Barrier Function
The skin is the body's primary barrier against the external environment. The stratum corneum provides physical, chemical, and microbial defense through its layered keratinocytes, lipid bilayers (ceramides, cholesterol, fatty acids), and acidic pH (~5.5 "acid mantle").
| Barrier Type | Mechanism | Key Molecules |
|---|---|---|
| Physical | Dense keratin in stratum corneum; tight junctions between keratinocytes | Filaggrin (loss-of-function mutations → atopic dermatitis) |
| Chemical | Acid mantle (pH 5.5) inhibits many pathogens; sebum with antimicrobial lipids | Fatty acids, defensins, lysozyme |
| Microbial (microbiome) | Commensal bacteria compete with pathogens | Cutibacterium acnes (normal flora at low levels) |
| Fluid | Prevents transepidermal water loss (TEWL) | Ceramides (lamellar bodies); lost in atopic dermatitis, burns |
⭐ Filaggrin and Atopic DermatitisFilaggrin mutations → impaired skin barrier → allergen penetration → sensitization → atopic dermatitis. The "atopic march": eczema → allergic rhinitis → asthma. Emollient therapy reinforces the barrier and reduces sensitization.
Thermoregulation
The hypothalamus (preoptic area) is the thermostat of the body (setpoint ~37°C). The skin is the primary effector organ for heat loss and heat conservation.
| Mechanism | Hot Environment | Cold Environment |
|---|---|---|
| Blood flow | Vasodilation of cutaneous vessels → heat radiation (up to 50-70% of heat loss) | Vasoconstriction → shunting blood to core |
| Sweating | Eccrine sweat evaporation → latent heat loss (most effective mechanism) | Absent |
| Piloerection | Absent | Arrector pili contract → "goosebumps" → traps air (minimal in humans) |
| Shivering | Absent | Involuntary muscle contractions → heat production |
| Non-shivering thermogenesis | Absent | Brown adipose tissue (UCP-1) → heat production (important in neonates) |
🩹 Heat Stroke vs Heat ExhaustionHeat exhaustion: profuse sweating, weakness, pale/cool skin, normal mentation, temp below 40°C. Heat stroke: HOT DRY skin (anhidrosis — thermoregulatory failure), altered mental status, temp above 40°C — medical emergency. Treatment: aggressive cooling.
Cutaneous Immune Function
- Langerhans cells — dendritic cells in stratum spinosum; capture antigens → migrate to lymph nodes → present to T cells → adaptive immunity
- Mast cells — dermis; IgE-mediated degranulation → histamine, tryptase, prostaglandins → urticaria, anaphylaxis, angioedema
- Keratinocytes — produce cytokines (IL-1, IL-6, TNF-alpha) → innate immune response; can present antigen
- Dermal macrophages — phagocytosis; cytokine production
- T cells — skin-resident memory T cells provide local adaptive immunity
⭐ Urticaria PathophysiologyIgE-mediated mast cell degranulation → histamine release → dermal edema (wheal) + erythema (flare) + pruritus. Acute: usually IgE-mediated (food, drug, insect). Chronic (greater than 6 weeks): usually autoimmune (anti-IgE receptor antibodies). Treatment: non-sedating antihistamines (H1 blockers); omalizumab (anti-IgE) for refractory cases.
Vitamin D Synthesis
The skin is the site of vitamin D3 synthesis: UV-B radiation (290-315 nm) converts 7-dehydrocholesterol (in keratinocytes) → previtamin D3 → vitamin D3 (cholecalciferol). Then: liver 25-hydroxylation → 25-OH vitamin D (storage form, measured in serum) → kidney 1-alpha-hydroxylation → 1,25-dihydroxyvitamin D (calcitriol, active form).
🧐 Vitamin D Activation Steps"Skin makes, Liver stores, Kidney activates." UV-B → D3 (skin) → 25-OH-D3 (liver) → 1,25-(OH)2-D3 (kidney). PTH stimulates final step. Calcitriol increases intestinal Ca2+ and PO4 absorption, bone mineralization, and renal Ca2+ reabsorption.
Wound Healing Phases
| Phase | Timing | Key Cells / Events |
|---|---|---|
| Hemostasis | Immediate (seconds-minutes) | Platelet aggregation; clot formation; thromboxane A2 and serotonin cause vasoconstriction |
| Inflammation | Hours to day 4 | Neutrophils (days 1-2) → macrophages (days 2-4); debridement; cytokine release; VEGF, TGF-beta |
| Proliferation | Days 4-21 | Fibroblasts: collagen III synthesis + granulation tissue; myofibroblasts: wound contraction; angiogenesis; re-epithelialization |
| Remodeling | Weeks to years | Collagen III replaced by collagen I; scar matures; max tensile strength 80% of original at 3 months |
🩹 Keloid vs Hypertrophic ScarHypertrophic scar: confined to original wound margins; regresses spontaneously; responds to pressure therapy. Keloid: grows BEYOND wound margins; does NOT regress; higher risk in African Americans, earlobes, sternum; treatment: intralesional steroids, silicone gel, surgical excision (often recurs).
Clinical Pearls
⭐ Psoriasis PhysiologyT-cell mediated autoimmune activation → IL-17, IL-23 → keratinocyte hyperproliferation → acanthosis (epidermal thickening), parakeratosis (nuclei retained in stratum corneum), Munro microabscesses. Stratum corneum transit time reduced from 14 days to 4 days. Targets for treatment: TNF-alpha, IL-17, IL-23.
🧐 Sweat Gland Innervation TrickEccrine sweat glands are sympathetically innervated BUT use ACh (not NE) as neurotransmitter. This is the ONLY sympathetic postganglionic neuron that releases ACh. All others release NE. Anticholinergics (atropine, scopolamine) → anhidrosis and hyperthermia by blocking sweat glands.