MSK, Skin and Connective Tissue Flashcards
Unhappy triad
- Common injury in contact sport due to lateral force applied to a planted leg
- Classically consists of damage to ACL, MCL and medial meniscus (attached to MCL)
- However lateral meniscus injury is more common
- Presents with acute knee pain and signs of joint injury and instability
Prepatellar bursitis
- Inflammation of knee’s largest sac of synovial fluid
- Can be caused by repeated trauma or pressure from excessive kneeling
Baker cyst
Popliteal fluid collection in gastrocnemius-semimembranous bursa commonly communicating with synovial space and related to chronic joint disease
Shoulder muscles that form the rotator cuff
Supraspinatus:
- Innervated by supraspinatus nerve
- Abducts arm initially (before the action of the deltoid)
- Most common rotator cuff injury (trauma or degeneration and impingement → tendinopathy or tear)
- Assessed by “empty/full can” test
Infraspinatus:
- Innervated by supraspinatus nerve
- Laterally rotates arm
- Pitching injury
teres minor:
- Innervated by axillary nerve
- Adducts and laterally rotates arm
Subscapularis:
- Upper and lower subscapular nerves
- Medially roates and adducts arm
“SItS”
Medial epicondylitis
- Golfer’s elbow
- Repetitive flexion (forehand shots) or idiopathic → pain near medial epicondyle
Lateral epicondylitis
- Tennis elbow
- Repetitive extension (backhand shots) or idiopathic → pain near lateral epicondyle
Most commonly fractured carpal bone
- Scaphoid (palpated in anatomic snuff box)
- Typically from a fall on an outstretched hand
- Prone to avascular necrosis owing to retrograde blood supply
Dislocation may cause acute carpal tunnel syndrome
Lunate
Fall on outstretched hand that causes ulnar nerve injury
Hook of the hamate
Carpal tunnel syndrome is associated with
- Pregnancy
- Rheumatoid arthritis
- Hypothyroidism
- Diabetes
- Dialysis-related amyloidosis
- Repetitive use
Guyon canal syndrome
- Compression of ulnar nerve at wrist or hand
- Classically seen in cyclists due to pressure from handlebars
Muscle conduction to contraction structure in skeletal and cardiac muscle
Skeletal muscle → 1 T-tubule + 2 terminal cisternae = triad
Cardiac muscle → 1 T-tubule + 1 terminal cisterna = dyad
What is mechanically coupled to the ryanodine receptor on the sarcoplasmic reticulum
Depolarization of the voltage-sensitive dihydropyridine receptor, mechanically coupled to the ryanodine receptor on the SR induces a conformational change in both receptors, causing Ca2+ release from SR
Contraction changes length of which bands
Contraction results in shortening of H and I bands and between the Z lines (HIZ shrinkage) but the A band remains the same length (A band is Always the same length)
Endochondral ossification
- Bones of axial skeleton, appendicular skeleton and base of skull
- Cartilaginous model of bone is first made by chondrocytes
- Osteoclasts and osteoblasts later replace with woven bone and then remodel to lamellar bone
- In adults, woven bone occurs after fractures and in Paget disease
- Defective in achondroplasia
Membranous ossification
- Bones of calvarium and facial bones
- Woven bone formed directly without cartilage
- Later remodeled to lamellar bone
Osteoblast
- Builds bone by secreting collage and catalyzing mineralization in alkaline environment via ALP
- Differentiates from mesenchymal stem cells in periosteum
Osteoclast
- Dissolves bone by secreting H+ and collagenases
- Differentiates from a fusion of monocyte/macrophage lineage precursors
PTH
- Low, intermittent levels → anabolic effects (building bone) on osteoblasts and osteoclasts (indirect)
- Chronically ↑ PTH levels (primary hyperparathyroidism) → catabolic effects (osteitis fibrosa cystica)
Estrogen induces and inhibits apoptosis in which cells
Inhibits apoptosis in osteoblasts and induces apoptosis in osteoclasts
What inhibits chondrocyte proliferation in achondroplasia
Constitutive activation of fibroblast growth factor receptor (FGFR3) inhibits chondrocyte proliferation, therefore interfering with endochondral ossification
Causes of osteoporosis
- Most commonly due to ↑ resorption related to ↓ estrogen levels and old age
- Can be secondary to drugs (eg steroids, alcohol, anticonvulsants, anticoagulants, thyroid replacement therapy) or other medical conditions (hyperparathyroidism, hyperthyroidism, multiple myeloma, malabsorption syndromes)
What causes osteopetrosis
Failure of normal bone resorption due to defective osteoclasts. Mutations (eg carbonic anhydrase II) impair ability of osteoclast to generate acidic environment necessary.
How does osteopetrosis cause pancytopenia and extramedullary hematopoiesis
Bone fills marrow space
What is potentially curative of osteopetrosis
Bone marrow transplant is potentially curative as osteoclasts are derived from monocytes
Presentation of osteomalacia/rickets
X rays show osteopenia and “looser zones” (pseudofractures) in osteomalacia, epiphyseal widening and metaphyseal cupping/fraying in rickets. Children with rickets have bow legs bead-like costochondral junctions (rachitic rosary), craniotabes (soft skull)
Stages of Paget disease
- Lytic → osteoclasts
- Mixed → osteoclasts + osteoblasts
- Sclerotic → osteoblasts
- Quiescent → minimal osteoclast/osteoblast activity
What type of fractures are seen with Paget disease
Long bone chalk-stick fractures
What causes heart failure in Paget disease
↑ blood flow from ↑ arteriovenous shunts may cause high-output heart failure
Causes of osteonecrosis
- Corticosteroids
- Alcoholism
- Sickle cell disease
- Trauma
- “the Bends” (caisson/decompression disease)
- LEgg-Calve-Perthes disease (idiopathic)
- Gaucher disease
- Slipped capital femoral epiphysis
“CAST Bent LEGS”
Lab values of osteoporosis
- Normal Ca2+, PO43-, ALP, PTH
- ↓ bone mass
Lab values of osteopetrosis
- Normal or ↓ Ca2+
- Normal PO43-, ALP, PTH
Lab values of Paget disease of bone
- Normal Ca2+, PO43-, PTH
- ↑ ALP
- Abnormal “mosaic” bone architecture
Osteitis fibrosa cystica - Primary hyperparathyroidism
- ↑ Ca2+
- ↓ PO43-
- ↑ ALP
- ↑ PTH
- “Brown tumors” due to fibrous replacement of bone, subperiosteal thinning
- Idiopathic or parathyroid hyperplasia, adenoma, carcinoma
Osteitis fibrosa cystica - Seondary hyperparathyroidism
- ↓ Ca2+
- ↑ PO43-
- ↑ ALP
- ↑ PTH
- Often as compensation for CKD
Osteomalacia/rickets
- ↓ Ca2+
- ↓ PO43-
- ↑ ALP
- ↑ PTH
- Soft bones
- Vitamin D deficiency also causes secondary hyperparathyroidism
Hypervitaminosis D
- ↑ Ca2+
- ↑ PO43-
- Normal ALP
- ↓ PTH
- Caused by oversupplementation or ganulomatous disease (eg sarcoidosis)
Osteochondroma
- Most common benign bone tumor
- Males
Giant cell tumor/ osteoclastoma
- 20-40 yo
- Epiphyseal end of long bones
- Often around knee
- Locally aggressive benign tumor
- “Soap bubble” appearance on x-ray
- Multinucleated giant cells
Osteosarcoma/ osteogenic sarcoma
- 2nd most common primary malignant bone tumor (after multiple myeloma)
- Bimodal distribution: 10-20 yo (primary), > 65 yo (secondary)
- Predisposing factor → Paget disease, bone infarcts, radiation, familial retinoblastoma, Li-fraumeni syndrome (germline p53 mutation)
- Metaphysis of long bones, often around knee
- Codman triangle (from elevation of periosteum)
- Sunburst pattern
- Aggressive
- Treat with surgical en bloc resection (with limb salvage) and chemotherapy
Ewing sarcoma
- Boys
Osteoid osteoma
- Diaphysis
- Nighttime pain
- Central nidus
Juvenile idiopathic arthritis
- Most common arthritis seen in pediatric patients
- Often presents as recurrent and relapsing fevers accompanied by polyarticular joint pain, an evanescent macular, salmon-pink rash (anywhere on body)
- Rheumatoid factor not usually present
- Also associated with chronic anterior uveitis and decreased growth rates
- 30-50% develop hemophagocytic syndrome
- In adults, JIA is known as “Still disease”
Which glycogen storage disease is associated with Gout
Overproduction of uric acid is seen in von Gierke disease
Calcium pyrophosphate deposition disease is associated with
- Idiopathic (most often)
- Hemochromatosis
- Hyperparathyroidism
- Joint trauma
In which disease where crystals are found in joints is distribution of disease between the sexes equal
Both sexes are affected equally in calcium pyrophosphate deposition disease where as gout is more common in males
Is underexcretion or overproduction of uric acid a more common cause of gout
Underexcretion of uric acid
Prophylactic treatment of gout vs calcium pyrophosphate deposition disease
Gout → xanthine oxidase inhibitors (eg allopurinol, febuxistat)
Calcium pyrophosphate deposition disease → colchicine (can be used for acute and chronic treatment)
Chondrocalcinosis is seen in
Chondrocalcinosis, cartilage calcification, is seen on x-ray in calcium pyrophosphate deposition disease
Findings in Sjogren syndrome
- Inflammatory joint pain
- Keratoconjunctivits sicca (↓ tear production and subsequent corneal damage)
- Xerostomia (↓ saliva production)
- Presence of antinuclear antibodies: SS-A (anti-Ro) and/or SS-B (anti-La)
- Bilateral parotid enlargement
Complications of Sjogren syndrome
- Dental caries
- Mucosa associated lymphoid tissue (MALT) lymphoma → may present as parotid enlargement
Gonococcal arthritis
STI that presents as either purulent arthritis (eg knee) or triad of polyarthralgias, tenosynovitis (eg hand), dermatitis (eg pustules)
Enthesitis
- Inflamed insertion sites of tendons
- Associated with seronegative spondyloarthritis
Dactylitis and “pencil-in-cup” deformity of DIP on x-ray are associated with
Psoriatic arthritis
Ankylosis (joint fusion), uveitis and aortic regurgitation are associated with
Ankylosing spondylitis
Causes of reactive arthritis/ Reiter syndrome
- Post-GI → Shigella, Salmonella, Yersinia, Campylobacter
- Chlamydia
Common causes of death in SLE
- Cardiovascular disease
- Infections
- Renal disease
What does “RASH OR PAIN” stand for with regards to SLE
- Rash (malar or discoid)
- Arthritis (nonerosive)
- Serositis
- Hematologic disorders (eg cytopenias)
- Oral/nasopharyngeal ulcers
- Renal disease
- Photosensitivity
- Antinuclear antibodies
- Immunologic disorder (anti-DNA, anti-Sm, antiphospholipid)
- Neurologic disorders (eg seizures, psychosis)
Antihistone antibodies are sensitive for
Drug-induced lupus (eg hydralazine, procainamide)
Antinuclear antibodies and SLE
Sensitive but not specific
Anti-dsDNA antibodies
Specific and indicates poor prognosis (renal disease)
Anti-Smith antibodies
- Directed against snRNPs
- Specific but not prognostic
Which complement components are decreased in serum in SLE
↓ C3, C4, and CH50 due to immune complex formation
Treatment of SLE
- NSAIDs
- Steroids
- Immunosuppressants
- Hydroxychloroquine (traditionally, anti-malarial)
Antiphospholipid syndrome
- Primary or secondary autoimmune disorder (most commonly SLE)
- Diagnose based on clinical criteria including history of thrombosis (arterial or venous) or spontaneous abortion along with laboratory findings of lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein antibodies
- Anticardiolipin and lupus anticoagulant can cause false positive VDRL/RPR and PROLONGED PTT
- Not corrected with 1:1 fresh frozen plasma
- Treat with systemic anticoagulation
Mixed connective tissue disease
- Features of SLE, systemic sclerosis, and/or polymyositis
- Associated with anti-U1 RNP antibodies (speckled ANA)
- U1 RNP = U1 snRNP → also associated with splicesome
Sarcoidosis is associated with
- Restrictive lung disease (interstitial fibrosis)
- Erythema nodosum
- Lupus pernio (skin lesions on face resembling lupus)
- Bell palsy
- Epithelioid granulomas containing microscopic Schaumann and asteroid bodies
- Uveitis
- Hypercalcemia
Polymyalgia rheumatica
- Pain and stiffness in shoulders and hips, often with fever, malaise, and weight loss
- Does NOT cause muscular weakness
- More common in women > 50 years old
- Associated with giant cell (temporal) arteritis
- ↑ ESR, ↑ CRP, normal CK
- Rapid response to low-dose corticosteroids
Fibromyalgia
- Most commonly seen in females 20-50 years old
- Chronic, widespread musculoskeletal pain associated with stiffness, paresthesias, poor sleep, fatigue, cognitive disturbance (“fibro fog”)
- Treatment: regular exercise, antidepressants (TCAs, SNRIs), anticonvulsants
Antibodies seen in polymyositis and dermatomyositis
- ↑ CK
- ANA +
- Anti-Jo-1 + → histidyl tRNA synthase
- Anti-SRP + → signal recognition particle, universally conserved ribonucleoprotein that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and plasma membrane in prokaryotes
- Anti-Mi-2 +
Compare polymyositis and dermatomyositis
Polymyositis:
- Progressive symmetric proximal muscle weakness, characterized by endomysial inflammation with CD8+ T cells
- Most often involves the shoulders
Dermatomyositis:
- Similar to polymyositis
- Malar rash (similar to SLE)
- Grotton papules
- Heliotrope (erythematous periorbital) rash
- “Shawl and face” rash
- “Mechanic’s hands”
- ↑ risk of occult malignancy
- Perimysial inflammation and atrophy with CD4+ T cells
Dermatomyositis - endomysial or perimysial inflammation
Perimysial inflammation and atrophy with CD4+ T cells
Polymyositis - endomysial or perimysial inflammation
Endomysial inflammation with CD8+ T cells
Compare the presentation of myasthenia gravis and Lambert-Eaton myasthenic syndrome
Myasthenia gravis → ptosis, diplopia, weakness; worsens with muscle use
Lambert-Eaton → proximal muscle weakness, autonomic symptoms (dry mouth, impotence); improves with muscle use
Myositis ossificans
- Heterotropic ossification of skeletal muscle following muscular trauma
- Most often seen in upper or lower extremity
- May present as suspicious mass at site of known trauma or as incidental finding on radiography
Scleroderma/ systemic sclerosis
- Triad → autoimmunity, noninflammatory vasculopathy and collagen deposition with fibrosis
- Commonly sclerosis of skin, manifesting as puffy, taut skin without wrinkles, fingertip pitting
- Also sclerosis of renal, pulmonary (most common cause of death), cardiovascular, GI systems
- 2 major types → diffuse and limited
Most common cause of death in scleroderma
Sclerosis of pulmonary system
Diffuse scleroderma
- Widespread skin involvement
- Rapid progression
- Early visceral involvement
- Associated with anti-Scl-70 antibody (anti-DNA topoisomerase I antibody)
Limited scleroderma
- Limited skin involvement confined to fingers and face
- Also with CREST syndrome
- Calcinosis
- Raynaud phenomenon
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasia
- More benign clinical course than diffuse scleroderma
- Associated with anti-Centromere antibody
Tight junction
- Zonula occludens
- Prevents paracellular movement of solutes
- Composed of claudins and occludins
Adherens junction
- Belt desmosome, zonula adherens
- Below tight junction, forms “belt” connecting actin cytoskeletons of adjacent cells with CADhereins (Ca+ dependent adhesions proteins)
- Loss of E-cadherin promotes metastasis
Desmosomes
- Spot desmosome, macula adherens
- Structural support via intermediate filament interactions
- Autoantibodies → pemphigus vulgaris
Gap junctions
Channel proteins called connexons permit electrical and chemical communication between cells
Integrins
Membrane proteins that maintain the integrity of basolateral membrane by binding to collagen and laminin in basement membrane
Hemidesmosome
- Connects keratin in basal cells to underlying basement membrane
- Autoantibodies → bullous pemphigoid
Compare the presentation of intradermal and junctional nevi
Intradermal nevi → papular
Junctional nevi → macule
What layers of the epidermis are increased and decreased in psoriasis
- ↑ stratum spinosum (a part of acanthosis)
- ↓ stratum granulosum
Also seen is acanthosis with parakeratotic scaling (nuclei still in stratum corneum)
What changes are seen in the epidermis of verrucae
Epidermal hyperplasia, hyperkeratosis (↑ thickness of stratum corneum), koilocytosis
What are characteristic findings of utricaria
Superficial dermal edema and lymphatic channel dilation
Hyperkeratosis
- ↑ thickness of stratum corneum
- Psoriasis, calluses
Parakeratosis
- Hyperkeratosis with retention of nuclei in stratum corneum
- Psoriasis
Hypergranulosis
- ↑ thickness of stratum granulosum
- Lichen planus
Spongiosis
- Epidermal accumulation of edematous fluid in intercellular spaces
- Eczematous dermatitis (utricaria)
Acantholysis
- Separation of epidermal cells
- Pemphigus vulgaris
Acanthosis
- Epidermal hyperplasia (↑ spinosum)
- Acanthosis nigricans
Angiosarcoma
- Rare blood vessel malignancy typically occuring in the head, neck and breast areas
- Usually in elderly, on sun-exposed areas
- Associated with radiation therapy and chronic postmastectomy lymphedema
- Hepatic angiosarcoma → associated with vinyl chloride and arsenic exposures
- Very aggressive and difficult to resect due to delay in diagnosis
Cystic hygroma
Cavernous lymphangioma of the neck. Associated with Turner syndrome.
Glomus tumor
Benign, painful, red-blue tumor, commonly under fingernails. Arises from modified smooth muscle cells of the thermoregulatory glomus body.
Pyogenic granuloma
Polyploid lobulated capillary hemangioma that can ulcerate and bleed. Associated with trauma and pregnancy.
Differentiate bacillary angiomatosis and Kaposi sarcoma
Bacillary angiomatosis → benign capillary skin papules found in AIDS patients; caused by Bartonella henselae infections; has neutrophilic infiltrate
Kaposi sarcoma → endothelial malignancy most commonly of the skin, but also mouth, GI tract, and respiratory tract; associated with HHV-8 and HIV; has lymphocytic infiltrate
Compare Staphylococcal scalded skin syndrome and TEN
Exotoxin of S aureus destroys keratinocyte attachments in stratum granulosum only, vs TEN which destroys dermal-epidermal junction
Staphylococcal scalded skin syndrome is seen in
Newborns, children and adults with renal insufficiency
Acantholysis is characteristic of
- Pemphigus vulgaris
- Acantholysis = keratinocytes in stratum spinosum are connected by desmosomes
Tense blisters of bullous pemphigoid contain
Eosinophils
Pemphigus vulgaris and bullous pemphigoid - which involves oral mucosa
Pemphigus vulgaris involves oral mucosa
Dermatitis herpetiforms
- Pruritic papules, vesicles, and bullae (often found on elbows)
- Deposits of IgA at tips of dermal papillae
- Associated with celiac disease
- Treatment → dapsone, gluten free diet
Erythema multiforme is associated with
- Infections (eg Mycoplasma pneumoniae, HSV)
- Drugs (eg sulfa drugs, beta lactams, phenytoin)
- Cancers
- Autoimmune disease
How many mucous membranes are usually involved with Stevens-Johnson syndrome
2
When is erythema multiforme/ Stevens-Johnson syndrome categorized as toxic epidermal necrolysis
> 30% of body surface involved
With actinic keratosis, the risk of SCC is proportional to
Degree of epithelial dysplasia
Erythema nodosum is associated with
- Sarcoidosis
- Coccidiomycosis
- Histoplasmosis
- TB
- Streptococcal infections
- Leprosy
- Inflammatory bowel disease
Lichen planus is associated with
Hepatitis C
Describe microscopic findings of lichen planus
Sawtooth infiltrate of lymphocytes at dermal-epidermal junction
Which skin cancer is associated with palisading nuclei
BCC
Which skin cancer is associated with chronic draining sinuses
SCC
Name 4 types of melanoma
- Superficial spreading
- Nodular
- Lentigo maligna
- Acral lentiginous
Vemurafenib benefits which patients
Patients with BRAF V600E mutations and metastatic or unresectable melanoma. Vemurafenib is a BRAF kinase inhibitor.
