Pathology - musculoskeletal

Question 1

Failure of longitudinal bone growth

Answer 1

Achondroplasia

Constitutive activation of FGF-receptor 3 inhibits chondrocyte proliferation

Membranous ossficiation not affected, so large head but small body

Question 2

Loss of trabecular bone mass w/ normal bone mineralization

Answer 2

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)

Question 3

Failure of normal bone resorption due to defective osteoclasts leads to thick dense bones prone to fracture

Answer 3

Osteopetrosis

Bone also fills marrow, so pancytopenia

Carbonic anhydrase mutation

Can also narrow foramina (leading to cranial nerve palsies)

Tx: bone marrow transplant

Question 4

Defective mineralization/calcification of osteoid

Answer 4

Osteomalacia

Vit. D deficiency (low Vit D –> low serum Ca –> high PTH –> loss of PO4)

Look for incr. Alk Phos (hyperactivity of osteoblasts)

Question 5

Localized disorder of bone remodeling, mosaic pattern of woven and lamellar bone

Answer 5

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

Question 6

Painful infarction of bone and marrow

Answer 6

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)

Question 7

Knee tumor vs. cartilaginous cap

Answer 7

Benign bone tumors

Giant cell tumor: multinucleated giant cells, end of long bones

Osteochondroma: most common (exostosis of bone), mature bone with cartilaginous cap

Question 8

Osteosarcoma vs. Ewing sarcoma (malignant bone tumors)

Answer 8

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)

Question 9

Rheumatoid arthritis immune mechanism

Answer 9

Type 3 and Type 4 hypersensitivity

Look for rheumatoid factor (anti-IgG antibody), anti-CCP, HLA-DR4

Question 10

Destruction of salivary glands by lymphocytic infiltrates

Answer 10

Sjogren’s

Sx: inflammatory, anti-SSA/anti-SSB (Ro/La)

Complications: dental caries, MALT lymphoma

Question 11

Mechanisms of gout

Answer 11

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)

Question 12

Gout treatment regimens (acute and chronic)

Answer 12

Acute: NSAIDs, steroids, colchicine (inhibits microtubule polymerization in neutrophils)

Chronic: allopurinol, febuxostat (xanthine oxidase inhibitor)

Question 13

Pseudogout

Answer 13

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)

Question 14

Seronegative spondylopathies (PAIR) - no rheumatoid factor (no anti-IgG)

Answer 14

HLA-B27

psoriatic arthritis
ankylosing spondylitis
IBD
reactive arthritis

Question 15

Classic triad of reactive arthritis

Answer 15

Conjunctivitis, Urethritis, Arthritis

Can’t see, can’t pee, can’t bend my knee

Question 16

Mechanism of lupus nephritis

Answer 16

Type 3 hypersensitivity

Nephritis - diffuse proliferative glomerulonephritis

Nephrotic - membranous glomerulonephritis

Question 17

Causes of death in SLE

Answer 17

cardiovascular disease

infections

renal disease

Question 18

SLE antibodies

Answer 18

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

Question 19

Anticardiolipin antibodies, lupus anticoagulant

Answer 19

Antiphospholipid syndrome

history of thrombosis (arterial/venous) or spontaneous abortion

note: false-positive VDRL, prolonged PTT

Question 20

Immune-mediated widespread non-caseating granulomas

Answer 20

Sarcoidosis

also, elevated serum ACE levels, incr. CD4:CD8 ratio

hypercalcemia (incr. VitD activation in macrophages)

Question 21

Pain/stiffness in shoulders/hips, fever, malaise, weight loss

Answer 21

Polymyalgia rheumatic

No muscular weakness!

Incr. ESR, CRP, Normal CK

Rapid response to low-dose steroids

Question 22

Antibodies in polymyositis/dermatomyositis

Answer 22

ANA, anti-Jo, anti-SRP, anti-Mi-2

proximal muscle weakness (most often in shoulders)

look for endomysial inflammation with CD8 T cells

Question 23

Dermatomyositis

Answer 23

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

Question 24

Metaplasia of skeletal muscle into bone following trauma

Answer 24

Myositis ossificans

May present as suspicious mass at site of known trauma or as incidental finding on radiography

Question 25

Autoimmunity, noninflammatory vasculopathy, collagen deposition

Answer 25

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