5. The Integumentary System

Skin, Hair, Nails, and the Body's First Line of Defense

Learning Objectives

5.1 The Skin as an Organ

Chapter 1 defined an organ as a discrete structure built from two or more tissue types performing a specific function. Chapter 4 showed you the four tissue types. The skin — the integument, from Latin integere, to cover — contains all four, in a fixed and predictable arrangement:

• Epithelial tissue — keratinized stratified squamous epithelium forming the epidermis, plus the epithelium of every gland and hair follicle.
• Connective tissue — the dense irregular collagen of the dermis, the areolar tissue of the papillary layer, and the adipose of the hypodermis beneath.
• Muscle tissue — smooth muscle in the arrector pili of every follicle, and in the walls of every dermal arteriole.
• Nervous tissue — an extraordinary density of sensory endings, plus the sympathetic fibers that control the vessels and glands.

It is, by most measures, the largest organ in the body. Not the largest by any single measure — that depends on which measure — but on the two that matter most:

Look hard at rows six and seven. The skin's blood flow can increase roughly thirty-fold, and at maximum it can claim more than half of everything the heart pumps. No other organ in the body has a comparable dynamic range, and virtually none of that flow exists to feed the skin — the skin's own metabolic requirement is modest and constant. That enormous, adjustable circulation exists almost entirely to move heat, and secondarily to be sacrificed when blood is needed elsewhere.

That single structural fact is the answer to Amara's first question, and we will spend §5.5 and §5.7 unpacking it.

The seven functions

Two of these are worth flagging now because they are consistently underrated.

The skin is a blood reservoir. The dermal vascular plexus normally holds a few hundred millilitres of blood at any moment. Under sympathetic drive that volume can be squeezed back into the central circulation, which is a fast, free autotransfusion. When Amara's blood pressure was threatened, this is one of the things her body did about it.

The skin is an endocrine and immune organ. Vitamin D synthesis begins here and nowhere else. And the epidermis contains a permanent resident population of antigen-presenting dendritic cells, so the skin is not merely a wall but a garrisoned frontier — exactly the arrangement Chapter 4 described for every epithelium and its underlying connective tissue.

5.2 The Epidermis: Five Strata and One Journey

The epidermis is keratinized stratified squamous epithelium. Like every epithelium (§4.2) it is avascular — not one blood vessel penetrates it — so every cell is fed by diffusion from the dermal capillaries beneath, and this single constraint explains the entire architecture. Cells at the bottom are close to the food supply and divide. Cells pushed upward get progressively farther from it and, at a certain distance, die. The epidermis is literally a gradient of starvation, and the body has made that gradient useful.

Four cell types live in it.

Keratinocytes — about 90% of epidermal cells. They produce keratin, a tough fibrous intermediate-filament protein, and they are the cells whose life cycle the five strata describe. They are also immunologically active, secreting cytokines when damaged.

Melanocytes — about 8%, confined to the deepest layer. Spider-shaped cells with long processes reaching between keratinocytes, they synthesize the pigment melanin in organelles called melanosomes and transfer those melanosomes to keratinocytes. There are roughly 1,000–2,000 melanocytes per mm² of skin, and one melanocyte serves about 30–40 keratinocytes as an epidermal-melanin unit. Crucially, all human beings have approximately the same number of melanocytes. Skin color differences arise from what those cells produce and how it is packaged, not from how many there are (§5.5).

Dendritic (Langerhans) cells — 2–8% of epidermal cells, derived from bone marrow, scattered mainly in the stratum spinosum. They are antigen-presenting cells: their long processes form a net through the epidermis, they capture antigens that penetrate the surface, and they migrate to regional lymph nodes to present them to T cells. They are the reason a substance touched on the skin can produce an immune reaction — contact dermatitis to nickel or poison ivy is a Langerhans-cell-initiated response. Their numbers fall substantially with age and with UV exposure, which matters in §5.9.

Tactile (Merkel) cells — sparse, in the deepest layer, each associated with a disc-like sensory nerve ending. They are slowly-adapting mechanoreceptors specialized for sustained light touch and fine spatial detail — texture, edges, and shape. They are densest in the fingertips and lips.

The five strata

 ═══ THE EPIDERMIS: FIVE STRATA AND THE KERATINOCYTE'S JOURNEY ════════════════
    (thick skin shown; thin skin lacks a distinct stratum lucidum)

  SURFACE ▲                                                    CELL STATUS
  ────────┼──────────────────────────────────────────────────────────────────
   ▒▒▒▒▒▒ │ 5 STRATUM CORNEUM  "horny layer"  20-30 layers        DEAD
   ▒▒▒▒▒▒ │   flat anucleate CORNEOCYTES: bags of keratin cross-  ├ days 15-45
   ▒▒▒▒▒▒ │   linked by involucrin/loricrin, mortared by LIPID    │
   ▒▒▒▒▒▒ │   LAMELLAE (ceramides, cholesterol, free fatty acids) │
   ▒▒▒▒▒▒ │   ──► "BRICKS AND MORTAR": THE water barrier.         │
   ▒▒▒▒▒▒ │   3/4 of the epidermis. Desquamates ~500 million/day. │
  ────────┼──────────────────────────────────────────────────────┼───────────
   ░░░░░░ │ 4 STRATUM LUCIDUM  "clear layer"  2-3 layers          DEAD
          │   THICK SKIN ONLY (palms, soles). Packed eleidin.     │
  ────────┼──────────────────────────────────────────────────────┼───────────
   ▓▓▓▓▓▓ │ 3 STRATUM GRANULOSUM  "granular layer"  3-5 layers    DYING
   ▓▓▓▓▓▓ │   • KERATOHYALIN granules → aggregate keratin into    │ ← THE
   ▓▓▓▓▓▓ │     tight bundles                                     │  DEATH
   ▓▓▓▓▓▓ │   • LAMELLAR granules → EXOCYTOSE lipid into the      │  LINE
   ▓▓▓▓▓▓ │     intercellular space = the waterproofing mortar    │
   ▓▓▓▓▓▓ │   • organelles and nucleus DEGRADE here               │
   ▓▓▓▓▓▓ │   ──► cells above this line are too far from the      │
          │       dermal capillaries to survive. Death is the     │
          │       PRODUCT, not the failure.                       │
  ────────┼──────────────────────────────────────────────────────┼───────────
   ▪▪▪▪▪▪ │ 2 STRATUM SPINOSUM  "prickly layer"  8-10 layers     ALIVE
   ▪▪▪▪▪▪ │   Cells appear spiny because processing SHRINKS them  │ ← daughter
   ▪▪▪▪▪▪ │   between DESMOSOMES that do not let go.              │   cells
   ▪▪▪▪▪▪ │   Thickest layer of living cells. Keratin bundles     │   pushed
   ▪▪▪▪▪▪ │   ("tonofilaments") accumulate. DENDRITIC CELLS here. │   upward
  ────────┼──────────────────────────────────────────────────────┼───────────
   ●○●○●○ │ 1 STRATUM BASALE  "basal / germinativum"  1 layer     DIVIDING
   ══════ │   • Cuboidal-columnar KERATINOCYTE STEM CELLS: 10-25% │ ← day 0
          │     in mitosis at any time                            │
          │   • MELANOCYTES (●) — 1 per 30-40 keratinocytes       │
          │   • TACTILE (MERKEL) CELLS with nerve discs           │
          │   • HEMIDESMOSOMES anchor it to the BASEMENT MEMBRANE │
  ────────┴──────────────────────────────────────────────────────┴───────────
   ≈≈≈≈≈≈  DERMAL PAPILLA — capillary loops. NEAREST BLOOD SUPPLY.
           Everything above this line eats by DIFFUSION only.

   ═══ THE JOURNEY ══════════════════════════════════════════════════════════
   mitosis at the base → pushed up → fill with keratin → make lipid →
   destroy own nucleus → become a cross-linked waterproof brick →
   ride up through the corneum → desquamate.   TOTAL: 25-45 DAYS
   (psoriasis: 3-5 days — too fast to mature, so scale accumulates)

The two ideas that matter most

First: the barrier is dead, and that is the design. Students often read "the outer layer of your skin is dead cells" as a slightly grim curiosity. It is the central engineering fact of the organ. A living cell must be permeable — it needs to take in oxygen and nutrients and release waste, which means a membrane through which water can pass. A structure built of living cells therefore cannot be waterproof. The stratum corneum solves this by using cells that have finished being alive: their contents cross-linked into an insoluble keratin matrix by the proteins involucrin and loricrin, their outer membranes replaced by a rigid cornified envelope, and the gaps between them filled with a lamellar stack of ceramides, cholesterol, and free fatty acids exocytosed from the granular layer.

The standard analogy is bricks and mortar, and it is precise: the corneocytes are the bricks and the intercellular lipid is the mortar, and — importantly — the mortar is the barrier. Water crossing the stratum corneum must take a tortuous path through the lipid lamellae. This is why detergents, solvents, and repeated hot water, all of which strip lipid, cause dry cracked skin, and why the treatment is to replace the lipid rather than to add water.

The performance figure: an intact stratum corneum limits water loss to roughly 300–400 mL/day across the whole body surface — the transepidermal water loss, part of what clinicians call insensible loss. Remove it, as a full-thickness burn does, and the same area can lose water more than ten times faster. Hold that number; it returns in §5.9.

Second: the epidermis is a conveyor belt with a fixed transit time. A keratinocyte born in the stratum basale takes about 25–45 days to reach the surface and shed. That transit is regulated, and diseases of regulation announce themselves as diseases of transit.

• In psoriasis, an immune-driven disorder, keratinocyte proliferation accelerates so that transit takes only 3–5 days. There is no time for the cells to complete maturation, so they arrive at the surface still nucleated (parakeratosis) and poorly cohesive, piling up as the characteristic thick silvery scale. The plaques are red because the underlying papillary dermis is packed with dilated capillaries — which is why scraping the scale causes pinpoint bleeding, the Auspitz sign.
• In calluses and corns, chronic friction increases basal mitosis locally, producing a thickened stratum corneum exactly where the pressure is. This is an adaptive, protective hypertrophy — the same reaction as a guitarist's fingertips.

5.3 The Dermis: The Structural Layer

The dermis is the skin's mechanical substance. It is connective tissue (§4.5), it is vascular, it is innervated, and it contains all of the appendages — every hair follicle, sweat gland, and sebaceous gland sits in the dermis and merely opens onto the epidermis above. It is also the layer that is tanned into leather, which is a useful thing to remember: leather is dermal collagen, and the properties of leather are the properties of your dermis.

It has two layers, and they differ in tissue type.

The papillary layer — the superficial 10–20%. Areolar connective tissue: loose, thin collagen, fine elastic fibers, and abundant ground substance, richly supplied with capillaries, lymphatics, and nerve endings. Its defining feature is the dermal papillae, peg-like projections that push up into the epidermis above. They serve three purposes: they multiply the surface area of the dermal–epidermal junction so that shear force is distributed; they bring capillary loops close to the avascular epidermis; and they carry the sensory receptors that need to be near the surface. Because it is loose areolar tissue, the papillary layer is also where inflammatory cells accumulate and where edema and blister fluid collect.

The reticular layer — the deep 80–90%. Dense irregular connective tissue: thick bundles of type I collagen interwoven in every direction, with a network of elastic fibers running through them. This is the layer that gives skin its strength and its elasticity, and its architecture is exactly what Chapter 4 predicted for a tissue loaded from unpredictable directions. Collagen supplies tensile strength and resists tearing; elastin returns the skin to shape after stretch. Between the bundles run the deep vascular plexus, the larger nerves, hair follicles, and glands.

Friction ridges: where the dermis shapes the surface

On the palms, soles, fingers, and toes, the dermal papillae are arranged in curving parallel rows — dermal ridges — and because the epidermis conforms to the surface beneath it, the skin surface is thrown into matching friction ridges. These are fingerprints.

Their function is mechanical and sensory. Ridged skin increases friction against smooth surfaces and, more subtly, channels sweat and improves grip in the way tire tread channels water. They also amplify vibration as a finger moves across a texture, which improves the performance of the Pacinian corpuscles beneath. The pattern is determined by the arrangement of dermal papillae, laid down between weeks 10 and 17 of fetal development, and it is genetically influenced but not genetically determined — identical twins have different fingerprints, because the exact folding of the developing dermis depends on local mechanical conditions in the womb. The pattern is permanent because it is a dermal feature: superficial burns and abrasions destroy only epidermis and the print returns, while injuries deep enough to destroy the papillary dermis erase it permanently.

Cleavage lines, and why surgeons care

The collagen bundles of the reticular dermis are woven in all directions, but not with equal probability. In any given body region they have a predominant orientation, which follows the direction in which the skin is habitually stretched — generally circumferentially around the limbs and neck, and horizontally across the trunk. The lines describing that predominant orientation are cleavage lines (Langer's lines, or in modern surgical use, relaxed skin tension lines).

The consequence is direct and practical. Skin under tension pulls apart across these lines and not along them.

• An incision made parallel to a cleavage line separates collagen bundles rather than cutting across them. The wound edges are pulled together by the surrounding tension, it heals faster, and it leaves a fine scar.
• An incision made perpendicular to the lines cuts the bundles transversely. The surrounding tension pulls the edges apart, the wound gapes, tension persists during healing, and — because §4.9 told you that sustained tension drives fibroblast collagen synthesis — the result is a wide, raised, sometimes hypertrophic scar.

This is why surgical incisions follow skin creases wherever a choice exists, and why the same laceration can heal invisibly on one part of the body and badly on another. It is also why an elliptical excision of a skin lesion is always oriented with its long axis along the tension lines.

Flexure lines are a related but distinct phenomenon: deep creases at joints — the palms, fingers, wrists, elbows, knees — where the dermis is tightly anchored to underlying fascia and the skin cannot slide. They exist so the skin folds in a predictable place rather than bunching, and they are the reason your palm has a fixed pattern of lines that does not change.

Sensory receptors of the dermis

Chapter 15 covers these fully, but the skin is where most of them live, and their depth follows their job.

Note the design logic. Receptors for fine spatial detail must sit close to the surface and in high density — Merkel discs and Meissner corpuscles crowd the dermal papillae of the fingertips, where two-point discrimination is 2–4 mm. Receptors for deep, diffuse mechanical events sit deep and are sparse — a single Pacinian corpuscle, an onion-like stack of concentric lamellae up to 4 mm long, has a huge receptive field and reports only that something vibrated. On the back, where only the deep receptors are dense, two-point discrimination is 40–50 mm, which you can verify on yourself in the Lab section.

5.4 The Hypodermis and Body Fat

Beneath the dermis lies the hypodermis, also called the subcutaneous layer or superficial fascia. Strictly it is not part of the skin — the integument proper is epidermis plus dermis — but it is functionally inseparable from it, and injections given "subcutaneously" go here.

It is areolar and adipose connective tissue, and its four jobs follow from that composition:

1. Anchoring with mobility. It attaches skin to underlying muscle and bone loosely enough that skin can slide. Where it is thin or absent — over the shin, the sternum, the skull — skin is nearly immobile, which is why those sites bruise, split, and heal differently.
2. Insulation. Fat has roughly one-third the thermal conductivity of muscle, so subcutaneous fat is the body's principal barrier to conductive heat loss (§5.7).
3. Shock absorption. A padded layer that spreads and dissipates mechanical load — which is why the sites where it is thinnest are the sites where pressure injuries occur (§5.9).
4. Energy storage and endocrine signaling. As §4.5 established, adipose is a genuine endocrine organ secreting leptin, adiponectin, and — when hypertrophied — inflammatory cytokines.

Distribution matters more than amount

Subcutaneous fat is not deposited uniformly, and the pattern is hormonally determined and clinically consequential.

• Gynoid ("pear") distribution — hips, thighs, buttocks; estrogen-associated; predominantly subcutaneous fat.
• Android ("apple") distribution — abdomen; androgen- and cortisol-associated; predominantly visceral fat around the abdominal organs.

Visceral adipose is metabolically different from subcutaneous adipose. It is more lipolytically active, drains directly into the hepatic portal vein (so its free fatty acids and cytokines reach the liver first and at high concentration), and it secretes proportionally more IL-6 and TNF-α. This is why waist circumference predicts cardiovascular and metabolic risk better than BMI does, and it is central to Amara's story: her BMI of 29.3 is only moderately elevated, but her waist circumference of 96 cm exceeds the threshold used in most definitions of metabolic syndrome, and it is the visceral component that is driving her insulin resistance and her hs-CRP. Chapter 24 assembles the whole picture.

Two other distribution facts. Fat is essentially absent from the eyelids and the penis and scrotum, which is why those sites swell so dramatically in generalized edema — the loose areolar tissue there has nothing to restrain it. And fat is deliberately structured in the heel and the palm into fibrous-walled compartments that behave as a hydraulic cushion rather than as a store; that is why the heel pad does not thin during weight loss, and why its degeneration with age causes heel pain.

 ═══ FULL-THICKNESS SKIN — ALL LAYERS AND APPENDAGES ═════════════════════════

   hair shaft         sweat pore        friction ridges (thick skin)
        │                 │             ╱╲╱╲╱╲╱╲╱╲╱╲
   ═════╪═════════════════╪════════════╱══════════════════════════════════
   ▒▒▒▒▒│▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒│▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒  STRATUM CORNEUM  ┐
   ▓▓▓▓▓│▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓│▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓  granulosum       │
   ▪▪▪▪▪│▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪│▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪  spinosum         │ EPIDERMIS
   ●○●○●│○●○●○●○●○●○●○●○●○│●○●○●○●○●○●○●○●○●○●●  basale           │ 0.05-1.5mm
   ╲╱╲╱╲│╱╲╱╲╱╲╱╲╱╲╱╲╱╲╱╲╱│╲╱╲╱╲╱╲╱╲╱ ← DERMAL PAPILLAE + rete    ┘
        │                 │             ridges interdigitating
   ─────┼─────────────────┼──────────────────────────────────────────────
    ╭───┴───╮         ╭───┴───╮   ≈≈≈ SUBPAPILLARY PLEXUS ≈≈≈    ┐
    │SEBAC- │         │ ECCRINE│   ⊙ Meissner corpuscle           │
    │EOUS   │         │ SWEAT  │   ⊙ free nerve endings           │ PAPILLARY
    │GLAND  │         │ DUCT   │   loose AREOLAR CT               │ DERMIS
    │holo-  │         │(spiral)│   fine collagen, capillary loops │
    │crine  │         │        │                                  ┘
    │→ hair │         │        │  ───────────────────────────────────────
    ╰───┬───╯         │        │   ▨▨ DENSE IRREGULAR COLLAGEN ▨▨  ┐
        │  ╭────────╮ │        │   thick type I bundles woven in   │
      ╭─┴──┤ARRECTOR│ │        │   ALL directions + elastic fibers │
      │HAIR│ PILI   │ │        │                                   │ RETICULAR
      │FOLL│(smooth │ │        │   ⊙ Ruffini ending                │ DERMIS
      │ICLE│ muscle)│ │        │   ≈≈≈ CUTANEOUS PLEXUS ≈≈≈        │ 80-90%
      │    ╰────────╯ │        │   ← AV ANASTOMOSES here:          │ of dermis
      │    APOCRINE ──┤        │     direct artery→vein shunts     │
      │    GLAND (axilla,      │     that bypass capillaries =     │
      │    groin) opens INTO   │     THE THERMAL VALVE             ┘
      │    the follicle        │
   ───┼───────────────────────┼──────────────────────────────────────────
      │ ○○○○○○○ ADIPOCYTES ○○○│○○○○○  ⊙ PACINIAN CORPUSCLE      ┐
      │○○○○○○○○○○○○○○○○○○○○○○○│○○○○○○○  (onion-layered, deep    │ HYPODERMIS
      ╰─ HAIR BULB (papilla   │        pressure + vibration)    │ (subcutan-
         with capillary)      ╰─ SWEAT GLAND SECRETORY COIL     │  eous)
      ═══ larger arteries and veins enter from below ═══        ┘
   ══════════ MUSCLE / DEEP FASCIA ══════════════════════════════════════

   TWO VASCULAR PLEXUSES, ONE VALVE:
   deep CUTANEOUS plexus (dermis/hypodermis border) ──► SUBPAPILLARY plexus
   AV anastomoses OPEN  = blood bypasses skin surface = HEAT RETAINED, PALE
   AV anastomoses SHUT  = blood floods subpapillary loops = HEAT LOST, PINK

5.5 Skin Color: Three Pigments and What They Report

Skin color has exactly three contributors. Everything you will ever observe about skin coloration — normal variation, tanning, cyanosis, jaundice, pallor, flushing, bronzing — is a change in one of them.

1 · Melanin — made in the skin, by melanocytes, from the amino acid tyrosine via the enzyme tyrosinase. Two forms exist: eumelanin, which is brown-black, and pheomelanin, which is reddish-yellow. Melanin is packaged into melanosomes and transferred through melanocyte dendrites into surrounding keratinocytes, where it is positioned as a supranuclear cap — a parasol over the nucleus on the side facing the sun.

The point about melanocyte number bears repeating because it is so widely misunderstood: all human populations have approximately the same density of melanocytes. What differs is:

• the amount of melanin synthesized (tyrosinase activity),
• the type — eumelanin versus pheomelanin, largely determined by variants of the melanocortin-1 receptor (MC1R),
• and the packaging — in darkly pigmented skin, melanosomes are larger, more numerous, individually dispersed, and degrade slowly as the keratinocyte rises; in lightly pigmented skin they are smaller, clustered into membrane-bound groups, and degraded early.

Melanin's job is photoprotection: it absorbs ultraviolet photons and quenches the free radicals they generate, protecting the DNA of the dividing basal cells. Deeply pigmented skin provides an intrinsic sun protection factor of roughly 13, against about 3 for lightly pigmented skin — a real and substantial difference, though far below the protection of sunscreen and not a reason to omit it.

Tanning is this system responding. UV exposure causes immediate darkening of existing melanin by photo-oxidation (within minutes, transient) and then, over 3–7 days, genuine upregulation of melanin synthesis and transfer. Delayed tanning is DNA damage having occurred and the epidermis responding to it; the tan is the record of the injury, not a shield against the injury that produced it.

Freckles (ephelides) are local patches of increased melanin production without increased melanocyte number, which darken with sun. Moles (nevi) are local proliferations of melanocytes. Albinism is a failure of the pathway itself, usually a tyrosinase mutation, producing normal melanocyte numbers making little or no pigment — with the eye involved, since retinal pigment epithelium is affected too. Vitiligo is autoimmune destruction of melanocytes in patches, leaving sharply demarcated depigmented skin.

2 · Carotene — a yellow-orange pigment that is not made by the body. It comes from the diet (carrots, sweet potatoes, squash) and, being fat-soluble, accumulates in the stratum corneum and in subcutaneous fat. It is most visible where the stratum corneum is thickest: the palms and soles. Excessive intake produces carotenemia, a harmless yellow-orange discoloration of the palms, soles, and nasolabial folds that is distinguished from jaundice by one reliable sign — carotenemia spares the sclerae, because carotene does not bind elastin and jaundice does.

3 · Hemoglobin — not a skin pigment at all, but the dominant contributor to the visible color of lightly pigmented skin, because the epidermis is somewhat translucent and the dermal capillaries lie just beneath it. Oxygenated hemoglobin is bright red; deoxygenated hemoglobin is dark blue-purple. The pink of lightly pigmented skin is capillary blood seen through translucent tissue, which is why it changes so fast with vasomotor state — and why the skin can serve as a live readout of the circulation.

The diagnostic colors

Each of these is a change in one of the three pigments, or in the blood behind them.

Two of these repay a closer look.

Cyanosis is a threshold phenomenon, not a percentage. It appears when the absolute concentration of deoxygenated hemoglobin in cutaneous capillaries reaches roughly 5 g/dL — not when saturation falls to a particular value. This has a counterintuitive and clinically critical consequence. A patient with a normal hemoglobin of 15 g/dL reaches 5 g/dL of deoxyhemoglobin at about 67% saturation. But a severely anemic patient with a hemoglobin of 7 g/dL cannot accumulate 5 g/dL of deoxyhemoglobin at any survivable saturation — they will die of hypoxia without ever turning blue. Conversely, a patient with polycythemia (hemoglobin 20 g/dL) looks cyanotic at a saturation that is nearly normal. Cyanosis is an unreliable indicator of oxygenation. Pulse oximetry and arterial blood gas exist because of this.

Distinguish also central cyanosis (tongue, lips, oral mucosa; means the arterial blood itself is desaturated — a lung or shunt problem) from peripheral cyanosis (fingers, toes, nail beds only, with a warm pink tongue; means flow is slow enough for tissues to extract extra oxygen — a circulation problem, or simply cold hands). Amara has neither at 96% saturation; she has pallor, which is a flow problem without desaturation, and telling those two apart at the bedside is a genuinely useful skill.

Bruise color is a chemistry timeline. The sequence purple → blue-green → yellow-brown is hemoglobin being enzymatically dismantled in the tissue by macrophages: heme → biliverdin (green) → bilirubin (yellow) → hemosiderin (golden brown, an iron storage protein that can persist for months). Reading the color tells you roughly how old the injury is. And, as §5.9 will show, an abnormal duration of that sequence — Adwoa's three weeks instead of one — is itself diagnostic information.

5.6 The Appendages: Hair, Nails, and Glands

Every skin appendage is an invagination of epidermis into the dermis — the same developmental move that §4.4 described for glands. That one fact explains a great deal, including why partial-thickness burns heal and full-thickness burns cannot (§5.9): the appendages are reservoirs of epidermal stem cells buried below the surface, and as long as they survive, the epidermis can be regenerated from them.

Hair

A hair is a flexible strand of dead, keratinized cells produced by a follicle. Humans have about 5 million follicles, of which roughly 100,000 are on the scalp — a density comparable to other primates. What differs is not follicle number but the type of hair each produces.

• Vellus hair — fine, pale, short, mostly unmedullated. The "peach fuzz" covering most of the body.
• Terminal hair — coarse, pigmented, long. Scalp, eyebrows, eyelashes, and after puberty the axillary and pubic regions, and in males the face and much of the body. The vellus-to-terminal switch is driven by androgens, which is why the same hormone that produces a beard produces androgenetic scalp balding — androgen-sensitive follicles on the scalp miniaturize in the opposite direction, terminal to vellus.

Hair keratin is hard keratin: more heavily cross-linked by disulfide bonds than the soft keratin of the epidermis, so it is tougher and does not desquamate. The number and position of those disulfide bonds also determine whether hair is straight or curly, along with the cross-sectional shape of the follicle — round follicles produce round shafts and straight hair; oval or curved follicles produce flattened shafts and curly hair. Chemical straightening and permanent waving both work by reducing those disulfide bonds, reshaping the hair, and re-oxidizing them in the new configuration.

 ═══ HAIR FOLLICLE IN LONGITUDINAL SECTION ═══════════════════════════════════

                     HAIR SHAFT (dead, keratinized, above skin)
                              │
                    ┌─────────┴─────────┐   SHAFT IN CROSS-SECTION:
    ════════════════╪═══════════════════╪═══  ┌──────────────────────┐
    ▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒│▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒│▒▒  │ CUTICLE — overlapping│
    ▪▪▪▪▪▪ EPIDERMIS│▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪│▪▪  │  scales, point UP    │
    ●○●○●○●○●○●○●○●○│●○●○●○●○●○●○●○●○●○│●○  │ CORTEX — bulk; keratin│
    ────────────────┼───────────────────┼──  │  + MELANIN = color   │
                    │  ╭─ SEBACEOUS ─╮  │    │ MEDULLA — soft core, │
        ╭───────────┤  │ GLAND       │  │    │  absent in fine hair │
        │ ARRECTOR  │  │ holocrine → │  │    └──────────────────────┘
        │ PILI      │  │ SEBUM into  │  │
        │ (smooth   │  │ the follicle│  │
        │  muscle;  │  ╰──────┬──────╯  │  ┌── FOLLICLE WALL, outside in ──┐
        │  sympath- │         │         │  │ CONNECTIVE TISSUE ROOT SHEATH │
        │  etic)    │◄────────┘         │  │  (dermal; vessels + nerve)    │
        │           │                   │  │ GLASSY MEMBRANE (thick base-  │
        ╰───────────┤   HAIR ROOT       │  │  ment membrane)               │
   ═════════════════╪═══════════════════╪  │ EXTERNAL ROOT SHEATH (epider- │
                    │                   │  │  mis, continuous with surface;│
                    │   ← BULGE: the    │  │  contains THE BULGE STEM CELLS│
                    │     STEM CELL     │  │ INTERNAL ROOT SHEATH (dis-    │
                    │     RESERVOIR ★   │  │  appears at sebaceous duct)   │
                    │                   │  └───────────────────────────────┘
                    │                   │
                  ╭─┴───────────────────┴─╮
                  │      HAIR BULB        │   MATRIX = the only mitotic
                  │  ┌─────────────────┐  │   region. Divides every
                  │  │ MATRIX (dividing│  │   ~24 h — among the fastest
                  │  │ cells) + MELANO-│  │   dividing tissue in the body
                  │  │ CYTES           │  │   → therefore hit hard by
                  │  └────────┬────────┘  │     chemotherapy
                  │    ╭──────┴──────╮    │
                  │    │ HAIR PAPILLA│    │   dermal papilla with the
                  │    │  ≈ capillary│    │   capillary that feeds it.
                  │    ╰─────────────╯    │   Destroy this = no regrowth
                  ╰───────────────────────╯

 ═══ THE GROWTH CYCLE (scalp) ════════════════════════════════════════════════
   ANAGEN  (growth)     2-7 YEARS   ~85-90% of follicles   0.33 mm/day
       │                                                    (~1 cm/month)
       ▼   ← sets MAXIMUM hair length
   CATAGEN (regression) 2-3 WEEKS   ~1%   follicle shrinks to the bulge
       │
       ▼
   TELOGEN (rest)       ~3 MONTHS   ~10-15%  club hair held, then shed
       │                                      → 50-100 hairs LOST per day
       └──────────► back to ANAGEN (new hair from BULGE stem cells)

   Follicles cycle ASYNCHRONOUSLY — which is why humans do not moult.
   A SYNCHRONIZING stress (illness, childbirth, surgery, severe diet)
   pushes many follicles into telogen at once → TELOGEN EFFLUVIUM,
   diffuse shedding beginning ~3 MONTHS AFTER the event.

Functions of hair. In humans, four are real: thermal insulation of the scalp (still significant — the scalp is a major site of heat loss), protection (eyelashes and vibrissae trigger blink and sneeze reflexes; eyebrows divert sweat from the eyes; scalp hair blocks UV), sensation (each follicle is wrapped in a rapidly-adapting nerve plexus, so hairs are levers that amplify light touch — you feel an insect land on a hair before it touches skin), and signaling (secondary sexual characteristics, and the pilomotor response).

The arrector pili is a slip of smooth muscle running obliquely from the follicle to the papillary dermis. Sympathetic stimulation contracts it, pulling the obliquely-set follicle upright and dimpling the skin — goosebumps (cutis anserina). In a furred mammal this fluffs the coat and traps an insulating air layer. In humans it is vestigial as thermoregulation but still diagnostically useful: goosebumps are a visible sign of sympathetic discharge, and they appear in cold, in fear, and in withdrawal states. Squeezing the follicle also helps express sebum.

Nails

A nail is a scale-like modification of the epidermis: a plate of hard keratin, corresponding to a hoof or claw. Its parts:

• Nail plate — the visible dead keratin. Grows from the nail matrix, which lies beneath the proximal nail fold and is visible at its distal end as the white crescent, the lunule (white because the underlying matrix is thicker and obscures the vascular bed).
• Nail bed — the epidermis beneath the plate, which contributes little to growth but supplies the pink color through its capillaries.
• Eponychium (cuticle) — the fold of stratum corneum sealing the proximal edge; a genuine barrier against infection, which is why aggressive cuticle removal predisposes to paronychia.
• Hyponychium — the seal beneath the free edge.

Growth rate: fingernails about 3 mm per month (a full replacement takes 4–6 months); toenails about 1 mm per month (12–18 months). That slow, steady, permanently recorded growth makes nails a retrospective medical record:

Sweat glands

Roughly 2–4 million sweat glands, of two distinct kinds that are frequently confused.

Three points repay attention. First, eccrine sweat glands are the body's only meaningful evaporative cooling mechanism, and their sympathetic innervation is cholinergic — the neurotransmitter is acetylcholine, not norepinephrine. This is why anticholinergic drugs block sweating and can cause hyperthermia, as Chapter 1's heat-stroke case demonstrated.

Second, body odor is bacterial, not glandular. Apocrine secretion leaves the gland odorless; resident Corynebacterium and Staphylococcus species metabolize its lipids and amino acids into volatile short-chain fatty acids and thioalcohols. Antiperspirants block the duct (aluminium salts); deodorants target the bacteria.

Third, palmar and plantar sweating is emotional, not thermal. It is driven by limbic input rather than by hypothalamic temperature signals, and its function appears to be improving grip. This is why your palms sweat when you are nervous but not when you are merely hot, and it is the physiological basis of the electrodermal response used in polygraphy.

Sebaceous, ceruminous, and mammary glands

Sebaceous glands are simple branched alveolar glands secreting sebum by the holocrine mode (§4.4) — the cell fills with lipid, dies, and disintegrates, taking about 7 days. Nearly all open into a hair follicle; they are absent from the palms and soles and largest on the face, scalp, and upper trunk. Sebum is a mix of triglycerides, wax esters, and squalene, and it does three things: lubricates hair and stratum corneum so they do not become brittle, contributes to the water barrier, and — being mildly acidic and containing free fatty acids — is bactericidal and fungistatic.

Sebaceous glands are androgen-driven, which is why they enlarge abruptly at puberty. Acne is the predictable consequence of that plus three other events in the same follicle: increased sebum production, abnormal keratinization plugging the follicular opening (forming a comedone), proliferation of Cutibacterium acnes in the resulting anaerobic lipid-rich pocket, and inflammation. Every acne treatment targets one of those four — retinoids the keratinization, antibiotics the bacteria, hormonal agents and isotretinoin the sebum, anti-inflammatories the inflammation.

Ceruminous glands are modified apocrine glands in the external auditory canal. Their secretion mixes with sebum to form cerumen (earwax), which waterproofs the canal, traps particles, is acidic and bactericidal, and is slowly transported outward by the migrating epithelium of the canal — which is why the ear canal is self-cleaning and why pushing a cotton swab into it defeats the mechanism.

Mammary glands are modified apocrine sweat glands specialized for milk production, and their mode of secretion is the textbook demonstration of §4.4: the protein and lactose of milk are released by merocrine exocytosis while the fat is released by true apocrine budding, wrapped in a fragment of the cell's apical membrane. Full treatment in Chapter 28.

5.7 Thermoregulation: The Chapter's Homeostasis Anchor

Your body must hold its core temperature near 37 °C within about ±0.6 °C over a normal day, while producing heat continuously and living in an environment that ranges over 60 °C. The skin is the effector organ for almost all of it.

This section covers thermoregulation as far as the skin can carry it — the four routes of heat loss, and the vascular and sweating responses the integument provides. Chapter 25 gives the full treatment: the hypothalamic controller, the two-threshold model, fever, acclimatization, and the thermal illnesses that result when the machinery described here is overwhelmed.

The physics is a simple balance:

Heat storage = heat produced + heat gained − heat lost

Heat production at rest is about 60–70 kcal/h in an adult (roughly 1 kcal/kg/h — a resting human is a 70-watt heater), rising 10–20 fold in hard exercise and up to 4–5 fold in shivering. Heat gain comes from the environment when it is hotter than the skin. Heat loss happens by exactly four physical routes, and there are no others.

 ═══ THE FOUR ROUTES OF HEAT LOSS ════════════════════════════════════════════
    resting adult, 21°C still air, normal clothing — total ~70 kcal/h

  1 ▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓  RADIATION          ~60%
       ))) ))) )))          Infrared photons emitted from skin to any
      SKIN ─────►  cooler   COOLER SURFACE, with no contact and no air
       ))) ))) )))  walls   movement needed. Depends on skin-to-surface
                            temperature difference and exposed area.
                            Largest single route at rest. REVERSES when
                            surroundings are hotter than skin (e.g. sun,
                            a fire, a hot room) and becomes heat GAIN.

  2 ░░░░░░░  CONVECTION                                    ~15%
       ↑ ↑ ↑    Air touching skin is warmed, becomes less dense, rises,
      SKIN      and is replaced by cooler air. Moving air (wind, a fan)
       ↑ ↑ ↑    strips the warmed boundary layer away and multiplies
                the rate — the basis of "wind chill". Water convects
                ~25x faster than air: immersion is the fastest cooling
                available, and the reason cold-water immersion is the
                treatment for exertional heat stroke.

  3 ▪▪▪▪▪▪▪  CONDUCTION                                    ~3%
      SKIN     Direct molecular transfer to a touching solid or liquid.
      ████     Small at rest because contact area is small. Enormous
      cold     lying on cold ground or in water. Subcutaneous FAT is
      floor    the body's insulation against this route.

  4 ≈≈≈≈≈≈≈  EVAPORATION                                   ~22%
       ↟ ↟ ↟    Water changing phase absorbs 0.58 kcal per GRAM
      SKIN      → 580 kcal per LITRE evaporated.
      + lungs   INSENSIBLE (always, unregulated): ~600-900 mL/day
                  transepidermal water ~300-400 mL + respiratory
                  ~300-500 mL  = ~350-500 kcal/day
                SENSIBLE SWEAT (regulated): 0 to >2 L/h

 ═══ THE CROSSOVER THAT MATTERS ══════════════════════════════════════════════
    Ambient temperature RISES above skin temperature (~33-35 °C):
      RADIATION  reverses → heat GAIN
      CONVECTION reverses → heat GAIN
      CONDUCTION reverses → heat GAIN
      EVAPORATION is the ONLY remaining route. 100% of heat loss.
    ...and evaporation is abolished by high humidity.
    HOT + HUMID + no sweating = no route out at all. This is heat stroke.

 ═══ THE CONTROL LOOP ════════════════════════════════════════════════════════
   STIMULUS: core temp deviates
      ▼
   RECEPTORS: peripheral thermoreceptors (skin) + central (hypothalamus,
              which senses blood temperature directly)
      ▼
   CONTROL CENTRE: PREOPTIC / ANTERIOR HYPOTHALAMUS — holds the set point
      ▼
   EFFECTORS, in recruitment order:
   TOO HOT ──► 1. cutaneous VASODILATION (AV anastomoses close; flow
                  250 mL/min → up to 6-8 L/min). Free. Instant.
               2. SWEATING (sympathetic CHOLINERGIC). Costs water + salt.
               3. behaviour: shed clothing, seek shade, reduce activity
   TOO COLD ─► 1. cutaneous VASOCONSTRICTION (α₁). Free. Instant. PALE.
               2. behaviour: clothing, curling up, seeking shelter
               3. SHIVERING — raises heat production 4-5x. Costs fuel.
               4. non-shivering thermogenesis (brown fat, thyroid) — slow

The thermal valve: arteriovenous anastomoses

The skin's blood supply has an unusual and purpose-built feature. In the acral regions — fingers, toes, palms, soles, ears, nose, lips — the deep cutaneous plexus contains arteriovenous anastomoses (AVAs): short, thick-walled, heavily innervated vessels that connect an arteriole directly to a venule, bypassing the capillary bed entirely.

They act as a valve, and their two positions are opposite:

• AVAs open → blood shunts from artery to vein deep in the skin without visiting the superficial capillary loops. Little heat reaches the surface. The skin looks pale and feels cool. This is the cold response, and it is also the shock response.
• AVAs closed → blood is forced through the subpapillary capillary plexus just beneath the epidermis, where it is separated from the air by a fraction of a millimetre. Heat radiates away. The skin looks pink and feels warm.

AVAs are controlled almost entirely by sympathetic α₁-adrenergic tone, and this is the key to understanding Amara. The hypothalamus can command AVA opening for thermoregulation, and the baroreflex can command it for blood pressure — through the same efferent nerves and the same receptors. One effector, two control systems, and the effector cannot tell which one is talking.

That is precisely why Amara's skin is cool and pale while her core temperature is a perfectly normal 36.8 °C. Her thermoregulatory system is not asking for vasoconstriction; her baroreflex is. The clinical skill Chapter 1 promised — distinguishing which control system is driving a shared effector — is exactly this, and the distinguishing evidence is her core temperature. A cold person and a shocked person have identical skin. Only the thermometer separates them.

Two further consequences of the same machinery:

Counter-current heat exchange. In the limbs, deep arteries run alongside deep veins. Warm arterial blood heading distally transfers heat directly across to cool venous blood returning proximally, so heat is recycled into the core before it ever reaches the hand. In the cold, venous return is shifted to these deep companion veins; in the heat, it is shifted to superficial veins where the heat can escape. This is why prominent superficial veins on the forearm appear when you are hot and disappear when you are cold.

The insulation shell. By varying skin blood flow, the body varies the thickness of its insulating shell. Maximally vasoconstricted, the shell (skin, subcutaneous fat, and the outer part of the limbs) can be several centimetres thick and the "core" shrinks to the trunk and head. Maximally vasodilated, the shell is almost eliminated and the core extends nearly to the skin. The body regulates its own insulation, continuously, without moving.

5.8 Barrier, Wound Healing, and Vitamin D

The barrier is three barriers

Physical. The stratum corneum's bricks-and-mortar arrangement (§5.2), reinforced by desmosomes throughout the living layers and hemidesmosomes anchoring the whole sheet to the dermis (§4.3), and backed by the collagen felt of the reticular dermis. Together these resist abrasion, penetration, and — most importantly — the outward loss of water. Note the direction of the greater threat: the skin exists at least as much to keep water in as to keep pathogens out. A human is a bag of salt water living in dry air, and without a stratum corneum that bag leaks fatally.

Chemical. Three components. The acid mantle — a film of sweat, sebum, and keratinocyte breakdown products holding the surface at pH 4.5–6.0 — inhibits most pathogenic bacteria, which prefer neutrality, while favoring the commensal flora that outcompete them. Sebum contains free fatty acids that are directly bactericidal and fungistatic. And keratinocytes and sweat glands secrete antimicrobial peptides — defensins, cathelicidin (LL-37), and dermcidin in sweat — that punch holes in bacterial membranes. Alkaline soaps transiently raise skin pH and disrupt this system, which is why frequent handwashing damages skin and why "pH-balanced" cleansers are not merely marketing.

Biological. The resident microbiome — roughly a trillion organisms across a thousand species, occupying niches by region (Cutibacterium in sebaceous areas, Staphylococcus and Corynebacterium in moist areas, greater diversity on dry areas) — competes with pathogens for space and nutrients and trains the local immune system. Above it sits the immune garrison: Langerhans cells in the epidermis, dermal dendritic cells, resident memory T cells, macrophages, and mast cells in the dermis. §4.5 made the general point; the skin is its most developed example.

What the barrier does not stop. Lipid-soluble substances cross the stratum corneum readily, because the mortar is lipid. This is the basis of transdermal drug delivery (nicotine, fentanyl, estradiol, nitroglycerin) and also of toxicity from lipid-soluble solvents, pesticides, and heavy metal compounds. Water-soluble substances cross poorly. So does anything above roughly 500 daltons — which is why most drugs cannot be given transdermally, and why a patch delivers a small potent molecule or nothing.

Wound healing in the skin

Chapter 4 gave the general programme — hemostasis, inflammation, organization, maturation — and the rule that decides the outcome: regeneration requires a dividing cell and a surviving scaffold. Skin applies that rule as cleanly as any tissue in the body, and the deciding variable is depth.

That middle row is the single most useful idea in burn and wound care. Appendages are buried epidermis, and they are the reason a scald that destroys the entire surface epidermis can still heal without a graft: the follicles and sweat ducts survive in the dermis and each becomes a seed point of new epithelium. Destroy the dermis and you destroy the seeds, and now the only epidermis available is at the edges — which is why a large full-thickness wound cannot close itself and needs a graft.

Healing by first versus second intention. A clean incision with apposed edges heals by first intention: minimal granulation tissue, minimal contraction, a fine scar. An open wound with separated edges heals by second intention: a large volume of granulation tissue, substantial myofibroblast contraction (which can reduce the area by 70–80%), and a large, often contracted scar. This is why wounds are closed when they can be safely closed, and why a wound left open across a joint or the neck risks a movement-limiting contracture.

What impairs it, and each for a mechanistic reason you now know: poor perfusion (delivers nothing — §4.9); diabetes (microvascular disease plus impaired neutrophil function plus AGE cross-linking — §4.5); corticosteroids (suppress the inflammatory phase and fibroblast collagen synthesis); smoking (nicotine vasoconstricts, carbon monoxide displaces oxygen); protein malnutrition (no substrate for collagen); vitamin C deficiency (no hydroxylation, so no stable triple helix — §4.5); zinc deficiency (metalloproteinases and cell division); infection and foreign material (hold the wound in the inflammatory phase); and mechanical tension (drives fibroblasts, producing hypertrophic scar — §4.9, §5.3).

Vitamin D synthesis: a hormone that begins in the skin

The skin performs an obligatory step in the synthesis of a hormone, and it is the only organ that can. The pathway:

1. 7-dehydrocholesterol, a cholesterol precursor, is abundant in the plasma membranes of keratinocytes in the stratum basale and spinosum.
2. UVB photons at 290–315 nm break the B-ring of that molecule, converting it to previtamin D₃. This is a photochemical reaction, not an enzymatic one — no enzyme is involved, and it cannot be regulated by the body.
3. Body heat isomerizes previtamin D₃ to cholecalciferol (vitamin D₃) over a few hours.
4. In the liver, it is hydroxylated to 25-hydroxyvitamin D — the storage form and the form measured in blood.
5. In the kidney, a second hydroxylation, tightly regulated by parathyroid hormone, produces 1,25-dihydroxyvitamin D (calcitriol) — the active hormone.

Calcitriol's principal action is to increase intestinal absorption of calcium and phosphate; without it, only 10–15% of dietary calcium is absorbed, against 30–40% with it. Chapter 6 will develop the consequences for bone, and Chapter 26 will explain why Amara's kidneys matter here.

Three features of that pathway are worth holding onto because they explain most of what goes wrong with it.

It is self-limiting at step 2 but not at step 5. Prolonged UV exposure converts excess previtamin D₃ into inert photoproducts, so you cannot overdose on vitamin D from sunlight. You can overdose from supplements, because that route bypasses the photochemical brake.

Everything that blocks UVB blocks synthesis. Melanin is a UV absorber, so deeply pigmented skin requires roughly 3–6 times the exposure of lightly pigmented skin for the same synthesis. Glass blocks UVB entirely — you cannot make vitamin D through a window. Sunscreen at SPF 30 blocks about 95–98% of UVB. Latitude above roughly 37° gives insufficient UVB intensity for synthesis for several winter months regardless of exposure. Time of day matters (the solar zenith angle determines how much atmosphere UVB traverses), as do clothing, air pollution, and season.

Age reduces it sharply. Cutaneous 7-dehydrocholesterol concentration falls with age, so a 70-year-old exposed to the same UVB as a 20-year-old produces roughly 25% as much vitamin D. Combine that with less time outdoors and reduced renal 1-α-hydroxylation, and the elderly are the population most reliably deficient.

Which is exactly what the Case File table shows. Amara's 25-hydroxyvitamin D is 18 ng/mL and Adwoa's is 14 ng/mL, against a sufficiency threshold usually taken as ≥ 30 ng/mL and deficiency below 20. Both are deficient, and the reasons are the ones just listed: twenty years of night shift sleeping through daylight for Amara, and age plus indoor living for Adwoa. In Chapter 6 this number becomes Adwoa's osteoporosis.

5.9 Advanced Topic · Burns and Skin Cancer

Two ways to destroy skin: all at once, and slowly. Each demonstrates the chapter in a different direction.

Burns

A burn is tissue damage from heat, electricity, radiation, or corrosive chemicals. Its severity is a function of two variables — depth and extent — and the two answer different clinical questions. Depth predicts whether the wound will heal itself. Extent predicts whether the patient will survive.

 ═══ BURN DEPTH MAPPED ONTO THE SKIN CROSS-SECTION ═══════════════════════════

  ┌──── SUPERFICIAL ────┐  1st degree                    HEALS 3-6 DAYS
  │ ▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒ │  EPIDERMIS ONLY                no scar
  │ ▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪▪ │  Red · PAINFUL · dry · no
  │ ●○●○●○●○●○●○●○●○●○● │  blisters · BLANCHES
  │ ─────────────────── │  Basal layer + ALL appendages
  │ ░░░░ papillary ░░░░ │  intact. Sunburn.
  │ ▨▨▨▨ reticular ▨▨▨▨ │  Peels — the corneum shedding.
  │ ○○○○ hypodermis ○○○ │  NOT counted in %TBSA.
  └─────────────────────┘

  ┌── SUPERFICIAL PARTIAL ──┐ 2nd degree superficial      HEALS 1-3 WEEKS
  │ ═══════ destroyed ═════ │ EPIDERMIS + PAPILLARY DERMIS  minimal scar
  │ ═══════════════════════ │ BLISTERS · weeping · red ·
  │ ░░░░ papillary ░░░░░░░  │ VERY PAINFUL (nerve endings
  │ ▨▨▨▨ reticular ▨▨▨▨▨▨▨  │ exposed but alive) · BLANCHES
  │ ○○○○ hypodermis ○○○○○○  │ Appendages in reticular dermis
  └─────────────────────────┘ SURVIVE → re-epithelialize from
                              hundreds of seed points.

  ┌─── DEEP PARTIAL ────────┐ 2nd degree deep             3-8 WEEKS, SCARS
  │ ═══════ destroyed ═════ │ + MOST OF RETICULAR DERMIS   often grafted
  │ ═══════════════════════ │ Mottled red-white · LESS
  │ ═══════════════════════ │ painful (some nerves gone) ·
  │ ▨▨ deep reticular ▨▨▨▨  │ SLUGGISH or ABSENT blanching
  │ ○○○○ hypodermis ○○○○○○  │ Few appendages left → slow,
  └─────────────────────────┘ contracted healing.

  ┌──── FULL THICKNESS ─────┐ 3rd degree              CANNOT SELF-HEAL
  │ ═══════ destroyed ═════ │ ALL EPIDERMIS + ALL DERMIS   REQUIRES GRAFT
  │ ═══════════════════════ │ White, waxy, leathery, or
  │ ═══════════════════════ │ charred · DRY · PAINLESS
  │ ═══════════════════════ │ (nerve endings destroyed) ·
  │ ○○○○ hypodermis ○○○○○○  │ NO blanching · ESCHAR
  └─────────────────────────┘ NO appendages survive →
                              epidermis only from margins.
       4th degree = through hypodermis into fascia, muscle, or bone.

 ═══ THE DIAGNOSTIC PARADOX ══════════════════════════════════════════════════
   THE MOST SEVERE BURN IS THE ONE THAT DOES NOT HURT.
   Pain requires living free nerve endings in the dermis. A full-thickness
   burn has destroyed them. A patient with a painless, dry, white, leathery
   burn is MORE injured than one screaming over a blistered one — and the
   surrounding partial-thickness rim will still hurt, which disguises it.

 ═══ THE TWO QUESTIONS ═══════════════════════════════════════════════════════
   DEPTH  → will it heal itself?   (appendages surviving = yes)
   EXTENT → will the patient live? (%TBSA drives fluid loss + infection)

Extent: the rule of nines

Extent is expressed as the percentage of total body surface area (TBSA) burned, counting partial- and full-thickness burns only — superficial burns are excluded, because they neither leak nor become infected.

 ═══ THE RULE OF NINES — ADULT ═════════════ vs ═══ INFANT/CHILD ═════════════

              ╭───────────╮                        ╭───────────╮
              │  HEAD &   │                        │  HEAD &   │
              │   NECK    │  9%                    │   NECK    │  18%
              ╰─────┬─────╯                        ╰─────┬─────╯
        ╭─────┬─────┴─────┬─────╮            ╭─────┬─────┴─────┬─────╮
        │ ARM │  ANTERIOR │ ARM │            │ ARM │  ANTERIOR │ ARM │
        │  L  │   TRUNK   │  R  │            │  L  │   TRUNK   │  R  │
        │     │           │     │            │     │           │     │
        │  9% │    18%    │  9% │            │  9% │    18%    │  9% │
        │each │ (chest 9  │each │            │each │           │each │
        │(front 4.5 +     │     │            │     │           │     │
        │ back 4.5)       │     │            │     │           │     │
        ╰──┬──┤ +abdo 9)  ├──┬──╯            ╰──┬──┤           ├──┬──╯
           │  │           │  │                  │  │           │  │
           ╰──┤ POSTERIOR ├──╯                  ╰──┤           ├──╯
              │  TRUNK    │                       │           │
              │   18%     │                       │           │
              ╰─────┬─────╯                       ╰─────┬─────╯
              ┌─────┴─────┐                       ┌─────┴─────┐
              │ LEG │ LEG │                       │ LEG │ LEG │
              │  L  │  R  │  18% each             │  L  │  R  │  13.5% each
              │     │     │  (front 9 +           │     │     │
              │     │     │   back 9)             │     │     │
              └─────┴─────┘                       └─────┴─────┘
                PERINEUM 1%                          PERINEUM 1%
              ─────────────                       ─────────────
              TOTAL = 100%                        TOTAL = 100%

 WHY THE DIFFERENCE: an infant's head is a far larger fraction of body surface
 and its legs a smaller one. Using the adult rule on a child OVERESTIMATES
 leg burns and UNDERESTIMATES head burns — and the resulting fluid error can
 be fatal in either direction. (Lund–Browder charts refine this by age.)

 ═══ THE PALM RULE ═══════════════════════════════════════════════════════════
   The patient's OWN palm INCLUDING the fingers ≈ 1% of their TBSA.
   Use it for scattered or irregular burns. Palm without fingers ≈ 0.5%.

 ═══ THE FLUID CALCULATION — PARKLAND FORMULA ════════════════════════════════
   First 24 h crystalloid  =  4 mL  ×  body weight (kg)  ×  %TBSA
                              ├─ HALF in the FIRST 8 HOURS
                              └─ half over the NEXT 16 HOURS
   ...timed from the MOMENT OF INJURY, not from arrival.

   Worked example — 70 kg adult, 40% TBSA:
      4 × 70 × 40 = 11,200 mL in 24 h
      5,600 mL in the first 8 h  = 700 mL/h
      5,600 mL over the next 16 h = 350 mL/h

   The formula is a STARTING ESTIMATE ONLY. It is then titrated against
   URINE OUTPUT — target 0.5 mL/kg/h in adults, 1 mL/kg/h in children —
   because urine output is the cheapest continuous readout of whether
   organs are actually being perfused.

Skin cancer

Skin cancer is the commonest malignancy in humans, and its biology is the biology of §5.2: the cells at risk are the ones that divide, and the mutagen is ultraviolet light — chiefly UVB (290–320 nm), which is directly absorbed by DNA and creates pyrimidine dimers, and UVA (320–400 nm), which penetrates deeper and acts largely through reactive oxygen species.

The ABCDE criteria for evaluating a pigmented lesion:

• A — Asymmetry. One half does not mirror the other.
• B — Border. Irregular, notched, scalloped, or poorly defined.
• C — Color. More than one color, or uneven distribution — browns, blacks, reds, whites, blues within one lesion.
• D — Diameter. Greater than 6 mm (about a pencil eraser). Useful but the weakest criterion, since melanomas can be found smaller.
• E — Evolving. Change in size, shape, color, elevation, or the development of bleeding, itching, or crusting. This is the most important single criterion, because it is the only one that does not require comparison with a population norm — the patient's own lesion last month is the control.

Add the "ugly duckling" sign: most of a person's moles resemble one another, so the lesion that looks unlike its neighbours deserves attention regardless of its individual features.

Why depth is everything in melanoma. The Breslow thickness — the vertical depth in millimetres from the granular layer to the deepest tumor cell — is the strongest single prognostic factor, and the reason is the anatomy of §5.3. The epidermis is avascular; a melanoma confined to it (melanoma in situ) has no access to vessels and cannot metastasize, and excision is essentially curative. Once the tumor penetrates the papillary dermis it reaches capillaries and lymphatics within a fraction of a millimetre. Five-year survival for a lesion under 1 mm thick exceeds 95%; beyond 4 mm it falls below 50%. The difference between those two numbers is about three millimetres of tissue, and it is the same principle §4.2 gave for every carcinoma: the basement membrane is where the prognosis changes.

Chapter Summary

§5.1 The skin is an organ containing all four tissue types, 1.5–2.0 m² in area and 3.5–5 kg in mass. Its blood flow ranges from about 250 mL/min to 6–8 L/min — a thirty-fold range that exists to move heat and to serve as a sacrificial blood reservoir, not to feed the skin. Its seven functions are protection, chemical and biological barrier, thermoregulation, sensation, vitamin D synthesis, blood storage, and minor excretion.

§5.2 The epidermis is avascular keratinized stratified squamous epithelium in five strata — basale, spinosum, granulosum, lucidum (thick skin only), corneum. A keratinocyte takes 25–45 days to travel from basal mitosis to desquamation, filling with keratin, secreting lipid, and destroying its own nucleus on the way. The barrier is the dead stratum corneum: corneocyte bricks in lipid mortar. Its other three cell types are melanocytes (pigment), dendritic/Langerhans cells (immune surveillance), and tactile/Merkel cells (touch).

§5.3 The dermis is papillary (areolar; dermal papillae, capillary loops, fine touch receptors, friction ridges) over reticular (dense irregular collagen with elastin; strength and recoil). Cleavage lines describe the predominant collagen orientation, and incisions parallel to them heal finely while incisions across them gape and scar. Capillary refill times how fast the subpapillary plexus refills, and it is set by perfusion pressure and cutaneous arteriolar tone.

§5.4 The hypodermis is areolar and adipose tissue providing anchorage with mobility, insulation, padding, and energy storage. Visceral fat is metabolically distinct from subcutaneous fat and drains to the portal vein, which is why waist circumference predicts risk better than BMI.

§5.5 Three pigments: melanin (made locally; equal melanocyte numbers in all populations, differing in amount, type, and packaging), carotene (dietary, in the corneum and fat), and hemoglobin (seen through translucent epidermis). Pallor, erythema, cyanosis, jaundice, bronzing, and bruising each have a distinct mechanism. Cyanosis requires ~5 g/dL of deoxygenated hemoglobin and is therefore unreliable in anemia. Color signs present differently across skin tones, so assessment must use conjunctivae, oral mucosa, nail beds, palms, and hard palate — and must use touch and comparison rather than color alone.

§5.6 Appendages are buried epidermis. Hair grows in an asynchronous anagen–catagen–telogen cycle, with anagen setting maximum length. Nails grow 3 mm/month and record systemic events. Eccrine glands are the thermoregulatory sweat glands, sympathetically but cholinergically innervated; apocrine glands open into follicles, activate at puberty, and are odorless until bacteria act on them. Sebaceous glands are holocrine and androgen-driven.

§5.7 Heat leaves by exactly four routes — radiation ~60%, evaporation ~22%, convection ~15%, conduction ~3% at rest — and the first three reverse once ambient temperature exceeds skin temperature, leaving evaporation as the sole route and humidity as its limiting factor. Evaporating one litre of sweat removes ~580 kcal. Arteriovenous anastomoses are the thermal valve, and they are controlled by the same sympathetic α₁ pathway that the baroreflex uses.

§5.8 The barrier is physical (corneum plus junctions), chemical (acid mantle pH 4.5–6.0, sebum, antimicrobial peptides), and biological (microbiome plus immune garrison). Healing outcome is set by depth: spare the basement membrane and appendages and the skin regenerates; destroy the dermis and it scars. Vitamin D synthesis begins with UVB acting photochemically on 7-dehydrocholesterol and is completed in liver and kidney; melanin, sunscreen, glass, latitude, and age all reduce it.

§5.9 Burns are classified by depth (which predicts self-healing, via surviving appendages) and extent (which predicts survival). The rule of nines estimates %TBSA, and the Parkland formula — 4 mL × kg × %TBSA, half in 8 hours from injury — starts resuscitation that is then titrated to urine output. Burn patients die of fluid loss (evaporative plus capillary leak) and infection. Pressure injuries occur over bony prominences because external pressure exceeds the ~32 mm Hg capillary closing pressure and because muscle dies before skin does. Skin cancers arise from the dividing cells of the epidermis, and melanoma's prognosis is governed by Breslow depth for the same reason every carcinoma's is: the basement membrane.

Case File 5 · Resolution

Question 1 — Why does the skin go pale and cool during a cardiac event when the core temperature is normal?

Because the skin is the body's sacrificial circulation, and the sympathetic nervous system has deliberately shut it down.

The chain, in order. Amara's infarcting myocardium ejects less blood per beat, so cardiac output and arterial pressure fall. Baroreceptors in the carotid sinus and aortic arch detect the fall, and the medullary cardiovascular centres respond with a surge of sympathetic outflow. That outflow reaches cutaneous arterioles and the arteriovenous anastomoses of the deep cutaneous plexus, where α₁-adrenergic stimulation constricts the arterioles and opens the AVAs. With the AVAs open, blood shunts from arteriole to venule deep in the dermis and largely bypasses the subpapillary capillary loops that lie a fraction of a millimetre beneath the translucent epidermis.

Two visible consequences follow immediately, and they are the two findings:

• Pallor. As §5.5 established, the pink of lightly pigmented skin and the red undertone of more deeply pigmented skin are both hemoglobin seen through the epidermis, in the subpapillary plexus. Empty that plexus and the color goes. In Amara's skin tone this reads as pallor with blanched nail beds; in a more deeply pigmented patient the same event would read as ashen or grey — loss of the red undertone rather than the appearance of whiteness.
• Coolness. Skin temperature is maintained almost entirely by convective heat delivery in blood from the core. Cut the flow from 250 mL/min toward a fraction of that and the surface cools toward ambient within minutes. Her skin is cool not because heat is being lost faster but because heat is no longer arriving.

The diaphoresis is the same efferent system acting on a different effector: eccrine sweat glands receive sympathetic cholinergic innervation (§5.6), and they are activated by the same discharge. Because her skin vessels are constricted, the sweat is not accompanied by the warm flush of thermoregulatory sweating — hence cool sweat, the specific and highly suggestive combination clinicians call "cool and clammy."

Why the skin and not something else? Because the skin's own metabolic requirement is small and almost all of its 250 mL/min is thermoregulatory reserve (§5.1). The body can withdraw it for hours without damage, whereas withdrawing flow from brain or myocardium is lethal in minutes. This is triage performed by the autonomic nervous system, and it is the same reflex that saves someone who is hemorrhaging.

And the core temperature is the point. A person standing in the snow has identical skin, but their vasoconstriction is a hypothalamic command defending a threatened core temperature, and their core is normal or falling with a subjective feeling of cold. Amara's core is a completely normal 36.8 °C and she does not feel cold. One effector, two control systems; the thermometer is what distinguishes them (§5.7). This was the question left open at the end of Chapter 1, and the answer is that her skin is not an integumentary finding at all.

Question 2 — What is being timed in capillary refill, and which variable is abnormal?

Pressing on the nail bed empties the capillary loops of the dermal papillae and the subpapillary venous plexus — the superficial vessels responsible for visible skin color. Releasing lets blood flow back in. What is being timed is therefore how fast blood re-enters the most peripheral capillary bed in the body.

That time is set by two variables:

1. Perfusion pressure — the driving pressure delivered to the limb, which depends on cardiac output and on systemic arterial pressure.
2. Cutaneous arteriolar resistance — how tightly the precapillary arterioles and AVAs are constricted.

In Amara, both are abnormal, and in the same direction. Her stroke volume is reduced by the infarct, so perfusion pressure at the fingertip is lower than normal. And her sympathetic response has maximally constricted the cutaneous arterioles, so resistance is higher than normal. Flow is pressure divided by resistance; a lower numerator over a higher denominator makes the quotient small, and a small flow takes a long time to refill a bed that has been emptied. Hence 4 seconds instead of under 2.

Note that her blood pressure is high — 168/98 — which seems to contradict a low perfusion pressure. It does not, and this is worth being precise about: her systemic pressure is high because of the intense vasoconstriction, and that same vasoconstriction is what is starving the capillary bed. Pressure is not flow. A garden hose with the nozzle nearly closed has high pressure and almost no flow. This distinction returns in Chapter 19.

Two honest caveats, both from §5.3. Capillary refill is prolonged independently by cold (always warm the hand first) and by age — which is why Adwoa's 3 seconds is normal for a 78-year-old with a thinner dermis and reduced capillary density, and Amara's 4 seconds at 45 is not. And it is a screening observation, not a measurement: its value lies in being free, instantaneous, and trended over time in the same patient.

Question 3 — Why does Adwoa bruise from a trivial bump, and why does the bruise take three weeks?

This is actinic (senile) purpura, and it is a mechanical failure of connective tissue, not a disorder of clotting. Layer by layer:

Dermis — the primary problem. Dermal collagen content falls roughly 1% per year after the mid-twenties, so at 78 Adwoa has lost about half; her forearm dermis measures 1.0 mm against 1.5–2.0 mm at Amara's age. Elastic fibers have fragmented and are not replaced, because elastin synthesis effectively ends after adolescence (§4.5). And because the extensor forearm is a maximally photoexposed site, ultraviolet-driven matrix metalloproteinase activity has actively degraded the remaining collagen and replaced the upper dermis with solar elastosis — a mass of abnormal elastic material with no useful mechanical properties.

The consequence for the vessels is direct. A dermal venule in young skin is embedded in a dense fibrous matrix that grips it, restrains it, and absorbs shear before it ever reaches the vessel wall. In Adwoa's dermis that supporting matrix is thin and degraded, so shear is transmitted straight to the vessel, which tears. Blood escapes into the papillary and upper reticular dermis. Because the lesion is extravascular blood rather than dilated vessels, it does not blanch — the bedside test that separates purpura from erythema.

Dermal–epidermal junction. The papillae and rete ridges that interdigitate in young skin have flattened, so contact area is reduced and the skin transmits shear between planes instead of distributing it. A glancing blow that would slide harmlessly over young skin instead drags one layer against another.

Hypodermis. Subcutaneous fat is lost from the forearms and dorsal hands with age, removing the padding that would otherwise dissipate the impact before it reached the dermis.

Why three weeks rather than one. Clearing extravasated blood is an active cellular job: macrophages must migrate into the tissue, phagocytose the red cells, and degrade heme through biliverdin to bilirubin to hemosiderin, with lymphatics carrying the products away. Every step is slower in aged skin — dermal blood flow and capillary density are reduced, so fewer cells are delivered; macrophage function is less efficient; and lymphatic drainage is diminished. The residual brown stain is hemosiderin, the iron-storage end product, which is cleared last and sometimes not completely.

What it is not. Adwoa's platelet count, INR, and PTT are normal. This is not a bleeding disorder, and investigating her coagulation would find nothing. The distinction between a bleeding problem and a bleeding disorder is the payoff of Chapter 4: sometimes the failure is not in the blood but in the matrix that holds the vessels. One question is worth asking, though — whether she takes corticosteroids for anything, since they suppress dermal collagen synthesis and produce or worsen exactly this picture.

Systems Integration Case File · Entry 5

Review

Level 1 · Recall

5.1 The epidermal layer in which mitosis occurs is the stratum:

a) corneum    b) granulosum    c) spinosum    d) basale

5.2 The waterproofing of the skin is produced chiefly by:

a) keratin inside corneocytes    b) lipid lamellae between corneocytes    c) sebum on the surface    d) the basement membrane

5.3 Cyanosis becomes visible when deoxygenated hemoglobin reaches approximately:

a) 2 g/dL    b) 5 g/dL    c) 10 g/dL    d) a saturation of 90%

5.4 Which sweat gland type is responsible for thermoregulation?

a) apocrine    b) eccrine    c) sebaceous    d) ceruminous

5.5 At rest in a cool room, the largest single route of heat loss is:

a) conduction    b) convection    c) radiation    d) evaporation

5.6 A burn that is dry, white and leathery, and painless is:

a) superficial    b) superficial partial-thickness    c) deep partial-thickness    d) full-thickness

5.7 Senile (actinic) purpura is caused by:

a) thrombocytopenia    b) a clotting factor deficiency    c) loss of dermal collagen and elastin supporting the vessels    d) increased capillary pressure

Level 2 · Comprehension

5.8 Explain why the same sympathetic reflex produces pallor in a person in shock and in a person standing in the cold, and how the two are distinguished at the bedside.

5.9 A partial-thickness burn and a full-thickness burn of identical size are treated identically for the first 24 hours but diverge completely thereafter. Explain both facts.

5.10 Why is the same 25-hydroxyvitamin D deficiency more likely in Adwoa at 78 than in Nia at 24, even if they spend the same time outdoors? Give at least three separate mechanisms.

Level 3 · Clinical Application

5.11 A 68-year-old with poorly controlled diabetes is admitted after a hip fracture and spends four days largely immobile. On day 5 a nurse notes a 4 cm area over the sacrum that is deep purple, does not blanch, feels boggy, and is warmer than the surrounding skin. The overlying skin is intact. What is this, why does the surface look intact, and what should be predicted?

5.12 A 30 kg child is scalded over the entire anterior trunk and the whole of the left arm. Calculate %TBSA and the first-hour fluid rate, and state two errors that would be made by using the adult rule of nines.

5.13 A patient presents with jaundice. Their skin is deeply pigmented and the color change is difficult to appreciate. Describe how you would assess them, and explain why your chosen sites work.

Level 4 · Integration and Synthesis

5.14 Construct a single causal chain from Amara's coronary occlusion to her capillary refill of 4 seconds, naming every system involved and identifying which links are negative feedback and which produce harm. Then explain why her blood pressure of 168/98 is not evidence against poor peripheral perfusion.

5.15 Argue that the skin should be classified as an endocrine, immune, and sensory organ as much as a protective covering, using at least four specific examples with the direction of causation. Then identify the single structural feature that makes all of these roles possible.

Concept Map to Complete

Copy this onto blank paper and fill every bracket from memory before checking.

                          THE INTEGUMENT
                                │
        ┌───────────────────────┼───────────────────────┐
   [ __________ ]         [ ________ ]           [ ___________ ]
    stratified sq.         2 layers:              areolar + adipose
    5 strata:              [ ________ ] (loose)   functions:
    1 [ _______ ] ← mitosis [ ________ ] (dense   [ ______ ] insulation
    2 [ _______ ]             irregular)          [ ______ ] padding
    3 [ _______ ] ← dies    contains ALL the      [ ______ ] storage
    4 [ _______ ] thick only [ __________ ]
    5 [ _______ ] = BARRIER   and the 2 vascular
      bricks = [ ________ ]   [ ________ ]
      mortar = [ ________ ]         │
          │                         │
    4 cell types:            AV ANASTOMOSES = the [ ________ ] valve
    [ __________ ] 90%        OPEN  → skin [ ____ ], heat [ ________ ]
    [ __________ ] pigment    SHUT  → skin [ ____ ], heat [ ________ ]
    [ __________ ] immune            controlled by sympathetic [ __ ]
    [ __________ ] touch                    ▲              ▲
                                            │              │
                              HYPOTHALAMUS ─┘              └─ BAROREFLEX
                              defends [ ______ ]     defends [ ________ ]
                                            │
                              ══ ONE EFFECTOR, TWO CONTROLLERS ══
                              distinguish them by measuring [ ________ ]
                                            │
        ┌───────────────────────────────────┴──────────────────────┐
   4 ROUTES OF HEAT LOSS                        HEALING depends on
   [ _________ ] ~60%   [ _________ ] ~22%      [ _____ ]:
   [ _________ ] ~15%   [ _________ ] ~3%       appendages survive →
   ALL BUT ONE REVERSE above skin temp:          [ ______________ ]
   the survivor is [ __________ ], and it        appendages destroyed →
   is limited by [ __________ ]                  [ ______________ ]

Lab / Self-Exploration

1. Time your own capillary refill, then break it. Press a fingernail firmly for 5 seconds, release, and count. Record the value. Now hold that hand in cold water for 60 seconds and repeat. Then hold it above your head for 30 seconds and repeat. You have just changed both variables in §5.3 — arteriolar tone and perfusion pressure — and you should be able to say which one each manoeuvre changed.
2. Map your own two-point discrimination. Bend a paperclip into a U and vary the gap. Find the smallest separation you can reliably feel as two points on the fingertip, the palm, the forearm, and the back of the shoulder. Expect roughly 2–4 mm, 10 mm, 30 mm, and 40–50 mm. Then explain the gradient using receptor type and density from §5.3.
3. Find your cleavage lines. Pinch the skin of your forearm and try to raise a fold running lengthwise along the limb, then one running around it. One direction lifts a crisp fold and one does not. Sketch the direction that resists, then predict where a surgeon would place an incision there and why.
4. Watch the thermal valve operate. Note the color and temperature of your hands, and whether the superficial forearm veins are visible. Now do two minutes of vigorous exercise and look again; then run cold water over your wrists for a minute and look a third time. Record color, temperature, and vein prominence at each stage, and account for all three using AV anastomoses and counter-current exchange.
5. Prove the barrier is lipid. Wash one forearm with a strong detergent soap and leave the other untouched. Two hours later compare them for tightness, flaking, and how they feel. Then apply a plain emollient to a patch of the washed arm and reassess after twenty minutes. You have removed and replaced the mortar of §5.2 — not the water.
6. Date a bruise, and audit a scar. If you have a bruise, photograph it daily and log the color sequence against the heme degradation pathway in §5.5. Separately, find a scar at least a year old and list every structure that failed to regenerate — hair follicles, sweat pores, pigmentation on tanning, normal light reflection. Each absence is one appendage the dermis did not rebuild.

Key Terms

Next: Chapter 6 · The Skeletal System I — where the vitamin D that begins in this chapter meets the calcium bank it was made to manage, and where Adwoa's bone density is measured.