Skin structure and function 1,2,3

How does the development of skin start embryologically?

• initally one layer of ectodermal cells overlying a dermis of loosely arranged mesenchymal cells

what does the ectoderm divide into in skin development?

Two layers:

1. basal cell layer = stratum germinativum

2. outer layer = periderm

What is the name of the layer between the stratum germinativum and periderm?

• stratum intermedium

What cell types further the embryological development of the 3 layers of skin?

• melanocytes

• Langerhans cells

Where do these cells originate?

• melanocytes

• langerhans cells

• neural crest origin

• bone marrow origin

How does the dermis develop embryologically into its adult structure?

• increase in thickness and number of fibres

• mesenchymal cells develop into fibroblasts

• collagen precedes elastin fibres

• ground substance accompanies them

• histiocytes and dermal melanocytes are worth noting

• nerves and blood vessels also develop

How does the subcutis develop?

• lipocytes in the second half of gestation

Which cells divide in order to develop the multi-layered epidermis?

• basal cells

What are these drawings showing the development of?

• embryology of the skin

How does the skin develop during mid-pregnancy?

• baal layers give rise to the layers of the stratified squamous epithelium

  • periderm lost

• mesodermal cells differentiate into connective tissue cells

what do we call the cells of the epithelium?

• keratinocytes

Name the 4 layers of the epidermis

• basal layer → spinous layer → granular layer → horny layer

How do hairs form embryologically

• epidermal basal cells divide into the dermis, this forms the hair bud/ped

• groups of mesenchymal cells (dermal papilla) project into the tip of the bud

• the epidermal cells grow around the papilla, forming the hair bulb

What are 3 things keratinocytes need in order to perform their function?

1. strength

2. attachment to each other - to prevent being torn apart from eachother

3. attachment to dermis underneath - so they don’t get riipped off

What are keratins

• intermediate filament forming proteins that provide mechanical support

What do keratins link?

• cell nuclear membrane to plasma membrane at desmosomes

What is palmopalmar hyperkeratinosis

• genetic defect which affects keratin 16 - in epidermis of foot pads

• causes splitting and main from 4 mo of age

• no cure

what is the function of desmosomes?

• anchor the keratinocytes together

3 functions/links of desmosomes/

1. they act as a strong link b/w keratocytes, linking keratin intermediate filaments.

2. provide intracytoplasmic signalling

3. may be involved in congenital and autoimmune disease

Why is it important to understand the role of desmosomes?

• skins shouldn’t have cracks in it, if the cells are being torn apart for some reason/not holding together, indicates something is going wrong

What is pemphigus foliaceus

• an immune-mediated disease with antibodies directed against desmocollin-1 (dogs) and desmoglein-1 (other species)

• forms prominent pustules

What are hemidesmosomes

• filaments from dermal collagen that anchor epidermis to dermis

What does the number and complexity of molecules involved in hemidesmosomes link to?

• a large number of congenital and autoimmune diseases

What are the epidermal basement membrane ultrastructures

1. keratin filmanets w/in cells

2. hemidesmosomes

3. anchoring filaments

4. lamina densa

5. anchoring fibrils

what is epidermolysis bullosa acquisita

• immune-mediated disease with antibodies directed against collagen VII

  • can lead to ulceration e.g. on ear flap

Do we get different forms of epidermolysis bullosa?

• yes

  • congenital abnormalities link to others

  • e.g. dystrophic or junctional EB

• bullous pemphigoid antigens 1+2 and plectin are important

What ISN’T there in the epidermis?

• blood vessels

What are the layers of epidermis top to bottom?

1. horny layer

2. stratum corneum

3. stratum granulosum

4. stratum spinosum

5. stratum basale

Label this histological image of the skin

Left: s. spinosum too, s. corneum lower

right: Superficial dermis = pink, lower = s.basale layer

In which part of the body do we see a much thicker layer of epidermis?

• foot pads

Identify the layers, top to bottom

1. stratum corneum

2. epidermal papillae

3. dermal papillae

4. epidermis (brackeet)

5. dermis

6. sweat glands

7. hypodermis

Identify the general skin thickness of:

1. dog and cat

2. cattle

3. sheep

4. goat

5. pig

6. horse

1. 0.5-7mm

2. 6mm

3. 2.6mm

4. 2.9mm

5. 2.2mm

6. 1.7-7.7mm

which 2 species have rete ridges

1. pigs

2. horses at mane and tail base

Keratinocytes:

1. embryological origin

2. features

3. same in whole body?

4. how do desmosomal proteins change in layers

1. epithelial origin

2. complex internal cytoskeleton

3. no, the keratin differs

4. under influence of calcium

What do keratinocytes produce?

• extracellular lipids - ceramides, cholesterols, fatty acids - from the golgi apparatus in the granular layer → lipid lamellae

How can lipid/protein metabolism dysfunction show itself in the skin?

• change secretion function → change structure and function of skin

What is the cytoskeleton in the keratinocytes attached to ?

• tight junctions

• desmosomes

• hemidesmosomes

Stratum basale:

1. structure

2. function

1. single layer of cuboidal cells

2. proliferation, anchoring, stem cell function (pluripotent)

Stratum spinosum:

1. no. cells

2. cell shape

3. prominent feature?

   1. what does the upper most layer produce?

1. 1-20 cells thick

2. polyhedral

3. prominent desmosomes

4. involucrin - part of cornified layer

Stratum basale:

1. type of cell found these

2. how do they divide?

3. what are they influenced by?

1. proliferative

2. one cell remains as germinative, other differentiates

3. growth factors and hormones, inflammatory mediators, drugs and vitamins

Stratum granulosum:

1. always there with haired skin?

2. cell structure?

3. secretions?

4. what do desmosomes do?

5. what are they essential for?

1. no, variably present in haired skin

2. slightly flat, shrunken nuclei, have intracellular keratohyaline granules with profilaggrin and ioricrin

3. lipid and enzymes are secreted extracellularly

4. corneodesmosin

Identify the layers

1. stratum corneum

2. stratum granulosum

3. stratum spinosum

4. stratum basale

5. dermis

Stratum lucidum:

1. visible?

2. cell type

3. what do they contain?

4. why do they stain poorly?

1. not in haired skin - somewhat in hairless and thickened skin

2. slightly flat, shrunken nuclei

3. keratohyalin

4. increased intracellular lipids

Stratum corneum:

1. composed of?

2. what replaces the plasma membrane

3. what helps solidify the structure?

   1. what do we call desmosomes, why?

1. anucleate flattened cells, variable thickness

2. cornified envelope of many molecules

3. hydrophilic bonding of lipids forms organised ‘mortar’

4. corneodesmosomes

What does flaggrin facilitate?

• collapse of corneocytes into ‘building blocks’ → impermeable surface barrier

What does the breakdown of flaggrin lead to?

• urocanic acid (UCA) and pyrrolidone carboxylic acid (PCA) = moisturiser and excellent UV protection

Consequence of TGM-1 mutation in jack russell terriers?

• skin can’t grow properly - it’s a defect in the protein of the CE

Outline desquamation

• homeostatic process - continual loss of cells

• partly mediated by proteinases and glycosidases

• destruction of corneodesmesome

• invisible rafts of attached comeocytes fall off

What is golden retriever ichthyosis caused by?

• an insertion-deletion mutation → lead to a premature stop codon

In the dermis:

1. what gives tensile strength?

2. what resist and absorb compressive forces?

3. what determines thickness of skin

4. layers?

5. what additional things does it contain

6. specific cells?

1. collagen and elastin

2. solbule polymers - proteoglycans + hyaluronan

3. thickeness of dermis determines skin thickness

4. deep and superficial

5. epidermal appendages, arrecter pili muscles, blood and lymph and nerves

6. perivascular lymphocytes, dermal dendritic cells, mast cells and fibroblasts

What causes ehler-danlos syndrome?

• skin has poor strength due to a collagen defect → extra stretchy skin → more easily wounded.

With what other condition do we see similar skin fragility as with Ehler-danlos syndrome?

• hyperadrenocorticism

3 layers of blood supply

1. deep dermal vascular plexus

2. mid-dermal vascular plexus

3. superficial dermal vascular plexus

Where in the dermis do we find:

1. deep dermal vascular plexus

2. mid dermal vascualr plexus

   1. superficial dermal vascular plexus

1. interface of dermis and subcutis

2. level of sebaceous gland

3. just below epidermis

What do each of these blood plexus supply:

1. deep dermal vascular plexus

2. mid-dermal vascular plexus

3. superficial dermal vascular plexus

1. lower hair follicle and epitrichial sweat glands

2. arrector pili muscles, mid hair follicle and sebaceous glands

3. capillary loops supply epidermis and upper hair follicle

What is the lymphatic structure in the skin?

• vessels and capillaries largely follow the course of blood vessels

What is an example disease of blood vessels

• type III hypersensitivity vasculitis (e.g. due to drug reaction)

how do sebaceous glands form?

• basal alyer of germinative cells divide and differentiate → large polygonal cells with abundant vacuolated cytoplasm

What does sebum form?

• triglycerides and other lipids e.g. transferrin, IgA and IgG

Functions of sebum?

• lubricates hair and skin

• required for normal hair shaft separation

What is sebum excreted by?

• via squameous duct to hair follicle

What is a histological feature to help identify a sebaceous gland (epitrichial gland)

• arector pili muscle

What is sebasceous adenitis

• dog lack sebaceous glands

  • scale, hair breakage and follicular casts are noted

Identify 6 specialised sebaceous glands

• meibomian glands

• circumanal glands

• supracaudal gland of dogs and cats

• submental glands in cats

• preputial glands in horses

• infraorbital, inguinal and interdigital glands

Epitrichial glands:

1. associated with?

2. structure

3. structure found within the glands?

4. find where?

5. located below what?

6. excretes into what?

7. innervated?

   1. properties of what is secreted?

1. hair follicles

2. single layer of flattened cuboidal cells

3. coiled and saccular/tubular

4. distributed throughout haired skin

5. sebaceous glands

6. sweat into piliary anal just above sebaceous gland opening

7. NO

8. pheromonal and antimicrobial

Atrichial glands:

1. what aren’t they associated with?

2. what surrounds them

3. structure of glands

4. innervation

5. where do we find them

1. hairs

2. single layer, flattened cuboidal cells, surrounded by myoepithelial cells - merocrine secretion

3. small tightly coiled glands

4. cholinergic nerve fibres

5. non-haired areas

6. carpus of pigs, frog and ungulates + nasolabila region of ruminants and pigs. Generally - non-hair areas e.g. nose and footpad in carnivores

What are 5 specialised atrichial glands

1. mammary glands

2. interdigital glands of small ruminants

3. external ear canal

4. nasolacrimal glands

5. apocrine glands of anal sac

What 2 types of hairs are there?

• primary - guard hairs

  • secondary downy hairs

State 3 functions of hairs

• insulation

• signalling

• physical portection

What are hairs

• specialised keratinised tubular structure

What are the hair and follicle structure for omnivores and herbivoress

• simple - each infundibulum contains a single hair shaft of approx same size

What type of hair follicle do we find in sheep

• compound

What follicles do we find carnivores

• compound

Label this diagram

What two different stages of hair growth are these hairs in?

• left = growing - see bulb

• right = resting hair - shallow depth and tapering

How do the number of hairs differ in:

1. simple follicles

2. compound follicles

1. single

2. several

3 hair phases?

1. anagen

2. catagen

3. telogen

Compare primary and secondary hair follicles:

1. bulb depth

2. associated with?

Primary: bulb deep in dermis, have sebaceous glands, sweat glands, arrector pili muscles

Secondary - not as deep, smaller - associated sebaceous gland (MAYBE)

Which hairs are pirmary, which are secondary

Top = secondary

Bottom = primary (deeper in dermis)

Which is primary, which is secondary

left = secondary

right = primary

Outline these phases:

1. anagen

2. catagen

3. telogen

4. exogen

1. growth phase, new hair produced underneath, distinctive hair bulb contains follicular dermal papilla

2. transitional phase, rarely seen in normal skin - feature of some diseases

3. process of hair being lost

What phase of growth is this hair in?

• growing - note bulb shape

What phase of hair growth is this hair in

• telogen phase - note small bulb

what is the isthmus

• where sebaceous gland attaches divides the hair between infundibulum and inferior portion

what is the growth pattern of hair for:

1. angora rabbit, mohair goat, poodle

   1. dogs, cats, horse, hedgehogs

1. anogenic

2. telogenic

what determines hair length

• duration of anagen phase

what is hair cycle regulated by?

• photoperiod

• termperature

• hormones

• nutrition and general health

• growth factors

• drugs

What hormones regulate hair cycle?

• thyroid, GH are stimulatory

• oestrogen and corticosteroids are inhibitory

What phases of growth are these hairs in?

Top = telogen

Bottom = anagen

What provides blood supply to anagen hairs?

• dermal papilla

What undergoes mitosis in anagen hairs?

• - hair bulb epithelium

What cells provide hair pigment

• melanocytes

What are the 6 layers of the hair? inner to outer?

1. medulla, cortex, cuticle of hair

2. Huxley layer, Henle layer (inner root sheath)

3. outer root sheath (continuous with epidermis)

4. glassy membrane (basement membrane)

What gives the hair strength in anagen phase?

• hair and IRS cuticle - fit together

what permits hair loss in exogen phase?

• IRS disappears in catagen

Label

Catagen phase:

1. where in the dermis

2. how do we identify the hairs this way?

3. what has the hair lost

4. what does it develop

5. slow or fast?

6. mediated by what?

1. mid dermis

2. involution of hair bulb and dermal papilla - also upwards migration

3. internal root sheath

4. thick glassy membrane, above bulb

5. fast

6. apoptosis

Telogen phase:

1. where in dermis

2. where do we find the conical bulb

3. what is the hair surrounded by

4. what is it separated from and by?

5. active/dormant bulb?

6. what forms beneath old follicle

7. how do new hairs replace old ones?

1. mid-upper

2. level of attachment of arrector pili muscle

3. external root sheath - terminates at sebaceous gland level

4. separated from dermal papilla by thick basement membrane

5. dormant

6. new bulb and papilla

7. new bulb forms a new hair and old hair is lost

Which phases of growth are these hairs in?

Left = telogen (narrow and straight)

Right = anagen (bulb, flexible)