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BASIC SCIENCE

Structure and function of in diseases such as psoriasis. Melanocytes, which are dendritic
cells derived from the neural crest, also sit in the basal layer.

skin, hair and nails Melanocytes synthesize melanin, which is packaged in subcel-
lular organelles (melanosomes) and then transported to the
neighbouring basal keratinocytes. The melanosomes form a
Joey E Lai-Cheong
‘melanin cap’ that protects basal keratinocyte nuclei from
John A McGrath harmful ultraviolet radiation. There is little racial variation in the
number of melanocytes. Skin colour is determined by the num-
ber and size of the melanosomes and the nature of the melanin
(eumelanin versus pheomelanin).2 The outermost stratum cor-
Abstract neum (cornified layer) is composed of about 10 layers of flat-
The skin is the largest organ of the human body. It is a complex epithelial
tened corneocytes, although it is thicker on the palms and soles.
and mesenchymal tissue comprising a multilayered stratified epidermis,
These cells are embedded within a hydrophobic extracellular
adnexal structures such as hair follicles, sweat glands and sebaceous
matrix derived from lipid precursors and lipid hydrolases, which
glands, a dermis containing collagen and elastic fibres, and underlying
are both secreted by lamellar bodies present within the subjacent
subcutaneous fat. More than 1000 disease entities involving the skin
granular layer.3 These hydrolases cleave the lipid precursors
have been described and up to 20% of all patient referrals to general
resulting in the formation of fatty acids, cholesterol and at least
practitioners involve skin pathology. Diseases such as psoriasis, eczema,
10 ceramides. These lipid components then organize themselves
urticaria and skin cancer impose a considerable burden on healthcare re-
into lamellar bilayers that integrate between the corneocytes,
sources and impact significantly on patients’ quality of life. Knowledge of
provide a watertight seal and maintain epidermal barrier
the structure and function of the skin and its appendages is paramount to
integrity.4
understanding the biology of healthy skin and the pathophysiology of
Langerhans cells are bone marrow-derived, antigen-present-
skin diseases.
ing dendritic cells and may be found throughout the epidermis.
Merkel cells within the epidermis transmit sensory information
Keywords dermis; epidermis; hair follicles; keratinocytes; melanocytes; from the skin to sensory nerves.
nail apparatus; subcutaneous fat
Dermaleepidermal junction
The epidermis is separated from the dermis by the cutaneous
basement membrane zone (BMZ) (Figure 2). Although less than
Structure of the skin 200 nm across, this region of skin is composed of an intricate
network of macromolecules that link the keratin intermediate fil-
The skin accounts for about 15% of the total body weight of an aments of basal keratinocytes with collagen fibres in the superfi-
adult and has a surface area of about 2 m2. In a 70-kg adult, the cial dermis. The main function of the proteins and glycoproteins
skin weighs about 13 kg, making it the largest organ in the within the BMZ is to provide adhesion between the epidermis and
human body. Skin consists of three main zones (Figure 1a): the dermis. Defects in these molecules result in skin blistering.5,6
 epidermis
 dermis Dermis
 subcutis. The dermis is 0.5e5 mm thick, depending on body site: a thin
Skin diseases can affect each region of the skin. dermis is found on the eyelid and a thick dermis is present on
back skin. It is subdivided into two main layers:
Epidermis
 papillary dermis, which is in contact with the BMZ and is
The epidermis is the outermost layer of the skin. The principal
richly supplied by blood vessels and sensory nerve
cell is the keratinocyte (95% of cells). Melanocytes, Langerhans
endings.
cells and Merkel cells account for the remaining 5%. The
 reticular dermis, which is the principal part of the dermis
epidermis is divided into four main layers depending on the state
that is in contact with the subcutis.
of keratinocyte differentiation (Figure 1b).
The dermis is composed of interstitial (collagen fibres, elastic
The basal layer consists of a single layer of keratinocytes.
tissue and ground substance) and cellular (fibroblast, mast cell,
These cells proliferate and commit daughter cells to terminal
plasma cell, lymphocytes, dermal dendritic cell and histiocyte)
differentiation, which ends in the formation of the stratum cor-
components. It also contains blood vessels (superficial and deep
neum.1 This process normally takes about 40 days but is shorter
plexi), lymphatic channels and sensory nerves (free nerve end-
ings and end corpuscles, which include Pacinian corpuscles that
sense vibration, and Meissner corpuscles, which are responsible
Joey E Lai-Cheong BMedSci(Hons) MBBS PhD MRCP is a Consultant for tactile and pressure sensations).
Dermatologist at King Edward VII Hospital, Windsor, UK. Competing About 70% of the dry weight of the dermis is made up of
interests: none declared. collagens,7 of which the predominant types are types I and III.8
Elastic fibres are less tough than collagen fibres but impart
John A McGrath MD FRCP FMedSci is Professor of Molecular Dermatology at extensible properties to the skin. They account for about 5% of
St John’s Institute of Dermatology, King’s College London, UK. the dry weight of the dermis and consist of elastin and elastic
Competing interests: none declared. microfibrils (e.g. fibrillin).

MEDICINE 41:6 317 Ó 2013 Elsevier Ltd. All rights reserved.


BASIC SCIENCE

Fibroblasts are derived from the mesenchyme. The dermis


Rete ridges Melanocytes also contains histiocytes, antigen-presenting cells that
a
Hair follicle Dermal phagocytose and degrade foreign substances and present
blood antigens to T cells. Mast cells are distributed near dermal
b vessels blood vessels and are responsible for the secretion of che-
motransmitters such as histamines during an allergic reac-
tion. Within the dermis there are 1.5e4  106 sweat glands,
which are subdivided into eccrine and apocrine glands. Most
thermoregulatory sweating and sweat fluid comes from
eccrine glands.

Subcutis
The subcutis is the innermost layer of the skin and is composed
of lipocytes. The lipocytes are arranged into fat lobules, which
are separated from one another by fibrous septae. Bundles of
fibres originating from the dermis into the subcutis strengthen
Sweat glands the connection between these two compartments. In non-obese
Arrector pili subjects, about 80% of all body fat is located within the
subcutis.

Structure of hair
(a) Haematoxylin and eosin staining of normal skin (chest) shows the three
layers of the skin, namely the epidermis, dermis and subcutis. Adnexal Humans have up to 5 million hairs. There are three types of hair:
structures such as hair follicles, arrector pili muscle and sweat glands are
clearly seen. (b) Higher magnification of normal skin shows the four principal  lanugo hair, which is shed soon after birth
layers of the epidermis. Melanocytes are scattered within the basal layer of  vellus hair, which is fine hair distributed mostly over the
the epidermis (bar = 50 µm).
body
 terminal hair, which is longer and coarser.
Figure 1 Fewer than 2% of men and 45% of women go through life with a
full head of hair.
Collagen and elastic fibres are bathed in a gelatinous sub- The hair follicle is a complex epithelial structure (Figure 3).
stance called ground substance, which is composed of pro- It is surrounded by an outer hair root sheath, which helps
teoglycans and glycoproteins. protect the growing hair, and an inner hair root sheath, which
The fibroblast is the predominant cell type in the dermis. follows the hair shaft up to the opening of the sebaceous gland.
It secretes collagens, elastic fibres and ground substance. The base of the hair follicle consists of the dermal papilla,
which is richly supplied by blood vessels and sensory nerves.
Within the hair papilla resides the hair bulb, which is the site
Dermal–epidermal junction where the growing hair originates. An important structure
Hemidesmosomes
within the hair follicle is the hair bulge, which has been
shown to harbour both epithelial and melanocytic stem cell
Keratin intermediate
populations (the former generate hair follicles, sebaceous
filaments
glands and, during wound healing, the interfollicular epithe-
lium). The hair bulb is the site of insertion of the arrector pili
muscle. Contraction of the arrector pili muscle leads to
‘goosebumps’.
Hair consists of three concentric areas:
 the cuticle, which is the outer covering of the hair
 the cortex, which is the largest portion of the hair and
imparts strength to the hair shaft
 the medulla, which is the central area of the hair and is not
200 nm always present.
Hair typically grows 10e15 mm per month. Its growth is dynamic
and consists of three phases:
 an anagen phase during which the hair is actively growing;
Lamina densa about 84% of hairs are in the anagen phase, which lasts
Anchoring fibrils 3e10 years
Ultrastructure of the cutaneous basement membrane zone by transmission  a catagen phase during which the hair stops growing but
electron microscopy. cellular activity still continues within the germinal centre
of the hair follicle; about 1% of hairs are in the catagen
Figure 2 phase, which lasts 2e3 weeks

MEDICINE 41:6 318 Ó 2013 Elsevier Ltd. All rights reserved.


BASIC SCIENCE

Structure of hair and associated adnexal components External architecture of the nail

Free edge of nail


Yellow line of Pinkus
Epidermal layers
Distal pink zone
Onychocorneal band
Basal layer
Accentuation of
Infundibulum nail bed erythema
Nail wall
Outer root sheath Sebaceous Proximal pink zone
gland
Lunula

Cuticle
Inner root sheath Hair follicle stem cells
Proximal nail fold

Hair shaft

Figure 4

 the nail bed e this is found at the base of the nail plate on
Dermal Hair follicle
which the latter rests. It is tightly connected to the nail
papilla matrix
plate and is continually keratinized to maintain adhesion.
Fingernails grow by about 3 mm/month, whilst toenails grow
more slowly.
Lineages derived from bulge stem cells
Differentiation pathways supplied by bulge stem cells Function of skin, hair and nails

This figure also defines the major source of stem cells within the follicular  Skin provides a physical barrier against the external
bulge. These cells can give rise to hair follicles, sebaceous glands and environment and helps reduce water loss by means of the
interfollicular epidermis. water-impermeable stratum corneum. The stratum cor-
neum also helps against the penetration of irritants and
Figure 3 other allergens that can cause skin inflammation, such as
in dermatitis.
 Skin contributes to innate and adaptive immunity.
Keratinocyte-derived endogenous anti-microbial peptides
 a telogen phase, which is the final stage during which there
such as defensins and cathelicidins are active against a
is no growth of hair or activity at the hair bulb; about 15 %
variety of bacteria, viruses and fungi.9 The sweat-derived
of hairs are in the telogen phase, which lasts 3e4 months.
dermcidin has been shown to have potent anti-microbial
In humans, these three phases occur simultaneously in different
activity against Staphylococcus aureus, Escherichia coli
hairs. Every human hair typically undergoes 10e20 complete
and Candida. The skin has a network of Langerhans cells,
cycles of anagenecatagenetelogeneanagen during an average
which act as sentinel cells to initiate immune responses
lifetime.
against microbial threats.
 The skin is important for thermoregulation. Regulation of
Structure of nail
heat loss is achieved by vasodilatation and vasoconstric-
Like hair, the nail is a keratinized epithelial structure (Figure 4) tion of both cutaneous superficial and deep vascular plexi.
and consists of: Thermoregulation is also achieved by sweating produced
 the nail plate e this is a rectangular convex plate of ker- by eccrine sweat glands.
atinized cells (onychocytes), which develops from the nail  The skin is important for sensory perception due to its rich
matrix outwards supply of free nerve endings and end corpuscles.
 the nail matrix e this is a wedge-shaped structure that  Skin is important for the synthesis of vitamin D and
contains a highly specialized epithelium consisting of thereby contributes to bone formation, calcium meta-
keratinocytes, and which generates the nail plate bolism, and aspects of immune regulation.
 the nail folds e these consist of a proximal and a lateral  The subcutaneous fat is important in cushioning trauma,
nail fold, which covers the sides of the nail plate and the providing insulation and is an important energy reserve. It
nail bed also has an endocrine function.

MEDICINE 41:6 319 Ó 2013 Elsevier Ltd. All rights reserved.


BASIC SCIENCE

 Nails protect the digits as well as participating in sensory 5 Fassihi H, Wong T, Wessagowit V, et al. Target proteins in inherited,
perception. and acquired blistering skin disorders. Clin Exp Dermatol 2006; 31:
252e9.
Conclusions 6 Lai-Cheong JE, Arita K, McGrath JA. Genetic diseases of junctions.
J Invest Dermatol 2007; 127: 2713e25.
The skin is a complex self-regenerating epithelial and mesen-
7 Gniadecka M, Nielsen OF, Wessel S, et al. Water and protein structure
chymal tissue. Knowledge of the structure of the skin and its
in photoaged and chronically aged skin. J Invest Dermatol 1998; 111:
appendages is essential in order to appreciate and understand the
1129e33.
wide variety of skin diseases faced by medical practitioners. A
8 Oikarinen A. The aging of skin: chronoaging versus photoaging.
Photodermatol Photoimmunol Photomed 1990; 7: 3e4.
9 Schittek B, Paulmann M, Senyurek I, et al. The role of antimicrobial,
REFERENCES peptides in human skin and in skin infectious diseases. Infect Disord
1 Candi E, Schmidt R, Melino G. The cornified envelope: a model, of cell Drug Targets 2008; 8: 135e43.
death in the skin. Nat Rev Mol Cell Biol 2005; 6: 328e40.
2 Lin JY, Fisher DE. Melanocyte biology and skin pigmentation. Nature
2007; 445: 843e50.
3 Elias PM, Menon GK. Structural and lipid biochemical correlates, of the Acknowledgements
epidermal permeability barrier. Adv Lipid Res 1991; 24: 1e26.
4 Elias PM, Wakefield JS. Therapeutic implications of a barrier-based Figures courtesy of St John’s Institute of Dermatology (King’s
pathogenesis of atopic dermatitis. Clin Rev Allergy Immunol 2011; 41: College London).
282e95.

MEDICINE 41:6 320 Ó 2013 Elsevier Ltd. All rights reserved.

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