Dermatology

Question 1

The skin arises from the juxtaposition of 2 major embryological elements. Name them and their origin

Answer 1

Epidermis - Originates from the ectoderm

Dermis - Arises from the mesoderm that comes into contact with the inner surface of the epidermis

Question 2

Outline the stages of skin development (include weeks as well)

Answer 2

1. Epidermis forms by week 4 as a single basal layer of cuboidal cells -> Superior mesoderm layer
2. Secondary layer of squamous, non-keratinizing cuboidal cells (periderm) develops in week 5 -> generates white, waxy protective substance (vernix caseosa)
3. From week 11, basal layer of cuboidal cells (stratum germinativum) proliferates to form a multi-layered intermediate zone → 4 more superficial strata: spinosum (spinous), granulosum (granular), lucidum (clear), and corneum (horny)
4. Epidermal ridges protrude as troughs into developing dermis beneath neurovascular supply and develops into dermal papillae
5. Weeks 9-13: Development of hair follicles in stratum germinativum, and appearance of lanugo hair

Question 3

List the layers of superficial strata of the epidermis from deep to superficial

Answer 3

Stratum germinativum -> stratum spinosum -> stratum granulosum -> stratum lucidum (in palms of hands and soles of feet) -> stratum corneum

Question 4

What are melanocytes derived from?

Answer 4

Neural crest → Melanoblasts (melanosomes).

Migrate dorsally between weeks 6-8 to developing epidermis, dermis, and hair follicles

Question 5

By what week have most melanoblasts reached their destination and differentiated into melanocytes?

Answer 5

Weeks 12-13

Question 6

What are melanocytes responsible for?

Answer 6

Melanin secretion, through melanogenesis.

Question 7

What do a subset of melanoblasts form and why?

Answer 7

Melanocyte stem cells in the hair follicle bulge to replenish differentiated melanocytes

Question 8

What regulates the quantity and quality of melanocytes produced and explain how it is controlled?

Answer 8

Melanocortin 1 receptor (MC1R) → G protein-coupled receptor. Controlled by agonists alpha-melanocyte-stimulating hormone (αMSH) and ACTH and antagonist agouti signaling protein (ASP).

Agonist activation of MC1R causes a melanogenic cascade (tyrosine activity), which causes the synthesis of eumelanin (dark pigment).
alpha-MSH + ACTH → MC1R activation → melanogenic cascade → synthesis of eumelanin

Antagonist interaction reverses the effect of agonists and elicits the production of pheomelanin (pale pigment).

UV exposure causes increased melanin production and increased uptake and distribution of melanosomes by keratinocytes.

Question 9

What does ACTH up-regulate the expression of?

Answer 9

MC1R gene

Question 10

What is the dermis?

Answer 10

A layer of connective tissue and subcutaneous fat, deep to the epidermis and separated by the basement membrane.

Question 11

Outline the structure of the skin

Answer 11

Epidermis (composed of keratinocytes) -> basement membrane (dermal-epidermal junction) -> dermis (mainly connective tissue) -> subcutaneous fat

Question 12

Outline the layers of the epidermis.

Answer 12

Composed of keratinized, stratified squamous epithelium, avascular structure.
Deep to superficial:
Basal layer (stratum basale) -> stratum spinosum -> stratum granulosum -> stratum lucidum (only in palms of hands and soles of feet) -> stratum corneum
Takes approximately 30 days to go from deep to superficial but this is accelerated in skin diseases

Question 13

What does the filamentous cytoskeleton of keratinocytes (in the epidermis) contain?

Answer 13

(Thin) actin-containing microfilaments
(Thick) tubulin-containing tubules
Intermediate filaments (keratin)

Question 14

What are the functions of the layers of the stratum corneum?

Answer 14

Outer -> Absorb solutes
Middle -> Absorb water for skin hydration
Inner -> Mechanical defense barrier (contains many lipids, which contribute to this)

Question 15

What are the roles of keratins?

Answer 15

Stress response 
Structural properties 
Cellular signaling 
Apoptosis
Wound healing

Question 16

What are desmosomes and what are they made of?

Answer 16

Major adhesion complex in the epidermis. Anchor keratin intermediate filaments to the cell membrane and bridge adjacent keratinocytes. Allow cells to withstand trauma.

Question 17

What are the junctions found in the epidermis and what are their functions?

Answer 17

Desmosomes - Major adhesion complex in the epidermis. Anchor keratin intermediate filaments to the cell membrane and bridge adjacent keratinocytes. Allow cells to withstand trauma.
Gap junctions - Clusters of intercellular channels, which directly form connections between the cytoplasm of adjacent keratinocytes. Essential for cell synchronization, differentiation, growth, and metabolic coordination.
Adherens junctions - Transmembrane structures that engage with the actin skeleton of keratinocytes.
Tight junctions - Role in barrier integrity and cell polarity.

Question 18

List the cells of the epidermis (not including keratinocytes).

Answer 18

Melanocytes - Dendritic, distribute melanin pigment in melanosomes to keratinocytes.
Langerhans cells - Dendritic, antigen-presenting cells
Merkel cells - Mechanosensory receptors
Mast cells - immune cell

Question 19

Are the number of melanocytes in people different?

Answer 19

No; the number of melanocytes is the same among skin types

Question 20

What is considered to be the dermal-epidermal junction, what does this structure consist of, and what are its roles/functions?

Answer 20

Basement membrane
Consists of glycoproteins, proteoglycans: collagen IV & VII, laminin, and integrin.
Roles in cell adhesion and migration.

Question 21

Outline the structure of the dermis.

Answer 21

The dermis consists of 2 layers of connective tissue composed of proteins, glycoproteins, and ground substance.
Provides resilience to the skin.
Papillary layer - superficial, loose connective tissue, vascular.
Reticular dermis - deep, dense, forms bulk of dermis

Question 22

What proteins are found in the dermis?

Answer 22

Collagen (type I and II) - 80-85% of the dermis. 
Elastic fibers (2-4%) - fibrillin + elastin 
Glycoproteins- Fibronectin, fibulin, integrins - facilitates cell adhesion and motility. 
Ground substance - Between dermal collagen and elastic tissue (Glycosaminoglycan/ proteoglycan)

Question 23

What is the main cell present in the dermis and also what are the other cells present?

Answer 23

Fibroblasts (main); others include histiocytes, mast cells, neutrophils, lymphocytes, and dermal dendritic cells.

Question 24

What is the vascular supply of the skin?

Answer 24

Deep and superficial vascular plexus - don’t cross into the epidermis.

Question 25

Outline the innervation of skin.

Answer 25

Sensory - Free, hair follicles, expanded tips | Autonomic - Cholinergic for eccrine (non-odorous); adrenergic for eccrine and apocrine (odorous)

Question 26

What are the 2 types of afferent nerve endings from the skin? Give where they're found, describe their receptors and examples of each.

Answer 26

Corpuscular (encapsulated receptors - dermis). E.g. Pacinian and meissners. Free (non-encapsulated receptors - epidermis). E.g. Merkel cell

Question 27

What are Meissner's corpuscles?

Answer 27

Encapsulated unmyelinated mechanoreceptors with a lamellated capsule that provide sensation of light touch and slow vibration. Senses low-frequency stimulation at the level of the dermal papilla.

Question 28

Where are Meissner's corpuscles most concentrated?

Answer 28

Located in the superficial dermis and most concentrated in thick hairless skin (finger pads and lips).

Question 29

What are Ruffini corpuscles (Bulbous corpuscles)?

Answer 29

Slow-acting mechanoreceptors that are spindle-shaped. They are sensitive to skin stretch and monitor slippage of objects.

Question 30

Where are Ruffini's corpuscles most concentrated?

Answer 30

Located at the deeper dermis and has the highest density around the fingernails

Question 31

What are Pacinian corpuscles (lamellar corpuscles)?

Answer 31

Ovoid, encapsulated, phasic (rapidly adapting) mechanoreceptors that detect deep pressure and vibration. Deep touch - vibrational role (detects surface texture).

Question 32

Where are Pacinian corpuscles found?

Answer 32

Dermal papillae of hands and feet.

Question 33

What are Merkel cells?

Answer 33

Oval-shaped, non-encapsulated mechanoreceptors that detect light or sustained touch and pressure.

Question 34

Where are Merkel cells found?

Answer 34

In modified epidermal cells, in the stratum basale (directly above basement membrane). Mostly found in the fingertips but also present in the palms, soles, oral, and genital mucosa.

Question 35

What detects pain?

Answer 35

Free nerve endings (nociceptor).