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Basic+Science+of+Skin

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hanalexian
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Basic Science of the Skin:

Structure and Function

Basic Dermatology Curriculum

Last updated September 2018


11
Goals and Objectives
 The goal of this module is to introduce learners to fundamental basic science
principles related to dermatology.
 By completing the module, the learner will be able to:
 Enumerate functions of the skin
 Recall the layers of the epidermis and the major roles of each.
 Based on a clinical photo, be able to distinguish two common blistering
dermatoses and the epidermal structures associated with each.
 Enumerate the major constituents of the dermis, including the structural and
cellular properties of each.
 Based on a clinical photo, be able to distinguish diseases associated with
disorders of dermal constituents.
 Name the major function of the pannus/subcutis and recognize some
inflammatory disorders of the fat.

2
Module Outline
 Functions of the skin
• Skin conditions related to disorder of
skin function

 Basic anatomy of the skin


• Related cutaneous diseases

 Take-home points

3
Functions of the Skin:
Barrier function
 The skin provides a physical barrier that regulates
water loss and protects against mechanical, chemical
and microbial insults from the external environment.
 Dysfunction of the skin barrier leads to injury,
dehydration, infection and inflammation.

• This child has atopic


dermatitis, a chronic skin
condition associated with
barrier dysfunction.

4
Functions of the skin:
Immunologic function
 The skin is an immunologic barrier that both
senses and responds to pathogens.
 Dysfunction of the immunologic barrier leads to
infection, skin cancer, inflammatory skin
conditions and allergy.
Image courtesy of UT
• This patient has impetiginized Southwestern
mycosis fungoides, a type of skin Department of
lymphoma. Dysfunction of Dermatology
cutaneous lymphocytes increases
risk for bacterial and fungal skin
colonization and subsequent
infection.

5
Functions of the skin:
Temperature regulation
 The skin helps maintain a constant body temperature
with the insulating properties of fat and hair and
through accelerating heat loss with sweat production
and a dense superficial microvasculature.
 Dysfunction of temperature regulation leads to hyper-
or hypothermia.
This patient is erythrodermic, in
which >90% of the skin is red
and/or inflamed. Extensive
cutaneous vasodilation can cause Image courtesy of UT
hypothermia and high-output Southwestern
cardiac failure. Department of
Dermatology

6
Functions of the skin:
Protection from radiation
 The pigment melanin in the epidermis protects
cells against ultraviolet radiation.
 Dysfunction of melanin production causes the
patient to be more susceptible to skin cancer.
• This patient with albinism
has a subtle melanoma
on the cheek.

Images courtesy of UT
Southwestern
Department of
Dermatology

7
Functions of the skin:
Nerve sensation
 Sensory receptors allow the skin to constantly monitor the
environment and mechanoreceptors in the skin are
important for the body’s interactions with physical objects
 Dysfunction leads to pruritus (itch), dysesthesia (abnormal
sensation), and insensitivity to injury (e.g. diabetes,
leprosy).

• This photo is of a chronic


ulcer on the foot of a patient
with peripheral neuropathy
related to diabetes.

8
Functions of the skin:
Injury repair
 The cutaneous wound repair process has four phases:
coagulation, inflammatory phase, proliferative-migratory
phase (tissue formation), and remodeling phase
 Loss of ability to repair injury (e.g. post-radiation
treatment) leads to delayed wound healing .

• This patient has a chronic ulcer


following trauma on the scalp in a
site previously irradiated as part
of treatment for squamous cell
carcinoma.

9
Functions of the skin:
Appearance, Quality of Life
 Skin defects and even physiologic aging can result in
considerable psychological distress, an important clinical
feature of many cutaneous diseases.
• The patient on the right has
HIV-associated lipoatrophy,
characterized by loss of fat
throughout the face. This finding
is stigmatizing in some patients.

• The patient on the left has
vitiligo which can impact self-
esteem and even result in
ostracization in some cultures.
• .

Photo courtesy: Amit Pandya, MD

10
Basic Anatomy of the Skin:
Layers of the skin
Skin is composed of three layers:
• Epidermis
• Dermis
• Subcutis
a

Can you name the layers of the


skin pictured here?
b

11
Basic Anatomy of the Skin:
Layers of the skin
 The epidermis is the topmost layer, and consists
primarily of keratinocytes.
 The dermis lies below the epidermis, and
consists primarily of fibroblasts, collagen, and
elastic fibers.

Epidermis

Dermis

12
Basic Anatomy of the Skin:
Layers of the skin
Below the dermis lies fat, also called subcutis,
panniculus, or hypodermis.
Epidermis

Dermis

Subcutis

13
Basic Anatomy of Skin:
Cutaneous Structure
 Layers of the skin
• Epidermis: layers, cell types, and
function
• Dermis: layers, cell types, and
function
• Subcutis
 Adnexal structures

14
Can you name the four major layers of
the epidermis?

15
Can you name the four major layers of
the epidermis?

Stratum corneum

Stratum granulosum
(granular cell layer)

Stratum spinosum
(spiny layer)

Stratum basale
(basal cell layer)

16
Functions of the layers of the epidermis

We will review the layers from bottom up, since that is the
order in which epidermal cells mature over their two-week
life cycle from the basal cell layer to the stratum corneum.
They are then shed two weeks after reaching the stratum
corneum (for a 28-day cycle). The cells differentiate as they
move upwards through the layers.
• Basal layer
• The basal layer is the source of
epidermal stem cells. Cell division
occurs here.
• Keratinocytes start in the basal
layer and move upwards.

17
Functions of the layers of the epidermis

Spinous layer
• Center of epidermis. Has a
“spiny” appearance due to
desmosomal junctions (see
slide 32), which hold the
keratinocytes together.
Basal layer

18
Functions of the layers of the epidermis

3. Granular cell layer


• Lipids produced by the
keratinocytes in the
granular cell layer and
secreted into the
extracellular space
between the keratinocyte
forms a water barrier that
keeps water in the skin
2. Spinous layer
1. Basal layer

19
Functions of the layers of the epidermis

Stratum corneum
• Made up of desquamating
keratinocytes. Thick outer
layers of flattened keratinized
non-nucleated cells provide a
barrier against trauma and
infection.
Granular cell layer
Spinous layer
Basal layer

20
The Stratum Corneum
• The stratum corneum is like a wall of bricks
and mortar
• Bricks: flattened keratinocytes filled with keratin and
filaggrin
• Mortar: lipid mixture, which surrounds the keratinocytes
and provides the water barrier

Keratin and Lipid


filaggrin-filled intercellular
corneocyte matrix

21
NOTE
Filaggrin - an important protein in barrier
function
 Filaggrin is a protein found in the granular cell
layer of the epidermis.
 Filaggrin retains water within keratinocytes
 Mutations in filaggrin cause
atopic dermatitis and other
atopic diseases, such as
asthma
• This child has atopic dermatitis.
Notice the dry, erythematous,
plaques on the lower leg

23
Diseases related to dysfunction of the
epidermal layers
 Certain diseases cause loss of adhesion:
• Bullous pemphigoid: an autoimmune blistering disease, typically
affecting older patients. Autoantibodies form to hemidesmosomes
that attach the basal layer of the epidermis to the basement
membrane. Clinical findings are tense bullae with background
edematous pink plaques. (mucous membranes are rarely affected)

24
Diseases related to dysfunction of the
epidermal layers
 Certain diseases cause loss of adhesion:
• Pemphigus Vulgaris: an autoimmune blistering disease predominantly
in young to middle-aged adults. Autoantibodies form to desmosomes that
attach the keratinocytes to one another, which are highlighted by direct
immunofluorescence (shown on the bottom right). Basal layer remains
attached via hemidesmosomes to the basement membrane. Clinical
findings are erosions or flaccid bullae, mucous membranes are often
affected.

Images courtesy of UT Southwestern Department of Dermatology

25
Diseases related to dysfunction of the
epidermal layers

 In psoriasis, the rate of


epidermal turnover is increased
and there is over-proliferation of
keratinocytes causing plaques.
 There is inadequate time for cell
differentiation and maturation
due to the accelerated rate of
cell turnover. This causes scale
in the stratum corneum.

26
In the next pathology slide, see if
you can identify this common skin
cancer based on what you have
learned about the layers of the skin

27
What type of skin cancer is pictured here?
(Hint: Which layer of the epidermis do these cells resemble?)

28
Basal Cell Carcinoma

 Most common form of


skin cancer.
 Composed of cells that
resemble basal
keratinocytes.
 Most commonly presents
as pearly, erythematous
papules or plaques with
rolled borders and
telangiectasias in sun-
exposed areas.

29
Epidermis: Types of Cells
• Four main types of cells make up the
epidermis:
• Keratinocytes
• “Clear Cells” of the lower/basal layers
of the skin:
• Melanocytes
• Langerhans cells
• Merkel cells

30
Note
Keratinocytes
 Keratinocytes are the main
structural cell of the epidermis.
They are held together by
adhesion proteins called
desmosomes. These
attachments microscopically
resemble spines between each
keratinocyte and are most visible
in the spinous layer.

32
“Clear Cells”: Melanocytes
 The second type of cell which resides in the epidermis is the
melanocyte.
 Melanocytes are staggered along the basal layer at around one to
every 10 keratinocytes.
 Melanocytes are pigment-producing cells that transfer a pigment
called melanin to the keratinocytes in the basal cell layer.

33
Nevi and Melanoma
 Melanocytic nevi or moles,
are benign collections of
melanocytes.
 Melanoma shown here, is a
malignancy of melanocytes.

Image Courtesy of UT
Southwestern
Department of
Dermatology

34
“Clear Cells”: Langerhans Cells
 Langerhans cells are dendritic antigen-presenting cells found in
the lower to mid-epidermis.
 Langerhans cells uptake and process antigen and can exit the
epidermis to travel to the closest skin-draining lymph nodes and
present antigen to naïve or memory T-lymphocytes.
 They are important in the induction of delayed-type
hypersensitivity.

• A common skin disease in which


Langerhans cells play a
prominent role is allergic contact
dermatitis, such as poison oak

35
“Clear Cells”: Langerhans Cells

36
“Clear Cells”: Merkel Cells
• Merkel Cells are a mechanoreceptor cell found in the basal layer of the
epidermis.
• They form a complex with afferent sensory nerve endings associated with touch,
and are found more densely in touch-sensitive areas of the skin; they are
essential for discrimination of fine spatial details.
• Merkel cell carcinoma is a very rare, aggressive form of skin cancer that typically
presents as a deep pink to red nodule. It may mimic a furuncle or inflamed cyst.
The photos below are clinical examples of this cancer.

Images courtesy of UT Southwestern Department of Dermatology


Outline: Basic Anatomy of Skin
 Layers of the skin
• Epidermis: layers, cell types, and
function
• Dermis: layers, cell types, and
function
• Subcutis
 Adnexal structures

38
Let’s move onto the dermis, which is shown
below. Name the two layers of the dermis.

39
The two layers of the dermis

Papillary
dermis

Reticular
dermis

40
Parts of the Dermis
 The dermis provides a flexible but tough support structure.
 Between 1-4 mm thick (depending on age and body location), making it
much thicker than the epidermis.
 Structural components are: collagen type I (strength), elastic fibers
(elasticity), and extrafibrillar matrix (gelatinous
glycosaminoglycans that bind water).
 Contains the blood vessels (surrounded by type III collagen) along with
lymphatic vessels, and nerves.

 Adnexal structures of the dermis include:


 Apocrine and eccrine sweat glands, sebaceous glands, and hair follicles.
 Cells of the dermis include:
 fibroblasts, macrophages, and mast cells.

41
Structural Components of the Dermis:
Collagen/Elastic Fibers
• Pictured here is a patient with • Pictured here is a patient with
Ehlers-Danlos Syndrome, a solar elastosis on his neck. This
family of genetic disorders in finding is a result of chronic UV
collagen type I and/or type III. exposure causing degradation of
Patients can have hyper- collagen and elastic fibers.
extensible joints, skin or vascular
aneurysms.

Images courtesy of UT Southwestern Department of Dermatology


Adnexal Structures of the Dermis
 This is a biopsy from the scalp
to show the follicles and
sebaceous (oil) glands, found
in the dermis.
 Note the many hair follicles
(yellow arrow) running through
the dermis.
 Each follicle has associated
sebaceous or oil glands (blue
arrow).
 Red arrow – epidermis
 Green arrow – reticular dermis

43
Adnexal Structures of the Dermis:
The pilosebaceous unit
 Adnexal structures include the
pilosebaceous unit and eccrine
gland
 Pilosebaceous unit consists of:
1. A hair follicle
2. Sebaceous (oil) glands
3. Apocrine* sweat glands
4. An arrector pili muscle (when these
contract you get goosebumps)
Apocrine glands are found in the axillary and anogenital
areas, which is why we do not see them on this biopsy of
the scalp. These glands open directly in to the hair follicle.

44
Adnexal Structures of the Dermis:
• Pictured here is a condition called keratosis pilaris, it is a disorder of
keratin retention in the infundibulum of the hair follicle.

Image courtesy of UT Southwestern Department of Dermatology


Adnexal Structures of the Dermis:
• Pictured here are normal sebaceous glands of the genital skin. In some
patients they are more prominent and are called “Fordyce spots.” These can
also occur on other mucosal surfaces.

Images courtesy of Klint Peebles, MD. All


Image courtesy of UT Rights Reserved.
Southwestern
Department of
Dermatology
Adnexal Structures of the Dermis:
Pilosebaceous Unit Disorders
 Acne vulgaris is a disorder of the
pilosebaceous unit.
 It is caused by 4 factors:
• Plugging of the hair follicle as a result of
abnormal keratinization of the upper
portion (gives rise to comedones)
• P. acnes (bacteria) in the hair follicle
(lives on the oil and breaks it down to free
fatty acids which cause inflammation)
• Presence of hormones (androgens)
• Sebaceous gland activity (increased in
presence of androgens)

47
Adnexal Structures of the Dermis:
Eccrine Sweat Glands:
 Eccrine sweat glands do not involve the hair follicle. They open
directly onto the skin surface and are present throughout the body.
 Eccrine glands help regulate body temperature by excreting sweat
onto the skin surface, where cooling evaporation takes place.
 Eccrine glands are sometimes genetically absent, which will
predispose a patient to hyperthermia.
• Pictured here is a patient
with hyperhidrosis, which
is due to cholinergic
over-stimulation of the
eccrine sweat glands,
which are innervated by
Image courtesy of UT Southwestern Department of Dermatology
the sympathetic nervous
system.

48
Cells of the dermis: Fibroblasts
 Fibroblasts are responsible for the synthesis and
degradation of connective tissue proteins
 They are instrumental in wound healing and
scarring

• Keloids (abnormal scars) result


from uncontrolled synthesis and
excessive deposition of
collagen at sites of prior dermal
injury and wound repair

49
Cells of the dermis: Mast Cells
 Mast cells are specialized
cells that are responsible
for immediate-type1
hypersensitivity reactions
in the skin
• The mast cell is the major
effector cell in urticaria,
which is a vascular
reaction of the skin Image courtesy of UT
characterized by wheals Southwestern
Department of
surrounded by a red halo Dermatology
or flare.

50
Outline: basic anatomy of skin
 Layers of the skin
• Epidermis: layers, cell types, and
function
• Dermis: layers, cell types, and
function
• Subcutis

51
The Subcutis
 The subcutis is the fat layer which
separates the dermis from deeper
underlying structures such as
fascia and muscles. It is mostly
comprised of adipocytes and Image courtesy of UT
connective tissue linked to the Southwestern
Department of
fascia below.
Dermatology

 The subcutis insulates the body,


serves as an energy supply,
cushions and protects the skin, Pictured here is a patient with morphea
and allows for its mobility over in which there can be loss of subcutis
causing the skin to become bound-down
underlying structures and causing limb contractures in some
cases.

52
Disorder of the subcutis
 Erythema nodosum is an example
of panniculitis (inflammation of the
subcutis)
• Clinically appears as deep-
seated erythematous nodules,
typically on the shins
• Erythema nodosum may be
idiopathic or a reaction to lung or
GI infections, sarcoidosis,
medication, or an underlying
autoimmune enteric tract
disease (e.g. Crohn’s disease)

53
Review, Layers of the skin
Epidermis
Papillary dermis

Reticular dermis

Subcutis

54
54
Basic Science of the Skin
Summary
 Layers of the skin
• Epidermis: basal, spinous, granular, corneum.
Melanocytes, Langerhans cells, Merkel cells
• Dermis: collagen, extracellular matrix, elastic
fibers, lymphatics, blood vessels, fibroblasts,
mast cells, antigen presenting cells
– Adnexal structures in dermis: hair follicles, apocrine
and eccrine sweat glands, sebaceous glands
• Subcutis: adipocytes and connective tissue

55
Acknowledgements
 This module was developed by the American Academy of
Dermatology’s Medical Student Core Curriculum Workgroup
from 2008-2012.
 Primary author: Elizabeth Buzney, MD.
 Contributors: Sarah D. Cipriano, MD, MPH; Ron Birnbaum, MD.
 Peer reviewers: Susan Burgin, MD, FAAD; Peter A. Lio, MD,
FAAD.
 Revisions: Sarah D. Cipriano, MD, MPH Joslyn S. Kirby, M.D.,
Heather W. Goff, MD, MPH.
 2018 Update and Review by Heather W. Goff, MD, MPH. Peer
Reviewed by J. Klint Peebles, MD, and Joslyn Kirby, MD, MEd,
MS.

56
References
 Berger T, Hong J, Saeed S, Colaco S, Tsang M, Kasper R. The Web-Based
Illustrated Clinical Dermatology Glossary. MedEdPORTAL; 2007. Available from:
www.mededportal.org/publication/462.

 Bolognia JL, Jorizzo JL, Rapini RP. Dermatology, 2003, Elsevier Limited.
 Chu David H, "Chapter 7. Development and Structure of Skin" (Chapter). Wolff K,
Goldsmith LA, Katz SI, Gilchrest B, Paller AS, Leffell DJ: Fitzpatrick's Dermatology
in General Medicine, 7e:
http://www.accessmedicine.com/content.aspx?aID=2950881.

 Proksch Ehrhardt, Jensen Jens-Michael, "Chapter 45. Skin as an Organ of


Protection" (Chapter). Wolff K, Goldsmith LA, Katz SI, Gilchrest B, Paller AS, Leffell
DJ: Fitzpatrick's Dermatology in General Medicine, 7e:
 http://www.accessmedicine.com/content.aspx?aID=2977622.
• https://www.cell.com/trends/immunology/fulltext/S1471-4906(17)30123-0?code=cell-site
• https://www.cell.com/trends/cell-biology/abstract/S0962-8924(14)00182-2

57

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