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169 Cards in this Set

  • Front
  • Back
receptors on osteoblasts bind what chemicals?
hormones (PTH, vit D, leptin, estrogen)
cytokines
growth factors
extracellular matrix proteins
what makes osteoblasts transform into osteocytes?
if they are surrounded by newly deposited organic matrix
osteoclasts are defived from progenitors that also give rise to what?
monocytes and macrophages
which cytokines and growth factors regulate osteoclast differentiation and maturation?
M-CSF, IL-1, TNF
what pathways regulate bone homeostasis?
RANK/RANKL/OPG pathway

M-CSF/M-CSFr pathway

WNT/b-catenin/OPG pathway
which two factors oppose each other in bone homeostasis?
RANKL and OPG
noncollagenous protein measured in the serum for osteoblast activity
osteocalcin
what factors determine age of peak bone mass?
polymorphisms in receptors for vit D and LRP5/6, nutrition, physical activity, age, hormonal status
which type of bone growth uses cartilaginous model?
endochondral (longitudinal) ossification
mutation of HOXD13 gene produces what abnormalities?
extra digit between 3rd and 4th digit and syndactyly
loss-of-fxn mutation of RUNX2 gene results in what abnormality?
cleidocranial dysplasia (loss of osteoblastogenesis and chondrocyte activity); patent fontanelles, delayed closure of cranial sutures, Wormian bones, delayed tooth eruption, primitive clavicles, short height
most common disease of the growth plate?
achondroplasia
pathogenesis of achondroplasia?
mutated FGFR3 inhibits chondrocyte proliferation --> lack of longitudinal bone growth
phenotype of pt affected by achondroplasia?
short limbs with normal sized trunk and normal sized head w/ bulging forehead and depressed root of nose
pathogenesis of thanatophoric dwarfism?
gain-of-fxn mutation of FGFR3
phenotype of thanatophoric dwarfism?
short limbs, frontal bossing, relative macrocephaly, small chest cavity, bell-shaped abdomen
Endosteal hypreostosis, Van Buchem dz, and autosomal dominant osteopetrosis 1 are caused by what mutation?
gain-of-fxn mutation of LPR5
(cell surface receptor that activates WNT/B-catenin pathway in osteoblasts)
osteoporosis pseudoglioma syndrome is caused by what mutation?
loss-of-fxn mutation of LPR5 (cell surface receptor that activates WNT/B-catenin pathway in osteoblasts)
most commonly inherited disorder of CT?
osteogenesis imperfecta (brittle bone disease)
what determines whether phenotype of osteogenesis imperfecta will be mild or severe?
mild = decreased synthesis of normal collagen
severe = abnml polypeptide chains that can't be assembled into collagen
disease that results from autosomal dominant mutations of genes for α1 and α2 chains of collagen?
osteogenesis imperfecta
disease that is fatal in utero and has extraordinary bone frailty with multiple intrauterine fracutres?
osteogenesis imperfecta type II
pts with this disease have normal life span w/ childhood fractures that decrease at onset of puberty; blue sclera; hearing loss; dental imperfections
osteogenesis imperfecta type I
what is type 1 collagen disease called?
osteogenesis imperfecta
diseases associated with mutations of types 2, 9, 10 and 11 collagen have defects in what type of tissue?
hyaline cartilage
deficiencies in enzymes that degrade dermatan sulfate, haparan sulfate and karatan sulfate are called what?
mucopolysaccharidoses
mucopolysaccharidoses cause problems in what process?
cartilage formation
(chondrocytes metabolize ECM mucopolysaccharides)
mucopolysaccharidoses manifest in what structures?
cartilage anlage, growth plates, costal cartilages, articular surfaces
basic problem in osteopetrosis?
mutations interfere with acidification of osteoclast resorption pit
mutations of which genes cause the various forms of osteopetrosis?
CA2
CLCN7
TCIRG1
RANKL
morphologic chgs of bones in osteopetrosis?
bones lack medullary canal, ends of long bones are bulbous and misshapen, primary spongiosa is not removed, bones are brittle
bone abnormality presenting with fracture, anemia, hydrocephaly, CN defects, repeated infections?
osteopetrosis
when the general term "osteoporosis" is used, what forms is it referring to?
senile and postmenopausal osteoporosis
what is an example of low-turnover variant osteoporosis?
senile osteoporosis
what is an example of high-turnover variant osteoporosis?
postmenopausal osteoporosis
pathogenesis of postmenopausal osteoporosis?
dec estrogen --> inc inflammatory cytokines from monocytes and BM cells --> inc osteoclast recruitment and activity
postmenopausal osteoporosis most frequently affects what areas?
cancellous compartment of vertebral bodies
mosaic bone pattern, inc Alk Phos, possible high-output heart failure. Dx?
Paget's disease (osteitis deformans)
severe complication of Paget's disease?
development of osteosarcoma
in children, it's called rickets; in adults, it's called osteomalacia - disorder?
vitamind D deficiency or disturbance in its metabolism
abnml lab values in osteomalacia?
dec Ca, inc PTH, dec serum phosphate
increased bone cell activity, peritrabecular fibrosis, cystic brown tumors?
osteitis fibrosa cystica, hyperparathyroidism
what causes brown tumors?
osteitis fibrosa cystica

microfractures and secondary hemorrhage elicit influx of macrophages and ingrowth of fibrous tissue
manifestations of chronic renal dz in bone?
- inc bone resorption
- osteomalacia
- osteosclerosis
- growth retardation
- osteoporosis
pathogenesis of bone changes in renal failure?
- phosphate retention --> inc PTH
- dec conversion of Vit D --> dec reabs of Ca and inc PTH
- metabolic acidosis --> inc bone resorption
MS complication of hemodialysis?
deposition of amyloid in bone and periarticular structures
closed (simple) fracture?
skin is intact
compound fracture?
fracture communicates with skin surface
comminuted fracture?
bone is splintered
most common regions of osteonecrosis?
medullary cavity of metaphysis or diaphysis, subchondral region of epiphysis
which type of osteonecrosis is worse: subchondral or medullary?
subchondral, as it is associated with chronic pain and collapse, predisposing to severe secondary osteoarthritis
in adults, osteomyelitis occurs as a complication of what?
open fractures, surgical procedures, diabetic infections of the feet
in children, osteomyelitis occurs as a complication of what?
trivial injuries to mucosa or minor skin infxns
MCC of pyogenic osteomyelitis?
S. aureus
MCCs of pyogenic osteomyelitis in pts w/ GU infxn or IVDU?
E. coli, Pseudomonas, Klebsiella
most common site of osteomyelitis in neonate?
metaphysis, epiphysis or both
most common site of osteomyelitis in children?
metaphysis
most common site of osteomyelitis in adults?
epiphyses and subchondral regions
how is an involucrum formed?
chronic inflammatory cells around initial infxn release cytokines that stimulate bone resorption and peripheral bone deposition
small intraosseous abscess of cortex, walled off by reactive bone?
Brodie abscess
complication of osteomyelitis that develops in the jaw, assocd with extensive new bone formation that obscures underlying bone structure?
sclerosing osteomyelitis of Garre
on x-ray of focal bone pain, you see a lytic lesion surrounded by a zone of sclerosis. Dx?
osteomyelitis
what can lead to chronicity in osteomyelitis?
delay in dx, extensive bone necrosis, inadequate abx therapy or debridement, weakened host defenses
difference btwn pyogenic and tuberculous osteomyelitis?
tuberculous is more destructive and resistant to control and has tropism for the spine, hips and knees
pt presents with low grade fever, chills, night sweats, wt loss, low back tenderness w/ pain on motion. Dx?
Tuberculous osteomyelitis
when do bone lesions begin to appear in congenital syphilis?
5th month of gestation
in acquired syphilis, when does bone disease begin?
early tertiary phase (2-5 y after infxn)
cause of saber shin?
skeletal syphilis
(massive reactive periosteal bone deposition on medial and anterior tibial surfaces)
most common primary cancer of bone?
osteosarcoma
most common benign bone tumors?
osteochondroma and fibrous cortical defect
bosselated, round-to-oval sessile tumors of subperiosteal surface of cortex, on or inside skull and facial bones; usually solitary, detected in middle age
osteoma
benign tumor <2cm in pt <25; often involve posterior spine, femur, or tibia; cause severe nocturnal pain responsive to aspirin
osteoid osteoma
benign tumor >2cm; usually in the spine; dull, achy pain unresponsive to aspirin; does not induce bony reaction
osteoblastoma
benign tumor associated with Gardner's syndrome (FAP), grows on existing bone?
osteoma
benign tumors of interlacing trabeculae of woven bone surrounded by osteoblasts?
osteoid osteoma and osteoblastoma
malignant tumor most common in men age 10-20 in metaphysis of long bones (esp around knee); elevation of periosteum produces "Codman's triangle" on x-ray
Osteosarcoma
most common benign bone tumor, usually in men < 25 on long metaphysis, cartilage-capped tumor attached by bony stalk,
osteochondroma (exostosis)
benign cartilaginous tumor usually found in intramedullary bone, usually of short tubular bones of hands and feet
chondroma/enchondroma
rare, benign cartilaginous tumor most commonly around the knee in young males; chicken-wire pattern of mineralization?
chondroblastoma
rarest cartilage tumor, variable morphology, most often young males, in metaphysis of long tubular bones; on x-ray, eccentric lucency, well delineated from adjacent bone by rim of sclerosis
chondromyxoid fibroma
malignant cartilaginous tumor of men age 30-60, usually in pelvis, spine, scapula, humerus, tibia, or femur; expansive glistening mass within medullary cavity
chondrosarcoma
developmental defect found in 30-50% of children >2 y.o., most arise eccentrically in metaphysis of distal femur and prox tibia
fibrous cortical defects
(non-ossifying fibroma if grows to >5-6cm)
benign tumor in which bone replaced by fibroblasts, collagen and irreg bony trabeculae, affects many bones; essentially a localized developmental arrest
fibrous dysplasia
multiple unilateral bone lesions assocd with endocrine abnormalities (precocious puberty) and unilateral pigmented skin lesions (cafe-au-lait spots)?
McCune-Albright syndrome
(polyostotic fibrous dysplasia)
anaplastic small blue cell malignant tumor most common in boys < 15; assoc'd with t(11;22); onion-skin appearance in bone; commonly in diaphysis of long bones, pelvis, scapula, and ribs
Ewing's sarcoma

(primitive neurectodermal tumor is a variant)
benign but locally aggressive tumor at epiphyseal end of long bones esp around knee; peak age 20-40; "soap bubble" on x-ray; spindle-shaped cells w/ multinucleated giant cells
giant cell tumor (osteoclastoma)
benign tumor w/ blood-filled spaces; most often in pts <20; most often in metaphyses of long bones and posterior vertebral bodies
aneurysmal bone cyst
most common form of skeletal malignancy?
metastatic tumors
most common origins of metastasis to bone in adults?
cancers of prostate, breast, kidney, and lung
most common origins of metastasis to bone in children?
Wilms tumor, osteosarcoma, neuroblastoma, Ewing sarcoma, rhabdomyosarcoma
cause of lytic bone lesions in metastatic tumors?
metastatic cells secrete PGs, cytokines, and PTH-related protein that stimulate osteoclast activity
why do metastatic tumors grow well in bone?
lysis of bone tissue rich in TGF-β, IGF-1, FGF, PDGF, and bone morphogenetic proteins helps create environment conducive to tumor cell growth
what activates degradative enzymes that break down cartilage?
IL-1 and TNF from chondrocytes, synoviocytes, fibroblasts, and inflammatory cells
the pathology of this disease of joints is d/t intrinsic breakdown of cartilage, not inflammation
osteoarthritis
causes of secondary osteoarthritis?
previous injuries to a joint, congenital joint deformity, diabetes, ochronosis, hemochromatosis, marked obesity
complications of osteoarthritis?
subchondral cysts, sclerosis, osteophytes, eburnation, heberden's nodes
deep, achy pain that worsens with use, morning stiffness, crepitus and limitation of ROM?
osteoarthritis
what joints are typically spared in osteoarthritis?
wrists, elbows, shoulders
chronic, inflammatory disorder producing nonsuppurative proliferative and inflammatory synovitis that often progresses to destruction of the cartilage and ankylosis of the joints?
rheumatoid arthritis
RA is seen ____ frequently in women than in men
more (3-5x)
RA has strong association with what HLA antigen?
HLA-DR4
what causes the joints to be red and warm in RA?
increased vascularity d/t vasodilation and angiogenesis
cause of subchondral cysts and osteoporosis in RA?
osteoclastic activity in underlying bone allows synovium to penetrate into bone
where is pannus formation most often seen?
MCP, PIP
what joints are characteristically spared in RA?
DIP, lumbosacral spine, hips
what are rheumatoid nodules?
fibrinoid necrosis surrounded by palisading histiocytes; arise in skin regions subject to pressure (ulnar FA, elbows, occiput, lumbosacral area)
40 yo female w/ BL pain, warmth, and swelling in ankles, fingers, and feet with morning stiffness?
Rheumatoid arthritis
purpura, cutaneous ulcers and nail bed infarction d/t leukocytocastic venulitis is seen in what disease?
RA
pathogenesis of RA?
activation of CD4+ --> stimulate synoviocytes and macrophages --> release proinflammatory mediators (IL-1, IL-6, IL-23, TNF, PGE2, NO, TGF-b, GM-CSF) --> activates endothelial cells --> increased leukocyte binding --> Ag-Ab complexes destroy cartilage and stimulate osteoclasts
radiographic hallmarks of RA?
joint effusions, juxta-articular osteopenia w/ erosions and narrowing of joint space w/ loss of articular cartilage
joint involvement pattern in RA?
usually symmetrical, small joints before larger ones (hands, feet first)
therapies for RA?
corticosteroids, methotrexate, antagonists of TNF
how does JIA differ from RA in adults?
- oligoarthritis is more common
- systemic dz more frequent
- large joints > small joints
- no rheumatoid nodules or RF
- ANA + is common
remitting, high spiking fevers, migratory and transient skin rash, hepatosplenomegaly, and serositis?
Systemic arthritis-type JIA
what type of hypersensitivity reaction is RA?
type III
what is rheumatoid factor?
anti-IgG antibody, present in 80% of RA pts
antibody other than RF used in dx of RA?
anti-CCP Ab
what systemic sxs are assocd with RA?
fever, fatigue, pleuritis, pericarditis
seronegative spondyloarthropathies have strong association with what?
HLA-B27
chronic inflammatory dz of spine and sacroiliac joints --> stiff spine, uveitis, and AR; RF negative.
Ankylosing spondylitis
triad of conjuctivitis/anterior uveitis, urethritis, and arthritis; caused by autoimmune rxn initiated by GI or chlamydial infxn
Reiter syndrome (reactive arthritis)
pt presents with thick red patches of skin with silvery-white scales, asymmetric dactylitis of DIPs and swelling of ankles, knees, hips, or wrists?
psoriatic arthritis
MCC acute suppurative arthritis?
bacterial arthritis
MCC bacterial arthritis in children under 2?
H. influenzae
MCC bacterial arthritis in older children and adults?
S. aureus
gonococcal arthritis is prevalent in what age groups?
late adolescents and young adults
Salmonella is a cause of bacterial arthritis in what subset of pts?
sickle cell disease pts
sudden development of single acutely painful and swollen joint w/ restricted ROM; fever, leukocytosis, elevated ESR?
bacterial arthritis
most common joint affected by bacterial arthritis?
knee
chronic, progressive monoarticular disease w/ confluent granulomas w/ central caseous necrosis most commonly in hips, knees, or ankles?
tuberculous arthritis
60-80% of untreated cases of what disease develop arthritic sxs in large joints?
Lyme disease
monoarticular, migratory arthritis with asymmetrical pattern; presents with synovitis, tenosynovitis, and dermatitis?
gonococcal arthritis
most individuals with chronic gout also develop what?
urate nephropathy
uric acid is the end product of what?
purine metabolism
hyperuricemia develops from what in 90% of cases?
reduced excretion of uric acid

(other 10% is from overproduction)
deficiency of what enzyme leads to increased purine synthesis by the de novo pathway?

in what inherited disorder is this seen?
HGPRT

Lesch-Nyhan syndrome (x linked)
what factors contribute to development of primary gout?
- Age
- inheritance
- alcohol consumption
- obesity
- thiazides
- Pb toxicity
what attracts neutrophils to sites of MSU crystal deposition?
MSU phagocytosed by macrophages => IL-1b, IL-18 => inc adhesion molecules and neutrophil chemokine CXCL8
what produces the actual tissue injury and inflammation of acute gouty arthritis?
neutrophils that phagocytose crystals release PGs and free radicals, and are eventually lysed and release lysosomal enzymes into joint
what are tophi?
large aggregates of precipitated crystals and the surrounding inflammatory reaction
first attack of gout usually occurs where?
1st MTP
systemic diseases associated with gout?
CV disease (atherosclerosis and HTN)

renal colic --> nephropathy
asymmetric joint disease w/ nodule formation on external ear, olecranon, or Achilles tendon; acute episodes occur after large meal or alcohol consumption?
gout
crystals aspirated in joint space are weakly birefringent, basophilic, rhomboid shape
pseudogout
crystal deposition disease more common in men
gout
why does alcohol predispose to gouty attack?
it competes for same excretion sites in kidney as uric acid, causing dec uric acid secretion and buildup in blood
small cyst almost always located near joint capsule or tendon sheath?
ganglion cyst
herniation of synovium through a joint capsule or massive enlargement of a bursa may produce what?
a synovial cyst
benign neoplasms of synovial linings, tendon sheaths and bursae; heavily infiltrated by macrophages that may have hemosiderin and lipid filled vacuoles; may form multinucleated giant cells?
tenosynovial giant-cell tumor
solitary, slow-growing, painless mass often on tendon sheaths of wrists and fingers, most common mesenchymal neoplasm of the hand?
localized tenosynovial giant-cell tumor
soft, well-encapsulated fat tumor. Benign. Simple excision is usually curative.
Lipoma
malignant fat tumor that can be large. Will recur unless adequately excised.
liposarcoma
Benign tumor derived from striated muscle. May occur in heart in tuberous sclerosis.
rhabdomyoma
Most common soft tissue tumor of childhood. malignant. Arises from skeletal muscle, most often in head/neck.
Rhabdomyosarcoma
mimics sarcoma, occurs in adults on volar aspect of forearm, also on chest and back. Deep dermis, subcutis, or muscle
nodular fasciitis
bone metaplasia that arises in musculature of athletic young adults, often after trauma. Initially filled with fibroblast/myofibroblast-like cells, eventually becoming ossified
myositis ossificans
similar malignant disease to myositis ossificans?

what is the major clinical difference?
extraskeletal osteosarcoma

osteosarcoma occurs in elderly and lacks zonation of myositis ossificans
benign nodular or broad fascicles of fibroblasts and myofibroblasts surrounded by abundant dense collagen, leading to contractures of the 4th and 5th digits of the hand and abnml curvature of the penis and urethral constriction
Superficial fibromatosis
what is the palmar variant fibromatosis called?
Dupuytren contracture
what is the penile variant fibromatosis called?
Peyronie disease
large, infiltrative masses of well-differentiated fibroblasts that do not metastasize, but may recur after excision; have mutations in APC or b-catenin gene
deep-seated fibromatosis
arises in musculoaponeurotic structures of anterior abd wall in women during or after pregnancy
abdominal fibromatosis
aggressive, malignant neoplasm commonly occuring in deep soft tissues of extremities. Unencapsulated, infiltrative, soft, fish-flesh masses w/ areas of hemorrhage and necrosis
Fibrosarcoma
benign fibroblast neoplasm f the dermis and subcutis. Painless, slow-growing, firm, small, mobile nodule of middle aged adults.
Benign fibrous histiocytoma (dermatofibroma)
skeletal muscle neoplasms are almost all ______?
malignant
benign smooth muscle tumors often arising in the uterus
leiomyomas
hereditary leiomyomatosis has a predisposition to develop what other neoplasm?
renal cell carcinoma
malignant tumor of smooth muscle that affects adults, women > men, mostly in skin and deep soft tissues of extremities and retroperitoneum
leiomyosarcoma
malignant neoplasm of unclear origin, pt age 20-40, arises in deep soft tissue, esp around knee/thigh; commonly biphasic or monophasic on histology. Positive for keratin and epithelial membrane antigen
Synovial sarcoma