Muscculoskeletal, Skin, and Connective Tissue - Pathology

evolv3's version from 2015-06-22 00:34

MSK path

Question Answer
AchondroplasiaFailure of endochondral ossification → short bones
Membranous bone is not affected → Lg head relative to limbs
>85% of mutations occur sporadically and are assoc w advanced paternal age - but also AD inheritance
Achondroplasia mech of diseaseConstitutive *activation* of fibroblast growth receptor (FGFR3) → inhibits chondrocyte proliferation
Which type of bone is affected in osteoporosis?Trabecular (spongy) bone
Type 1 osteoporosisPost-menopausal: ↑ bone resorption d/t ↓ estrogen levels
Femoral neck fracture or distal radius fractures
Type 2 osteoporosisSenile osteoporosis - men & women >70y/o
PPX: regular weight-bearing exercise and adequate calcium/VitD intake
Tx: estrogen (SERMs) and/or calcitonin, bisphosphonates or pulsatile PTH for severe cases
No glucocorticoids
Osteopetrosis - other name?
x-ray finding?
neurologic finding/cause? hem labs?
marble bone disease
Failure of normal bone resorption d/t defective osteoclasts → thickened, dense bones that are prone to fracture
Bone fills marrow → pancytopenia, extramedullary hematopoiesis
X-rays show bone-in-bone appearance
Can lead to CN nerve impingement d/t narrowed foramina
Can be caused by mutations such as carbonic anhydrase II which impair ability of osteoclast to generate acidic environment
bone marrow transplant bc osteoclasts come from monocytes
Osteomalacia/ricketsVitD deficiency
Adults - osteomalacia, kids - rickets
Defective mineralization/calcification of osteoid → soft bones that bow out
↓ VitD → ↓ serum calcium → ↑ PTH secretion → ↓ serum phosphate
↑ alk phos d/t hyperactivity of osteoblasts
Paget's disease (osteitis deformans)Localized disorder of bone remodeling d/t ↑ activity of osteoblasts & clasts.
Serum Ca, phos, and PTH levels are normal
↑ Alk phos
Presents with hat size increase, loss of hearing, or long bone chalk-stick fractures: ↑ blood flow from ↑ AV shunts may cause high output heart failure
↑ risk of osteogenic sarcoma
Labs of osteoporosisNormal Ca, phos, ALP, PTH
Labs of osteopetrosis↓ Ca, normal phos, ↑ Alk phos, normal PTH
Labs of osteomalacia/rickets
Ca, P, AP, PTH
↓ Ca, ↓ phos, ↑ Alk phos, ↑ PTH
Labs of osteitis fibrosa cystica↑ Ca, ↓ phos, ↑ Alk phos, ↑ PTH
"Brown tumors" of hyperparathyroidism
Labs of Paget's diseaseonly ↑ ALP
Polyostotic fibrous dysplasiaBone is replaced by fibroblasts, collagen, irregular bony trabeculae --> unmineralized whorled pattern
assoc w/ mccune-albright = coast of maine spot, endocrine abnormalities
McCune-Albright syndromeA form of polyostotic fibrous dysplasia
Multiple unilateral bone lesions assoc w endocrine abnormalities (precocious puberty) and cafe-au-lait spots


Question Answer
Osteoarthritis bone findings*Subchondral cysts
DIP (Heberden's nodes), PIP (Bouchard's nodes)
NO MCP involvement
Rheumatoid arthritis bone findingsPannus formation (MCP, PIP) (fibrovascular/granulation tissue)
Subcutaneous rheumatoid nodules (fibrinoid necrosis) --> boutoniers = flex pip, extend dip; swan = extend pip, flex DIP
Ulnar dev. of fingers
Baker's cyst (in popliteal fossa)
NO DIP Involvement
What type of hypersensitivity is RA?Type 3 hypersensitivity
Markers of RArheumatoid factor (anti-IgG antibody)
anti-cyclic citrullinated peptide antibody
RA vs osteoarthritis, morning stiffness and useRA - morning stiffness and improves with use
Osteoarthritis - less than 30 mins of morning stiffness - worse w/ use
Sjogren's syndrome triadXerophthalmia (dry eyes, conjunctivitis, "sand in my eyes")
Xerostomia (dry mouth, dysphagia)
Sjogren's syndrome findings, associations and risksLymphocytic infiltration of exocrine glands, esp lacrimal and salivary
Parotid enlargement
Dental caries
Anti-SSA (Ro), anti-SSB (La)
↑ risk of B-cell lymphoma
Assoc with RA
Females between 40-60 y/o
Gout findingsMonosodium urate crystals in joints
needle shaped and negatively birefringent = yellow crystals under parallel light
Causes of goutLesch-Nyhan syndrome
PRPP excess
↓ excretion of uric acid (thiazide diuretics)
↑ cell turnover
von Gierke's disease
Most often due to underexcretion → hyperuricemia
Gout sxsAsymmetric joints
Swollen, red, and painful
Classically: painful MTP joint of big toe (podagra)
Tophus formation (often on external ear, olecranon bursa, or achiles tendon)
often after large meal and alcohol consumption - EtOH metabolites compete for same excretion sites as uric acid in kidney
Gout txAcute: NSAIDs (indomethacin), glucocorticoids
Chronic: xanthine oxidase inhibitors (allopurinol, febuxostat), probenicid, colchicine
PseudogoutDeposition of calcium pyrophosphate crystals in joint space
Basophilic rhomboid crystals that are weakly positively birefringent
Large joints (knee) > 50 y/o
Crystals are blue when parallel to light
Tx: NSAIDs, steroids or colchicine
Common pathogens in infectious arthritisStaph a, Strep, and N. gonorrhoeae
Gonococcal arthritis - migratory, asymmetric
Causes of osteonecrosis (avascular necrosis)Trauma, high-dose corticosteroids, alcoholism, sickle cell
Seronegative spondyloarthropathiesArthritis without rheumatoid factor (no anti-IgG antibody)
PAIR - Psoriatic arthritis, Ankylosing spondylitis, Inflamatory bowel disease, Reactive arthritis (Reiter's syndrome)
Psoriatic arthritisSeronegative spondyloarthropathy
Joint pain/stiffness with psoriasis
Dactylitis ("sausage fingers")
"Pencil-in-cup" deformity on xray
in fewer than 1/3 of pts with psoriasis
Ankylosing spondylitisSeronegative spondyloarthropathy
Chronic inflammatory disease of spine and sacroiliac joints → ankylosis (vertebral fusion), uveitis, aortic regurgitation
Reactive arthritis (Reiter's syndrome)Seronegative spondyloarthropathy
triad: Conjuctivitis & anterior uveitis

Follows 2 weeks after an infxn of Campylobacter, Shigella, Salmonella, Yersinia, Chlamydia, Bartonella


Question Answer
SLE presentations
symp - heart - lung - hand - MCC death
fever, fatigue, weight loss
Libman-sacks endocarditis - verrucous, wart-like, steril vegetations on both sides of valve
hilar adenopathy
Raynaud's phenomenon
Nephritis (common cause of death)
Nephritic - diffuse proliferative glomerulonephritis
nephrotic - membranous glomerulonephritis
Antinuclear antibodies (ANA)sensitive, but not specific for SLE
Anti-dsDNAvery specific, poor prognosis = SLE
Anti-Smith antibodiesSLE very specific, not prognostic
Antihistone antibodiesmore sensitive for drug-induced lupus
Other signs/sxs of SLE

Malar rash
Discoid rash - sores that scar, on face
Mucositis (oropharyngeal ulcers)
Serositis (pleuritis, pericarditis)
Sarcoidosis characteristicsimmune-mediated, widespread noncaseating granulomas w elevated serum ACE levels
Black females
Bilateral hilar adenopathy and/or reticular opacities on CXR
Associations w sarcoidosis

Lungs, Skin, CNS, Histology, Eyes, Lab
Restrictive lung disease (interstitial fibrosis)
Erythema nodosum (tender, red nodules on both shins)
Bell's palsy
Epithelial granulomas w microscopic Schaumann and asteroid bodies
Hypercalcemia (d/t elevated 1α-hydroxylase-mediated VitD activation in epithelioid macrophages)
Tx of sarcoidosissteroids
Polymylagia rheumaticaPain/stiffness in shoulders/hips, w fever, malaise, weight loss
No muscular weakkness
Women > 50; assoc w temporal arteritis
ESR, normal CK
Tx: rapid response to low-dose corticosteroids
signs ----- what type of of inflamm ----- where is the inflamm --- 3 increased markers
Progressive symmetric proximal muscle weakness
Endomysial inflammation w CD8 T cells
Involves shoulders
CK, +ANA, + anti-Jo-1 antibodies
Tx: steroids
Association, inflam location/cells, increased labs, treatment
Progressive symmetric proximal muscle weakness (similar to polymyositis)
malar rash, Gottron's papules, heliotrope rash, "shawl and face" rash, "mechanic's hands"
risk of occult malignancy
Perimysial inflammation and atrophy w CD4 T cells
↑ CK, +ANA, +anti-Jo-1 antibodies
Tx: steroids
Myasthenia gravisMost common NMJ disorder
Autoantibodies to postsynaptic ACh receptor
Reversed with AChE inhibitor
Myasthenia gravis presentation & ASSOCIATIONS!Ptosis, diplopia, weakness
worsens with muscle use
Assoc w thymoma, thymic hyperplasia
Lambert-Eaton myasthenic syndromeUncommon
Autoantibodies to presynaptic Ca channel → ↓ ACh release
No help with AChE inhibitor
Lambert-Eaton myasthenic syndrome presentation and associationsProximal muscle weakness
Improves with muscle use
Assoc w small cell lung cancer
Myositis ossificanstrauma → ossification in muscle
SclerodermaExcessive fibrosis and collagen deposition throughout the body
Sclerosis of skin → puffy, taut skin with absence of wrinkles
Most likely cause of death: pulmonary sclerosis
Can also cause sclerosis of renal, cardiovascular, and GI systems
75% females
Diffuse sclerodermaWidespread skin involvement
Rapid progression
Early visceral involvement
Assoc. w Scl-70 antibody (anti-DNA topoisomerase I antibody)
CREST syndromeCalcinosis
Raynaud's phenomenon
Esophageal dysmotility
Telangiectasia - small dilated vessels near the skin or mucous membranes
---limited to skin and face. More benign clinical course---
Assoc w anti-Centromere antibody

Bone tumors

Giant cell tumor (osteoclastoma)Benign
20-40 y/o
Epiphyseal end of long bones (typically distal femur, proximal tibial region)
Locally aggressive beign tumor
"double bubble" or "soap bubble" appearance on xray
Spindle-shaped cells with multinucleated giant cells
Osteochondroma (exostosis)Most common benign tumor
Males <25 y/o
Mature bone with carilaginous cap
Commonly originates from long metaphysis
Osteogenic sarcoma2nd most common 1° malignant bone tumor after multiple myeloma
M>F, 10-20 y/o
Risk factors: Paget's, bone infarcts, radiation, familial retinoblastoma
Occurs at metaphysis of long bones, often around knee region
Codman's triangle (elevation of periosteum) or sunburst pattern on xray
Tx w resection and chemo
Ewing's sarcomaMalignant
Boys < 15y/o
Diaphysis of long bones, pelvis, scapula, and ribs
Anaplastic small blue cell tumor
Extremely aggressive w early mets, but chemo-responsive
"Onion skin" appearance in bone
t(11;22) translocation
Men 30-60 y/o
Pelvis, spine, scapula, humerus, tibia, or femur
Cartilaginous tumor
May be 1° or from osteochondroma
Expansile glistening mass within medullary cavity