing
-Healing of a wound with minimal tissue loss, no infection
-Clean wound with good apposition of wound edges
-Minimal parenchymal and stromal loss —> resolution and/or regeneration possible
-Original tissue structure and function restored
-Minimal if any visible scarring
-Minimal if any loss of normal function
-Eg. Surgical incision, minor cuts that heal quickly
86
Secondary Intention Healing
-Healing of large wound (open wound)
-High risk for infection
-Requires abundance of granulation tissue for wound closure
-Extensive Debridement required; wound edges are separated
-Wounds have significantly more parenchymal and stromal tissue loss —> resolution and regeneration difficult; requires repair processes
-Noticeable scar formation
-Weakness and/or loss of normal tissue function may occur
-Eg. lacerations, burns, ulcers
87
Tertiary Intention Healing
-Aka delayed healing (delayed primary intention or delayed closure)
-Healing of a complicated wound that is purposely left open (usually for 3-5 days)
-Infected wound needs lots of debriding, presence of necrotic tissue, crush injuries, poor vascularization, drainage required
-Once healthy granulation tissue is present and wound is clean of debris and infection wound edges are approximated and closed with sutures, staples, or skin graft
-scarring probable
88
Examples Tertiary Intention Healing
-Surgical incision left open for drainage due to edema and/or infection
-Slow wound healing due to poor blood flow (decubitus ulcer, diabetic ulcer
-Severe crush injuries with extensive vascular damage (presence of necrotic dead tissue)
-Severely infected wounds requiring extensive Debridement over several days/weeks
89
Common name for decubitus ulcer
Bed sore, pressure sore
90
Eschar
-Area of necrotic tissue on the skin surface
-Also called slough
-Forms a hard crust or scab of black tissue common in diabetic ulcers and burns
-Is a normal part of wound healing process
91
Phase 1 Key Steps
-Hemostasis
-Acute Inflammatory Response
-Physical Debridement
92
Phase 2 Key Steps
-Cellular Debridement
-Angiogenesis and Revascularization
-Granulation Tissue Formation
-Fibrosis
-Re-epithelialization
-Clot dissolution
-Wound contraction
93
Phase 3 Key Steps
-Resolution, Regeneration, and/or Repair of parenchymal and stromal tissues
-Fibrosis and wound contraction complete
94
Primary also a
Bone break the heals good
95
Suture/staples
Secondary intention, surgical line is primary intention
96
In phase 2 fibroblasts ..
-Establish a collagen framework to help stabilize the tissue and provide new home for parenchymal cells
-Framework will be remodelled many times as healing progresses
97
If Large Amount of Collagen Remains at end of Phase 3
Then that fibrous tissue is a scar
98
Re-epithelialization
-Secondary
-Epithelial cells at surface are dividing to replace those lost
-Then fibroblasts contract to pull on wound edges =both seal wound to prevent pathogens from entering and decrease size to limit scarring
99
Matrix Metalloproteinases (MMP)
-Stimulated by angiogenic factor
-Help with constant remodelling of the wound site as the healing progresses
100
During Organization
Histamine levels return to normal, 5 inflammatory signs diminish
101
Healing begins when..
Granulation tissue starts to grow into wound site from surrounding healthy tissue including new blood and lymphatic capillaries (angiogenesis), fibroblasts and collagen they make
102
When cells from opposite sides meet..
They secrete basement membrane, anchor, and begin to divide in a vertical plane to seal wound
103
Contact Inhibition
Once wound is closed contact inhibition between adjacent epithelial cells stops further mitosis that could cause production of excess epithelial cells
104
Myoparenchymal
Parenchymal cells use collagen framework as a guide to where they should be, move into area by myoparenchymal movement
105
Fibrosis, angiogenesis and epithelialization are regulated by
-Variety of growth factors made by fibroblasts and macrophages
106
Collagen Production Factors
-Transforming Growth Factors
-Fibroblast Growth Factor
107
Angiogenesis Factors
-Vascular Endothelial Growth Factor
-Fibroblast Growth Factor
108
Extracellular Matrix and Collagen Remodelling Factors
-Matrix Metalloproteinase
109
Healthy fibroblasts need
Vitamin C and O2
110
Abnormal Gene Expression Of Wound Healing Growth Factors
-implicated in cancer pathogenesis
111
Granulation Tissue Is
Healing tissue
Composed of Myofibroblasts that migrate from the edges of the wound site and newly formed capillary buds and loops
-New capillaries are fragile and very leaky so Edema will still be present in injury site
112
Myofibroblasts are responsible for
Fibrosis
-secrete extracellular matrix including protein procollagen, = precursor to mature stronger collagen fibers during next several weeks or months of wound healing
113
Newly formed collagen is
Very weak but does provide a framework for both revascularization and epithelialization to proceed
114
Wound Healing Phase 2 Within 14 Days
-Re-epithelialization complete
-Parenchymal cells begin to reestablish function if possible, fill in wound
-Clot dissolution (fibrinolysis) completed by Plasmin
-Scab forms (dried epithelial cells and dried blood clot loosens and falls off, new tissue under scab is pink or red
-Wound contraction may be complete
-Prostaglandins stimulate might be itchy
115
By the end of day 14
Uncomplicated wounds should be well underway in the healing process
116
Once wound is sealed by new epithelium…
-Scab will loosen and fall off
-Parenchymal cells in the tissue should be re-establishing their functions by this time
-Any living platelets or RBCs that were trapped in the clot can go back to their normal functions
-Old or dead blood cells will be sent to spleen or liver where macrophages will chew them up
117
Wound Contraction
-Most noticeable in larger wounds such as surface abrasions
-Helps to decrease dehydration and infection (not so necessary in a paper cut)
118
Clot Dissolution should not begin until
-Re-epithelialization is complete
-Since endothelial cells are a type of epithelium, mitotic replacement of endothelial linings of blood or lymphatic vessels is a type of re-epithelialization
119
Removal of blood clot should not occur until
Re-epithelialization is complete, otherwise wound site will bleed again
120
Time Course of Cells Infiltrating Wound
Platelets: inflammatory (phase 1, 0-1 days)
Neutrophils: inflammatory and proliferation (phase 1 and 2, 0-6 days)
Macrophages: Inflammatory, Proliferation, Remodelling (Phase 1,2,3, 0-13 days
Fibroblasts: Inflammatory, Proliferation, Remodelling (Phase 1,2,3, 0-15 days)
Lymphocytes: Inflammatory, Proliferation (Phase 1,2, 0-10 days)
121
During wound healing, neutrophils are prominent during phase __ whereas macrophages are prominent in phase __
Primary, secondary
122
Collagen is made by CT ___ cells called ___
Stromal, fibroblasts
123
The ability of damaged tissue to return to normal physiological activity depends on the relative balance between ___ cell and ___ cell activity
Stromal, parenchymal
124
What is Fibrosis
Production of collagen
125
Is Fibrosis normal or abnormal
Normal
126
Does all fibrosis cause permanent scarring?
No, part of creation of CT
127
Where does scar tissue form?
Forms from CT (Dermis) not on epithelial cells
128
Why is granulation tissue pink?
Full of blood vessels
129
Many wounds done by
Phase 2
130
What is a scab?
Dried epithelial cells, blood clot
131
What do you see if you pick a scab
Pink granulation tissue
132
What determines the extent of scar tissue formation within a wound
Race/Time amount of collagen deposited in wound site
133
Why are scare white?
Collagen is avascular
134
Why does picking a scab increase ur risk of scarring?
Increases time of healing, have to go back to phase 1
Promotes fibroblast production of excess collagen
135
Types of Dysfunctional Wound Healing
1) Contracture’s
2) Adhesions
3) Keloids
4) Hypertrophic scars
5) Dehiscence
6) Proud flesh
136
Dysfunctional wound healing means
Normal tissue function is not restored
137
Contractures
-Thick scar tissue and excessive wound contraction
-Severely impedes normal function
-Possible disfigurement
-Eg. Severe burns, prolonged hypertonic spasticity
138
Adhesions
-Secretion of excessive Fibrinous (fibrin containing) exudate
-Causes serous membrane to adhere to each other restricting organ movement
139
Serous membranes
-Pleural membranes, Pericardial membranes, Peritoneal membranes
-Serous membranes surround the thoracic and abdominopelvic body cavities
-They secrete clear watery lubricating fluid that allows the organs they enclose to move freely without friction
140
Inflammation Pleural Membranes
-Surround lungs
-Pleurisy
141
Inflammation Pericardial Membrane
-Surround the heart
-Pericarditis
142
Inflammation Peritoneal Membranes
-Surround Abdominal and Pelvic Organs
-Peritonitis
143
Keloids
-Due to overproduction of collagen
-Overgrow the size of the wound
-Do not decrease over time
-Most common in those with darker skin tones
144
Hypertrophic scars
-Are raised but remain within the wound boundary
-May reduce in size over time
145
Risk Factors Keloids/Hypertrophic scars
-Familial predisposition to both scar types and location of the lesion
146
Common Locations Keloids/Hypertrophic scars
-Neck, Thorax, Shoulders, Upper arms
147
Dishiscence
-Breaking open of a poorly healed sutured wound
-Most common in the abdomen due to high intra abdominal pressure
148
Other causes Dehiscence
-Infected site, presence of foreign object, obesity, steroid use
-Co-morbiditites Eg diabetes, renal or liver disease, presence of neoplastic tissue
149
Proud Flesh
-Overproduction of pink granulation tissue that protrudes out of the wound
-Caused by poor healing due to persistent infection or foreign object
-often problem in horses or cattle legs
