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Peer Review

Peer Reviewed

Case Q&A

Skin Anatomy

Stephen M Milner, MBBS, BDS, DSc (Hon), FRCSE, FACS

June 2023
1937-5719
ePlasty 2023;23:QA8

Questions

1.  What are the structural layers of the unburned skin of the arm?

2.  How is the epidermis configured?

3. How is the structure of the dermis organized?

4. How is skin prevented from shearing?

Case Description

A 56-year-old male sustained a deep flame burn to his trunk following a propane explosion at his home (Figure 1). 

Figure 1
Figure 1. Appearance on presentation in the burn unit. 

 

Q1. What are the structural layers of the unburned skin of the arm?

Most organs are composed of 3 different types of tissue that are grouped together: an avascular cellular epithelium that spontaneously regenerates, a basement membrane of thin extracellular matrix (ECM), and a supporting vascular stroma comprising ECM that does not regenerate (Figure 2A).1 These are referred to as the tissue triad. 2 In the skin, these layers constitute, respectively, the epidermis, a basement membrane zone (BMZ), and the dermis, which rests on the hypodermis that contains abundant fat (Figure 2B). 3 The BMZ incorporates the zone of adherence between the basal layer of the epidermal keratinocytes and the dermis, whereas the term basement membrane refers to the structure seen with routine staining under light microscopy. Injury confined to the epithelium is followed by regeneration of missing tissue that is anatomically and functionally normal. If the basement membrane is breached, however, tissue continuity occurs by repair, with contraction and formation of scar tissue. 

Figure 2
Figure 2. (A) The anatomical distribution of the layers of the tissue triad. Epithelia are found in the skin, the exocrine glands, and the nervous and endocrine systems. They line the genitourinary, respiratory, and gastrointestinal tracts as well as the pericardial, pleural, and peritoneal cavities and constitute the endothelial cells of the cardiovascular system. The stroma contains bone, cartilage, their associated cells and collagen, elastin, and fibroblasts. (B) Structure of the skin.

Q2. How is the epidermis configured?

The epidermis is a stratified epithelium. The portion of the epidermis between the pilosebaceous units (the hair follicle and sebaceous gland) is called the interfollicular epidermis and is composed of keratinocytes delineated by cell size, shape, nucleation, and keratin expression (Fig 3). Signaling pathways for the growth and differentiation of skin require molecular interactions between cells, which requires correct cellular orientation, called polarity.4 The basal layer of cells is anchored to the basement membrane by hemidesmosomes, while the apical side is specialized to differentiate into a keratinized epidermis.

Figure 3
Figure 3. The interfollicular epidermis. Keratinocytes from the basal layer undergo programmed differentiation with enucleation and accumulation of cytokeratins. The stratum lucidum is a clear layer of cells beneath the stratum corneum and is only present in the palms and soles (not shown).

A subpopulation of stem cells in the basal layer undergoes asymmetric divisions, resulting in the renewal of epidermal stem cells and the development of transient amplifying cells. These progenitor cells express keratins K5 and K14 and morph into the suprabasal cells, which express keratins K1 and K10 (keratinization).5 

The cells of the basal layer are cuboidal to columnar with a large nucleocytoplasmic ratio. Above the basal layer is the stratum spinosum in which the high number of desmosomes give a spiny appearance under the light microscope. Keratinocytes in the stratum granulosum are distinguished by (1) membrane-bound keratohyalin granules and (2) lamellar bodies that discharge their lipid contents into the intercellular space, which impedes transepidermal water loss. As the cells become progressively flatter and accumulate keratin and lipid, they transform their plasma membrane from a fluid phospholipid bilayer to a tough, protein-rich cornified cell envelope to form a layer of dead keratinocytes (corneocytes) embedded in a lipid matrix (stratum corneum).6 The epidermis also contains non-epithelial cells. These include antigen-presenting Langerhan’s cells,7 Merkel cells, which are mechanoreceptors that relay tactile discrimination,8 and melanocytes. Melanocytes transfer melanosomes through their dendrites to keratinocytes where they form melanin caps above the nuclei to absorb harmful ultraviolet radiation. Since these are terminally differentiated, deep burns often lead to cutaneous hypopigmentation.9

Q3. How is the structure of the dermis organized?

The much thicker dermis reinforces the epidermis and incorporates the vascular, neural, lymphatic, and adnexa of the skin (hair follicles as well as sebaceous and sweat glands). A superficial papillary zone of thin, loosely packed collagen fibers has dermal papillae with their vascular loops and unmyelinated sensory nerve endings, which interdigitate with epidermal projections called rete pegs (Figure 4). The deeper reticular zone forming most of the bulk of the dermis is composed of ECM, a 3-dimensional complex of extracellular macromolecules that provides scaffolding, growth factors, and other bioactive molecules. The primary cell type is the fibroblast, which produces fibrous proteins and proteoglycans. The fibrous proteins include collagens, elastin, and fibronectin. Collagens provide tensile strength and elastin provides flexibility, both necessary to absorb substantial mechanical forces delivered to the skin. Proteoglycans are composed of glycosaminoglycan (GAG) chains covalently linked to a protein core. They are strongly hydrophilic and form hydrated gels, which give the skin turgor enabling resistance to compressive forces. Fibronectin is an adhesive protein that binds to cells, mainly fibroblasts and endothelial cells, implicating the molecule as an extracellular mechano-regulator. Trans-membrane proteins, integrins, bridge the ECM to the cytoskeleton and interact with matrix ligands to trigger signaling pathways that regulate gene expression and hence cell proliferation, polarity, contractility, adhesion, migration, and apoptosis. The ECM can also sequester and regulate the bioavailability of growth factors and cytokines (Figure 5).10

Figure 5
Figure 4. Hematoxylin and Eosin staining of skin. Shearing is in part prevented at the dermal-epidermal junction by the interlocking of the epidermal rete pegs and the dermal papillae. Inset: mechanism illustrated by egg crate analogy.

Q4. How is skin prevented from shearing?

Figure 4
Figure 5. The extracellular matrix.

The skin is prevented from shearing by: (1) desmosomes and a meshwork of tonofilaments that anchor the keratinocytes to each other, (2) interlocking of the epidermal projections (rete pegs) into the dermis with the dermal papillae (Figure 4), and (3) the basement membrane zone (BMZ).11 The BMZ is the collective name for 4 distinct cell-free and avascular layers, whereby hemidesmosomes from the basal keratinocytes anchor the epidermis to the basal lamina (lamina lucida and lamina densa), which is in turn bound to the sublamina densa (superficial papillary dermis) by fibrils of type VII collagen that form semicircular loops around collagen type I and III in the dermal matrix (Figure 6). Disturbance in expression of genes within the BMZ gives rise to hereditary blistering disorders of the skin (eg, epidermolysis bullosa).11 Immaturity of the hemidesmosomes and anchoring fibrils also contributes to the friability of cultured epithelial autograft in the resurfacing of excised full-thickness burn wounds.12

Figure 6
Figure 6. Schematic representation of the BMZ indicating the extracellular matrix molecules. The 4 layers of the basement membrane zone: (1) basal keratinocyte, containing intermediate keratin filaments and hemidesmosomes [plectin, bullous pemphigoid antigen 1 (BPAg1), bullous pemphigoid antigen 2 (BPAg2/Collagen XVII), and α6β4 integrin]; (2) the lamina lucida consisting of laminin 332 and 311, and the extracellular portions of type XVII collagen, and α6β4 integrin; (3) the lamina densa containing a meshwork of type IV collagen molecules bound to the laminins of the lamina lucida by nidogen proteins; (4) the sublamina densa (superficial papillary dermis) containing fibrils of type VII collagen that weave around collagen I and III fibrils in the superficial papillary dermal matrix.

 

Acknowledgments

Affiliations: Professor of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Retired, Baltimore MD; Director, Johns Hopkins Burn Center, Retired, Baltimore, MD

Correspondence: Stephen M Milner, MBBS, BDS, DSc (Hon), FRCSE, FACS; stephenmilner123@gmail.com

Disclosures: The author discloses no financial or other conflicts of interest.

References

1.        Yannas IV. Nonregenerative Tissues. In: Yannas Ioannis V, ed. Tissue and Organ Regeneration in Adults. Second Edition. Springer; 2015:27-46.

2.        Vracko R. Basal lamina scaffold-anatomy and significance for maintenance of orderly tissue structure. Am J Pathol. 1974;77(2):314-346.

3.        Abdo JM, Sopko NA, Milner SM. The applied anatomy of human skin: A model for regeneration. Wound Medicine. 2020;28:1-10. doi:10.1016/j.wndm.2020.100179

4.        Muroyama A, Lechler T. Polarity and stratification of the epidermis. Semin Cell Dev Biol. 2012;23(8):890-896. doi:10.1016/j.semcdb.2012.08.008

5.        Staniszewska M, Słuczanowska-Głąbowska S, Drukała J. Stem cells and skin regeneration. Folia Histochem Cytobiol. 2011;49(3):375-380. doi:10.5603/fhc.2011.0053

6.        Menon GK, Cleary GW, Lane ME. The structure and function of the stratum corneum. Int J Pharm. 2012;435(1):3-9. doi:10.1016/j.ijpharm.2012.06.005

7.        Romani N, Holzmann S, Tripp CH, Koch F, Stoitzner P. Langerhans cells - dendritic cells of the epidermis. APMIS. 2003;111(7-8):725-740. doi:10.1034/j.1600-0463.2003.11107805.x

8.        Hoffman BU, Baba Y, Griffith TN, et al. Merkel cells activate sensory neural pathways through adrenergic synapses. Neuron. 2018;100(6):1401-1413.e6. doi:10.1016/j.neuron.2018.10.034

9.        Cichorek M, Wachulska M, Stasiewicz A, Tymińska A. Skin melanocytes: biology and development. Postepy Dermatol Alergol. 2013;30(1):30-41. doi:10.5114/pdia.2013.33376

10.      Yue B. Biology of the extracellular matrix: an overview. J Glaucoma. 2014;23(8 Suppl 1):S20-S23. doi:10.1097/IJG.0000000000000108

11.      Christiano AM, Uitto J. Molecular complexity of the cutaneous basement membrane zone. Revelations from the paradigms of epidermolysis bullosa. Exp Dermatol. 1996;5(1):1-11. doi:10.1111/j.1600-0625.1996.tb00086.x

12.      Compton CC. Cultured epithelial autografts: skin regeneration and wound healing. A long-term biopsy study. Skin Res. 1996;38(1):148-159. doi:10.11340/skinresearch1959.38.148

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