2. SKIN
Largest organ of body
S.Area approaching 2 msq
wt= 16-20% of body wt
TISSUE- epithelial: epidermis,dermis
-adipose: hypodermis
Accessory/appendageal strs- hair, nail, glands,
receptors
Types of skin- glabrous & hair bearing
3. Types of skin
a) Hairy skin
Has hair follicle & sebaceous gland
Majority of area of body
b) Non hairy skin
Glabrous
Thick epidermis
Lack of hair follicle & sebaceous gland
Palms and soles, Areola, glans, labia
Dermatoglyphics
5. Development of skin
Stages of Development
Specification
– from 0 – 60 days [ EMBRYONIC PERIOD]
– division of structures committed to
forming epidermis and dermis
- patterning of future layers
Morphogenesis
– from 2-5 months [EARLY FETAL PERIOD]
– specialized structures form
Differentiation
– from 5-9 months [LATE FETAL PERIOD]
– specialized tissues further develop
6. Development of skin
a) Ectoderm
Epidermis
Folliculosebaceous apocrine unit
Eccrine sweat glands
Nail
b) Neuroectoderm
Melanocytes
Nerves
Specialized sensory receptors
7. Development of skin
c) Mesoderm
Macrophages
Mast cells
Muscles
Langerhans cells
Fibrocytes
Blood vessels
Lymph vessels
Adipocytes
8. Epidermis
Terminally Differentiated
Stratified squamous epithelium
Cornifying epithelium
Thinnest component
Thickness is 0.4 mm to 1.6 mm [avg- 1mm]
Metabolically active
4 types of cells
9. Layers of Epidermis
A. Stratum basale
B. Stratum spinosum
C. Stratum granulosum
D. Stratum corneum
13. A. Stratum basale
Germinative layer
Single layer
Keratinocytes are cuboidal or columnar cells
Most basophilic cytoplasm in epidermis & Large oval
nucleus
Attatched to BMZ by hemidesmosomes & to each other
by desmosomes
Contain membrane bound vacuoles with pigmented
melanosomes
Transferred from melanocytes by phagocytosis
Primary site for mitotically active cells
Contains tonofilaments which form the developing
cytoskeleton
14. B. Stratum spinosum
Suprabasal keratinocytes
5-10 cell layer thick
Polygonal in shape with rounded nucleus
Have delicate spine like processes
Spinous processes contact with adjacent keratinocytes &
resists mechanical stress
On moving up become flatter & develop organelles-
lamellar granules/odland bodies
Have large bundles of keratin filaments around mucleus &
inserted into desmosomes peripherally
15. Keratinocyte – keratinocyte adhesion is through cadherins:
desmogleins and desmocollins
Desmosomal cadherins are linked to intracytoplasmic Ifs by
plakoglobin and desmoplakin
16. C. Stratum granulosum
Flat diamond shaped cells
1-3 cell layer thick usually but up to 10 layers thick in
palms and soles
named so due to – KHG-Coarse basophilic granules
composed of profilaggrin, keratin filaments & loricrin
Lamellated granules /Membrane coating granules /
odland bodies seen
Cornified cell envelope begins to form here
17. D. Stratum corneum
Cells called corneocytes , outermost layer
flattened,Anucleated, dead cells
Lost nuclei & cell organelles
Contain high molecular wt. Keratins stabilized by
disulfide bonds
5-20 cell layer thick
Arranged regularly & orderly
Provide mechanical protection, barrier to h2o loss &
permeation of soluble substances from envt
18. STRATUM LUCIDUM
Seen in areas of thick epidermis- palms & soles
Electron luscent & hence the name
b/w S.C & S.granulosum
Cells nucleated & called transitional cells
Stratum conjunctus
Odland bodies rich in protein bound lipids
19. Keratohyaline granules
Form the amorphous protein in which
tonofilaments are embedded
First appear in Stratum spinosum
Mainly seen in Stratum granulosum
Hygroscopic, repeated hydration and
dehydration contributes to normal desquamation
of S.corneum
20. Contain protein – profilaggrin
Profilaggrin degraded to filaggrin in Granular layer
(FILAGGRIN – Filament aggregating protein)
Contain cystine rich proteins whose disulfide
bonds – chemical inertness & strength of cornified
layer
Filaggrin -
Histidine rich
Cationic protein
Acts as ‘interfilamentous glue’
Aggregate & align KIF
Water retention in S.corneum
21. Lamellar granules
Membrane coating granules or Odland bodies
300 nm diameter
Appear near golgi apparatus
Spinous ,granular layer
Arranged in orderly repeating pattern of light and
dense lamellae
Dense lamellae maybe thick or thin
22. Light lamellae contain phospholipid
Dense lamellae contain proteins and hydrolytic
enzymes, have acid phosphatase activity
Contain free sterols, polar lipids, hydrolytic
enzymes, lipases and glycosidases
Organized crystalline lamella acts as effective
waterproof mantle, due to remodelling of Polar
lipids to Neutral lipids
Mediate s.corneum cell cohesion due to
presence of lipids
23. Cornification
Cornified cells – end products of
differentiation of epidermal & adenexal
keratinocytes
Involves
1. Synthesis of distinctive proteins & lamellar
granules
2. Alteration of nuclei, cytoplasmic organelles,
plasma membrane, desmosomes
24. Cornified cellular envelope
Also called’ ‘marginal band
Plasma membrane of upper granular layer
thickens internally
15 nm thick
Forms cutaneous barrier to injurious agents, chemicals,
enzymes
Loricrin is the major component
25. Formed as a result of Calcium dependent enzyme
epidermal transglutaminase
Lipid envelope – determinant of cohesiveness of
stratum corneum
26. Desmosomes
Specialized for Cell to cell adhesion
Major Junctional Adhesion Complex
Anchors KIF to Cell membrane and Bridges
adjacent keratinocytes
Helps to resist shearing forces
27. Desmosomes
Ultrastructure :-
Present in the junction between 2 adjacent cells
Contain electron dense material in the cytoplasm running
parallel to the junctional region
3 ultrastructural bands present,
- An electron dense band next to Plasma
membrane
- A less dense band
- A fibrillar band
Intermediate Filaments loop through this region
30. Desmosomes
Dsg1 and Dsc1 expressed in superficial layers of
Epidermis
Dsg3 and Dsc3 expressed in Basal Keratinocytes
Desmosome formation requires presence of
Desmoplakin, Plakoglobin and Plakophilin2
Plakophilin1 stabilizes Keratinocyte adhesion on
differentiated keratinocytes
34. KERATINOCYTES
Most abundant cell in epidermis (95%)
Ectodermal in origin
Role in biochemical & Immune functions of skin
Form desmosomes
Contain Keratin intermediate filaments or
Tonofilaments (7nm diameter)
Mol.wt. of keratin varies from 40-70 kDa
Divided into 2 types after electrophoresis
- Basic (type 1-8)
- Acidic(type 9-19)
35. KERATINOCYTES
The genes coding for these are similarly grouped
as Basic or Acidic
Keratins Co-express in pairs according to tissue
patterns of differentiation, eg.
K8/K18 - Simple Epithelium
K5/K14 - Str. Sq. Epithelium (Basal Layers)
K1/K10 - For Epidermal
Differentiation(Suprabasal)
36. Tonofilaments increase in number and
molecular weight as cell ascends
Tonofilaments form a ‘cytoskeleton’
In corneocytes, tonofilaments form a fibrous
protein – alpha keratin
Alpha keratin -
- Embedded in sulphur rich matrix
- No disulfide bonds for alpha keratin
- Provides flexibility & elasticity to St.corneum
37.
38. Melanocytes
Dendritic cells
Cells responsible for skin pigmentation
Derived from neural crest
Present in basal layer
2nd most abundant cells in epidermis
Most commonly seen in face and exposed areas
Also seen in mucous epithelium, hair follicles, retina,
uveal tract, leptomeninges, inner ear, mesentery
Enter epidermis in 7-8 wks
By 10th wk – contain melanosomes
39. Melanocytes
Stained by Silver salts
Nuclei are smaller & more basophilic than basal
keratinocytes
Ovoid nucleus with Pale staining cytoplasm
Contain melanosomes within them which synthesize &
secrete melanin
Dendrites arborize in all directions b/w keratinocytes
Connected to keratinocytes by processes & not
junctions
1 melanocyte associated with 36 basal & suprabasal
keratinocytes (Epidermal – melanin unit)
42. Described by Paul Langerhans in 1868
Dendritic cells present in basal spinous &
granular layers
Appear by 7th week of fetal life
Originate from mesenchymal precursors in the
Bone Marrow
Responsible for skin immunity
3rd most abundant cell in epidermis (3%)
Replicate within the epidermis (cc – 16d)
Number 460 – 1000/mm2 of epidermis
Don’t form junctions
43. Appear as Clear cells by H&E staining &
convoluted nuclei
Special staining needed to differentiate from
melanocytes
Identification –
Immunostaining by CD1a , S-100 or vimentin
Impregnation by AuCl2
Staining by ATPase
Staining by alpha D mannosidase
L-DOPA Fluorescence
Most reliable method – Electron Microscopy-
show rod/raquet shaped granules- birbeck
granules
44. Express C3b, Fc component of IgG and
CD 1a on their surface
Responsible for recognition, uptake,
processing & presentation of soluble
antigen to sensitized T lymphocytes
But may also cause Allograft rejection
Reduced in psoriasis, sarcoidosis, UVB
irradiation
45. Birbeck’s Granules
Rod-shaped structures specific to epidermal LC’s
Langerin is a protein implicated in Birbeck granule
biogenesis
BG’s represent secretory structures formed in the
Golgi area
Involved in transport of cargo molecules to cell
membrane
In mature LC’s, Langerin traffic is abolished and loss
of internal Langerin leads to depletion of Birbeck
granules
Langerin is a transmembrane type II Ca2 -dependent
lectin
46.
47. Merkel cells
Touch receptors
Least abundant cell in epidermis
Present in basal layer of epidermal cells
Slow adapting, type 1 mechanoreceptores
Located in sites of high tactile sensitivity
Receive stimuli as keratinocytes are deformed
& respond to secretion of chemical transmitters
Found in both hairy & glabrous skin
48. Cells have pale staining cytoplasm
Nucleus lobulated
Margins of cells project spines towards
keratinocytes
Immunohistochemical markers include
----- K18, K19, K20 (more specific)
Make synaptic contact with nerve ending to
form merkel cell neuritic complex
49.
50. Functions Of Skin
Maintain integrity of body
Protects from injurious stimuli
Absorbs & excretes liquids
Regulation of body temperature
Absorbs UV light
Metabolism of vitamin D
Conducts sensory stimuli
Acts as immunological barrier
Psychosocial function
51. Epidermis
Barrier is largely situated in the epidermis
Once epidermis is removed the residual dermis is
almost completely permeable
Epidermal barrier is localised to stratum
corneum
52.
53. Barrier function
There is uniformly good diffusion barrier throughout
stratum corneum
The barrier depends upon both the cornified material of
keratinocytes & intercellular material – lipids
The two compartment “Bricks & Mortar” model has been
currently accepted
The Corneocytes are compared to Bricks
Extracellular matrix is compared to Mortar
54.
55. Barrier function
Within the stratum corneum two types of proteins are synthesized
1) Fibrous proteins of keratin
2) Histidine rich proteins known as Keratohyalin & Filaggrin
56. Barrier function
Around each corneocyte an envelop is formed by cross
linking of precursors Involucrin & Keratohyalin which
forms an insoluble exoskeleton & acts as scaffold for
internal keratin filaments
The intracellular cement is the product of ovoid
organelles, 0.2 – 0.3 micrometer known as membrane
coating granules or Odland bodies/Lamellar
bodies/cementosomes
57. Barrier function
Lamellar bodies become identifiable in cells of spinous
layer & migrate to cell periphery & fuse with plasma
membrane in granular layer
Then they discharge their contents into intercellular
spaces which expand to form 10 – 40% of total volume of
tissue
Lamellar bodies originally contain neutral sugars linked
to proteins & lipids, hydrolytic enzymes & sterols but
composition changes as they move outwards
58. Barrier function
In consequence of their origin by fusion of flattened
vesicles, the intercellular lamellae consists of two lipid
bilayers
So stratum compactum has been considered to form
principle diffusion barrier
This shows that epidermal barrier resides almost
completely in the stratum corneum
59. Barrier function
For certain materials there may be a second barrier at
or near the dermoepidermal junction, but
for most substances the stratum corneum remains the
principle barrier
Damage to or reduction in stratum corneum is followed
by
1) Increased percutaneous absorption
2) Increased transepidermal water loss
60. Barrier to UV radiation
The sun radiation is made up of IR, visible, & UV light & it is the UV light
that affects the skin
Shorter wavelength UV-B is the main cause of sun burn & in longterm causes
skin cancer
UV-A rays penetrate more deeply & play role in ageing
61.
62. Barrier to UV radiation
Skin has two barriers
1) Melanin barrier in epidermis
2) Protein barrier in stratum corneum
These function by minimizing absorption of UV radiation
by DNA & other cellular constituents
63. Barrier to UV radiation
Melanin is synthesized by melanocytes in basal layer &
transferred to surrounding keratinocytes
Partially protective mechanism of delayed tanning is
associated with increased melanocytes & melanosomes
Absorption of radiation by epidermal lipids also
contribute to protection from UV radiation
64. Mechanisms by which melanin protects
Being an opaque molecule, melanin physically blocks and
scatters UV light
It acts as an in vivo thermophile, absorbs light & converts
it into heat
Melanin traps the free radicals formed by action of UV
rays on tissue, thus minimizing damage
65. Percutaneous absorption
Skin is considered to be a composite membrane with 3 anatomically distinct
layers
1) The stratum corneum (10 micrometer)
2) The viable epidermis (100 micrometer)
3) Uppermost papillary layer of dermis (100 – 200 micrometer)
Each has a different diffusion constant
66. Percutaneous absorption
Even healthy, adult human skin allows some permeation of almost every
substance
Properties of skin barrier have a purely physicochemical basis & do not
depend upon energy requiring activities of living cells
67. Percutaneous absorption
Three possible anatomic pathways have been identified by which
substances pass
1) Through intercellular spaces
2) Through appendages
3) Through stratum corneum
Diffusion through stratum corneum is the most critical & rate limiting step
68. Factors influencing stratum corneum barrier function
Site : Face, scrotum & back of hands are more
permeable
Age : Due to finer structure, skin of infants & elderly
is more permeable
Lipid concentration of stratum corneum
Appendages
Environmental factors
69. Barrier to micro organisms
AMP (Antimicrobial peptides) acts as a chemical barrier
Intact stratum corneum prevents invasion of skin by normal skin flora or
patho.micro organisms
Minor injury / skin diseases Microbes
Appendages Microbes Folliculitis
Microbes colonize readily in moist & flexural areas
70. Barrier to micro organisms
Sustained microbial growth is prevented by
Dryness of skin surface
Continuous shedding of corneal cells
Sebaceous lipids antibacterial activity
Glycophospholipids & FFA of stratum corneum bacteriostatic activity
71. Antimicrobial peptides (AMP)
Group of peptides present on epithelial surfaces such as epidermis & its
appendages
These act as first line of immune defence
Directly kill a broad spectrum of micro organisms including gram positive &
gram negative bacteria, fungi & certain viruses
Two major families of AMP
Defensins
Cathelicidins
72. Defensins
Family of gene encoded antibiotics that are
subdivided according to the alignment of the disulfide
bridges into
Alfa-defensins
Beta-defensins
73. Alpha defensins
Six in number
First four 1,2,3,4 : Human neutrophil peptides (HNPs)
These increase the expression of TNF-alpha & IL-1 in human monocytes
Alpha-defensins 5,6 : Human defensins (HDs)
These are expressed in paneth cells of small intestinal crypts & epithelial
cells of female genital tract
74. Beta defensins
Four types have been identified
Referred to as Human beta defensins (HBDs) 1 – 4
Broad spectrum antimicrobial activity
Chemotactic for immature dendritic & memory T cells
As an adjuvant in enhancing antibody production
76. LL-37
Has two leucin residues
37 amino acids long
Broad spectrum antimicrobial activity
Chemotactic for inflammatory cells
Potential to participate in innate immune response
by killing bacteria
by recruiting cellular immune response
77. hCAP-18
Cationic AMP whose mass before proteolytic
processing is approx 18 K Da
Impaired production of AMPs has been observed in
atopic dermatitis
79. Sensory & autonomic functions
The skin is innervated by a dense three dimensional network
of highly specialized afferent sensory & efferent autonomic
nerve branches
The sensory nervous system detects the sensations of touch,
vibration, pressure, change in temperature, pain & itch
The autonomic nervous system is innervated by Post ganglionic
Cholinergic parasympathetic nerves
Adrenergic & cholinergic sympathetic nerves
80. Sensory & autonomic functions
Autonomic nervous system has an important role in
maintaining cutaneous homeostasis by regulating vasomotor
functions, pilomotor activity & eccrine sweat gland
secretion
The sensory nerves are either myelinated A fibres or
unmyelinated C fibres
In upper dermis, small myelinated nerves lose their nerve
sheaths & together with unmyelinated nerves end in either
Free nerve ending
Specialized sensory receptors
Meissner’s corpuscles
Merkel’s receptor
81. Sensory & autonomic functions
Categories of afferent unit are
Mechanoreceptors
Thermoreceptors
Nociceptors
83. Temperature regulation
Lying at the boundary between body & the environment, the skin plays an
important role in thermoregulation
The internal body temperature is maintained near 37 C
The skin provides a sensory input to thermoregulation i.e serves as source of
thermal information
84. Temperature regulation
Functions to allow heat loss or conservation i.e serves as effector organ for
controlling heat loss from the body
The thermoreceptor cells of skin are distributed irregularly over the skin
Warm sensitive thermoreceptors
Cold sensitive thermoreceptors
85. Temperature regulation
These receptors send information regarding change in temperature to
hypothalamus
This causes either
Inhibition of sweating or
Stimulation of shivering
Skin temperature has a greater role in mediating behavior
Use of shelter
Space heating &
clothing
86. Temperature regulation
Heat can be lost through the skin by
Radiation
Convection
Conduction &
Evaporation
Of importance in these mechanisms is the rich blood supply of the dermis
which is much greater than that needed for nutrition
87.
88. Temperature regulation
The cutaneous circulation, particularly system of A-V shuns which are
plentiful in the feet, hands, lips, nose & ears enable blood flow to an
extensive & more superficial venous plexus
In high temperatures the process of evaporation is considerably enhanced by
eccrine sweating
89. Mechanical functions
Mechanical properties of skin depends mainly on the dermis
Skin can be compressed & is elastic due to presence of ground substance,
collagen & elastic fibres in dermis
Proteins, lipids & low molecular weight byproducts of keratohyalin
breakdown seen in stratum corneum are referred to as natural moisturizing
factors
These bind & retain water in stratum corneum thus maintaining elasticity
90. Vitamin D
Vitamin D3 is derived from 7-dehydrocholesterol
Occurs in the basal layer of the epidermis
7 – dehydrocholesterol
Previtamin D3
Vitamin D3
UVB
Thermal
isomerization
91. Vitamin D
Vitamin D3 is chemically inert – has to be activated
It is first hydroxylated at C25 in the liver
Then at C1a in the kidney
Eventually activated to 1,25 – dihydroxy - D3
92. Vitamin D3
1,25 – dihydroxy - D3 acts like PTH
Increases the concentration of serum calcium
Stimulates active transport of calcium across intestine
Also mobilizes calcium from bone
Plays a major role in growth and differentiation of tissues
Receptors present on keratinocytes, pilosebaceous structures, and in the dermis
Causes decrease in proliferation
And increase in terminal differentiation
93. Social & sexual communication
Skin by virtue of its visual appeal, smell & feel has an important role in social
& sexual communication in humans
94. Immunological functions
Skin has an important role in immunological host defense
It is due to
Cells residing in skin
Keratinocytes & langerhans cells
Cells passing through the epidermis
T lymphocytes
95. Immunological function
Antigens
Exogenous external environment
Endogenous newly formed in cell itself
T lymphocytes are able to recognize antigen only when it has been
presented by specialized cells, termed as antigen presenting cells (APCs)
96. Immunological function
Immunological dysfunction has a pathological role in a wide range of skin
diseases
Immunobullous disorders
Allergic contact dermatitis
Atopic dermatitis
Psoriasis
Cutaneous T cell lymphoma (mycosis fungoides)
97. Conclusion
The most important function of human skin is to act as a two way barrier
Preventing the loss of water, electrolytes & other body constituents
Preventing the entry of noxious or unwanted molecules from the
environment
