Pathology - musculoskeletal Flashcards
Failure of longitudinal bone growth
Achondroplasia
Constitutive activation of FGF-receptor 3 inhibits chondrocyte proliferation
Membranous ossficiation not affected, so large head but small body
Loss of trabecular bone mass w/ normal bone mineralization
Osteoporosis
Type 1: incr. bone resorption due to low estrogen levels
Type 2: old people, tx w/ bisphosphonates, PTH analogs, SERMs, denosumab (monoclonal Ab against RANKL)
Failure of normal bone resorption due to defective osteoclasts leads to thick dense bones prone to fracture
Osteopetrosis
Bone also fills marrow, so pancytopenia
Carbonic anhydrase mutation
Can also narrow foramina (leading to cranial nerve palsies)
Tx: bone marrow transplant
Defective mineralization/calcification of osteoid
Osteomalacia
Vit. D deficiency (low Vit D –> low serum Ca –> high PTH –> loss of PO4)
Look for incr. Alk Phos (hyperactivity of osteoblasts)
Localized disorder of bone remodeling, mosaic pattern of woven and lamellar bone
Paget disease of bone
Incr in osteoblastic and osteoclastic activity
incr blood flow from AV shunts –> high output heart failure
incr. risk of osteogenic sarcoma
Painful infarction of bone and marrow
Osteonecrosis/avascular necrosis
Femoral head, due to insufficiency of medial circumflex femoral artery
ASEPTIC: Alcoholism, Sickle cell disease, Storage, Exogenous/Endogenous steroids, Pancreatitis, Trauma, Idiopathic, Caisson (decompression disease)
Knee tumor vs. cartilaginous cap
Benign bone tumors
Giant cell tumor: multinucleated giant cells, end of long bones
Osteochondroma: most common (exostosis of bone), mature bone with cartilaginous cap
Osteosarcoma vs. Ewing sarcoma (malignant bone tumors)
Osteosarcoma - sunburst pattern, Codman triangle (elevation of periosteum), surgical resection!
Ewing sarcoma - young boys, anaplastic small blue cell, onion skin periosteal reaction, t(11;22)
Rheumatoid arthritis immune mechanism
Type 3 and Type 4 hypersensitivity
Look for rheumatoid factor (anti-IgG antibody), anti-CCP, HLA-DR4
Destruction of salivary glands by lymphocytic infiltrates
Sjogren’s
Sx: inflammatory, anti-SSA/anti-SSB (Ro/La)
Complications: dental caries, MALT lymphoma
Mechanisms of gout
Underexcretion of uric acid (90% of pts): idiopathic, alcohol (competes for excretion sites in the kidney)
Overproduction of uric acid (10%): PRPP excess, incr. cell turnover (tumor lysis), Lesch-Nyan
negatively bifringent needle-shaped (yellow under parallel light)
Gout treatment regimens (acute and chronic)
Acute: NSAIDs, steroids, colchicine (inhibits microtubule polymerization in neutrophils)
Chronic: allopurinol, febuxostat (xanthine oxidase inhibitor)
Pseudogout
deposition of calcium pyrophosphate crystals in the joint space
basophilic, rhomboid crystals that are weakly birefringement in large joints (the knee!)
tx: NSAIDs, steroids, colchicine (ppx)
Seronegative spondylopathies (PAIR) - no rheumatoid factor (no anti-IgG)
HLA-B27
psoriatic arthritis
ankylosing spondylitis
IBD
reactive arthritis
Classic triad of reactive arthritis
Conjunctivitis, Urethritis, Arthritis
Can’t see, can’t pee, can’t bend my knee
Mechanism of lupus nephritis
Type 3 hypersensitivity
Nephritis - diffuse proliferative glomerulonephritis
Nephrotic - membranous glomerulonephritis
Causes of death in SLE
cardiovascular disease
infections
renal disease
SLE antibodies
anti-nuclear (ANA)** most sensitive
anti-dsDNA
anti-Smith (directed against snRNPs)
anti-histone (drug-induced lupus)
decr. C3, C4, due to immune complex formation
Anticardiolipin antibodies, lupus anticoagulant
Antiphospholipid syndrome
history of thrombosis (arterial/venous) or spontaneous abortion
note: false-positive VDRL, prolonged PTT
Immune-mediated widespread non-caseating granulomas
Sarcoidosis
also, elevated serum ACE levels, incr. CD4:CD8 ratio
hypercalcemia (incr. VitD activation in macrophages)
Pain/stiffness in shoulders/hips, fever, malaise, weight loss
Polymyalgia rheumatic
No muscular weakness!
Incr. ESR, CRP, Normal CK
Rapid response to low-dose steroids
Antibodies in polymyositis/dermatomyositis
ANA, anti-Jo, anti-SRP, anti-Mi-2
proximal muscle weakness (most often in shoulders)
look for endomysial inflammation with CD8 T cells
Dermatomyositis
vs. polymyositis: also involves malar rash, papules on knuckles (Gottron), periorbital rash (heliotrope)
incr. risk of malignancy
perimysial inflammation and atrophy with CD4 T cells
Metaplasia of skeletal muscle into bone following trauma
Myositis ossificans
May present as suspicious mass at site of known trauma or as incidental finding on radiography
Autoimmunity, noninflammatory vasculopathy, collagen deposition
Systemic scleroderma
Diffuse: skin involvement, rapid progression, early visceral involvement. Associated with anti-Scl70 antibody (anti-DNA topoisomerase antibody)
Limited: CREST - calcinosis, Raynaud, esophageal, sclerodactyly, telangiectasia. Associated with anti-centromere antibody
