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Core Concepts: an introduction.

The materials on this page provide an account of some of the key concepts we use in the clinic. The first few videos are meant to be accessible to year 1 students, but all of this material  is essential for our clinical students in (new) year 5. The approach is unashamedly clinical — using disease examples to illuminate basic skin science, and vice versa.

The précis is self explanatory. The notes are metaphorically like footnotes in an academic text, seeking to add caveats or riders to some of what I say. The copy of figures are exactly that, not clinical images. There are PDFs of questions and answers , together with a SoundCloud audio of me  speaking and talking around the questions and answers. The questions are meant to stimulate interest, test knowledge and allow more engagement: they are not in an MCQ format.

The videos are:

  1. Video 1. An introduction to skin biology.
  2. Video 2. Sunburn, DNA and skin cancer.
  3. Video 3. The biology of human pigmentation.
  4. Video 4. Urticaria, from nettle stings to autoimmunity.
  5. Video 5. Itch, and the utility of scratch.
  6. Video 6. The biology of the skin barrier: the eczema connection.
  7. Video 7. Physics matters! UVR and the skin.
  8. Video 8. Blisters, molecular glues and pemphigus.
  9. Video 9. Skin immunology: KISS (keep it simple, stupid).

Core Concepts, Video 1:

An introduction to skin biology (13 min)

Précis of the video

This is a whirlwind tour of the basics of skin biology. I describe the two main compartments of skin, the epidermis and the dermis. The main cells of the epidermis are the keratinocytes, melanocytes and langerhans cells. In the dermis we need to know about fibroblasts, the extracellular materials such as collagen and ground substance fibroblasts produce, and mast cells. I then describe the appendageal structures: the hair follicles, sebaceous glands and the eccrine sweat glands. Most of this material will be expanded upon in the subsequent videos

Video 1 supporting material:

  • Some notes on the video.
  • A copy of any figures
  • Questions on the video
  • Answers to the questions on the video are on the SoundCloud track below.

Core Concepts, Video 2:

Sunburn, DNA and skin cancer (9 min)

Précis of the video

In this video I link why some people develop erythema in the sun, with DNA damage and, in the long term, skin cancer. Erythema is a consequence of UVR (ultraviolet radiation) induced DNA damage. The erythema subsides because you repair (most) of the damage induced by UVR. We know this to be the case because (i) the action spectrum for erythema and DNA damage is very similar and (ii) because we see abnormal erythema and high cancer rates in the disorder xeroderma pigmentosum (XP). XP is an autosomal recessive disorder, in which subjects are unable to repair UVR induced DNA damage. The failure of repair leads to the accumulation of mutations, leading to the development of many different types of skin cancer.

Video 2 supporting material:

  • Some notes on the video.
  • A copy of any figures
  • Questions on the video
  • Answers to the questions on the video are on the SoundCloud track below.

Core Concepts, Video 3:

The biology of human pigmentation (15 min)

Précis of the video

DNA repair (see previous video) is not the only way humans protect against the harmful effects of UVR. In this video, I explain how melanin pigmentation protects against UVR. In particular I seek to answer a few related questions: how do we know melanin works; how does melanin work; how well does tanning work in comparison with baseline pigmentation (constitutive pigmentation); and how did evolution come up with this novel purpose for melanin? Along the way, we learn what pigmentary disorders like vitiligo and albinism can teach us, and how the various shades of humanity are generated.

Video 3 supporting material:

  • Some notes on the video.
  • A copy of any figures
  • Questions on the video
  • Answers  to the questions on the video are on the SoundCloud track below

Core Concepts, Video 4:

Urticaria, from nettle stings to autoimmunity (10 min).

Précis of the video

In this video I make an analogy between what happens to your skin when you roll around in the nettles, and the groups of conditions called urticaria. In the former, exogenous chemicals provoke the reaction; in the latter, it is a variety of stimuli that provokes the release of endogenous chemicals. Key to the pathogenesis of urticaria is the mast cell. We need to understand what mediators mast cells contain, what provokes mast cells to release these mediators, and how these mediators produce the rash — characterised by erythema and weals — we see with our eyes. I explain the triple response, and use as examples, dermographism (literally writing on the skin), and solar urticaria. This account suggest ways that urticaria might be treated, but also explains why our treatments are not wholly effective.

Video 4 supporting material:

  • Some notes on the video.
  • A copy of any figures
  • Questions on the video
  • Answers  to the questions on the video are on the SoundCloud track below

Core Concepts, Video 5:

Itch, and the utility of scratch (8 min).

Précis of the video

In this video I explain some of what we know about itch, and it’s reflex response, scratch. Itch is a cardinal feature of skin disease, and whereas once itch was viewed as being transmitted along ‘pain’ fibres, we now know different. The major clinical issues are that whilst we know histamine and histamine sensitive itch fibres play a role in some skin diseases, the majority of itch is not histamine mediated. I describe the peripheral mechanisms of itch, the processing at the level of the spinal cord, and the central control of itch. I use examples to show non-histamine mediated pathways.

Video 5 supporting material:

  • Some notes on the video.
  • A copy of any figures
  • Questions on the video
  • Answers  to the questions on the video are on the SoundCloud track below

Core Concepts, Video 6:

The biology of the skin barrier: the eczema connection (10 min).

Précis of the video

In this video I explore in greater depth the biology of the epidermis with a focus on barrier formation and the creation of of the stratum corneum. Skin is a stratified squamous epithelium, and keratinocyte stem cells reside in the basal layer. Differentiation leads to the production of a range of proteins, including keratins and filaggrin, and the production of lipid. A key enzyme is transglutaminase.
The bricks and mortar model reflects the formation of the heavily crosslinked cornified envelope, and surrounding lipid. Unfortunately, many agents we are exposed to can attack this hydrophobic lipid rich barrier. One result is irritant dermatitis, and one risk factor for irritant dermatitis, is the syndrome of atopic dermatitis. Mutations of filaggrin are common in many populations, and increase the risk of developing atopic dermatitis.

Video 6 supporting material:

  • Some notes on the video.
  • A copy of any figures
  • Questions on the video
  • Answers  to the questions on the video are on the SoundCloud track below

Core Concepts, Video 7:

Physics matters! UVR and the skin (20 min)

Précis of the video

Few people may go to medical school because of a love of physics, but physics and engineering underpin whole areas of modern medicine. In this video I focus on the area of physics of great interest to the dermatologist and student of skin disease, the physics of one part of the electromagnetic spectrum: ultraviolet radiation (UVR).
We run through  what an erythema action spectrum is, the distribution of UVR emitted from the sun (and received at ground level), and the crucial importance of understanding the relation between wavelength and biological activity. I end by highlighting the problems that have arisen from a failure to understand basic photobiology, and highlight some of the myths surrounding ultraviolet radiation.

Video 7 supporting material:

  • Some notes on the video.
  • A copy of any figures
  • Questions on the video
  • Answers  to the questions on the video are on the SoundCloud track below

Core Concepts, Video 8:

Blisters, molecular glues and pemphigus (4 min)

Précis of the video

Blisters are — to paraphrase Yeats — all about when the centre cannot hold. A simple design constraint on skin (in particular) is that it has to be physically resilient. How is this achieved? This brief video explores how keratinocytes are designed to resist stress and how a family of adhesion molecules (desmogleins) are targeted in the autoimmune disease pemphigus.

Video 8 supporting material:

  • Some notes taken from ed.derm.101 on pemphigus.
  • Some questions on the video (plus, to be fair, some stuff in ed.derm.101)
  • No figures for this presentation
  • SoundCloud answers below.

Core Concepts, Video 9:

Skin immunology (KISS!) (4 min)

Précis of the video

Clinical dermatology fall naturally into two halves: cancer and rashes. Some of the earlier core concept videos have covered the scientific underpinnings of skin cancer (and skincancer909 says more about them, too).

By contrast, the foundational science for most rashes is immunology. In this short video, I use the traditional classification of hypersensitivity reactions, to provide insights into some common inflammatory diseases of skin.

This  video uses examples from  core concept videos 4, 6 and8. I suggest you will get the most out of it if you have already  watched these other videos.

Video 9 supporting material:

None.

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