introduction to dermatology part 1

Question 1

what does the skin arise from in the embryo?

Answer 1

juxtaposition of ectoderm and mesoderm to form the epidermis and dermis respectively

Question 2

what is the mesoderm essential for?

Answer 2

differentiation such as hair follicles

Question 3

how does the skin develop?

Answer 3

Epidermis forms by week 4 as single basal layer of cuboidal cells
Secondary layer of squamous, non-keratinising cuboidal cells (periderm) develops in week 5
Generates white, waxy protective substance - vernix caseosa
From week 11, basal layer of cuboidal cells ( stratum germinativum) proliferates to form multilayered intermediate zone → four more superficial strata
Spinosum(spinous),granulosum(granular),lucidum(clear; found on palms of hands and soles of feet), andcorneum(horny).
Epidermal ridges protrude as troughs into developing dermis beneath neurovascular supply develops into dermal papillae
Weeks 9-13 development of hair follicles in stratum germinativum and appearance of lanugo hair

Question 4

how do melanocytes develop?

Answer 4

Melanocytes → derived from neural crest →melanoblasts → migrate dorsally between week 6-8 to developing epidermis (& dermis) and hair folliicles
By week 12-13, most melanoblasts have reached destination and differentiate into melanocytes
Subset of melanoblasts form melanocyte stem cells in hair follicle bulge that replenish differentiated melanocytes

Question 5

what are the 2 ways of regulating melanocytes?

Answer 5

exposure to UV light

melanocortin 1 receptors

Question 6

outline how melanocytes are regulated using melanocortin 1 receptors

Answer 6

Melanocortin 1 receptor (MC1R), a G protein-coupled receptor regulates quantity and quality of melanins produced:
Controlled by agonists α-melanocyte-stimulating hormone (αMSH) & adrenocorticotropic hormone (ACTH) and antagonist, Agouti signaling protein (ASP).
Activation of MC1R by agonist → melanogenic cascade → synthesis of eumelanin
ASP reverses those effects & elicit production of pheomelanin
ACTH can also up-regulate expression of the MC1R gene

Question 7

outline how UV regulates melanocytes

Answer 7

Increased expression of MITF & downstream melanogenic proteins, including Pmel17, MART-1, TYR, TRP1, and DCT → increases in melanin content
Increased PAR2 in keratinocytes → increases uptake & distribution of melanosomes by keratinocytes

Question 8

what is the overall structure of the skin?

Answer 8

Epidermis:

Basement membrane (dermal-epidermal junction)
Dermis:
Connective tissue
Subcutaneous fat

Question 9

what is the structure of the epidermis?

Answer 9

Epidermis- > composed of keratinocytes
Division of cells in basal layer
Progressive differentiation / flattening:
Stratum spinosum
Stratum granulosum
Stratum lucidum (palms and soles only)
Stratum corneum (no nuclei or organelles)

Cellular progression from basal layer → surface in ~ 30 days
Accelerated in skin diseases (e.g. psoriasis)

Question 10

what does the Filamentous cytoskeleton of keratinocytes comprise of?

Answer 10

Actin‐containing microfilaments (7nm)
Tubulin‐containing microtubules (20-25nm)
Intermediate filaments (keratins) (7-10nm)

Question 11

what are the roles of keratin

Answer 11

Structural properties
Cell signalling
Stress response
Apoptosis
Wound healing

Question 12

what are desmosomes and what do they do?

Answer 12

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

Question 13

what do the gap junctions do?

Answer 13

Clusters of intercellular channels (connexons)
Directly form connections between cytoplasm of adjacent keratinocytes
Essential for cell synchronization, cell differentiation, cell growth and metabolic coordination

Question 14

what do adherens junctions do?

Answer 14

Transmembrane structures

Engage with the actin skeleton

Question 15

what do tight junctions do?

Answer 15

Role in barrier integrity and cell polarity

Question 16

what are the other cells in the epidermis and what do they do?

Answer 16

Melanocytes -
Dendritic
Distribute melanin pigment (in melanosomes) to keratinocytes
Number of melanocytes = among skin types.

Langerhans cells -
Dendritic
Antigen‐presenting cells

Merkel cells -
Mechanosensory receptors

Mast cells

Question 17

what makes up the basement membrane?

Answer 17

Aka dermal-epidermal junction
Proteins and glycoproteins
Collagens (IV, VII), laminin, integrins

Question 18

what is the purpose of the basement membrane?

Answer 18

Cell adhesion

Cell migration

Question 19

what are the two parts of the dermis?

Answer 19

papillary dermis

reticular dermis

Question 20

what is the papillary dermis like?

Answer 20

Superficial
Loose connective tissue
Vascular

Question 21

what is the reticular dermis like?

Answer 21

Deep
Dense connective tissue
Forms bulk of dermis

Question 22

what is quite high in the dermis?

Answer 22

Proteins
Collagen (80-85% of dermis) – mainly types I and III
Elastic fibres (2-4%) – fibrillin, elastin
Glycoproteins – fibronectin, fibulin, intregrins – facilitate cell adhesion and cell motility
Ground substance – between dermal collagen and elastic tissue – glycosaminoglycan / proteoglycan

Question 23

what is the main cell of the dermis?

Answer 23

fibroblasts

Question 24

what are all the types of cell in the dermis?

Answer 24

Histiocytes
Mast cells
Neutrophils
Lymphocytes
Dermal dendritic cells
fibroblasts

Question 25

describe the blood supply of the skin

Answer 25

Blood supply – deep and superficial vascular plexus | Does not cross into epidermis

Question 26

describe the innervation of the skin

Answer 26

Sensory – free, hair follicles, expanded tips Autonomic- Cholinergic – eccrine Adrenergic – eccrine and apocrine

Question 27

what is the difference between apocrine and eccrine glands?

Answer 27

eccrine- all over (salty water) | apocrine- body odour (arm pits and genitals)

Question 28

what is the pilosebaceous unit?

Answer 28

hair follicle

Question 29

what are the types of afferent nerve in the skin?

Answer 29

corpuscular(dermis)- encapsulated receptors (e.g Pacinian, Meissner's) free(epidermis)- non encapsulated receptors (e.g merkel cell )

Question 30

what is a messner's corpuscle?

Answer 30

tactile corpuscles Encapsulated, unmyelinated mechanoreceptors Lamellated capsule Superficial dermis Most concentrated in thick hairless skin, (finger pads and lips) Light Touch (+slow vibration) Senses low-frequency stimulation at level of dermal papilla

Question 31

what is a Ruffini corpuscle?

Answer 31

``` bulbous corpuscle Slow acting mechanoreceptor Deeper in dermis Spindle-shaped Sensitive to skin stretch Highest density around fingernails Monitors slippage of objects ```

Question 32

what is a pacinian corpuscle?

Answer 32

lamellar corpuscle Encapsulated Rapidly adapting (phasic) mechanoreceptor Deep pressure and vibration (deep touch) Vibrational role - detects surface texture Ovoid Dermal papillae of hands and feet

Question 33

what is a merkel cell?

Answer 33

Non-encapsulated mechanoreceptors Light / sustained touch, pressure Oval-shaped Modified epidermal cells Stratum basale, directly above basement membrane Most populous in fingertips Also in palms, soles, oral & genital mucosa

Question 34

describe the microbiome of the skin?

Answer 34

Microbiota: bacteria, fungi and viruses ~ 1 million bacteria /cm2 skin Predominantly Actinobacteria (including Propionibacteria and Corynebacteria), Firmicutes (Clostridia and Bacilli [Staphylococcus] , Bacteroidetes & Proteobacteria Composition of each niche depends on environment Role in immune-modulation and epithelial health Role in disease

Question 35

what are the functions of the skin?

Answer 35

``` Immunological barrier Physical barrier Thermoregulation Sensation Metabolism Aesthetic appearance ```

Question 36

what do the langerhans cell do in terms of immune barrier?

Answer 36

Dendritic cell (DC)/macrophage family Sentinel cells in epidermis Initiate immune response against microbial threats Also contribute to immune tolerance Form dense network with which potential invaders must interact.

Question 37

how do langerhans cells create an immune response?

Answer 37

Specialized at “sensing” environment Extend dendritic processes through intercellular tight junctions to sample outermost layers of skin (stratum corneum) Interpret microenvironmental context a → determine appropriate quality of immune response. In absence of danger, promote expansion and activation of skin-resident regulatory - cells (Tregs) When sense danger (PAMP) → rapid initiation of innate antimicrobial responses Induction of adaptive response - power and specificity of T-cell

Question 38

what else carries out immune surveilance?

Answer 38

Tissue‐resident T-cells Macrophages Dendritic cells

Question 39

how does skin act as a physical barrier?

Answer 39

Physical barrier against external environment Cornified cell envelope and stratum corneum restrict water and protein loss from skin – NB high-output cardiac failure and renal failure in extensive skin disease Subcutaneous fat has important roles in cushioning trauma UV barrier Melanin in basal keratinocytes - protection against UV-induced DNA damage

Question 40

how does skin thermoregulate?

Answer 40

Vasodilatation or vasoconstriction in deep or superficial vascular plexuses → regulate heat loss. Eccrine sweat glands → cooling effect Role in fluid balance

Question 41

what are the skins metabolic functions?

Answer 41

Vitamin D synthesis Subcutaneous fat Calorie reserve 80% of total body fat (in non-obese individuals) Hormone (leptin) release - acts on hypothalamus → regulates hunger and energy metabolism