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422 Cards in this Set
- Front
- Back
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what is a dysostoses? |
congenital malformation, realtively benign
|
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what is a craniorachischisis?
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failure of closure of spinal column and skull
*meningomyelocele - when meninges herniates *meningoencephalocele - when meninges AND CNS herniate |
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inheritance of osteogenesis imperfecta?
mutation results in? |
AD
*defect in synthesis of collagen type I |
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manifestations of osteogenesis imperfecta?
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prominent skeletal malformations
joints eyes (blue) ears teeth skin *leads to osteopenia |
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which form of OI is lethal?
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OI type II
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where is the mutation in achondroplasia?
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short arm of chromosome 4
(FGF receptor 3) |
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consequences of the FGF receptor - 3 mutation seen in achondroplasia?
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mutation causes FGF receptor 3 to be constantly activated -> this inhibits cartilage proliferation in growth plate)
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phenotype of an individual with achondroplasia?
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dwarfism
shortened proximal extremities enlarged head normal trunk length (normal intelligence, longevity, repr. status) |
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osteopetrosis is due to?
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mutation in gene for osteoclast formation/function
(causes net bone overgrowth and increased bone density) |
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what are the consequences of the following in osteopetrosis: bone lacks a medullary canal
|
decreased hematopoiesis
-anemia (extramedullary hematopoiesis, hepatosplenomegaly) -neutropenia |
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what are the consequences of the following in osteopetrosis: small neural foramina
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see nerve compression
-visual disturbance, deafness |
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describe the bones seen in osteopetrosis
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"brittle bone disease" - bones fracture like a piece of chalk
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treatment for osteopetrosis?
|
bone marrow transplant
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describe Albers-Schonberg disease
|
*group of RARE genetic diseases that manifest as osteopetrosis
*variable inheritance |
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describe AD type II osteopetrosis
|
*more common benign form
*seen in adolescents/adults *may be asymptomatic -or see- *repeated fractures *mild anemia *mild CN deficits |
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describe the AR malignant type of osteopetrosis
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*infantile, severe, often fatal
*manifests in utero or shortly after birth *fractures *anemia *hydrocephaly (if survive into infancy - CN entrapment, death from severe anemia, infections) |
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what is an osteochondroma?
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benign cartilage outgrowth of the metaphysis, arises from the epiphyseal cartilage(growth plate) of long bones
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describe a solitary osteochondroma
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*slow growing mass, diagnose in late adolescence, young adult
*often incidental finding *painful if nerve entrapment, fracture of stalk *usually stop growing at time of growth plate closure |
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describe a hereditary exostosis
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multiple osteochondromas, AD inheritance
*men affected 3x>women *underlying bones may be bowed and shortened |
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hereditary exostosis may have an increased risk of developing?
|
chondrosarcoma
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describe a chondroma
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* benign tumor of hyaline cartilage
* develops from rests of growth plate cartilage * cartilage rest proliferates and slowly enlarges |
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what is an endochondroma?
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a chondroma that lies within the medullary cavity
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what is a juxtacortical or subperiosteal chondroma?
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a chondroma that lies at the bone surface
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are chondromas MC multiple or solitary?
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solitary
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are chondromas usually symptomatic or asymptomatic?
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most often asymptomatic
(sometimes painful and cause pathologic fractures) |
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both ollier's disease and maffuci syndrome are syndromes involving?
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multiple endochondromas
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1. ollier's disease is?
2. Maffuci sydrome is? |
1. multiple endochondromas
2. multiple endochondromas PLUS soft tissue hemangiomas |
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maffuci syndrome may have an increased risk of developing?
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other malignancies
(ovarian carcinoma, brain gliomas) |
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endochondromatosis in general has a risk of what kind of transformation?
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sarcomatous
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in pyogenic osteomyelitis, how do most bacteria reach the bone?
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hematogenous spread
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80% of all cases of pyogenic osteomyelitis are caused by?
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Staph aureus
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virulence factors of S. aureus when it comes to pyogenic osteomyelitis?
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produces receptors to bone matrix components (collagen) -> facilitates adherence to bone tissue
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3 bacteria that cause pyogenic osteomyelitis that could come from a GU tract infection or IV drug abuse?
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E. coli
Pseudomonas Kelbsiells |
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2 bacteria causing pyogenic osteomyelitis in neonates?
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Group B strep
H. influenzae |
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which bacteria is known to cause pyogenic osteomyelitis in sickle cell disease patients?
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Salmonella
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where is pyogenic osteomyelitis commonly found in diabetics?
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small bones in feet
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why is pyogenic osteomyelitis found in different locations depending upon the age of the patient?
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vascular circulation varies with age
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where is osteomyelitis MC found in neonates and why?
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metaphysis, epiphysis or both
(metaphyseal vessels penetrate the growth plate) |
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where is osteomyelitis MC found in kids?
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metaphyseal leasions
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where is osteomyelitis MC found in adults and why?
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epiphyses and subchondral bone
(metaphyseal vessels reuinte with epiphyseal counterparts after growth plate closure) |
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pathophysiology of pyogenic osteomyelitis?
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*bacteria proliferate in bone
*acute inflammation *death of osteocytes *necrosis of bone |
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define:
1. sequestrum 2. involucrum 3. Brodie abscess |
1. dead piece of bone
2. sleeve of reactive bone surrounding sequestrum 3. intraosseous abscess walled off by reactive bone |
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in infants: where does an epiphyseal osteomyelitis infection tend to spread
|
joint
(septic joint) |
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symptoms of pyogenic osteomyelitis?
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variable (malaise, chills, fever, leukocytosis, throbbing pain in affected bone)
* adults - localized bone pain w/o fever *infants - unexplained fever (more subtle) |
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what would be seen in an Xray of a bone with osteomyelitis?
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lytic bone destruction with surrounding sclerosis
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treatment for pyogenic osteomyelitis?
|
surgical drainage
Abx |
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complications of pyogenic osteomyelitis?
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*acute flare-ups
*pathologic fractures *secondary amyloidosis *endocarditis *sepsis *SCC in sinus tract *sarcoma in infected bone (rare) |
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1/3 of patients with TB have this bone complication
|
tuberculous osteomyelitis
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where is tuberculous osteomyelitis MC found?
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thoracic/lumbar vertebrae
(usually solitary, multifocal in AIDS) |
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which is more destructive: tuberculous or pyogenic osteomyelitis?
|
tuberculous
(extensive necrosis) |
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what is Pott's disease?
|
tuberculous osteomyelitis, with involvement of the thoracic/lumbar spine
*multiple vertebrae *see necrosis of intervertebral discs with extension to soft tissues (causes deformities) |
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deformities and complications seen in Pott's disease?
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*permanent compression fractures -> kyphosis
*nerve impingement -> deficits |
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3 complications of pathologic fractures?
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tumor
osteoporosis infection |
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overview of steps in fracture repair?
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soft tissue callus -> provisional callus -> Bony callus
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describe formation of a soft tissue callus
|
*hematoma forms between broken bones
*this provides a firbin mesh which seals fracture stie *osteoprogenitor cells are activated, see osteoclast and osteoblast activity *formation of fusiform uncalcified soft tissue (no structural support) |
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describe the formation of a provisional callus from a soft tissue callus
|
*activated progenitor cells deposit trabeculae
*mesenchymal cells differentiate in to chondroblasts -> form fibrous and hyaline cartilage *endochondral ossification occurs |
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describe the formation of a bony callus
|
remodeled and matured provisional callus (forms along weight bearing lines)
*unstressed portions are resorbed *medullary cavity restored |
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complications of fracture repair?
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*delayed healing/deformed callus
*malalignment *devitalized bone fragments *inadequate immobilization (may result in delayed union, pseudoarthrosis) *infection **complications may be caused by malnutrition, vascular insufficiency, systemic disease, old age** |
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what is one reason that the elderly have an increased risk of osteoporosis?
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*decreased osteoblastic activity
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connection between physical activity and rate of bone loss?
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physical activity decreases the rate of bone loss
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a calcium deficiency at which time in life will put an individual at greatest risk of osteoporosis?
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rapid bone growth (adolescence)
*stunted peak bone mass |
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changes in bone metabolism during menopause?
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*estrogen deficiency leads to increased osteoclast activity (increased IL-1)
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Rickets/Osteomalacia is a defect in bone mineralization due to?
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liack of vitamin D or a disturbance in metabolism
(results in accumulation of unmineralized bone matrix) |
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manifestations of Rickets in children?
|
rickets - "to twist"
irregular epiphyseal growth plates around kneww and wrist (bowed legs) |
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what is osteomalacia and what does it result in?
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undermineralized bone, results in osteopenia and fractures
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what is seen upon Xray of rickets or osteomalacia?
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generalized osteopenia
also, stress fractures (multiple bilateral and symmetrical liner fractures) |
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how is rickets or osteomalacia diagnosed?
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biopsy of long bone or iliac crest
adults - wide noncalcifies matrix of newly formed bone kids - thickened, poorly defined growth plate |
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metabolic bone disease is due to what parathyroid disorder?
|
hyperparathyroidism
(increased PTH) |
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what is a musculoskeletal complication of hyperparathyroidism if it is not caught early?
|
osteitis fibrosa cystica
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1. two primary reasons for increased PTH?
2. secondary reasons for increased PTH? |
1. hyperplasia or adenoma of PT gland
2. chronic hypocalcemia, renal disease, Vit. D deficiency |
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for osteitis fibrosa cystica, describe:
1. early stage 2. second stage 3. third stage |
1. increased osteoclastic acticity - osteitis
2. resorped bone replaced by fibrosis, hemorrhage, hemosiderin, microfractures (fibrosa) 3. cystic degeneration (cystica) |
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what is a Brown tumor?
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reparative reaction, not a true tumor
(multinucleated cells, osteoclasts, hemosiderin, fibrosis, hemorrhage) |
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skeletal changes due to chronic renal disease is called?
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renal osteodystrophy
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what are some manifestations of renal osteodystrophy?
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*increased resorption of bone
*phosphate retention (secondary hyperparathyroidism) *delayed matrix mineralization *otosclerosis *growth retardation *osteoporosis |
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describe osteonecrosis
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avascular/ischemic necrosis
-necrosis of bone and marrow IN THE ABSENCE OF INFECTION ("aseptic necrosis") |
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what is Legg-Calve-Perthes disease?
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osteonecrosis of the femoral head in children
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where does Osgood-Schlatter's manifest?
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tibial tuberosity
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pathophysiology of osteonecrosis?
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*initially necrosis of trabecular bone and marrow
*then see subchondral infarcts (triangular shaped necrosis with subchondral bone as its base) *overlying articular cartilage normal *creeping substitution (dead trabeculae serve as scaffolds for deposition of new living bone) |
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gross manifestatons of osteonecrosis?
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intact overlying articular cartilage, underlying yellow necrotic area
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micro manifestations of osteonecrosis?
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*dead trabeculae with empty lacunae
*Ca++ salts due to necrotic fatty marrow |
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other disorders associated with osteonecrosis?
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fracture
*corticosteroids thrombosis & embolism vessel injury |
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how common is Paget's disease?
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very
(90% of patients >65 yrs) MC in whites |
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hypothesis for the etiology of paget's disease?
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slow virus infection (paramyxovirus)
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two types of Paget's disease?
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polyostotic (85%)
monostotic (15%) |
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where is polyostotic Paget's disease MC found?
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pelvis
spine skull |
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where is monostotic Paget's disease MC found?
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tibia, ilium, femur, skull, vertebrae, humerus
(often asymptomatic) |
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late Xray findings for Paget's disease?
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increased bone density, loss of distinction between cortex and medulla
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Symptoms of Paget's?
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*mild localized pain due to microfractures
*osteoarthritis *high output CHF in polyostotic form (hypervascular bone) |
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Labs in Paget's disease?
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elevated alk. phos.
elevated urinary hydroxyproline |
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Rx. of Paget's disease?
|
calcitonin
diphosphanates |
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complications of Paget's?
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development of a sarcoma (osteosarcoma, malignant fibrous histiocytoma, chondrosarcoma)
5-10% |
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three phases/descriptions of Paget's disease?
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1. osteolytic phase (excessive osteoclastic bone absorption, large osteoclasts with excessive nuclei)
2. mixed osteoclastic/osteoblastic phase (hectic bone formation) 3. osteosclerotic/burnt out phase (gain in bone mass but disordered, mosaic bone pattern, jigsaw puzzle) |
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describe fibrous dysplasia
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localized developmental abnormality of bone forming mesenchyme, hyperfunction of mesenchymal cells, bone arrested at woven stage
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3 MC locations of fibrous dysplasia?
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craniofacial bones
femur ribs |
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in relation to fibrous dysplasia:
1. 70% of cases are of which type? 2. 27% of cases are of which type? |
1. monostotic
2. polyostotic |
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gender differences in monostotic fibrous dysplasia?
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male=female
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where does monostotic fibrous dysplasia MC manifest?
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ribs, femur, tibia, jaw
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what is a major difference between monostotic and polyostotic fibrous dysplasia?
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monostotic - resolves after puberty
polyostotic - persists into adulthood (progression) |
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describe the progression of polyostotic fibrous dysplasia
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recurring fractures, long bone and facial deformities
(rare malignant transformation) |
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what is McCune Albright syndrome?
|
polyostotic fibrous dysplasia + endocrinopathies
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describe the manifestations of McCune-Albright syndrome
|
cafe-au-lait spots
precocius puberty in girls also see endocrinopathies (sexual precocity, hyperthyroidism, pituitary adenomas w/ GH secretion, primary adrenal hyperplasia) *skin pigmentation on same side of body as bone lesion |
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hypertrophic osteoarthropathy is due to a paraneoplastic syndrome. what are the three components seen?
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1. clubbing of fingers
2. periostitis with new bone formation at distal end of long bones 3. arthritis |
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hypertrophic osteoarthropathy is MC seen with which cancer?
|
bronchogenic carcinoma
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most bone tumors are benign in what age group and malignant in what age group?
|
benign - kids
malignant - elderly |
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clinical significance of an osteoma?
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benign, rare, slow growing (little clinical significance, but may obstruct sinus cavity, impinge on brain, eye; cosmetic problem)
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osteoid osteomas are MC in:
1. what age group 2. what sex? 2. what bones? |
1. under 25 yrs
2. males (2:1) 3. femur/tibia (50%) |
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why is an osteoid osteoma so painful?
|
pain is caused by excess prostaglandin E2 produced by proliferating osteoblasts
(pain relief with ASA) |
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Xray manifestations of an osteoid osteoma?
|
small round lucency with variable mineralization surrounded by extensive sclerosis
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Treatment for an osteoid osteoma?
|
excision
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what is the MC primary bone tumor after myeloma?
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osteosarcoma
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pathophysiology of an osteosarcoma?
|
*malignant spindle osteoblasts produce malignant bone matrix. *arise in the metaphyseal region of long bones (60% around the knee)
*associated with p53 mutation |
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what would be seen upon Xray of an osteosarcoma?
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large destructive lesion or blastic mass
Codman's triangle |
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What is Codman's triangle and what is it a result of?
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triangular shadow between cortex and raised periostium (result of reactive bone formation)
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clinical sx. of an osteosarcoma?
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painful, rapidly enlarging mass
(fracture may be 1st symptom) |
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10-20% of people with osteosarcoma have what else at the time of diagnosis?
|
lung mets
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treatment of osteosarcoma?
|
chemotherapy
limb salvage therapy (5 yr survival - 70%) |
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what is the 3rd MC bone malignancy after myeloma, osteosarcoma?
|
chondrosarcoma
|
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chrondoma may arise from?
|
osteochondroma
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chondrosarcoma MC effects:
1. what age group? 2. what sex? 3. what sites? |
1. 40 yrs +
2. men > women 3. large bones (pelvis, ribs, femur, humerus, vertebrae) |
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what is seen upon Xray of a chondrosarcoma?
|
large tumor
fluffy calcifications |
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what does a chondrosarcoma look like grossly?
|
pearly white or light blue
focal calcifications |
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micro characteristics of a chondrosarcoma?
|
malignant chonrocytes produce cartilagenous matrix
|
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is a giant cell tumor of bone benign or malignant?
|
benign (but locally aggressive)
|
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in a giant cell tumor of bone what forms the giant cells?
|
fusion of monunuclear cells
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in relation to a giant cell tumor of bone:
1. MC age? 2. MC site? |
1. 20-40 yrs
2. knee (but any bone can be involved) |
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treatment for a giant cell tumor of bone?
|
surgical curetage
(radiation only if surgery impossible) |
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Ewing sarcoma involves what genetic mutation?
|
11:22 translocation
|
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age group affected by Ewing sarcoma?
|
majority <20 yrs
|
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where does Ewing sarcoma MC arise?
|
medullary cavity of diaphysis of long bones (femur, tibia, humerus, fibula)
|
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how does Ewing sarcoma present?
|
painful enlarging mass
*site is tender, warm, swollen |
|
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gross manifestations of ewing sarcoma?
|
white fleshy/necrotic
|
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treatment for ewing sarcoma?
|
preop chemo
surgery radiation |
|
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prognosis for ewing sarcoma?
|
ok
5 yr survival ~75% |
|
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what four carcinomas commonly metastasize to bone?
|
breast
lung kidney prostate |
|
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what are the 3 pathways of spread for metastatic cancer to bone?
|
1. direct extension
2. lymphatic or hematogenous spread 3. intraspinal seeding |
|
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which type of arthritis is caused by bacterial infections in general?
|
pyogenic arthritis
|
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which type of arthritis is caused by mycobacterium tuberculosis?
|
tuberculous arthritis
|
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which type of arthritis is a sequelae to a Group A Strep infection?
|
arthritis of acute rheumatic fever
|
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which type of arthritis is caused by borrelia burgdorferi?
|
Lyme arthritis
|
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pyogenic arthritis is also known as?
usual result of? |
acute suppurative arthritis
(usually the result of hematogenous spread, occasionally bacteria infect joints) |
|
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what are the MC organisms in pyogenic arthritis?
|
Cocci (gonococcus, staphylococcus, streptococcus)
Gram neg. bacilli (E.coli, salmonella, pseudomonas) |
|
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MCC of pyogenic arthritis in children <2 yrs?
|
H. infuenzae
|
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MCC of pyogenic arthritis in adults and older children?
|
staph aureus
|
|
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MCC of pyogenic arthritis in sexually active young adults?
|
N. gonorrhea
(oligoarthritis - only a few joints involved) |
|
|
MCC of pyogenic arthritis in sickle cell disease?
|
Salmonella
|
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predisposing conditions to pyogenic arthritis?
|
IV drug abuse
immune deficiencies debilitating illness joint trauma chronic arthritis |
|
|
is pyogenic arthritis usually monoauricular or polyauricular?
|
mononauricular
(mainly large joints) |
|
|
describe the synovial effusion seen in pyogenic arthritis
|
type III (septic,pus)
|
|
|
in pyogenic arthritis, if the culture fails to yield a common pyogen - what should we be thinking?
|
TB
|
|
|
what would be seen upon a synovial biopsy of a joint with pyogenic arthritis?
|
acute inflammation
(congestion, edema, neutrophilic infiltrates) |
|
|
tuberculous arthritis is a complication of?
|
tuberculous osteomyelitis
primary TB infection |
|
|
what is the MC site of tuberculous arthritis?
|
spine
(tuberculous spondylitis = Pott's disease) |
|
|
what type of effusion would be seen in a case of tuberculous arthritis?
|
type III effusion (septic)
|
|
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what is seen in the synovium of a joint with tuberculous arthritis?
|
granulomatous inflammation
(more destructive process than pyogenic arthritis - may see obliteration of the joint space, infection may erode the joint capsule) |
|
|
how is tuberculous arthritis diagnosed?
|
tissue biopsy and culture
(see caseating granulomas and acid fast bacilli) |
|
|
arthritis of acute rheumatic fever primarily effects which age group?
|
children
|
|
|
describe the arthritis seen in acute rheumatic fever arthritis
|
*acute onset (few wks. after group A strep URI)
*polyarticular (large joints) *migratory |
|
|
what type of synovium is seen in acute rheumatic fever arthritis?
|
type II (inflammatory, slightly turbid due to increased white cells, sterile culture)
|
|
|
lyme disease is a multisystem infection. besides the joints, what else is affected?
|
nervous system
heart |
|
|
three manifestations/stages of lyme disease
|
1. erythema migrans (bullseye rash at bite site)
2. neurologic/cardiac abnormalities 3. oligoarthritis |
|
|
describe the clinical features of oligoarthritis seen in lyme disease
|
*usually involves 1 or 2 large joints
*transient remitting migratory polyarthritis *most resolve w/o permanent joint damage (may have chronic symmetric polyarthritis) |
|
|
describe the gross anatomic changes seen in lyme disease arthitis.
|
resemble RA
*chronic proliferative synovitis, pannus formation *hyperplastic "onion skin" thickening of arteriole walls |
|
|
treatment for lyme arthritis?
|
antibiotics
|
|
|
what is the primary feature of RA?
|
progressive inflammatory synovitis
destruction of synovial cartilage |
|
|
systemic affects of RA?
|
may affect
skin blood vessels heart lungs muscles |
|
|
which sex is RA MC seen in?
|
females (2-3x)
|
|
|
where does RA begin?
|
small joints
*hands - MCP and PIP *feet (MTP and IP) larger joint involvement follows (wrists,ankles, elbows, knees) |
|
|
describe the synovial fluid seen in RA
|
type II (inflammatory)
-increased neutrophils, low mucin |
|
|
radiologic findings seen in RA?
|
narowing of joint space
(loss of articular cartilage, bone erosions) |
|
|
describe some characteristic joint deformities seen in RA
|
*destruction of tendons, ligaments, joint capsules (see radial deviation of wrist, ulnar deviation of fingers)
*deformed joints with no stability, limited to no ROM |
|
|
some complications of RA that may ultimately lead to fatalities?
|
systemic amyloidosis
vasculitis iatrogenic effects of therapy (GI bleeding due to NSAIDs, infections due to chonic steroid use) |
|
|
what can be found in the serum that helps us make the diagnosis of RA?
|
serum rhematoid factor (seen in 80% of cases)
-not specifically diagnostic for RA, also occurs in collagen vascular diseases, others |
|
|
where are rheumatoid nodules most likely to develop?
|
in skin subject to pressure (ulnar forearm, elbows, occiput, lumbosacal area)
|
|
|
can rheumatoid nodules develop in the viscera?
|
YES!
(lungs, pleura, spleen, heart) |
|
|
what is the characteristic histology of a rheumatoid nodule?
|
*central fibrinoid necrosis
*palisading epithelioid histiocytes, lymphocytes, plasma cells |
|
|
the pathogenesis of RA is multifactorial. major contributing factors?
|
*genetics
*arthritogen (? microbial antigens) *autoimmune (see activated CD4+ T cells, B-lymphocytes, immune complexes) |
|
|
some mediatiors of joint damage?
|
cytokines
TNF-a IL-1 |
|
|
what is the antimicrobial antigen that is thought to be arthritogenic?
|
parvovirus B19
|
|
|
the diagnosis of RA requires 4 of what?
|
morning stiffness
arthritis in 3 or more joints arthritis of typical hand joints symmetric arthritis rheumatoid nodules serum RF typical radiographic changes |
|
|
describe the panus found in RA
|
*edematous and thick hypertrophic synovium
*may invade bone at articular margin, joint capsule, periarticular soft tissue |
|
|
micro characteristics of RA?
|
proliferative/hyperplastic synovitis
rheumatoid nodules fibrin deposition fibrosis increased vascularity with hemosiderin |
|
|
when is juvenile RA MC found?
which sex is it MC in? |
early childhood
females (2:1) |
|
|
how long must a child have arthritis before it can be classified as juvenile RA?
|
>6 wks
|
|
|
what is meant if juvenile RA is classified as:
1. oligoarthritis 2. polyarticular 3. systemic variant |
1. <5 joints involved (MC)
2. >5 joints 3. equal sexes, abrupt onset of fever, skin rash, hepatosplenomegaly |
|
|
how does childhood RA differ from adult RA?
|
oligoarthritis MC
large joints > small joints systemic onset more frequent NO rheumatoid nodules NO rheumatoid factor HAVE antinuclear antibody |
|
|
how is childhood RA similar to adult RA?
|
similar extra-articular manifestations
similar pathogenesis similar joint pathology |
|
|
what is a group of disorders with seronegativity for RA, have an association with HLA-B27, MC seen in young men?
|
spondyloarthropathy
|
|
|
what are the 4 spondyloarthropathies?
|
ankylosing spondylitis
Reiter syndrome psoriatic arthritis enteropathic arthritis |
|
|
ankylosing spondyloarthritis MC affects which joints?
|
axial (SI joint)
|
|
|
ankylosing spondyloarthritis MC affects which sex?
|
males
|
|
|
ankylosing spondyloarthritis is associated with what HLA?
|
HLA-B27
|
|
|
what is ankylosing spondylitis?
|
inflammation of the teninoligamentous insertion sites
*see ossification and bony outgrowths *leads to severe spinal immobility |
|
|
how do patients with ankylosing spondylitis present?
|
low back pain that is chronic/progressive
|
|
|
complications of ankylosing spondylitis?
|
fracture of the spine
aortitis amyloidosis |
|
|
which type of arthritis am I?
episode of non-infectious arthritis that occurs within 1 month of a primary infection elsewhere (AI rxn initiated by prior infx) |
reactive arthritis
|
|
|
pathogen from GU system that can cause reactive arthritis?
|
chlamydia
|
|
|
GI pathogens that can cause reactive arthritis?
|
shigella
salmonella yersinia campylobacter |
|
|
mechanism of LPS causing reactive arthritis?
|
LPS antigen stimulates an immune response - see an abrupt onset in knees and ankles which lasts about a year
|
|
|
what is the triad seen in reiter's syndrome?
|
arthritis
nongonococcal urethritis or cervicitis conjunctivitis "can't see, can't pee, can't climb a tree" |
|
|
joint symptoms seen in reiter's syndrome?
|
low back pain
joint stiffness asymmetric pattern |
|
|
clinical course of reactive arthritis?
|
*waxes and wanes over several weeks to months
*50% have functional disability (recurrent arthritis, tendinitis, fasciitis, lumbosacral back pain) |
|
|
psoriatic arthritis primarily affects which joints?
|
DIP of hands and feet (symmetric)
*may involve large joints or SI joints |
|
|
extraarticular manifestations of psoriatic arthritis?
|
conjunctivitis
iritis |
|
|
what is the MC form of joint disease?
|
OA
(intrinsic disease of articular cartilage) |
|
|
where is OA commonly seen?
|
hips (men)
knees and hands (women) |
|
|
secondary OA is due to a predisposing condition. examples?
|
*abnormal mechanical stressors (sprotes, congenital defects)
*underlying systemic disease (DM, obesity) |
|
|
etiology of primary OA?
|
unknown
("wear and tear arthritis") |
|
|
what is chondromalacia?
|
a subcategory of OA
affects patellar surface of femoral condyles of young persons (produces pain and stiffness of the knee) |
|
|
what are Heberden nodes
|
osteophytes at the DIP joints of the fingers, characteristic in women and seen in OA
|
|
|
which joints in the feet are commonly affected in OA?
|
first carpometacarpal joints
DIP joints |
|
|
besides fingers and feet: other joints that are affected in OA?
|
knees
hips cervical, lumbar spine |
|
|
pathogenesis of OA?
|
*degeneration of cartilage, weakening of cartilage network
*increased levels of IL-1, TNF, NO (appear to be responsible for cartilage changes) *death of chondrocyte -> viable chondrocytes aggregate -> fibrillation -> parralel surface cracks -> synovial fluid fills cracks -> cracks become more vertical -> cartilage pieces break off -> loose bodies -> synovial inflammation/hypertrophy. *eventually it's bone against bone |
|
|
biochemical abnomalities seen in OA?
|
decreased proteoglycan content
increased water content |
|
|
clinical features of OA?
|
moning stiffness
deep achy pain (worse w/use) limited ROM enlarged, tender, boggy, crepitus |
|
|
when would nerve root compression be seen in OA?
|
when osteophytes impinge on spinal foramina
|
|
|
what is seen upon Xray of a joint with OA?
|
narrowed joint space
hypertrophied subchondral bone subchondral bone cysts osteophytes (peripheral bone/cartilage growths) |
|
|
cause of gouty arthritis?
|
hyperuricemia
|
|
|
above what serum levels of uric acid does crystal deposition begin to ocur?
|
>7mg/dL
|
|
|
risk factors for the development of gout?
|
age>30 yrs
familial etoh, obesity, thiazides, lead toxicity |
|
|
uric acid is the end product of what metabolism?
|
purine
|
|
|
what are the two pathways of uric acid synthesis?
|
1. de novo (purines from nonpurine precursors)
2. salvage (free purine bases from breakdown of nucleic acids, HGPRT enzyme) |
|
|
why does uric acid crystallize in the joints?
|
synovial fluid is a poorer solvent than plasma for urates
(also lower T in foot, therefore crystallize there) |
|
|
characteristics of synovium seen in acute gouty arthritis?
|
edema
congestion dense neutrophilic infiltrate |
|
|
what happens in acute gouty arthritis when the crystals are resolubilized?
|
acute attack subsides
|
|
|
describe the clinical s/s of acute gouty arthritis
|
*sudden onset of excruciating pain
*extremely tender and warm joints with hyperemia |
|
|
where do most cases of acute gouty arthritis occur?
|
first metatarsophalangeal joint (big toe)
*then see in ankles, heels, knees, wrists, fingers, elbows |
|
|
chronic gouty arthritis is repetetive urate crystal deposition from acute attacks. where do these crystals MC deposit?
|
joints
periarticular joint tissue (deposits become grossly visible) |
|
|
describe the synovium of chronic gouty arthritis
|
Pannus - hypertrophy, fibrosis, inflammatory cells
(see cytokine mediated cartilage destruction and juxta-articular bone erosions -> loss of joint function) |
|
|
what type of synovial effusion is seen in gout?
|
type IV synovial effusion
(grossly white-gray granular appearance, birefringent needle shaped crystals under polarized light) |
|
|
gross appearance of chronic gout?
|
chalky white chunky deposits in and around joints in soft tissue
|
|
|
what is a tophi?
|
large aggregates/masses of urate crystals with surrounding inflammatory rxn. Involves articular and periarticular tissues
|
|
|
what is gouty nephropathy?
|
deposition of urate crystals in the renal medulla.
see tophi, intratubular precipitates, free uric acid crystals and uric acid renal stones |
|
|
four stages of gout?
|
1. asymptomatic hyperuricemia
2. acute gouty arthritis (monoarticular) 3. intercritical gout (recurrent-relapsing, polyarticular) 4. chronic tophaceous gout (bone erosion) |
|
|
"pseudogout" involves deposition of what kind of crystals?
|
calcium pyrophosphate crystals. (common in arthritic joints)
|
|
|
avg. age of pts affected by calcium crystal arthritis?
|
50 yrs or older
|
|
|
which areas does calcium crystal arthritis tend do affect?
|
menisci
intervertebral discs knee |
|
|
describe the hereditary variant of calcium crystal arthritis
|
symptoms early in life
severe OA |
|
|
secondary type of calcium crystal arthritis is associated with what disorders?
|
prior joint damage
hyperparathyroidism hypothyroidism hypomagnesemia DM hemachromatosis |
|
|
what type of synovial fluid is seen in calcium crystal arthritis?
|
group IV
(chalky white deposits) micro - see small rectangular crystals, weakly birefringent |
|
|
a synovial cyst in the popliteal space is known as?
|
Baker's cyst
(herniation of the synovial membrane through the posterior joint capsule due to excess fluid) |
|
|
Baker's cysts are associated with?
|
DJD
RA |
|
|
micro characteristics of a Baker's cyst?
|
cyst lined by synovial epithelium
|
|
|
treatment of a Baker's cyst?
|
treat cause of excess fluid
|
|
|
clinical s/s of bursitis?
|
pain, erythema, swelling of bursa
(result of chronic trauma) |
|
|
gross characteristics of bursitis?
|
thickened, erythematous, shaggy bursal wall with fibrinous exudate
|
|
|
micro characteristics of bursitis?
|
fibrous scarring of the wall with chronic inflammation
|
|
|
a cystic mass near a joint capsule or tendon sheath is called?
|
ganglion
|
|
|
where are the MC sites of a ganglion cyst?
|
wrist and fingers
(due to overuse injury) |
|
|
gross characteristics of a ganglion cyst?
|
small cystic mass
usually does not communicate with joint space multilocular fluid similar to synovial fluid |
|
|
micro characteristics of a ganglion cyst?
|
fibrous walled cyst with no synovial or epithelial lining
|
|
|
what exactly herniates in an intervertebral disc protrusion?
|
bulging of nucleus pulposus through weakened annulus fibrosus
|
|
|
what exactly happens in an intervertebral disc prolapse?
|
rupture of nucleus pulposus through annulus fibrosus
|
|
|
what exactly happens in an intervertebral disc extrusion?
|
rupture of nucleus pulosus through annulus fibrosus
AND posterior or anterior longitudinal ligament |
|
|
which meniscus is the MC one that is torn?
|
medial
(sports injury in young pts) |
|
|
describe a giant cell tumor of tendon sheath
|
*localized and well circumscribed
*MC seen in wrists and fingers |
|
|
describe a pigmented villonudular synovitis
|
*hyperplastic papillary synovium with foam cells and hemosiderin macrophages
*MC seen in knee *presents with pain, locking, swelling, limited ROM |
|
|
metaplastic cartilage within synovial tissue is called?
|
chondrometaplasia
|
|
|
describe chondrometaplasia
|
*may contain bone (osteochondromatosis)
*may detach and free float in joint space *commonly secondary to underlying disease (DJD, various arthropathies) *usually monoarticular (knee, hip, elbow) |
|
|
origins of synoviosarcoma?
|
unknown
(at one time thought to be derived from synovium) |
|
|
where do synoviosarcomas MC occur?
|
around extremity joints in deep soft tissue
(lower extremity around knee/thigh) |
|
|
which age group are synoviosarcomas MC seen in?
|
20-40yrs
|
|
|
in a synoviosarcoma:
1. which cells are found in the monophasic type? 2. biphasic type? |
1. usally only spindle cells
2. spindle and epithelioid cells |
|
|
chromosome abnormality seen in synovosarcoma?
|
translocation at X,18
|
|
|
treatment for a synoviosarcoma?
|
aggressive
(limb sparing therapy and chemo) |
|
|
prognosis of synoviosarcoma?
|
10 yr. survival rate: 11-30%
common mets. to lung, skeleton, regional lymph nodes |
|
|
where do the majority of soft tissue neoplasms originate?
|
thigh
|
|
|
are most soft tissue tumors benign or malignant?
|
benign
|
|
|
two MC benign soft tissue neoplasms?
|
lipomas
hemangiomas |
|
|
treatment for benign soft tissue tumors?
|
excision (curative)
|
|
|
a malignant tumor of soft tissue is called?
|
sarcoma
|
|
|
MC sites of sarcomas?
|
extremities
retroperitoneum |
|
|
prognosis of a low vs. high grade sarcoma?
|
low grade - good survival with local recurrences
high grade - usually fatal, treatment rarely successful |
|
|
four components of the grade of a sarcoma?
|
mitoses
cellularity anaplasia necrosis *grade correlates with prognosis |
|
|
whic sex in general has a poorer prognosis when it comes to sarcomas?
|
males
|
|
|
sarcomas are derived from which embryonic cell type?
|
mesenchymal cells
|
|
|
MC site of occurance of a benign histiocytoma?
|
skin
|
|
|
what is the MC form of benign fibrous histiocytoma?
|
dermatofibroma
(mass in the dermis composed of spindle cells and collagen fibers) |
|
|
benign fibrous histiocytomas are primary composed of what cell type?
|
spindle cells
|
|
|
malignant fibrous histiocytomas (MFH) MC occur in which age group?
|
7th decade
|
|
|
where do most MFHs arise?
|
lower extremities
|
|
|
gross characteristics of MFH?
|
multilobulated, gray-white
fleshy, infiltrative, *unencapsulated mass hemorrhage, necrosis |
|
|
5 histologic variants of MFH?
|
1. storiform-pleomorphic (MC, spindle cells)
2. myxoid variant (abundant myxoid stroma) 3. giant cell 4. inflammatory 5. angiomatoid |
|
|
what is the most frequent soft tissue tumor?
|
lipoma
|
|
|
peak age of incidence of a lipoma?
|
50-60
(rare under age 20) |
|
|
lipomas are MC found where?
|
subcutanous -> back, shoulder, neck
|
|
|
gross characteristics of a lipoma?
|
delicate capsule, poorly delineated from surrounding adipose tissue
*usually small (1-4 cm) |
|
|
histo characteristics of a lipoma?
|
indistinguishable from normal adult fat
|
|
|
a liposarcoma arised from what cell type?
|
primitive mesenchymal cells
(NOT adult fat cells) Not from preexisting lipomas |
|
|
peak incidence of liposarcoma?
|
50-70
|
|
|
gross characteristics of a liposarcoma?
|
opaque, grey-white to slightly yellow
*may be myxoid, gelatinous *multilobular *can get big (5-10cm) *areas of hemorrhage, necrosis, cystic softening |
|
|
what is an important histo characteristic in the diagnosis of liposarcoma?
|
lipoblasts
(fat cells with a vacuolated cytoplasm) |
|
|
liposarcomas are very aggressive. where do they metastasize to?
|
lungs
viscera serosal surface (85-90% metastasize) |
|
|
where do leiomyomas and leiomyosarcomas MC occur?
|
female genital tract
|
|
|
where are fibromas MC found?
|
ovary (cortical fibromas)
also found along nerve trunks (neurofibromas) |
|
|
are fibrosarcomas common?
|
NO (very uncommon - many lesions previously diagnosed as fibrosarcomas are reclassified)
|
|
|
where do fibrosarcomas commonly occur?
|
deep soft tissue
-retroperitoneum -thigh |
|
|
gross characteristics of a fibrosarcoma?
|
unencapsulated, infiltrative, soft tissue mass
(fish-flesh appearance, also see hemorrhage, necrosis) |
|
|
micro characteristics of a fibrosarcoma?
|
cellular
spindle cells herringbone pattern |
|
|
prognosis of a fibrosarcoma depends on (3)?
|
cytologic atypia
tumor size location |
|
|
recurrence rates of a fibrosarcoma?
|
HIGH (>50%)
also,mets in ~25% at time of diagnosis 5 yr survival rate 60-80% |
|
|
fibromatosis in neck muscles is called?
|
fibromatosis colli
|
|
|
fibromatosis of the penis is called?
|
Peyronie's disease
|
|
|
fibromatosis of the feet is called?
|
plantar fibromatosis
|
|
|
what is a Dupuytren's contracture?
|
fibromatosis of the palms of the hand
*irregular or nodular thickening of the palmar fascia *may trap tendons or attach to skin *causes flexion contractures, leads to deformity and limitation of motion |
|
|
gross and histo appearance of Dupuytren's contracture?
|
gross - dense white fibrous tissue mass
micro - acellular or cellular nodules of fibrous tissue |
|
|
which sex is MC affected by fibromatosis?
|
males
|
|
|
disease course of fibromatosis?
|
20-25% of the time the fibromatosis stabilizes with time or resolves spontaneously
|
|
|
what is a very aggressive form of fibromatosis?
|
desmoid tumor
(infiltrative fibrous proliferation) |
|
|
where does a desmoid tumor arise from?
|
CT and aponeuroses of skeletal muscle
|
|
|
a desmoid tumor resembles a low grade ?
|
fibrosarcoma
|
|
|
peak age of incidence of desmoid tumors?
|
20-40
|
|
|
desmoid tumors MC affect which sex?
|
females
(esp. frequently after pregnancy - abdominal desmoid) |
|
|
syndrome involving familial polyposis, osteomas, fibrosis (desmoid)?
|
Gardner's syndrome
|
|
|
gross morphology of desmoid tumors?
|
gray-white, firm, unencapsulated poorly demarcated masses infiltrating between muscles
|
|
|
histology of a desmoid tumor?
|
*central region - dense collagenous fibrous tissue
*may see trapped atrophic muscle fibers *regenerative activity creates muscle giant cells |
|
|
why is it important to differentiat a desmoid tumor from a sarcoma?
|
desmoids are curable by excision, good prognosis
|
|
|
describe the bimodal distribution of inflammatory myopathies
|
children
40-60 yrs |
|
|
which sex are inflammatory myopathes MC in?
|
women
|
|
|
inclusion body myositis primarily effects which age group?
|
adults >50 yrs
|
|
|
which one, dermatomyositis or polymyositis is MC seen in both kids and adults?
|
dermatomyositis
|
|
|
chronic inflammatory myopathy is MC seen in which muscles?
|
proximal muscles
(symmetric) |
|
|
which type of rash is commonly seen in dermatomyositis?
|
heliotrope rash
|
|
|
describe the muscle weakness seen in dermatomyositis?
|
slow onset muscle weakness
*affects proximal muscles first *bilateral, symmetric *often see dysphagia |
|
|
extramuscular manifestations of dermatomyositis?
|
interstitial lung disease
myocarditis vasculitis **increased risk of visceral cancers** |
|
|
describe the muscle involvement seen in inclusion body myositis
|
*distal muscles first
*may be asymmetric *insidious disorder |
|
|
is inclusion-body myositis associated with malignancy?
|
no
|
|
|
etiology of inflammatory myopathies?
|
thought to be autoimmune
*see other AI disorders *autoantibodies are found in some cases (RF, ANA) |
|
|
which antibody is found that is characteristic of inflammatory myopathy?
|
Jo-1 autoantibody
|
|
|
pathogenesis of polymyositis?
|
cell mediated injury
(CD8+ cytotoxic T cells and macrophages found in muscle) |
|
|
what seem to be the principal targets in dermatomyositis?
|
capillaries
(microvasculature is attacked by antibodies and complement - results in ischemic myocyte necrosis) |
|
|
where are the lymphocytic infiltrates found in:
1. PM 2. DM |
1. lymphocytes found in endomysium
2. perivascular and perymisial lymphocytic infiltrates |
|
|
histo characteristics of a regenerating muscle fiber?
|
nucleus in the middle of the muscle fiber, not on the periphery (as in a normal muscle fiber)
|
|
|
perifascicular atrophy is seen in which inflammatory myopathy?
|
DM
(probably related to a state of hypoperfusion of muscle fascicles) |
|
|
4 diagnostic criteria for an inflammatory myopathy?
|
1. clinical findings
2. EMG findings 3. elevated serum levels of muscle related enzymes 4. muscle biopsy req'd for definitive diagnosis |
|
|
describe the clinical findings necessary for the diagnosis of an inflammatory myopathy
|
*characteristic history of muscle weakness (proximal and symmetrical)
*muscle pain and tenderness detectable on PE *characteristic rash for DM |
|
|
describe the EMG findings indicative of an inflammatory myopathy
|
consistent with spontaneous activity and myopathic changes
|
|
|
exactly what "muscle enzymes" are elevated in inflammatory myopathies
|
aldolase
CPK (reflects muscle injury and enzyme release) |
|
|
therapy for inflammatory myopathies?
|
immunosuppressive therapy
|
|
|
what is the source of trichinosis?
|
inadequately cooked pork
|
|
|
pathogenesis of trichinosis?
|
*human ingests larvae
*cyst wall is digested, larvae released into stomach *mature to adult worms in duodenum *female worm deposits larvae, enter the bloodstream, *larvae invade striated muscle |
|
|
where is trichinosis MC found?
|
most active muscles (richest blood supply)
*diaphragm *EOM *extremity muscles *intercostals |
|
|
reaction of the muscle cells to Trichinella larvae penetration?
|
*muscle becomes collagenous capsule - "nurse cell"
*eventually larvae and host cell die *inflammatory rxn. occurs *fibrosis and calcification of cyst (see radiodensities on Xray) |
|
|
clinical s/s seen in a trichinosis infection?
|
*normally mild or subclinical disease
*severe infx: vomiting, diarrhea *hematogenous dissemination, muscular invasion (fever, myalgia, swelling, weakness) |
|
|
manifestations of brain involvement in trichinella infection?
|
H/A
disorientation encephalitis |
|
|
where would you want to do a muscle biopsy when looking for trichinella?
|
deltoid
gastroc |
|
|
treatment of trichinosis?
|
predinsone
albendazole |
|
|
how common are rhabdomyomas?
|
extremely rare
|
|
|
which areas do rhabdomyosarcomas MC involve?
|
head and neck region
(benign - cured by local excision) |
|
|
what is the MC malignancy of soft tissues in children <15 yrs of age?
|
rhabdomyosarcoma
|
|
|
what are the 3 variants of rhabdomyosarcoma?
|
1. embryonal
2. alveolar 3. pleomorphic |
|
|
what type of rhabdomyosarcoma is the boytroid form?
|
embryonal
|
|
|
rhabdomyosarcoma has the following genetic abnormalities:
t(2;13) (35;14) and (1;13) what is the ultimate result of these mutations? |
dysregulation of muscle differentiation by chimeric PAX3-FKHR protein
|
|
|
in relation to an adult pleomorphic rhabdomyosarcoma:
1. where is it MC seen? 2. growth rate? 3. MC age? |
1. extremities, retroperitoneum
2. extremely rapid 3. >45 yrs |
|
|
gross morphology of a pleomorphic rhabdomyosarcoma?
|
situated deep w/i muscle
soft gray fish flesh appearance (areas of necrosis and hemorrhage) |
|
|
in what age group does alveolar rhabdomyosarcoma MC occur in?
|
10-25 yrs
|
|
|
where are alveolar rhabdomyosarcomas MC seen?
|
lower or upper extremity
(occasionally involve trunk) |
|
|
histo morphology of alveolar rhabdomyosarcoma?
|
undifferentiated round to oval tumor cells in small nests with a fibrovascular stroma, occasional multinucleated giant cells
**resembles alveolar pattern of lung** |
|
|
characteristics of rhabdomyosarcomas in general?
|
HIGH GRADE MALIGNANT AGRESSIVE TUMORS
*widespread dissemination occurs early (20-40% have mets at time of diagnosis) |
|
|
prognosis of a rhabdomyosarcoma?
|
usually death occurs w/i months
median survival: 3-5 yrs |
|
|
which type of rhabdomyosarcoma has the best prognosis?
|
botyroid subtype
(then embryonal, pleomorphic, alveolar) |
|
|
who has a better prognosis when it comes to a rhabdomyosarcoma: adults or kids?
|
kids (65% cured)
|
|
|
7 preventative interventions for osteoporosis?
|
1. good diet with adequate Ca++ and vit. D intake (avoid soda)
2. regular weight bearing xercise 3. quit smoking 4. loose weight if overweight 5. moderate etoh intake 6. reduce or d/c meds that predispose to osteoporosis 7. fall prevention education |
|
|
what are the indications for pharmacological therapy in osteoporosis?
|
* postemenopausal women with a T score of <-2 and no risk factors
* T score <-1.5 if other risk factors present * previous hip or vertebral fracture |
|
|
which Ca++ supplement has the most absorbable elemental calcium?
|
Calcium carbonate
|
|
|
which two forms of calcium are better tolerated than calcium carbonate?
|
calcium citrate
calcium gluconate (less GI upset) |
|
|
dose of elemental Ca++ and vit. D in a postmenopausal woman?
|
Ca++: 1000-1500 mg/day
vit. D: 400-800 IU/day |
|
|
how does an estrogen deficiency promote osteoporosis?
|
*osteoclasts & osteoblasts have estrogen receptors
*estrogen promotes apoptosis of osteoclasts and inhibits their function *estrogen deficiency increases production of IL-1, IL-6 and TNF in osteoblasts. this indifectly stimulates osteoclast differentiation and production -> net increased bone resorption and bone loss |
|
|
how does HRT work in increasing bone mass?
|
acts on osteoblasts to reduce IL-6. result is reduced osteoclast production, reduced bone resorption.
|
|
|
SERMs have estrogen action where (and not where)?
|
have action on bone and lipids
NOT on breast and endometrium |
|
|
SERM of choice to treat osteoporosis?
|
Raloxifene (evista)
|
|
|
raloxifene has been shown to reduce the incidence of what kind of fractures?
|
vertebral
(not hip or others) |
|
|
MOA of bisphosphonates?
|
BISPHOSPHONATES SLOW BONE TURNOVER
bound to bone mineral when administered *slowly released as bone is resorbed, taked up by osteoclasts *inhibits formation of ruffled border of osteoclast(where active resorption occurs) *this inhibits osteoclast function and decreases bone resorption |
|
|
connection between long term bisphosphonate therapy and bone mineral content?
|
increases
|
|
|
adverse effects of bisphosphonates?
|
GI
(heartburn, esophageal irritation, abd. pain, diarrhea) |
|
|
patient directions for taking bisphosphonates?
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*in am on an empty stomach
*must be upright *take with 8 oz of water *remain upright, eat nothing for 30 minutes |
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effects of Ca++ and antacids on absorption of bisphosphonates?
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interfere (reduce absorption)
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what is teriparatide (Forteo)
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recombinant hPTH
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what is unique about the effects of hPTH in relation to osteoporosis?
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only approved therapy that stimulates bone formation rather than inhibition of bone resorption
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if PTH is given continuously it has a catabolic effect. how does it work then?
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when administered once per day "pulsatile secretion," it stimulates bone formation
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where has hPTH been shown to increase bone mineral density?
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spine
hip (reduces incidence of vertebral and nonvertebral fractures) |
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adverse effects of teriparatide?
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nausea, dizziness, leg cramps, H/A
*orthostatic hypotension with first few doses *mild hypercalcemia, hypercalciuria |
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contraindications for teriparatide and why?
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Paget's disease, unexplained elevations in serum Alk Phos, prior skeletal radiation, children or young adults with open epiphyses
INCREASED RISK OF OSTEOSARCOMA (in mice) |
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which osteoporosis therapy also has the benefit of analgesic properties for bone pain?
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calcitonin
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what are the two LETHAL osteochondrodysplasias?
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Achondrogenesis II
chrondrodysplasia punctata (rhizomelic type) |
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physical features of achondrogenesis II?
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short trunk with prominent abdomen
severe micromelia flat midfacies micrognathia cleft palate hydropic appearance |
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radiologic features of achondrogenesis II?
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*absent or severely retarded ossification of vertebral bodies, sacrum, pubic & ischial bones
*barrel shaped thorax, short ribs *small iliac bones *very short tubular bones with metaphyseal flare and cupping |
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genetics of achondrogenesis II?
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AD
mutation in COL2A1 gene chromosome 12 |
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what does the COL2A1 gene encode?
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collagen type II apha I chain
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MCC of death is chondrodysplasia punctata - rhizomelic type?
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repeated infections
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physical characteristics of chondrodysplasia punctata - rhizomelic type?
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*rhizomelic, disproportionate short stature
*flat face with small saddle nose *bilateral cataracts *multiple contractures |
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radiologic characteristics of chondrodysplasia punctata - rhizomelic type?
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*vertebral coronal clefts
*short humeri and femurs with metaphysial splaying *punctate epiphyses at end of long bones *abnormal grey-white matter relationship on MRI (MR) |
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inheritance pattern of chondrodysplasia punctata - rhizomelic type?
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AR
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mutations in chondrodysplasia punctata - rhizomelic type affect which genes?
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PEX 7 (encodes peroxisomal targeting)
DHAPAT alkyl-DHAP synthase |
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physical characteristics of metaphyseal chondrodysplasia - McKusic type?
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short limb dwarfism
fine, sparse hair, eyebrows, lashes limited elbow extension ligamentous laxity short, pudgy hands and feet |
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abnormal lab values seen in metaphyseal chondrodysplasia - McKusic type?
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impaired in vitro T cell function
anemia lymphopenia neutropenia |
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radiologic abnormalities seen in infancy in metaphyseal chondrodysplasia - McKusic type?
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shortened long bones
curved femurs with rounded distal ephiphyses short ribs anterior angulation of sternum |
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radiologic abnormalities seen in adults in metaphyseal chondrodysplasia - McKusic type?
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shortened tubular bones
metaphyseal dysplasia of long bones metaphyseal irregularities: knee>proximal femurs ling fibula |
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inheritance pattern of metaphyseal chondrodysplasia - McKusic type?
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AR
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in metaphyseal chondrodysplasia - McKusic type: which gene do the mutations occur in?
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RMRP gene (chromosome 9)
encodes for RNA component of a ribonucleoprotein endoribonuclease |
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non-skeletal manifestations of metaphyseal chondrodysplasia - McKusic type?
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Hirschprung's disease
recurrent childhood infections severe varicella rxns increased non-Hodgkin lymphomas normal intellectual development |
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what is unique about the onset of pseudoachondroplasia?
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normal growth for 12-18 months, then growth retardation
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physical characteristics of pseudoachondroplasia?
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short-limbed dwarfism (proximal shortening)
normal head and face, long trunk accentuated lumbar lordosis, mild-moderate scoliosis knock knees or bowed legs hypermobile joints (except elbows) |
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in relation to pseudoachondrodysplasia: mental status and life expectancy?
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normal for both
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radiologic abnormalities in a child with psudoachondrodysplasia?
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vertebral flattening, biconvex deformity
end plate deformities tongue-like protrusions of vertebral body central portion |
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radiologic abnormalities in an adult with psudoachondrodysplasia?
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partial restoration of normal vertebral form
marked femoral head dysplasia |
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radiologic abnormalities in both children and adults with psudoachondrodysplasia?
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shortening of long bones
expanded, irregular metaphyses small, deformed epiphyses |
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genetics of psudoachondrodysplasia?
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AD
mutation in COMP gene (chromosome 19) encodes cartilage oligomeric matrix protein (COMP) |
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what is a skeletal dysplasia with major involvement of the spine?
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Diastrophic dysplasia
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genetics of diastrophic dysplasia?
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AR
mutation in DTDST (diastrophic dysplasia sulfate transporter)gene *result is no cellular sulfate transportation -> production of undersulfated cartilage proteoglycans, disrupts assembly of cartilage matrix |
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hallmark physical manifestations of diastrophic dysplasia?
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small stature, short extremities
joint contractures hypermobile thumbs club feet, incr. distance btwn first and secodn toes cauliflower pinnae cleft palate progressive kyphoscoliosis |
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two skeletal dysplasias with multiple dislocations?
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Larsen syndrome
dysostosis multiplex |
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inheritance pattern of Larsen syndrome?
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both AD and AR
AD has mutation on chromosome 3 |
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physical manifestations of Larsen syndrome?
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multiple joint dislocations
craniofacial abnormalities (prominent forehead, low nasal bridge, wide spaced eyes, flat face, cleft palate/uvula) pes equinovarus (club foot) forefoot torsion |
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dysostosis multiplex is a mutation in?
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GLB1 gene (encodes lysosomal enzyme B-galactosidase)
*result is complex carbohydrate storage disease (GM1 - gangliosidosis I) |
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physical characteristics of dysostosis multiplex?
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facial edema
ascites at birth failure to thrive motor retardation coarse facial features ginvigal hypertrophy, large tongue hepatosplenomegaly *rarely survives 2nd yr of life |
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lab values seen in dysostosis multiplex?
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*increased urinary excretion of galactose rich oligosaccharides
*increased urinaty keratan sulfate *absent B-galactosidase activity |
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name a skeletal dysplasia with predominant involvement of a single site or segment
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cleidocranial dysplasia
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genetics of cleidocranial dysplasia?
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AD
mutation in CBFA 1 gene (encodes protein, part of bone morphogenetic protein signaling cascade) |
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physical features of cleidocranial dysplasia?
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clavicular hypoplasia
small maxilla small or winged scapulae broad forehead, widely separated eyes persistence of deciduous teeth, late dental erruption spinal deformities |
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name a skeletal dysplasia with increased bone density and tubular undermodeling
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pyknodyostosis
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genetics of pyknodyostosis?
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AR
mutation in CSTK (cathepsin K) gene chromosome 1 gene encodes cathepsin K; absence causes proteolytic degradation of organic matrix by osteoblasts |
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physical characteristics of pyknodyostosis?
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short limbed dwarfism
small face, hypoplastic maxilla bulging eyes beak-like nose receding chin persistance of primary teeth, enamel hypoplasia short terminal phalnges increased bone fragility |
