Hair Follicle, Cycle Flashcards
Causes of follicular atrophy (4)
1) Hormonal dermatosis
2) Follicular dysplasia + ischemia
3) Scarring alopecia
4) Traction alopecia
Type of keratinization in the isthmus
Tricholemmal
Type of granules in the infundibulum
Keratohyaline
Type of granules in the inferior portion
Trichohyaline
Type of granules in the isthmus
NO GRANULES in isthmus
What is the difference between a flame figure and flame follicle?
Flame FIGURE: eosinophilic granules adhered to collagen. Cats with ECG, insect bite, MCT
Flame FOLLICLE: Excessive tricholemmal keratinization. Hair cycle arrest, Pomeranians/nordic breeds
Which animals develop all hair follicles AFTER birth?
Marsupials
Which animals develop secondary hair follicles after birth?
Dogs
(Gain an adult coat, don’t “lose” a puppy coat)
-Secondary coat develops in 3-7 months post birth
What is the cellular origin of the sebaceous glands?
Ectoderm, hair follicle stem cells
(hair follicle + apocrine glands too)
What is the origin of the connective tissue sheath?
Mesoderm
(also dermal papilla)
Which are the first hair follicles to develop on the body?
Sinus hairs
Where are sinus hairs location on the body?
Chin, eyebrows, upper lips, palmar carpus
Do hairs first develop on the head or the tail?
Head and move caudally
Which signal is most important for initiating epithelial placode development?
Wnt
What does the epithelial placode develop into?
Hair peg
What does the mesenchymal condensation of the epithelial placode develop into?
Dermal papilla
Which signaling molecule is responsible for hair follicle elongation and dermal papilla development?
Shh
As the hair peg elongates and widens, what does the deepest part become?
Bulb -> hair follicle matrix
What is the significance of the 3 bulges on the outer root sheath?
Attachment of:
Superficial
1) Epitrichial sweat gland
2) Sebaceous gland
3) Arrector pili muscle
Deep
Which gene is responsible for nonrandom, symmetrical distribution of follicles?
HOX
Which gene is responsible for hair length?
FGF5
Which gene is responsible for hair curl?
Keratin-71
Which gene is responsible for hair size/texture?
R-spondin 2
What is the “master switch” of hair follicle formation? Required for induction and placode development?
Wnt
Which cell releases Wnt, to allow hair follicle development to initiate?
Epidermal cells
Which cell signals are needed to induce anagen in adult follicles?
Wnt, Shh, BMP antagonists (noggin), KGF
Which cell signal inhibits anagen in adult follicles?
BMP
Which cell signal is constantly activated in pilomatricomas and trichofolliculomas?
B-catenin (downstream from Wnt)
-Interacts with Lef-1 transcription factor in nucleus
Which cell signal is essential for dermal papilla formation?
Shh
Which cell signal is responsible for elongation of the hair germ?
Shh
Does Shh induce anagen or telogen in adult hair follicles?
Anagen
Which cells release Shh
Hair germ cells AND dermal papilla
-Autocrine and paracrine functions
Which cell signal inhibits follicle and placode development
BMP
Which cell signal induces catagen in mature follicles (4)
BMP
TGFα
EGF
FGF5
(+ vitamin D receptor activity)
Which cell signal is essential for the differentiation of the inner root sheath and hair shaft?
BMP (and Wnt)
Which portion of the hair is most responsible for follicle structure/shape?
Inner root sheath
Which cell signal maintains hairs in telogen (inhibiting anagen)?
BMP
2 major roles of BMP in hair follicle development?
1) Differentiation of IRS and hair shaft
2) Induce catagens, maintains telogen, inhibits anagen
What is a BMP antagonist?
Noggin
Is Noggin an anagen inducer or inhibitor?
Induces
inhibits BMP, which is an anagen inhibitor
Which transcription factor does Noggin interact with to induce anagen?
Lef-1
Role of TGFα in the hair cycle?
Induces catagen
Role of FGF5 in the hair cycle?
Induces catagen
A deficiency of _____ results in angora hair (long anagen)?
FGF5
Which signal promotes hair follicle development at the placode level, and is associated with X-linked ectodermal dysplasia?
EDA/EDAR
What are 3 types of cells that live in a hair bulb?
Matrix cells, melanocytes, ORS cells
What phase of the hair cycle would you find a “club” hair?
Catagen or telogen
Fully keratinized
What is the mesodermal signaling center of the hair follicle?
Dermal papilla
What are the 3 layers of the inner root sheath (from hair shaft to ORS)?
Cuticle, Huxley, Henle
Which hairs do NOT have epitrichial sweat glands?
Secondary hairs
Which animals have NONmedullated hairs?
Sheep wool, angora goats, Sphynx cats
What are lanugo hairs?
Prenatal hairs
Simple or compound hairs: rabbit
Compound
Simple or compound hairs: mice
Simple
Simple or compound hairs: cats
Compound
Simple or compound hairs: sheep
Compound
Simple or compound hairs: goats
Compound
Simple or compound hairs: pigs
Simple
Simple or compound hairs: cows
Simple
How long after birth does secondary follicles develop in dogs?
3-7 months
What are the 2 types of tactile hairs in mammals?
1) Sinus hairs
2) Tylotrich hairs
What is a “sinus pad”?
Thickened cushion of mesenchymal projections ito the nontrabecular sinus of vibrissae
Where are Pacinian corpuscles?
Near sinus hairs
What kind of mechanoreceptors are sinus hairs?
Slow adapting mechnoreceptors
Where are tylotrich hairs on the body?
Scattered throughout
Where is the neurovascular tissue on a tylotrich hair?
Level of sebaceous gland (junction of infundibulum/isthmus)
What are “tylotrich pads”?
Thickened epidermis over connective tissue that contains a high concentration of vessels and nerves
What kind of mechnoreceptors are tylotrich hairs?
Fast acting mechanoreceptors
What type of collagen makes up the fibrous connective tissue sheath?
Type III collagen
Where is the ORS glycogenated?
Inferior portion + lower isthmus
Where do keratinocyte and melanocyte stem cells live in the hair?
Near the bulge under the arrector pili muscle in the isthmus
(in dogs, more spread throughout isthmus)
-Also melanocyte SC also in ORS
What is the equivalent of the BMZ on the hair follicle?
Glassy membrane
Outside of the ORS, inside the fibrous connective tissue sheath
Which dogs have mineralization of the glassy membrane?
Toy poodles
Bedlington terriers
*Aging dogs
In which phase of the hair cycle is the IRS gone?
Telogen
Which is the first layer of the IRS to keratinize?
Henle layer
At what point in the hair follicle does the Huxley layer keratinize?
Adamson’s fringe
How deep into the hair follicle can dermatophytes infect?
Adamson’s fringe in the deeper isthmus
Dermatophytes can only infect fully keratinized tissues
What is the clinical significance of the Adamson’s fringe?
Point where Huxley layer begins keratinization
–> as deep as dermatophytes can infect
–> need fully keratinized tissue to infect
What keratinizes first: hair shaft vs IRS?
IRS
This is how the IRS can mold the hair
Where is most of the melanin pigment in the hair, to dictate hair color?
Cortex
Other than the IRS in the inferior portion, where else in the hair follicle is there trichohyaline granules?
Medulla
What happens to melanocytes during catagen?
1) Apoptosis
2) Scattered to dermal papilla
What protects hair from reactive oxygen species? Esp highly metabolically active matrical cells in the bulb?
Melanin!
Free radical scavanger!
When are melanocytes producing melanin?
Anagen only
Apoptosis/flee to dermal papilla during catagen
Where can you find melanocyte stem cells?
Bulge
ORS
2 theories on greying:
1) Depletion of melanocyte stem cell reservoir
2) Damage to pigmentary unit via ROS
What is the wild type hair color in dogs?
Agouti (light tip, pigmented body, yellow/red base)
What is the wild type hair color in cats?
Tabby/agouti (black tip, yellow banding in body, blue base
What does color dilution alopecia look like in the hair shaft?
Large, irregular melanin granule clumps –> fracutres hair shafts
What condition causes pointed coats in cats?
Acromelanism
In cats with acromelanism, what temperature produces DARKER hair colors?
Cooler areas
How does hair cycling occur in rodents? Mosaic vs synchronized waves?
Synchronized
How does hair cycling occur in rabbits? Mosaic vs synchronized waves?
Synchronized
How does hair cycling occur in guinea pigs? Mosaic vs synchronized waves?
Mosaic!
Where does synchronized hair cycling begin on the body?
Front legs –> progresses dorsally and caudally
What determines length of hair coat?
Time spent in anagen
How does IGF-1 relate to the hair cycle?
Potent anagen stimulator
How does vitamin D receptor relate to the hair cycle?
Increased vitamin D receptor activity INDUCES catagen
What is more important on hair cycle: photoperiod vs temperature?
Photoperiod
During which season does hair growth INCREASE?
Summer
(in summer, less melatonin, so less prolactin, so anagen continues)
During which season does hair growth DECREASE?
Winter
(In winter, more melatonin, so more prolactin, so catagen is induced)
During which seasons does shedding occur?
Spring, Fall
What season is associated with seasonal alopecia in ferrets?
Spring
“Spring molt”
What happens to melatonin production in long photoperiods?
Long photoperiods cause DECREASED melatonin production
How does melatonin affect prolactin?
melatonin INCREASES prolactin levels
How does prolactin affect the hair cycle in most species?
Induces catagen
Inhibits hair shaft elongation
In cashmere goats, how does prolactin affect the hair cycle?
Induces anagen
How does melatonin influence estrogen receptor expression (and apoptosis) in hair follicles?
Downregulates estrogen receptor expression and apoptosis
(Negative feedback loop with prolactin??)
How is melatonin protective to the hair follicle?
Free radical scavenger
DNA repair inducer
(protects from metabolically active anagen bulb)
T or F: Melanonin interacts with sex hormone concentrations, which can affect hair cycling?
True
How does thyroxine affect the hair cycle?
Stimulates anagen
Stimulates stem cell differentiation
How do T3 and T4 affect melanin?
Increase melanogenesis in the follicles
How does T3 and T4 affect keratinocyte apoptosis?
Inhibits apoptosis –> inhibits catagen
How do glucocorticoids affect the hair cycle? (3)
1) Suppress anagen
2) Induce catagen (mice)
3) Reduced synthesis of hyaluronans and proteoglucans needed for follicular function
Which receptors does progesterone interact with?
1) Binds to glucocorticoid receptor (suppress anagen)
2) Cross reacts with testosterone receptor ( no effect in dogs)
How do estrogens affect the hair cycle?
1) Shorten anagen
2) Induce catagen
3) Lengthen telogen
4) Stimulates BMP expression (which inhibits anagen)
(Has the OPPOSITE effect in people, dif receptor expression?)
How does estrogen interact with BMP?
Estrogen upregulates BMP expression (which inhibits anagen)
How do androgens affect the hair cycle?
Humans: promote growth everywhere except eyelashes and scalp. On scalp –> high androgens miniaturize hairs & shorten androgen. Act on dermal papilla. On eyelashes –> no effect
Dogs: minimal effect
How does spaying/neutering affect the hair cycle?
Affects 20% of animals, unknown mechanism
Woolly coat: increased undercoat, increased curl, dulling of coat
Which type of immune cells live in hair follicles? Where?
Langerhans cells
Upper portion of ORS (isthmus, infundibulum)
Acts as a reserve for epidermis
Which immune cells are present in the lower hair follicle?
None
Immune privileged area
Which 2 regions of the hair follicle have primary immune privilege?
1) Bulge/ORS stem cells
2) Anagen bulb
What is absent in areas with immune privilege?
No MHC class I expression
*Melanocytes downregulate MHC class I expression
*β-2 microglobulin downregulated (which usually stabilizes MHC class I)
*Increased CD200 expression –> “no danger” signal
How does β-2 microglobulin affect immune privilege?
Downregulated in immune privileged sites
Normally, it works to stabilize MHC class I
How do melanocytes affect immune privilege?
Increased in immune privileged sites
Downregulate MHC class I
How does CD200 affect immune privilege?
Increased in immune privileged sites
“No danger” signal
How does the extracellular matrix affect immune privilege?
Increased glycosaminoglycans –> impedes T cell trafficking to the follicle
Which immunosuppressive signals are produced by the hair follicle?
1) TGF-β2
2) α-MSH
*Impair antigen presentation
*Prevent NK/CD8+ attacks
What is the function of TGF-β2 on hair follicle immunity?
-Impair antigen presentation
-Prevent NK/CD8+ attacks
What is the function of α-MSH on hair follicle immunity?
-Impair antigen presentation
-Prevent NK/CD8+ attacks
What immunosuppressive signals are present to support hair follicle immune privilege (other than TGF-β2, α-MSH)?
IL-10
MIF (macrophage migration inhibition factor)
What is the result of a collapse in immune privilege?
Alopecia areata
When does telogen effluvium occur after inciting incident?
1-3 months later
What causes telogen effluvium?
High stress event
-Fever
-Birthing (anagen during prefnancy)
-Severe illness
-Surgery
-Anesthesia
-Drugs (Doxorubricin)
What neurotransmitter may be related to telogen effluvium?
Substance P
What triggers anagen effluvium?
Toxins, chemotherapy
When does anagen effluvium occur after the inciting incident?
Days later
What happens to the hair cycle with anagen effluvium?
Hair is damaged during anagen phase, but hair growth continues
What is a diagnostic test supportive of anagen effluvium?
Trichogram: Hair shaft damage
Which species have X-linked ectodermal dysplasia?
Dogs, cattle, humans
What gene is associated with X-linked ectodermal dysplasia?
EDA/EDAR
What disease is caused by EDA/EDAR mutations?
X-linked ectodermal dysplasia
Which dog breeds have congenital alopecia that is autosomal dominant? Gene?
-Mexican hairless
-Chinese crested
FOX 13
Which cat breed has congenital alopecia that is autosomal recessive? Gene?
Sphynx
Keratin 71 (IRS)
In addition to alopecia, which other changes can be seen with ectodermal dysplasia?
-Dentition
-Claws
-Eptrichial/atrichia sweat glands
-Lacrimal glands
-Sebaceous glands
-Bronchial glands
*Decreased glandular secretions lead to difficulty thermoregulating, corneal abnormalities, respiratory illness
Which species have black hair follicular dysplasia?
Dogs, cows
What causes black hair follicular dysplasia?
Disorder of melanosome transfer, migration
–> disorderly proliferation of hair matrix cells
What is the age of onset for black hair follicular dysplasia?
By 4 weeks old
Which species have color dilution alopecia?
Dogs, cats
What causes color dilution alopecia?
Irregular melanin transfer/storage –> macromelanosomes –> hair loss due to hair fracture
What is the age of onset for color dilution alopecia?
Gradual onset, by 3 years old
What causes follicular lipidosis?
Lipid accumulation in the matrical keratinocytes of anagen bulb
Which breed gets follicular lipidosis?
Rottweiler
On MAHOGANY points of face, paws
Age of onset of follicular lipidosis
< 1 year old
Histopath change from pattern baldness?
Hair follicle miniaturization in affected areas
Which breeds have Alopecia X?
Plush coated dogs –pomeranians; poodles; schipperke
Which breed gets spiculosis?
MALE kerry blue terriers
Which sex gets spiculosis?
Male kerry blue terriers
Clinical sign of spiculosis
Hard, brittle follicular spicules. Follicular hyperkeratosis. Pruritic/painful
Clinical signs of pili torti
Secondary hairs are flattened/rotated
Clinical sign of hair shaft disorder of Abyssinian cats
Onion-shaped swelling at tip of WHISKERS and PRIMARY HAIRS
*hairs fracture easily
*coat appears rough, lusterless
Trichorrhexis nodosa cause
Fractured nodes within hair shaft
External insult, damage to cuticle
Trichoptilosis cause
Split ends
External insult, damage to cuticle
Medullary trichomalacia cause
Longitudinal splitting of hairs
External insult, damage to cuticle
GSDs
What happens if beta-catenin (and Lef-1) are constantly activated?
Pilomatricomas and Trichofolliculomas
Target of alopecia areata
Trichohyaline granules
(only present in inferior hair, bulb IRS)
Which type of antibodies are present in alopecia areata
IgG
Cell signals that induce alopecia areata
IFN gamma, Substance P
Type of immune cell in alopecia areata
CD8+ T cells in bulb
Which part of the body is affected by alopecia areata
Face
Breeds predisposed to alopecia areata (dog, horse, cow)
Dog: GSD, Dachshund, Beagle
Horse: Appaloosa
Cow: Eringer
Trichogram finding with alopecia areata
Exclamation point hairs
(Stubby, with frayed, fractured, tapered ends)
T or F: most dogs with alopecia areata have hair regrowth
True
Treatment for alopecia areata
60% have spontaneous regrowth
Otherwise, glucocorticoids, cyclosporine
Type of inflammation with pseudopalade
T cell
Location on hair follicle affected by pseudopalade
Mid-isthmus, near the bulge
T or F: most dogs with pseudopalade have hair regrowth
False
Affects stem cell niche in the bulge
Species affected by pseudopalade
Dogs, cats
Location on body affected by pseudopalade
Spares head/neck
(opposite of alopecia areata)
Histopath findings with cyclic flank alopecia
Infundibular hyperkeratosis
Base of follicles has misshapen bulbs –> “Witches foot”
Gene for color dilution alopecia
MLPH
Breed that develops trichorrhexis nodosa
Golden retrievers
Medication that can cause trichorrhexis nodosa
Amitriptyline
Sex overrepresented in degenerative mucinotic mural folliculitis (cat)
Males
Infection associated with degenerative mucinotic mural folliculitis (cat)
FIV+
