Skin

Question 1

What are the anatomical skin structures, starting with the most superficial?

Answer 1

Epidermis - includes stratum corneum & stratum germinativum; keratinocytes, melanocytes, Langerhans cells, Merkel cells

Basement membrane zone - separates dermis from epidermis

Dermis - contains the appendageal system of sweat glands, sebaceous glands & hair follicles

Subcutaneous muscle

Subcutaneous fat

Question 2

**Skin serves 11 functions: **

Enclosing barrier

Antimicrobial action

Motion & shape

Produces follicles & adnexal glands

Temperature regulation

Motor

Sensory

Sweat

Storage & Metabolism

Pigmentation

Immunoregulation

How does the skin act as an enclosing barrier & what are the associated cells/structures to aid this function?

Answer 2

Skin acts as an impermeable barrier to loss of fluids, electrolytes, minerals, nutrients, and water

Skin also prevents penetration of infectious or noxious agents into the skin.

Associated structures:

Stratum corneum - produced by keratinisation (programmed cell death) & mitosis of keratinocytes migrating up from basement membrane. SC undergoes regular & orderly desquamation in healthy skin.

Question 3

What are the skin’s anti-microbial properties? What associated structures in skin enable it to act against bacteria, fungus and yeasts?

Answer 3

Anti-fungal & anti-bacterial properties:

Keratinocytes release antimicrobial peptides.

Langerhans cells are mononuclear dendritic cells that process allergenic & antigenic material to present to T-cells locally & in lymph nodes to induce hypersensitivity reactions.

Commensal bacteria in skin:

In immunosuppressed &/or undernourished animals, Dermatophilus congolensis, a commensal bacteria in many ruminants, cats, dogs, humans, can cause rainscald, rain rot & Mud Fever in horses, sheep (“lumpy wool”).
Staphylococci, amid natural reservoir of commensals, can lead to chronic infection.

Question 4

How does skin fulfil the functions of motion & shape?

Answer 4

Skin has properties of toughness, stretchiness (elasticity) and flexibility.

Associated structures:

Collagen & elastin fibres (& their fibroblasts) in dermis.

NB Collagen can become target of disease eg., scurvy in humans, hyperextensible skin & laxity of joints in dogs, foot-pad hyperkeratosis

Question 5

The produce of follicles & adnexal glands in the skin dermis are important for animals. What are their properties and their associated structures?

Answer 5

1. Hair - mechanical barrier, protect from actinic (sun) damage, thermoregulation, camouflage, status.

2. Formed by: **Simple & compound follicles - **Growing (anagen) follicle has inferior section as well as isthmus & infundibulum, ie., ; resting (telogen) follicle doesn’t, has regressed.

3. Hooves/Claws - Made from keratinocytes; hoof is horny (keratinous) layer protecting corium, bone

4. Horns/Antlers - Horns are live bone covered by keratin & other proteins; Antlers are dead bone (destroyed by osteoclasts); can be shed & regrown (initially covered by heavily vascularised “velvet”)

Question 6

What are the properties of temperature regulation by the skin?

What are the associated structures that facilitate temperature regulation by the skin?

Answer 6

Skin blood supply & sweating

The hair coat helps temperature regulation.

Question 7

What is/are the motor function(s) served by the skin? What are the associated structures?

Answer 7

Twitching & raising/lowering fur or hair

Associated structures:

Panniculous carnosus - major subcutaneous muscle that causes twitching

Pilomotor apparatus aka arrector pili muscles in dermis

Sympathetic fibres only
Blood vessels

Sweat glands

Question 8

What sensory functions do skin provide and what are the associated structures?

Answer 8

Pain & itch sensation - Many free nerve endings; plexus of nerve fibres, superficial & deep

Touch & vibration sensation - Merkel cells, free nerve endings, “corpuscles”

Merkel cells are oval receptor cells found in the skin of vertebrates that have synaptic contacts with somatosensory afferents. They are associated with the sense of light touch discrimination of shapes and textures. They can turn malignant and form the skin tumor known as Merkel cell carcinoma.

Question 9

How does skin “sweat”? What are the associated structures in skin that enable animals to sweat?

Answer 9

Evaporation of sweat from the skin is the primary cooling mechanism for horses and primates and, to a lesser degree, pigs, sheep, and goats.

• Some clinical evidence suggests limited sweating occurs in dogs and cats, maybe a minor role in cooling.
• Cats sweat through their paws esp. when excited

Protection against microbes

Friction

Pheromones, Milk

Two types of sweat glands:

Epitrichial (formerly apocrine) - discharges sweat directly into hair follicle

Atrichial (formerly eccrine) - discharges sweat directly to epidermal surface, no need for hair follicle

Question 10

How does skin perform the functions of storage and metabolism?

Answer 10

Skin is a storage reservoir of water, fat & vitamins.

Carbohydrate, protein
Vitamin D production

Question 11

How does skin perform the function of pigmentation? What are the associated structures?

Answer 11

Skin & coat colour - Melanocytes produce granules that enter keratinocytes; melanocytes also present in follicle bulb, transferring pigment granules directly to hair follicle

Protection from solar radiation - Melanin cap protects cell nucleus

Camouflage, social recognition

Question 12

How does skin participate in immunoregulation? What are the associated structures?

Answer 12

Inflammation, Chemotaxis, Wound-healing

Associated structures:

• *Cellular & humoral components:**
• *Cells in epidermis:** Langerhans cells (dendritic cells)
• *Cells in dermis:** eg. resident mast cells, recruited neutrophils & eosinophils, recirculating lymphocytes & plasma cells
• *Humoral: Innate & Adaptive:**
• *Blood vessels** - dilate, white blood cells recruited to area around blood vessel, inflaming, causing perivascular dermatitis; usually accompanied by epidermal hyperplasia as skin tries to get rid of antigen by increasing speed of keratinocyte production

Question 13

How does a simple hair follicle differ from a compound hair follicle?

Which species have simple vs compound?

Answer 13

Simple hair follicles only have one hair per follicle; compound follicles have more than one hair per follicle.

Humans, horses & cattle have simple hair follicles.

Sheep, goats, cats & dogs have compound hair follicles.

Question 14

What is the morphology of human skin vs cattle?

Answer 14

Human skin is thick because there is a lack of full-body hair follicles to protect it; cattle, horses, dogs, cats and sheep have relatively thin skin because they are protected by hair.

Question 15

What is the morphology of fish epidermis?

Answer 15

No hair follicles but covered in scales.

Generally lacks a layer of dead, fully keratinized cells

Question 16

What is the morphology of reptile epidermis?

Answer 16

No hair follicles; covered in plates.

High degree of cornification; may be shed all at once; almost no glands

Question 17

What is the characteristic about the bird epidermis?

Answer 17

No hair follicles but feathers instead.

Two epidermal layers & no sebaceous or sweat glands.

Question 18

What are the four epidermal layers, starting at the basal membrane, and what occurs at each layer?

Answer 18

Basal membrane

Stratum basale - proliferation

Stratum spinosum - differentiation

Stratum granulosum - has dark-staining enzymatic structures that essentially “kill” live keritinocytes into squamous cells

Stratum corneum - dead layer, exposed to outside; can look like basket-weave in H& E stain (artifact) rather than flat layers; squames

Question 19

In general how long does it take for a cell to reach the stratum corneum after leaving the basal membrane?

Answer 19

About 21 days to die.

Question 20

Cats sweating directly through their foot pads when nervous are examples of animals using which type of sweat gland?

A. Apocrine

B. Eccrine

C. Atrichial

D. Epitrichial

Answer 20

B & C

Eccrine & Atrichial are the SAME THING, referring to glands that deposit sweat directly onto the surface of the epidermis.

Apocrine & Epitrichial refer to sweat glands that deposit sweat into the hair follicle.

Question 21

In the hair growth cycle, which parts are present during the anagen phase, starting from the most superficial part of the shaft?

Answer 21

Anagen (growth) phase:

The tip of the hair shaft, protruding through the epidermis, is the infundibulum.

Below that is the isthmus. The erector-pili muscle is attached at the isthmus.

Below that, closest to the base of the follicle is the inferior.

Question 22

What part of the hair shaft is missing during the telogen (resting) phase of hair growth?

Answer 22

Inferior.

Question 23

What are the distinctive features of the** Stratum basale/Germinal layer?**

Answer 23

Proliferation:

Composed mainly of proliferating and non-proliferating keratinocytes, attached to the basement membrane by hemidesmosomes.

Melanocytes are present, connected to numerous keratinocytes in this and other strata through dendrites. Merkel cells are also found in the stratum basale with large numbers in touch-sensitive sites such as the fingertips and lips. They are closely associated with cutaneous nerves and seem to be involved in light touch sensation.

Question 24

What are the distinctive features of the stratum spinosum?

Answer 24

Increase in adhesions:

Keratinocytes become connected through desmosomes and start to produce **lamellar bodies **from within the Golgi, enriched in polar lipids, glycosphingolipids, free sterols, phospholipids and catabolic enzymes.

Langerhans cells, immunologically active cells, are located in the middle of this layer.

Question 25

What are the distinctive features of the stratum granulosum?

Answer 25

**Lipid extrusion, loss of nucleii**: Keratinocytes lose their nuclei and their **cytoplasm appears granular**. ***Lipids, contained in those keratinocytes within lamellar bodies, are released into the extracellular space through exocytosis to form a lipid barrier.*** Those polar lipids are then converted into non-polar lipids and arranged parallel to the cell surface. For example **glycosphingolipids become ceramides** and **phospholipids become free fatty acids.**

Question 26

What are the features of the stratum corneum?

Answer 26

Composed of layers of **polyhedral, anucleated corneocytes** (final step of keratinocyte differentiation), with the paws having more layers. Corneocytes are surrounded by a **protein envelope** (cornified envelope proteins), filled with **water-retaining keratin proteins, attached together through corneodesmosomes** and surrounded in the extracellular space by stacked layers of lipids. Most of the barrier functions of the epidermis localize to this layer.

Question 27

How is epidermal homeostasis maintained?

Answer 27

**Desquamation**, ie., the sloughing off of anucleated cells from the stratum corneum, helps the epidermis maintain homeostasis.

Question 28

What is the reaction of epidermis to damage from within & outside, and what are the first and second-level barriers?

Answer 28

Barrier perturbation **stimulates synthesis and “jacking up” of more lipids** to repair its permeability-protection function, while **inducing more desquamation** to help the skin recover. If the perturbation is more severe, or if the external injury persists, then **hyperplasia and inflammation** take place. Also, if the external injury persists, inflammation will also occur. **1st level barrier**: **Stratum corneum** senses change in Ca2+ gradient via “biosensors” **2nd level barrier**: **Nucleated epidermis (stratum spinosum & stratum basale)** where keratinocytes have sensors for bacteria/microbes, release *antibacterial peptides & inflammatory mediators*

Question 29

What happens if the first- and second-level barriers (basically, the whole epidermis) are breached in terms of injury or damage?

Answer 29

If the first-level barrier or second-level barrier are perturbed, for example by a change in pH, epidermal injury, psychological stress (glucocorticoids/ cortisol released), dehydration or cornification defects (pathological, such as retention keratosis or parakeratosis), then **the epidermal biosensors will trigger cytokine synthesis & release,** leading to: 1) ***lipid synthesis & extrusion to the epidermial surface*** 2) ***hyperplasia of keratinocytes*** 3) ***inflammation of the dermis***

Question 30

Describe the processes of epidermal differentiation **(cornification).**

Answer 30

Cornification is the process of forming an epidermal barrier in **stratified squamous epithelial tissue**. The stratified squamous epithelium is maintained by **cell division (mitosis) within the stratum basale**. Differentiating cells **delaminate** from the basement membrane and are displaced outwards through the epidermal layers, undergoing multiple stages of differentiation until, in the **stratum corneum, losing their nucleus and fusing to squamous sheets**, which are eventually shed from the surface **(desquamation).** At the cellular level, cornification is characterised by: • **production of keratin** • **production of proteins and enzymes** which eventually form a **cornified cell envelope** beneath the plasma membrane • **terminal differentiation** • **loss of nuclei and organelles,** in the final stages of cornification metabolism ceases and the cells are almost completely filled by keratin Differentiated keratinocytes **secrete keratin proteins** which contribute to the formation of an **extracellular matrix** and is an integral part of the skin barrier function. During the process of epithelial differentiation, **cells become cornified as keratin protein is incorporated into longer keratin intermediate filaments.** Eventually the nucleus and cytoplasmic organelles disappear, metabolism ceases and **cells undergo a programmed death as they become fully keratinized**. Cells in the epidermis contain a structural matrix of **keratin, which makes this outermost layer of the skin almost waterproof, and along with collagen and elastin, gives skin its strength.** Keratinized epidermal cells are constantly shed and replaced. These hard, integumentary structures are formed by **intercellular cementing of fibers formed from the dead, cornified cells generated by specialized beds deep within the skin.** Hair grows continuously and feathers moult and regenerate.

Question 31

Explain the relationship between lipids and barrier function.

Answer 31

The ability of the skin to hold water is primarily due to the **stratum corneum** and is critical for maintaining healthy skin. Lipids arranged **through a gradient and in an organized manner** between the cells of the stratum corneum form a barrier to transepidermal water loss.

Question 32

What makes up the lipid matrix in the stratum corneum?

Answer 32

Ceramides Free fatty acids Cholesterol

Question 33

What is hyperkeratosis and when does it happen?

Answer 33

It's excess scale - thicker than normal stratum corneum, or disorderly desquamation •Default response for troubled epidermis Causes: • **Metabolic** • Endocrine • Nutritional **• External assault/challenge** • Ectoparasites • Skin infections • Toxic substances, solvents, detergents • Physical damage, low humidity **• Intrinsic inflammatory** • Hypersensitivity skin diseases • Immune mediated diseases, drug eruptions **Genetic defect of cornification (rare)** * Desquamation * Formation of lipid bilayer * Cornified envelope formation * Keratin deposition

Question 34

What is parakeratosis & what causes it?

Answer 34

**Persistence of nucleated cells into stratum corneum** - nucleus isn't lost as cells move up. * Represents abnormal cornification * Clinically scale or scale/crust * With ‘sick/damaged' keratinocytes in metabolic disorders or epidermal attack * With epidermal hyperplasia in chronic inflammation NB: Aquatic animals will have non-gappy, thick stratum corneum with nucleus retained - they don't need water barrier since they live in water.

Question 35

How do you diagnose for perakeratosis?

Answer 35

Pick up squames with sticky tape, stain view under microscope. Look for nucleii.