L01 MSK Histology General principles of skin

Overview

This lecture builds the skin from the outside in: what skin is and what it does, then its three tiers (epidermis, dermis, hypodermis), then the detail within each. Most of the time goes on the epidermis — a self-renewing stratified epithelium whose keratinocytes are born in the basal layer and progressively differentiate upward through the spinous, granular and cornified layers, a process (keratinization) that simultaneously builds the water barrier and the mechanical barrier. Alongside the keratinocytes sit three minority cell populations with distinct jobs (immune, pigment, sensory). The dermis provides the connective-tissue scaffold and is split into papillary and reticular layers; the hypodermis provides fat, vessels and mobility. The final third covers the epidermal derivatives (hair, sebaceous glands, sweat glands) and the sensory receptors that make skin a sensory organ, linking each corpuscle back to the dermal layer it lives in.

Course and lecture objectives

Where this sits in ELM 2 Histology: skin (1 lecture, 1 lab); musculoskeletal system (4 lectures, 3 labs); cardiovascular system (2 lectures, 4 labs); respiratory system (1 lecture, 1 lab); gastrointestinal system (3 lectures, 3 labs).

Objectives for this lecture:

1. Identify the layers of the skin and the basic tissue forming these layers.
2. Explain how these basic tissues have been modified to carry out specific functions.
3. Identify the stages of the process of keratinization and explain the cellular features of each stage.
4. Epidermal derivatives of the skin.

Skin as an organ: facts and functions

Key points:

• Largest organ of the human body.
• 15% of body weight.
• Thickness ranges from 1.5–5 mm.

Functions, as grouped in the lecture:

• Protective — barrier against microbial organisms; protection against mechanical, chemical, osmotic, thermal and UV radiation damage; immunological response.
• Biomechanical synthesis — vitamin D, under the influence of UVB.
• Homeostasis — control of body temperature; sweating via sweat glands.
• Major sensory organ — touch, temperature, pain etc.

Basic architecture: the three tiers

Order from superficial to deep:

1. Epidermis — stratified epithelium at the surface, with a wavy interface with the dermis.
2. Dermis — contains the dermal papillae, and houses arrector pili, sebaceous glands, merocrine (sweat) glands and hair follicles.
3. Hypodermis — adipose tissue, with vessels running through it.

The hair shaft runs obliquely through all three layers, from the hair bulb sitting deep (in the deep dermis/hypodermis) up to the surface. On section, the hair follicle appears with its associated sebaceous glands and arrector pili muscle; follicles may be cut in cross-section; pale adipose tissue marks the deepest layer.

Transcript flag (slide 5)

The micrograph extends past the bottom edge of the slide and several leader lines at the lower right and lower left point to structures whose label text is cut off; those labels are not readable.

Epidermis: what it is and who lives in it

Definition and key points:

• A self-renewing stratified epithelial tissue.
• Predominant cell: the keratinocyte.
• Other cell types: Langerhans cells (immune function); Merkel cells (sensory nerve ending); melanocytes (produce melanin pigment).

Where the minority cells sit: Langerhans cells lie in the upper/prickle-cell region; melanocytes and Merkel cells sit at the basal layer on the basal lamina, with a sensory nerve terminal contacting the Merkel cell.

Keratinocytes:

• Predominant cell type, making up the mass of the epidermis.
• Undergo continuous renewal throughout life.
• Turnover is mediated by stem cells in the basal layer.

Layers of the epidermis

From superficial to deep:

1. Cornified layer (stratum corneum) — pale, superficial.
2. Clear layer (stratum lucidum) — a thin, intensely eosinophilic band immediately beneath the cornified layer.
3. Granular layer (stratum granulosum) — just deep to the clear layer.
4. Spinous/prickle cell layer (stratum spinosum) — the thick middle zone.
5. Basal layer (stratum basale) — deepest, at the junction with the dermis.

In thick skin the epidermis sends deep, finger-like downgrowths (rete pegs/epidermal pegs) that alternate with the upward dermal papillae.

Basal layer and the dermo-epidermal junction

Key points:

• Contains the keratinocyte stem cells; it is the site of epidermal cellular proliferation.
• Basal keratinocytes are columnar in shape.
• Basal keratinocytes are in contact with the basal lamina (lamina lucida and lamina densa).
• Cytoplasm contains melanosomes and keratin filament bundles (keratin tonofilaments).
• Desmosomes connect the plasma membranes of basal keratinocytes to each other.
• Hemidesmosomes connect basal keratinocytes to the basal lamina.
• Other cells present at this level: melanocytes, Langerhans cells, Merkel cells.

Architecture at the junction, seen on EM (scale bar 200 nm), from the cell outward: basal cell cytoplasm containing keratin filaments → hemidesmosomes along the cell membrane → lamina lucida → lamina densa → lamina reticularis, with anchoring fibrils extending from the basal lamina into the underlying tissue. A desmosome appears as a dense plaque bridging the plasma membranes of two adjacent cells.

Labels used on the basal-epidermis EM: BC = basal keratinocyte; Me = melanocyte; BM = basement membrane; TF = tonofibrils.

Related landmarks on light microscopy: basal layer (deepest cell layer of the epidermis); rete pegs/epidermal pegs (downward epidermal projections); dermal papillae (upward dermal projections that interdigitate between the rete pegs).

Prickle/spiny cell layer

Key points:

• Closely packed keratinocytes.
• Connected to each other by desmosomes, which provide tensile strength.
• Cytoplasm contains melanosomes.
• Langerhans cells are also present.

On histology it is the broad zone lying beneath the narrow, deeply stained granular layer. On EM the keratinocyte shows a large nucleus with dense desmosomal plaques (D) around the cell periphery.

Granular layer and formation of the water barrier

Key points:

• 3–4 layers of flattened cells.
• Nuclei and organelles become disintegrated.
• Cytokeratin filament bundles become more compact.
• Densely stained keratocyte hyaline granules act as the water barrier.

The differentiation sequence conveyed by the schematic, deep to superficial: basal cell → spinous cell → granular cell → flattened cornified cell. Organelles/structures encountered along that sequence, deep to superficial: basal lamina, ribosomes, intermediate filaments, rER, lamellar bodies, mitochondria, Golgi apparatus, keratohyalin granules, water barrier. Desmosomal junctions are present between adjacent cells at every level.

Important

At the granular cell, the contents of the lamellar bodies are released; the released material forms the water barrier at the interface between the granular and cornified cells.

Cornified layer: the end of keratinization

Key points:

• Final stage of epidermal differentiation.
• Closely packed flattened cells, the corneocytes.
• Cells lack a nucleus and membranous organelles.
• Packed with keratin filaments.
• Superficially, squames detach from the cornified layer.

The non-keratinocyte cells compared

Melanocytes:

• Present on the basal lamina.
• Produce melanin pigment.
• Lack desmosome connections with keratinocytes.
• Have hemidesmosome connections with the basal lamina.
• On pigment/H&E micrographs they appear among the basal cells and contain brown pigment.

Langerhans cells:

• Immune function.
• Distributed in both the basal and spiny layers.

Merkel cells:

• Present on the basal lamina.
• Sensory nerve ending, for touch sensation.
• Have desmosome connections to keratinocytes.

Dermis

Composition:

• Irregular, moderately dense connective tissue.
• Meshwork of collagen (tensile strength) and elastin (stretch and recoil) fibres.
• Ground substance: glycosaminoglycans, glycoproteins and water.

Contents: fibroblasts, plasma cells, macrophages, blood vessels, nerves, lymphatics, and epidermal appendages (hair, sweat glands and sebaceous glands).

Two regions: the papillary layer (superficial, immediately beneath the epidermis, containing the dermal papillae) and the reticular layer (the deeper, coarser-fibred zone).

	Papillary layer	Reticular layer
Position	Immediately next to the epidermis	No proper boundary between papillary and reticular layer
Rete ridges	Present, interdigitating with rete pegs	Absent
Fibre type	Predominantly collagen type III with some elastic fibres	Collagen type II with some elastin fibres
Collagen arrangement	Fine and loosely packed	Thick, irregular bundles
Sensory receptors	Meissner’s corpuscles	Pacinian corpuscles (also present in hypodermis)

Note on the table: the slide gives the reticular fibre type as “Collagen type II”; this is transcribed as shown on the slide.

Hypodermis

Key points:

• Layer of connective tissue of variable thickness, deep to the dermis.
• Mainly consists of adipose tissue.
• Blood vessels, nerves and lymphatics travel through it.

Functions:

• Increases mobility of the skin.
• Adipose contribution: thermal insulation; shock absorption; storage of metabolic energy.

Accessory structures (epidermal derivatives)

• Hair — sensory and thermoregulation.
• Sebaceous glands — produce sebum; contribute to the epidermal barrier. Lobulated, pale and vacuolated on histology, sitting alongside the hair follicle.
• Sweat glands (apocrine and eccrine/regular) — thermoregulation.
• Arrector pili muscle — attached to the hair follicle, running obliquely from the follicle towards the epidermis.

Spatial relationships: the sebaceous gland and arrector pili are both associated with the hair follicle; eccrine sweat glands are coiled and lie in the dermis with a duct running to the surface; apocrine sweat glands are larger and lie deeper than the eccrine glands.

Eccrine sweat glands in detail:

• Secretions from the secretory cells are passed to the eccrine duct.
• The duct is deeply stained.
• Within one coiled gland, the duct profiles are smaller and deeply stained (dark purple), while the secretory component profiles are larger and paler with wider lumina.

Sensory receptors

The skin carries receptors for touch, pressure, temperature and pain.

Nerve-ending types shown, described by their component parts:

• a — free endings of afferent axon, ending between epidermal cells.
• b — Merkel’s cell with the terminal disk of an afferent axon, at the base of the epidermis.
• c — terminal of afferent axon within a multilayered capsule (concentric lamellae around a central axon), sited deep.
• d — terminal branches of afferent axon within a capsule (an encapsulated ending with branching terminals).
• e — within a dermal papilla: spiral terminals of afferent axon, tortuous Schwann cells, and a capsule (an elongated encapsulated ending).
• f — terminal branches of afferent axon within a capsule (an encapsulated ending, deeper).

Transcript flag (slide 22)

The six panels are labelled only by their component parts (a–f) and are not named as specific receptor types on the slide; the pairing of each panel to a named receptor is not stated.

Meissner’s corpuscles:

• Found at the dermal papillae.
• Rapidly adapting mechanoreceptor (slide reads “rapidly adoptive”).
• Sensitive to touch.
• On histology: ovoid, pale, layered structures within the dermal papillae immediately beneath the epidermis.

Pacinian corpuscles:

• Deep in the dermis and hypodermis.
• Rapidly adapting mechanoreceptors.
• Sensitive to pressure and vibration.
• Structure: a capsule, an intermediate zone and a central core.
• The central core contains an axon terminal.
• On histology: concentric onion-like lamellae around a central core, with a darkly stained linear axon terminal in the core.

Self-test

1. State the three quantitative facts the lecture gives about skin as an organ (size, weight, thickness).
2. List the four functional categories of skin given in the lecture, with one example of each.
3. Name the three tiers of skin from superficial to deep, and state the predominant tissue of the deepest one.
4. List the five layers of the epidermis from superficial to deep, giving both the descriptive and Latin names.
5. Name the four cell types of the epidermis and give the function of each.
6. Describe where each of the melanocyte, Langerhans cell and Merkel cell sits within the epidermis.
7. Distinguish the melanocyte from the Merkel cell by their junctional connections.
8. Explain why the basal layer is described as the site of epidermal renewal.
9. Describe, in order from inside the basal cell outward, the layers of the dermo-epidermal junction seen on electron microscopy.
10. Distinguish a desmosome from a hemidesmosome by what each connects.
11. Explain how desmosomes in the prickle cell layer contribute to the function of the epidermis.
12. Describe the four cellular changes that characterise the granular layer.
13. Describe the steps by which the water barrier is formed, naming the organelle and the site.
14. Describe the cellular features of the corneocyte, and explain why the cornified layer is called the final stage of epidermal differentiation.
15. Write out the keratinocyte differentiation sequence from deep to superficial in four named cell stages.
16. List the three components of the dermis and give the mechanical property contributed by collagen and by elastin.
17. List the cells and structures contained within the dermis.
18. Distinguish the papillary from the reticular dermis on five features.
19. Define rete pegs and dermal papillae, and explain how they relate to each other.
20. List the three functions attributed to the adipose tissue of the hypodermis, plus the one function of the hypodermis as a layer.
21. Name the three epidermal derivatives and give the function of each.
22. Explain how the eccrine duct can be distinguished from the secretory component within the same coiled gland on histology.
23. Distinguish apocrine from eccrine sweat glands on the two features the lecture gives.
24. Distinguish Meissner’s from Pacinian corpuscles on location, adequate stimulus and structure.
25. A histology section of thick skin shows a thin, intensely eosinophilic band lying immediately beneath the pale superficial layer. Name the band and state its position in the full sequence of epidermal layers.
26. On a skin section you see a coiled gland in the dermis, lobulated pale vacuolated cells alongside a hair follicle, and an oblique band of muscle running from the follicle toward the epidermis. Identify all three structures and state which two are associated with the follicle.
27. A section shows an ovoid, pale, layered structure sitting inside a dermal papilla. Identify it, and predict which sensory modality would be affected if these structures were lost.
28. A patient’s skin section is examined and the lamellar bodies of the granular cells fail to release their contents. Predict which barrier function is compromised and explain why.
29. Integrative: trace a single keratinocyte from its origin to its loss from the skin surface, naming the layer it occupies at each stage and the key structural change occurring in each.
30. Integrative: explain how the layered organisation of the skin supports its role as a sensory organ, using the location of Merkel cells, Meissner’s corpuscles and Pacinian corpuscles.
31. State what the abbreviations BC, Me, BM and TF denote on the electron micrograph of the basal epidermis.

Answers

Reveal answers

1. Largest organ of the human body; 15% of body weight; thickness 1.5–5 mm.
2. Protective (barrier against microbial organisms; protection against mechanical, chemical, osmotic, thermal and UV damage; immunological response); biomechanical synthesis (vitamin D under the influence of UVB); homeostasis (control of body temperature, sweating via sweat glands); major sensory organ (touch, temperature, pain etc.).
3. Epidermis → dermis → hypodermis; the hypodermis is mainly adipose tissue.
4. Cornified layer (stratum corneum); clear layer (stratum lucidum); granular layer (stratum granulosum); spinous/prickle cell layer (stratum spinosum); basal layer (stratum basale).
5. Keratinocyte — predominant cell, forms the bulk of the epidermis and undergoes continuous renewal; Langerhans cell — immune function; Merkel cell — sensory nerve ending (touch); melanocyte — produces melanin pigment.
6. Melanocyte on the basal lamina at the basal layer; Merkel cell also on the basal lamina at the basal layer, contacted by a sensory nerve terminal; Langerhans cells distributed in both the basal and spiny (prickle cell) layers, sitting in the upper/prickle cell region on the schematic.
7. The melanocyte lacks desmosome connections with keratinocytes but has hemidesmosome connections with the basal lamina; the Merkel cell has desmosome connections to keratinocytes.
8. It contains the keratinocyte stem cells and is the site of epidermal cellular proliferation; keratinocyte turnover throughout life is mediated by these basal stem cells.
9. Basal cell cytoplasm with keratin filaments → hemidesmosomes along the cell membrane → lamina lucida → lamina densa → lamina reticularis, with anchoring fibrils extending from the basal lamina into the underlying tissue.
10. Desmosomes connect the plasma membranes of adjacent keratinocytes to each other; hemidesmosomes connect basal keratinocytes to the basal lamina.
11. The prickle cells are closely packed and joined to each other by desmosomes, which provide tensile strength to the epidermis.
12. 3–4 layers of flattened cells; nuclei and organelles become disintegrated; cytokeratin filament bundles become more compact; densely stained keratocyte hyaline granules appear and act as the water barrier.
13. At the granular cell, the contents of the lamellar bodies are released; the released material forms the water barrier at the interface between the granular and cornified cells. The densely stained keratocyte hyaline granules of the granular layer are also described as the water barrier.
14. Corneocytes are closely packed flattened cells that lack a nucleus and membranous organelles and are packed with keratin filaments; it is the final stage of epidermal differentiation, after which squames detach from the surface.
15. Basal cell → spinous cell → granular cell → flattened cornified cell.
16. Irregular, moderately dense connective tissue; a meshwork of collagen and elastin fibres; ground substance of glycosaminoglycans, glycoproteins and water. Collagen provides tensile strength; elastin provides stretch and recoil.
17. Fibroblasts, plasma cells, macrophages, blood vessels, nerves, lymphatics, and epidermal appendages (hair, sweat glands, sebaceous glands).
18. Papillary: immediately next to the epidermis; has rete ridges interdigitating with rete pegs; predominantly collagen type III with some elastic fibres; fine and loosely packed collagen; contains Meissner’s corpuscles. Reticular: no proper boundary between it and the papillary layer; rete ridges absent; collagen type II with some elastin fibres (as printed on the slide); thick, irregular collagen bundles; contains Pacinian corpuscles, which are also present in the hypodermis.
19. Rete pegs (epidermal pegs) are the downward projections of the epidermis; dermal papillae are the upward projections of the dermis; they interdigitate with each other, with the dermal papillae sitting between the rete pegs.
20. Adipose: thermal insulation, shock absorption, storage of metabolic energy. The hypodermis as a layer increases the mobility of the skin.
21. Hair — sensory and thermoregulation; sebaceous glands — produce sebum and contribute to the epidermal barrier; sweat glands (apocrine and eccrine/regular) — thermoregulation.
22. The duct profiles are smaller and deeply stained (dark purple); the secretory component profiles are larger and paler with wider lumina.
23. The apocrine gland is larger than the eccrine gland and lies deeper; the eccrine gland is coiled in the dermis with a duct running to the surface. [Slide does not elaborate further on their secretions.]
24. Meissner’s: at the dermal papillae, rapidly adapting, sensitive to touch, appearing as ovoid pale layered structures beneath the epidermis. Pacinian: deep in the dermis and hypodermis, rapidly adapting, sensitive to pressure and vibration, with a capsule, intermediate zone and central core containing an axon terminal, seen as concentric onion-like lamellae.
25. The clear layer (stratum lucidum); it lies second from the surface, between the cornified layer above and the granular layer below.
26. The coiled gland is a sweat gland (eccrine glands are coiled and lie in the dermis with a duct to the surface); the lobulated pale vacuolated structure is a sebaceous gland; the oblique muscle band is the arrector pili. The sebaceous gland and the arrector pili are the two associated with the hair follicle.
27. A Meissner’s corpuscle; touch sensation would be affected, as it is a rapidly adapting mechanoreceptor sensitive to touch.
28. The water barrier would be compromised, because the water barrier is formed from the material released by the lamellar bodies at the granular cell, at the interface between the granular and cornified cells.
29. It arises from a stem cell in the basal layer (columnar, attached to the basal lamina by hemidesmosomes, cytoplasm containing melanosomes and keratin tonofilaments); it moves into the spinous/prickle cell layer (closely packed, joined by desmosomes for tensile strength, melanosomes in cytoplasm); then the granular layer (flattened, nuclei and organelles disintegrate, cytokeratin bundles compact, keratohyalin granules form and lamellar bodies release their contents to build the water barrier); then the cornified layer as a corneocyte (flattened, no nucleus or membranous organelles, packed with keratin filaments); finally it detaches from the surface as a squame.
30. Sensation is sampled at different depths: Merkel cells sit at the basal layer of the epidermis on the basal lamina, contacted by a sensory nerve terminal, for touch; Meissner’s corpuscles sit in the dermal papillae of the papillary dermis, rapidly adapting for touch; Pacinian corpuscles sit deep in the reticular dermis and hypodermis, rapidly adapting for pressure and vibration. Free afferent endings also run between the epidermal cells.
31. BC = basal keratinocyte; Me = melanocyte; BM = basement membrane; TF = tonofibrils.