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Skin Anatomy, Physiology, and Healing Process

Online Course: Skin Anatomy, Physiology and Healing

Introduction

Our skin, which is part of the integumentary system, is the largest organ system in the human body.
However, it is often overlooked and underappreciated for the role it plays in overall health.[1] Many
people only consider the role skin plays in our appearance and how we are perceived by the society.
Facial expressions are an important form of non-verbal communication and can have a strong social
influence.[2] While our skin is an important part of our outer appearance, it provides a greater
contribution to human life and wellbeing than just aesthetics.[1]

This article will overview the anatomy and physiology of skin, skin's response to injury, normal tissue
healing, the phases of acute wound healing, and the altered healing in chronic wounds.

Wound healing is complex and involves the coordination of many intricate processes. There are many
factors that can impact wound healing, both positively and negatively.

The Role of the Skin

Skin provides numerous functions vital to life and is important for overall health.[1] The skin's health
and appearance can be an indicator of general health, and skin integrity failure often accompanies the
failure of other organ systems within the body.[3]

Eight Key Functions of the Skin[1]:

Protection: Skin acts as a physical barrier to the external environment and provides protection for
internal organs against external threats[1][4][5]

Immune function: Our skin contains a protective acidic barrier called the acid mantle. This acidic layer
has a pH between 4.2 and 6.0, which creates a hostile environment for harmful invading organisms
while maintaining a favourable environment for beneficial microbes.[1] The acid nature of skin is a key
requisite for healthy skin. Skin pH can affect the synthesis and maintenance of a competent skin barrier,
play a role in skin pigmentation, and ion homeostasis.[6]

The skin's acid mantle

Skin pH tends to be lower in people with darker skin because melanin by-products are acidic. Skin pH
also tends to increase slightly as we age, which can contribute to an increased risk of infection and alter
our healing ability.[1]

Specific immune cells and proteins contained in the dermis activate the immune response and attack
invading microbes. These cells include: Langerhans cells, memory T cells, and lymphoid cells.[4]

The surface of our skin houses millions of bacteria, fungi and viruses that compose the skin microbiome
and serves as a physical barrier to prevent the invasion of pathogens. As in our gut, the skin microbiome
plays essential roles in the protection against invading pathogens, the education of the immune system,
[7] and contributing back to the pH of the acid mantle.[1]

Thermoregulation and body homeostasis

Thermoregulation: Humans, and all mammals, can maintain a stable core body temperature via
thermoregulatory responses. By increasing blood flow to the skin through vessel dilation, body
temperates are lowered by evaporative cooling of moist/sweaty surfaces to release body heat.[1][8]
However, if water lost to evaporative cooling is not replaced, body fluid homeostasis will be challenged.
[8]

Prevention of fluid loss: In addition to the physical barrier provided by skin, it also contains lipids,
proteins, amino acids, and salts that work to maintain internal body homeostasis by attracting and
holding onto water. Due to this mechanism, under normal circumstances, the outer layer of our skin is
about 30% water.[1]

Synthesis of vitamin D: Vitamin D is recognised as a pro-hormone, also known as calciferol. There are
two major forms of vitamin D: D2 which is human-made and fortified into foods (such as milk, cheese,
yogurt, cereals, and juices) and D3 which is synthesised by the skin and from eating animal-based foods
(fatty fish, fish liver oil, and egg yolk).[9] While vitamin D can be ingested through food or supplements,
the skin and exposure to sunlight is the body's primary source of vitamin D.[1] Vitamin D is essential for
calcium and phosphate absorption, bone formation, renal function, and our immune function.[1] [9]

Skin sensory organs are located throughout the layers of the skin.

Protection from ultraviolet radiation:[10] Ultraviolet radiation (UVR) can cause DNA photodamage,
sunburn, and both local and systemic immunosuppressive properties.[11] Melanin and carotene give
skin its colour and serve to reflect UVR as a protective mechanism to radiation damage.[1] Melanin also
has antioxidant and radical scavenging properties.[11] Melanin is produced by melanocytes in response
to increased sunlight, which is why populations that evolved in areas with more sun exposure tend to
have darker skin.[1]

Interaction with the environment: Our skin gathers sensory information through free nerve endings,
hairs, receptors to touch, temperature, and pain. In addition, through physiological processes like
sweating or blushing, information is shared about our internal state to the outside world.[1]

Healing: Tissue restoration in response to injury.[1]

The following optional video provides an overview of the roles and functions of the skin.

[12]

Skin Anatomy and Physiology

It is important to understand the layers of our skin so that we can understand how healing occurs
differently based on depth. The skin has two principal layers, the epidermis and the dermis. The
hypodermis is considered an extension of the skin by some sources, but not by others.[1]

The Epidermis

Epidermis.jpeg
Composed of five layers

It is avascular

Its thickness varies based on location. For example, it is thickest on the heels and thinnest on the
eyelids. Areas that have increased use from friction or weight bearing can build up thicker layers of skin
(e.g., where a pencil rubs your writing finger or shoe rubs against your foot).

It has no nerves, but free nerve endings from the dermis do extend into the mid layers of the epidermis.

Five layers of the epidermis (most to least superficial):

Stratum corneum

Composed of 15 to 30 layers of keratinocytes called squames or corneocytes. These are dead

keratinocytes. They contain a high concentration of keratin which provides a waterproof barrier for the
skin, hair, and nails.

This layer is continually being shed from the body. Shed cells are replaced via the process of skin cell
migration from the stratum basale. This process takes an average of 30 days, but this varies based on
age and certain health conditions.[1]

Stratum lucidum

Contains two to three layers of keratinocytes and is not living. It can be penetrated or shaved off
without awareness.

It is only found in areas of thick skin, like the palms of the hand and the soles of the feet. Present in
calluses.[1]

Stratum granulosum

This layer contains the greatest concentration of free nerve endings that extend from the dermis. Free
nerve endings are unencapsulated dendrites originating from a sensory neuron. They are the most
common nerve endings in skin and provide sensory information about painful stimuli, hot and cold, and
light touch. However, they are less sensitive to abrupt changes in stimulation.[13]

This is the most superficial layer of the epidermis which contains living cells.[1]

Stratum spinosum

Contains Langerhans cells and lymphocytes which play an important role in the immune system.[1]

Stratum basale
The only layer that undergoes continuous mitosis to produce new cells.[1]

Keratinocytes are constantly being produced in the stratum basale and they move up through the layers
until they reach the outermost layer.[1] Keratinocytes are the most dominant cell type in the skin. They
play a critical role in wound healing as they are structural cells and they perform important immune
functions.[14]

Melanocytes are also produced in the stratum basale. They produce melanin, which contributes to the
colour of skin. Humans have approximately the same amount of melanocytes. Therefore, skin colour is
based on the amount of melanin that these melanocytes produce in response to their environment.[1]

This layer also contains Merkel cells which can perform both nervous and endocrine actions. They can
synthesise and store locally produced hormones and neurotransmitters. They function as
mechanoreceptors[1] for light and selective tactile perception, but not for hard touch and vibration;
they are also involved in the transfer of nociceptive signals.[15]

The Dermis

Located deep to the epidermis

Contains blood vessels and nerves which supply the epidermis via capillary loops and free nerve endings

Composed of two layers[1]

Two layers of the dermis (most to least superficial):

Papillary layer

Layers of human skin.jpeg

Interdigitates with the epidermis

The ridges of this layer give rise to our unique fingerprints.

Contains fibroblasts which are responsible for the production of collagen, elastin, and proteins. These
qualities give skin strength and flexibility.

Contains mast cells which produce heparin and histamine, important factors in clot formation and the
inflammatory response.

Contains macrophages which play an important role in the immune response, wound repair, cancer
defence, salt balance, and hair regeneration. They are known for destroying foreign invaders through
phagocytosis[1] (the process by which a phagocyte, a type of white blood cell, engulfs and digests
foreign cells and removes dead cells[1][16]).
Contains leukocytes[1] which are crucial to the inflammatory response following an injury to the skin.
Leukocytes are essential for clearing infection and normal wound healing.[17]

Reticular layer

Sensory receptors of the skin.jpeg

Located between the papillary layer and the subcutaneous layer or hypodermis.

It is made up of collagen, blood vessels, nerve endings, T-cells, hair follicles and glands.

The hair follicles contain stem cells that produce keratinocytes that will become hair. They play an
important role in wound healing by contributing epithelial cells for wound closure.

The T-lymphocytes are responsible for destroying pathogens and malignant cells.

Nerves located within the dermis detect sensations such as itching, touch, pressure, vibration, pain, and
temperature.

Injuries which reach into the dermis can result in pain due to nerve exposure and or damage. There will
be an absence of pain if the nerves are completely destroyed and or severed by an injury. [1]

The Hypodermis

Located below the dermis and contains subcutaneous tissue.

It is made up of loose connective tissue, adipose tissue. It is well vascularised and well innervated.

It helps to attach the skin to the muscles and bones through superficial fascia, and provides insulation
and cushioning through fat storage.

Wounds

"A wound is an injury that breaks the skin or other body tissue. Wounds can be open, with broken skin
and exposed body tissue, or closed when there is damage to tissue under intact skin."[18]

When there is injury to the skin, wounds and tissue loss can be categorised based on their depth and
also the tissues involved.

Wound categorisation by wound depth:[1]

Type of tissue loss Bleeding Examples Healing process Clinical presentation

Erosion Loss of the superficial epidermis only, no dermal loss Unlikely

Superficial abrasions

Stage one pressure injuries

Superficial burns (first-degree burns)

Local inflammatory process and epidermal replacement from keratinocyte migration upward

Erythema and

Mild and short-lived pain

Partial Thickness Loss of the epidermis and part of the dermis Yes

Stage two pressure injuries

Superficial and deep partial-thickness burns (second-degree burns)

Skin tears

Some deep abrasions

Re-epithelialisation as a result of epithelial cell migration from the wound edges towards the centre of
the wound

Bleeding

Seeping of serous fluid

Blistering

Pain

Full Thickness Loss of both the epidermis and dermis with extension into the subcutaneous tissue
Yes

Full-thickness burns (third-degree burns)

Stage three and four pressure injuries

Surgical incisions

Traumatic wounds

Necrotic wounds which require debridement

Via secondary intention (see below for definition)

May involve bone, tendon, ligament, or muscle

Bleeding

Seeping of serous fluid

Pain

Normal Tissue Healing

A clear understanding of the normal or expected healing process is important to recognise when
improper healing is occurring in a wound. The process of tissue repair is incredibly complex, and involves
many body systems and complex mechanisms.

There are four basic mechanisms by which healing takes place:[1]

Continuous cell cycling

Normal intact skin is replaced via keratinocyte production in the stratum basale, followed by upward
migration through the layers of the epidermis.

Cell proliferation

Healthy cells undergo mitosis to repair damage. The new tissue formed through this process is called
granulation tissue.

The structure and function of the replaced tissue cannot be duplicated, but it is similar to the original.

Results in scarring.

Regeneration

This type of healing can be performed by only a few types of tissue in the human body, including: the
liver, kidney, gastrointestinal tract and the epidermis. No other tissue types can heal in this manner.

This type of healing involves a complete duplication of structure and function.

Fibroproliferative healing

This is a form of pathological healing where lost tissue is replaced by a fibrous scar.

Occurs in deep wounds, persistent inflammation, fibroproliferative diseases

The following optional video provides a time lapse of wound healing. Can you note the various stages of
tissue healing?

[19] The longer a wound is open, the more significant the residual scar will be. It is important to reduce
healing time and provide the patient with realistic expectations.

Four categories of healing/closure:[1]

Primary intention

Surgical wounds, made by an incision.

The tissue is free from contamination with minimal tissue loss.

These wounds are closed with external force using sutures, staples, adhesive strips or glue.

The primary mechanism of healing is epidermal regeneration. Scarring should be minimal.

There should be no complications. Wound healing and closure occurs in about two weeks time.

Delayed primary intention

Surgical wounds, made by an incision. However, the wound is left open (did not approximate the wound
edges) due to concern about contamination, active infection, or significant tissue loss which could result
in the wound reopening (dehiscing).

The wound is closed with sutures, staples, grafting, or skin flap placement after it has undergone further
healing, oedema management, infection control/antibiotics, or debridement of debris.

There is potential for significant scarring if closure is delayed or chronic inflammation sets in.

Secondary intention

This is the process that the majority of wound care practice revolves around.

Wounds extend into the subdermal tissue and heal as a result of the body's inflammatory response,
formation of new granulation tissue to fill the empty space, and then closure via re-epithelialisation
(migration of new skin cells over the surface of the wound).

The edges are approximated through wound contraction due to myofibroblasts.

Wounds typically take weeks to months to close, depending on size and other factors that may
complicate the process.

Partial thickness wounds that heal by re-epithelialisation

Not often treated with skilled wound care practice.

Subdermal layers are not involved, so wound contraction is not required to approximate the wound
edges.

Minimal to no granulation tissue, minimal to no scarring.

The duration to closure depends on depth, but ranges from one to two weeks.

The body goes through four phases of tissue healing with every wound, regardless of depth or severity.
These phases are not consecutive, but they can overlap. An acute wound typically closes in about 21
days, but the entire healing process can last up to two years. A wound is considered chronic when
healing is disrupted and the wound is still open after four weeks.

Four phases of healing:[1]

Haemostasis or clot formation

Blood vessels respond to injury immediately with vasoconstriction to prevent blood loss and further
tissue injury.

Platelets and fibrin arrive at the site to form a clot which creates a temporary barrier to the external
environment. Once dry, these clots form a scab. The scab is the body's temporary wound dressing that
prevents blood loss and provides protection from the outside world while tissue repair and healing take
place underneath.

This process begins within seconds and it continues for the first 12 hours after injury.

Inflammatory phase

This phase involves the destruction of any pathogens that may have entered the body, debris and
necrotic tissue removal, and the stimulation of new blood vessel growth.

Neutrophils, mast cells, and macrophages play a big role in this phase.
The inflammatory phase occurs in the first 24 hours after injury and typically lasts for about one week. It
is seen clinically as redness, swelling, heat, and pain. The process is essential to acute wound healing,
but can become problematic if it persists for too long.

Proliferative phase

This phase of repair is characterised by new blood vessel formation or angiogenesis, connective tissue
growth or fibroplasia, new skin cell formation or epithelialisation, and continued cleaning out of any
remaining debris.

Neutrophils, mast cells, and macrophages are still present during this phase. However, the most
predominant types are fibroblasts and endothelial cells, which are responsible for the growth of
granulation tissue and capillaries. Fibroblasts initially produce type three collagen, which tends to be
weaker and more disorganised than type one collagen. New tissue growth will be weaker than the
original tissue and more susceptible to injury from outside sources.

Granulation tissue is bright red, beady, vascular tissue that fills in the wound cavity. It is made up of
collagen, elastin, and blood vessels.

Within hours of injury, re-epithelisation begins with upward migration of the existing keratinocytes.
Within a few days, the process continues with cell proliferation via mitosis.

The time it takes for a wound to be considered closed varies based on the circumferential size and also
the depth. There will be a visible scar if the wound takes more than three to four weeks to re-
epithelialise.

The proliferative phase begins four to six days after injury and can last from three weeks to two months.
The wound may appear closed once it is re-epithelialised, but it is not considered healed until the next
phase is complete.

Remodelling phase

During this phase, the wound contracts, granulation tissue settles, blood flow returns to pre-injury
levels, and the wound tensile strength increases.

Myofibroblasts are responsible for wound contraction.

Fibroblasts, myofibroblasts, endothelial cells, and macrophages are the most predominant cells, their
numbers slowly decrease as this phase progresses.

Type three collagen is slowly replaced by type one collagen, which has increased tensile strength.

The remodelling phase begins around two weeks after injury and lasts up to two years. The wound may
appear healed before this process is complete.
Around six weeks after injury, the wound has about half its ultimate tensile strength. Once the
remodelling phase is complete, that injured area will have approximately 80% of its original strength.
These timelines are important to keep in mind when treating patients with chronic or repeated wounds.

The overlapping phases of wound healing

Chronic Wounds

Chronic wounds are those that do not follow this normal process of healing. They are not closed or
making significant progress towards healing in three weeks due to a disruption in the healing process.
These are the wounds most likely to be treated in wound care practice.[1]

The skin microbiome of chronic wounds often tips in favour of the harmful microbiome over the
beneficial ones. These microbes can trigger the immune system to attack the body's cells required for
healing rather than attacking the invaders. Chronic wounds may become stuck in one or more phases
that persist for months or years; the inflammatory phase is the most common phase to be stuck in. It is
common for chronic wounds to go through periods of healing, stagnation, regression, and reoccurrence.
[1]

Chronic wounds typically have one or more of the following characteristics:[1]

Multifactorial aetiology

Advanced age or obesity

Have had a previous wound, injury or surgery, especially in the same area

Multiple co-morbidities particularly vascular diseases, diabetes, or auto-immune conditions

Poor tissue perfusion or oxygenation

Prolonged standing or dependent positioning

Mechanical forces, pressures, or recurrent trauma

Medications that can affect wound healing

Inadequate or inappropriate care

Malnutrition
Active infection, presence of a bacterial biofilm or changes in the skin microbiome

Five most common types of chronic wounds:[1]

Venous insufficiency wounds: most common

Neuropathic wounds (related to diabetic neuropathy)

Pressure injuries (formerly known as pressure ulcers or decubitus ulcers)

Arterial ulcers

Non-healing surgical wounds

Optional Additional Resources and References

Wound Care Basic Principles:

Ayello EA, Baranoski S. Wound Care Essentials. Practice Principles [Electronic Resource]: Fourth edition.
Wolters Kluwer; 2016. Accessed November 3, 2021.

Kirkby J. Dermatology: A Quick Reference Guide [Electronic Resource]. Class Professional Publishing;
2020. Accessed October 10, 2021.

Kuo, SH, Shen, CJ, Shen, CF, Cheng, CM. Role of pH value in clinically relevant diagnosis. Diagnostics.
2020;10(2):107.

Sussman C, Bates-Jensen BM, editors. Wound care: a collaborative practice manual.Lippincott Williams
& Wilkins; 2007.

Yousef H, Alhajj M, Sharma S. Epidermis [Electronic Resource]. In: StatPearls; Updated July 26, 2021.
Accessed November 20, 2021.

Skin Anatomy and Physiology Topics:

Alhajj M, Bansal P, Goyal A. Physiology, Granulation Tissue [Electronic Resource]. In: StatPearls; Updated
November 2, 2020. Available at: https://www.ncbi.nlm.nih.gov/books/NBK554402/ (last accessed
25/08/2022).

Cohen B, Hull K. Memmler’s The Human Body in Health and Disease [Electronic Resource]: 14th edition.
Jones & Barlett Learning; 2019. Accessed October 18, 2021.
Dubin AE, Patapoutian A. Nociceptors: The sensors of the pain pathway. J Clin Invest.
2010;120(11):3760-3772

Lawton S. Skin 1: The structure and functions of the skin. Nursing Times. 2019;115(12): 30-33.

Naik S. One Size Does Not Fit All: Diversifying Immune Function in the Skin. The Journal of Immunology.
2022 Jan 15;208(2):227-34.

Wound Healing Topics:

Hanna KR & Katz AJ. An update on wound healing and the nervous system. Ann Plast Surg. 2011; 67: 49-
52.

Landén NX, Li D, Ståhle M. Transition from inflammation to proliferation: A critical step during wound
healing. Cell Mol Life Sci. 2016;73(20):3861-3885.

Morgun, EI, Vorotelyak, EA. Epidermal stem cells in hair follicle cycling and skin regeneration: A view
from the perspective of inflammation. Front Cell Dev Biol. 2020;8:581697.

Sorg HA, Tilkorn DJ, Hager, SA, Hauser JA, Mirastshcijski, UB. Skin wound healing: An update on the
current knowledge and concepts. Eur Surg Res. 2017;58:81-94.

Xue M, Jackson CJ. Extracellular matrix reorganization during wound healing and its impact on abnormal
scarring. Adv Wound Care. 2015;4(3):119-136.

Nutrition and Microbiome Topics:

Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nature Reviews Microbiology. 2018
Mar;16(3):143-55.

T. H. Chan School of Public Health, Harvard University. The nutrition source: Vitamin D. Published May,
2020. Available at: https://www.hsph.harvard.edu/nutritionsource/vitamin-d/ (last accessed
25/08/2022).

Tomic-Canic M, Burgess JL, O’Neill KE, Strbo N, Pastar, I. Skin microbiota and its interplay with wound
healing. Am J Clin Dermatol. 2020;21:36-43.

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Related articles

Skin - Physiopedia

Description Skin is part of the integumentary system and is the largest and primary protective organ of
the human body[1]. It covers the body's entire external surface and serves as a first-order physical
barrier against the outer environment. Structure[edit | edit source] The skin is made up of three
layers[1]. The epidermis, the outermost layer of skin, provides a waterproof barrier and contributes to
skin tone. The dermis, found beneath the epidermis, contains connective tissue, hair follicles, blood
vessels, lymphatic vessels, and sweat glands. The deeper subcutaneous tissue (hypodermis) is made of
fat and connective tissue. Epidermis[edit | edit source] The epidermis is further divided into:[2] 5 layers
on thick skin like the palms and soles (stratum basale, stratum spinosum, stratum granulosum, stratum
lucidum, and stratum corneum) 4 layers in other places (lacking the stratum lucidum) The epidermis is a
stratified squamous epithelium that contains four to five layers depending on its location[1]: Stratum
Basalis (Basal cell layer): It is deepest and closest to the dermis. The stratum basale contains basal
keratinocytes, immune cells such as Langerhans cells and T cells, and melanocytes that provide the skin
with pigmentation[3]. Keratinocytes from this layer evolve and mature as they travel outward/upward
to create the remaining layers. Stratum Spinosum (Prickle cell layer): This layer compromises most of the
epidermis and contains several layers of cells connected by desmosomes who keep cells tightly bound to
one another and resemble "spines". Stratum Granulosum (Granular cell layer): This layer contains
several layers of cells that contain lipid-rich granules. In this layer, cells begin to immortalize and lose
their nuclei, as they move away from the nutrients located in the deeper tissue. Keratinocytes in the
stratum granulosum contain cysteine- and histidine-rich granules, which bind keratin filaments
together[3]. Stratum Lucidum: This layer is only present in the thick skin of soles and palms and consists
of mostly immortalized cells. It is a thin, clear layer of dead keratinocytes. Instead of keratin,
keratinocytes in the stratum lucidum contain eleidin, a clear intracellular protein, which gives this layer
its transparent appearance[3]. Stratum Corneum (Keratin layer): It is the outermost layer of the
epidermis. This keratinized layer serves as a protective overcoat and due to keratinization and lipid
content, this layer allows for the regulation of water loss by preventing internal fluid evaporation.
Dermis[edit | edit source] Dermis lies deep to the epidermis. It is a thick layer of connective tissue
consisting of collagen and elastin which contributes to skin’s strength and flexibility, respectively. It also
contains nerve endings, blood vessels, and adnexal structures such as hair shafts, sweat glands, and
sebaceous glands. The dermis is divided into two layers[1][2]: Papillary dermis (the upper layer): The
apical layer of dermis folds to form papillae that extend into the epidermis like tiny finger-like
projections and is referred to as the papillary dermis. It contains capillaries that facilitate the transport
of nutrients. Reticular dermis (the lower layer): The lower layer of the dermis is referred to as the
reticular dermis. It contains skin appendages such as hair follicles, sebaceous glands, and sweat glands.
The presence of a dense concentration of collagenous and reticular fibers interwoven within this layer
makes the reticular dermis is significantly thicker than the papillary dermis.[3] Both dermal layers
contain fibroblasts, myofibroblasts, and immune cells such as macrophages, lymphocytes, and mast
cells. Fibroblasts synthesize an extracellular matrix comprising of collagen, proteoglycans, and elastic
fibers that provide the structural integrity of the dermis.[3] Hypodermis[edit | edit source] The
hypodermis is the third and deepest layer, consisting mainly of adipose tissue[1]. Skin adipose tissue
stores energy in the form of fatty acids and functions as an endocrine organ important for glucose
homeostasis and lipid metabolism.[3] This layer consists of fibrocytes and adipocytes and is rich in
proteoglycans and glycosaminoglycans, which confer mucus-like properties [3]to the layer.[3] This layer
also produces a variety of mediators such as growth factors, adipokines, and cytokines, and contains
multiple immune cells. Subcutaneous fat serves as an insulating layer for the body, as fat is a poor
conductor of heat.[3] Physiological Factors[edit | edit source] Thickness of Skin[2]: It varies based on its
location, age, gender, medications, and health affecting the skin’s density and thickness. As explained
above the varying thickness is due to changes in the dermis and epidermis. The palms and soles have a
thick skin where there is marked keratinization and the stratum lucidum layer and thinner skin is found
on eyelids, axillae, and genitals, as well as the mucosal surfaces exposed to the external environment
such as oral mucosa, vaginal canal, and other selected internal body surfaces. The skin thins during the
fifth decade of life, primarily due to changes in the dermis with loss of epithelial appendages, elastic
fibers, and ground substance, among others. Genetics also influence natural skin contour. For example,
people of African-American descent typically exhibit thicker and more lustrous skin compared to people
of Anglo-Saxon ancestry. Environmental factors also affect skin thickness. For example, a person with an
occupation requiring much outdoor exposure to the sun and ultraviolet radiation show premature skin
aging signs sooner than a person working indoors. Innervation[edit | edit source] The skin is innervated
by sensory nerves expressing receptors that can sense pain (nociceptors), itch (pruriceptors),
temperature (thermoreceptors), and touch (low-threshold mechanoreceptors). These receptors are
present as nerve free endings. [3] Nociceptive nerves are in close contact with hair follicles and
epithelial cells with their free nerve endings terminating at various levels of the epidermis Merkel cells
are involved in mechanosensation (light touch) theses are oval-shaped cells interspersed in the basal
layer of the epidermis and innervated with sensory fibers. Meissner’s corpuscles are localized in the
papillary dermis and are sensitive to touch Pacinian corpuscles are located in the reticular dermis and
are responsive to pressure and vibration. Both types of corpuscles are supplied by Aα and Aβ sensory
nerve fibers that are situated in the sensory ganglia. Thermoreceptors, critical for sensing thermal
differences between the skin and the external environment, are expressed on both heat- and cold-
sensitive nerves, with the skin being more densely populated by cold-sensitive nerves. Activation of
thermally sensitive nerves to either heat or cold results in vasodilation, vasoconstriction, sweating, or
shivering. Other mechanoreceptors are present in the skin as corpuscles. Cell bodies of nerves
innervating the skin are present in the trigeminal and dorsal root ganglia. Blood Supply and
Lymphatics[edit | edit source] The skin is highly vascularized and is supplied by plexuses found between
the reticular and papillary layers of the dermis. The blood supply originates from an extensive network
of larger blood vessels and capillaries that extend from regional branches of the systemic circulation to
local sites throughout subcutaneous tissue and dermis, respectively. There is an extensive lymphatic
framework that runs alongside many of the skin’s blood vessels, particularly those attached to the
venous end of the capillary networks[2]. Muscles[edit | edit source] Arrector pili muscles are the
smallest skeletal muscles of the body, that are found in all areas of the skin that contain hair follicles.
These muscles control the positioning of hairs and the activity of sebaceous glands in response to
environmental induction, such as heat and abrasion. The arrector pili muscles contract and raise the
hairs under conditions of stress when the sympathetic nervous system is activated such as during the
fight or flight response[2]. Functions of the Skin[edit | edit source] The functions of the skin are[2]:
Protection: Protects against microorganisms, dehydration, ultraviolet light, and mechanical damage.
Skin is the first physical barrier that the human body has against the external environment. Sensation:
pain, temperature, touch, and deep pressure. Mobility: allows smooth movement of the body.
Endocrine Activity: Skin initiates the biochemical processes involved in Vitamin D production, which is
essential for calcium absorption and normal bone metabolism. Exocrine Activity: by the release of water,
urea, and ammonia. Skin secretes products like sebum, sweat, and pheromones, and also exerts
important immunologic functions by the secretions of bioactive substances such as cytokines. Immunity
development against pathogens. Temperature Regulation: Skin participates in thermal regulation by the
conservation or release of heat and helps to maintain the body’s water and homeostatic balance Clinical
Relevance[edit | edit source] Skin Pigmentation[edit | edit source] The melanin molecule plays a role in
skin pigmentation. It offers photo-protection to the organism by absorbing the Sun's ultraviolet
radiation. The melanic pigments and determine the colour of the skin, hair, and eyes[4]. White Colour -
Lack of Melanic Pigment Black Colour - Increased Melanin Density The ratio between the two types of
melanic pigments (eumelanin-pheomelanin) determines the differences in pigmentation of the human
skin.[4] Quantity of Pheomelanin > Quantity of Eumelanin = Light colour skin and has a higher
susceptibility to sunburns. Research shows that the skin with a higher quantity of pheomelanin has a
cancer risk following the exposure of the sun ultraviolet radiation, as higher quantity of reactive species
of oxygen are produced, leading to a cellular lesion and initiating the carcinogen process[4]. Skin
Response in Wound Healing[edit | edit source] The wound healing process consists of four phases:
haemostasis, inflammation, proliferation, and remodelling.[3] Disruptions in any of the phases of wound
healing result in impaired healing. A prolonged inflammatory phase may result in chronic wounds and
inefficient wound healing. Perturbed proliferative and remodelling phases may lead to irregular wound
closure, fibrosis, and scarring. Common Non-healing Chronic Wounds[edit | edit source] Venous stasis
ulcers, arterial stasis ulcers, pressure ulcers, and diabetic wounds are the most common non-healing
chronic wounds. Burns[edit | edit source] First-degree burn affects the epidermal layer of the skin
Second-degree, which affects the dermis, Third-degree injury that goes as deep as the subcutaneous
tissue. Burn injuries are characterized by an intense inflammatory phase and edema. Blistering is also
commonly found in burn patients with second-degree injuries. Severely burned patients usually present
a variety of systemic complications, such as depressed or aggravated immune responses, electrolyte
imbalance, sepsis and multiple organ dysfunction syndromes, and inflammation-associated
psychological effects are seen in severely burned patients[3]. Early wound closure reduces the risk of
infection and fluid losses and reduces mortality, length of hospital stay, and subsequent hypertrophic
scarring.[5] Wound Complications[edit | edit source] Infections[edit | edit source] Impaired wound
healing can lead to systemic or local infections. Deregulated immune responses characterize the milieu
of non-healing wounds and it facilitates colonization of the wounded tissue by pathogenic bacteria.
Biofilms, commonly formed in non-healing wounds, are single- or multi-strain communities of microbes.
Diabetic wounds are associated with various antibiotic-resistant bacterial strains such as S. aureus,
Escherichia coli, Klebsiella, and pathogenic forms of S. epidermidis. Burn patients are affected with
common bacterial infections, with the most common strains being Klebsiella pneumoniae,
Acinetobacter baumanii, Pseudomonas aeruginosa, and S. aureus. Many of these strains can form
biofilms, and if these infections persist, may lead to bacteraemia and ultimately to sepsis.[3] Nerve
Damage[edit | edit source] Wounds extensive in skin depth usually result in nerve damage. Patients with
nerve damage suffer a partial or complete loss of sensory or motor functions in the affected area,
numbness, and pain[3]. A nerve can be transected during lacerations. Burn injuries, especially third-
degree burns, manifest nerve damage resulting in complete loss of sensation at the affected site.
Hypertrophic Scarring and Keloids[edit | edit source] It is the result of over production of collagen in the
wound bed by fibroblasts. Scar tissue is characterized by the lack of skin elements such as hair follicles
and sebaceous glands. Hypertrophic scarring is common in burns and cutaneous injuries affecting the
dermal layer of the skin[3]. Skin Microbiome[edit | edit source] Skin is colonized by beneficial
microorganisms that serve as a physical barrier to prevent the invasion of pathogens. The skin
microorganisms play an essential role in protecting against invading pathogens, the education of our
immune system, and the breakdown of natural products[6]. Staphylococcus epidermidis and
Propionibacterium acnes are the major commensal microbes that inhabit the skin. They protect the host
by competing for habitable space, preventing colonization of the skin by pathogenic microbes.
Commensal strains can secrete their antimicrobial agents, such as bacteriocins, which inhibit the growth
of pathogenic bacterial strains. Colonization of the skin by pathogenic strains is usually associated with
low commensal strains[3]. The fungi kingdom is not very diverse and the viral microbiome is not well
delineated and although not as diverse as the bacterial kingdom, it exhibits more diversity than that of
fungi[3]. Skin as an Immune Organ[edit | edit source] Skin protects the host from invasion by employing
physical barriers, biomolecules, immune and non-immune cell intricate network and skin structures
Physical Barrier[edit | edit source] Corneocytes in the Stratum Corneum contribute to the barrier
function of the epidermis. These cells are arranged in “bricks and mortar” fashion interspersed by lipids
such as ceramides, cholesterol, and free fatty acids. Each corneocyte contains a lipid envelope linked to
keratin filament bundles that fill the intracellular compartments of the corneocyte, thus increasing its
rigidity. The stratum corneum is made of three layers and it is both an outside‒in barrier to prevent the
entry of foreign substances and microorganisms, and an inside‒out barrier to prevent water loss.[3]
Junction adhesion molecules and tight junction proteins (Claudin-1/zonula occludins-1) found in
epidermal layers also add to the formation of the physical barrier. Disruptions in the expression or
function of these components may cause improper barrier formation or skin disorders or inflammatory
conditions in the skin. Studies have shown that the skin of patients with atopic dermatitis has reduced
expression levels of ZO-1 and claudin-1.[3] Skin pH[edit | edit source] Skin pH is acidic and ranges
between 4 to 6 The body’s internal environment maintains a near-neutral pH (7–9). There is a gradient
of 2–3 units between the SC and underlying epidermis and dermis[7]. Recent research suggests skin pH
depends on several key enzymes involved in the synthesis and maintenance of a competent skin barrier.
Age, anatomic site, sebum, sweat, genetic predisposition affect the pH along with the use of creams,
soaps, and cosmetics[7]. Various mechanisms maintain a low pH of the skin: Enzymatic processes and
fatty acids, sweat glands in the SC lower the pH of the skin.[3] Sweat glands secrete a vast collection of
antimicrobial peptides, which restrain various microbes' growth on the skin. During rigorous physical
exercise, dermcidin, an antimicrobial peptide, is secreted by the sweat glands onto the skin's epidermal
surface. Research suggests that dermcidin gets activated in salty and slightly acidic sweat, which can
perforate microbe membranes, allow water, and charged Zinc in sweat to gush across the cell
membrane, kill the microbe. [8] Besides, the physiological pH of the skin is for commensal bacteria such
as Staphylococcus epidermidis, which helps in preventing pathogenic strains such as Staphylococcus
aureus from establishing infections in the host[3]. Immune and Non-immune Cells[edit | edit source]
Skin-resident immune cells promote tissue function in homeostasis and guard the body by actively
sampling environmental antigens. Some resident immune cells migrate to lymph nodes to either induce
peripheral tolerance to tissue self-antigens or initiate robust immune responses.[3] In infections or
tissue injury, immune cells resident in the skin and those infiltrating from the periphery interact to
create an intricate defense network to resolve the insult and restore the tissue to its original state.[3]
Skin-resident myeloid cells include Langerhans cells, dermal dendritic cells, macrophages, mast cells, and
eosinophils that contribute to skin homeostasis by secreting growth factors needed for the survival of
keratinocytes, fibroblasts, and endothelial cells. They phagocytose debris and apoptotic cells and
support vasculature integrity. In inflammatory conditions, myeloid cells respond immediately and
produce pro-inflammatory mediators that drive cell activation and infiltrate the affected area by
peripheral immune cells. Skin myeloid cells also serve as a link between the innate and adaptive immune
systems.[3] Biomolecules[edit | edit source] Antimicrobial peptides (AMPs) and lipids are the main
classes of biomolecules that participate in skin defense by disrupting bacterial membranes.[3] Skin and
Circadian Rhythm[edit | edit source] Skin makes an exclusive interface between the environment and
the host body; it receives and generates signals related to timing from the light. Skin cells have
peripheral clocks. There is a growing body of research in circadian and ultradian (an oscillation that
repeats multiple times during a 24 hours period) cutaneous rhythms, including clock mechanisms,
functional manifestations, and stimuli that entrain or disrupt the normal cycle. It has therapeutic and
clinical implications of circadian rhythm in skin health and disease.[9][10] The circadian rhythm regulates
the sleep-wake cycle. The central clock (neurons comprising the suprachiasmatic nucleus of the
hypothalamus) coordinates the phase of the peripheral clocks impacts different organs mediated
indirectly by hormones and neurons. Skin maintains an active circadian clock that is under the influence
of the central clock. [11]This clock, which probably operates in all types of skin cells, may influence the
regulation of several circadian physiological phenomena, including cell proliferation. Skin Conditions[edit
| edit source] Psoriasis[edit | edit source] Psoriasis is a chronic inflammatory skin disease, characterized
by over proliferation of keratinocytes and inflammation, which leads to epidermal hyperplasia, a
hallmark of lesional psoriatic skin. The psoriatic plaques are most seen over the elbows, knees and
scalp[12]. Acne[edit | edit source] Acne vulgaris (or simply acne) is a very common skin disease affecting
skin with the densest population of sebaceous follicles, including the face, the upper part of the chest,
and the back. It is characterized by increased colonization of P. acne anaerobic bacteria, increased
sebum production from the sebaceous glands, inflammation, and hyper-keratinization[12]. Atopic
Dermatitis[edit | edit source] Atopic dermatitis is a chronic and relapsing inflammatory skin disease
often associated with eczema and itch. Genetic, environmental, and immunological factors play a role in
atopic dermatitis[12]. Summary[edit | edit source] The skin is a complex organ and is in constant contact
with the environment. It performs major roles in protecting the host from the external environment,
infections, synthesis of Vitamin D, regulating immune responses, and tissue reconstruction.
Integumentary System - Physiopedia

The Integumentary System The integumentary system is the largest organ of the body that forms a
physical barrier between the external environment and the internal environment that it serves to
protect and maintain. The integumentary system includes Skin (epidermis, dermis) Hypodermis
Associated glands Hair Nails. In addition to its barrier function, this system performs many intricate
functions such as body temperature regulation, cell fluid maintenance, synthesis of Vitamin D, and
detection of stimuli. The various components of this system work in conjunction to carry out these
functions[1]. General Function[edit | edit source] The integumentary system has several functions that
provide several purposes[2]: Physical protection: The integumentary is the covering of the human body
and its' most apparent function is physical protection: skin - a tightly knit network of cells, with each
layer contributing to its strength. The epidermis has an outermost layer created by layers of dead
keratin that can withstand wear and tear of the outer environment, the dermis provides the epidermis
with blood supply and has nerves that bring danger to attention amongst other functions; hypodermis
provides physical cushioning to any mechanical trauma through adipose storage; glands secrete
protective films throughout the body; nails protect the digits; hairs throughout the body filter harmful
particles from entering the eyes, ears, nose, etc. Immunity: The skin is the body’s first line of defense
acting as a physical barrier preventing direct entry of pathogens. Antimicrobial peptides (AMPs) and
lipids on the skin also act as a biomolecular barrier that disrupts bacterial membranes. Resident immune
cells, both myeloid and lymphoid cells are present in the skin, and some, eg Langerhans cells or dermal
dendritic cells, can travel to the periphery and activate the greater immune system[1] Wound healing:
When our body undergoes trauma with a resulting injury, the integumentary system orchestrates the
wound healing process through hemostasis, inflammation, proliferation, and remodeling.[1][1]
Thermoregulation: The skin has a large surface area that is highly vascularized, which allows it to
conserve and release heat through vasoconstriction and vasodilation, respectively[1]. Vitamin D
synthesis: The primary sources of vitamin D are sun exposure and oral intake (crucial for bone health)
[1]. Sensation- Skin innervation is by various types of sensory nerve endings that discriminate pain,
temperature, touch, and vibration. Each type of receptor and nerve fiber varies in its adaptive and
conductive speeds, leading to a wide range of signals that can be integrated to create an understanding
of the external environment and help the body to react appropriately[1]. Organ Systems Involved[edit |
edit source] Skin[edit | edit source] Accounts for about 16% of your total body weight. Its surface area
covers between 1.5-2m2 [3] Made up of two layers—the superficial epidermis and the deeper dermis.
Epidermis: Tough, outer layer that acts as the first line of defense against the external environment
Regenerates from stem cells located in the basal layer that grow up towards the corneum. The
epidermis itself is devoid of blood supply and derives its nutrition from the underlying dermis Image:
Overview of the integumentary system[4] Composed of stratified squamous epithelial cells that further
break down into four to five layers (see image R). From superficial to deep, the primary layers are the
Stratum corneum Stratum granulosum Stratum spinosum Stratum basale In the palms and soles where
the skin is thicker, there is an additional layer of skin between the stratum corneum and stratum
granulosum called the stratum lucidum. Dermis Underlying connective tissue framework that supports
the epidermis The dermis as a whole contains blood and lymph vessels, nerves, sweat glands, hair
follicles, and various other structures embedded within the connective tissue. Further subdivides into
two layers Superficial papillary dermis - forms finger-like projections into the epidermis, known as
dermal papillae, and consists of highly vascularized, loose connective tissue. Deep reticular layer - has
dense connective tissue that forms a strong network[1]. Pathophysiology and Injury eg Burns eg of the
hand Psoriatic Arthritis Epidermolysis Bullosa Cellulitis Cancer eg melanona Pressure Sore Wounds
Hypodermis[edit | edit source] The hypodermis lies between the dermis and underlying organs.
Commonly referred to as subcutaneous tissue Composed of loose areolar tissue and adipose tissue.
Provides additional cushion and insulation through its function of fat storage and connects the skin to
underlying structures such as muscle[1]. Hair[edit | edit source] Hair is a component of the
integumentary system and extends downward into the dermal layer where it sits in the hair follicle. The
presence of hair is a primary differentiator of mammals as a unique class of organisms. In humans, it is a
cherished and highly visible indicator of health, youth, and even class. It has a sensory function, protects
from cold and UV radiation. Areas of clinical significance include diseases of hair loss, excess, alterations
due to nutritional deficiencies, infectious causes, and effects of drug reactions[5] Nail[edit | edit source]
Nails form as layers of keratin and appear at the dorsal tips of the fingers and toes. Nails function to
protect the fingers and toes while increasing the precision of movements and enhancing sensation.
Pathophysiology: Onychomycosis (fungal infection,common clinical presentation involves nail
discoloration, subungual hyperkeratosis, onycholysis, and splitting or destruction of the nail plate),
Pitting (presents in conditions such as psoriasis, eczema) Koilonychia (spoon nail, been associated with
iron deficiency anemia but can be due to idiopathic changes) Clubbing (the most common manifestation
of hypertrophic osteoarthropathy and correlates with many systemic conditions).[1] Associated
Glands[edit | edit source] Four types of exocrine glands within human skin—Sweat, sebaceous,
ceruminous, and mammary glands. Sweat glands, are further divided into eccrine and apocrine glands.
Eccrine glands are distributed throughout the body and primarily produce serous fluid to regulate body
temperature. Apocrine glands are present in the axilla and pubic area and produce milky protein-rich
sweat. These glands are responsible for odor as bacteria break down the secreted organic substances.
Sebaceous glands are part of the pilosebaceous unit, which includes the hair, hair follicle, and arrector
pili muscle. Secretes an oily substance called sebum, a mixture of lipids that forms a thin film on the
skin. This layer adds a protective layer, prevents fluid loss, and also plays an antimicrobial role[1].
Pathophysiology eg Seborrheic dermatitis, Hyperhidrosis Conclusion[edit | edit source] The
integumentary system provides numerous functions necessary for human life while also maintaining an
optimal internal environment for other critical components to thrive. When there is an imbalance in this
system, many disorders can manifest. The integumentary system also acts as a reflection of underlying
pathologies eg showing jaundice with liver disfunction, displaying petechiae with thrombocytopenia;
decreased skin turgor with dehydration. It is a system that can provide many external clues regarding an
individual’s physiological state and is a vital component of a complete clinical picture[1].

Wound Healing - Physiopedia

Introduction Skin is the largest organ in the body and covers the body's entire external surface. Figure.1
Overview of the Integumentary System (Skin) [1] Made up of three layers, the epidermis, dermis, and
hypo-dermis. Skin's structure is made up of an intricate network that serves as the body’s initial barrier
against pathogens, UV light, and chemicals, and mechanical injury, and regulates temperature and the
amount of water released into the environment. A skin wound results from the breakdown of the
epidermal layer integrity[2]. Wound healing mostly means healing of the skin. Begins immediately after
an injury to the epidermal layer and might take years. Dynamic process including highly organized
cellular, humoral, and molecular mechanisms. Has 3 overlapping phases which are inflammation,
proliferation, and remodelling. Any disruption leads to abnormal wound healing[3]. See also Soft Tissue
Healing Figure.2 Healing Timelines Types of Wounds[edit | edit source] The definition of a wound in
general is damage to the integrity of biological tissue, including skin, mucous membranes, and organ
tissues.Wounds can be separated into open or closed wounds: Closed Wound: The surface of the skin is
intact, but the underlying tissues may be damaged. e.g. contusions, haematomas, or Stage 1 Pressure
Ulcers. Open Wounds: the skin is split or cracked and the underlying tissues are exposed to the outside
environment. Figure.3 Closed Wound - Contusion Figure.4 Open Wound Also it can be classified
according to the cleanliness and condition of wounds into four classes of wound status:[4] Class 1
wounds are considered to be: clean uninfected no inflammation is present primarily closed these
wounds do not enter respiratory, alimentary, genital, or urinary tracts. Class 2 wounds are considered to
be: clean-contaminated lack unusual contamination Class 2 wounds enter the respiratory, alimentary,
genital, or urinary tracts under controlled conditions. Class 3 wounds are considered to be:
contaminated These are fresh, open wounds caused by an insult to sterile techniques or by
gastrointestinal tract leakage into the wound. incisions that result in acute or lack of purulent
inflammation are classified as class 3 wounds. Class 4 wounds are considered to be: dirty-infected result
from improperly cared for traumatic wounds. demonstrate devitalized tissue Types of Wound
Healing[edit | edit source] Wound healing is classified as primary, secondary, and tertiary wound
healing. Primary Healing or primary intention Uncomplicated healing of a non-infected, well-
approximated wound is defined as primary healing. e.g. Surgical wounds. Secondary Healing or
secondary intention If the wound healing course in this wound is disrupted by infection, dehiscence,
hypoxia or immune dysfunction, the secondary healing stage begins. During secondary healing,
granulation tissue formation and epithelization over this new tissue take place. These types of wounds
are more susceptible to infections and poor healing. Tertiary healing or third intention it is delayed
primary wound healing after 4–6 days. This occurs when the process of secondary intention is
intentionally interrupted and the wound is mechanically closed. This usually occurs after granulation
tissue has formed. Wound Healing Stages in Adults[edit | edit source] In adults, optimal wound healing
should involve four continuous and overlapping phases: Haemostasis, inflammation, proliferation, and
remodelling .[5] Figure.4 Wound Healing Stages Hemostasis Phase[edit | edit source] The process of the
wound being closed by clotting. Happens very quickly. Starts when blood leaks out of the body, then
blood vessels constrict to restrict the blood flow. The platelets aggregate and adhere to the sub-
endothelium surface within seconds of the rupture of a blood vessel's epithelial wall. After that, the first
fibrin strands begin to adhere in about sixty seconds. As the fibrin mesh begins, the blood is transformed
from liquid to gel through pro-coagulants and the release of prothrombin. The formation of a thrombus
or clot keeps the platelets and blood cells trapped in the wound area. The thrombus is generally
important in the stages of wound healing but becomes a problem if it detaches from the vessel wall and
goes through the circulatory system, possibly causing a stroke, pulmonary embolism or heart attack[6]
[3]. Inflammatory Phase[edit | edit source] Begins right after the injury when the injured blood vessels
leak transudate (made of water, salt, and protein) causing localized swelling. Inflammation both controls
bleeding and prevents infection. The fluid engorgement allows healing and repair cells to move to the
site of the wound. During the inflammatory phase, damaged cells, pathogens, and bacteria are removed
from the wound area. The white blood cells, growth factors, nutrients and enzymes create the swelling,
heat, pain and redness commonly seen during this stage of wound healing. Inflammation is a natural
part of the wound healing process and is only problematic if prolonged or excessive. Proliferative
Phase[edit | edit source] When the wound is rebuilt with new tissue made up of collagen and
extracellular matrix The wound contracts as new tissues are built. A new network of blood vessels must
be constructed so that the granulation tissue can be healthy and receive sufficient oxygen and nutrients.
Myofibroblasts cause the wound to contract by gripping the wound edges and pulling them together
using a mechanism similar to that of smooth muscle cells. In healthy stages of wound healing,
granulation tissue is pink or red and uneven in texture. Healthy granulation tissue does not bleed easily.
Dark granulation tissue can be a sign of infection, ischemia, or poor perfusion. Finally epithelial cells
resurface the injury. Epithelialization happens faster when wounds are kept moist and hydrated.
Generally, when occlusive or semi-occlusive dressings are applied within 48 hours after injury, they will
maintain correct tissue humidity to optimize epithelialization. Maturation Phase (Remodelling Stage)
[edit | edit source] Collagen is remodelled from type III to type I and the wound fully closes. The cells
that had been used to repair the wound but which are no longer needed are removed by apoptosis, or
programmed cell death. The collagen laid down during the proliferative phase, it is disorganized and the
wound is thick. Collagen is remodelled into a more organized structure along lines of stress, thereby
increasing the tensile strength of the healing tissues. Fibroblasts secrete matrix metalloproteinases. The
enzymes facilitate remodelling of type III collagen to type I collagen[5]. Generally, remodelling begins
about 21 days after an injury and can continue for a year or more. Even with cross-linking, healed wound
areas continue to be weaker than uninjured skin, generally only having 80% of the tensile strength of
unwounded skin[6]. Clinical Significance[edit | edit source] Any disruption in wound healing phases
leads to excessive wound healing or chronic wound formation. Excessive Wound Healing[edit | edit
source] The pathogenesis of the excessive wound healing is not fully understood. An abnormal form of a
wound healing that is characterized by a continuous localized inflammation. Excessive collagen
synthesis, abnormal collagen turnover and exaggerated ECM accumulation in these wounds. e.g.
"Keloid" and "hypertrophic scars". Chronic Wound Formation[edit | edit source] A wound that has failed
to heal in 4 weeks is defined as a chronic wound. Risk Factors; Age, immune status, malnutrition,
infection, insufficient oxygenation or perfusion, smoking, diseases, medications, radiation, and
chemotherapy are the main risk factors. Chronic wounds are usually classified as vascular ulcers (venous
or arterial ulcers), diabetic ulcers, and pressure ulcers.[3] See image. Other Complications can include:
Deficient scar formation. Exuberant granulation. Deficient contraction (in skin grafts) or excessive
contraction (in burns). Others: Dystrophic calcification[7], pigmentary changes[8], painful scars,
incisional hernia.[9] Factors Affecting the Wound Healing[edit | edit source] Main Risk factors are: age,
immune status, malnutrition, infection, insufficient oxygenation or perfusion, smoking, diabetes,
metabolic diseases, medications, radiation, and chemotherapy[3]. Also, consider: Extrinsic factors which
include: support surfaces, friction, and shear and effective repositioning schedules. Local factors:
moisture (keeping a wound moist improves healing)[10]; edema; faulty technique of wound closure;
Ischemia and necrosis; foreign bodies[11]. Wound Care in Physiotherapy[edit | edit source] The most
common wounds that are treated by wound care physical therapist are:[12] Necrotic wounds. Stage III,
IV or unstageable pressure ulcers. Diabetic wounds, see image. Chronic wounds. Venous and/or arterial
wounds. Extremity wounds with oedema. Non-healing surgical wounds. Physiotherapy Role[edit | edit
source] Physical therapy wound care begins with a comprehensive evaluation and the development of
an individualized care plan. [12] Wound Assessment Wound Debridement Common treatment
approaches can include: Measurement and documentation of the wound characteristics. Cleaning of the
wound. Debridement (removal) of any dead tissue. Selection and application of wound dressing.
Application of compression if necessary. Education of the patient, caregivers and/or family members
regarding wound care and dressing changes. Treatment modalities may include: Ultrasound mist
therapy Electrical stimulation Pulsed lavage Whirlpool Negative pressure vacuum therapy Compression
therapy. Related Resources[edit | edit source] Ultrasound in Wound Healing

Factors Affecting Wound Healing - Physiopedia

Introduction Disclaimer: This page discusses the use of sharp debridement of the wound bed. This is an
advanced treatment technique which requires specialised training to be properly and safely performed.
Please be aware of your profession's practice act. Traditionally, sharp excisional debridement into
healthy viable tissue can only be performed by a medical doctor with advanced training, while other
health professionals in some areas can perform sharp debridement of nonviable tissue with advanced
training. There are many factors to take into consideration when practising wound care. Some of these
factors are within the control of the rehabilitation professional, and some are not. By gaining an
understanding of these key factors, the rehabilitation professional will be able to adjust the wound care
treatment plan to obtain the best possible healing outcome. There are three types of factors which can
affect wound healing: (1) intrinsic, (2) extrinsic, and (3) iatrogenic.[1] Understanding the influence of
these factors can help shape and inform a wound care assessment, treatment plan, and prognosis. For
example, it is unrealistic to expect a wound to heal in the same manner in a young healthy person as in
an older person with multiple comorbidities. Providing patients with realistic expectations of the healing
process improves goal setting and builds trust between patients can care providers.[1] Intrinsic
Factors[edit | edit source] Intrinsic factors are those related to the person that cannot be changed, but
may be managed.[1] Age. The epidermis becomes thinner with age and has a slower turnover. Collagen,
elastin, and hyaluronic acid production also decreases as skin ages. This makes older skin more
susceptible to tears and wounds. Human growth hormone plays a significant role in tissue healing and
this decreases with age as well. Once older skin is wounded, it heals slower due to slower turnover of
keratinocytes, reduced blood flow to the dermis, and a slowing of the complex healing cascade.[1]
Genetics. In 2020, Tipton et al.[2] looked at the microbiomes of chronic wounds and found that people
tend to be susceptible to infections by certain pathogens depending on their genotype. They also found
that the variety of bacteria present is significantly related to wound healing. The more varied a wound
microbiome, the faster that wound will close. While a person's microbiome is somewhat modifiable,
much of the baseline is related to genotype and to the microbiome you are born with and seeded from
during the birthing process.[1] [2] Skin elasticity and the ability to lay down collagen and fibrin is also
genetically linked. This process can be seen in the body's ability to form scars, stretch marks, and
wrinkles. Research in mice has found wound healing to be genetically controlled with a heritability rate
of up to 86%. Other research in humans has found specific gene expression to be associated with the
onset and progression of wound healing.[1][3] This graphic is specifically looking at genetically
determined sex hormone averages and does not take into account those with altered sexual expression
or hormonal levels outside of the average range. Sex hormones. This is a complex topic. The research is
mixed. Some research shows oestrogens speed healing and other research is in favour of androgens,
depending on what phase the wound is in.[4] For most patients, this will not be of concern. However, it
may need to be considered for patients taking synthetic hormones or going through an abrupt hormonal
change, such as menopause.[1] Systemic diseases. Common medical conditions that may affect healing
are (1) diabetes, (2) vascular diseases, (3) pulmonary diseases, (4) immunocompromised or autoimmune
conditions, and (5) conditions that affect the autonomic nervous system. Both sympathetic and
parasympathetic divisions play important roles in the wound healing phases.[1] Diabetes.
Hyperglycaemia delays healing, therefore blood glucose levels need to be kept as close to the ideal
range as possible. Ideally, blood glucose levels should be kept as close to the normal range as possible.
However, even a reduction of blood glucose to 11.1 millimoles per litre, (200 milligrammes per decilitre)
will have a beneficial effect on wound healing. Likewise, patients with an A1C of less than 7.1% have
improved healing time. Providing this education to patients can help them to feel motivated in their
progress toward more controlled blood glucose levels.[1] Venous insufficiency. A wound will not heal
when persistent oedema is present. Oedema results in fibrinogen leaking out of capillaries into the
dermis, which blocks oxygen and nutrients from being delivered to the tissues. This reduces blood flow
and results in tissue hypoxia. Tissue hypoxia impairs tissue repair and increases susceptibility to infection
by anaerobic microbes. It also inhibits fibroblast function and suppresses epithelial cells.[1] Arterial
insufficiency. Blood flow to tissue needs to be optimised to facilitate wound closure. Insufficient
perfusion reduces the delivery of the oxygen cells and nutrients necessary for healing.[1] Idiopathic
pulmonary fibrosis. Pulmonary fibrosis reduces tissue oxygenation and negatively affects the tissue
repair mechanisms via widespread epithelial injury.[1] Other chronic pulmonary diseases that affect
tissue oxygenation can also impact healing.[1] Immunocompromised conditions. Such conditions
prevent the necessary inflammatory response to initiate the healing cascade. This leads to an increased
risk of infection, decreased phagocytosis, and decreased fibroblast activity.[1] Sensory and autonomic
neuropathy. The neurotransmitters and neuropeptides produced by the cutaneous nerves are essential
for all phases of repair. These substances are responsible for plasma extravasation, vasodilation, and
neurogenic inflammation. Neuropathy limits the production of these substances.[1] Extrinsic
Factors[edit | edit source] Extrinsic factors are things external to the wound that we can directly control.
[1] Medications. It is important to perform a medication review and investigate any potential effects
which could delay healing. Listed below is a non-exhaustive list of common medications which interfere
with wound healing.[1] Steroids will delay all phases of wound healing. They can also contribute to
elevated glucose levels with long-term use, recall how hyperglycaemia can delay healing as discussed
above.[1] Anticoagulants inhibit the coagulation cascade and can result in tissue necrosis. This is
especially common in fatty tissue.[1] Long-term non-steroidal anti-inflammatory drugs (NSAIDs) use
delays wound healing by (1) suppressing the inflammatory response, (2) decreasing collagen synthesis,
(3) reducing tensile strength and (4) increasing the risk of infection.[1] Chemotherapy drugs interfere
with (1) cell proliferation, (2) prolong inflammation, (3) inhibit protein synthesis, and (4) decrease
collagen synthesis. Chemotherapy-associated nausea and vomiting may also impair nutrition (see below
for more details on nutrition).[1] Immunosuppressive or anti-rejection medications (1) impair fibroblast
formation, (2) increase risk of infection and (3) decrease wound tensile strength. The gastrointestinal
side effects of these medications can also impair nutrition (see below for more details on nutrition).[1]
Nutrition. The nutritional requirements for tissue healing are greater than the levels recommended for
routine tissue maintenance or the recommended daily allowance (RDA).[5] [6][7] For example,
additional water is needed to help with tissue repair depending on the size of the wound and the
patient's overall health. It is estimated that a person's water requirements during wound healing are
increased by approximately 20 to 30% above their normal requirements. Dietary adjustments will be
made by dietitians or physicians while the patient is healing. Typically, the patient will be prescribed
supplements at a dose that is above a nutrient's RDAs for two to 12 weeks while wound healing is
initiated. This will then be reduced back to the RDA levels or the patient will be weaned off completely
once healing is complete and a regular diet is established.[1] Stress and elevated cortisol levels. Stress
results in (1) an increase in the incidence of opportunistic infection, (2) reduced expression of human
growth hormone, and (3) delayed healing.[1] Gouin et al.[8] compared the healing rate of a small punch
biopsy wound on a group of dental students. They found that the participants healed an average of
three days slower when they were under the stress of exams as compared to when they were on
vacation break. This represented a 40% longer healing time for a small standardised wound in a young
and otherwise healthy population.[8] Older persons with multiple comorbidities are already at risk for
delayed healing, and stress further compounds that risk.[1] People who are stressed are more likely to
engage in other habits that can delay wound healing, such as the (1) use of alcohol, tobacco or drugs, (2)
less physical activity, (3) less sleep, (4) poor nutrition, and a (5) lack of medication compliance.[1] Sleep
deprivation. Lack of quality sleep can lead to (1) increased cortisol production, (2) elevated rates of
illness and infection, (3) delayed skin barrier recovery, (4) reduced growth hormone production, and (5)
impaired healing potential. It is important to recall that sleep disturbances can be a common side effect
of many medications and underlying health conditions.[9] Therefore, a thorough patient interview and
medication review are indicated. Ideally, adults should get 8-9 hours of sleep per night.[1] Smoking.
Smoking leads to (1) hypoxia, (2) tissue ischaemia, (3) blood vessel inflammation, and (4) interferes with
every phase of wound healing. Smoking a single cigarette has been shown to reduce tissue oxygen
concentrations, whereas pack-per-day smokers experience tissue hypoxia for a significant portion of
each day. It is possible to reverse the damage caused by smoking: After 12 hours without smoking, the
blood oxygen levels return to near normal levels. After 24 hours without smoking, nerves begin to
recover. Smoking cessation has been shown to restore the tissue microenvironment and cellular
functions within four weeks. For heavy smokers who are unable to quit, decreasing the number of
cigarettes smoked may cause improvement in tissue healing ability. Smokers have also been shown to
have significantly lower levels of plasma vitamin C compared to non-smokers. Therefore, diets that are
higher in vitamin C or including vitamin C supplementation should be considered to mitigate blood
vessel damage and then further promote healing.[1] Please watch the following optional short video for
a concise summary of how smoking affects wound healing. [10] Alcohol. Drinking alcohol (1) delays
wound closure, (2) increases the risk of infection, (3) reduces angiogenesis, (4) impairs collagen
production, (5) interferes with epithelialisation, and (6) induces tissue hypoxia. Wound healing can be
affected after just a few exposures to alcohol drinking above the legal limit.[1] Infection. Bacterial
infection. All skin surfaces, including open wounds, are colonised with bacteria. Some bacteria are
harmless and are part of the skin's biome. They are necessary for wound healing. Chronic wounds will
have more bacterial colonisation than acute wounds and tend to have more pathogenic bacteria. This
does not create a problem as long as the body can manage the level of bacterial colonisation. The
amount of bacteria present in the wound is categorised on a spectrum. Local infection delays wound
healing by (1) reducing collagen production, (2) decreasing nutrients available for healing and (3) killing
cells vital for the healing process.[1]. Please see special topic box at the end of this section for a 2022
update of this information. Fungal infection. These infections are particularly problematic for patients
who are immunocompromised. They can occur more often with compression therapy dressings, which
stay in place for up to seven days. Wound drainage and sweat create a moist environment within
compression dressings that is ideal for fungal growth. This is especially true in hot and humid
environments. Fungal infections are best managed through (1) topical antifungals, (2) more frequent
dressing changes and (3) adequate absorption via dressing selection to manage wound drainage.[1]
Biofilm. This is a topic of new and emerging research and is not yet fully understood. Bacteria have
evolved a variety of strategies to ensure their survival, one of these is the development of a
polysaccharide capsule that shields them from destruction by the host's immune defences. Biofilm
adheres to the wound bed and is difficult to remove, making the wound resistant to healing. Biofilm can
be invisible to the naked eye (will make the wound surface appear shiny or slimy) or it can also resemble
a thin layer of slough (yellow in colour) on the wound's surface. Mature biofilm can form in a matter of a
few days - 90% of chronic wounds will have biofilms. Biofilm must be removed for wound healing.
Regularly repeated sharp debridement is the preferred method to remove biofilm. Antimicrobial
dressings are not an acceptable treatment method because they cannot penetrate the biofilm in order
to kill the invading bacteria.[1] Please watch this optional short video to learn more about the
fascinating role the biofilm plays in delaying wound healing. [11] Obesity. Obesity is a known risk factor
for multiple diseases. It also increases the risk of (1) wound infections, (2) haematomas, (3) surgical
complications, (4) venous ulcers, and (5) pressure injuries.[1] These risks are likely due to (1) decreased
tissue perfusion and ischaemia in adipose tissue, (2) increased tissue tension on wound edges, and (3)
inadequate delivery of antibiotics. Adipocytes have been shown to secrete factors that interfere with
normal inflammatory and immune responses. Other concerns which have the potential to affect wound
healing in patients with obesity include increased risk of (1) pressure, (2) friction, (3) maceration, (4)
limited mobility and or a sedentary lifestyle, and (5) oedema.[1] Special Topic: The IWII Wound Infection
Continuum (IWII-WIC) The IWII-WIC is an assessment tool which provides a framework for wound care
professionals to understand the impact microorganisms have on (1) the host, (2) the wound and on (3)
wound healing. The five stages in the IWII-WIC increase in severity as the microbial presence increases
and begins to affect the host and wound functioning.[12]. The creation of the IWII-WIC included the
elimination of the descriptive term critical colonisation for local infection.[13] The IWII-WIC includes five
conceptual stages:[12] Stages Clinical Observations/Signs and Symptoms Host Reactions 1 (least
microbial burden) Contamination Microoganisms are present within the wound but are not proliferating
No significant host reaction is evoked No delay in healing is clinically observed Host defences destroy
microorganisms via phagocytosis 2 Colonisation Microorganisms are present and undergoing limited
proliferation No significant host reaction is evoked No delay in wound healing is clinically observed Due
to the protective function of the skin microbiome, all open wounds are colonised with microorganisms
at the time of skin breakdown Microorganisms that colonise a wound may also arise from exogenous
sources or as a result of environmental exposure 3 Local infection Microorganisms are present and
undergoing proliferation Host reaction is evoked which can include a delay in wound healing Local
infection is contained within the wound and the immediate periwound region (less than 2cm) Local
infection often initially presents as covert signs and symptoms which may not be immediately
recognised as a sign of infection As infection progresses, overt signs and symptoms become evident and
are more recognisable as an indicator of wound infection 4 Spreading infection (also known as cellulitis)
Extending induration Spreading erythema Inflammation or erythema >2cm from wound edge Crepitus
Wound breakdown/dehiscence Lypmphagitis (swelling of lymph glades) Spreading infection may involve
deep tissue, muscle, fascia, organs or body cavities and result in more wide-spread signs and symptoms
such as crepitis or lymphangitis 5 (greatest microbial burden) Systemic infection Malaise Lethargy Loss
of appetite Fever/pyrexia Severe sepsis Septic shock Organ failure Death Invading microorganisms can
spread throughout the body via the vascular or lymphatic systems, evoking a massive whole-body host
response with fever Potential systemic inflammatory response syndrome (SIRS) Systemic inflammatory
response can also be triggered by a local wound infection via other pathways, such as (1) the release of
toxins or a (2) dysregulated immune system Table adapted from the IWII-WIC 2022 update[12]
Iatrogenic Factors[edit | edit source] Iatrogenic factors are related to how the wound is managed. The
rehabilitation professional can have the biggest influence over this factor by modifying the treatment
plan throughout the healing process after assessing the wound's response to interventions.[1] Dressing
selection and management.[1] Compression is essential for venous wounds, and is indicated for oedema
reduction in other wounds as well. Care must be taken to apply compression appropriately and monitor
patient response regularly. Compression applied over an arterial wound or with an incorrect technique
can reduce tissue perfusion and or create a tourniquet effect that damages both the wound and the
peri-wound tissue. Dressing removal with poor technique can result in trauma to the healing wound
tissues. Inappropriate dressing choices for a wound can cause tearing or maceration. Wounds require a
moist environment for proper healing. Proper dressing selection is finding a balance between keeping
the wound bed too moist or too dry. Proper dressing selection requires consideration of the drainage
type and the amount and planned frequency of dressing changes. Repeated assessments must be
performed to monitor the wound's response to the selected dressings. Too many dressing changes can
also delay healing. When the wound bed is exposed to the outside environment during a dressing
change, it can take up to 40 minutes for wound tissue to return to proper temperatures optional for
healing. In addition, cellular mitosis is disrupted for up to three hours after a dressing change. Incorrect,
unnecessary, or too frequent debridement. Excessive debridement is detrimental to healing because it
causes a disruption of the wound bed. While maintenance debridement is often needed, attempts
should be made to limit interruption to the healing process. This means when debridement is
performed, care should be taken to remove as much necrotic tissue and biofilm as possible to allow for
wound healing. This may require debridement by a medical doctor or surgeon who can debride deeper
into viable tissue and a bleeding base.[1] Oedema management via positioning. Many chronic wounds
are associated with oedema, particularly venous ulcers. Dependent positioning of an extremity will (1)
increase oedema, (2) reduce the return of blood and lymphatic flow out of the extremity, and (3)
increase pain. Leg elevation should be higher than the heart and combined with calf pump exercises. If
the patient is unable to tolerate or achieve this position, attempt to elevate the distal leg to the level of
the hip. The only wounds that should be kept dependent are wounds where tissue perfusion is
compromised, such as arterial ulcers. In this case, gravity can help to improve blood flow to the wound.
[1] Topical antiseptics and antibiotic ointments. Cytotoxic antiseptics have a wide spectrum of action on
bacteria. However, they also cause eradication of beneficial bacteria and damage to the healing cells.
Common examples used in wound care include (1) betadine (povidone-iodine), (2) Dakin's solution
(sodium hypochlorite), (3) chlorhexidine, (4) hydrogen peroxide, (5) Burow's solution (aluminium
acetate), and (6)silver nitrate.[1] Topical antibiotics have a more narrow spectrum of action and are less
cytotoxic than antiseptics. They are typically less destructive to healing cells, but can still be detrimental
when used inappropriately. Research in both human and animal models has demonstrated that broad-
spectrum topical antibiotics slow skin healing. Common topical antibiotics used in wound care include
(1) bacitracin, (2) mafenide acetate, (3) mupirocin, (4) neomycin, (5) Neosporin, (6) Polysporin, and (7)
silver sulfadiazine. In addition to delayed wound healing, some of these products can be harmful to the
kidney and liver and should be avoided in those with pre-existing kidney or liver impairment. When
indicated, these products are effective if used correctly. However, they should be chosen with careful
consideration and used for the shortest amount of time necessary to achieve the desired outcome and
minimise detrimental effects.[1] Local trauma.[1] External pressure applied over tissues will collapse
capillaries which results in reduced blood flow and tissue oxygenation. Friction and shear forces from
footwear and dressings can cause tissue damage which can lead to wound formation and also impair
current wound healing. This includes bumping, rubbing, scratching, excessive movement, or other
disruption of the wound. These local traumas can occur through wound cleansing, dressing changes,
loose compression dressings, footwear, or patient positioning. Factors that can Optimise Wound
Healing[edit | edit source] Five key factors that can optimise wound healing are:[1] Address underlying
disease processes. This can include: (1) blood pressure, (2) blood glucose levels, (3) tissue perfusion, (4)
oedema management, (5) reinforce medication compliance, (6) offloading, and (7) pressure relief. The
rehabilitation professional can provide education on how these factors can affect wound healing. When
appropriate, reinforce treatment plans established by other healthcare providers and refer the patient
to other members of the healthcare team as needed. Promote nutrition. The rehabilitation professional
can (1) refer to a dietitian or nutritionist, (2) reinforce compliance with the prescribed diet, (3)
emphasise the importance of hydration for tissue healing, (4) educate on the benefits of nutrition for
healing. Exercise and physical activity. Physical activity (1) increases circulation and tissue perfusion, (2)
reduces oedema, (3) improves overall health, and can (4) reduce the negative impact of systemic
disease.[14] Peer support and mindfulness. We know that beliefs and attitudes can contribute to chronic
health conditions and this includes chronic wounds. This may mean that the patient puts the onus on
the healthcare provider to heal them rather than taking responsibility for the control that they have
over their healing process. Alternatively, the patient may feel powerless or feel unsure about how to go
about making the recommended changes. Therefore, patients who have been dealing with wounds for a
long time and/or have seen multiple healthcare providers may feel hopeless. Peer support groups can
be helpful in increasing patient adherence to a treatment programme. Examples include (1) walking or
exercise groups, (2) nutrition groups, (3) support for health challenges and setbacks, (4) breath-work
and breathing exercise groups. Mindfulness. Research has found that mindful stress-reduction
techniques, relaxation, and guided imagery have been associated with improved wound healing.
Examples include (1) positive self-talk about the healing ability of the body, (2) fostering belief in the
potential for healing, (3) mindfulness exercises that address tissue oxygenation, nutrition, tissue repair,
body resiliency, or (4) turning the focus inward to body repair rather than outward to life stresses.
Guided imagery can also be used to talk the patient through (1) the phases of tissue healing, (2)
breathwork, (3) directing healing breath and healing cells towards the wound, or (4) positive
affirmations. These exercises can be in spoken, written, or audio form. Many patients utilise a
combination of these methods. Education. Patient education specific to the patient's wound and the
underlying condition is key yet this is often overlooked as part of the plan of care. Patient understanding
of the plan of care and specific recommendations can greatly improve adherence to a treatment plan
and improve compliance of interventions that promote healing. Patient education should be an
interdisciplinary effort and be provided at all levels of the care team. It helps with intrinsic versus
extrinsic locus-of-control; the patient knows what factors are changeable, what factors can be modified,
and what factors are completely within their control. Education assists the patient in goal setting and
prioritising. Patient education can be provided as needed. Rehabilitation professionals are ideal for this
role as they often spend more time with the patient and can provide education in smaller and better-
retained amounts. Resources[edit | edit source] Optional Additional Reading: Intrinsic Factors: Demling
RH. The role of anabolic hormones for wound healing in catabolic states. J Burns Wounds. 2005 Jan
17;4:e2. Engeland CG, Sabzehei B, Marucha PT. Sex hormones and mucosal wound healing. Brain,
behaviour, and immunity. 2009 Jul 1;23(5):629-35. Tipton CD, Wolcott RD, Sanford NE, Miller C, Pathak
G, Silzer TK, Sun J, Fleming D, Rumbaugh KP, Little TD, Phillips N. Patient genetics is linked to chronic
wound microbiome composition and healing. PLoS pathogens. 2020 Jun 18;16(6):e1008511. Zhu HJ, Fan
M, Gao M. Identification of potential hub genes associated with skin wound healing based on time
course bioinformatic analyses. BMC Surg. 2021;21:303. Extrinsic Factors: Aberg KM, Radek KA, Choi EH,
Kim DK, Demerjian M, Hupe M, Kerbleski J, Gallo RL, Ganz T, Mauro T, Feingold KR, Elias PM.
Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of
cutaneous infections in mice. J Clin Invest. 2007Nov;117(11): 3339-49. Attinger C, Wolcott R. Clinically
addressing biofilm in chronic wounds. Adv Wound Care. 2012 Jun;1(3):127-132. Besedovsky L, Lange T,
Born J. Sleep and immune function. Pflugers Arch. 2012 Jan;463(1):121-37. Clinton A, Carter T. Chronic
wound biofilms: Pathogenesis and potential therapies. Laboratory Medicine. 2015;46(4):277-284.
Garbarino S, Lanteri P, Bragazzi NL, Magnavita N, Scoditti E. Role of sleep deprivation in immune-related
disease risk and outcomes. Communications biology. 2021 Nov 18;4(1):1-7. Gouin JP, Kiecolt-Glaser JK.
The impact of psychological stress on wound healing: methods and mechanisms. Immunology and
Allergy Clinics. 2011 Feb 1;31(1):81-93. Heitzer T, Just H, Mu¨nzel, T. Antioxidant vitamin C improves
endothelial dysfunction in chronic smokers. Circulation. 1996;94:6-9. Jung MK, Callaci JJ, Lauing KL, Otis
JS, Radek KA, Jones MK, Kovacs EJ. Alcohol exposure and mechanisms of tissue injury and repair. Alcohol
Clin Exp Res. 2011 Mar;35(3):392-9. McDaniel JC, Belury M, Ahijevych K, et al. Omega-3 fatty acids effect
on wound healing. Wound Repair Regen. 2008;16(3):337–45. Meesters A, den Bosch-Meevissen YMCI,
Weijzen CAH, Buurman WA, Losen M, Schepers J, Thissen MRTM, Alberts HJEM, Schalkwijk CG, Peters
ML. The effect of Mindfulness-Based Stress Reduction on wound healing: A preliminary study. J Behav
Med. 2018 Jun;41(3):385-397. Szabo G, Mandrekar P. A recent perspective on alcohol, immunity, and
host defense. Alcohol Clin Exp Res. 2009 Feb;33(2):220-32. Thorpe J. The importance of water: In
modern wound care. Wounds UK. 2010;5:115-118. Iatrogenic Factors: Keylock KT, Vieira VJ, Wallig MA,
et al. Exercise accelerates cutaneous wound healing and decreases wound inflammation in aged mice.
Am J Physiol Regul Integr Comp Physiol. 2008;294(1):R179–84
Physiology of Burns - Physiopedia

Skin Overview Skin is a cutaneous membrane which covers the surface of the body. It is the largest
organ of the body in terms of weight and surface area. Table 1. Illustrating the layers of the skin Figure
1. Layers of the Skin Epidermis Superficial layer Provides a waterproof barrier and contributes to skin
tone Composed of epithelial tissue Avascular Dermis Deeper, thicker layer Connective tissue Contains
blood vessels, nerves, glands and hair follicles Highly vascularised Hypodermis Deepest layer Storage for
fat/ insulation Attaches to underlying facia Areolar and adipose tissue Contains large blood vessels For
more information, please see Skin Healing Process[edit | edit source] When treating a burns patient the
knowledge of tissue healing is beneficial to the patient and to the possible outcomes. Your knowledge of
tissue healing combined with the information gathered from your assessment will influence the decision
of when to rest, exercise, stretch and to what level to strengthen during the recovery period. Please
note that these timescales are variable according to the size of the burn, surgical intervention and any
other complicating factors. Clinical reasoning is essential when applying the following in practice. STAGE
TIMESCALE PROCESS SIGNS AND SYMPTOMS TREATMENT Haemostasis The process of the wound being
closed by clotting Begins when blood leaks out of the body, then blood vessels constrict to restrict the
blood flow The platelets aggregate and adhere to the sub-endothelium surface within seconds of the
rupture of a blood vessel's epithelial wall. After that, the first fibrin strands begin to adhere in about
sixty seconds. As the fibrin mesh begins, the blood is transformed from liquid to gel through pro-
coagulants and the release of prothrombin. The formation of a thrombus or clot keeps the platelets and
blood cells trapped in the wound area Reduce heat and oedema and pain. Prevent infection and
disruption of wound. Useful: Immobilisation, positioning and splinting. Inflammation 0-5 days
Vasoconstriction followed by vasodilatation and influx of inflammatory mediators and WBCs.
Increased capillary permeability. Exudate leaks into tissues. Pus may be produced. Redness, Heat,
Swelling, Pain Reduce heat and oedema and pain. Prevent infection and disruption of wound. Useful:
Immobilisation, positioning and splinting. positioning, splinting. Proliferation (fibroplasia) Begins day
3- 5. Lasts 2-6 weeks. Fibroblasts synthesize collagen. Laid down haphazardly. Angiogenesis
continues. Moist red raised tissue over wound Early: Positioning and immobilisation Later: Gentle
stress with splinting and exercise. Reduce oedema and prevent contractures. Remodelling
(maturation) Begins week 4-6. Lasts up to 2 years. Synthesis of collagen balanced by degradation.
Organisation of collagen fibres along lines of stress. Wound closure Scar red and raised progresses to
flat pale and pliable. Scar tissue tightens. Optimise function Splinting Positioning Exercise Stretching
Strengthening. Table 2: Tissue healing process following burn injury (Glassey 2004) Figure 2. The 4
Stages of Wound Healing For more information on the Healing Process, the following two pages are
available to read: Wound Healing Soft Tissue Healing Systemic Response to Burns[edit | edit source] In
severe burn injury, >30% TBSA complex reaction occurs both from the burn area and in the area distant
to the burn. Cytokines, chemokines and other inflammatory mediators are released in excess resulting in
extensive inflammatory reactions within a few hours of injury. The initial response depending on the size
of the burn injury is similar to the inflammation that is triggered after tissue destruction such as trauma
or major surgery. Different factors contribute to the magnitude of the host response, they include: Burn
severity (percentage TBSA and burn depth) Burn cause Inhalation injury Exposure to toxins Other
traumatic injuries Patient-related factors Age Pre-existing chronic medical conditions Drug or alcohol
intoxication Timing of presentation to care This inflammatory response leads to rapid oedema formation
This is caused by: Increased microvascular permeability Increased hydrostatic microvascular pressure
Vasodilation Increased extravascular osmotic activity. These reactions are due to the direct heat effect
on the microvasculature and to the chemical mediators of inflammation. Vasodilation and increased
venous permeability at the early stage of the injury are caused by the release of histamine. Also,
prostaglandin is released by damage to the cell membranes which causes the release of oxygen-free
radicals released from polymorphonuclear leucocytes which activate the enzymes catalyzing the
hydrolysis of prostaglandin precursor. These hemodynamic changes lead to continuous loss of fluid from
the blood circulation causing increased haematocrit levels and a rapid fall in plasma volume, leading to a
decrease in cardiac output and hypoperfusion on the cellular level. Burn shock occurs if fluid loss is not
adequately restored. (Evers et al 2010) In addition to the local effects of a burn, a severe burn injury has
an effect on different organs and systems in the body. The effects include: Cardiovascular Respiratory
Renal Endocrine Metabolic Immunological Changes Oedema Formation The essence of burn shock is the
rapid and extensive fluid transfer in burn and non-burn tissues (6). After severe burns, the local and
systemic vascular permeability increase, causing intravascular fluid extravasation, leading to a
progressive decrease in effective circulation volume, an increase in systemic vascular resistance, a
decrease in cardiac output, peripheral tissue edema, multiple organ failure, and even death (7,8). The
increase in vascular permeability is characterized as a significant change in the permeability of capillaries
and post-capillary venules. In other words, the normal physiological barrier function of endothelial cells
(ECs) is destroyed 1. Effect on the Cardiovascular System[edit | edit source] The initial response to a
burn injury of more than 30% TBSA is shock which results in a decrease in cardiac output and metabolic
rate. This decrease in cardiac output, initially, is caused by hypovolemia and a decrease in the venous
return. There is also a decrease in contractibility of the muscles in the heart, this is thought to be caused
by an increase of vasoconstrictors in the body. The damage to the cardiovascular system can cause
effects for up to two years post injury. Compromised cardiac function results in: Organ hypoperfusion
Impaired peripheral microcirculation Extension of the burn zone Reduced resistance to bacterial
infection at the wound site. Definitions: Hypervolemia is a decrease in blood volume. Hypovolemic
Shock is when there is a loss of approximately 1/5 or more of the normal amount of blood in the body,
Hypovolemic shock is treated by replacing the fluid and/or blood, usually done through an IV line, in
addition to treating the cause. This is caused by: Blood loss from bleeding, it can be bleeding from a cut,
or internal bleeding. Loss of blood plasma due to severe burns, this happens due to loss of skin and
damage to the blood vessels. Dehydration ie, diarrhea or vomiting (loss of a lot of body fluids may lead
to a drop in the amount of circulatory blood). For more information on Hypovolemic Shock, please see
Burn Shock. 2. Effect on the Respiratory System[edit | edit source] The effect of burns on respitation is
mainly attributed to the following three complications: Heat Injury to the Upper Airway The result of a
heat injury to airway structures includes extensive swelling of the the tongue, epiglottis, and
aryepiglottic folds which causes an accompanying obstruction. Chemical Injury to the Lower Airway
Most commonly, following smoke inhalation, inflammatory mediators are released in the lungs leading
to bronchoconstriction, pulmonary oedema and adult respiratory distress syndrome (ARDS). Systemic
Toxicity Inhalation of chemicals, cytotoxic liquids, fumes, mist and gases can cause systemic toxic
changes. Smoke can combine with these toxins and cause increased mortality due to tissue hypoxia,
metabolic acidosis, decreased oxygen supplu to the brain and decreased metabolism. For more
information, please read Inhalation Injury 3. Effect on the Renal System[edit | edit source] Early kidney
injury is due to: Low blood volume Inflammatory mediators Increased release of protein in the
bloodstream Extensive tissue damage Medications that are toxic to the kidneys The renal system
complications are caused by the alterations in the cardiovascular system. Blood flow to the kidneys is
decreased due to hypervolemia and decreased cardiac output. This marks the beginning of kidney
failure. This can be prevented by conducting an accurate assessment for the correct fluid recusitation to
be administered. The rehabilitation team should always keep an eye out for decreased urine output as
this is an early sign of renal compromise. 4. Effect on the Endocrine System[edit | edit source] The
endocrine system is made-up of glands in the body, which secrete hormones. Following a burns trauma,
there are distinct responses in the endocrine system. Trauma can affect the HPA Axis (Hypothalamic-
pituitary-adrenal axis), which controls the interaction between the hypothalamus, pituitary gland, and
adrenal glands. The hypothalamus and pituitary gland are located just above the brainstem, while the
adrenal glands are found on top of the kidneys. Firstly, due to the burn injury, individuals commonly
have an elevated sympathetic drive. This is due to an increase in the release of cortisol and glucagon.
These hormones effect the metabolic system, mentioned below. Prolonged excess cortisol can result in
hypercortisolemia. Which is associated with infection rates in post burn patients and lengthened
durations of severe infection. Secondly, oxytocin production is decreased, which is associated with
empathy and love. This can cause long term side effects emotionally for the individual. 5. Effects on
Metabolic System[edit | edit source] The metabolic state is initially suppressed by the effects of acute
shock. Initial effects to the body following a burn can cause: Impaired gastrointestinal motility Impaired
digestion and absorption Increased intragastric pH Feeding difficulties, which exacerbate effects of hyper
metabolism (Evers et al 2010) Hypermetabolism begins approximately five days post burn.
Hypermetabolism is when the basal metabolic rate increases up to three times its original rate. The
cause of hypermetabolism is not entirely defined and appears very complex and is most likely activated
and sustained by stress induced hormonal releases and inflammation. The decreased perfusion among
the organs in the abdominal cavity, necessitates early and aggressive enteral feeding to decrease
catabolism and maintain gut integrity. It causes muscle wasting, mucosal atrophy, reduced absorptive
capacity, and increased surface permeability. Effects can be seen for up to two years post burn.
Hypermetabolism causes: Increased body temperature Increased oxygen and glucose consumption
Increased CO2 and minute ventilation Increased heart rate for up to 2 years post burn (Jeschke et al
2007; Grisbrook et al 2012a; Hurt et al 2000) Catabolism occurs when food is digested and the large,
complex molecules in the body are broken down into smaller, simple ones to be used as energy. 6.
Immunological Changes: (Hettiaratchy and Dziewulski 2004)[edit | edit source] As mentioned above,
following a burn injury, individuals commonly have an elevated sympathetic drive, causing the release of
cortisol. Prolonged excess cortisol can result in hypercortisolemia, which is associated with infection
rates in post burn patients and lengthened durations of severe infection. Patients also suffer from a high
risk of infection while wounds are open. 7. Oedema formation[edit | edit source] A burn wound causes
an increased inflammatory response. Blood tests show an increased level of CRP (C-reactive protein)
following a burn injury. This protein is made by the liver and assists the inflammation process. CRP
causes increased inflammaorty symptoms of When body tissues are burned, histamine is released from
mast cells, act on ECs, fibroblasts, and smooth muscle cell tissues, exert a strong vasodilator effect, and
can significantly increase the permeability of microvascular endothelium Why do burns increased
capillary permeability? The major reasons for this systemic microvascular leakage in burns include an
increase in vascular permeability triggered by inflammatory mediators and the increase of vascular
hydrostatic pressure caused by vessel dilation. o Capillary permeability is increased o leads to loss of
intravascular proteins and fluids to the interstitial compartment ∙ Hypovolemia o Secondary to oedema
and rapid fluid loss from surface of wound ∙ Peripheral and splanchnic vasoconstriction occurs

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