Intro to Derm Part 1

Question 1

describe the embryological formation of the skin

Answer 1

Skin arises by juxtaposition of two major embryological elements:

1. Epidermis - originates from ectoderm
2. Dermis - arises from mesoderm that comes into contact with inner surface of epidermis

mesoderm is essential for inducing differentiation of epidermal structures (e.g. hair follicle)

Question 2

describe the cellular changes that occur during the embryological development of skin

Answer 2

week 4 - Epidermis begins to form (from surface ectoderm) as single basal layer of cuboidal cells

week 5 - Secondary layer of squamous, non-keratinising cuboidal cells (periderm) develops on top of the basal layer

periderm generates vernix caseosa - white, waxy protective substance

week 11 - basal layer of cuboidal cells ( stratum germinativum) proliferates to form multilayered intermediate zone

weeks 9-13 - development of hair follicles in stratum germinativum and appearance of lanugo hair (Very fine hair)

weeks 10-17 - epidermal ridges protrude as troughs into developing dermis and neurovascular supply develops into dermal papillae

week 20 - 4 superifical strata have formed - spinosum, granulosum, lucidum, corneum

Question 3

what is the funciton of the vernix caseosa

where is it produced

Answer 3

during gestation - protects fetus from amniotic fluid during gestation

during birth - protects baby from bacterial and environmental damage

produced by the periderm

Question 4

label the layers in the development of skin

Answer 4

Question 5

where is the neruovascular supply in the skin

Answer 5

dermal papillae

(part of dermis and is beneath the epidermis)

Question 6

what cells give skin, hair, eyes colour

give their sequence of embryological development

Answer 6

melanocytes - contain pigment

precursors are melanoblasts which are derived from the neural crest in the embryo

week 6-8 - melanoblasts migrate dorsally to the developing epidermis, dermis and hair follicles

by week 12-13 - most melanoblasts have reached their destination and differentiate into melanocytes

a subset of melanoblasts form melnaocyte stem cells in hair follicle bulge which are a reserve to replenish differentiated melanocytes

Question 7

how are melanocytes regulated

with no exposure to external factors

Answer 7

Melanocortin 1 receptor (MC1R), a G protein-coupled receptor regulates quantity and quality of melanins produced:

MC1R is controlled by agonists α-melanocyte-stimulating hormone (αMSH) & adrenocorticotropic hormone (ACTH) and antagonist, Agouti signaling protein (ASP).

Activation of MC1R by agonist (αMSH or ACTH) → causes melanogenic cascade → synthesis of eumelanin (dark pigment)

ASP reverses those effects & elicits production of pheomelanin (pale pigment)

ACTH can also up-regulate expression of the MC1R gene

Question 8

what effect does ACTH have on pigment produced

how does it do this

Answer 8

increases pigment production

by acting as a MC1R agonist and upregulating gene expression of MC1R on melanocytes

Question 9

how are melanocytes regulated

using external factors

Answer 9

Exposure to UV

directly increases melanin:

results in Increased expression of MITF & downstream melanogenic proteins, including Pmel17, MART-1, TYR, TRP1, and DCT → increases melanin production

indirectly increases melanin:

also increases PAR2 in keratinocytes → increases uptake & distribution of melanosomes by keratinocytes

Question 10

how can melanocytes be regulated

Answer 10

either by agonists (ACTH alphaMSH) and antagonist (ASP) of the MC1R receptor

or by UV light exposure

Question 11

how is the structure of melanocytes related to their function

Answer 11

dendritic cells

processes allow to effectively distribute melanosomes to keratinocytes

Question 12

give an overview of the structure of the skin

Answer 12

superficial to deep:

epidermis - mostly made up of keratinocytes

basement membrane (dermal-epidermal junction)

dermis - mostly made up of connective tissue

subcutaneous fat

Question 13

label this diagram of the skin

Answer 13

Question 14

what is the extra layer of epidermis present in palms and soles of feet only

Answer 14

strutum lucidum

Question 15

how are keratinocytes able to undergo progressive differentiation

Answer 15

cytoskeleton of keratinocytes is made up of keratin intermediate filaments

filaggrin - protein which regulates progressive differentiation/flattening of keratinocytes from cuboidal to flat

Question 16

what is the structure of the epidermis

what process occurs in it and how does it happen

Answer 16

composed of keratinocytes

cells layers (superficial to deep):

stratum corneum
stratum lucidum (only present in palms and soles)
stratum granulosum
stratum spinosum
basal layer

progressive differentiation/flattening of keratinocytes occurs - cells progress from the basal layer to surface layer/stratum corneum in 30 days

Question 17

what are the characteristics of cells in the different epidermal cell layers

Answer 17

basal layer - keratinocytes originate here and are simple cuboidal shaped

stratum spinosum

stratum lucidum - found only in palms and soles

stratum granulosum - cells contain granules of keratohyalin

stratum corneum - keratinocytes are flattened and have no nuclei or organelles, but have specific functions

Question 18

what is the function of the keratinocytes in the stratum corneum

Answer 18

outer layer - absorb solutes

middle layer - absorbs water

lower/inner layer - mechanical defence barrier, contains lipids e.g. FFA, sterols to carry out its function

Question 19

how does cellular progression of keratinocytes in erpidermis change in skin disease

Answer 19

it is accelerated

e.g. psoriasis

Question 20

label this diagram of the epidermis

Answer 20

Question 21

describe the intracellular structure of keratinocytes:

Answer 21

filamentous cytoskeleton: (from thickest to thinnest)

Tubulin‐containing microtubules (20-25nm)

Intermediate filaments (keratins) (7-10nm)

Actin‐containing microfilaments (7nm)

Question 22

what is the function of keratins

Answer 22

Structural properties - part of cytoskeleton

Cell signalling

Stress response

Apoptosis

Wound healing

Question 23

what are desmosomes

where are they found

what is their function

what is their structure

Answer 23

major adhesion complex

found in epidermis

anchors keratin intermediate filaments to cell membrane and bridges adjacent keratinocytes

allows cells to withstand trauma

composed of several smaller proteins - desmoglein, desmocollin, plakoglobin, plakophilin, desmoplakin, keratin

Question 24

what are the cell to cell connections in the epidermis

Answer 24

desmosomes

gap junctions

tight junctions

adherens junction

Question 25

what are gap junctions what is their function

Answer 25

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 26

what are adherens junctions how do they work

Answer 26

Transmembrane structures Engage with the actin cytoskeleton of adjacent keratinocytes

Question 27

what is the function of tight junctions

Answer 27

involved in barrier integrity and cell polarity, which is important in wound healing

Question 28

label these cell to cell connections

Answer 28

Question 29

what are the cells in the epidermis

Answer 29

keratinocyte - majority melanocyte langerhans cells merkel cells mast cells

Question 30

what is the strucutre of melanocytes what is their function

Answer 30

dendritic cells distribute melanin pigment in melanosomes to keratinocytes using processes number of melanocytes is the same amongst all skin types only the amount of eumelanin (dark pigment) produced varies

Question 31

what is the structure of langerhans cells what is their function where are they

Answer 31

immune cells - dendritic part of the innate immune system - antigen presenting cell epidermis

Question 32

what are merkel cells where are they

Answer 32

mechanosensory receptors epidermis

Question 33

what are the immune cells present in the epidermis

Answer 33

langerhan cells mast cells

Question 34

what is another name for the dermal-epidermal junction of the skin what is it made up of what is its function

Answer 34

basement membrane proteins and glycoproteins - especially collagens IV and VII, laminins, integrins invovled in cell adhesion facilitates cell migration - e.g. in wound healing or immune rsponse

Question 35

what is the dermis composed of where is it what is its function

Answer 35

mainly made up of connective tissue and ECM epidermis ⇒ basement membrane ⇒ dermis provides resilience to skin

Question 36

what is the structure of the dermis

Answer 36

2 main layers papillary dermis: superificial connective tissue is loose vascular reticular dermis: deep dense connective tissue (thicker than papillary dermis) forms the bulk of the dermis

Question 37

label the skin below the stratum corneum

Answer 37

Question 38

give the composition of the dermis what are the functions of the components

Answer 38

**1.Proteins** a)Collagen (80-85% of dermis) – mainly types I and III very resistant b)Elastic fibres (2-4%) – fibrillin, elastin provides elasticity **2.Glycoproteins** fibronectin, fibulin, intregrins facilitates cell adhesion and cell motility **3.Ground substance** glycosaminoglycan / proteoglycan found between dermal collagen and elastic tissue maintains hydration, as contains hyaluronic acid which has high water binding capacity 60% of dermis weight is water

Question 39

what is the structure of collagen found in the dermis

Answer 39

mainly types I and III collagen is arranged in triple helix ⇒ polymerised into fibres and then fibrils stabilised by intra and intermolecular cross links ⇒ therefore collagen fibres are very resistant

Question 40

what are the cells in the dermis

Answer 40

fibroblasts (main cells) - produce connective tissue Histiocytes Mast cells Neutrophils Lymphocytes Dermal dendritic cells (immune cells)

Question 41

embryologically where are the dermis and epidermis derived from

Answer 41

epidermis - ectoderm dermis - mesoderm

Question 42

what provides the blood supply to the skin where is it

Answer 42

deep and superficial vascular plexus in the dermis (does not cross into epidermis)

Question 43

describe the innervation of the skin

Answer 43

sensory innervation: provided by free nerve endings, hair follicles, expanded tips autonomic innervation: cholinergic - supplies eccrine sweat glands adrenergic - supplies eccrine and apocrine sweat glands eccrine - no odour, all over body apocrine - odour, from armpit and genitals

Question 44

what is the pilosebaceous unit

Answer 44

pilosebaceous unit - hair follicle, arrector pili muscle, and sebaceous gland

Question 45

what is the smooth muscle in the skin

Answer 45

Arrector pili muscle - raises hairs arterioles shunts

Question 46

describe the afferent nerve innervation of the skin

Answer 46

One million afferent nerve fibers supplying skin Form branching network, often accompanying blood vessels, to form a mesh of interlacing nerves in superficial dermis distribution of afferent fibres in skin varies greatly according to body site face, extremities and genitalia have much more sensory nerve innervation than rest of skin

Question 47

what are the different nerve endings in the skin give examples

Answer 47

Question 48

what are Meissner's corpuscles what is its structure where are they what is their function

Answer 48

(sensory receptor)

Question 49

what is the ruffini corpuscle what is its structure where is it located what is its function

Answer 49

Question 50

what is the pacinian corpuscle what is its structure what is its function where is it found

Answer 50

Question 51

what are merkel cells what is their structure what is their function where are they found

Answer 51

Question 52

fill in this table on nerve endings and nerve fibres in skin

Answer 52

Question 53

what is the microbiota of the skin how is it related to the microbiome

Answer 53

bacteria, fungi and viruses that live on the skin genome of the microbiota = microbiome microbiome encodes 150millionx more genes than human genome very important in host defence, immune regulation, metabolism

Question 54

how does microbiota of skin relate to chronic skin diseases

Answer 54

chronic skin diseases are due to disorders of the microbiota as the microbiota is very important in immune-modulation and epithelial health

Question 55

what makes up the microbiota of skin

Answer 55

Predominantly composed of: Actinobacteria (including Propionibacteria and Corynebacteria) Firmicutes (Clostridia and Bacilli [Staphylococcus] Bacteroidetes Proteobacteria but the exact composition of the microbita varies between different parts of the body varies due to the different environment/niche

Question 56

what are the functions of skin

Answer 56

Immunological barrier Physical barrier Thermoregulation Sensation Metabolism Aesthetic appearance

Question 57

what does this man have how will this affect him

Answer 57

erythroderma - over 90% of his body has a rash skin failure - compromise skin functions: susceptible to infection impaired thermoregulation ⇒ heart failure water loss transepidermally ⇒ kidney failure and high output cardiac failure

Question 58

what cells in the skin allow it to act as an immunological barrier

Answer 58

epidermis - langerhans cells and keratinocytes dermis - Tissue‐resident T-cells, Macrophages, Dendritic cells

Question 59

how does the epidermis contribute to the skin's role as an immunological barrier

Answer 59

**langerhans cells** - involved in adaptive and innate immunity sentinel cells in epidermis dendritic processes form dense network in epidermis which invading agents then have to interact with Extend dendritic processes through intercellular tight junctions to sample outermost layers of skin (stratum corneum) when they detect PAMPs (released by microbes) ⇒ they rapidly initiate innate immune response presents antigens to specific CD4 and CD8 t cells (adaptive immune response) In absence of danger, promote expansion and activation of skin-resident regulatory cells (Tregs)cells determine the appropriate adaptive immune response (inflammation or immune tolerance) by interpreting the microenvironmental context in which they encounter foreign substances **keratinocytes** - innate immunity produce endogenous antibiotics - defensins and cathelicidins which provide innate defnece against bacteria, viruses and funghi

Question 60

how does the dermis contribute to the skin's role as an immunological barrier

Answer 60

Immune surveillance is also carried out in dermis by: ➢Tissue‐resident T-cells ➢Macrophages ➢Dendritic cells Rapid, effective immunological backup if epidermis breached

Question 61

how does the skin acts as a physical barrier, against what?

Answer 61

Physical barrier against external environment Cornified cell envelope and stratum corneum restrict waterand 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 provides protection against UV-induced DNA damage

Question 62

what is the role of skin in thermoregulation

Answer 62

central thermoreceptors in hypothalamus and peripheral thermoreceptors - sense temperature of blood hypothalamus initiates either vasodilatation or vasoconstriction in deep or superficial vascular plexuses → regulate heat loss via skin also activates eccrine glands to secrete sweat ⇒ causes heat loss due to evaporative cooling effect

Question 63

why does disruuption to skin affect fluid balance

Answer 63

disrupts functioning of eccrine sweat glands there are many eccrine sweat glands so it has a large role in fluid balance due to cumulative amount of liquid it can secrete

Question 64

what are the metabolic functions of the skin

Answer 64

Vitamin D synthesis – 7-dehydrocholesterol is converted to cholecalciferol in skin Subcutaneous fat: ➢Calorie reserve ➢80% of total body fat is sub-cutenous (in non-obese individuals) Leptin is released from sub-cutaneous fat - acts on hypothalamus → regulates hunger and energy metabolism (without leptin body would keep wanting food)

Question 65

what is the aesthetic appearance function of the skin

Answer 65

aesthetic appearance of skin can affect psychosexual function and cause increased suicide risk