Hair as a structural and functional unit being described.

1. STRUCTURE AND DEVELOPMENT
OF HAIR
HAIR CYCLE &
ETIOPATHOGENESIS OF
ANDROGENETIC ALOPECIA
PRESENTER – DR PRATEEK MAHARANA
MODERATOR – DR MANJULATA DASH, Assoc Prof

3. TYPES OF HAIR
LANUGO (WOOL LIKE) HAIR VELLUS HAIR TERMINAL HAIR
Prenatal Postnatal Postnatal
Soft Soft Coarse
Unmedullated Unmedullated Medullated
Unpigmented Occasionally pigmented Pigmented
Length – 1-2 cm Length – less than 2 cm Length – upto 100 cm
Diameter – 40 micrometer Diameter – less than 30 micrometer Diameter – 60 micrometer
Hair bulb in reticular dermis Hair bulb in subcutaneous fat
Present – elsewhere in body
(before puberty)
Present – scalp, eyebrows, eye lashes
(at birth);
Genitalia, axilla, trunk, beard (after
puberty)
Anagen duration – 1-3 months 1-2 weeks More than 1 year
Shed in 8th to 9th month of gestation
*Terminal hairs miniaturized to vellus hair proportions are described as vellus like hairs seen in AGA and AA
* A normal scalp averages 7:1 (terminal hair: vellus hair)

4. DEVELOPMENT OF HAIR
• Begins at 8 weeks of fetal life
• Initial hair population is complete by 22 weeks and shed by 36 weeks IUL in a
synchronized manner.
• A second coat of lanugo hair appears and shed in a synchronized wave pattern at 3-4
months of life, gives rise to NEONATAL ALOPECIA
Appearance of placode in the epidermal basal layer
Specialized mesenchymal cells organize in a small condensate
Stimulate epithelial stem cells to invaginate and penetrate into the dermis forming an
epidermal peg
Epidermal peg continues to grow downward enclosing the dermal condensate forming
the dermal papilla
Tip of the epidermal peg becomes the matrix of the hair bulb
Cells of the follicular matrix differentiate into inner root sheath and hair shaft that exits
from the skin surface

7. ANATOMY OF HAIR (ANAGEN HAIR)
• Hair follicular unit = hair follicle + sebaceous gland + arrector pili
• Divided into 4 broad parts
1. Hair bulb
2. Suprabulbar region
3. Isthmus
4. Infundibulum
Continuous cycle
Constant structure

10. A. Hair Bulb
• Usually located in the subcutaneous fat, consists of hair matrix,
basophilic germinative layer which surrounds the dermal papilla
• A line along the widest part of the dermal papilla called AUBER’s LINE
divides the hair bulb into broad 2 parts-
1.Lower undifferentiated part- a) Matrix/ germinative layer
b) Dermal papilla
2.Upper differentiated part- a) Keratogenous zone
b) Prekeratogenous zone
c) Elongation region
d) Preelongation region

12. Dermal papilla
• Flask shaped structure
• Mesenchymal derivative
• Enveloped by matrix epithelium
• Contains fibroblasts, collagen bundle, mucopolysaccharide rich stroma,
nerve fibres and capillary loop.
• Continuous with perifollicular sheath that envelopes the lower follicle
• Functions -
1. It has Powerful inductive property (releases many growth factors) which
helps in maintenance of follicular epithelial differentiation
2. Number of matrix cells -> Volume of papilla -> Size of the hair shaft
3. Presence of Androgen dependent growth receptors
4. Nourishment of hair follicle

13. Perifollicular sheath
It has 2 parts :
1) Inner basement membrane (Hyaline/ vitreous membrane)-
continuous with interfollicular basement membrane
most prominent around outer root sheath at the bulb of anagen phase
2) Outer connective tissue (type III collagen)-
ability to form new dermal papilla
thickens and disintegrates during catagen phase
even transplantation to other individual shows no evidence of immunological
rejection

14. B. Suprabulbar region
• From the hair matrix to insertion of arrector pili muscle
• From outermost to innermost ->
1. Outer root sheath (ORS)
2. Inner root sheath (IRS) – Companion cell layer
Henley layer
Huxley layer
Inner root sheath cuticle
3. Hair shaft – Cuticle
Cortex
Medulla

16. Bulb Suprabulbar region Isthmus Infundibulum
Single flattened cell layer till
the base of the follicle
Multilayered cells Lacks granular layer Differentiation same as
epidermis
Cells larger in size Undergoes Trichilemmal
keratinization (IRS sloughs)
Abundant glycogen Keratinocytes form a bulge at
lower border (High N:C ratio)
OUTER ROOT SHEATH
INNER ROOT SHEATH- from base of bulb to isthmus
hard keratin present (moulding of hair)
all layers contain large eosinophilic cytoplasmic inclusion
(TRICHOHYALINE GRANULES) which is rich in arginine
Companion cell layer Henley layer Huxley layer Inner root sheath cuticle
Flat cells Single cell layer Multilayered Shingled root appearance
Thicker hair follicles First to develop trichohyaline
granules
FLUEGELZELLEN or WING
CELLS for nutrition
Intertwin with hair shaft
cuticle
Slips between ORS and IRS First to keratinize Last to keratinize Acquire trichohyaline granules
halfway of follicle
Keratinization from above

17. ADAMSON’s FRINGE- inverted ‘V’ shape
- only in anagen hair
- point above which hair cornifies
- dermatophytes only infect the above cornified layer
- above it no keratohyaline granules in Huxley layer

18. Hair shaft
Cuticle Cortex Medulla
Comprised of interlocking
flattened cells of hairshaft cuticle
and IRS cuticle.
5-10 overlapping cell layers of size
350-450nm thick
Bulk of shaft Present in large thick hairs
Endures weathering. If weathering
is severe, may lead to exposure of
cortex and hair shaft fracture
Contains melanin, hard alpha keratin (high
Sulfur content) -> HIGH TENSILE STRENGTH,
intermediate filaments (low sulfur)
Most fragile
Barrier to physical and chemical
insults
Filaments arranged in organised manner by
disulphide bonds
Species differentiation
Maintains the integrity of hair
shaft
Keratinization takes place in keratogenous zone
cause intense protein synthesis
May be continuous, discontinuous or
absent

19. C. Isthmus
Important transitional zone of follicular keratinization
From insertion of the arrector pili muscle to opening of sebaceous
gland duct
No IRS here (IRS desquamates) and ORS undergoes trichilemmal
keratinization
Bulge present at lower part of isthmus close to the insertion of arrector
pili muscle – highly proliferative cells
D. Infundibulum
From sebaceous duct opening to skin surface
Differentiation same as epidermis
2 parts- acroinfundibulum, infrainfundibulum

20. CATAGEN hair anatomy
• Matrix disappears, epithelium degenerates
• Thickening of perifollicular connective tissue -> papilla follows
disintegrated column upward to dermis -> collapsed sheath left
behind known as STELA or FOLLICULAR STEAMER (derived from Greek
word- Pillar)

21. TELOGEN hair anatomy
• Dermal papilla becomes condensed ball of spindle shaped nuclei within a scanty
stroma just below the epithelium called SECONDARY GERM CELL
• When sectioned transversely the secondary germ cell appears like an Asterix

22. HISTOLOGY

23. Hair follicle innervation
• Humans – free nerve ending
pilo-ruffini nerve ending
Merkel nerve ending
• Other species – Vibrissae
(lamellated nerve endings are
found in richly innervated sinus
hair follicles), which have
specialized sensory function

24. HAIR CYCLE
Hair follicle undergoes repetitive sequence of growth and rest known
as Hair Cycle
Three phases – 1. Anagen (growth phase)
2. Catagen (regression phase)
3. Telogen (resting phase)
Extra phases – 4. Exogen (shedding phase)
5. Kenogen (lag phase)
Anagen Catagen Telogen
2-7 years 2-3 weeks 3 months
80-90% hair 1% hair 8-9% hair

26. Seven stages of Anagen (Chase et al)
SEVEN STAGES OF ANAGEN ( Chase et al)
1 Growth of dermal papilla and onset of mitotic activity in the germ like overlying epithelium
2 Bulb matrix cells envelop the dermal papilla and begin differentiation
Bulb descend along fibrous steamer
3 Matrix cells show differentiation
Maximum lengthening of follicle
Complete formation of bulge
Melanocytes align along papillary cavity and develop granules
IRS is an elongated cone extending upto capsule and club of old hair
4 Reactivation of melanocytes
Develop dendrites and begin to form melanin
Hair still within the cone of IRS, extends upto sebaceous gland
Keratogenous zone becomes established
Cuticle clearly visible
Cone of cell in upper part of bulb -> future cortex and medulla
Papilla becomes narrow and long
5 Hair shaft emerges and dislodges telogen hair
Tip of hair emerges from IRS, grown upto epidermis
Bulb attains its final shape
6 New hair shaft emerges from the skin (maximum duration)
Duration determines the length of hair
7 Stable growth

27. CATAGEN
• Transitional stage
• Apoptosis of follicular keratinocytes
• Ceasation of follicular melanogenesis
• Highly regulated event
• Loss of layered differentiation of lower follicle
• Condensation of dermal papilla -> moves upward -> rests beneath hair
follicle bulge. (important for continuous cycling – Atrichia)
• Extracellular matrix remodelling and shrinkage of inferior follicle via
apoptosis
• Severe stress, trauma, chemicals and hormones like ACTH, 17 beta
estradiol can induce catagen

29. Divided into 8 subphases-
• Extensive destruction of lower follicle marks the onset of catagen
• First indicator of regression is withdrawal pf papilla cell projection from basement membrane
• Papilla shrinks through the loss of ECM substance
• Matrix and lower outer root sheath abruptly stop proliferating and undergo apoptosis
• Melanocytes stop producing pigments-> proximal tip of telogen club hair becomes nonpigmentd
• Ceasation of cytoskeleton protein production like trichohyaline, transglutaminase 1, desmoglein
• Progressive shrinkage of lower follicle which withdraws as an epithelial strand
• Basement membrane thickens dramatically and lower follicle retracts upward with dermal papilla
• Perifollicular sheath collapses and fibrous streamer is formed
• ORS within the isthmus become rounded surrounding the bulbous terminal portion of the hair
• Lower follicle degenerates -> ORS looses glycogen and IRS disappears
• ORS keratinizes forming a rigid thick eosinophilic layer anchoring the lower portion of hair shaft
• At the end the thickened BM disintegrates and replaced by normal one

30. TELOGEN
• Period between completion of follicular regression and onset of next
anagen phase
• Club hair appearance
• Resting or quiescence stage
• About 1% of follicle shed everyday
• 5-15% scalp hair, 40-50% trunk hair
EXOGEN
• Active hair shedding occurs
KENOGEN
• Lag period from telogen/exogen to anagen

31. Bulge Activation Hypothesis
• Most widely accepted. Explains mechanism of hair cycling
• Stem cells reside in the bulge region at the insertion of arrector pili muscle
• Cells divide at the end of telogen forming transient amplifying cells -> multiply to form
matrix cells.
• After this bulb disappears and follicle returns to telogen only to restart cycle
• Dermal papilla which moves upward during telogen phase, interact with the bulge cells to
start their activation
• Keratinocytes of the bulge area differ from others by expressing a different set of keratins –
keratin 19, alpha 3 beta 1 integrin, slow cycling nature
CONTROL OF HAIR GROWTH
Hair follicle is a highly dynamic organ with one of the fastest proliferating tissues in body
1) Cytokines and growth factors
2) Hormonal control – androgenetic and non androgenetic
3) Neural control
4) Immunological control

32. 1) Cytokines and growth factors
HAIR MORPHOGENESIS HAIR REGENERATION HAIR DIFFERENTIATION
ACTIVATOR- beta catenin
neurotrophin
BDNF
laminin 10
ACTIVATOR OF ANAGEN- FGF 7
SHH
Whn
HGF receptor
PTH receptor
BMP 2
Notch
Noggin
HOXC 13
Whn
INHIBITOR- FGF 2 INHIBITOR OF ANAGEN- TGF beta 1
ACTIVATOR OF CATAGEN- BDNF
NT 3,4
TGF beta 1
ACTH
17 beta estadiol
Dexamethasone
Stress
Trauma
INHIBITOR OF CATAGEN- Tretinoin
FGF 5
IGF 1

33. 2) Hormonal control
HORMONES EFFECT ON HAIR
Androgens Increase duration of anagen -> increases the thickness of hair shaft
Increase the size of hair follicle
Estrogen Prolongs anagen and delays the transition to telogen
Prolactin ~androgen like activity
Insulin Through IGF 1 -> hair growth
Growth hormone Induce sebocyte differentiation
Thyroid hormone Enhance onset of follicular cycle but retard rate of hair growth
Retain club hair in follicle
Both hypo and hyper secretion can cause alopecia
Cortisol Enhance action of IGF 1
Independent of androgen Sensitive to even small amount Responds to high level Reverse response
Eye brows
Eye lashes
Lanugo hair
Axillary hair
Lower pubic hair
Facial hair, ears
Chest hair
Upper pubic triangle
Scalp hair
Androgenetic response of hair

34. • Effect of testosterone is mediated by 5 alpha dihydrotestosterone in all body hair except
axilla and pubic region
• Conversion of testosterone to 5 alpha DHT is by enzyme 5 alpha reductase
• 3 types – type 1 – sebaceous glands esp. after puberty, acne prone areas like
. Face, epidermis, eccrine sweat glands, apocrine sweat glands, (ORS, . .
. papilla, matrix) of hair follicle
type 2 – prostate and epididymis, hair follicles in neonates, fetal genitalia, .
. companion layer of hair follicle and granular layer of epidermis
type 3 – widely expressed
(Inhibitors of type 1 & 2 show clinical response. FINASTERIDE inhibits type 2, DUTASTERIDE
inhibits both type 1 & 2)
• Androgen response is determined at the level of follicle or its immediate environment. It is
converted to active DHT in skin immediately prior to binding to androgen receptors present
in the dermal papilla
• Dermal papilla is the primary target of androgen which express 5 alpha reductase type 1,
hair follicle epithelium type 1
• Androgen causes loss of hair at one site (MPB, FPHL) and overgrowth of hair at other site
(hirsutism, hypertrichosis). This could be due to difference in the sensitivity of androgen
receptors or difference in androgen metabolism
• Estrogen retains the club hair in follicle. (POST PARTUM ALOPECIA – loss of retained telogen
hairs as estrogen level falls)

35. 3) Neural control
• NT 3,4
• Glial derived neurotropic factors (GDNF)
• Neurturin
• Brain derived neurotropic factors (BDNF)
4) Immunological control
• IL 1, TNF alpha, FGF 5 secreted by macrophage induce catagen
• IMMUNE PRIVILEGE – ability to tolerate the introduction of antigens without
eliciting an inflammatory immune response
• Downregulation of MHC 1, APC and upregulation of local immunosuppressant
secretion by follicular epithelium
• Immune privilege is lost in ALOPECIA AREATA

36. ETIOPATHOGENESIS OF ANDROGENETIC ALOPECIA
• After puberty androgens triggers a series of events within these genetically
programmed hair follicles, predominantly of the frontoparietal scalp, that
transforms terminal to miniaturized hair follicle.
• ETIOLOGY OF AGA -
1. genetics
2. systemic hormonal effects (androgen) – men castrated before puberty didn’t
develop balding unless treated with testosterone
3. local hormonal effect
4. role of oxidative stress –> TGF beta1 secretion by dermal papilla cells causes hair
growth suppression
5. contact between arrector pili muscle and the bulge -> reversal of hair follicle
miniaturization
6. hair cycle dynamics – duration of anagen decreases with each successive cycle
with prolongation of telogen phase

37. GENETICS –
• Autosomal dominant, polygenic (Kuster & Happle’s analysis) and inherited
from either parent
• Gene association – polymorphism of androgen receptor gene (X
chromosome), SRDA1, SRDA5
• Single nucleotide polymorphism (SNP), cytochrome p450 alpha aromatase
• FPHL -Androgen receptor genes, aromatase gene, estrogen receptor gene
(ESR2)
LOCAL HORMONE EFFECTS –
• Intrafollicular androgen overactivity (increased no of androgen receptors,
functional polymorphism of androgen receptor, increased local production of
DHT, reduced local degradation of DHT
• Type 2 5-alpha reductase accounts for 80% circulating DHT

38. DIFFERENCE IN PATTERN HAIR LOSS AMONG MEN AND WOMEN
• Women have 3-3.5% less 5 alpha reductase in frontal hair follicles
• Lower level of circulating androgens
• Estrogens play a protective role
• Total androgen receptors concentration is 40% less
• Aromatase is 6 times more in frontal follicles and 4 times more in occipital
follicles
FURTHER GENETIC RESEARCH-
• Signalling pathways- FGF, WNT proteins, beta catenin, LEF1, FOXN1, noggin,
bone morphogenic protein 2&4, sonic hedgehog, PDGF, follistatin and
Epidermal growth factor
• Two major genetic risk loci- AR/EDA2R locus on X chromosome and
PAX1/FOX A2 locus on chromosome 20. Recent studies indicate HAD C9 locus
on chromosome 7 as a new susceptible locus

39. THANK YOU

40. TOMORROW CASE PRESENTATION
BY- DR DINESH RANJAN PANDA
MODERATOR – DR BINODINI BEHERA
CASE- PSORIATIC ERYTHRODERMA