SKIN Renewal:

-largest organ -continually renewed by mitosis of cells in the

-16% of body wt basal layer and displacement towards the
surface.
-differentiate during transit by enlarging and
Functions:
accumulating increasing amt of keratin filaments
1. Barrier against injury and desiccation. in the cytoplasm.
2. Receive stimuli from environment thru its -transit time: 20-30 days.
tactile sense organ.
3. Thermoregulation and water balance.
Cytomorphosis
- structural modifications that they undergo
2 Principal Layers: during the passage.
1. Epidermis- surface epithelium
- give rise to 4 zones:
2. Dermis- Subjacent connective tissue 1. Stratum Basale
Other layer: 2. Stratum Spinosum (Stratum Malpighii)
3. Hypodermis- loose connective tissue which 3. Stratum Granulosum
is loosely attached to underlying deep fascia or
4. Stratum Corneum
periosteum of the bone.
4. Mucocutaneous Junction- natural epithelial
transition zone between skin and mucosa.
- with mucous membrane
lining this structures: lips, nose, eyelids,
vulva and prepuce.

Dermal papillae- projections of the dermis

Inter papillary pegs- down growth of epidermis.

EPIDERMIS
-stratified squamous epithelium made up of
multiple layers of Keratinocyte.
Usual thickness: 0.07-0.12mm
Palms: 0.8mm
Soles of the feet: 1.4mm
Stratum Basale
-single layer of cuboidal or low columnar cell
which have a large nucleus and basophilic
cytoplasm.
-supported by a typical basal lamina and
resting on the underlying dermis.
-Organelles: Small golgi complex, few
mitochondira, ER, cytoplasmic matrix rich in
ribosomes.
-formerly called Stratum Germinativum since
mitotic figures are common in this layer and is
responsible for the continual renewal of the
epithelium due to the proliferation of its cells.
-as the cell goes up to the Stratum Spinosum,
it assume a flattened polyhedral form with
elongated nucleus.
Stratum Spinosum (Stratum Mapighii)
- same complement of organelles but less
intense basophilic.
-Prominent feature: numerous bundles of
cytokeratin intermediate filaments that radiate
from perinuclear region to end in the dense
plague of numerous desmosomes along the
highly interdigitated cell boundaries.
-also have the Membrane-coating granules or
lamellar granules which is a secretory granule
measuring 0.1-0.4 um in diameter and have a
limiting membrane and a distinctive internal
structure consisting of closely packed parallel
lamellae.
*These stacks are said to be made of discoid
flattened vesicles with their outer surface tightly
apposed due to the alternating electron-dense
and electron-lucent thin bands within the
granules which resembles those of myelin and
other multilayered membrane system. Also, the
pair of dense bands are seen to be continuous
with one another at their ends.
Stratum Granulosum
- 3-5 layers of more flattened cells than those
of stratum spinosum.
-nuclei begin to degenerate in the outer row
-lamellar granules first seen in stratum
spinosum are present in great number which
collect near cell membrane and occupy as much
as 15% of cytovolume.
-then they undergo exocytosis and their
content coalesces to form a continuous
multilayered coating of cell membrane.
-due to this, there is an increase EC space
from <1% to 5-30% of tissue volume and is
occupied by lipid-rich secretory product ( a
waterproof sealant that is a major component of
the epidermal permeability barrier)
Principal distinguishing feature: Keratohyaline
Granules
-bodies of large size and very irregular shape
that stain intensely with basic dyes.
-do not have a limiting membrane.
-bundles of abundant keratin filaments in the
cytoplasm may be incorporated in their periphery
or pass thru them.
-exact chemical nature is unclear but
believed to be precursors of the Interfibrillar
Matrix that is distributed throughout the
cytoplasm of fully keratinised cells in the
underlying stratum corner.
Stratum Lucidum
-layer of thin, lightly satining, refractile cells
between stratum granulosum and stratum corner
in thick skin of palms and soles.
-not identifiable in thinner skin of other
regions.
-4-6 rows of very flat cells
-nuclei are rarely seen
-keratin filaments in the cytoplasm are closely
aggregated and more consistent in their
orientation parallel to the skin surface.
-cell membrane appears thickened by
deposition of dense material on its inner surface.
Stratum Corneum
-consist of many layers of very flat, heavily
keratinized cell containing no nucleus or
cytoplasmic organelles.
-plasmalemma appear thickened and entire
cell is filled with keratin filaments embedded in
an amorphous matrix.
 -cells of lower layers are still closely adherent
but the desmosomes have been greatly
modified.
-Stratum disjunction -> where in the outer
layers, the fully keratinized, lifeless cells loosen
and ultimately desquamate but cells are still
identical to those in deeper layer of stratum
corneum.
Basal Lamina (Basement membrane)
-consists of lamina densa parallel to the
membrane of the basal cells of the epithelium
and separated from it by a thin lamina lucida.
Lamina Lucida
-traversed by exceedingly thin filaments
crossing from the cell membrane to the lamina
densa.
Lamina Densa
-fine meshwork of type IV collagen, also
containing heparin sulfate and glycoprotein
Anchoring fibrils
- Slender; extend from the lamina downward,
arching around collagen bundles in the dermis
and terminating in anchoring plaques.
-other connect neighbouring anchoring
plaques
-loose network of anchoring fibrils around
collagen bundles is believed to bind epithelium
firmly to the dermis.
-at high magnification, it have the beaded or
cross-striated appearance characteristic of type
VII collagen (a rare family of collagen).
Anchoring plaques
-small bodies having the same density
substructure as the lamina densa.
4 Types of Keratin Seen in Keratinocytes of
Skin
a.) K5 (58kD) and K14 (50kD) -loose
networks of these are seen in the cytoskeleton of
the basal cells.
b.) K1 (67kD) and K10 (56kD) -these forms
coarser bundles of filaments than those in the
stratum basal and seen in the metabolically
active stratum spinosum.
Metabolically Active Stratum Spinosum
-cells in this zone also produce involucrin and
other “envelope protein” that are deposited on
the inner aspect of plasmalemma.
-they also begin to form the membrane-
coating granules that will later release complex
lipid and lipoproteins into the cellular spaces
( the one that is mentioned above that constitute
a major component of the permeability barrier of
the epidermis)
-as the cells moves to the stratum granulare,
they cease to produce keratins and envelope
proteins BUT they begin to produce filaggrin and
loricin.
-They will cause the cell to become
permeable to calcium ions that activate an
enzyme which crosslinks the various envelope
proteins to form a very tough layer beneath the
plasmalemma (plasma membrane).
-by then, the lysosomes will be release and
lytic enzymes will terminate all metabolic activity
and so the cells moving up to the stratum
corneum will be reduced to tough, inert shells
packed with coarse bundle of keratin filaments.
-and again, the the intercellular spaces will be
filled with secreted lipid-rich compounds which
renders the epithelium impermeable.
Filaggrin -a basic protein that is believed to
involved in the assembly of keratin filaments into
still coarser bundles.
Loricin -an additional component of the cell
envelope.
Cytokines involved:
1. Epidermal growth factor (EGF)- can be
synthesised by by epidermal cell so that they
may auto regulate their own growth.
2. Interleukin-1 alpha (Il-1a)- stimulatory
3. Transforming growth factor- suppress
keratinocyte proliferation and differentiation
Generally:
1. Epidermis over the rest of the body are
similar to that of palms and sole but just thinner
stratum corner.
2. Thin stratum spinosum is always present.
3. Stratum granulosum is usually identifiable but
only 2-3 cells thick.
4. Distinct stratum lucida is seldom found.
CELLS
Langerhans Cells
-dendritic cells found throughout epidermis,
3-8% of cell population, may reach numbers as
high as 800 per square ml (also occasionally
found in the dermis)
-usually located in the upper layers of stratum
spinosum.
-H&E: dark-staining nucleus and pale,clear
cytoplasm.
-Gold Chloride: blackens them and reveal
more clearly their stellate or dendritic form
(selective stain)
- cell processes extend into the spaces bet.
the surrounding keratinocyte.
-they also take up methylene blue and other
supra vital dye
-also have an affinity for catecholamines and
1,3,4 dihydroxyphenylalanine (L-DOPA) which
rendered fluorescent to form aldehyde vapour.
-may also found in the stratified squamous
epithelium of the oral cavity, oesophagus and
vagina.
-participate in body’s immune response and
possess surface receptors and immunological
markers similar to this of macrophage.
-they come from a precursors in the BM
-they incorporate thymidine in vitro w/c
makes them capable of mitosis.
Distinguishable feature from keratinocytes:
a. nuclear shape which is irregular
b. absence of desmosomes on their surface
c. absence of conspicuous bundles of
intermediate filaments in their cytoplasm.
d. MOST RELIABLE: presence of Birbeck or
Vermiform granules, a unique membrane-limited
granules.
-discoid in their 3-D form but appear
rodlike in section and are 15-50nm in length and
about 4nm in thickness, with a central linear
density from w/c faint striations radiate to the
listing membrane.
-racquet-like appearance and no enzymatic
activity
Functions:
1. Bind the Fc fragment of IgG and IgA and the
C3 component of the complement.
2. Carry the T-4 Ag on their surface.
3. At sites of allergic contact dermatitis,
lymphocytes are observed to gather around
langerhans cells. —-WHY? Because the
langerhans cells are the one taking up the
allergen and present it to the lymphocyte
afterwards.
Merkel Cells
-found in the basal layers of the epidermis but
more abundant in areas w/special role in sensory
reception such as fingertips.
-usually occur singly but may cluster in
specialised areas of skin
-their ultrastructure bear a superficial
resemblance w/ Keratinocytes
-Nucleus: deeply invaginated and may
contain a bundle of short parallel filaments.
-Cytoplasm: low electron density and
contains loose bundles of cytoskeletal filaments
in the perinuclear region and at cell periphery
-the filaments contains K8, K18 and K19.
Distinctive Structure
-presence of many dense-cored granules
(80-130nm) located in the perinuclear cytoplasm
and in dendrite-like cell processes.
*The basal lamina of the epidermis is traversed
by the naked terminals of myelinated afferent
nerves and these end in close apposition to the
Merkel cells forming Merkel cells-neurite
complex.
Melanocytes
-situated in basal layer of epidermis or in the
underlying dermis.
-ratio to basal epidermal cell is 1:4 to 1:10.
-may be as few as 1000/mm2 on the arms
and thighs
-as many as 4000/m2 on face and neck
3 Components Affecting Color of Skin:
1. Carotene -inherent yellowish color
2. Oxygenated Hemoglobin -reddish tint
3. Melanin- brown to black; only one that is
produced in the skin.
- product of epidermal melanocyte
only—- WHY? Because they are the only cells
that posses Tyrosinase w/c is essential for the
synthesis of this pigment.
-occurs in granules called
Melanosomes in the cytoplasm of melanocytes
and keratinocytes-— HOW? Fully formed
melanosomes are transferred from melanocyte
dendrites to keratinocytes by CYTOCRINE
SECRETION.
Epidermal Melanin Unit
-melanocyte plus its satellite epidermal cells
Best studied by:
-whole mounts of epidermis separated from
underlying dermis
-treated with 1,3,4-dihydroxyphenylalanine
(DOPA)
-Appearance: Blackened cells with quite
apparent highly branched dendritic processes.
MUCOCUTANEOUS JUNCTIONS
-transitions from skin to mucous membrane
lining the orifices of the body (mouth and anus)
-stratified squamous epithelium
-more resemble mucosa than skin
-have very thin stratum corneum but NO hair,
sebaceous or sweat glands.
-their surface are moistened by mucous
gland situated deeper on orifice.
-cornified layer is very thin showing red tint
because the color of blood in the underlying
capillary bed shows thru (reason why lips are
reddish)
DERMIS (CORIUM)
-tough leathery layer of connective tissue that
makes up the greater part of thickness of the
skin.
-Depth: 0.6mm (in thin skin) to 3mm (thick
skin), Average: 2mm.
-thinner in ventral surface and extremities
than dorsum
-thinner in women than men
-have a rich vascular bed from w/c networks
or capillaries extend into the dermal papillae,
permitting nutrients to diffuse into the avascular
epidermis
Dermatoglyphic Pattern
-ridges reflected on corresponding primary
ridges on the upper surface of the dermis.
-separated from one another by deep
grooves into w/c processes of the dermis project
-rows of conical papillae: 0.1-0.2mm height,
project upward from these ridges into conforming
concavities on the underside of the epidermis.
-approx. 80/mm2
HOW to separate epidermis from dermis:
1. incubate sample of skin for 2h in balanced
salt sol’n containing calcium-chelating agent
EDTA.
2. Lift off the epidermis then expose the
surface of the dermis for scanning electron
microscopy w/c provides 3D images.
WHAT can you see (palms and soles):
1. Dermis is characterized by parallel dermal
ridges separated by primary grooves.
2. A slight thickening of the epidermis
occupies a shallow 2ndary groove or sulcus
along the midline of each primary ridge, flanked
by two 2ndary ridges.
3. A row of dermal papillae runs along the
each 2ndary dermal ridges.
4. Papillae occurs in group of 3 or 4 sharing a
common base
IN SHORT: Each primary ridge bears 2 parallel
rows of papillae separated by a shallow groove.
Inter-papillary peg- in intact skin, primary groove
is occupied by long, ridge like, downward
projection of epidermis that was inappropriately
called.
IN THIN SKIN:
Dermal papillae
-simpler, shorter, broader and less
numerous than of the palms and they are not
arranged in the precise rows corresponding to
ridges on the skin surface.
2 LAYERS OF DERMIS:
1. Superficial Papillary Layer
-consists of fibroblasts and other
connective tissue cell types widely dispersed
among randomly interwoven bundles of thin
collagen fibres (type 3)
-also contains loose network of elastic
fibres and many capillaries.
2. Deeper Reticular Layer
-made up of closely packed coarse
bundles of thicker fibes(type 1 predominates)
-oriented less parallel to the skin surface
but some may run obliquely or nearly
perpendicular to the majority.
-intermingling with collagen bundles is a
network of elastic fibres w/c are abundant
around sebaceous and sweat glands that extend
downward from epidermis to dermis.
-interstices bet. fibrous components are
occupied by proteoglycans (Major component:
Dermatan sulfate)
CELL TYPES:
1. Fibroblast
2. Macrophages
3. Lymphocytes
4. Mast Cells
5. Adipose Cells(occasionally found in deeper
portion of reticular layer in cluster)
Loose Plexus of Smooth Muscle Cells
-found in the deeper portion of the reticular
layer of the skin of penis, scrotum and the areola
around nipples
-skin is wrinkled, owing to contraction of this
smooth muscle
Arrestor Pili Muscles
-insert into the body of hair follicles
-responsible for the erection of hairs in cold
environment (goose-flesh)
Muscles of Facial Expression
-cross striated muscle fibres terminating in
the dermis of face, scalp and the base of the
ears
 -involved in smiling, frowning and voluntary
movements of ears and scalp.
Panniuclus Carnosus
-those muscles above are the vestiges of this
extensive subcutaneous layer of skeletal muscle
which is present in many animal species.
HYPODERMIS
-subcutaneous layer deep to reticular of the
dermis
-looser connective tissue in w/c thin collagen
finer bundles are oriented mainly parallel to the
skin surface
-permits movement of the skin over the
underlying structures in some regions such as
the back of the hand.
-adipose cells accumulate in greater number
in this layer than that of the dermis (Panniculus
Adiposus -> layer of fat)
APPENDAGES OF THE SKIN
HAIRS
-develop from cells lining the hair follicles
(deep invagination of the epidermis)
-important in tactile sensation
-act as minute lever and when deformed they
exert pressure that is detected by sensory
nerves around the hair follicles
Hair is absent in the:
1. palms and soles.
2. lateral surfaces of the feet
3. glans penis
4. clitoris and inner surface of the prepuce
and labia minor and majora
On eyelid: hair do not project beyond their follicle
On scalp: hair may grow to over 1m in length
Arrector Pili Muscle
-originate in the papillary layer of dermis
-hair and follicles are always inclined at an
angle and contraction of this muscle moves it to
vertical position (Goose-pimple)
Sebaceous Gland
-found immediately above the insertion of
arrestor pili muscle
-they discharge their secretion into the
follicular canal
Hair Bulb
-terminal expansion of an active hair follicle
w/c has a deep recess in its under side occupied
by a papilla of dermal connective tissue
Cells of Papilla
- have inductive properties influencing the
activity of the follicle and nutrients from its
capillaries are essential for normal function
Hair Matrix
-form by epithelial cells covering the papilla
-their proliferation is responsible for hair
growth
Vitreous Layer (Glassy Layer)
-noncellular; exceptionally thick basal lamina
of the outer layer of follicular epithelium(external
root sheath)
 -One cell of the matrix is large melanocyte
whose long dendrites contribute melanosomes
to cell that will form the cortex of the hair
*the graying of the hair in old age is attributed
to a gradual loss in the capacity of these cells to
produce Tyrosine.

3 Layers of Internal Root Sheath

1. Henle’s Layer -single row of elongated
cells in close contact with the innermost cells of
the external root sheath
2. Huxley’s Layer - made up of 2 or 3 rows of
less flattened cells
3. Cuticle - composed of flat, scale-like cells
imbricated with their free edges directed
downward.

Cell Matrix
-mass of cells in the interior of the bulb,
around the papilla
-proliferation, differentiation and upward
movement of these cells give rise to the hair
-cells situated above the apex of papilla
produce vacuolated cells that form Medulla
which contains little keratin
-more peripheral matrix cells give rise to the
Cortex of the hair which synthesise a great
quantity of keratin filaments and many
trichohyaline granules.
-the granules are insoluble and have a high
content of glutamic acid, glutamate and citrulline.
-matrix cells still move farther toward the
periphery of bulb to become very keratinised and
form hair cuticle.