Bone, joint & muscle,
mapped for boards.

OA vs RASpondyloarthropathiesGout

Osteoarthritis vs. Rheumatoid Arthritis — the core contrast

Systemic Juvenile Idiopathic Arthritis

• Presents before age 16 with daily spiking (quotidian) fevers, an evanescent salmon-pink macular rash that appears with the fever spikes, and arthritis in two or more joints
• Associated with anterior uveitis and a markedly inflammatory picture — leukocytosis, thrombocytosis, elevated ESR/CRP — that can mimic an occult infection or malignancy workup

Seronegative Spondyloarthropathies (HLA-B27 family)

• Shared features: rheumatoid factor negative, HLA-B27 association, axial/enthesis involvement, asymmetric peripheral arthritis

Crystal Arthropathies

• Allopurinol — xanthine oxidase inhibitor, blocks urate production; first-line chronic prophylaxis
• Probenecid — uricosuric, promotes renal urate excretion; avoid in patients with uric acid stones or sulfa allergy, and it is not used for an acute attack
• Lesch-Nyhan syndrome — X-linked HGPRT deficiency causing massive urate overproduction; triad of gout, intellectual disability, and compulsive self-mutilation

Infectious (Septic) Arthritis

• Orthopedic emergency — untreated infection destroys cartilage within days
• Nongonococcal: usually S. aureus/streptococci, monoarticular, positive synovial Gram stain/culture
• Gonococcal: most common cause of septic arthritis in sexually active young adults; migratory polyarthralgia with pustular rash, cultures often negative
• Lyme arthritis — late manifestation of Borrelia burgdorferi infection (tick-borne, Ixodes); look for a preceding erythema migrans (expanding "bull's-eye") rash and, in some patients, cardiac (AV block) or neurologic involvement earlier in the disease course
• Always tap the joint before starting antibiotics when septic arthritis is suspected

Polymyalgia Rheumatica & Its Vasculitis Partner

• Polymyalgia rheumatica — bilateral aching and morning stiffness of the shoulder and hip girdles in patients over 50, without true muscle weakness and with a normal CK; strongly associated with a markedly elevated ESR/CRP and a dramatic response to low-dose glucocorticoids
• Roughly a third of patients with polymyalgia rheumatica also have or go on to develop giant cell (temporal) arteritis — a granulomatous large-vessel vasculitis causing unilateral headache, jaw claudication, and scalp tenderness, with irreversible vision loss as the feared complication if untreated
• Because vision loss can be sudden and permanent, suspected giant cell arteritis is treated empirically with high-dose glucocorticoids before temporal artery biopsy (the confirmatory test) even returns

Fibromyalgia — the Great Mimic of Inflammatory Disease

• Chronic, widespread musculoskeletal pain lasting >3 months, most common in women 20–50 years old
• Accompanied by multiple tender points, fatigue, non-restorative sleep, paresthesias, and cognitive slowing ("fibro fog")
• Inflammatory markers (ESR, CRP) and imaging are normal — a key feature that separates it from the autoimmune and crystal arthropathies covered above, since there is no synovitis or joint destruction
• Management centers on regular aerobic exercise, cognitive behavioral therapy, and medications aimed at central pain processing — TCAs, SNRIs (duloxetine), and gabapentinoids — rather than anti-inflammatory or immunosuppressive therapy

OsteoporosisOsteomyelitisBone Tumors

Genetic & Congenital Bone Disorders

Acquired Metabolic Bone Disease

Other named metabolic entities

• Scurvy — vitamin C deficiency impairs prolyl/lysyl hydroxylase → defective collagen cross-linking → poor wound healing, perifollicular hemorrhage, gum bleeding
• Paget disease of bone — disordered osteoclast/osteoblast coupling of unclear etiology (possible paramyxoviral trigger); progresses through lytic → mixed → sclerotic phases; mosaic "cement line" pattern on histology; complications include high-output heart failure from AV shunting and secondary osteosarcoma
• Osteitis fibrosa cystica — hyperparathyroidism–driven resorption producing hemorrhagic "brown tumors"

Osteonecrosis (Avascular Necrosis)

• Final common pathway: interruption of the end-arterial blood supply to bone
• Mechanisms — vessel compression (steroids, most common overall cause), trauma/fracture disrupting the supply, intravascular occlusion (sickle cell disease, decompression/caisson disease, embolism), and less commonly SLE (vasculopathy plus steroid treatment) or Gaucher disease (lipid-laden macrophages infiltrating marrow and compromising local blood flow)
• Preferred sites: femoral head, scaphoid, talus, humeral head — areas with limited collateral flow
• Leads to secondary osteoarthritis if untreated

• Osteochondrosis is the umbrella term for avascular necrosis occurring at growing epiphyseal ossification centers in children
• Legg-Calvé-Perthes disease — idiopathic AVN of the femoral head in children; presents with an insidious limp and reduced hip internal rotation
• Osgood-Schlatter disease — traction apophysitis (not true AVN) at the tibial tuberosity, the patellar tendon insertion site, from repetitive quadriceps loading in adolescents

Infectious Bone Disease (Osteomyelitis)

Route: hematogenous seeding (children — metaphysis of long bones) vs. contiguous spread from adjacent infection/open fracture/surgery (adults). The metaphyses of the distal femur, proximal tibia, and proximal humerus are the classic hematogenous seeding sites — they're the most richly vascularized, slow-flow regions of the growing skeleton.

• Necrotic bone left behind by the infection forms a sequestrum
• New reactive bone laid down by the periosteum around it forms an involucrum — a shell that can wall off and perpetuate the infection

Bone & Cartilage Tumors

• Predisposing factors for osteosarcoma: Paget disease, prior radiation, hereditary retinoblastoma (RB1), Li-Fraumeni syndrome (germline TP53), and pre-existing bone infarcts
• Osteosarcoma is the single most common primary bone sarcoma in children, with Ewing sarcoma a close second
• Gardner syndrome — autosomal dominant FAP variant with colonic polyps plus skull osteomas, fibromas, thyroid cancer, epidermoid cysts, and sebaceous cysts

Distinguishing Bone Disorders by Lab Pattern

A single lab panel — calcium, phosphate, alkaline phosphatase, PTH — separates most of the metabolic bone diseases above at a glance.

Compartment SyndromeACL TearOveruse Syndromes

Orthopedic Emergency — Compartment Syndrome

• Fascial compartments are non-distensible — bleeding or edema (crush injury, fracture, reperfusion) raises intracompartmental pressure above capillary perfusion pressure
• Progressive ischemia of muscle and nerve within the compartment
• Classic exam findings — pain out of proportion to injury and pain with passive stretch are the earliest and most sensitive signs; pulselessness is a late finding
• Diagnosis can be confirmed with compartment pressure measurement; treatment is emergent fasciotomy

Named Fractures & Their Signature Displacements

Knee & Ankle Ligamentous Injury

• ACL tear — noncontact pivoting injury; positive anterior drawer and Lachman tests; frequently part of the "unhappy triad" with medial collateral ligament and medial meniscus injury from a lateral blow to a planted knee
• PCL tear — direct blow to the anterior tibia with the knee flexed (classically a dashboard injury in a car accident); positive posterior drawer test
• Collateral ligament tears — valgus stress (force from the lateral side) sprains the MCL; varus stress sprains the LCL; tested with gentle valgus/varus stress at 30° of knee flexion
• Meniscal tear — twisting injury on a weight-bearing knee; joint-line tenderness and a positive McMurray test (pain or a palpable click with combined flexion, rotation, and extension of the knee)
• Ankle sprain — inversion injury is far more common than eversion because the lateral ligament complex (anterior talofibular ligament first) is weaker than the medial deltoid ligament
  • Grade I: stretch, no instability
  • Grade II: partial tear
  • Grade III: complete tear, joint instability

Overuse / Entrapment Syndromes

Scoliosis

• Complex lateral curvature of the spine combined with vertebral rotation/torsion
• Most cases are idiopathic (typically adolescent); can also be congenital or secondary to a structural cause such as leg-length discrepancy, hip pathology, or a neuromuscular disorder (e.g., polio, cerebral palsy)

Pediatric Orthopedic Conditions

• Greenstick fracture — an incomplete fracture through one cortex, with the bone bending but not breaking on the opposite side; reflects the greater elastic flexibility of pediatric bone
• Torus (buckle) fracture — compressive axial loading buckles the cortex outward without a clear fracture line crossing the bone; typically at the metaphysis of the distal radius after a fall on an outstretched hand
• Both patterns are unique to the more pliable, still-growing pediatric skeleton and are managed more conservatively than a complete fracture in an adult

COX pathwayOpioid ReceptorsToxicology

The Arachidonic Acid Pathway

Acetaminophen vs. NSAIDs — Why They're Not Interchangeable

• Because acetaminophen lacks meaningful antiplatelet or GI-mucosal effects, it remains the preferred option in patients with peptic ulcer disease, platelet dysfunction/bleeding risk, or gout — settings where NSAIDs and aspirin are relatively contraindicated
• Low-dose aspirin's irreversible platelet COX-1 inhibition is exploited deliberately for cardioprotection, distinct from its higher-dose anti-inflammatory use
• Tramadol is a weak opioid-receptor agonist with additional serotonin/norepinephrine reuptake inhibition, commonly used for chronic osteoarthritis pain when NSAIDs are insufficient or contraindicated — note its added seizure risk and serotonergic interaction potential

Opioid Pharmacology

• Agonists at μ (primary analgesia), κ, and δ opioid receptors — Gi-coupled, hyperpolarize neurons and reduce neurotransmitter release
• Reserved for pain uncontrolled by NSAIDs/acetaminophen given the abuse and respiratory-depression liability
• Overdose triad: respiratory depression, miosis ("pinpoint pupils"), CNS depression — plus constipation and urinary retention; miosis results from disinhibited (enhanced) parasympathetic output via the Edinger-Westphal nucleus
• Naloxone — rapid-acting competitive antagonist for acute reversal; short half-life (~2h) may require redosing as it can be outlasted by the opioid it displaced
• Naltrexone — same receptor antagonism, much longer acting (up to 48h), used for relapse prevention rather than acute overdose reversal
• Methadone — long-acting agonist with lower euphoric potential, used for structured opioid-use-disorder maintenance/taper
• Meperidine carries a distinct risk of serotonergic CNS excitation/hyperpyrexia when combined with MAOIs — an important drug-interaction exception among the opioids
• At therapeutic doses several opioids (loperamide, diphenoxylate, codeine) are also used specifically for their antidiarrheal and antitussive gut/brainstem effects, separate from analgesia

Biologic Therapy for Inflammatory Joint & Skin Disease

• TNF-α inhibitors are not interchangeable in mechanism: etanercept is a decoy-receptor fusion protein (soluble TNF receptor bound to an IgG1 Fc fragment) that intercepts circulating TNF-α, while adalimumab and infliximab are monoclonal antibodies that bind TNF-α directly. All three raise infection risk — particularly reactivation of latent TB, since TNF-α is required to form and maintain granulomas — and can trigger drug-induced lupus
• Psoriasis biologics target the IL-23/IL-17 axis that drives psoriatic epidermal hyperproliferation: ustekinumab blocks IL-12/23 (the shared p40 subunit); guselkumab, risankizumab, and tildrakizumab block IL-23 alone; and secukinumab, ixekizumab target IL-17 itself, with brodalumab instead blocking the IL-17 receptor

Nerve Injury PatternsRoot Levels

Brachial Plexus — Organizing Principle

Roots (C5–T1) → Trunks (superior/middle/inferior) → Divisions (anterior/posterior) → Cords (lateral/posterior/medial, named for their position around the axillary artery) → Branches. Rather than memorizing the whole diagram, anchor high-yield lesions to a mechanism.

• Carpal tunnel contents at the wrist: tendons of flexor digitorum superficialis, flexor digitorum profundus, and flexor pollicis longus, plus the median nerve itself — the flexor carpi radialis and palmaris longus tendons run outside the tunnel
• Wrist drop is not unique to radial nerve trauma — it is also a classic finding in lead poisoning, from lead-induced peripheral neuropathy
• The median nerve has two other injury sites worth knowing beyond the supracondylar/carpal tunnel pattern: fracture of the distal third of the humerus or elbow region (causing complete loss of thumb opposition), and lacerating "slashing" injuries at the wrist

Shoulder — Rotator Cuff Muscles

Four muscles stabilize the glenohumeral joint by compressing the humeral head into the shallow glenoid fossa throughout the arc of motion — remembered with the mnemonic SItS.

• Full overhead abduction is a team effort: supraspinatus starts it (0–15°), the deltoid drives the bulk of the arc (15–90°), and upward rotation of the scapula itself (via trapezius and serratus anterior) contributes the final degrees past 90°
• Chronic impingement of the supraspinatus tendon under the acromion is the usual mechanism behind rotator cuff tears and the subacromial bursitis already noted in the trauma section below — pain classically worsens with overhead reaching and disrupts sleep on the affected side

Hand — Intrinsic Muscles & the Claw Hand Spectrum

• The intrinsic hand muscles split almost entirely along a median/ulnar line, which is why the pattern of weakness after each nerve injury is so predictable
• Median nerve supplies the thenar muscles (opposition, abduction, and flexion of the thumb) plus the first and second lumbricals
• Ulnar nerve supplies almost everything else in the hand: the hypothenar muscles, all the interossei (palmar = adduct the fingers toward the middle finger — "PAD"; dorsal = abduct the fingers away from it — "DAB"), the third/fourth lumbricals, and adductor pollicis
• Lumbricals flex the metacarpophalangeal joints while extending the interphalangeal joints — losing them is what tips the balance toward clawing

Lumbosacral Plexus (L1–S4)

• Lumbar plexus (L1–L4) supplies anterior thigh/hip flexors — femoral and obturator nerves are the major branches
• Sacral plexus (L4–S4) supplies the posterior thigh, leg, and foot via the sciatic nerve and its tibial/common peroneal divisions
• Nearly every nerve of the sacral plexus, plus the pudendal nerve, exits the pelvis through the greater sciatic foramen passing below the piriformis muscle — the superior gluteal nerve is the lone exception, passing above it, which is why piriformis syndrome tends to selectively spare hip abduction while affecting other sacral plexus territory

Hip Muscle Actions

Segmental Nerve Levels Worth Memorizing (Lumbosacral)

Peripheral Nerve Injury & Regeneration

SLEMarfan / Ehlers-DanlosAutoantibodies

Systemic Lupus Erythematosus

• Prototypical multisystem autoimmune disease from immune complex deposition; strongly female-predominant (roughly 9:1 during reproductive years), with a disproportionately higher incidence and severity in Black women
• Organ involvement
  • Skin — malar ("butterfly") rash, discoid lesions, photosensitivity
  • Renal — immune-complex glomerulonephritis, ranging from mesangial to diffuse proliferative disease with subendothelial "wire-loop" deposits
  • Cardiac — Libman-Sacks endocarditis (sterile verrucous vegetations on both surfaces of the mitral valve), pericarditis
  • Hematologic — cytopenias, antiphospholipid antibody–driven hypercoagulability (despite a paradoxically prolonged PTT in vitro, since the antibody interferes with the phospholipid substrate used in the lab assay, not with clotting in the living patient)
  • Serositis (pericarditis, pleuritis), pulmonary fibrosis/diffuse alveolitis, arthralgia, Raynaud phenomenon, cotton-wool spots on funduscopic exam

Raynaud Phenomenon

• Cold- or stress-triggered vasospasm of digital arterioles produces the classic white → blue → red sequence: pallor from ischemia, cyanosis from hypoxia, then rubor as blood flow returns
• Primary (Raynaud disease) — idiopathic, typically young women, symmetric, no tissue damage
• Secondary (Raynaud syndrome) — associated with an underlying connective tissue disease (systemic sclerosis/CREST, SLE, mixed connective tissue disease); more likely to be asymmetric and to progress to digital ulceration from critical ischemia
• First-line treatment is calcium channel blockers, which relax the vascular smooth muscle driving the spasm

Other Autoimmune Connective Tissue Diseases

Heritable Disorders of Connective Tissue

Sliding FilamentMyasthenia GravisDuchenne

Excitation-Contraction Coupling

Comparing the Three Muscle Types

Type I vs Type II Skeletal Fibers

Neuromuscular Junction Disease

Muscle Wasting

• Net loss of muscle mass and strength when catabolic signaling (ubiquitin-proteasome pathway, autophagy) outpaces anabolic drive — a final common pathway for several distinct triggers: disuse/immobilization, lower motor neuron denervation, cachexia from chronic disease (TNF-α/IL-1/IL-6 driven), and endocrine causes like Cushing syndrome or hyperthyroidism
• CK is a useful discriminator — normal in disuse atrophy, steroid myopathy, and age-related sarcopenia, but elevated in the inflammatory myopathies (polymyositis/dermatomyositis)
• Sarcopenia — the age-related decline in muscle mass and strength from falling IGF-1/mTOR signaling; managed with resistance exercise and adequate protein intake

Myositis Ossificans

• Heterotopic (ectopic) bone formation within skeletal muscle, classically the quadriceps, following blunt trauma
• Presents as a firm, painful, enlarging soft tissue mass that can easily be mistaken for a sarcoma on imaging or exam
• Characteristic "eggshell" peripheral calcification pattern on imaging; histology shows metaplastic bone surrounding a zone of reactive fibroblastic proliferation — a benign process despite its alarming presentation

Other Muscle Metabolic & Mitochondrial Disease

• Lactic acidosis — excess anaerobic metabolism from shock, sepsis, toxin exposure (methanol, metformin), or hepatic failure; presents as an elevated anion-gap metabolic acidosis with markedly increased serum lactate and can progress to coma if uncorrected
• Mitochondrial myopathy — mutations in mitochondrial DNA, inherited exclusively through the maternal line since sperm mitochondria are not transmitted; proximal weakness with characteristic "ragged red fibers" on muscle biopsy (subsarcolemmal mitochondrial aggregates on trichrome stain)

Muscular Dystrophies

• Duchenne — X-linked recessive, frameshift/deletion mutation causing near-total absence of dystrophin, which normally anchors the cytoskeleton to the membrane; progressive proximal weakness beginning in early childhood, calf pseudohypertrophy (early true muscle hypertrophy is progressively replaced by fat and connective tissue as the disease advances, so the calf stays enlarged even as function is lost), positive Gower sign, markedly elevated CK, wheelchair dependence and cardiomyopathy leading to early death
• Becker — same gene (dystrophin, locus Xp21), in-frame mutation → partially functional dystrophin → milder, later-onset course

Soft Tissue Muscle Tumors

Neuromuscular Blockade (Pharmacology)

• Neuromuscular blockers fall into two functional classes — centrally acting agents and peripheral neuromuscular endplate (NMEP) blockers, which are further split into depolarizing and non-depolarizing types

Peripheral (NMEP) — depolarizing

• Succinylcholine is the only depolarizing agent in clinical use — it activates rather than blocks the nicotinic receptor
• Phase 1 block — sustained receptor activation produces visible fasciculations, then flaccid paralysis as the receptor stays depolarized and unresponsive to further stimulation
• Phase 2 block — with prolonged exposure the endplate repolarizes but the receptor remains desensitized, mimicking a non-depolarizing block
• Rapidly hydrolyzed by plasma cholinesterase (not acetylcholinesterase), giving a short duration of action — ideal for rapid-sequence intubation and electroconvulsive therapy
• Can trigger malignant hyperthermia in genetically susceptible patients, classically when combined with a volatile anesthetic like halothane — treat with dantrolene and active cooling

• Paralysis order: small fast-twitch muscles (face/eyes) first → limbs/trunk → diaphragm last; recovery proceeds in reverse

Epidermal LayersPigmentary DisordersMelanoma

Epidermal Architecture (Deep to Superficial)

• Basal layer is the mitotically active source for the other four — epidermis fully turns over roughly every 3–4 weeks
• Epidermis is ectodermal in origin; dermis is mesodermal
• Melanocytes are neural crest–derived, residing in the basal layer
• Stratum lucidum is present only in thick (glabrous) skin — palms, soles
• Core functions of skin: barrier against infection, thermoregulation, and protection against fluid/water loss (desiccation)

Epithelial cell junctions

• Tight junctions (claudins/occludins) seal the space between adjacent cells, blocking free paracellular movement of solutes
• Adherens junctions form a continuous adhesive belt using cadherins, linking the actin cytoskeletons of neighboring cells — losing E-cadherin is a well-known step that promotes cancer metastasis
• Desmosomes are spot-welds that anchor intermediate filaments between adjacent keratinocytes via desmoglein; autoantibodies against desmoglein cause pemphigus vulgaris
• Hemidesmosomes anchor the deepest keratinocytes to the underlying basement membrane; autoantibodies here cause bullous pemphigoid
• Gap junctions (connexons) allow direct electrical and chemical communication between adjacent cell cytoplasms

Describing a Lesion — The Vocabulary Exam Questions Assume You Know

Dermatology questions lean heavily on precise descriptive terms — the size and depth cutoffs below are what turn one term into another.

Histologic descriptors

Pigmentary & Inflammatory Skin Disease

Papulosquamous & Common Inflammatory Disorders

Skin & Soft Tissue Infections

Blistering (Bullous) Skin Disorders

Other blistering & severe cutaneous drug reactions

Cutaneous Ulcers

Vascular & Soft Tissue Tumors of Skin

Burn Classification

Burn extent is estimated with the "rule of 9s": each arm ≈ 9% of total body surface area, each leg ≈ 18%, the anterior and posterior trunk ≈ 18% each, the head ≈ 9%, and the perineum ≈ 1% — a quick way to gauge severity and fluid resuscitation needs at the bedside.

Skin Cancer — Compare & Contrast

Osteoblast/OsteoclastPTH · Vitamin D · Calcitonin

The Bone Remodeling Unit

• Osteocyte — former osteoblast trapped in a lacuna, connected to neighbors via canalicular processes; senses mechanical strain and orchestrates local remodeling

Calcium-Regulating Hormones

OssificationSomitesPharyngeal Arches

Two Routes of Bone Formation

Muscle Origin From Somites

• Paraxial mesoderm segments into somites along the neural tube
• Each somite differentiates into three compartments
  • Sclerotome → vertebrae and ribs
  • Myotome → skeletal muscle of that segment
  • Dermatome → the overlying dermis of the skin
• This segmental organization is why a single dermatome/myotome pairing can localize a spinal level clinically

Pharyngeal Arch Derivatives

Neural crest–derived mesenchyme populates six arches (5 forms, arch 5 regresses); each carries its own artery, cartilage bar, nerve, and muscle group. Reasoning through nerve → muscle is far more testable than memorizing lists.

Direct vs IndirectHesselbach Triangle

Inguinal Canal Walls & Contents

• Contents in males — spermatic cord (vas deferens, testicular artery, pampiniform venous plexus, genital branch of the genitofemoral nerve) plus the ilioinguinal nerve running alongside (not truly within the cord)
• Contents in females — round ligament of the uterus, plus the ilioinguinal nerve
• Ilioinguinal nerve carries sensation to the anterior labia/scrotum and medial thigh

The Inguinal Canal in One Landmark: The Inferior Epigastric Vessels

Nearly every testable question about groin hernias reduces to the position of a defect relative to the inferior epigastric artery.