BASIC PRINCIPLES

PHYSIOLOGY OF THE
SKIN
CHAPTER 2
LUCTURER :DR HASSAN
MBBS
 CONTINIOUS

The skin is a metabolically active

organ with vital functions [Table 1)
including the protection and
homeostasis of the body.
 Functions of skin

Presents barrier to physical agents

Protects against mechanical injury
Prevents loss of body fluids
Reduces penetration of UV radiation
Helps regulate body temperature
Acts as a sensory organ
Affords a surface for grip
Plays a role in Vitamin D production
Acts as an outpost for immune surveillance Cosmetic
association
 Keratinocyte maturation

The differentiation of basal cells into dead, but

functionally important, corneocytes is a unique
feature of the skin. The horny layer is important
in preventing all manner of agents from entering
the skin, including microorganisms, water and
particulate matter. The epidermis also prevents
the body's fluids from getting out. Epidermal
cells undergo the following sequence during
keratinocyte maturation
 CONTINIOUS

1. Undifferentiated cells in the basal layer and the

layer immediately above divide continuously. Half
of these cells remain in place and half progress
upwards and differentiate.
2. In the prickle cell layer, cells change from being
columnar to polygonal. Differentiating
keratinocytes synthesize keratins which aggregate
to form tonofilaments. The desmosomes
connecting keratinocytes are condensations of
tonofilaments. Desmosomes distribute structural
stresses throughout the epidermis and maintain a
distance of 20 nm between adjacent cells.
 CONTINIOUS

3. In the granular layer, enzymes induce

degradation of nuclei and organelles.
Keratohyalin granules mature the keratin and
provide an amorphous protein matrix for the
tonofilaments. Membrane-coating granules
attach to the cell membrane and release an
impervious lipid containing cement which
contributes to cell adhesion and to the horny
layer barrier.
 CONTINIOUS

4. In the horny layer, the dead, flattened corneocytes

have developed thickened cell envelopes encasing a
matrix of keratin tonofibrils. The strong disulphide
bonds of the keratin provide strength to the stratum
corneum, but the layer is also flexible and can absorb
up to three times its own weight in water. However,
if it dries out (i.e. water content falls below 10%),
pliability fails.
5. The corneocytes are eventually shed from the skin
surface
 Hair growth

In most mammals, hair or fur plays an essential

role in survival, especially in the conservation of
heat; this is not the case in 'nude' humans. Scalp
hair in humans does function as a protection
against the cancer-inducing effects of ultraviolet
radiation; it also protects against minor injury.
However, the main role of hair in human society
is as an organ of sexual attraction
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The rate of hair growth differs depending on the site.

For example, eyebrow hair grows faster and has a
shorter anagen than scalp hair. On average, there
are about 100 000 hairs on the scalp, and the normal
rate of growth is 0.4 mm/24 h. Hair growth is
cyclical, with three phases, and is randomized for
individual hairs, although synchronization does
occur during pregnancy.
 The three phases of hair development
1. Anagen is the growing phase. For scalp hair this lasts
from 3-7 years, but for eyebrow hair it lasts only 4 months.
At any one time, 80-90% of scalp hairs are in anagen, and
about 50-100 scalp follicles switch to catagen per day.
2. Catagen is the resting phase and lasts 3-4 weeks. Hair
protein synthesis stops and the follicle retreats towards the
surface. At any one time 10-20% of scalp hairs are in
catagen.
3. Telogen is the shedding phase, distinguished by the
presence of hairs with a short club root. Each day 50-100
scalp hairs are shed, with less than 1% of hairs being in
telogen at any one time.
 Melanocyte function

Melanocytes (located in the basal layer) produce the

pigment melanin in elongated, membrane-bound
organelles known as melanosomes .These are
packaged into granules which are moved down
dendritic processes and transferred by phagocytosis
to adjacent keratinocytes.
 CONTINIOUS

Melanin granules form a protective cap over the

outer part of keratinocyte nuclei in the inner layers
of the epidermis. In the stratum corneum, they are
uniformly distributed to form a UV-absorbing
blanket which reduces the amount of radiation
penetrating the skin.
 Blood flow

Skin temperature is highly responsive to skin

blood flow. Dilation or contraction of the dermal
blood vessels results in vast changes in blood
flow, which can vary from 1-100 ml/min per 100
g of skin for the fingers and forearms.
Arteriovenous anastomoses under the control of
the sympathetic nervous system shunt blood to
the superficial venous plexuses , affecting skin
temperature. Local factors, both chemical and
physical, can also have an effect.
 Sweat

The production of sweat cools the skin through

evaporation. The minimum insensible perspiration
per day is 0.5 litre. Maximum daily secretion is 10
litres, with a maximum output of about 2 litres per
hour.
 CONTINIOUS

Men sweat more than women. Watery isotonic sweat,

produced in the sweat gland, is modified in the excretory
portion of the duct so that the fluid delivered to the skin
surface has:
 a pH of between 4 and 6.8
•a low concentration of Na+ (30-70 mEq/1) and Cl (30-70
mEq/1)
 a high concentration of K* (up to 5 mEq/1), lactate (4-40
mEq/1), urea, ammonia and some amino acids. Only small
quantities of toxic substances are lost. Sweating may also
occur in response to emotion and after eating spicy food.
 Thermoregulation

The maintenance of a near-constant body core

temperature of 37°C is a great advantage to humans,
allowing a constancy to many biochemical reactions
which would otherwise fluctuate widely with
temperature changes. Thermoregulation depends on
several factors, including metabolism and exercise,
but the skin plays an important part in control
through the evaporation of sweat and by direct heat
loss from the surface.
 Biochemistry of the skin

Keratins are high-molecular-weight polypeptide

chains produced by keratinocytes . They are the
major constituent of the stratum corneum, hair
and nails. The stratum corneum comprises 65%
keratin [along with 10% soluble protein, 10%
amino acid, 10% lipid and 5% cell membrane).
Keratin polypeptides are of different molecular
weight (e.g. 50, 55, 57 and 67 kDa), and
different keratins are found at each level of the
epidermis, depending on the stage of
differentiation. Epidermal keratin contains less
 Melanin

Melanin is produced from tyrosine in melanocytes

and takes two forms:
Eumelanin, which is more common and gives a
brown-black colour
 phaeomelanin, which is less common and produces
a yellow or red colour.Most natural melanins are
mixtures of eumelanin and phaeomelanin. Melanins
act as an energy sink and free-radical scavengers,
and absorb the energy of UV radiation.
 Collagen

Collagen is synthesized by fibroblasts (Fig. 3) and is

the major structural protein of the dermis, forming 70-
80% of its dry weight. The main amino acids in
collagen are glycine, proline and hydroxyproline.
There are over fourteen types of collagen, at least five
of which are found in skin:
type I - found in the reticular dermis
 « type III — found in the papillary dermis
types IV and VII - found in the basement membrane
structures
type VIII - found in endothelial cells.
 Glycosaminoglycan (GAG)
The 'ground substance' of skin is largely made
up of GAGs, providing viscosity and hydration.
In the dermis, chondroitin sulphate is the main
GAG, along with dermatan sulphate and
hyaluronan. GAGs often exist as high-
molecularweight polymers with a protein core.
These structures are known as proteoglycans
 Skin surface secretions

The skin surface has a slightly acidic pH (between 6

and 7). Sebum (Table 1), sweat and the horny layer
(including intercellular lipid) contribute to the
surface conditions, which generally discourage
microbial proliferation.
 Subcutaneous fat

Triglyceride is synthesized from a-glycerophosphate

and acyl Co-A. Triglyceride is broken down by lipase
to give free fatty acid (FFA) - an energy source - and
glycero
 Immunology of the skin

The skin is an important immunological organ and

normally contains nearly all the elements of cellular
immunity, with the exception of B cells. Much of the
original research into immunology was done using
the skin as a model.
 Hypersensitivity reactions and the skin

Hypersensitivity is the term applied when an

adaptive immune response is inappropriate or
exaggerated to the degree that tissue damage results.
The skin can exhibit all the main types of
hypersensitivity response.
 Molecular genetics and the skin

Recent and rapid advances in genetics have

had an impact on our understanding of skin
diseases. The Human Genome Project has
now mapped all human genes, of which there
are about 30,000.
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Genetics has been found to be more complicated

than the original Mendelian concept, and common
conditions such as atopy occur due to a complex
interaction between multiple susceptibility genes and
the environment. An average pregnancy carries a
1% risk for a single gene disease and a 0.5% risk for
a chromosome disorder but genetically influenced
traits e.g. atopy, are much more common.