Textbook of Chronic Wound Care: Chapter 1

  • Herbert B. Slade MD, FAAAAI, and Jamie M. Slade, MD.
  • Volume 08 - Issue 1

Textbook of Chronic Wound Care: An Evidence-Based Approach to Diagnosis and Treatment by Drs. Jayesh Shah, Paul Sheffield, and Caroline Fife, editors, is a companion reference book for the Wound Care Certification Study Guide, 2nd edition. Due for publication by Best Publishing Company in the first quarter of 2017, this textbook provides the best diagnostic and management information for chronic wound care in conjunction with evidence-based clinical pathways illustrated by case studies and more than 350 pictures. The textbook provides up-to-date information for the challenging chronic wound care problems in an easy-to-understand format. What follows is a reprinted excerpt from Chapter 1, Anatomy of the Skin, written by Herbert B. Slade MD, FAAAAI, and Jamie M. Slade, MD.

Chapter 1: ANATOMY OF THE SKIN

Introduction

Skin is an integumentary system at the interface between the human organism and its environment (Table 1). The boundary limits of skin are found at its transition to mucosal surfaces of the respiratory, alimentary, and urogenital systems; at the conjunctival epithelium of the eye; at the ductal epithelium of the lacrimal and mammary ducts; and at the tympanic membrane of the ear.

Anatomically, skin is organized into an outer layer of epidermis covering a deeper layer of dermis, which is further subdivided into papillary dermis and reticular dermis. The epidermal epithelium gives rise during fetal development to the skin appendages, namely the hair follicles and associated sebaceous glands (pilosebaceous units), eccrine and apocrine sweat glands, and nails. Beneath the dermis is the hypodermis or subcutaneous fat layer (the panniculus adiposus). Connections between skin and its underlying hypodermis include ligaments, nerves, blood vessels, and lymphatic vessels.

The gross appearance of skin varies between individuals, within an individual by anatomic location at any point in time, and within an individual over a lifetime. Variation is found with respect to texture, tone, distribution and amount of pigmentation, and expression of hair. For example, scrotal skin is very thin, with readily visible hair roots, specialized sebaceous glands, and few or no elastic fibers but consider- ably greater laxity compared with skin covering the trunk. By contrast, the glabrous skin of the palms and soles is tightly fixed to the underlying fascia, lacks hair follicles and sebaceous glands, and contains sweat pores opening into ostia located along prominent friction ridges. The epidermis is considerably thicker.

The overall thickness of skin across the body is determined by the thickness of the several layers of epidermis and the thickness of the underlying dermis. Typical thickness in a young adult ranges from the eyelids (epidermis ~50 µm, dermis ~1,000 µm) to the back (epidermis~40 µm, dermis ~5,000 µm), to the palms of the hands (epidermis ~600 µm).(1-2) The thickness of the outermost cornified layer (the stratum corneum) is greatest in areas of callous but also varies among flexor forearm, thigh, back and abdomen across a range of ~13µm (flexor forearm) to ~8µm (abdomen).(3) Published values for these measurements differ considerably, likely as a result of differences in location of sampling, methods of visualization, and methods of preservation in the case of biopsy material. (4-5) 

The structure of the skin (Figure 1) is established through the orchestrated arrival, arrangement, and differentiation of a broad array of cell lineages during embryogenesis and fetal development.(6) When it is fully developed, approximately 20 different types of cells are found in association with a complex extracellular matrix that provides both strength and flexibility(7) (Table 2). 

I. Epidermis

Full keratinization of the outermost keratinocytes is achieved prior to birth, by gestational weeks 26-28. The epidermis at birth is still relatively thin with only 2-3 cell layers in the stratum spinosum and 5-6 layers in the stratum corneum.(8) The thick whitish “vernix caseosa” covering the epidermis at birth is a product of the sebaceous glands combined with shed periderm and squames. A mixture of water, proteins, antimicrobial enzymes and lipids, the vernix is thought to provide a degree of protection against maceration while the skin is exposed to amniotic fluid, while allowing the skin to hydrate itself more rapidly following birth.(9) Removal of the vernix at birth leaves the stratum corneum drier than adult skin for some time.

Four distinct epidermal layers persist into adult life, with a basal germinative layer resting upon a basement membrane elaborated through cooperative effort between the basal keratinocytes and the underlying mesodermal fibroblasts. A fifth layer of cells can be found beneath friction ridges on the palms of the hand and soles of the feet, between the granular and horny layers. Fully developed epidermis is thus a stratified squamous arrangement consisting of a basal layer of stem and transit-amplifying cells,(10-11) above which are the spinous, granular, clear, and horny layers. The corresponding Latin descriptive terms – stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum – remain in use. The integrity of epidermis is maintained by various connections between cells and at the basal layer, with the basement membrane. Basal cells use hemidesmosomes, integrins, and anchoring fibrils to maintain contact with the basement membrane, while desmosomes, gap junctions, and adherens junctions keep them connected with each other and with cells of the spinous layer. Desmosome, gap junctions, and adherens junctions persist in the spinous layer, while in the granular layer the gap junctions give way to tight junctions. Adherens junctions and desmosomes persist in the granular layer, while in the stratum corneum the predominant connections are corneodesmosomes and tight junctions. Although epidermis is commonly thought of in terms of a “bricks and mortar” organization, cells other than keratinocytes make their way into the epidermis, some of them sending dendritic extensions between the keratinocytes (melanocytes, Langerhans cells) or crawling into and through the epidermis to perform immunologic surveillance.

TABLE 1. Functions of the integumentary system
Function Major structure(s) or cells
Waterproofing Stratum corneum
Protection against minor trauma Stratum corneum
Prevent entry of toxins Stratum corneum
Moisture balance Epidermis
Vitamin D, hormone production Keratinocytes
Prevention of invasion by pathogens Epidermis, dermis, lymphatics
Regeneration Basal epithelium, hair follicles, blood vessels
UV radiation protection Melanocytes
Physical cushioning Dermis, subcutaneous fat
Insulation Hair, subcutaneous fat, arrector pili muscles
Temperature regulation Vasculature, sweat glands, motor nerves
Sensation Sensory nerves
Immunity Dendritic cells, lymphocytes, lymphatic channels

Melanocytes have a remarkably different shape compared with resting keratinocytes, with long extensions termed “dendrites” passing between and around their keratinocyte neighbors. These cells take up residence in the stratum basale and in the hair bulb. Within the stratum basale, the ratio of melanocytes to basal keratinocytes is approximately 1:10, with each melanocyte associating with 30-40 keratinocytes above the basal layer through dendritic extensions.(12) An essential role of melanocytes is to protect the basal cells from ultraviolet radiation, accomplished through the production and transfer of melanin via melanosomes. The darkness of skin pigmentation does not depend on the number of melanocytes, which is constant across all skin tones, but rather on the extent to which melanin is produced and the size of the melanosomes, which serve as transport vehicles from the melanocytes to the keratinocytes.

Epidermal Langerhans cells are found in the epidermis, replicating there to replace dying cells and cells which have migrated to the draining lymph nodes. There does not appear to be any need for replenishment from the circulation, although circulating monocytes can enter the skin and differentiate into scavenging and antigen presenting dendritic cells.

II. Dermis

Development of the dermis is largely controlled by fibroblasts. Each of the embryonic fibroblast precursor lines is thought to split into distinct lineages, giving rise to “upper lineage” fibroblasts, which include fibroblasts of the papillary dermis, the hair follicle dermal papilla, dermal sheath cells surrounding hair shafts, and the arrector pili muscle. It also includes “lower lineage” reticular fibroblasts, pre-adipocytes, and adipocytes. Cells of the lower lineage are primarily involved in replacement of extracellular matrix following wounding, while cells of the upper lineage sup- port repithelialization.(13) The depth of injury determines the types of cells, which become engaged in repair, with lacerations extending into the middle depth of reticular dermis leading to a scarring response. Lacerations of the superficial dermis can repair themselves without visible scarring.(14) In addition to depth of injury, the amount of tension experienced by fibroblasts and the duration of inflammation also affect scarring. Primary closure of lacerations reduces tension, while control of infection limits inflammation, resulting in reduced scarring.

Hair follicles are widely distributed in skin. Epidermal cells form the primitive hair germ, penetrating as a column into the underlying dermis. An invagination or papilla is formed at the column tip into which mesodermal blood vessels and nerve endings develop. Fibroblasts within this dermal papilla seem to induce the follicular epithelial cells in the center of the follicle to undergo differentiation into central cortex cells, which generate the keratinized hair shafts. The dermal papilla and surrounding epithelial matrix cells constitute the bulb of the hair follicle. The hair shaft itself eventually consists of a medullary core, surrounded by the cortex and hair shaft cuticle.(15)

Along the upper portion of the hair follicle, superficial to what will become the upper cutaneous plexus of blood and lymphatic vessels, one or more small out buddings of the epithelial follicular sheath develop into the dermal sebaceous glands. These glands generate a lipid-rich material (sebum) that rises to the skin surface alongside the hair shaft, lubricating the skin and occluding the shaft. Deeper along the hair follicle below the forming vascular plexus, mesodermal cells give rise to smooth muscle fibers which develop into the arrector pili muscles.(16) These muscle fibers are anchored to the follicle at the “bulge region” of the outer root sheath and superficially to connective tissue beneath the basement membrane, such that a sebaceous gland is often located between the muscle and the hair follicle. Activation of these muscles results in the hairs becoming more vertical and a small amount of sebum being expressed from the glands between the shaft and muscle.

 

TABLE 2. Cells found in healthy adult skin
Name Location Function Subsets
Keratinocyte Epidermis Regeneration of the stratum corneum, re-epithelialization of denuded skin, acidification of the skin surface, antimicrobial peptide production, inflammatory signaling. Terminally differentiated keratinocyte providing a physical and chemical barrier Basal, transit amplifying granular, corneocyte
Fibroblast Dermis Generation of extracellular matrix, repair Papillary, reticular, myofibroblast
Melanocyte Basal layer of epidermis, hair follicle bulb Protection against ultraviolet radiation, hair coloration ---
Merkel cell Epidermis at dermal-epidermal boundary, upper portion of hair follicle Touch sensation through connection with nerve endings in Touch Domes ---
Endothelial cell Blood vessel lining, lymphatic vessel lining Vascular channels Blood vascular, lymphatic vascular
Pericyte Abluminal basement membrane of endothelial cells Support endothelial cells, participate in angiogenesis ---
Neuronal axons Nerves Sensory and motor nervous functions Based on neurotransmitters, end structures, efferent or afferent function
Schwann cell Surrounding neuronal axons Create myelin sheaths to insulate nerves ---
Endoneural cell Surrounding Schwann cells Protect and support Schwann cells ---
Perineurial cell Surrounding endoneural cells Create nerve fascicles ---
Myocytes Smooth muscles Express the contents of glands, cause "goosebumps" and hair erection, modulate blood flow Arrector pili, vascular smooth muscle, glandular smooth muscle
Mast cell Near blood vessels Innate immune defense, immune modulation, wound healing, angiogenesis ---
Macrophage Near blood vessels Immune surveillance, cell killing, phagocytosis of cell debris M1, M2
Dendritic cell Epidermis and dermis Immune surveillance Langerhans cells, conventional dendritic cells, plasmacytoid dendritic cells
Lymphocyte Epidermis and dermis Immune survieillance, cell killing, regulation of adaptive immune responses Memory CD4+, memory CD8+, γδ-T cell, invariant αβ-NKT, variant αβ-NKT, anergic CD4+, Tr1 T-regulatory, Th3 T-regulatory 
Adipocyte Hypodermis Energy storage (triglycerides), thermal insulation, modulation of inflammation (adipokines) Pre-adipocytes, adipocytes
Stem cell Hypodermis, basal epithelium, hair follicle "bulge region" Regeneration of various cell lines Keratinocyte stem cells, mesenchymal stem cells, skin-derived precursor cells

 

Along the upper portion of the hair follicle, superficial to what will become the upper cutaneous plexus of blood and lymphatic vessels, one or more small out buddings of the epithelial follicular sheath develop into the dermal sebaceous glands. These glands generate a lipid-rich material (sebum) that rises to the skin surface alongside the hair shaft, lubricating the skin and occluding the shaft. Deeper along the hair follicle below the forming vascular plexus, mesodermal cells give rise to smooth muscle fibers which develop into the arrector pili muscles.(16) These muscle fibers are anchored to the follicle at the “bulge region” of the outer root sheath and superficially to connective tissue beneath the basement membrane, such that a sebaceous gland is often located between the muscle and the hair follicle. Activation of these muscles results in the hairs becoming more vertical and a small amount of sebum being expressed from the glands between the shaft and muscle.

A single hair follicle with its associated sebaceous gland(s), arrector pili muscle, and papilla is termed a pilosebaceous unit. Arrector pili muscles may attach to several adjacent fol- licles within a follicular unit consisting of 2-6 follicles. Pilosebaceous units serve as reservoirs of Langerhans cells. They are normally absent from the glabrous skin of the palms and soles. Pilosebaceous units differ between the scalp and beard region (terminal units), the axilla and groin (apopilosebaceous units), the face, back, and chest (sebaceous units), and the remainder of the skin (vellus units). Vellus hair follicles extend to the upper or middle reticular dermis, while terminal hair follicles and surrounding dermis protrude down through the interface with the hypodermis.

Eccrine sweat glands (“true” sweat glands) develop over most parts of the skin, beginning in a similar manner to hair follicles with an extension of germinative epidermal cells down into the developing dermis. The coiled secre- tory gland is located at or below the level of the hair follicle bulb, with a relatively straight dermal portion of duct becoming a spiraled duct as it passes through the epidermis (the acrocyringium).

Apocrine sweat glands develop normally as a third bud from hair follicles, superficial to the sebaceous glands. These are notably present in the axilla and pubic regions, areola and nipple of the breast, eyelids, and circumanal region. With the exception of the modified apocrine glands forming the ciliary glands in the eye- lids and the ceruminous glands in the auditory canal, these specialized structures do not begin development until puberty. Other distinguishing features are that the secreted product of apocrine glands normally exit the skin from the hair follicle and includes remnants of the secretory vesicles which are released from the glandular cells. The milk-producing mammary glands are modified apocrine glands. Myoepithelial cells arising from the basal layer of the glands provide a smooth muscle shroud that can squeeze the contents of the gland out through the duct.(17)

Multipotential hematopoietic stem cells arising from the fetal liver and bone marrow give rise to mast cell committed progenitors, which interact with fibroblasts in their environment to determine their differentiation into connective tissue mast cells which are found associated with blood vessels, nerves, and skin appendages of the subpapillary dermis.(18)

III. Dermal-epidermal junction

The boundary separating the epidermis from the dermis is marked by a basement membrane, occupied along its superior border by basal keratinocytes, which bind to basement membrane anchoring filaments. On the inferior aspect of the basement membrane are anchoring fibrils attaching into the extracellular matrix of the papillary dermis. Including the anchoring elements, the “basement membrane zone” is typically described as having four layers:

  • A basal keratinocyte hemidesmosome layer
  • The lamina lucida
  • The lamina densa
  • A lamina reticularis (or fibroreticularis)

The epidermis extends into the papillary dermis at regular intervals to form rete pegs, thus increasing the amount of contact between epidermis and dermis. The rete pegs deepen following term birth. On the palms and soles, the dermal-epidermal boundary forms extended ridges and troughs termed friction ridges, most prominently visible at the fingertips (fingerprints).(19)

IV. Hypodermis and Dermal

The loose connective tissue beneath the dermis is termed the hypodermis or subcutaneous layer. A prominent feature of this layer is adipocytes (fat cells) organized into prominent lobules separated by fibrous septa containing the blood and lymphatic vessels. Fibroblasts, macrophages, mast cells, and mesenchymal stem cells are also found in the hypodermis. A thin layer of smooth muscle termed the tunica dartos scroti (male) and tunica dartos labia majora (female) is found within the subcutaneous fascia of the genital region, where it will contract in response to cold temperatures to tighten and wrinkle the skin. Muscle fibers are also found in reticular dermis adjacent to the nipple, in the penis, and perineum. Immediately beneath the hypodermis is a more densely fibrous deep fascia. Human skin attaches to underlying skeletal muscle groups indirectly via small fibrous bands termed skin ligaments (retinacular ligaments), extending through the hypodermis to connect the deep reticular dermis with the underlying fascia.(20) Although widely distributed, the skin ligaments are not uniform across the body. In the upper trunk, limbs, head, and neck, the ligaments provide a close association with underlying muscles. Elsewhere, such as the abdominal region and buttocks, attachments are less dense. In particular regions these ligamentous structures are prominent, as with Cooper’s suspensory ligaments in the breast. Various degrees of tethering create greater or lesser limits to the movement of skin over the underlying fascial planes.

The depth of sharp debridement can be gauged by key differences in the appearance of these distinctive layers. Bleeding occurs at the papillary dermis and deeper, white collagen bundles are prominent in the reticular dermis, yellow bundles of adipocytes mark the hypodermis, while fascial planes, ligaments, and muscle fibers indicate the lower boundary of the skin.

V. Vascularization

The epidermis contains no blood vessels (Figure 2). Nutrients arrive by diffusion from capillaries in the papillary dermis, while oxygen arrives both by diffusion through tissue and by direct uptake from the atmosphere. It is currently estimated that atmospheric oxygen penetrates to a depth of 250 – 400 mm, which includes the full epidermis and much of the papillary dermis.(21) Atmospheric oxygen flux through skin decreases when more skin capillaries open up, but shutting off capillary flow results in only a small increase in oxygen flux directly from the atmosphere.(22) Thus a lack of vascular perfusion cannot be overcome by direct diffusion except under hyperbaric conditions.

 

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