wound healing by dr. gaurav salunkhe

1. Factors Affecting Wound Healing
Dr.Simona Naik
09/02/2011

2. • Wound healing is normal biological process in
human body, is achieved through 4 precisely and
highly programmed phases:
-:Hemostasis
-:Inflammation
-:Proliferation
-:Remodelling
• These phases and their functions must occur in
proper sequence, at specific time, continue for a
specific duration at an optimal intensity

5. The wound healing process
• Interuptions, abberrancies, or prolongation in
the process can lead to delayed wound
healing or a non healing chronic wound
• There are many factors that can affect wound healing
which interfere with one or more phases , thus
causing improper or impaired tissue repair
• This article reviews the recent literature on most
significant factors that affect wound healing

6. Factors affecting wound healing
• Multiple factors can lead to impaired wound
healing
• In general terms the factors that influence
wound healing are categorized into local and
systemic.
• Local factors are that directly influence the
characteristics of the wound, while systemic
factors are the overall health and disease state
of the individual that affect his or her ability to
heal

7. Factors affecting wound healing
• Local factors Systemic factors
• 1.Oxygenation 1. Age and gender
• 2.Infection 2. sex hormones
• 3.foreign body 3. Stress
• 4.Venous 4. Ischemia
sufficiency 5. Diabetes,
6 .Obesity
7 .Medication
8 . Alcoholism and smoking
9 . nutrition

8. Oxygenation
• Oxygen is important for cell metabolism,
especially energy production by means of ATP
• It prevents wound from infection, induce
angiogenesis, increases keratinocyte
differenciation, migration, and re-
epithelialization, enhances fibroblast proliferation
and collagen synthesis and promotes wound
contraction.
• Due to vascular disruptions and high oxygen
consumption by metabolically active cells, the
microevironment of the early wound is depleted
of oxygen and is quite hypoxic

9. • In normal wound after the initial hypoxia
progressive microcapillary neovascularization
takes place and oxygen supply is restored
• But in case of injury or any systemic condition
, including advancing age and diabetics can
create impaired vascular flow, thus setting the
stage for poor tissue oxygenation resulting in
impaired healing
• Due to this prolonged hypoxia delays healing
process chronic wounds are formed. Tissue
oxygen tension have been measured

10. • In summary, proper oxygen level is crucial for
optimal wound healing
• Hypoxia stimulates wound healing such as
release of growth factors and angiogenesis,
while oxygen is needed to sustain the healing
process.
• One therapeutic option that can sometimes
overcome the influence of tissue hypoxia is
hyperbaric oxygen therapy(HBOT)
• While HBOT can be effective treatment for

11. Infections
• Once skin is injured microorganisms that are
normally sequestered at the skin surface
obtain access to the underlying tissues
• Inflammation is normal part of wound healing
and is important to removal of contaminating
microorganisms
• In absence of effective decontamination
inflammation is prolonged,since microbial
clearance is incomplete

12. • Both bacteria and endotoxins can lead to
prolonged elevation of proinflammatory
cytokines such as interlukin-1 and TNF-α and
elongate the inflammatory phase
• If this continues ,the wound may enter chronic
state and fail to heal
• This prolonged inflammation also leads to
increased levels of matrix metalloproteases
(MMPs) a family of proteases that can
degrade ECM.

13. • Also these bacteria in infected wounds occur
in the form of biofilms, complex communities
of aggregated bacteria embedded in a self
secreted extracellular polysaccharide matrix
(EPS)
• Mature biofilms develop protected
microenvironment and are more resistant to
conventional antibiotic treatment.

14. Systemic Factors- Age
• The elderly population (people over 60 years)
is growing faster than any other age
group.(World Health Organisation)and
increased age is a major risk for impaired
wound healing
• Many clinical and animal studies have been
done and concluded that aging causes
temporal delay in healing but not an actual
impairment in terms of quality of healing
• Delayed wound healing in aged is associated
with an altered inflammatory response , such

15. - Intrestingly, exercise has been reported to
improve cutaneous wound healing in older
adults
- The improved healing response may be due to
an exercise induced anti inflammatory
response in the wound (Emery et al,. 2005;
Keylock et al,.2008)

16. Sex hormones in aged individuals
• Sex hormones play arole in age related wound
healing deficits
• Compared with aged females aged males have
been shown to have delayed healing of acute
wounds
• Female estrogens and male androgens have
significant effect on wound healing
process(Giliver et al., 2007)
• Estrogen affects wound healing by
regeneration matrix production, protease

17. • Studies indicate that estrogen can improve age
related impairment in healing in both men and
women while androgens regulate cutaneous
wound healing negetively (Gulliver etal.,2007)

18. Stress
• Stress has great impact on human health and
social behaviour
• Many diseases – such as cardiovascular
disease, cancer, compromised wound healing,
and diabetes- are associated with stress
• Studies in both humans and animals have
demonstrated that psychological stress causes
a substantial delay in wound healing.
• Caregivers of persons with Alzheimer’s and
students undergoing academic stress during
examination demonstrated delayed wound

19. • Stress up regulates glucocorticoids(GC’s) and
reduces level of proinflammatory cytokines at
the wound site
• Stress also reduces the expression of IL-1α and
IL-8 at wound site – both chemoattractants
that are necessary for the initial inflammatory
phase of wound healing.
• GC cortisol functions as an anti-inflammatory
agent and modulates the immune responses
that are essential for initial phase of healing

20. • Stress can lead anxiety and depression,which
may lead to unhealthy habbits like poor sleep
patterns, inadequate nutrition, less exercise
and a greater propensity for abuse of
alchohol, cigrattes and other drugs
• All of these may come into play in negatively
modulating the healing process

21. Diabetes
• Diabetes affects hundreds of millions of
people worldwide
• Diabetic individuals exibit a documented
impairment in healing of acute wounds.
• Moreover diabetics are prone to develop
chronic nonhealing diabetic foot ulcers which
is serious complication of diabetics and
precede 84% of all diabetic related lower leg
amputations.(Brem and Tomic-Canic, 2007)
• The influence of following factors on wound

22. Impaired
Wound
healing
hypoxia
Keratinocyte
dysfunction
Higher MMP’s
Impaired
angiogenesis
Decreased host
immunity
Neuropathy
hyperglycemia

23. • The impaired wound in diabetics involves
multiple complex pathophysiological mechanism
which is always associated with hypoxia
• The situation of prolonged hypoxia , which may
be derived from both insufficient perfusion and
insufficient angiogenesis is detrimental for wound
healing
• Hyperglycemia, is also responsible for impaired
wound healing in diabetics
• High levels of metalloproteases which are a
feature of Diabetic foot ulcer and also levels of
which are 60 times higher in chronic wound

24. • Several Dysregulated cellular functions are
involved in diabetic wounds, such as defective
T-cell immunity, defects in leukocyte
chemotaxis, phagocytosis, and bactericidal
capacity and dysfunctions of fibroblast and
epidermal cells
• These defects are responsible for inadequate
bacterial clearance and delayed or impaired
repair in individuals with diabetes
• Neuropathy that occurs in diabetic individuals

25. Medications
• Many medications, such as those which
interfere with clot formation or platelet
function, or inflammatory responses and cell
proliferation have the capacity to affect
wound healing.
• Here commonly used medications that have
significant impact on healing are:

26. 1.Glucocorticoid Steroids:
• Systemic glucocorticoids (GC) which are
frequently used as antiinflammatory agents
inhibit wound repair
• Systemic steroids cause wounds to heal with
incomplete granulation tisssue and reduced
wound contraction(Franz et al.,2007)
• Beyond effects on repair systemic
corticosteroids may increase the risk of wound
infection
• But topical low dosage corticosteroid

27. Non-steroidal Anti-inflammatory Drugs
• NSAID’s such as ibuprofen are widely used for
treatment of inflammation and for pain
management.
• There are few data to suggest that short term
NSAID’s have negative impact on healing.
• Systemic use of ibuprofen has demonstrated
an anti proliferative effect on wound healing
resulting in decrased numbers of fibroblasts,
reduced wound contraction, delayed
epithelialization and impaired angiogenesis
• Whereas topical application of NSAID’s on

28. Chemotherapeutic Drugs
• Most chemotherapeutic drugs inhibit cellular
metabolism, rapid cell division, and
angiogenesis and thus inhibit pathways critical
for wound repair
• These medications result in decrease
fibroplasia and neovascularization. They also
delay cell migration into the wound, ↓ Wound
matrix formation, lower collagen production,
impair fibroblast and inhibit contraction of
wounds

29. • Impaired wound healing due to
chemotherapeutic drugs such as adriamycin is
most common
• A new generation of tumour
chemotherapeutics are angiogenesis inhibitors
such as bevacizumab which limit blood supply
to tumour but may result in many wound
healing complications.

30. Obesity
• Obesity is well known to increase risk of many
diseases and these individuals frequently face
wound complication.
• There is higher rate of surgical site infection in
obese patients.
• Many of these complications may be result of
relative hypoperfusion and ishemia that
occurs in subcutaneous adipose tissue.
• Also increased tension on wound edges
increases tissue pressure, reducing

31. • Increase in pressure ulcers or pressure related
injuries due to hypoascularity and poor
perfusion makes tissue more suseptible to this
type of injury
• Moreover skin folds harbour microorganisms
that thrive on moist areas that contribute to
infections and tissue breakdown
• Systemic factors also contribute in impaired
wound healing in obese as obesity is
commonly associated with diabetes,

32. • More recent findings have documented that
adipose tissue secretes large variety of
bioactive substances collectively named
adipokines and have profound effect on
immune and inflammatory response
• The negative influence of adipokines on
systemic immune response seems likely to
influence healing process , although direct
proof for this is lacking

33. Alcohol consumption
• Clinical evidence and animal experiments have
shown that exposure to alcohol
 impairs wound healing
 increases the incidence of infection
diminishes host resistance.
• A recent review on alcohol induced alterations
on host defence after traumatic injury
suggested that short term acute alcohol
exposure results in suppressed pro-
inflammatory cytokine release in response to
an inflammatory challenge

34. • The most significant impairment seems to be
in wound angiogenesis which is reduced by
upto 61% following alcohol exposure
• Thus acute alcohol exposure can lead to
impaired wound healing by impairing early
inflammatory response , inhibiting wound
closure, angiogenesis, collagen production
and altering protease balance at wound site
• Analysis of clinical data indicates chronic
alcohol exposure causes impaired wound

35. Smoking
• Negative effects of smoking on wound healing
outcomes have been known for a long time
• Postoperatively, patients who smoke show delay
in wound healing and variety of complications
such as infection, wound rupture, decrease in
strength of wound.
• Also impaired healing has been noticed in both
oral surgery and in placement of dental implants
• Substances in tobacco smoke Nicotine, carbon
monoxide, hydrogen cyanide have been identified
and have shown to have negative impact on
healing

36. • In inflammatory phase smoking causes
impaired white blood cell migration resulting
in lower number of monocytes and
macrophages in wound site resulting in poor
wound healing and increased risk of
oppurtunistic wound infection
• During proliferative phase exposure to smoke
yield decreased fibroblast migration , reduced
wound contraction decreased ECM production
and upset in balance of proteases
• Thus smoking cesation leads to improved

37. Nutrition
• Malnutrition or specific nutrient deficiencies
can have a profound impact on wound healing
• Energy, carbohydrate, fat, vitamin, and
mineral metabolism all can affect healing
process
• Carbohydrate, protein, amino acids: glucose is
a major source that provides energy for
angiogenesis and deposition of new tissues
• Protein is important nutrient factor affecting
wound healing

38. • A deficiency of protein can impair capillary
formation, fibroblast proliferation,
proteoglycan synthesis, collagen synthesis,
and wound remodelling
• It also affects immune system which increases
suceptibility to infections
• Amino acids like arginine and glutamine by
their deficiency affect wound healing process

39. • Fatty acids: Lipids are used as nutritional
support for surgical or critically ill patients to
help meet energy demands and provide
essential building blocks for wound healing
and tissue repair
• They have also reported to affect
proinflammatory cytokine production, cell
metabolism, gene expression, and
angiogenesis in wound sites

40. Vitamins,Micronutrients and Trace
Elements
• VitaminC deficiency -impaired healing
 decreased collagen synthesis,
 fibroblast proliferation,
decreased angiogenesis,
 increased capillary fragility
 impaired immune response
• Vitamin A deficiency also leads to impaired
wound healing
• Vitamin E has anti-inflammatory properties
and has been suggested to to have a role in

41. • Several micronutrients have been shown to be
important for optimal repair:
Magnesium -protein and collagen synthesis
Copper -crosslinking of collagen
 Zinc deficiency causes significant impairment
in wound healing
Severe iron deficiency also leads to impaired
collagen production

42. Conclusion
• Wound healing is a complex process that
consist of hemostasis, inflammation,
proliferation and remodelling.
• Large number of cell types – including
neutrophils, macrophages, lymphocytes,
keratinocytes, fibroblast and endothelial cells-
are involved in process
• Multiple factors cause impaired wound
healing by affecting one or phases of the
process
• The influences of these factors are not

43. THANK YOU