2. Skin
Skin is the largest organ in the body.
In a 70kg individual, the skin weighs over 5 kgs and
covers a surface area approaching 2 square meter.
Human skin is of two types:-
o Non hairy (glabrous)skin : as seen on palms and soles.
o Hair bearing skin
5. Contents Of Epidermis And Dermis
Cells Other structures
Epidermis Keratinocytes,melanocyte
s,langerhans cells and
merkel cells
Hair follicles,apocrine
glands and sweat glands
which are derived from
epidermis and extend to
dermis
Dermis Fibroblasts,mast
cells,histiocytes,macroph
ages and lymphocytes
Matrix of polysaccharides
and protein
6. Epidermis
It is stratified squamous epithelium which is terminally
differentiated.
Thickness:0.05-0.1mm.
Keratinocytes constitute more than 95% of epidermal cells.
The “brick like “ shape of keratinocyte is provided by
cytoskeleton made of keratin intermediate filaments.
As epidermis differentiates, cells gets flattened. This
process involves the filament aggregating protein called
filaggrin.
Keratin and filaggrin comprises 90% of mass of
epidermis.
7. Epidermis
On morphological grounds, the epidermis can be
divided into four distinct layers:
o Stratum basale or stratum germinativum
o Stratum spinosum
o Stratum granulosum
o Stratum corneum
9. Stratum Basale
Continuous layer ,generally one cell thick but can be
2 -3 cell layer thick in glabrous skin and
hyperproliferative skin.
Basal cells are small and cuboidal with large dark
staining nuclei and dense cytoplasm.
It contains ribosomes , tonofilaments and
melanosomes transferred from melanocytes by
phagocytosis.
It contains three types of cells: stem cells ,transient
amplifying cells and post mitotic cells.
10. Stratum Spinosum
Aka prickle cell layer.
Contains 8-10 layers of cells.
Cells are polyhedral with a round nucleus.
The cells in upper spinous layer are more larger and
flattened and contains “lamellar granules”.
They are named spinous for the spine like appearance
which corresponds to abundant desmosomes
histologically.
11. Stratum Granulosum
It is 2 -5 cells thick .
Contains intracellular granules of keratohyalin.
The cytoplasm of upper spinous layer and granular cell
layer contains lamellated granules known as
membrane coating granules or odland bodies.
They discharge their lipid component into intercellular
space playing an important role in barrier function and
intercellular cohesion.
12. Stratum Corneum
Outermost skin layer.
Consist of 20-25 layers of cornified cells called as
corneocytes which are largest cells of epidermis.
They are flattened with no nuclei and cytoplasmic
organelles.
The corneocyte has a highly insoluble, cornified
envelope within the plasma membrane formed by
soluble protein precursor called as involucrin.
13. Stratum Lucidum
An electron-lucent layer present in palms and soles
between stratum granulosum and stratum corneum
with nucleated transitional cells.
14.
15. Epidermal cells
Keratinocytes
o Ectodermal in origin.
o They contain keratin intermedite filaments or
tonofilaments.
o The keratins are separated into two gene families :
Type 1 (basic)
Type 2(acidic)
18. Merkel Cells
o Slow adapting ,type 1 mechanoreceptors.
o They are found in both in hairy skin and glabrous skin
of digits ,lips ,region of oral cavity and outer root
sheath of hair follicle.
o applied: in merkel cell carcinoma ,neuroendocrine
carcinoma.
21. o Distributed in basal,spinous and granular cell layers
o Cells are pale staining and have convoluted nuclei
and clear cytoplasm, well developed endoplasmic
reticulum and lysosomes.
o They have distinctive rod or racquet shaped granules
called as birbeck granules.
o Function: antigen presentation,stimulatiom of t-cell
response and phagocytosis.
o IHC markers: CD1a,S100.
22. o Applied: cells are implicated in pathogenecity of
allergic contact dermatitis,cutaneous leishmaniasis
and HIV infection.
o In psoriasis ,sarcoidosis and contact dermatitis ,their
number is reduced.
25. Melanocytes
They are dendritic cells derived from neural crest that are
involved in pigment synthesis.
Melanocytes are in contact with keratinocytes through
their processes but do not form junctions with them at any
level.
One melanocyte is in contact with 36 basal and suprabasal
keratinocyte forming an epidermal melanin unit.
26. There is no difference in the density of melanocytes in
different races.
The racial differences are due to the distribution and
size of melanosomes with keratinocytes.
27. Melanosomes
Melanin is produced in melanosomes (pigment
granules or organelles) within melanocytes.
The major hormone controlling melanin synthesis is
alpha-MSH (MELANOCYTE STIMULATING
HORMONE) from pituitary gland.
Two types of melanin present :
Eumelanin (brown/ black)
Pheomelanin (red/yellow)
28. Applied:
in vitiligo ,melanocytes are destroyed.
In albinism ,number of melanocytes are normal but
they are unable to synthesize fully pigmented
melanosomes .
Freckles result from a localized increase in production of
pigment by normal number of melanocytes.
Nevi are benign proliferations of melanocytes and
Melanomas are malignant counterpart .
29. Desmosomes
• major adhesion complex in epidermis.
•Anchor keratin filaments to the cell membrane.
•Bridge the adjacent keratinocytes.
30. Desmosomes
•have a characteristic ultra structure with cell
membranes of two adjacent cells forming a symmetrical
junction with a 30nm intercellular space containing a
dense line.
• core has calcium binding glycoproteins called
desmogleins and desmocollins.
31. There are three epidermis- specific desmogleins (Dsg
1-3) and desmocollins (Dsc 1-3)..
Upper dermis expresses Dsg1 and Dsc 1 more.
basal keratinocytes expresses Dsg 3 and Dsc 3 more.
The intercellular parts 0f Dsg and Dsc are attached to
keratin via desmoplakin ,plakoglobin and plakophilin.
32.
33. Adherens junctions
Electron dense transmembrane structures that
associate with actin skeleton.
Their main component is calcium dependent E-
cadherin.
The main linkage to actin cytoskeleton is via alpha –
catenin.
34.
35. Gap junctions
Comprise a cluster of intercellular connections known
as connexons.
They allow transfer of molecules and ions (<1000 Da)
between two cells.
36.
37. Tight junctions
Major regulators of permeability of epithelia.
Composed of transmembrane and intracellular
molecules that includes:-
occludin
junction adhesion molecules(JAM)
claudins
38.
39. Dermis
It makes the bulk of skin.
Unlike epidermis , it is highly acellular and consist of
extracellular matrix of connective tissue .
Thickness varies from 0.5mm to 5mm.
There are four major components:
o Collagen fibres : provide tensile strength.
o Elastic structures: :provide elasticity and resilience .
o Glycoproteins such as fibrillins,fibulins and integrins :
organizers of matrix
o Proteoglycans /glycosaminoglycans (GAGs): provide
hydration.
40. Organization Of Dermis
Dermis is organized into : papillary dermis
reticular dermis
A horizontal plane of vessels marks the boundary
between them.
The papillary dermis and periadnexal dermis are
together known as adventitial dermis.
41. Papillary Dermis
It is the superficial and thin part of the dermis that
interdigitates with the ridges .
Characterized by small bundles of collagen fibres and
oxytalan fibres.
Mature elastic fibres usually not found.
high density of fibroblastic activity and a high
metabolic rate.
42. Reticular Dermis
It constitutes the lower part of the dermis and
merges with the subcutaneous fat.
Composed of large diameter collagen fibrils.
Mature elastic fibres form a superstructure around the
collagen fibre bundles.
43. Connective Tissue Matrix
The main fibrous connective tissue of dermis is made
of collagen and elastin fibres.
collagen
44. Connective Tissue Matrix
The main fibrous connective tissue s of the dermis are
collagen and elastic connective tissues.
Type of collagen Function
Type I Larger in diameter forming large
and coarse bundles present in
reticular dermis.
Type III Fibrils are smaller and form small
and fine network mainly in
papillary dermis and around
blood vessels and adnexa.
Type IV Limited to basal lamina.
Type V Localized in papillary dermis.
Type VI Abundant throughout the dermis
and is associated with
interfibrillar spaces.
Type VII Forms anchoring fibrils in DEJ
45. Ultrastructure Of Collagen
The molecules are made of three chains.
Each chains have a helical domain consisting of
(gly-X-Y) in repetition where X and Y are typically
proline and hydroxy proline .
On electron microscopy ,collagen is seen as regular
cross striated fibrils with a 60-70nm periodicity, which
is characteristic banding pattern of collagen.
47. Type of collagen Sites Diseases
Type I Dermis ,bones ,tendons Ehler-danlos syndrome
Osteogenesis imperfecta
Type III Dermis in embryonic life
GI tract
uterus
Vascular type of ehler
danlos syndrome
Type IV Basement membrane of
DEJ , glomeruli and blood
vessels
Alport syndrome
Epidermal blister
formation
Renal insufficiency
Type V On surface of large
collagen fibres and regulate
their growth
Irregularity of individual
fibre giving ‘flower
like’appearance
Type VII Organizes to anchoring
fibrils
Skin fragility in
epidermolysis bullosa
48. Elastic Tissue
The elastic tissue forms a continuous network
throughout the dermis that extends from the lamina
densa of the DEJ to the connective tissue of subcutis.
Because of their elasticity, they maintain normal
configuration of skin.
49. Ground substance
It is the supporting matrix of dermis consisting of PGs and
GAGs.
Functions:
o Bind a large amount of water thereby influencing dermal
volume and compressibility .
o Bind to growth factors thereby influencing proliferation
,tissue repair and morphogenesis.
• The major PGs in the adult dermis are :
• Chondroitin sulfates/dermatan sulfates
(biglycan,decorin,versican)
• Heparan
• chondrotin-6 sulfate proteoglycans.
50. fibroblasts
Derived from mesenchymal tissue.
Most common cells found in the dermis.
Function: provide a ECM framework .
they synthesize and degrade fibrous and nonfibrous
proteins of connective tissue and matrix.
They appear as bipolar spindle shaped cells with
elongated ovoid nuclei. Cytoplasm contains multiple
dilated rough endoplasmic reticulum and Golgi
complexes.
52. Electron microscopy of active fibroblast showing
abundant rough endoplasmic reticulum in cytoplasm.
53. Cutaneous Blood vessels
The cutaneous vasculature is limited to dermis and
epidermis has no blood vessels.
Dermal vasculature is divided into two:-
Superficial vascular plexus between papillary and
reticular dermis.
Deep vascular plexus between reticular dermis and
subcutaneous fat.
Vasculature regulates the body temperature by controlling
the blood flow through capillaries in upper dermis so that
opening blood vessels allow dissipation of excess heat and
constriction slows the blood flow and conserve core energy.
54. Nerves of skin
Somatic sensory fibres Sympathetic autonomic fibres
Myelinated
Cutaneous branches of
musculocutaneous nerve
innervates the skin.
Responsible for sensations of
touch ,pain, temperature,
itching and mechanical
stimuli.
Unmyelinated
Innervate the hair follicle
,sweat glands, arrector pili
muscle and smooth muscles
of blood vessels.
55. Sensory receptors
Free endings Corpuscular receptors
Present in papillary dermis.
Have schwann cell sheath and
basal lamina.
Penicillate nerve endings
Rapidly adapting receptors of
touch , temperature,pain and
itch present in hair bearing skin.
Discrimination is generalised.
Papillary nerve endings
Free nerve endings of hair
follicles
Either encapsulated or
noncapsulated present in
epidermis and dermis.
pacinian corpuscles ovoid
shaped mechanoreceptors
responding to vibratory
stimuli.
Golgi-mazzoni corpuscles
Krause end bulb
Meissner’corpuscles
Ruffini corpuscles
56. Subcutaneous fat
80% of fat of the human body is present in the
subcutis and the rest surrounds the internal organs.
Fat comprises of white and brown adipose tissue.
Brown fat is more common in infants and children and
is characterized by different mitochondrial properties
and increased heat production.
57. Subcutaneous fat
Functions:
o Provide insulation.
o Provide mechanical cushioning and energy store.
o It also secretes leptin molecule which regulate
appetite.
o Multipotent stem cells have also been found .