Skin and Subcutaneous Tissue

The skin is the largest and among the most complex organs of the body. Although
the skin functions simply as a protective barrier to interface with our environment,
its structure and physiology are complex. The skin protects against
most noxious agents, such as chemicals (by the impermeability of the epidermis),
solar radiation (by means of pigmentation), infectious agents (through
efficient immunosurveillance), and physically deforming forces (by the durability
of the dermis). Its efficient ability to conserve or disperse heat makes
the skin the major organ responsible for thermoregulation. To direct all these
functions, the skin has a highly specialized nervous structure. The palms and
soles are particularly thick to bear weight. The fingertips have the highest density
of sensory innervation and allow for intricate tasks. Even the lines of the
skin, first described by Langer, are oriented perpendicularly to the long axis
of muscles to allow the greatest degree of stretching and contraction without
The skin is divided into three layers: the epidermis, the basement membrane,
and the dermis. The epidermis is composed mainly of cells (keratinocytes),
with very little extracellular matrix. The deep, mitotically active, basal cells are
a single-cell layer of the least-differentiated keratinocytes. Some multiplying
cells leave the basal layer and begin to travel upward. In the spinous layer, they
lose the ability to undergo mitosis. These differentiated cells start to accumulate
keratohyalin granules in the granular layer. Finally, in the horny layer, the
keratinocytes age, the once-numerous intercellular connections disappear, and
the dead cells are shed. The keratinocyte transit time is between 40 and 56
days. The internal skeleton of cells (intermediate filaments), called keratins
in epithelial cells, play an important role in the function of the epidermis.
Intermediate filaments provide flexible scaffolding that enables the cell to
resist external stress. Different keratins are expressed at different stages of
keratinocyte maturation. In the mitotically active inner layer of the epidermis,
the keratinocytes mainly express keratins 5 and 14. Patients with epidermolysis
bullosa simplex, a blistering disease, were found to have a point mutation in
one or the other keratin gene, thus revealing the etiology of one of the more
baffling skin diseases.
Melanocytes migrate to the epidermis from precursor cells in the neural
crest and provide a barrier to radiation. There are 35 keratinocytes for every
melanocyte. The melanocytes produce the pigment melanin from tyrosine and
cysteine. The pigment is packaged in melanosomes and transported to the tips
of dendritic processes and phagocytized by the keratinocyte (apocopation), thus
transferring the pigment to the keratinocyte. The melanin aggregates on the superficial
side of the nucleus in an umbrella shape. The density of melanocytes
is constant among individuals of different skin color. The rate of melanin
production, transfer to keratinocytes, and melanosome degradation determine