Musculoskeletal System, Skin & Subcutaneous Tissue
Musculoskeletal System
Bone biology
Osteoblasts form bone, express alkaline phosphatase, and secrete RANK ligand; osteoclasts resorb bone under RANK stimulation and are TRAP positive. PTH drives bone resorption indirectly, vitamin D increases gut calcium absorption, calcitonin inhibits osteoclasts, and estrogen restrains osteoclast activity. Osteoporosis is low bone mass with normal mineralization; osteomalacia is defective mineralization with low calcium and phosphate; Paget disease shows mosaic bone with elevated alkaline phosphatase but normal calcium and phosphate; osteopetrosis shows dense but brittle bone from failed resorption.
Muscle and junction
A sarcomere spans Z line to Z line, with actin sliding over myosin; calcium binds troponin C, moving tropomyosin. T-tubule depolarization activates the dihydropyridine receptor, which opens the ryanodine receptor and releases sarcoplasmic reticulum calcium. Type I fibers are slow oxidative and fatigue resistant; type II are fast glycolytic. Myasthenia gravis is postsynaptic with decremental response and improvement with rest; Lambert-Eaton is presynaptic, incremental, and associated with small cell lung cancer; botulism prevents acetylcholine release.
Joints and injury
Osteoarthritis involves weight-bearing joints with osteophytes and joint space narrowing; rheumatoid arthritis is symmetric, involves MCP and PIP joints, and is associated with anti-CCP. Gout shows needle-shaped, negatively birefringent crystals; pseudogout shows rhomboid, positively birefringent calcium pyrophosphate crystals in the knee. Fracture complications include fat embolism, compartment syndrome, nonunion, and avascular necrosis of the scaphoid, femoral head, and talus.
Traps
Reading alkaline phosphatase without calcium and phosphate in metabolic bone disease. Mixing pre- and postsynaptic neuromuscular disease. Calling any monoarthritis gout without aspirating.
Worked rule
Needle-shaped, negatively birefringent crystals equal gout; rhomboid, positively birefringent crystals equal pseudogout.
Skin & Subcutaneous Tissue
Structure
Epidermis matures from basal layer to stratum corneum over about 28 days; melanocytes derive from neural crest; Langerhans cells are antigen presenting; Merkel cells mediate light touch. The dermis contains collagen and elastin; the subcutis contains fat. Deep burns and pressure injury are staged by depth, and wound healing proceeds through hemostasis, inflammation, proliferation, and remodeling. Hypertrophic scars stay within the wound; keloids extend beyond it.
Blistering disease
Pemphigus vulgaris targets desmoglein 3 and causes intraepidermal acantholysis, flaccid bullae, oral erosions, and a positive Nikolsky sign. Bullous pemphigoid targets hemidesmosomal antigens and causes a subepidermal split with tense bullae in elderly patients and a negative Nikolsky sign. Dermatitis herpetiformis shows granular IgA at dermal papillae and is associated with celiac disease.
Tumors
Basal cell carcinoma is the most common skin cancer: pearly papule with telangiectasia, palisading nuclei, local invasion but rare metastasis. Squamous cell carcinoma shows keratin pearls and intercellular bridges, arising from actinic keratosis, with metastatic potential. Melanoma is graded by Breslow depth, shows asymmetric borders, and is associated with BRAF mutations. Kaposi sarcoma is linked to HHV-8.
Inflammatory patterns
Psoriasis shows silvery scale over extensor surfaces with parakeratosis and Munro microabscesses. Atopic dermatitis is pruritic with flexural distribution. Erythema multiforme has target lesions; Stevens-Johnson syndrome and toxic epidermal necrolysis involve mucosal sloughing and epidermal detachment.
Traps
Using Nikolsky sign without knowing which disease it supports. Assuming all pigmented lesions need biopsy by size alone. Confusing cellulitis with stasis dermatitis.
Worked rule
Intraepidermal acantholysis causes flaccid bullae with a positive Nikolsky sign; a subepidermal split causes tense bullae with a negative Nikolsky sign.