In this section, we briefl y review the anatomy and physiology of young and aged skin and subcutaneous soft tissues to help you appreciate how aging and the depth of loss of skin and soft tissue affect how wounds heal as well as the role of the different structures in tissue regeneration or repair. Figure 2.1 is a dia- gram of skin and soft tissues, which is included here to help you visualize the anatomic arrangement of the structures.
As we will see shortly, wounds are defi ned according to the level of skin and soft tissue structure lost.
Young Skin
The skin or integument is the largest organ in the body and con- sists of two primary layers. The outermost layer, the epidermis, At the completion of this chapter, the reader will be able to:
1. Identify structures that are part of skin and soft tissue anatomy.
2. Determine wound severity based on depth of tissue loss.
3. List three acute wound healing models.
4. Identify and list the benchmarks of each of the four phases of wound healing.
5. List the benchmarks of wound phase changes for acute and chronic wound healing.
6. Describe the role of basic scientifi c research in understanding pathophysiology and developing wound treatments.
7. Apply knowledge of the wound microenvironment to identifi cation of factors that can affect the healing process.
Carrie Sussman and Barbara M. Bates-Jensen
Wound Healing Physiology
2
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Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratum germinativum Dermis
Epidermis lifted to reveal papillae of the dermis Dermal papillae
Nerve endings
Sweat glands Nerve to hair follicle
Hypodermis (subcutaneous tissue) Dermis
Arrector pili muscle of hair Blood vessels Sebaceous gland
Hair Epidermal ridge
Epidermis
Epidermis
Capillary loop
Adipose tissue Hair root
Sweat pore
Reticular layer of dermis Papillary layer of dermis Nerve ending
FIGURE 2.1 Diagram of skin and soft tissues.
is itself composed of several layers of epithelium. The fi rst epi- dermal layer is the stratum corneum, also known as the horny layer, which is composed of keratinocytes. The innermost skin layer is the dermis, a connective tissue layer that contains neu- rons and blood vessels.
The primary function of the skin is protection—from bac- teria and other microbes, from mechanical trauma, harmful chemicals, and excessive heat, cold, moisture, dryness, and ultraviolet radiation. Thus, when the skin is injured, the body is subject to invasion by outside agents, loss of body fl uids, and other problems. In addition to its barrier function, skin is important for thermal regulation, vitamin D metabolism, and immune defense. Also, skin health is a mirror of general health, and skin failure often accompanies other system failures within the body.
Epidermis
The epidermis consists almost entirely of keratinocytes, cells that produce keratin, a fi brous protein. The epidermal keratinocytes are arranged into fi ve layers as shown in Figure 2.2. The most superfi cial is the stratum corneum. Deeper layers of the epider- mis include the stratum lucidum, stratum granulosum, stratum
spinosum, and stratum basale (also called the stratum germina- tivum). Keratinocytes arise from the stratum basale and, as they mature, they migrate upward toward the stratum corneum, increasing their keratin load. Keratinocytes reproduce continu- ously and produce a protein called keratin, which is insoluble in water and prevents water loss and entrance of irritants into the body. They live for only a few weeks and, by the time they reach the skin surface, have died. In fact, the stratum corneum consists entirely of dead keratinocytes. Deposits of dry keratin on the skin surface are called scale. Hyperkeratosis (thickened layers of keratin) is often found on the heels and can indicate loss of sebaceous glands and sweat gland functions.
In addition to keratinocytes, the epidermis contains other functional cells. For instance, Langerhans cells, which are immune cells that help fi ght infection, and melanocytes, which produce the pigment protein melanin as well as have an immune function.3 An important function of the epidermis in wound healing is to close the wound quickly and effi ciently. As we’ll discuss in detail later in this chapter, epidermal wounds heal primarily by cell migration called epithelialization. Clusters of keratinocytes migrate into the area of damage and cover the defect. These lead cells are phagocytic and clear the surface
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of debris and plasma clots. Repair cells originate from local sources, primarily the dermal appendages and from adjacent intact skin areas. Healing occurs rapidly, and the skin is regenerated and is left unscarred.
pH of the Stratum Corneum
The normal pH of the stratum corneum is between 4 and 6.5.
This low pH forms an acid mantle that enhances the skin’s barrier function. Recent studies have demonstrated that enzy- matic activity is involved in the formation of this acid mantle.
Together, the acid mantle and stratum corneum make the skin less permeable to water and other polar compounds and indi- rectly protect the skin from invasion by microorganisms.
Damage to the stratum corneum increases the skin pH and, thus, the susceptibility of the skin to bacterial skin infections.4 For example, hand washing three times a day with cleansing agents alters the acid mantle for several hours, and multiple washings alter the barrier functions, including the skin pH, for up to 14 hours. Increased alkalinity can also be caused by perspi- ration or urine and stool from incontinence. Systemic diseases, such as diabetes, chronic renal failure, and cerebrovascular
disease, can also cause increased skin pH. Wound dressings and diapers have also been known to raise skin pH.4
If the pH of the skin shifts toward alkaline, it can become prone to secondary bacterial and fungal infections. These thrive, for example, in the perineal skin. Other problems asso- ciated with increased skin surface pH include eczema, contact dermatitis, atopic dermatitis, perineal dermatitis, and dry skin.
An association between wound surface pH and wound heal- ing has been made. The pH of open wounds tends to be alkaline or neutral (range 6.5–8.5). As new epithelium is formed at the wound edges, the pH on the surface is restored.5
Maintenance of the Stratum Corneum
Hydration and lubrication of the stratum corneum are impor- tant in keeping the skin intact. Extremes of either dryness or hydration are equally damaging, as is mechanical trauma.
Indeed, any disruption in the stratum corneum allows increased transepidermal water loss, impairing the barrier function.6 Barrier disruption causes a localized infl ammatory cascade, which can prompt infl ammatory skin diseases such as eczema.
For example, removal of wound dressing adhesives can strip the stratum corneum and cause noticeable transepidermal water loss.7 This in turn triggers an infl ammatory wound healing response, proportional to the amount of damage to the skin.
Following such insults, normal adult skin has the capacity to recover its barrier function within 6 hours. Recovery of the bar- rier is slower in aged skin. During recovery, there is an increase in lipid production within the stratum corneum. Application of effective moisturizer products containing the appropriate mix of lipids can reduce the epidermal water loss during the recov- ery period. In particular, petrolatum and lanolin-based skin care products have been shown to enhance barrier recovery by reducing water loss and inhibiting the infl ammatory reaction of the cells.6,8
Skin cleansers and moisturizers that have low or neutral pH are recommended for maintaining the acid mantle of the skin.
Soaps are more alkaline than most synthetic detergents and nonionic surfactants (which are slightly acidic or neutral) and should not be used to clean open wounds.4
Melanin and Skin Color
Melanin pigmentation accounts for the variation in skin color among humans from very dark to very light. Although the num- ber of melanocytes present in dark and light skin is similar, the size and activity of the melanocytes are greater in dark skin than in light skin. In people with dark skin, the melanin pigmenta- tion is concentrated in a layer of the stratum corneum that can be wiped off when washing. Of course, this does not mean that
Dead keratinocytes
Stratum corneum Stratum lucidum (found only in palm, sole of foot, and fingertips) Stratum granulosum
Stratum spinosum
Stratum germinativum Basement membrane Dermis
Keratinocyte Langerhans cell
Melanocyte Merkel cell
Tactile disc
Sensory neuron Lamellar granules Superficial
Deep FIGURE 2.2 Diagram of the epidermal layers.
RESEARCH WISDOM
Effect of Hand washing on Skin Health of Health-Care Professionals
Health-care professionals wash their hands between each patient, typically more than three times per day, and often develop eczema, contact dermatitis, atopic dermatitis, and dry skin.
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CLINICAL WISDOM
Care of Darkly Pigmented Skin
Care of darkly pigmented skin requires keeping the skin lubricated. Petrolatum, lanolin-based lotions, and sparing use of soaps are recommended.9
all the color is removed, just the superfi cial layer. In addition, although the thickness of the stratum corneum in both dark and light skin is the same, the cells in dark skin are more compact and have more cell layers. For this reason, dark skin is more resistant to external irritants. Healthy dark skin is usually smooth and dry, whereas dry dark skin can have an ashen appearance.9
Basement Membrane and Dermal-Epidermal Junction
The basement membrane is a thin layer of protein that both separates and connects the epidermis and dermis at the dermal epidermal junction.
Dermal Appendages
Dermal appendages, which include hair follicles, sebaceous and sweat glands, fi ngernails, and toenails, originate in the epider- mis and migrate into the dermis.10 Hair follicles and sebaceous and sweat glands contribute epithelial cells for rapid closure of wounds that do not penetrate through the dermis. The seba- ceous glands are responsible for secretions that lubricate the skin, keeping it soft and fl exible. They are most numerous in
the face and in the palms of the hands and soles of the feet.
Sweat gland secretions control skin pH and thereby reduce the risk of infection. The sweat glands, dermal blood vessels, and small muscles in the skin (responsible for goose pimples) control temperature on the surface of the body. Nerve endings in the skin include receptors for pain, touch, heat, and cold.
Loss of these nerve endings, as occurs in peripheral neuropathy, increases the risk for skin breakdown by decreasing the toler- ance of the tissues to external forces. Figure 2.3 shows an anno- tated sonogram of the skin and the dermal appendages.
Dermis
The dermis, or the true skin, is a vascular structure that sup- ports and nourishes the epidermis.10 In addition, sensory nerve endings in the dermis transmit signals regarding pain, pressure, heat, and cold.
The dermis is divided into two layers: the superfi cial dermis and deep dermis. Figures 2.4 and 2.5 show superfi cial and deep dermis structures.
Superfi cial (Papillary) Dermis
The superfi cial dermis is connective tissue. It consists of an extra- cellular matrix (ECM) (collagen, elastin, and ground substances) and fi broblasts, which produce the collagen and elastin compo- nents that give the skin its turgor and toughness. Fibroblasts also secrete fi bronectin and hyaluronic acid (HA) or hyaluronan, major components of the ECM that are primarily proteins and can be found in skin, joints, eyes, and most other organs and tis- sues. They are also thought to have important biological roles in skin wound healing, by virtue of the presence in high amounts in skin. The hyalurnan content in skin is further elevated tran- siently in granulation tissue during the wound healing process.11
FIGURE 2.3 Sonogram of the skin shows the dermal appendages and layers of the skin. (Copyright © Paul Wilson, Longport Inc.)
Dermis
Subcutaneous tissue Erector muscle of hair Sebaceous gland Hair follicle Epidermis Hair
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It also consists of fi broelastic connective tissue, which is yellow and composed mainly of collagen. Fibroblasts are also present in this tissue layer. Wounds that breach this level of tis- sue are considered to be partial-thickness wounds. They will heal by regeneration as described in the upcoming section about the healing cascade.
Aged Skin
The skin aging process is continuous, and by the fourth decade, morphological changes are seen histologically that affect the function and appearance of the skin including change in skin topography (e.g., lines, wrinkles, and texture) and microcirculation.12 Since many patients who have poor or nonhealing wounds are elderly, age related changes to the skin are very relevant to wound healing but are not often given adequate consideration due to a lack of awareness and/or knowledge. Therefore, the following materials are included to help you understand the underlying anatomic and physiologic changes that occur in the skin during aging, which affect the speed and healing of wounds in otherwise healthy elders.
Epidermis
During aging, several changes occur in the epidermis that alter function and appearance of the skin structures. These include
• Epidermal changes
• Thickening of the stratum corneum
• Appearance of redness
• Decrease in both Langerhans cells and melanocytes
• Keratinocytes and senescence
• Atrophy of the basal membrane and fl attening of the dermal epidermal junction
Epidermal Changes
Age-associated epidermal changes include the atrophy of the epidermis. It becomes thinner and more transparent, and there is increased visibility of the vascular structure in the dermis giving the appearance of redness.12 There is a thinning of the stratum spinosum and thickening of the stratum corneum. The later thickening is not directly age related but is the body reac- tion over time to protect the skin from sunlight.3
Langerhans Cells
Langerhans cells are the most important antigen-presenting cell population in the skin. Melanocytes are abundant in the hair follicles and also have immune function. In elderly skin, both cell types are decreased in number and Langerhans cells have reduced antigen-trapping capacity, which may explain the diminished cutaneous immune function in the elderly.3,13
The superfi cial dermis also contains blood vessels, lymphat- ics, epithelial cells, small muscles, and neurons. The dermal vascular supply is responsible for nourishing the epidermis, regulating body temperature and skin color. One mechanism of thermoregulation is via blood fl ow. In this skin layer, there are capillary loops, which are the source of nutrition for the tissues and which also function for thermal regulation through skin surface heat exchange.12 Younger people have the ability for the dermal vessels to vasodilate as blood fl ow increases and permit heat to be dissipated from the skin.
Deep (Reticular) Dermis
The deep dermis is located over the subcutaneous fat; it con- tains larger networks of blood vessels and collagen fi bers to provide tensile strength.10 The well-vascularized dermis will withstand pressure for longer periods of time than will subcuta- neous tissue or muscle.
CLINICAL WISDOM
Because of the highly vascularized anatomy of the dermis, dermal wounds can exude serum, blood, or pus, that lead to formation of clots or crusts; however, they typically heal rapidly.
1
2
FIGURE 2.4 Superfi cial Dermis (1) and (2) macerated dermis.
FIGURE 2.5 Acute infl ammatory phase, partial-thickness stage II pres- sure ulcer located over bony prominence. Note: (1) Erythema and edema. (2) Reticular layer of dermis. (Copyright © B.M. Bates-Jensen.)
1
2
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Diabetes causes early aging of the body and that includes the skin. What has been said about elders can be applied to the diabetic population as well. In this population, the skin blood fl ow response is profoundly more diminished than in the elderly or even absent.18
Impairment of Vascular Endothelial Cells
As part of the aging process, there is damage of the vascular endothelial cells of blood vessels in the skin as well as elsewhere, which causes reduced nitric oxide (NO) and other vasodila- tor production. NO function is described more fully on page 21. Thus, due to another age related change, the microcircula- tion capacity needed for heat dissipation of the skin is severely impaired, which allows the skin to heat up more quickly at the same temperature than for younger subjects and to become vulnerable to damage.
Other Soft Tissue Types and the Skeleton
It is critically important for you to be knowledgeable about the anatomy of the structures beneath the skin as well as the skin itself. Once the skin, epidermis, and dermis are breached, other tissues are exposed including superfi cial fascia, deep fas- cia, subcutaneous fat, skeletal muscle, tendon, ligament, nerve, bursa, and skeleton. Breach of the tissues beneath the dermis is considered a full-thickness wound meaning that it penetrates through the full thickness of the skin layers. Wounds with this loss of tissue integrity will heal by repair and scar formation, which is described below.
Figure 2.6 is a cadaver dissection of a lower leg that shows the anatomy of the soft tissues located beneath the skin and can be used as a guide through this section.
Different anatomical locations have different depths and types of soft tissue covering the skeleton. For example, over the sacrum, anterior tibial, ankle, and scapula, there is minimal soft tissue. Over the buttocks and calf, there are muscle masses and other soft tissues. All of these anatomi- cal structures are seen in open full-thickness and deeper wounds during wound assessment. Appropriate evaluation of the type and depth of tissue loss is critical for developing a wound severity diagnosis, to appropriately use wound clas- sifi cation systems described in Chapter 3, as well as to spare critical structures during wound debridement and cleansing procedures and to develop a plan of care.
Superfi cial Fascia
Superfi cial fascia is located directly beneath the dermis and when healthy looks like a fi ne mesh network and functions to let the skin move freely. Fascia then wraps around the subcutaneous fat.
Deep Fascia
Deep fascia is a dense fi brous connective tissue that enve- lopes and separates muscles, tendons, ligaments, blood ves- sels, nerves, and bones. Healthy deep fascia has a gleaming appearance. In some areas, it attaches muscles to bones such as the iliotibial band that connects the gluteus maximus to the femur. The space between muscle bundles is called the fas- cial plane. Fascial planes are seen in wounds that have been surgically or sharp debrided where the integrity of the tissue Keratinocytes
Keratinocyte proliferative activity decreases and the cells become senescent or approach senescence. Senescent cells sur- vive a long time but are unable to divide or die by the process of apoptosis. Cells accumulate with DNA mutations and protein damage until transformation to an “immortal cell” occurs, thus producing a dysfunctional skin repair process due to ineffec- tive DNA repair mechanism resulting in genetic instability and mutations.3 When the cells stop reproducing or do so slowly, the ability to reepithelialize a wound is impaired. More about this is explained ahead under chronic epithelialization.
Basement Membrane and Dermal-Epidermal Junction As skin ages, the basement membrane atrophies, and there is a fl attening of the dermal-epidermal junction, reduced dermal- epidermal adhesion, and a decrease in epidermal thickness.3 A consequence of these, and other soon to be explained changes, is limitation of heat transfer to the deeper tissues allowing heat to accumulate at the surface and creating the risk of hyper- thermia related skin damage.14 Another major consequence related to the fl attening of the epidermal-dermal junction is the increased fragility of aged skin to shear stress and the readiness of the skin to form blisters.3
Dermis
Age-related changes also occur in the dermis including
• Damage to the elastic and collagen fi bers
• Increasing skin stiffness
• Papillary capillary loop decrease
• Diminished skin blood fl ow and risk of hyperthermia
• Sympathetic nervous system (SNS) impairment
• Loss of endothelial vascular activity Elastic and Collagen
Aging skin suffers superfi cial dermis changes including damage to elastic and collagen fi ber organization with the result that the tensile or breaking strength of the collagen is impaired and the skin is more easily broken or torn.3
Capillary Loops
As we learned, the dermis is nourished by the blood fl ow in cap- illary loops; as aging progresses, the number of loops decreases and the distance between loops increases and over time they dis- appear. Perhaps this is why persons over 80 do not have increased skin blood fl ow in response to thermal stimulation.15 However, elders exhibit increased blood fl ow in remaining microvessels, but this may be due to SNS impairment as explained next.12 Sympathetic Nervous System
SNS impairment occurs with aging and that affects the dermal vasculature. Since blood fl ow is dependent on peripheral vas- cular resistance, which is under SNS control, and blood fl ow controls thermoregulation, impaired SNS function markedly impairs thermoregulatory control.16 The reserve capability of the vascular system to vasodilate in response to increased blood fl ow is reduced and plateaus at a certain point in elderly skin, putting the skin at risk for hyperthermia and burns from inability to dissipate heat quickly enough from the skin.17
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