What are the anatomical skin structures, starting with the most superficial?
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
Skin serves 11 functions:
Motion & shape
Produces follicles & adnexal glands
Storage & Metabolism
How does the skin act as an enclosing barrier & what are the associated cells/structures to aid this function?
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.
Stratum corneum - produced by keratinisation (programmed cell death) & mitosis of keratinocytes migrating up from basement membrane. SC undergoes regular & orderly desquamation in healthy skin.
What are the skin's anti-microbial properties? What associated structures in skin enable it to act against bacteria, fungus and yeasts?
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.
How does skin fulfil the functions of motion & shape?
Skin has properties of toughness, stretchiness (elasticity) and flexibility.
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
The produce of follicles & adnexal glands in the skin dermis are important for animals. What are their properties and their associated structures?
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”)
What are the properties of temperature regulation by the skin?
What are the associated structures that facilitate temperature regulation by the skin?
Skin blood supply & sweating
The hair coat helps temperature regulation.
What is/are the motor function(s) served by the skin? What are the associated structures?
Twitching & raising/lowering fur or hair
Panniculous carnosus - major subcutaneous muscle that causes twitching
Pilomotor apparatus aka arrector pili muscles in dermis
Sympathetic fibres only
What sensory functions do skin provide and what are the associated structures?
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.
How does skin "sweat"? What are the associated structures in skin that enable animals to sweat?
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
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
How does skin perform the functions of storage and metabolism?
Skin is a storage reservoir of water, fat & vitamins.
Vitamin D production
How does skin perform the function of pigmentation? What are the associated structures?
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
How does skin participate in immunoregulation? What are the associated structures?
Inflammation, Chemotaxis, Wound-healing
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
How does a simple hair follicle differ from a compound hair follicle?
Which species have simple vs compound?
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.
What is the morphology of human skin vs cattle?
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.
What is the morphology of fish epidermis?
No hair follicles but covered in scales.
Generally lacks a layer of dead, fully keratinized cells
What is the morphology of reptile epidermis?
No hair follicles; covered in plates.
High degree of cornification; may be shed all at once; almost no glands
What is the characteristic about the bird epidermis?
No hair follicles but feathers instead.
Two epidermal layers & no sebaceous or sweat glands.
What are the four epidermal layers, starting at the basal membrane, and what occurs at each layer?
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
In general how long does it take for a cell to reach the stratum corneum after leaving the basal membrane?
About 21 days to die.
Cats sweating directly through their foot pads when nervous are examples of animals using which type of sweat gland?
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.
In the hair growth cycle, which parts are present during the anagen phase, starting from the most superficial part of the shaft?
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.
What part of the hair shaft is missing during the telogen (resting) phase of hair growth?
What are the distinctive features of the Stratum basale/Germinal layer?
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.
What are the distinctive features of the stratum spinosum?
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.
What are the distinctive features of the stratum granulosum?
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.
What are the features of the stratum corneum?
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.
How is epidermal homeostasis maintained?
Desquamation, ie., the sloughing off of anucleated cells from the stratum corneum, helps the epidermis maintain homeostasis.
What is the reaction of epidermis to damage from within & outside, and what are the first and second-level barriers?
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
What happens if the first- and second-level barriers (basically, the whole epidermis) are breached in terms of injury or damage?
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
Describe the processes of epidermal differentiation (cornification).
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.
Explain the relationship between lipids and barrier function.
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.
What makes up the lipid matrix in the stratum corneum?
Free fatty acids
What is hyperkeratosis and when does it happen?
It's excess scale - thicker than normal stratum corneum, or disorderly desquamation
•Default response for troubled epidermis
• External assault/challenge
• 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)
•Formation of lipid bilayer
•Cornified envelope formation
What is parakeratosis & what causes it?
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.
How do you diagnose for perakeratosis?
Pick up squames with sticky tape, stain view under microscope. Look for nucleii.