Appearance
14.1 — The Layers of Skin
Your skin covers about 1.8 square metres, weighs around 4 kilograms — making it the largest organ in the body by both measures — and is between 0.5 millimetres thick on your eyelids and about 4 millimetres on your heels.
You shed around 30,000 to 40,000 dead skin cells every minute, roughly a kilogram a year, and replace the entire outer layer about every four weeks.
It is a barrier, a thermostat, a sense organ, a vitamin D factory, an immune organ, and — uniquely among organs — the one whose appearance carries social meaning, which is why dermatological conditions cause psychological distress out of proportion to their physical effect.
The three layers
Epidermis — the outer layer. Stratified squamous epithelium (Chapter 4.2), and it contains no blood vessels at all. Everything diffuses up from below.
Dermis — the substantial layer, containing collagen, elastin, blood vessels, nerves, glands, hair follicles and immune cells. This is the layer that matters mechanically.
Hypodermis (subcutaneous fat) — insulation, energy store, cushioning, and the layer that anchors skin to what lies beneath.
The epidermis
Four or five sublayers, and the cells move upward through them over about four weeks, changing as they go.
Basal layer — a single row of dividing cells sitting on the basement membrane. This is the only layer that divides.
Spinous layer — cells connected by strong junctions that look like spines under a microscope. These junctions are what hold the epidermis together mechanically.
Granular layer — cells fill with keratin granules and begin releasing lipids into the spaces around them.
Clear layer — present only in thick skin, on palms and soles.
Cornified layer — 15 to 30 layers of flattened dead cells, filled with keratin and glued together by the lipids released below.
And the structure of that outer layer is described as "bricks and mortar", which is exactly right and explains almost every skin problem and every moisturiser.
The bricks are the dead keratin-filled cells. The mortar is the lipid — ceramides, cholesterol and fatty acids — filling the gaps.
Water is kept in and irritants are kept out by the mortar rather than by the bricks.
Which is why anything that strips the lipid damages the barrier: hot water, soap, detergents, alcohol gels, and repeated hand washing. And it is why the treatment for dry skin is to replace lipid rather than to add water.
The commonest genetic risk factor for eczema is a mutation in filaggrin, a protein required to make the outer layer properly. Around 10 percent of people of European descent carry one, and it substantially raises the risk of eczema, asthma and hay fever.
Which reversed the direction of thinking about eczema. It was long seen as an immune disease that damaged the barrier; the evidence now suggests a defective barrier lets allergens in, which drives the immune response. "Outside-in" rather than "inside-out", and it explains why emollients — pure barrier repair — are so effective.
Skin pH is 4.5 to 5.5 — the "acid mantle" — maintained by sweat, sebum and the metabolism of skin bacteria. It inhibits pathogens and is required for the enzymes that process the barrier lipids.
And most soaps are alkaline, at pH 9 to 10, which is why they disrupt the barrier and why pH-balanced cleansers are genuinely preferable rather than merely a marketing claim.
The other epidermal cells
Melanocytes — pigment cells, in the basal layer, about one for every ten basal cells.
And a fact that surprises everyone: all humans have essentially the same number of melanocytes. Skin colour differences come from how much melanin is made, what type, and how it is packaged and distributed — not from cell counts.
Each melanocyte transfers pigment to around 30 to 40 surrounding cells through long processes, and the melanin is positioned as a cap over the nucleus on the sun-facing side. It is literally a parasol over the DNA.
Two types. Eumelanin — brown-black, and strongly protective. Pheomelanin — red-yellow, poorly protective, and it produces damaging free radicals when exposed to ultraviolet light, which is why red hair and fair skin carry a disproportionately high melanoma risk.
Tanning is DNA damage. Ultraviolet light damages DNA, and the pigment response is a repair-and-protect reaction. A tan provides a sun protection factor of only about 2 to 4 — far less than people assume — and it is evidence that damage has already occurred.
Langerhans cells — dendritic cells within the epidermis, sampling and carrying antigen to lymph nodes (Chapter 13.1). The skin's immune sentinels, and the reason contact dermatitis happens.
Merkel cells — touch receptors (Chapter 11.13).
The dermis
Two layers, and the deeper one does the mechanical work.
Papillary dermis — thin, with finger-like projections into the epidermis that increase the contact area and anchor the two layers. Rich in capillaries and nerve endings.
Reticular dermis — thick, dense collagen and elastin.
And the collagen is not randomly arranged. It is oriented in consistent directions across the body — Langer's lines.
A cut along a Langer's line gapes less and heals with a finer scar than a cut across one, which is why surgeons plan incisions along them wherever possible, and why the same length of cut in two directions gives visibly different results.
Elastin allows recoil. Its loss with age is why pinched skin returns slowly — the test used to assess dehydration, which becomes unreliable in the elderly for exactly this reason (Chapter 10.3).
The dermis contains: blood vessels, in two networks; nerve endings; hair follicles; sebaceous and sweat glands; and immune cells.
Blood supply, and its second job
The skin receives about 5 percent of cardiac output at rest — far more than its metabolic needs require.
Because most of that flow is for temperature control rather than for nutrition (Chapter 14.2).
And it can vary enormously — from almost nothing in severe cold or shock to around 30 percent of cardiac output in extreme heat.
Which is why skin appearance is such a useful sign of circulatory state. Pale, cold, clammy skin means the circulation has been centralised — an early sign of shock, appearing before blood pressure falls. Flushed skin means heat loss. Mottled skin means very poor perfusion, and it is an ominous sign in a sick patient.
Capillary refill time — press for five seconds and release; colour should return within two — is a bedside test of peripheral perfusion that requires no equipment at all.
The glands
Eccrine sweat glands — 2 to 4 million, over essentially the whole body, densest on palms, soles and forehead.
They produce watery sweat for cooling (Chapter 14.2). Directly innervated by sympathetic nerves but using acetylcholine rather than noradrenaline — one of the two exceptions in Chapter 11.9, and why anticholinergic drugs cause dry skin and are used to treat excessive sweating.
Apocrine sweat glands — in the armpits, groin and around the nipples, becoming active at puberty.
They open into hair follicles and produce a thicker, protein-rich secretion.
And the secretion itself is odourless. Body odour is produced by skin bacteria metabolising it, which is why antibacterial deodorants work and why antiperspirants — which block the duct with aluminium salts — work differently.
Sebaceous glands — attached to hair follicles, producing sebum: an oily mixture of lipids.
Sebum lubricates the hair and skin, contributes to the acid mantle, and has some antimicrobial activity.
And they are controlled by androgens, which is why they enlarge at puberty in both sexes and why acne is a puberty disease (Chapter 14.5).
What skin does
Barrier. Against water loss, mechanical injury, chemicals, ultraviolet light and microorganisms (Chapter 13.1).
And the water-loss function is the one that kills when it fails. Extensive burns lose enormous volumes of fluid through the damaged surface, which is why fluid replacement is the first priority in major burns (Chapter 23.7) — before pain, before dressings.
Temperature regulation — Chapter 14.2.
Sensation — touch, pressure, vibration, temperature and pain (Chapter 11.13).
Vitamin D synthesis. Ultraviolet B converts a cholesterol derivative in the skin into vitamin D₃, which is then activated in the liver and kidney (Chapter 5.1).
The practical points are worth having. The amount of sun needed is modest — roughly 10 to 30 minutes of midday sun on the forearms and face, several times a week, for a light-skinned person in summer. Darker skin needs substantially longer, because melanin absorbs the UVB. Glass blocks UVB entirely, so sunlight through a window produces none. And essentially none is produced at high latitudes in winter, which is why deficiency is so common there.
Immune function — Langerhans cells, antimicrobial peptides, and the resident microbiome.
And the skin microbiome varies enormously by site: oily areas, moist areas and dry areas support quite different communities, and each helps exclude pathogens.
Absorption — limited but real, and it is what makes transdermal drug delivery possible. Nicotine patches, hormone patches, glyceryl trinitrate and fentanyl patches all cross the intact barrier, and the ones that work are small, fat-soluble molecules.
Which is also why some substances applied to skin are absorbed when they should not be — potent topical steroids over large areas, particularly in children, can cause systemic effects.
Skin colour
Determined by melanin amount and type, plus blood in the dermis, plus carotenoids from diet.
And the evolutionary story is a good demonstration of selection in both directions.
High UV near the equator selects for dark skin, which protects DNA from damage — and, importantly, protects folate, which is destroyed by UV and is essential in pregnancy (Chapter 4.4). Folate destruction may have been a stronger selective pressure than skin cancer, since skin cancer usually strikes after reproduction.
Low UV at high latitudes selects for light skin, because vitamin D synthesis becomes limiting.
Light skin evolved independently in Europeans and East Asians, through different genes (Chapter 3.5), which is why skin colour is such a poor guide to overall ancestry.
Vitiligo — patchy loss of melanocytes, autoimmune in origin. Affects around 1 percent of people. Physically harmless and psychologically significant, particularly where the contrast is greater, and treatments include topical immunosuppressants, phototherapy and newer targeted drugs.
Albinism — an inherited inability to produce melanin. It affects the eyes as well as the skin and hair, because melanin is needed for normal retinal development — so reduced visual acuity and nystagmus are part of the condition, not a separate problem.
And people with albinism face lethal discrimination in parts of the world, which is a fact that belongs in a medical account rather than being left out of it.
Ageing skin
Intrinsic ageing — genetically programmed. Thinning, reduced collagen, less elastin, drier, slower healing.
Extrinsic ageing — photoageing — from ultraviolet exposure, and it accounts for the large majority of visible skin ageing.
The clearest demonstration is comparing sun-exposed and sun-protected skin on the same person. The skin of the inner upper arm at 70 looks decades younger than the skin of the face, and the difference is entirely cumulative UV.
UVA penetrates deeper and drives most photoageing; UVB causes burning and most DNA damage. Both cause cancer.
And a striking published case: a lorry driver photographed after 28 years of driving showed dramatically more wrinkling, sagging and thickening on the left side of his face — the window side — than the right. One person, one exposure difference, one result.
Which makes the practical conclusion straightforward: sun protection is the most effective anti-ageing intervention available, and it is cheaper than everything marketed as one.
Menopause accelerates skin ageing, with around 30 percent of skin collagen lost in the first five years afterwards (Chapter 12.6).
Smoking accelerates it substantially, through reduced blood flow and increased collagen breakdown.
What actually works on skin
Worth stating plainly, because skincare is one of the most heavily marketed areas in health.
Strong evidence:
Sunscreen — prevents burning, photoageing and skin cancer. Broad spectrum, SPF 30 or above, applied generously and reapplied. Most people apply about a quarter of the amount used in testing, so a stated SPF 30 delivers far less in practice.
Retinoids — vitamin A derivatives. The best-evidenced topical anti-ageing agents, increasing collagen and improving fine wrinkles and pigmentation. Also first-line for acne. They cause irritation initially and are avoided in pregnancy.
Emollients — for dry skin and eczema. Replacing barrier lipids, and the most effective intervention in eczema by a wide margin.
Not smoking, and sun avoidance.
Moderate evidence: vitamin C serums, niacinamide, and alpha hydroxy acids.
Weak or absent evidence: collagen supplements — collagen taken by mouth is digested into amino acids like any other protein, and does not travel to the skin as collagen, though there is some limited trial evidence of modest effects, probably through other mechanisms. Most anti-ageing creams. Detox products.
And "chemical-free" is a marketing term with no meaning — everything, including water, is a chemical.
What the next page fixes
The skin's largest job by blood flow is not protection. Chapter 14.2 covers temperature regulation — how the body holds 37 °C from freezing to desert heat, and what happens at both extremes.