Muskuloskeletal System Flashcards
Name the carpal bones
Some = scaphoid (most common break)
Lovers = Lunate (most common dislocation)
Try = triquentum
Positions = pisiform
That = trapezium (by the thumb)
They = trapezoid (looks like a trapezoid)
Can’t = capitate
Handle = hamate
Denosumab
Monoclonal antibody against RANKL
Indicated for treatment of osteoporosis
Osteopetrosis
Carbonic anhydrase II defect leads to decreased acidification and failure of osteoclasts
Abnormally thick, stone-like but brittle bone, long ends of the bone are thicker than the middle (Erlenmeyer flask deformity)
Bone fills marrow space → pancytopenia, extramedullary hematopoiesis
Narrowing foramina → cranial nerve impingement and palsies
Tx: bone marrow transplant
Rickets/Osteomalacia
Vitamin D deficiency → defective mineralization/calcification of osteoid
Rickets in children - bowed legs, pigeon-break deformity, enlarged forehead, rachitic rosary
Osteomalacia in adults - soft bones
Labs: ↓ calcium, ↓ phosphate, ↑ PTH, ↑ ALP
Paget disease of bone
Imbalance between osteoclast and osteoblast activity
Increased bone but disordered and weak → fractures easily
Mosaic pattern of woven and lamellar bone (see picture)
Increasing hat size, nerve compression → hearing loss
↑ risk of osteosarcoma
Labs normal except ↑ ALP
Tx: calcitonin, bisphosphonates
Stages:
- Osteolytic via osteoclasts
- Mixed
- Osteosclerotic via osteoblasts
Osteogenesis Imperfecta
Autosomal dominant defect in synthesis of collagen type 1 by osteoblasts, fibroblasts → impairmement of bone matrix formation
Type II is fatal in utero
Type I - increased fractures in childhood, blue sclera (thinning of scleral collagen exposes choroidal veins), hearing loss, dental abnormalities, often mistaken for child abuse
Giant cell tumor
Benign tumor in the epiphyseal end of long bones, especially the knee
20-40 y/o
Multinucleated giant cells in a background of stromal cells
“Soap bubble” appearance on x-ray
Osteochondroma
Most common benign tumor of bone
Males < 25 y/o
Osteosarcoma
Malignant mesenchymal tumor of osteoblasts often found in the metaphysis of long bones (femur, tibia)
Bimodal distriution: 10-20, > 60 y/o
Risk factors include: Paget disease of the bone, bone infarcts, familial retinoblastoma, Paget disease, radiation exposure, Li-Fraumani (germline p53 mutation)
Codman triangle (elevation of periosteum) or sunburst pattern on x-ray
20% have pulmonary metastases at time of diagnosis
Tx: resection + chemotherapy
Ewing sarcoma
Malignant tumor of poorly-differentiated cells derived from neuroectoderm commonly in diaphysis of long bones, pelvis scapula, ribs
Associated with t(11;22)
Boys < 15 y/o
Onion-skin layering, IMC stain for CD99
Tx: neoadjuvant chemo, surgery, radiation
Chondrosarcoma
Malignant cartilaginous tumor
Expansile glistening mass within the medullary cavity
X-ray findings for osteoarthritis vs. rheumatoid arthritis
Osteoarthritis: subchondral cysts, sclerosis, osteophytes, eburnation, joint space narrowing
Rheumatoid arthritis: pannus formation, one and cartilage erosions, increased synovial fluid
Clinical features of osteoarthritis vs. rheumatoid arthritis
Osteoarthritis: DIP involvement, Heberden nodes (DIP), Bouchard nodes (PIP), no MCP involvement, pain increases with use
Rheumatoid arthritis: DIP sparing, subcutaneous rheumatoid nodules (fibrinoid necrosis), ulnar deviation of fingers, Baker cyst, morning stiffness that improves with use
Sjogren Syndrome
Autoimmune destruction of exocrine glands (especially lacrimal and salivary)
Characterized by xeropthalmia, xerostomia, bilateral parotid enlargement → dental caries, MALT lymphoma
Anti-SS-A/Ro and anti-SS-B/La
Gout vs. pseudogout crystals
Gout = monosodium urate crystals are negatively birefringent, needle-shaped, yellow in parallel light and blue in perpendicular light
Acute tx: NSAIDs, glucocorticoids, colchicine
Chronic tx: allopurinol, febuxostat (xanthine oxidase inhibitors)
Pseudogout = calcium pyrophosphate crystals are weakly positively birefringent, rhomoid-shaped, and blue in parallel light
Tx: NSAIDs, glucocorticoids, colchicine
Polymyositis
Autoimmune endomysial inflammation with CD8+ T cells (overexpression of MHC class I on the sarcolemma)
Characterized by progressive symmetric proximal muscle weakness, often involving the shoulders
Labs: ↑ CK, +ANA, + anti-Jo-1 (histidyl-tRNA synthase), + anti-SRP, + anti-Mi-2
Complications: interstitial lung disease, myocarditis
Tx: steroids
Dermatomyositis
Autoimmune perimysial inflammation with CD4+ T cells
Characterized by progressive symmetric proximal muscle weakness, malar rash, Gottron papules, heliotrope rash, “shawl and face” rash, “mechanic’s hands”
↑ risk of occult malignancy
Labs: ↑ CK, +ANA, + anti-Jo-1, + anti-SRP, + anti-Mi-2
Tx: steroids
Myasthenia gravis
Autoantibodies to postsynaptic acetylcholine receptors
Characterized by ptosis, diplopia, weakeness that worsens with muscle use
Associated with thymoma, thymic hyperplasia
Tx: acetylcholinesterase inhibitors
Lambert-Eaton
Autoantibodies to presynaptic voltage-gated calcium channel → ↓ acetylcholine release
Characterized by proximal muscle weakness and improves with muscle use, autonomic symptoms (dry mouth, impotence), cranial nerve involvement (esp. oculobulbar)
Associated with small cell lung cancer
Systemic sclerosis
Excessive fibrosis and collagen deposition
Diffuse scleroderma: widespread skin involvement, rapid progression, early visceral invovlement (renal, pulmonary, cardiovascular, GI), anti-DNA topoisomerase I/Scl-70
Limited scleroderma/CREST: involvement limited to skin of fingers and face, calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia, anti-centromere
Cx: pulmonary arterial hypertension → cor pulmonale → right heart failure
Albinism
Failure of neural crest cell migration or normal melanocyte number with decreased melanin production due to decreased tyrosinase actiity of defective tyrosine transport
↑ risk of skin cancer
Psoriasis
Chronic inflammatory dermatosis causing excessive keratinocyte proliferation, possibly autoimmune
Sharply demarcated erythematous or salmon-colored papules and plaques covered by white, silvery scales, on the scalp, sacral region, extensor surfaces of the extremities, umbilicus, penis, nails
Epithelial hyperplasia (acanthosis), parakeratotic scaling (excess keratin and retention of nuclei in stratum corneum), elongation of rete ridges, elongation of papillary dermis and thinning of epidermis (pinpoint bleeding = Auspitz sign), collections of neutrophils in stratum corneum (Munro microabscesses)
Tx: vitamin D analogs (calcipotriene, calcitriol, tacalcitol), cyclosporine, etanercept, methotrexate, ustekinumab (anti-IL-12 and IL-23)
Seborrheic keratosis
Benign squamous cell proliferation
Flat, round, pigmented (pale to dark brown), sharply demarcated lesions, “stuck-on” appearance, warty, waxy, or greasy surface on the trunk, face, neck, extremities
Hyperkeratosis, acanthosis, papillomatosis, melanocytic hyperplasia, horn cysts, keratin pseudocysts
Leser-Trelat sign
Leser-Trelat sign is the sudden onset of multiple seborrheic keratoses and suggests underlying carcinoma of the GI tract
Pemphigus vulgaris
IgG autoantibodies directed against desmoglein (1, 3) in desmosomes causing epidermal cell detachment → reticular/net-like pattern on immunofluorescence
Painful mucosal mouth ulcers, blisters/bullae on the face, scale, torso, Nikolsky +
A/w drugs, SLE, HIV, HSV
Poor prognosis
Bullous pemphigoid
IgG autoantibodies directed against hemidesmosomes between basal cells and basement membrane → linear immunofluorescence
Severe pruritus, tense blisters/bulla on the trunk and extremities that do not rupture easily, Nikolsky -
More commonly seen in the elderly (> 70) and a/w drugs and neurologic disorders
Dermatitis herpetiformis
IgA antibodies formed against gliadin protein in gluten cross-reacts with reticulin that is a component of the anchoring fibrils that attach the basement membrane to the dermis → IgA localization at tips of dermal papillae
Pruritic vesicles and bullae that are grouped (herpetiform)
Strong association with celiac disease
Tx: gluten-free diet
Staphylococcal scalded skin syndrome
Staph produces an exotoxin that destroys keratinocyte attachents in the stratum granulosum only
Characterized by fever, generalized erythematous rash with sloughing of the upper layers of the epidermis that heals completely
Stevens-Johnson syndrome
Often associated with adverse drug reaction
Characterized by fever, bulla formation and necrosis, sloughing of skin, erythema multiforme-like target lesions, typically involves 2 mucous membranes, Nikolsky +, and a high mortality rate
Toxic epidermal necrolysis is a more severe form that involves > 30% of the body surface area
Acanthosis nigricans
Epidermal hyperplasia (↑ spinosum) causing symmetrical, hyperpigmented, velvety thickening of skin, espeially on the neck and axilla
A/w hyperinsulinemia (diabetes, obesity, Cushing syndrome) and visceral malignancy
Erythema multiforme
Hypersensitivity reaction to infection (HSV, mycoplasma), drugs (penicillin, sulfonamides), or autoimmune (SLE) mediated by cytotoxic T lymphocytes or CD4 cells
Macules and papules with a red or vesicular center; acral, bilateral, symmetric, targetoid due to central necrosis surrounded by erythema
Actinic keratosis
Premalignant lesions caused by sun exposure
Small, rough/sandpapery, scaly, erythematous or brownish papules or plaques on sun damaged skin (face, arms, back, dorsal hands)
Risk of squamous cell carcinoma proportional to degree of epithalial dysplasia
Erythema nodosum
Inflammatory reaction that affects connective tissue between fat lobules
Painful erythematous plaques, usually on anterior shins
Can be idiopathic or associated with sarcoidosis, coccidioidomycosis, histoplasmosis, TB, strep, leprosy, and Chron’s disease
Lichen planus
6 Ps: pruritic, purple, polygonal, planar (flat) papules and plaques
Mucosal involment (reticular white lines) = Wickham striae
Saw-tooth infiltrate of lymphocytes at dermal-epidermal junction
Associated with chronic hepatitis C infection
Basal cell carcinoma (most common skin cancer)
Malignant proliferation of basal cells in the epidermis
Risk factors: sun exposure (UVB-induced damage; pyrimidine dimers), albinism, xeroderma pigmentosum (autosomal recessive defect in nucleotide excision repair)
Gross: nodular, slowly enlarging, pink, pearly papule, may have telangiectasia and central ulceration, rolled borders often found on the head, neck, trunk, upper lip
Histology: nodules/islands of basal cells with peripheral palisading
Prognosis: locally invasive but rarely metastasizes
Tx: surgical excision
Squamous cell carcinoma
(second most common skin cancer)
Malignant proliferation of squamous cells in the epidermis
Risk factors: sun exposure (UVB-induced damage; pyrimidine dimers), albinism, xeroderma pigmentosum (autosomal recessive defect in nucleotide excision repair), scarring from burn injury, irradiation, arsenic poisoning, immunosuppression
Gross: nodule with central ulceration and pink, elevated, indurated border that does not heal spontaneously on the face, lower lip, ears, hands
Histology: keratin pearls
Prognosis: locally invasive, may spread to local lymph nodes, but rarely metastasizes
Tx: surgical excision
Melanoma
Malignant neoplasm of melanocytes; associated with mutation in BRAF protein kinase
Risk factors: sun exposure (UVB-induced damage; pyrimidine dimers), albinism, xeroderma pigmentosum (autosomal recessive defect in nucleotide excision repair), dysplastic nevus syndrome
Variants: superficial spreading, nodular (early vertical growth), lentigo maligna, acrolentiginous (palms and soles, not a/w UV)
Look for: asymmetry, borders irregular, color variations, diameter > 6 mm, evolution over time
Prognosis: radial (good prognosis) vs. vertical growth (bad prognosis – Breslow tumor depth measured between top of granular layer and the deepest point of invasion)
Tx: surgical excision with wide margins
Bisphosphonates
Pyrophosphate analog that binds to hydroxyapatite in bone and inhibits osteoclast activity via increased apoptosis and reduced development/recruitment
Indicated for osteoporosis, hypercalcemia, Paget disease of bone
SA: corrosive esophagitis, osteonecrosis of the jaw, atypical femur fractures with prolonged use
Colchicine
Binds and stabilizes tubulin to inhibit microtubule polymerization, impairing leukocyte chemotaxis and degranulation
Indicated for acute treatment of gout (NSAIDs are first line)
SA: diarrhea, nausea, vomiting, abdominal pain
Allopurinol
Inhibits xanthine oxidase to decrease convertion of xanthine to uric acid
Indicated for chronic treatment of gout and to prevent tumor lysis-associated urate nephropathy
Febuxostat
Inhibits xanthine oxidase to decrease convertion of xanthine to uric acid
Indicated for chronic treatment of gout and to prevent tumor lysis-associated urate nephropathy
What drugs should you avoid in patients with gout?
Salicylates (low-dose) and thiazide diuretics
Both decrease renal tubular excretion of uric acid
Probenecid
Inhibits reabsorption of uric acid in the proximal convoluted tubule
Etancercept
Fusion protein (receptor for TNF-α + IgG1 Fc)
Indicated for rheumatoid arthritis, psoriasis, ankylosing spondylitis
SA: infection (TNF blockade prevents activation of macrophages and destruction of phagocytosed microbes)
Infliximab
Anti-TNF-α
Indicated for IBD, rheumatoid arthritis, psoriasis, ankylosing spondylitis
SA: infection (TNF blockade prevents activation of macrophages and destruction of phagocytosed microbes)
Adalimumab
Anti-TNF-α
Indicated for IBD, rheumatoid arthritis, psoriasis, ankylosing spondylitis
SA: infection (TNF blockade prevents activation of macrophages and destruction of phagocytosed microbes)
How is estrogen protective of bone mineral density
Estrogen stiimulates osteoclast apoptosis, suppresses osteoblast apoptosis, and reduces levels of pro-resorptive cytokines
Describe the role of RANKL and OPG in bone regulation
RANKL and OPG is produced by osteoblasts
RANKL binds to RANK on osteoclasts and stimulates proliferation and differentiation
OPG has the opposite affect
Xeroderma pigmentosum
Autosomal recessive defect in nucleotide excision repair (endonucleases that recognize thymine dimers and excise the short stretch of ssDNA around them)
Characterized by photosensitivity, poikiloderma, hyperpigmentation in sun-exposed areas, and skin cancer
Describe the pathway of collagen synthesis
Collagen consists of 3 polypeptide α-chains in a triple helix held together by hydrogen bonds. The amino acid sequence is repetitive (Gly-X-Y)n with Gly being necessary in every third position to ensure compact coiling.
It is synthesized by fibroblasts, osteoblasts, and chondroblasts through the following steps:
- Translation begins in the cytoplasm and an signal at the N-terminus of the pre-pro-α-chain facilitates binding to the RER
- In the RER, the pre-pro-α-chain is cleaved to form pro-α-chain
- Proline and lysine at the Y positions are hydroxylated (vitamin C dependent)
- Some hydroxylysine residues are glycosylated
- Disulfide bonds between the C-terminals of 3 α-chains align the procollagen
- Procollagen is transported through the Golgi into the extracellular space
- The N- and C-terminal propeptides are cleaved by procollagen peptidases converting the molecule into a less soluble tropocollagen
- Tropocollagen monomers self-assemble into collagen fibrils
- Lysyl oxidase creates covalent crosslinks between collagen fibrils
Ehlers-Danlos syndrome
Hereditary disorders characterized by defective collagen type IV synthesis (e.g. mutated procollagen peptidase)
Characterized by joint laxity, hyperextensible skin, fragile tissue with easy bruising, poor wound healing → soluble collagen that does not properly crosslink
Vitiligo
Partial or complete loss of epidermal melanocytes
Describe normal wound healing
- Days 0-1: vasoconstriction, platelet aggregation, fibrin deposition
- Days 1-3: neutrophil migration and macrophage phagocytosis of necrotic debris and bacterial contaminants
- 3 days - 3 weeks: fibroblasts form connective tissue + endothelial cells begin to form blood vessels → granulation tissue, wound contraction
- 3+ weeks: fibroblasts continue to synthesize connective tissue matrix (collagen, elastin), slow, progressive increase in tensile strength of new tissue
Excess TGF-β → excess and disorganized collagen production can cause a keloid/hypertrophic scar
Excess metalloproteinase activity and myofibroblast accumulation → contractures
Acrochorda
Skin tag
Ephelides vs. solar lentigines
Ephelides (freckles) = increased melanin production by melanocytes
Solar lentigines = increased proliferation of melanocytes, more common in adults
Types of nevi
Melanocytic nevi are benign neoplasms of mitotically quiescent melanocytes
Junctional nevus: malenocytes limited to the dermoepidermal junction, flat, darker coloration in the center than the periphery
Compound nevus: melanocytes extend into the dermis, raised, uniformly pigmented
Intradermal nevus: nests of melanocytes are lost and remaining cell lose tyrosinase activity and produce little pigment, dome-shaped or pedunculated lesions
Angiosarcoma
Malignant tumor of endothelial origin
Can be located in the liver or cutaneously (Stewart-Treves)
Increased risk with chronic lymphedema (e.g. post-radical mastectomy with axillary lymph node dissection)
Associated with exposure to arsenic, vinyl chloride
Histology of atopic dermatitis (eczema) vs urticaria
Atopic dermatitis (eczema) → epidermal spongiosis (intercellular epidermal edema)
Urticaria → dermal edema
Polyarteritis nodosa
Multisystem involvement with segmental, transmural inflammation of the arterial wall with fibrinoid necrosis seen in young adults
Renal: glomerulonephritis, HTN
Nervous: peripheral neuropathy
GI: mesenteric ischemia
MSK: myositis, arthritis
Associated with hepatitis B
Endochondral vs. intramembranous ossification
Endochondral ossification = long bones are formed when mesenchymal cells differentiate into chondroblasts which secrete cartilage matrix → cartilage template → calcification and invasion by osteoblasts, osteoclasts, and blood vessels from the periosteum → woven bone undergoes remodeling into compact bone
Intramembranous ossification = skull bones are formed when mesenchymal cells differentiate directly into osteoblasts and begin osteoid matrix secretion without the formation of cartilagnious bone
Pathology of long bones by location
Epiphysis: giant cell tumor
Metaphysis: hematogenous osteomyelitis in children (vertebra in adults), osteosarcoma
Diaphysis: Ewing sarcoma, chondrosarcoma
McCune-Albright syndrome
Mosaic somatic mutation in the BNAS gene encoding stimulatory α subunit of G protein → constitutive activation of adenylate cyclase
Characterized by cafe-au-lait spots, endocrine abnormalities (e.g. precocious puberty, hyperthyroidism), and fibrous dysplasia (osteolytic-appearing lesions in bone)
Legg-Calve-Perthes disease
Isolated idopathic osteonecrosis of the hip in young children
Rotator cuff exam
Damage to supraspinatus (most common) → limited or painful abduction (esp. first 10-15 degrees then deltoid helps)
Damage to infraspinatus and/or teres minor → limited or painful external rotation
Damage to subscapularis → limited or painful internal rotation
Duchenne muscular dystrophy
X-linked recessive deletion of the dystrophin gene, a structural protein of muscle fibers
Onset at age 2-5 with ambulation difficulties, Gower sign, calf pseudohypertrophy (fibrofatty muscle replacement), kyphoscoiosis
Complications: wheelchair bound by age 12, worsening scoliosis c/b restrictive pulmonary function
Most common shoulder dislocation
Anterior dislocation (impact while arm in the overhead throwing position) → flattening of the deltoid leads to “square shoulder” deformity, axillary nerve may be injured
Lateral vs. medial epicondylitis
Lateral epicondylitis AKA “tennis elbow” is caused by overuse of the wrist extensors
Medial epicondylitis AKA “golfers’ elbow” is caused by overuse of the wrist flexors
MSK nerve injuries to the lower extremities
Damage to obturator nerve (traverses obturator canal) → weakness of thigh adductor muscles, sensation over distal medial thigh
Compression of the neck of the fibula (lateral) → compression of common peroneal (fibular) nerve:
Deep peroneal nerve (anterior compartment) → weakness of foot dorsiflexion (foot drop), impaired sensation of the webspace between the first and second toes
Superficial peroneal nerve (lateral compartment) → weakness of foot eversion and impaired sensation of the lateral shin and dorsal foot
Tibial nerve damage (posterior compartment) → weakness of foot plantarflexion, inversion, toe flexion (difficulty standing on toes) and impaired sensation over the sole
Brachial plexus injuries
Damage to the upper trunk (traction between head and shoulder) → Erb palsy (“waiter’s tip”)
Damage to the lower trunk (upward force on arm) → Klumpke palsy (claw hand)
Damage to the long thoracic nerve (axillary node dissection, chest tube insertio) → denervation of serratus anterior → winged scapula
MSK nerve injuries to the upper extremities
Damage to the radial nerve (mid-shaft humerus fracture) → wrist drop (weak wrist extensors), impaired sensation over lateral dorsum of hand
Damage to the ulnar nerve (damage to medial epicondyle of humerus, hook of the hamate) → “ulnar claw,” atrophy of the hypothenar eminence, weankness of wrist flexion
Damage to the median nerve (compression of carpal tunnel via pregnancy, hypothyroidism, etc.) → pain/paresthesias over palmar aspects of first 3 1/2 digits, thenar atrophy and weakness on thumb abduction/opposition
Damage to the axillary nerve (fracture at the surgical neck of the humerus) → paralysis of deltoid, teres minor
Antiphospholipid antibody
Associated with SLE and antiphospholipid syndrome which is characterized by hypercoagulability, paradoxical PTT prolongation, and recurrent miscarriages
What does the Trendelenberg sign indicate?
Trendelenberg sign = hip tilts towards the unsupported leg
It indicates contralateral hip abductor weakness
Hip abductors, the gluteus minimus, gluteum medius, and tensor fascia lata are innervated by the superior gluteal nerve which can be damaged in the superiomedial aspect of the gluteus
Musle fiber types
Type I (slow twitch) fibers perform actions requiring low-level sustained force (e.g. postural maintenance) and are primarily aerobic (high myoglobin and mitochondria concentrations)
Type IIb (fast twitch) fibers perform rapid forceful pulses of movement derive ATP via anaerobic glycogenolysis and subsequent glycolysis
Type IIa fibers are intermediate between type I and type IIb and generate ATP via aerobic metabolism
Fibromyalgia
Chronic (> 3 months), widespread MSK pain associated with stiffness, paresthesias, poor sleep, fatigue, pschiatric disturbances likely due to abnormal central processing of painful stimuli
Most commonly seen in females 20-50 y/o
Tx: regular exercise, antidepressants (TCAs, SNRIs), and anticonvulsants
Polymyalgia rheumatica
Pain and stiffness in the shoulders and hips often with fever, malaise, and weight loss; no muscle weakness
Most common in women > 50 y/o
Labs: ↑ ESR, ↑ CRP, normal CK
Tx: rapid response to low-dose corticosteroids
Features of a fat embolism
Risk factors: long bone and pelvic fractures, orthopedic procedures
Triad: respiratory distress, neurological symptoms, petechial rash
Malignant hyperthermia
Autosomal dominant defect in ryanodine receptors that release excessive calcium into muscle cells after exposure to an anesthetic → excess intracelluar calcium stimulated ATP-dependent reuptake by the SR → excessive ATP consumption generates heat which damages muscles
Characterized by fever, muscle rigidity, tachycardia, hypertension, hyperkalemia, myoglobinemia
Tx: dantrolene (inhibits ryanodine receptor preventing further intracellular calcium release)
Marfan vs. homocystinuria
Features in common: pectus deformity, tall stature, arachnodactyly, joint hyperlaxity, skin hyperelasticity, scoliosis
Marfan (fibrillin-1 gene mutation): AD, normal intellect, aortic root dilation, upward lense dislocation
Homocystinuria (cystathionine-beta-synthase mutation): AR, intellectual disability, thrombosis, downward lens dislocation, megaloblastic anemia, fair complexion
