HAIR Anatomy- Basic structure and function.pptx

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

2. 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 8 th to 9 th 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)

3. 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

4. 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

5. 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

6. 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 - It has Powerful inductive property (releases many growth factors) which helps in maintenance of follicular epithelial differentiation Number of matrix cells -> Volume of papilla -> Size of the hair shaft Presence of Androgen dependent growth receptors Nourishment of hair follicle

7. 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

8. 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

9. 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 ADAMSON FRINGE

10. 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

11. 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

12. 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

13. 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)

14. 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

15. HISTOLOGY

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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)

26. 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

27. 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

28. 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

29. 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

30. THANK YOU

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