Integumentary System

Dr. Ameet Kumar Jha, Ph.D.,(Med)

Associate Professor, Anatomical Sciences
School of Medicine, Saint Matthews University

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 Objectives
1. Overview of the skin and appendages
2. Layers of the skin: Epidermis and Dermis
3. Cells of the epidermis: Keratinocytes, Melanocytes,
Langerhans’ cells & Merkel’s cells
4. Dermis: Papillary and Reticular layer, Arteriovenous
anastomosis
5. Skin annexa (epidermal derivatives): Hair follicles & Nails

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 Introduction
• Integument, Cutis consists of
– Skin, which is made up of the
• Epidermis: Stratified Squamous Keratinized Epithelium – derived from ectoderm
• Dermis: Dense Connective Tissue – derived from mesoderm

– Epidermal derivatives including

• glands
– eccrine and apocrine sweat glands
– sebaceous glands
– mammary glands
• hair
• nails
• The hypodermis binds the skin to underlying tissues
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Integument, hypodermis, subjacent tissue

Epidermis

Dermis

Hypodermis

Subjacent structure - tendon

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 Functions of the skin
• Protection against:
– Abrasive forces (thick skin in palms and soles)
– UV, chemical and thermal damage
– Desiccation – due to water barrier
– Microbial invasion – normal skin microbiota cannot enter skin
except if there is a cut
• Thermoregulation:
– AV anastomosis can redirect blood flow to cause heat loss or
retention
– Eccrine sweat gland secretion helps cool the body when hot
• Exteroception:
– Largest sensory organ for environmental perception of touch,
pressure, temperature, and pain stimuli
• Synthesis of Vitamin D3 (cholecalciferol):
– Absorbs UV radiation for conversion of 7-dehydrocholesterol to
vitamin D3.
– D3 is further converted to active 1,25-dihydroxycholecalciferol in
the liver and kidney

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 Configuration of the skin
• Has narrow epidermal ridges separated by
furrows
• Impressions of the ridges create fingerprint and
footprint patterns (dermatoglyphs), useful for
forensic identification
• Each epidermal ridge follows the outline of an
underlying dermal ridge
• A downgrowth of the epidermal ridge splits the
dermal ridge into two secondary dermal ridges
or dermal papillae
• The epidermal ridge downgrowth is designated
interpapillary peg
• This arrangement provides tight fit interface at the
dermal-epidermal junction, stabilized by
hemidesmosomes 6
 Epidermis – cell types

Stratified squamous epithelial layer

Four distinct cell types:
• Keratinocytes - predominant epidermal cell type,
produce keratin, an intermediate filament protein
• Melanocytes - neural crest–derived cells,
produce melanin
• Langerhans cells - resident dendritic cells
derived from a bone marrow precursor, acting as
antigen-presenting cells
• Merkel cells - neural crest–derived cells involved
in tactile sensation
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 Keratinocyte layers of epidermis
Keratinocyte development creates five recognizable
cytomorphogenic layers or strata:

• Stratum basale (basal cell layer – germ cell layer)

• Stratum spinosum (spinous or prickle cell layer)
• Stratum granulosum (granular cell layer –
keratohyalin granules)
• Stratum lucidum (clear cell layer – only in thick skin)
• Stratum corneum (cornified cell layer)
• Cells of the last two layers undergo keratinization,
or cornification
• Stratum basale and stratum spinosum form the
stratum of Malpighi
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 Epidermal cell layers
SC
SL SG

SS

SB
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 Stratum basale
• Single layer of basophilic columnar/cuboidal cells on the basement membrane
• Hemidesmosomes binds the cells to the basal lamina
• Desmosomes bind them together at their lateral and upper surfaces
• Stem cells: Characterized by
intense mitotic activity
• Stratum basale and stratum
spinosum produce epidermal
cells and vitamin D3
• Keratinocytes in the stratum
basale contain intermediate Stratum basale
filaments composed of
keratins.
• Melanocytes.
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 Stratum spinosum
• Thickest epidermal layer
• Consists of polyhedral keratinocytes and Langerhans
cells
• Cells close to stratum basale may still divide, and this
combined zone is sometimes called the stratum
germinativum
• Keratin filaments form microscopically visible bundles
called tonofibrils (bundles of tonofilaments) which
converge at the numerous desmosomes
• Short cytoplasmic extensions around the tonofibrils on
both sides of each desmosome cause appearance of
many short spines or prickles at the cell surfaces –
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hence the name
 combined zone is sometimes called the stratum germinativum. The keratin filaments form microscopically visible bundles
and terminate at the numerous desmosomes, by which the cells are joined together strongly to resist friction. Cytoplasm i
extensions around the tonofibrils on both sides of each desmosome (and these are elongated if the cells shrink slightly whe

Stratum spinosum
to the appearance of many short spines or prickles at the cell surfaces (Figure 18–4). The epidermis of areas subjected to
(such as the soles of the feet) has a thicker stratum spinosum with more abundant tonofibrils and desmosomes.

Figure 18–4.

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 Stratum granulosum
• 3–5 layers of flattened polygonal cells undergoing
terminal differentiation
• Prominently seen in thick skin
• Cytoplasm is filled with intensely basophilic masses
called keratohyalin granules (dense masses of
filaggrin associated with the keratins of tonofibrils)
• Tight junctions, containing claudin-1 and claudin-4,
bind the cells
*decrease in
claudin-1 is
reported in human
atopic dermatitis
Stratum granulosum
https://doi.org/10.1080/21688370
.2017.1336194

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 Keratinization
Stratum granulosum Stratum lucidum/Stratum
corneum

Keratohyalin granules Keratinization

Contains Filaggrin and

Trichohyalin (major intermediate Conversion of granular
filaments-associated proteins) cells to cornified cell

Filaggrin and Trichohyalin

Marker of Release of contents aggregates tonofilaments
apoptosis in Cytoplasm to tonofibrils 14
 Stratum lucidum (lucid = bright/shinning)
• Only seen in thick skin
• Thin, translucent layer of extremely flattened cells
• Nuclei and organelles have been lost
• Cytoplasm consists almost entirely of densely packed keratin
filaments

Stratum lucidum

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 Stratum corneum
• 15–20 layers of flattened, anucleated keratinized cells
• Cells contain only fibrillar and amorphous proteins with thickened
plasma membranes (called squames or horny, cornified cells)
• Squames are continuously shed at the surface of the stratum
corneum

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 Thick and thin skin
• Skin is generally classified into two types based on thickness of the epidermis
(and dermis):
– Thick skin
– Thin skin
• Thick skin (400 – 600 um thick)
– covers the palms and soles
– thick epidermis
– stratum lucidum is very distinct (only seen here)
– prominent stratum corneum and granulosum
• Thin skin (75 to 150 um in thickness)
– lines the rest of the body;
– epidermis is thin
– generally lacks stratum lucidum and granulosum (though cells of these layers may be
found)
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Thick and thin skin

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Keratinocyte differentiation - Keratin formation
 Stratum corneum
 Squames filled with keratin

 Stratum lucidum
 Dead cells filled with keratohyalin granules (called
Eleidin)

 Stratum granulosum
 Filled with keratohyalin granules

 Stratum spinosum
 Keratin 1 and 10 in tonofilaments
 Keratohyalin (filaggrin and trichohyalin) surround tonofilaments

• Stratum basale
– Keratin 5 and 14 in tonofilaments
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 Epidermal water/permeability barrier
Formed by
• Lipid envelope - multi-lamellar lipid layer
– Lipids released from lamellar bodies in stratum spinosum and granulosum
– covalently linked to involucrin
• Cornified cell envelope
– specialized structures at desmosome plaques
– aggregates of small proline-rich proteins (SPRs) cross-linked to structural proteins
– Structural proteins include
• cystatin, desmosomal proteins (desmoplakin), elafin, envoplakin, filaggrin,
involucrin, keratin chains, and loricrin.
• transglutaminase (TG1, TG3, and TG5) mediates cross-linkage
• Tight junctions in the stratum granulosum, containing claudin-1 and claudin-4
• Squames of stratum corneum

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 Melanocytes
• Located in the stratum basale
• Derive from neural crest precursor, melanoblasts
• Development is controlled by a ligand, stem cell factor
interacting with c-kit receptor
• Remain independent without desmosome attachment to
keratinocytes
• Attached to basal lamina by hemidesmosomes

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 Melanocytes
• Melanocytes produce melanin, contained in melanosomes
• Melanin is transferred to keratinocytes through branching
processes, called melanocyte dendrites
• Melanin pigments provide the skin and hairs and eyes (RPE,
ciliary body and iris) with dark color
• Melanin consist of copolymers of
– black and brown eumelanins
– red and yellow pheomelanins.
• The number of melanocytes per unit area of skin is the same
in dark and light-skin
• Pigmentation differences are due to
– rate of melanin synthesis, melanosome size
– content, rate of transfer
– degradation patterns
• Melanin protects skin from UV radiation damage

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 Determination of Skin colour
• Melanocytes : Keratinocytes in the basal
layer of the epidermis (Epidermal Melanin
Unit).
• EMU differs between different parts of the
body but is essentially the same in all races.
• Skin color differences between the races -
related to the fate of melanin.

• Dark skin individual • Light skin individual

• Degradation of melanin (lysosomes) • Degradation of melanin (lysosomes)
proceeds at a slower rate. proceeds faster rate.
• Melanosomes are more widely • Melanosomes are sparse in the upper
distributed throughout the epidermis. layers of the epidermis.
• Increased number of melanocytes and increased synthesis of melanin are biological 23
responses to UV radiation.
phagocytosis (Figure 14–5).

MEDICAL APPLICATION

Langerhans (dendritic) cells

Tissue grafts and organ transplants are classified as autografts when the transplanted tissues are taken from the same
individual receiving them, isografts when taken from an identical twin, homografts or allografts when taken from an
individual (related or unrelated) of the same species, and heterografts or xenografts when taken from an animal of a
different species.

• Bone marrow–derived
The body readily accepts autografts and isografts as long as an efficient blood supply is established for the organ. There is
no rejection in such cases, because the transplanted cells are genetically identical to those of the host and present the
same MHC on their surfaces. The organism recognizes the grafted cells as self (same MHC) and does not react with an
immune response.

• Process and present antigens to T helper cells

Homografts and heterografts, on the other hand, contain cells whose membranes have class I and class II MHC molecules
that are foreign to the host; they are therefore recognized and treated as such. Transplant rejection is a complex process
due to the activity of T lymphocytes and antibodies that react to and destroy the transplanted cells.

• Located in stratum spinosum and associate with keratinocytes

Antigen-Presenting Cells (APCs)
APCs are found in many tissues and constitute a heterogeneous population of cells that includes dendritic cells, macrophages,

through E-cadherin
and B lymphocytes. Dendritic cells (not to be confused with cells of nervous tissue) occur not only in the lymphoid organs, but are
also abundant in epidermis and many mucosae, where they are called Langerhans cells. A common feature of APCs is the
presence of class II MHC molecules on their surfaces. CD4+ T (helper) cells interact with complexes formed by peptides and class
II MHC molecules on APCs. However, CD8+ T (cytotoxic) cells interact with peptides complexed with class I MHC molecules which

• Cytoplasm contains racket-shaped inclusions (Birbeck granules)

can be presented by any nucleated cell. APCs, being recognized by helper lymphocytes, are essential for triggering and
development of a complex immune response.

associated with the protein langerin

The Langerhans cells of the epidermis constitute a very efficient system for trapping antigens that enter the epidermis (Figure
14–6). Like APCs of other organs, these cells have many processes and upon capturing antigens, they retract the processes, move
toward the dermis, and enter a lymphatic vessel.

Figure 14–6.
Birbeck granules
Immunohistochemistry - Langerhans cells are yellow

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 Merkel (epithelial tactile) cells
• Are mechanoreceptor/dendritic cells for
fine touch
• Resemble modified keratinocytes (contain
keratin)
• But….Neural crest-derived (NOT
keratinocytes)
• Located in stratum basale
• Numerous in the fingertips and lips
• Contact an afferent unmyelinated nerve
fiber expansion (nerve plate)…Merkel disc
• Cytoplasm contains abundant granules,
presumably neurotransmitters
• Functions also related to diffuse
neuroendocrine system
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 Dermis
• Consists of two layers without distinct
boundaries:
• Papillary layer – loose connective
tissue
– consists of numerous dermal papillae
– form the dermal-epidermal junction
– provides support and nutrients to epidermis
• Reticular layer – dense irregular
connective tissue
– contain thick type I collagen bundles
– coarse elastic fibers – skin elasticity
• Hair follicles and sweat and sebaceous
glands are epidermal derivatives present
at various levels in the dermis
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 Skin circulation

• Primary function of skin vasculature:

– Thermoregulation
• Secondary function
– Nutrition of the skin and appendages
• The arrangement of blood vessels permits rapid
modification of blood flow according to the required loss or
conservation of heat

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 Cutaneous circulation
Two interconnected networks
– Subpapillary plexus – runs along papillary layer of the dermis – extend loops into
dermal papillae
– Cutaneous plexus – at the boundary of papillary and reticular dermis

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 Arteriovenous anastomosis and Glomus body
• Arteriovenous anastomoses (shunts)
between the arterial and venous Glomus body

circulation bypass the capillary network

– common in the hands, feet, ears, lips, nose
– involved in thermoregulation
• Glomus body
– Convoluted segments of AV-shunts
– Surrounded by dense collagenous connective
tissue
– Glomus tumors are benign, usually very small
red-blue nodules, associated with sensitivity to cold
and severe intermittent focal pain
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 Sensory receptors - overview
• Are specialized neurons and epithelial-like cells
– Receive and convert a physical stimulus into an electrical signal
transmitted to the central nervous system
• Full into three general categories:
– Exteroceptors
• provide information about the external environment
– Interoceptors
• provide sensory information from the internal organs of the body
– Proprioceptors
• provide information about the position and movement of the body
• located in muscles (such as the muscle spindle), tendons, and joint capsules

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 Sensory receptors of the skin (exteroceptors)

Classified based on the type of stimulus:

• Mechanoreceptors respond to mechanical deformation (detect
changes in touch, pressure, position or acceleration)
• Thermoreceptors respond to temperatures (sensitive to heat or
cold)
• Nociceptors respond to pain stimuli (detect physical or chemical
damage to tissues)

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 Mechanoreceptors of the skin
• Respond to stretch, vibration, pressure, and touch
• They are encapsulated receptors (except Merkel disc)
• Four primary types in human skin
RECEPTORS LOCATIONS FUNCTIONS
Merkel Cell & Epidermal-dermal Crude touch & static 2 point
Disc junction(Stratum basale) discrimination
Meissner Epidermal-dermal junction Light/fine touch & dynamic/moving 2
corpuscle (in dermal papillae) point discrimination
Ruffini Deep dermis and Stretch (prolonged pressure) and
ending hypodermis warmth
Pacinian Deep dermis & Vibration
corpuscle hypodermis

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 Mechanoreceptors of the skin
• Merkel disk (tactile receptor)
discriminates fine touch and 2 point
discrimination
• Meissner corpuscle
– elliptical structures perpendicular to the epidermis
in the dermal papillae
– found primarily in the fingertips, lips, and eyelids
– unmyelinated nerve endings surrounded by
Schwann cells in spiraling layer
– best for the detection of shape and texture during
touch (low frequency stimulation or light touch)

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Meissner corpuscles

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 Mechanoreceptors of the skin
• Ruffini ending or bulbous corpuscle
– Located in the deep dermis
– Detects skin stretch and deformation (pressure)
– Provide feedback when gripping objects and
controlling finger position and movement
• Pacinian corpuscle
– Found in the deep dermis and hypodermis
– Large oval structures with outer capsule and
concentric lamellae surrounding an unmyelinated
axon
– Responds to stimuli of deep, transient pressure
and high-frequency vibration
– Also found in periosteum, joint capsules,
pancreas, peritoneum, breast, and genitals
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Pacinian corpuscles

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 Thermoreceptors of the skin

• Respond to temperature stimulus, either warm or cold

• Krause end bulb
– encapsulated thermoreceptor that detects cold
– found in the conjunctiva of the eye, in the mucosa of the lips and tongue,
epineurium of nerves

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 Nociceptors of the skin

• Respond to pain stimuli

• Free nerve endings: the simplest form of pain detector
– form dermal or epidermal nerve endings
• Peritrichial nerve endings or root hair plexuses
– wrap around the hair follicle
– stimulated when the hairs bend (detect movements of the hairs)

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 Skin sensory receptors – the big picture
• Nociceptive receptors
– are found near the skin surface and respond to pain
• Merkel disks and Meissner corpuscles (fine
mechanoreceptors)
– are located at the epidermal-dermal junction so they can detect gentle
touch
• Pacinian corpuscles and Ruffini endings (large
encapsulated mechanoreceptors)
– are found in the deep dermis and hypodermis and respond to transient
deeper touch

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 Hair follicles
• Tubular invaginations of the epidermis responsible for hair growth
• Constantly cycling between:
– Growth (anagen) phase
– Regression (catagen) phase
– Resting (telogen) phase
• Quiescent during the first 28 days of the telogen due to inhibitory
signals from the dermis (mainly from BMP’s)

• Increased Wnt/beta-catenin signaling promotes stem cell activation

to initiate the growth of new hair during the transition from telogen
to anagen.

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 Hair follicle - structure
• Hair follicle consists of two parts
– hair shaft – filamentous keratinized structure
– hair bulb – expanded invaginated portion
• associated with sebaceous and apocrine sweat glands

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 Hair follicle - structure
• Cross section of the shaft of thick
hair reveals three concentric zones:
– cuticle
– cortex
– medulla (absent in thin hair)
• The hair shaft consists of hard
keratin
• Vascularized connective tissue core
(dermal/hair papilla) projects into
the hair bulb, in close proximity to
matrix cells

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Hair bulb

Matrix cells

Dermal/hair papilla

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 Hair follicle - structure
Hair shaft is surrounded by:
• The external root sheath, a
downgrowth of the epidermis
• The internal root sheath,
– generated by the hair matrix cells
– made up of three layers of soft keratin
• Henle’s layer (outermost)
• Huxley’s layer (middle)
• cuticle of the inner root sheath

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 Arrector pili muscle
• Attaches hair follicle to epidermis at an
oblique angle
• The autonomic nervous system
controls the arrector pili muscle
• Contraction
– helps squeeze out sebum
– causes hair to stand up
– attachment site at the epidermis forms a small
groove, the so-called goose bump

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 Bulge stem cell pathways
• Follicular bulge - region of external root sheath between
near insertion of arrector pili muscle
• Follicular bulge stem cells can:
– re-establish the epidermis (basal cells)
– give raise to hair follicles (matrix cells)
– give rise to sebaceous glands
• Different activated oncogenes expressed in cells exiting
the bulge can give rise to specific tumor types:
– squamous cell carcinoma (Ras oncogene activation),
– basal cell carcinoma (PTCH/Gli1/2 activation of the Hedgehog signaling
pathway)
– hair-follicle tumors (Wnt/beta-catenin signaling pathway).

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 Sebaceous glands

• Holocrine gland present in entire skin except

palms and soles
• Secretory portion lies in the dermis, and the
excretory duct opens into hair follicle
• Can be independent of the hairs (hairless parts)
and open directly on to the surface.
E.g.,skin of the lips, corner of the mouth, glans
penis,labia minora, and the nipple
• Blockage, infection, and chronic inflammation
causes acne vulgaris

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 Sebaceous glands
• Branched acinar glands
• Excretory duct is lined by stratified squamous epithelium
• Holocrine secretion – cells die and contribute to secretion
• Produce oily secretion called sebum
• Also produce
– cathelicidin
– beta-defensins (BD1, BD2, and BD3),
• endogenous antimicrobial peptides (AMPs) that are part of the innate
immune system

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18. Skin http://accessmedicine.com/popup.aspx?aID=6182554&print=yes_chapter
Sebaceous glands

Sebaceous glands.

Sebaceous glands secrete a complex mixture of lipids called sebum into short ducts which generally open into hair follicles (a): Micrograph shows small cells near the
connective tissue capsule which proliferate and give rise to an acinus composed of large sebocytes (S), which undergo terminal differentiation by filling with small lipid
droplets and then disintegrating at the ducts (D) near the hair (H) shaft, with the loss of nuclei and other organelles. X122. H&E. (b): Micrograph showing the gland's capsule
Steady proliferation of the peripheral cells inside the capsule pushes sebum slowly and
and differentiating sebocytes at higher magnification X400. H&E. Sebum production is the classic example of holocrine secretion, in which the entire cell dies and contributes
to the secretory product. Steady proliferation of the peripheral cells inside the capsule pushes sebum slowly and continuously into the ducts. Myoepithelial cells are not

continuously into the ducts. Myoepithelial cells are absent

present.

Sebum is a complex mixture of lipids that includes wax esters, squalene, cholesterol and triglycerides which are hydrolyzed by bacterial enzymes after secretion.
Secretion from sebaceous glands greatly increases at puberty, stimulated primarily by testosterone in men and by ovarian and adrenal androgens in women. Specific
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functions of sebum appear to include helping maintain the stratum corneum and hair, as well as exerting weak antibacterial and antifungal properties on the skin surface.
 Sweat glands
• Two types:
– Eccrine sweat glands - merocrine mode of secretion
– Apocrine sweat glands - merocrine mode of secretion

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 Eccrine sweat glands
• Simple coiled tubular glands
• Involved with control of body temperature
• Innervated by cholinergic/parasympathetic nerves
• Secretory portion is composed of three cell types:
– Clear cells
– Dark cells
– Myoepithelial cells
• Clear cells
– separated from each other by intercellular
canaliculi,
– secrete most of the water and electrolytes (mainly
Na+ and Cl–) of sweat
– show basal domain infolding with abundant
mitochondria,
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– having membranes rich in Na+/K+-ATPase
 Eccrine sweat glands
• Dark cells
– rest on top of the clear cells
– secrete glycoproteins, including antimicrobial peptides: human
beta-defensins (BD1 and BD2), cathelicidin, and
dermicidin
• Myoepithelial cells
– located between the basal lamina and clear cells
– contract to assists in the release of secretion into the
glandular lumen
• Excretory duct portion is lined by a bilayer
of cuboid cells (stratified cuboidal)
– cells partially reabsorb NaCl and water under the influence of
aldosterone
– reabsorption of NaCl is deficient in patients with cystic fibrosis
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 Apocrine sweat glands
• Coiled glands
• Occur in the axilla, mons pubis, and
perianal area
• Contain secretory acini larger than those
in the eccrine sweat glands
• Excretory duct opens into the hair
follicle
• Functional after puberty and are
supplied by adrenergic nerves
• Two special examples of apocrine sweat
glands are:
– ceruminous glands in the external auditory
meatus – produce cerumen
– glands of Moll at the margins of the eyelids

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Apocrine and eccrine sweat glands

Apocrine sweat
glands

Eccrine sweat
glands

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 Fingernails
• Hard keratin plates (nail plate) on nail beds (only stratum
basale and stratum spinosum of the epidermis)
• Proximal edge of the plate is the root or matrix, where the
whitish crescent-shaped lunula is located
• Proximal edge is covered by a projecting fold of the
stratum corneum called eponychium (cuticle)
• Under the distal and free edge of the nail plate, the
stratum corneum forms a thick structure, the
hyponychium

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 Nail

A micrograph of a sagittal section from a fetal finger shows of the proximal nail fold (PNF) and its
epidermal extension, the eponychium (E) or cuticle. The nail root (NR), the most proximal region of the
Nails.

Nails are hard, keratinized derivatives formed in a process similar to that of the stratum corneum and hair. (a): Surface view of a finger shows the nail's major parts, including
nail plate (NP), is formed by a matrix of proliferating, differentiating keratinocytes. These cells make up
the crescent-shaped white area called the lunula, which derives its color from the opaque nail matrix and immature nail plate below it. (b): Diagram of a sagittal section
includes major internal details and shows the hyponychium at which the free end of the nail plate is bound to epidermis.

the dorsal nail matrix (DNM) and ventral nail matrix (VNM), which contribute keratinized cells to the
(c): A micrograph of a sagittal section from a fetal finger shows of the proximal nail fold (PNF) and its epidermal extension, the eponychium (E) or cuticle. The nail root (NR),
the most proximal region of the nail plate (NP), is formed like the hair root by a matrix of proliferating, differentiating keratinocytes. These cells make up the dorsal nail matrix
(DNM) and ventral nail matrix (VNM), which contribute keratinized cells to the nail root. The mature nail plate remains attached to the nail bed (NB), which consists of basal
nail root. The mature nail plate remains attached to the nail bed (NB), which consists of basal and
and spinous epidermal layers over dermis (D), but is pushed forward on this bed by continuous growth in the nail matrix. X100. Mallory trichrome.

spinous epidermal layers over dermis (D), butOFis

GLANDS pushed
THE SKIN forward on this bed by continuous growth in
Sebaceous Glands
the nail matrix Sebaceous glands are embedded in the dermis over most of the body surface, except the thick, hairless (glabrous) skin of the palms and soles. There is an average of
about 100 such glands per square centimeter of skin, but the frequency increases to 400–900/cm2 in the face and scalp. Sebaceous glands are branched acinar glands
with several acini converging at a short duct which usually empties into the upper portion of a hair follicle (Figure 18–12). The bulge region of the follicle is a stem cell
niche generating cells of the hair follicle and matrix, the neighboring epidermis, and associated sebaceous glands. In certain hairless regions, such as the genital glands, 57
eyelids, and nipples, sebaceous ducts open directly onto the epidermal surface. The acini consist of a basal layer of undifferentiated flattened epithelial cells on the basal
lamina. These cells proliferate and are displaced toward the middle of the acinus, undergoing terminal differentiation as distinctly large, lipid-producing sebocytes which
have their cytoplasm filled with small fat droplets (Figure 18–15). Their nuclei shrink and undergo autophagy along with other organelles and near the duct the cells