Wound Healing

Question 1

When a wound occurs, there is a protective ——- response to the injury = aims to neutralise the source of inflammation, remove necrotic material, and promote healing and repair

Answer 1

When a wound occurs, there is a protective inflammatory response to the injury = aims to neutralise the source of inflammation, remove necrotic material, and promote healing and repair

Question 2

What are the 4 distinct phases/ stages to wound repair?

Answer 2

1. Haemostasis
2. Inflammation
3. Proliferation
4. Maturation

Question 3

What is haemostasis (wound healing)?

Answer 3

• Injury to blood vessels exposes collagen (in vascular endothelial cells) = activates platelets = adhere to the vessel walls = form platelet plug
  
  • A brief period of vasoconstriction, due to 5-hydroxy-tryptamine (5-HT) and thromboxane A2 (TXA2) released from activated platelets reduces bleeding = homeostatic plug
  • Platelets secrete platelet-derived growth factor (PDGF) = recruits neutrophils and monocytes
  • Anything which disrupts the clotting process may delay the commencement of the healing cascade, leaving the wound vulnerable to infection

Question 4

What is inflammation (wound healing)?

Answer 4

• Process lasts typically from 0-3 days
  
  • Histamine leaks out of injured tissues causing vasodilation = redness, heat, swelling, pain and loss of function
  • Neutrophils phagocytose debris and microorganisms and provide first-line defence against infection
  • Macrophages phagocytose bacteria and secrete metalloproteases (MMPs) to degrade necrotic tissues. MMPs are balanced by tissue inhibitor of metalloproteases (TIMP) which are released locally by cells and inactivate MMPs. Macrophages also secrete a variety of cytokines and growth factors to direct the next stage

Question 5

What is Proliferation (wound healing)?

Answer 5

• From day 2-24: destruction occurs including increased activity of neutrophils and macrophages which remove wound debris
  
  • Fibroblasts (cells found in connective tissue) move into the wound space and proliferate = production of extracellular matrix (ECM) and collagen for the formation of granulation tissue
  • Fibroblasts secrete the collagen framework on which dermal regeneration occurs and are responsible for wound contraction (most important cell of the reconstructive phase - require an acidic environment to manufacture collagen (dietary Vitamin C is essential).
  • Collagen is the basic building protein and is a major component of granulation tissue
  • In granulation tissue, transforming growth factor beta (TGF-𝛽) induces some fibroblasts into myofibroblasts which are specialised cells responsible for wound contraction

Question 6

What is Maturation (wound healing)?

Answer 6

• Day 24 to 12 months
  
  • Process aims to increase the tensile (structural) strength in the wound
  • Original collagen (pro-collagen) produced in granulation tissue is weak; this is replaced by more organised collagen to improve tensile strength
  • Fibroblasts are predominantly involved in tissue remodelling with the deposition of collagen into an organised matrix. Myofibroblasts (subgroup of fibroblasts), assist in wound shrinkage. Tensile strength will not be more than 70-80% of what it was before
  • In the acute epithelialisation phase, thin layers of scar tissue form and thicken over time

Question 7

What is a wound?

Answer 7

injury to the skin or underlying structures that may or may not result in a loss of skin integrity. The aim of wound healing (treatment) is to repair and restore the physical form and normal anatomical structural and functional ability

Question 8

What are the classifications of wounds?

Answer 8

• Classified by incision, laceration ulcer or abrasion. These can be further classified into acute and chronic depending on the stage of healing

1. Surgical wound
2. Penetrating wound
3. Crushing wound
4. Burns

**Consideration should also be taken on the amount of tissue loss associated with the wound. These can be graded as superficial (epidermal layer only); partial-thickness (epidermal and dermal layers); or full thickening (epidermis, dermis, hypodermis, and possibly muscle and bone)

Question 9

What are acute wounds?

Answer 9

Typically have an identifiable mechanism of the injury which leads to damage to skin integrity
• Specific biological markers characterise and orchestrate the phases healing of the acute wound - contain metabolically active cells and levels of growth factors present
• Balance between metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate the ECM to assist healing
• Common types of acute wounds: abscess, drain site surgical wounds, and lacerations

*In healthy individuals, with no underlying factors, an acute wound should heal within three weeks with remodelling occurring over the next year with or without assistance

Question 10

What are chronic wounds?

Answer 10

• If a wound does not follow the normal trajectory, then it may become stuck in a state of chronic inflammation and fibrosis
  
  • May be due to prolonged and ineffective inflammation caused by an infective process, tissue ischemia, or other factors slowing healing
  • Slow healing causes poor quality granulation and epithelium which leads to an overproduction of scar tissue (hypertrophy)
  • Include burns, leg ulcer (arterial, venous or mixed), pressure sores and some skin tears

Question 11

What are the types of wound healing?

Answer 11

primary and secondary intention

Question 12

What is primary intention?

Answer 12

• Wound edges are clean and usually have defined edges
  
  • An incision or laceration which is uncontaminated (surgical wound or a cleaned and new wound usually made within the last 4-8 hours) = minimal tissue loss
  • Can be closed by sutures, staples, tapes or tissue glue = usually leaves little or better scar
  • If the wound can be closed by primary intention but is contaminated, this increases the risk of infection = preferable for the wound to be closed later once it is clear of debris
  • Possible to have a wound treated by delayed primary intention (tertiary) because the wound is infected or requires more thorough intensive cleaning prior to closure (can take place 3-7 days later)
  • Another possibility to heal a wound by primary intention is skin grafts - harvested from other fleshy parts of the body and are used to fill in the gap caused by the wound

Question 13

What is secondary intention?

Answer 13

• Wound healing through the process of granulation, contraction and epithelialisation = caused by a prolonged phase of inflammation = due to any number of contributing factors delaying wound healing which require more time to complete phagocytosis of necrotic tissue
  
  • Healing over a long period of time generates a large amount of granulation tissue
  • Usually scar the most = healing continues for months - years
  • Occurs in big wounds - chronic pressure injuries, ulcers or dehisced wounds either due to the mechanisms of damage or the contributing factors of wound healing
  • Increased heal time = increases risk of infection or further infection

Question 14

Impaired wound healing can be caused by both —— and —— factors which can lead to chronic non-healing wounds

Answer 14

Impaired wound healing can be caused by both intrinsic and extrinsic factors which can lead to chronic non-healing wounds

Question 15

What are the determinants of wounds healing?

Answer 15

• blood flow
• age-related changed of the skin of older people
• anemia
• diabetes
• infection
• medication
• nutritional status
• impact of body shape
• Mechanical stress and wound debris
• Mental health
• smoking

Question 16

How does blood flow effect wound healing? How does this relate to other determinants of wound healing?

Answer 16

supplies the wound with oxygen and nutrients and removes carbon dioxide and metabolic by-products associated with wound healing
• Any condition that reduces blood flow to a wound (arterial occlusion, vasoconstriction, external pressure) impedes healing

Anaemia: (Common in older people) - Iron is an essential component of haemoglobin = delivers oxygenated blood to body tissues = important for normal healing

	• Cigarette smoking causes multiple health problems in relation to wound healing
	• Nicotine = vasoconstrictor = reduces blood flow to wounds = decrease nutrients and oxygen to cells and waste products away from cells
	• Increases platelet adhesiveness = clot formation = hamper blood flow
Contains carbon monoxide and hydrogen cyanide = decrease oxygenation of cells required for wound repair

Question 17

How does age-related changes to the skin of older people determine wound healing?

Answer 17

• Dermis loses 80% of its original thickness, there is 40% less collagen and a decrease in elastin fibres
  
  • Small blood vessels diminish by 40% and sebum, and sweat production, is reduced
  • Epidermis separates more easily from the dermis
  • Decrease in Langerhans cells (infection risk increases) and the reduction of sensory nerves increases this risk of impaired wound healing
  • Medical conditions that occur in many elderly persons can adversely affect healing
  • Tend to be malnourished and poorly hydrated, and have compromised respiratory and immune functions
  • Loss of dermal and subcutaneous mass increases the risk of pressure-induced tissue injury

Question 18

How does nutritional status and the impact of body shapes determine wound healing?

Answer 18

Nutritional Status:
• All patients with wounds require a nutritional assessment - malnutrition not always obvious
• Wound healing and immune response require adequate supply of various nutrients
• Indirect causes of malnutrition: how the person is able to ingest food(e.g. dental health, ability to chew, swallow and psychosocial factors - quality and frequency of food)
• Loss of more than 15% of lean body mass interferes with wound healing

Proteins: Individuals with chronic wounds may need more protein and calories than the recommended daily allowances and may require dietary supplements
Vitamins and Minerals: 
	○ Vitamin C deficiency: associated with impaired fibroblastic function and decreased collagen synthesis = delay healing, contributes to the breakdown of old wound, loss of resistance to infection
	○ Vitamin A deficiency: associated with retarded epithelialisation and decreased collagen synthesis (deficiency is uncommon because it is fat-soluble and stored in the liver)
	○ Other vitamins, such as thiamine and riboflavin, are also necessary for collagen organisation and the resultant tensile strength of the wound
	○ Various minerals - Fe, Cu, Mn, and Mg, play a role in wound healing
Hydration: Wound healing occurs more rapidly when dehydration is prevented. Hydration affects the level of circulatory volume, which in turn affects blood flow to and from wounds to promote healing and remove waste

Impact of Body Shape:
• Obese patients are at risk of impaired wound healing = prone to be less mobile, have poor circulation (adipose tissue is poorly vascularised), and have increased moisture in skin folds = increases the infection risk
• Very thin patients are at risk = less protection against pressure, and a lack of energy stores to maintain metabolic processes = early breakdown of protein

Question 19

How does diabetes, medications, mental health, infection and mechanical stress and wound debris determine wound healing?

Answer 19

Diabetes:
• High levels of glucose compete with the transport of ascorbic acid (necessary for the deposition of collagen into cells for wound healing)
• Tensile strength and connective tissue production are significantly lower
• May have arterial occlusive disease = impair healing
• Reduced sensation = leave wounds undetected to become infected = chronic wound
• More difficulty resisting infection and their wounds heal more slowly

Medications:
• Several medications can suppress the inflammatory response (inflammation is necessary to trigger the wound-healing cascade) - prolong healing process
• Steroid therapy and anti-inflammatory drug usage commenced after the inflammatory phase of healing (4-5 days after the wound) have a minimal effect. Prior administration can disrupt this process
• Cytotoxic drugs - suppress rapidly dividing cells, or immunosuppressive medications, can prolong and disrupt wound healing

Mechanical Stress and Wound Debris:
• Mechanical stress on the skin/wound: can be caused by pressure (e.g. dressing removal) or by the patients themselves (e.g. pressure-related ulceration). Prolonged stress = necrotic tissue and dry scabs = impairs epithelial migration and supply of nutrients
• Wound debris: prevents the formation of granulation tissue and prolongs the inflammatory phase of healing (foreign material in the wound - cotton wool fibres or dog and cat hair)
• Urinary and faecal incontinence may create problems from excessive moisture and chemical irritation to the wound

Infection: Infection risk increases with any wound contamination; disrupts fibroblast activity, = prolonged inflammatory phase

Mental Health:
• Mental health disorders (depression and anxiety) may alter the patient’s perception of the wound = can lead to poor wound hygiene = increase risk of infection and wound contamination
• Stress impairs the immune system by increasing levels of inflammatory chemicals and = prolonging wound healing