Bones & Joints Flashcards
RANKL is expressed on ___ and is upregulated by which 2 hormones?
RANKL is expressed on osteoblasts and is upregulated by:
PTH
vitamin D3
the function of RANKL is inhibited by ___
the function of RANKL is inhibited by osteoprotegrin (TNF family)
the condition seen in the image most commonly occurs in ___ and ____
the condition seen in the image most commonly occurs in elderly and post-menopausal women
in the condition seen in the image, there is bone loss due to ____ and ____
in the condition seen in the image, there is bone loss due to defective osteoblasts and increased activity of osteoclasts
in the condition seen in the image, in post-menopausal women, there is decrease in serum ____ which leads to increased ___ (3 cytokines) levels and therefore activates osteoclasts
in the condition seen in the image, in post-menopausal women, there is decrease in serum estrogen which leads to increased IL-1, IL-6, TNF levels and therefore activates osteoclasts
describe the blood levels in the condition seen in the image
calcium, phosphate and ALP are ALL NORMAL
the most common cause of death in the condition seen in the image is ____
the most common cause of death in the condition seen in the image is DVT (due to immobility from fractures) → pulmonary embolus
on biopsy of the condition seen in the image, ___ is seen
on biopsy of the condition seen in the image, thinning of the trabeculae is seen
list 4 causes of the secondary form of the condition seen in the image
hyperparathyroidism
vit. D deficiency
vit. C deficiency
corticosteroids
describe the effects of estrogen on osteoblasts and osteoclasts
list the endocrine disorders that can lead to the condition seen in the image
hyperparathyroidism
hyperthyroidism
diabetes
Addison’s disease
pituitary tumors
list the neoplasias that can lead to the condition seen in the image
- carcinomatosis
- multiple myeloma
- paraneoplastic syndrome
- hyperPTH caused by squamous cell ca. of the lung
list the GI disorders that can lead to the condition seen in the image
- malnutrition
- hepatic insufficiency
- vit. D or vit. C def.
- malabsorption
list the drugs that can lead to the condition seen in the image
- corticosteroids
- chemotherapy
- alcohol
“a woman has a history of rheumatoid arthritis and has been on corticosteroids–which condition is she at increased risk for?”
osteoporosis
describe the pathogenesis of hyperparathyroidism
describe the pathogenesis of renal osteodystrophy
chronic renal failure → hyperphosphatemia → hypocalcemia → secondary increase in PTH
in renal osteodystrophy, ___ and ___ accumulation in the bone (from ___) prevents ____
in renal osteodystrophy, iron and aluminum accumulation in the bone (from dialysate) prevents further bone deposition
describe the etiology of the condition seen in the image
parathyroid adenoma (most common) or parathyroid hyperplasia
can be part of MEN1 and MEN2a
describe the pathogenesis of the condition seen in the image
increased PTH → acts on osteoblasts → increased interaction between RANK + RANKL → activates osteoclasts → demineralization of bone → lose calcium and phosphate from bone
describe the blood levels of Ca, PTH, ALP and phosphate in the condition seen in the image
increased Ca, PTH and ALP
decreased phosphate
describe what is seen on biopsy of the condition seen in the image
medullary cavity has brown cystic deposit (brown tumor) = osteitis fibrosis cystica (ONLY in primary hyper-PTH)
this is due to angiogenesis needed by osteoblasts to form bone → after 2 weeks, turn to hemosidering
describe the presentation of the condition seen in the image
usually asymptomatic
-
bone pain, kidney stones, GI pain, confusion
- “painful bones, renal stones, abdominal groans, and psychic moans”
-
polydipsia and polyuria
- hypercalcemia causes aquaporin in CD to become insensitive to ADH → nephrogenic diabetes insipidus
___ is the most common cause of death in the condition seen in the image
hypercalcemia → arrhythmias
osteomalacia & rickets is characterized by abnormal ____
osteomalacia & rickets is characterized by abnormal mineralization
list the causes of osteomalacia & rickets
- lack of exposure to sun
- malnutrition
- malabsorption
- liver & renal failure
- when caused by renal failure, phosphate is HIGH in blood
describe the blood levels seen in osteomalacia & rickets
decreased Ca, phosphate, vit. D
increased PTH, ALP (measure of osteoblastic activity)
in osteomalacia & rickets, there is under-mineralized matrix which leads to persistent ____
in osteomalacia & rickets, there is under-mineralized matrix which leads to persistent hyaline cartilage
in rickets, there is:
frontal bossing due to ___ on the skull
rachitic rosary due to ___ at the costochondral junction
frontal bossing due to osteoid deposition on the skull
rachitic rosary due to osteoid deposition at the costochondral junction
in scurvy, there are fragile ___ and ___ which can lead to ___
in scurvy, there are fragile capillaries and venules which can lead to subperiosteal hemorrhages
in scurvy, there is defective ____ which can lead to ____
in scurvy, there is defective osteoid synthesis which can lead to microfractures
in scurvy, which is caused by ___ def., there is failed ____
in scurvy, which is caused by vit. C def., there is failed cross-linking of collagen
the condition seen in the image is associated with which infection?
associated with Paramyxovirus (measles) in childhood
the condition in the image can be caused by a genetic predisposition with a mutation in ____
the condition in the image can be caused by a genetic predisposition with a mutation in p62 → increased RANK-RANKL interaction → increased osteoclasts
describe the pathogenesis of the condition seen in the image
virus stimulates IL-6 → IL-6 and M-CSF activate osteoclasts → osteoclasts are hyperresponsive to RANKL and vit. D → abnormal bone remodeling
describe the 3 phases of the condition seen in the image
- osteolytic/osteoclastic phase
- dark and radiolucent on x-ray
- mixed phase
- requires angiogenesis → warm skin
- osteosclerotic (burnt-out) phase
- bright and radioopaque on x-ray
describe what is seen on biopsy of the condition in the image
mosaic pattern of lamellar bone w/ cement lines & resorption pits d/t haphazard laying of bone osteoid
describe the blood levels in the condition seen in the image
Ca, phosphate and PTH are NORMAL
increased ALP
describe the urine findings in the condition seen in the image
increased hydroxyproline due to high collagen turonver
part of type 1 collagen; signifies osteoclast fxn (stage 1 of the disease)
____ is the most common cause of death in the condition seen in the image
high output congestive cardiac failure d/t mixed phase → high osteoblastic activity and angiogenesis → AV shunts (volume overload)
in the condition seen in the image, patients are at an increased risk for developing ____
in the condition seen in the image, patients are at an increased risk for developing secondary osteosarcoma (malignant tumor of osteoblasts)
describe how the condition seen in the image can lead to hearing loss
thick bones → press on cranial nerves in skull, especially CN VIII → hearing loss
the condition seen in the image is caused by a mutation in ____ which ____
the condition seen in the image is caused by a mutation in FGFR3 which inhibits chondrocyte proliferation
“an elderly male comes to the physician complaining that his hat size is getting bigger”
what is he at increased risk of developing?
osteosarcoma
the condition seen in the image is caused by a mutation in ____ located on chr. ____
the condition seen in the image is caused by a mutation in FGFR3 located on chr. 4
in the condition seen in the image, there is no ______ at the growth plate and therefore affects all bones with ___ ossification
in the condition seen in the image, there is no chondrocyte proliferation at the growth plate and therefore affects all bones with endochondral ossification (long bones)
in patients with the condition seen in the image, are other aspects of their life affected?
NO impact on intelligence, life span, and fertility
how can the condition seen in the image can be contrasted with GH deficiency dwarfism?
GH deficiency (dwarfism) = proportionally shortened limbs
how can the condition seen in the image can be contrasted with dwarfism seen in cretinism (hypothyroidism)?
short stature with mental retardation, protruding belly and protruding tongue
Ehler-Danlos syndrome (EDS) is caused by inappropriate ____
Ehler-Danlos syndrome (EDS) is caused by inappropriate cleavage of collagen fibers
list the clinical features of EDS
- hyperextensibility of skin
- easy bruising
- hypermobile joints
- blue sclerae may be present
list the complications of EDS
- aortic dissection
- osteopenic bone → kyphoscoliosis, spondylolisthesis
Marfan’s syndrome is caused by a mutation in ___ gene on chr. ____
Marfan’s syndrome is caused by a mutation in fibrillin-1 gene on chr. 15
describe the clinical features of Marfan’s syndrome
- tall with long extremeities
- hyperflexible joints
- kyphosis
- scoliosis
- pectus excavatum
- subluxation of lens (ectopia lentis)
describe the CVS clinical features seen in Marfan’s syndrome
MVP; aortic dilatation (due to cystic medionecrosis); aortic regurgitation
the condition seen in the image is caused by dysfunction in _____
how does this lead to the condition?
the condition seen in the image is caused by dysfunction in carbonic anhydrase
without acidic environment → osteoclastic activity is impaired → primary spongiosa layer which is normally broken down by osteoclasts is retained → narrowed medullary cavity → no hematopoiesis → pancytopenia
in the condition seen in the image, the ___ layer, which is normally broken down by ___, is retained
in the condition seen in the image, the primary spongiosa layer, which is normally broken down by osteoclasts, is retained
the condition seen in the image leads to a ___-facies due to ____
the condition seen in the image leads to a lion-facies due to coarse facial features
describe what is seen on x-ray in the condition in the image
radiopaque & bright
normal demarcation of cancellous (medullary) bone & cortical bone is lost
metaphyseal flaring (Erlenmeyer flask deformity) = more prominent around the knee and hips
describe the neurological complications of the condition seen in the image
thick bones → compress CN 7 & 8 → hearing impairment
the most common cause of death in the condition seen in the image is from ____
the most common cause of death in the condition seen in the image is from recurrent infections (due to the pancytopenia)
since the condition in the image causes pancytopenia, there is _____ caused by ____ hematopoiesis
since the condition in the image causes pancytopenia, there is hepatosplenomegaly caused by extramedullary hematopoiesis
____ is the most common organism that causes osteomyelitis
S. aureus is the most common organism that causes osteomyelitis
____ are the genitourinary infections that can cause osteomyelitis
E. coli and Klebsiella are the genitourinary infections that can cause osteomyelitis
____ is a bacteria that can cause osteomyelitis in patients that are IVDU
Pseudomonas is a bacteria that can cause osteomyelitis in patients that are IVDU
____ is the bacteria that can cause osteomyelitis in sickle-cell patients
Salmonella is the bacteria that can cause osteomyelitis in sickle-cell patients
___ and ____ are the bacteria that can cause osteomyelitis in neonates
H. influenzae and Group B streptococcus (S. agalactiae) are the bacteria that can cause osteomyelitis in neonates
osteomyelitis begins in ___ because ____ terminate int he venous sinusoids and eventually leads to the formation of ____
osteomyelitis begins in the metaphysis because nutrient arteries terminate in the venous sinusoids and eventually leads to the formation of abscesses within medulla & under periosteum and bone necrosis
osteomyelitis commonly occurs in (bone location):
___ in children
____ in adults
osteomyelitis commonly occurs in (bone location):
metaphysis in children
diaphysis (shaft) in adults
osteomyelitis is caused by ____ spread (____ from systemic disease)
osteomyelitis is caused by hematogenous spread (seeding from systemic disease)
direct inoculation leading to osteomyelitis can be caused by ____
direct inoculation leading to osteomyelitis can be caused by mixed bacteria
list predisposing factors for osteomyelitis
- catheter
- trauma
- infection
- underlying disease
- IV drug abuse
osteomyelitis can lead to sequestrum, which is progressive ____ leading to segmental ____ surrounded by viable new bone (____)
osteomyelitis can lead to sequestrum, which is progressive ischemia leading to segmental bony necrosis surrounded by viable new bone (involucrum)
chronic osteomyelitis can lead to Brodie abscess, which is an _____
chronic osteomyelitis can lead to Brodie abscess, which is an intracortical abscess (abscess within the bone)
chronic osteomyelitis can lead to sclerosing OM of Garre, which is when _____
chronic osteomyelitis can lead to sclerosing OM of Garre, which is when extensive new bone obscures the underlying bone
chronic osteomyelitis can lead to renal and heart failure due to ____
chronic osteomyelitis can lead to renal and heart failure due to secondary amyloidosis (Associated Amyloid, AA)
rarely, chronic osteomyelitis can have malignant complications which can lead to ___ or ____
rarely, chronic osteomyelitis can have malignant complications which can lead to squamous cell carcinoma of fistula tract or sarcoma of infected bone
“patient with chronic osteomyelitis develops a new heart murmur”
how?
endocarditis
the condition seen in the image occurs from ____ spread of ____
the condition seen in the image occurs from hematogenous spread of TB
the condition seen in the image destroys the ____ first and then damages the ____
the condition seen in the image destroys the intervertebral discs first and then damages the vertebral bodies
the condition seen in the image affects the:
____ vertebrae in children
____ vertebrae in adults
the condition seen in the image affects the:
thoracic vertebrae in children
lumbar vertebrae in adults
describe what is seen on biopsy of the condition in the image in immunocompetent vs. immunocompromised
immunocompetent = caseating granulomas
immunocompromised = AF bacilli in macrophages
the condition seen in the image can lead to a ___ abscess
the condition seen in the image can lead to a psoas abscess
cold abscess d/t minimal inflammatory response; no spiking fevers seen in normal abscesses
the condition seen in the image can cause ___ anemia; explain how
the condition seen in the image can cause myelophthisic anemia
metastasis to bone → caseating granulomas replacing normal bone marrow → inadequate cell formation
the most important risk factor for the condition seen in the image is ____
the most important risk factor for the condition seen in the image is age
list predisposing factor for the condition seen in the image
- diabetes
- hemochromatosis
- ochronosis = accumulation of homogentisic acid in connective tissues
- obesity
- congenital deformity
the primary problem in the condition seen in the image is _____
the primary problem in the condition seen in the image is enzymatic breakdown of articular cartilage
in the beginning stages of the condition seen in the image, there are changes in ____ which release ____ that break down the matrix and inhibit ____ synthesis
in the beginning stages of the condition seen in the image, there are changes in chondrocytes (proliferation) which release IL-1 and TNF-a that break down the matrix and inhibit type II collagen synthesis
the condition seen in the image can lead to deeper cracks in the bones that dislodge as ____
the condition seen in the image can lead to deeper cracks in the bones that dislodge as joint mice (have a central core of necrotic bone)
presentation of the condition seen in the image shows ____ nodes in the DIP and ___ nodes in the PIP
presentation of the condition seen in the image shows Haberden’s nodes in the DIP and Bouchard’s nodes in the PIP
the condition seen in the image is (symmetric or asymmetric?) and (unilateral or bilateral?)
the condition seen in the image is asymmetric and unilateral
the condition seen in the image has morning stiffness that lasts for ___ and ___ with activity (because the condition is ____)
the condition seen in the image has morning stiffness that lasts for 15-30 min. and worsens with activity (because the condition is degenerative)
in the condition seen in the image, there is an attempt at new bone formation which forms ____
in the condition seen in the image, there is an attempt at new bone formation which forms osteophytes
in the condition seen in the image, there is leakage of ____ which leads to ____
in the condition seen in the image, there is leakage of synovial fluid which leads to subchondral cysts
the condition seen in the image is associated with HLA-___ and HLA-____
the condition seen in the image is associated with HLA-DR4 and HLA-DRB1
what are other predisposing factors that can lead to the condition seen in the image?
smoking
infections (EBV, E. coli)
stress
in the condition seen in the image, there is progressive joint destruction due to formation of a ____
explain this
in the condition seen in the image, there is progressive joint destruction due to formation of a pannus
pannus = synovial cell hyperplasia, organizing fibrin, CD4 T cells which form lymphoid aggregates, neutrophils (b/c acute on chronic inflammation), granulation tissue (col. III) → col. 1
the condition seen in the image affects small joints but NEVER the ____
the condition seen in the image affects small joints but NEVER the DIP
describe what subarticular osteoporosis is seen in the condition in the image
the condition seen in the image is (symmetric or asymmetric?) and (unilateral or bilateral?)
the condition seen in the image is symmetric and bilateral
in the condition seen in the image, there is morning stiffness which lasts for ____ and ____ as the day progresses
in the condition seen in the image, there is morning stiffness which lasts for >1 hour and gets better as the day progresses
the condition seen in the image is associated with Caplan syndrome; explain the symptoms seen
Caplan syndrome = RA, pneumoconiosis, rheumatoid nodules in the lung
the condition seen in the image is associated with Felty syndrome; explain the symptoms seen
Felty syndrome = RA, splenomegaly, neutropenia
on x-ray investigation of the condition seen in the image, what is seen?
x-ray = narrowing of the joint space & bony erosions
describe how the condition in the image affects the heart
- heart:
- MI due to accelerated atherosclerosis
- pericarditis → pericardial effusion → pericardial tamponade
- restricted cardiomyopathy due to amyloidosis
describe how the condition seen in the image can affect the kidney
chronic inflammatory condition → AA amyloidosis
the condition seen in the image causes vasculitis; what can this cause?
- MI
- cerebrovascular disease
- renal failure
- mesenteric and intestinal infarction (watershed area = splenic flexure)
- gangrene
the condition seen in the image is rheumatoid factor positive or negative?
rheumatoid factor POSITIVE = IgM directed at the Fc portion of IgG
what serum levels are increased in the condition seen in the image?
increased ANA, CRP, ESR and neutrophils
____ is the most specific antibody found in the condition seen in the image
anti-CCP (cyclic citrullinated peptide) is the most specific antibody found in the condition seen in the image
summarize the differences between RA and OA
list the seronegative spondyloarthropathies
list predisposing factors for the condition seen in the image
- obesity
- red wine
- red meat
- leukemia
- alcohol (competes with uric acid in the nephron)
- Lesch Nyhan (HGPRT def.)
- thiazides
in the condition seen in the image, ____ engulf uric acid crystals and activate the ____ pathway that brings in ____
in the condition seen in the image, macrophages engulf uric acid crystals and activate the complement pathway that brings in neutrophils
in the chronic form of the condition seen in the image, ___ form in the articular cartilage of joints & soft tissue and induces ____ inflammation
in the chronic form of the condition seen in the image, tophi form in the articular cartilage of joints & soft tissue and induce foreign body type of granulomatous inflammation
the crystals seen in the condition in the image are composed of ____ and are (positively or negatively?) birefringent
the crystals seen in the condition in the image are composed of monosodium urate and are negatively birefringent
the crystals seen in the condition in the image are composed of _____, are ___-shaped and are ____ (color)
the crystals seen in the condition in the image are composed of monosodium urate, are needle-shaped and are yellow
list the bacterial organisms that can cause infectious arthritis
- bacteria: rapid joint destruction
- S. aureus (children)
- N. gonococcus (adults)
- Mycobacteria
- Borrelia (Lyme disease)
list the viral organism (1) that can cause infectious arthritis
Parvovirus B19
the most common malignant tumor of the bone is caused by ____
the most common malignant tumor of the bone is caused by metastasis
____ is an important predictor of behavior in bone tumors
histologic grade is an important predictor of behavior in bone tumors
histologic grade of a bone tumor determines ____
histologic grade of a bone tumor determines likelihood of adjuvant therapy
____ predicts the clinical outcome of a bone tumor
tumor stage predicts the clinical outcome of a bone tumor
osteoid osteomas have a predilection for _____
osteoid osteomas have a predilection for appendicular skeleton
appendicular skeleton = the portion of the skeleton that consists of the girdles and the limbs. The primary function of the pectoral girdle, which is composed of the clavicle and the scapula, is to attach the upper limbs to the axial skeleton.
in osteoid osteoma, there is nocturnal pain that is _____
in osteoid osteoma, there is nocturnal pain that is alleviated by aspirin
list the 3 characteristics of osteoid osteomas
- small size
- self-limited growth
- tendency to cause extensive reactive changes in adjacent tissues
osteomas have a predilection for ____
osteomas have a predilection for craniofacial bones
osteomas are part of ____ syndrome; what else is found in this?
osteomas are part of Gardner’s syndrome
DOPES =
desmoid tumors, osteomas, papillary thyroid tumor, epidermal cysts, supernumerary teeth
the hereditary form condition seen in the image is associated with mutations in ___ and ___
the hereditary form condition seen in the image is associated with mutations in p53 (LiFraumeni) and retinoblastoma (Rb)
the sporadic form of the condition seen in the image is associated with which 3 mutations?
p53
Rb
MDM2 (inactivates apoptotic capacity of p53)
describe how the condition seen in the image has bimodal distribution
seen in teenagers (who may have had a history of bilateral retinoblastomas as a child)
seen in older patients with Paget’s disease
explain how the anatomic location of the condition seen in the image affects the grade
intramedullary = low grade
intracortical = high grade
juxtacortical = low or high grade
the condition seen in the image arises from the ___ (part of bone) and is a tumor of ____ (cells)
the condition seen in the image arises from the metaphysis and is a tumor of osteoblasts → imperfect laying of the osteoid
the condition seen in the image has a predilection for sites around ____ (where on the body?)
the condition seen in the image has a predilection for sites around the knee (distal femur, prox. tibia)
on x-ray of the condition seen in the image, ____ and ___ is seen
on x-ray of the condition seen in the image, Codman’s triangle (periosteal elevation) and reactive bone formation (sunburst appearance) is seen
on biopsy of the condition seen in the image, there is ____ laid down by malignant ____
on biopsy of the condition seen in the image, there is lace-like osteoid laid down by malignant osteoblasts
what is a complication for the condition seen in the image?
hematogenous spread to lungs → hemoptysis, chest pain and breathlessness
osteochondroma is a benign cartilage tumor of the ___ (part of bone?)
osteochondroma is a benign cartilage tumor of the metaphysis
osteochondromas only occur in bones with _____
osteochondromas only occur in bones with endochondral ossification
the condition seen in the image is a benign tumor made of ___ and ___
the condition seen in the image is a benign tumor made of hyaline and myxoid cartilage
the condition seen in the image affects the bones of the ___ and ____
the condition seen in the image affects the bones of the hands and feet
describe how the condition seen in the image is related to Ollier’s disease
Ollier’s disease = multiple enchondromas on one side of the body → increased risk of chondrosarcoma
describe how the condition seen in the image is part of Mafucci’s disease
Mafucci’s disease = multiple enchondromas on BOTH sides
+ 20% chance of developing chondrosarcoma
+ 100% chance of developing extraskeletal malignancies (soft tissue angiomas, CNS gliomas, ovarian carcinomas)
on x-ray investigation of the condition seen in the image, there is an incidental finding of ____ sign
on x-ray investigation of the condition seen in the image, there is an incidental finding of “O-ring” sign
the condition seen in the image can follow Ollier’s or Mafucci and arise from the ____ (part of bone?)
the condition seen in the image can follow Ollier’s or Mafucci and arise from the metaphysis
the condition seen in the image can occur sporadically and arise from the ____ (part of bone?)
the condition seen in the image can occur sporadically and arise from the diaphysis
the condition seen in the image affects the ___ skeleton
the condition seen in the image affects the axial skeleton
the condition seen in the image can occur due to ____
the condition seen in the image can occur due to Paget’s disease
the condition seen in the image arises from the ___ (part of bone?)
the condition seen in the image arises from the the epiphysis
describe what is seen on biopsy (histology) of the condition seen in the image
multinucleated osteoclast-like giant cells (reactive) + neoplastic mononuclear stromal cells
on x-ray of the condition seen in the image, a _____ appearance is seen because ____
on x-ray of the condition seen in the image, a soap bubble appearance is seen because it’s very cystic and radiolucent
the condition seen in the image is also called ____
the condition seen in the image is also called primitive neuroectodermal tumor (PNET)
name the 2 translocations associated with the condition seen in the image
t(11,22)
t(21,22)
the condition seen in the image arises from the ___ (part of bone?)
the condition seen in the image arises from the diaphysis
describe the histology of the condition seen in the image
sheets of small round blue cells with small amounts of clear cytoplasm
on biopsy of the condition seen in the image, a ____ appearance is seen
on biopsy of the condition seen in the image, an onion-skin appearance is seen
In Ewing sarcoma, the t(11;22) chromosomal translocation leads to production of _____
In Ewing sarcoma, the t(11;22) chromosomal translocation leads to production of EWS-FLI-1, an overactive transcription factor
