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BASIC SCIENCE

Basic physiology of the skin Stratum basale (basal cell layer)


This layer is generally only one cell thick, but in glabrous skin
and hyperproliferative epidermis it can be two to three cells
Matt Venus
thick. The main cell type is the keratinocyte that may be dividing
Jacqueline Waterman or non-dividing. Melanocytes are present in the basal layer and
Ian McNab make up 5e10% of the cell population.

Stratum spinosum (spinous or prickle cell layer)


Basal cells move towards the surface and form a layer of poly-
Abstract hedral cells which are connected by desmosomes. These are the
This article aims to increase the knowledge of the surgical trainee of both the ‘prickles’ seen under the microscope. Within this layer Langer-
anatomy and the physiological functions of the skin. The skin is often clas- hans cells can be identified.
sified as the largest organ of the body and it is one that all surgeons will oper-
ate on or through. It is therefore vital that the surgeon understands the layers Stratum granulosum (Granular cell layer)
of the skin and the structures that are found within these layers. The skin can Keratinocytes in the granular layer contain intracellular granules of
be injured in a number of situations including burns. It is important to under- keratohyalin. The cytoplasm also contains smaller lamellated
stand how these injuries can affect the physiological function of the skin, for granules (Odland bodies). The cells discharge their lipid compo-
example with fluid loss. The skin has interesting biomechanical properties nents into the intercellular space which plays an important role in
and demonstrates anisotropy, which are important concepts to understand barrier function and intercellular cohesion within the stratum
especially in relation to siting of incisions. Finally, by having a thorough corneum.
understanding of the skin the surgeon will be able to understand how
disease processes affect the different components of the skin. Stratum corneum (horny layer)
This is the outermost layer of the epidermis. It is comprised of
Keywords Anatomy; biomechanics; physiology; skin cells that have migrated from the stratum granulosum. The cells
(now called corneocytes) have lost their nuclei and cytoplasmic
organelles. The cells appear flattened and the keratin filaments
The integument is often said to be the largest organ in the body, align into disulphide cross-linked macrofibres. This layer may be
comprising 16% of total body weight. The word ‘integument’ is several cells thick on the palms and the soles, but is less thick
derived from the Latin integere, meaning to cover. This covering is elsewhere. In palmoplantar skin there is an additional zone, the
the only organ that almost all surgeons will operate either on or stratum lucidum. The cells found in this layer are still nucleated
through in their patients, so an understanding of the anatomy and and are termed transitional cells. The time from cell division to
physiology of skin is fundamental. For those surgeons dealing with shedding from the horny layer is approximately 28 days, but this
skin grafts, skin flaps and burns it becomes particularly pertinent to can be altered in various disease processes.
daily practice. This article discusses the anatomy and the physio-
logical functions of the skin in terms of protection, sensation, Dermis
circulation, and biomechanics.
The dermis is bounded externally by its junction with the epidermis
and internally by subcutaneous fat. The dermis varies widely in its
Anatomy
thickness being less than 1 mm thick on the eyelids but over 5 mm
Epidermis on the back. The dermis is a tough, resilient layer that protects the
The skin consists of two layers, the epidermis and the dermis. body against mechanical injury and contains specialized structures.
Epidermis is a terminally differentiated stratified squamous epithe- The papillary dermis is the thin upper layer of the dermis.
lium, the major cell type of which is the keratinocyte. Keratinocytes This lies below and interdigitates with the epidermal rete ridges.
synthesize keratin, a protein-containing coiled polypeptide chains Deeper to this is the reticular dermis.
which combine to form supercoils of several polypeptides linked by Being connective tissue, the dermis contains cells, ground
disulphide bonds between adjacent cysteine amino acids. Kerati- substance and fibres. The ground substance consists of poly-
nocytes also produce cytokines in response to injury. The epidermis saccharides and proteins which interact to produce hygroscopic
may be divided into four layers (Figure 1). proteoglycan macromolecules. The cells are fibroblasts that
synthesize collagen and elastin fibres. Collagen represents 75% of
the dry weight and up to 30% of the volume of the dermis. Seventy-
five percent is type I collagen and 15% type III collagen.
Matt Venus FRCS (Plast) is a Hand Fellow at the Nuffield Orthopaedic
The properties of collagen change both qualitatively and
Centre. Oxford, UK. Conflicts of interest: none declared.
quantitatively with ageing.
Elastin fibres are also present within the dermis and these
Jacqueline Waterman FRCS (Trama & Orth) is a Hand Fellow at the Nuffield
provide a degree of elasticity to the skin.
Orthopaedic Centre. Oxford, UK. Conflicts of interest: none declared.

Nails
Ian McNab FRCS (Trauma & Orth) is a Consultant Hand Surgeon at the
Nuffield Orthopaedic Centre. Oxford, UK. Conflicts of interest: Nails serve to protect the fingertips, improve tactile sensation
none declared. and are useful for scratching the skin. They have also assumed

SURGERY 29:10 471 Ó 2011 Elsevier Ltd. All rights reserved.


BASIC SCIENCE

Skin structure and function

LAYER STRUCTURE FUNCTION


Surface
Hair Display and attraction;
thermal properties
Stratum corneum Barrier protection against
(horny layer) unregulated loss of salt and
water and entry of particles
(e.g. chemicals, microbes)
Granular layer Adhesion, cytokine production,
(keratinocytes) keratin production, production
Epidermis of vitamin D
Sebaceous gland Waterproofing and moisturizing

Lymphatic Drainage and removal of


particulate waste
Basement Adhesion of epidermis to
membrane underlying zone supporting
dermis
Basal cell layer Reduplication and repair

Melanocyte Protection against ultraviolet


Subpapillary radiation
network
Arterioles and Delivery of nutrients
venules and removal of waste;
Dermis
temperature regulation
Deep vascular
network
Hair follicle
Eccrine: temperature regulation
Sweat gland Apocrine: production of
pheromones
Dermis and Strength with suppleness,
subcutaneous fat shock absorption, insulation

Figure 1

a cosmetic importance in society. The nail itself is more Protection by skin


correctly termed the nail plate and is made of keratin. It arises
Protection as a physical barrier
from under the nail fold and grows along the nail bed. It is
Of the two component parts of the skin, it is the epidermis that
bordered by the paronychium and ends at the hyponychium.
provides protection from the environment. The dermis is very
The hyponychium contains the highest density of dermal
permeable once the epidermis is removed, a fact amply demon-
lymphatics of anywhere in the body. The germinal matrix of the
strated in partial-thickness burns which readily soak overlying
proximal nail bed produces 90% of the nail plate, the remainder
dressings with protein-rich exudate and serve as a focus for
being produced by the sterile matrix of the distal part which
invasive infection. The stratum corneum layer of the epidermis is
provides adherence for the nail. The roof of the nail fold gives
relatively impermeable owing to two main factors. Firstly, the
the nail its sheen.
keratinocytes are arranged in a scaffold-like lattice, bound
together by the fibrous protein keratohyalin and a histidine-rich
Hair
protein involucrin. Secondly, the intercellular spaces are filled
Hair is also derived from keratin. It arises from hair follicles which with a lipid-rich matrix arranged in a laminar fashion providing
comprise a hair bulb, a papilla, associated sebaceous and sweat a robust and waterproofing barrier. However, it is important to
glands and an arrector pili muscle. There are three phases of hair appreciate that the skin is not completely impervious to
growth. In anagen, hair actively grows. Anagen lasts approxi- absorption. In fact most materials will cross the skin barrier, but
mately 1000 days in men and 2e5 years longer in women. In will do so at different rates. For example, skin is relatively
catagen, the hair follicle degenerates, a process taking 2e3 weeks. impermeable to polar molecules such as water, sodium, potas-
In telogen, the hair is shed and the follicle enters a resting phase sium and other ions in solution but more highly permeable to
that lasts 3e4 months. Ten percent of hairs are usually in this aliphatic alcohols. Furthermore, different body sites are differ-
phase leading to 50e100 hairs falling out on a daily basis. entially permeable, the face, forehead and dorsum of the hand

SURGERY 29:10 472 Ó 2011 Elsevier Ltd. All rights reserved.


BASIC SCIENCE

being the most permeable, the palms of the hand being the least Function of skin in sensation
permeable.
Cutaneous innervation is highly complex and is involved in
Protection by immune functions perception of external stimuli, thermoregulation and sociosexual
The skin functions as a first line of defence against invading communication.
microorganisms. The mechanisms by which it is able to do this
include the production of anti-microbial peptides, resident Sensory afferent modalities include touch, vibration, tempera-
epidermal Langerhans cells, and transient epidermal T-cells. In ture, pressure, pain and itch. Various receptors detect and transmit
addition, the dryness of the outer layer of the epidermis and the stimuli to the central nervous system. In hairless (glabrous) skin,
continual shedding of keratinocytes assists in preventing any Meissner’s corpuscles detect changes in light touch and vibration.
sustained growth of organisms on the skin. Merkel cell receptors detect light touch and sustained pressure. In
the deep dermis and subcutaneous fat, Pacinian corpuscles detect
Anti-microbial peptides (AMPs) are produced by the viable pressure and vibration changes and Ruffini receptors detect skin
cells of the epidermis. They are a group of peptides that kill stretch and contribute to joint position sense. Meissner’s and
Gram-positive and Gram-negative organisms, fungi and some Pacinian corpuscles are quickly-adapting receptors, responding at
viruses. There are two major families, the defensins and the the onset and end of a stimulus. Merkel cell and Ruffini receptor are
cathelicidins. The defensins are further grouped as either a or b. slowly-adapting receptors, giving a continuous response
The cathelicidins have a broad spectrum of anti-microbial throughout the stimulus. Detection of the sensation of pain is
activity and act as chemoattractants for a range of inflamma- nociception and can be defined as appreciation of a stimulus that
tory cells. can could cause tissue damage. Pain receptors are free nerve
endings and are polymodal in their function, that is they can detect
Langerhans cells function as antigen-presenting cells (APCs). a number of stimuli (e.g. pain, heat, cold, chemical injury). Itch is a
Following injury to the epidermis, Langerhans cells undergo complex sensation that is poorly understood. It can be defined as
changes that allow them to leave the epidermis, enter dermal a sensation that produces the urge to scratch and is mediated by
lymphatics and migrate to the paracortical areas of draining lymph c-fibres. It has been classified as pruricoceptive (dermatitis),
nodes. Here they present antigen-MHC class II-complexes to T-cells. neuropathic (multiple sclerosis), neurogenic (cholestasis), mixed
Interestingly, the T-cell blasts then return to the site of the antigen (uraemia) or psychogenic (Twycross). A low-intensity stimulus
source in the skin. may be perceived as a tickle and the sensation of itch probably has
its origins in the need to rid the body of parasites. However, chronic
T-cells are transient in the epidermis and are typically found itch can be extremely disabling to a patient.
around post-capillary venules in the dermis and around the skin Thermoreceptors exist for cold and warmth as free nerve
appendages. endings, irregularly distributed in the skin. Cold receptors
Dysfunction of the immune system in the skin is an impor- are activated when the body temperature falls by 1e20 below core
tant factor in wound healing and in conditions such as temperature. Warmth receptors maintain a steady action potential
dermatitis, bullous disorders, psoriasis and cutaneous T-cell discharge between 34 and 45 , but increase in frequency with
lymphoma. increasing temperature. At over 45 , heat is perceived as pain.
Changes in temperature tend to produce changes in behaviour to
conserve or lose heat e.g. turning on the heating or taking off
Protection from ultraviolet (UV) radiation
a jumper. However, large or sustained changes in temperature may
Ultraviolet radiation is composed of electromagnetic energy with
produce efferent effects such as sweating or shivering.
wavelengths from 400 nm to 200 nm. The UV spectrum is divided
into UVA (400e315 nm), UVB (315e290 nm) and UVC
The skin circulation
(290e200 nm). UVA radiation is responsible for actinic (ageing)
damage to the skin and can act as a co-carcinogen with UVB radi- An angiosome is a composite block of tissue with overlying skin that
ation. UVB radiation is responsible for sunburn and can induce skin is supplied by an underlying source artery and associated draining
cancer. The oncogenic effect occurs as a result of photochemical veins. The body is composed of numerous angiosomes that fit
damage to epidermal cell DNA, damage to DNA repair mechanisms together like a jigsaw. The angiosomes are linked by communi-
and suppression of cell-mediated immunity. The tumour cating vessels (choke arteries and oscillating veins) that allow blood
suppressor gene p53 has been found to be mutated in over 90% of flow between them under certain circumstances. The skin itself is
squamous cell carcinomas of the skin. UVC radiation is highly supplied by arteries that arise from their underlying source vessels
carcinogenic, but is mostly absorbed by the ozone-rich strato- that are either destined specifically for the skin (direct perforators)
sphere. With ozone depletion, UVC radiation may become a more or from secondary branches of vessels that supply other underlying
important factor in skin cancer in the future. tissues (indirect perforators). En route to the skin, the vessels form
The skin functions as a protective layer for UV radiation in plexuses that lie in different body planes: subfascial, suprafascial,
two ways. The stratum corneum reflects radiation, so reducing subdermal, subepidermal. This knowledge of the blood supply to
the exposure dose. Sun exposure increases the activity of mela- the skin has revolutionized reconstructive plastic surgery and
nocytes, the number of melanosomes produced and the rate of allowed the design of versatile skin flaps.
transfer of melanin to the epidermal keratinocytes. This helps to The blood supply of the dermis far outstrips that which is
decrease absorption of UV radiation by DNA and cellular required for its nutritional needs. A system of arteriovenous
constituents. shunts enables blood flow to be redistributed to the subdermal

SURGERY 29:10 473 Ó 2011 Elsevier Ltd. All rights reserved.


BASIC SCIENCE

capillary and venous plexuses which act as reservoirs for cuta-


neous blood flow: flow can be varied from as little as 1 to as Stress strain curve
much as 150 ml/100 g skin/minute. The control of this blood
flow is both systemic, via neural and humoural mechanisms, and
local. There exists a continuous vasoconstrictor tone in cuta-
neous blood vessels, vasodilation occurring through a reduction
in constrictor tone and not through any known vasodilatation

Stress (force)
efferent pathway. Vasoconstriction is mediated via a-adrenergic
receptors and vasodilatation through b-adrenergic receptors at
the level of arterioles and arteriovenous anastomoses. Examples
of systemic (humoural) vasoconstrictors included adrenaline,
noradrenaline, serotonin, thromboxane A2 and prostaglandin-
F2a; vasodilators include prostaglandin-E1, -I2, histamine and
bradykinin. Skin also maintains an element of autoregulation of
its blood flow through local factors. Local factors producing
vasodilatation include hypercapnia, acidosis, hypoxia, hyper- Strain (change in length)
thermia and reduced perfusion pressure.

Biomechanical properties of skin Figure 2

The skin has interesting biomechanics properties. It shows prop-


erties both of elasticity of solids and viscosity of fluids
i.e. viscoelasticity in response to a deforming force, usually stretch. squeezed out between the fibres. Once the collagen fibres are at
Skin is anisotropic, which means that its elasticity variation is maximal length, the force required to produce further strain
dependent on the direction in which a force is applied. This was increases markedly. Furthermore, the effect of deformation on the
demonstrated by Langer who stabbed the skin of cadavers with an skin is time-dependent. A slowly applied constant force will result
awl. The wounds produced were not circular, but fell into ellipses in a hyperplastic response in skin and skin expansion. This
that when joined formed lines of cleavage in the skin: ‘Langer’s property is called ‘creep’. The corollary of creep is ‘stress-relaxa-
lines’. It is along these lines that skin incisions may leave the best tion’, which is where a force required to keep skin at a certain
scar. length decreases with time. However, if a force is applied too
The skin’s response to being stretched is non-linear. If the force rapidly then the collagen fibres will rupture. This is seen clinically
applied to skin (stress) is plotted against the change in length in pregnancy where a relatively rapid increase in the volume of the
(strain), a graph similar to (Figure 2) is seen. Initially, a small force abdomen can lead to rapid stretch and dermal injury, manifesting
produces a large change in length. This is primarily due to align- as stretch marks. Skin expansion is an important technique in
ment of the elastin fibres in the dermis. A greater force is required plastic surgery that allows the generation of autologous tissue by
to deform the skin, which corresponds to a change in orientation of the gradual inflation of a subcutaneous silicone device, for
collagen fibres and displacement of extracellular matrix as it is example in breast reconstruction. A

SURGERY 29:10 474 Ó 2011 Elsevier Ltd. All rights reserved.

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