Skin & Appendages

As a keratinocyte travels from basale to corneum it switches on a sequence of structural proteins as predictable as a recipe. At the bottom it makes a “soft” keratin pair (K5/K14) that lets it divide and stretch. The moment it commits to differentiation in the spinosum it swaps for a “hard” pair (K1/K10) that bundles into tonofilaments and gives the cell its mechanical strength. In the granulosum it begins to build the cornified envelope — loricrin and involucrin are cross–linked under the plasma membrane by transglutaminases, while profilaggrin is cleaved to filaggrin, which then bundles the keratin filaments into the dense matrix you will see as bright pink keratin.

At the same time, granulosum cells dump the contents of their lamellar bodies (Odland bodies) into the intercellular space — glycolipids, sterols and free fatty acids that solidify into the lipid mortar between the corneocytes. This lipid is the waterproof barrier of the skin. Lose the granulosum, and you lose the ability to hold water in: that is exactly what happens in severe burns and in filaggrin–deficient ichthyosis.

Thick versus thin skin is the second classic compare–and–contrast. Once you understand that thick skin exists because palms and soles must take heavy mechanical wear and produce a lot of cooling sweat, every difference falls out logically: more strata for armour, dermal ridges to lock the epidermis onto the dermis like Velcro, no hair (which would be uncomfortable to grip with), no sebaceous glands (oil + grip do not mix), and a forest of eccrine glands for thermoregulation.

Recall Protein switch: K5/K14 (basale) → K1/K10 (spinosum) → filaggrin + loricrin + involucrin (granulosum) → cross–linked envelope (corneum). Lamellar bodies = lipid mortar = water barrier. Thick skin = palms/soles, all 5 layers, no hair, no sebaceous. Pemphigus vulgaris = anti–desmoglein, intra–epidermal; bullous pemphigoid = anti–hemidesmosome, sub–epidermal.

Melanocytes are wanderers. Embryologically they come from the neural crest, migrate during development through the dermis and finally take up residence in the stratum basale, where they sit on the basement membrane between keratinocytes. On routine H&E they look like small rounded cells with a pale halo around the nucleus — this halo is partly fixation artefact and partly the fact that their dendritic processes do not stain. Special stains (DOPA reaction, S100, HMB–45, Melan–A) reveal long branching dendrites that reach up into the spinosum, each one delivering pigment to neighbouring keratinocytes.

Inside the melanocyte, the enzyme tyrosinase oxidises tyrosine through DOPA to produce melanin, which is packaged in lysosome–like organelles called melanosomes. There are two pigments: brown–black eumelanin and red–yellow pheomelanin. The ratio is genetically set and tunes your skin and hair colour. Fully packed melanosomes are then transferred to keratinocytes by a unique mechanism called cytocrine secretion — the dendrite tip is essentially phagocytosed by the keratinocyte. Inside the keratinocyte the melanin granules pile up like a cap on the sun–facing side of the nucleus and physically absorb UV photons before they can damage DNA. Skin colour difference is not the number of melanocytes (everyone has roughly the same number) but the size and distribution of melanosomes.

Recall Melanocyte = neural crest, basal layer, dendritic. Tyrosinase converts tyrosine → melanin in melanosomes. Cytocrine transfer to keratinocytes; melanin caps the nucleus for UV shielding. Eumelanin (brown) vs pheomelanin (red). Vitiligo = autoimmune loss; albinism = tyrosinase defect; melanoma = malignancy, Breslow depth prognostic.

Two cells with similar–sounding names but completely different jobs share the epidermis. Langerhans cells are immune cells: bone–marrow–derived dendritic cells that live mainly in the stratum spinosum, where they patrol the epidermis like security guards. They pick up foreign antigens (microbes, contact allergens), migrate down through the dermis to a draining lymph node and present those antigens on MHC class II to naive T cells. On electron microscopy they have a unique tennis–racquet–shaped granule called the Birbeck granule, which is essentially endocytic. They are the front line in contact dermatitis (think nickel allergy, poison ivy) and are also the cell of origin of Langerhans cell histiocytosis.

Merkel cells, in contrast, are sensory. They sit in the stratum basale, often clustered in “touch domes” on fingertips and lips, and form synapse–like contacts with a flattened terminal of a sensory nerve (the Merkel disc). Together they form a slowly–adapting mechanoreceptor exquisitely sensitive to steady pressure and fine spatial detail — the receptor you use when reading Braille or feeling the shape of a key in your pocket. Their malignant counterpart, Merkel cell carcinoma, is a rare but aggressive neuroendocrine skin tumour associated with Merkel cell polyomavirus.

Recall Langerhans = bone marrow origin, spinosum, dendritic APC, MHC II, Birbeck granule, contact dermatitis. Merkel = basal, mechanoreceptor for fine touch, synapses with sensory nerve, neuroendocrine origin, Merkel cell carcinoma (polyomavirus).

A hair follicle is a cylindrical down–growth of epidermis into the dermis, and on a longitudinal section you can read it like a set of nested tubes. From outside in you cross a connective–tissue sheath, a glassy membrane (a thickened basement membrane), the external root sheath (which is continuous with surface epidermis and is the stem–cell reservoir), the internal root sheath in three sub–layers (Henle's, Huxley's and the IRS cuticle), and finally the hair shaft itself with its cuticle, cortex and medulla.

All of these layers are born from the same place: the matrix at the bottom of the bulb, a cap of rapidly dividing keratinocytes sitting on the dermal papilla. The dermal papilla is a small lump of vascularised connective tissue that signals to the matrix — it is the inductive switch for the entire follicle. Knock out the papilla and the hair stops growing; surgical hair transplants succeed only when the papilla travels with the graft.

Every hair lives a three–stage life cycle. Anagen is active growth, lasting years for scalp hairs and weeks for eyebrows — that ratio determines maximum length. Catagen is a brief regression in which the follicle shrinks and the bulb retracts upward. Telogen is the resting phase; the old shaft is held loosely until a new anagen pushes it out. About 85–90% of scalp hairs are in anagen at any moment; physiological or emotional shocks can synchronise many hairs into telogen and produce diffuse shedding (telogen effluvium) months later.

Recall Hair follicle layers out→in: CT sheath / glassy BM / ERS (with bulge stem cells) / IRS (Henle → Huxley → cuticle) / hair shaft (cuticle/cortex/medulla). Matrix on dermal papilla = growth engine. Cycle: anagen (growth) → catagen (regression) → telogen (rest). Arrector pili = smooth muscle attached at bulge.

The eccrine sweat gland is the most abundant of all skin appendages and the master thermoregulator. On a section you will see two very different epithelial profiles for one gland: a deep secretory coil sitting in the deep dermis or hypodermis, and a duct that climbs up through the dermis, corkscrews into the epidermis and opens directly on the surface as a sweat pore. They differ in epithelium, function and staining.

The secretory coil is a simple columnar/cuboidal tube with three cell types: pale clear cells rich in mitochondria that secrete the watery primary fluid (an isotonic NaCl solution), darker mucoid (dark) cells with apical glycoprotein granules, and underneath them flat myoepithelial cells that contract on sympathetic command to squirt the primary secretion into the duct. The duct then becomes a two–layered stratified cuboidal epithelium, stains slightly darker, and actively reabsorbs Na⁺ (and Cl⁻ follows) from the lumen so that the final sweat reaching the skin is hypotonic.

Recall Eccrine gland = simple coiled tubular merocrine. Coil (simple cub/columnar) = clear + dark + myoepithelial cells → isotonic primary secretion. Duct (stratified cuboidal, 2 layers) = reabsorbs Na⁺/Cl⁻ → final sweat hypotonic. CF = defective Cl⁻ reabsorption → salty sweat → sweat chloride test. Cholinergic sympathetic innervation.