pathoma 18 Musculoskeletal Pathology zhester
Terms in this set (153)
What mutation and type of mutation causes achondroplasia?
AD- activation mutation in FGFR3
*constitutive activation actually inhibits chondrocyte proliferation in growth plates
*> 85% of mutations occur spradically and are associated with advanced paternal age, but condition also demonstrates autosomal dominant inheritance
Patient presents with short extremities with normal-sized head and chest.
impaired cartilage proliferation at growth plate.
*mental function, life span, and fertility are not affected
*failure of longitudinal bone growth (endochondral ossification)
*intramembranous ossification not affected → normal head and body
What type is defective in osteogenesis imperfecta? Cause?
collagen type 1 synth (bONE). AD defect.-> weak bone.
List 3 clinical features of osteogenesis imperfecta.
multiple fractures of bone (mimics child abuse but with no bruises)
blue sclera (exposure of choroidal veins)
hearing loss (fx of bones of middle ear (ossicles- malleus, incus, stapes) )
Inherited defect of bone resorption resulting in abnormally thick, heavy bone that fractures easily. Mechanism?
osteopetrosis. D/t poor osteoclast fxn d/t carbonic anhydrase 2 mutation.
What is the mutation in osteopetrosis?
carbonic anhydrase 2 mutation- results in loss of acidic environment required for bone resorption. H2O and CO2 -(CA2)-> H2CO3 -> H+ and HCO3. H+ goes to make acidic environment for osteoclasts.
How does Carbonic anhydrase 2 work?
H2O and CO2 -(CA2)-> H2CO3 -> H+ and HCO3. H+ goes to make acidic environment for osteoclasts. In kidney tubular cells, same process, but H+ goes into lumen to bind with NH3-> NH4+ to be able to excrete NH3. HCO3 goes into blood, lowering pH.
Osteopetrosis s/s (3/6). tx?
-anemia, thrombocytopenia, leukopenia (replacement of medullary cavity with bone (myelofissic process))-> extramedullary hematopoiesis
vision and hearing impairment (cranial nerve disruptions)
hydrocephalus (narrowing of foramen magnum)
renal tubular acidosis (carbonic anhydrase deficiency-> dec. tubular resorption of HCO)
tx- marrow txplant (clasts are derived from monocytes)
What is caused by low levels of vitamin D
rickets/osteomalacia- defective mineralization of osteoid
List 5 causes of vitamin D deficiency. What does vitamin D do?
decreased sun exposure
malabsorption (fat soluble)
liver failure and renal failure (can't activate)
Works on intestines, kidney, bone to resorb Ca and PO4.
Rickets s/s (3)
pigeon breast deformity
- inward bending of ribs with anterior protrusion of sternum
frontal bossing (osteoid deposition on forehead)
rachitic rosary- deposition of osteoid at the costochondral junction make beads
bowing of legs
Osteomalacia: def., levels of:
alkaline phosphatase- why?
weak bone with ^risk for fx in weight bearing areas (vertebrae, hip)
decreased serum calcium
decreased serum phosphate
elevated alkaline phosphatase
- due to activation of osteoblasts
- alkaline environment required to calcify unmineralized osteoid
osteoporosis- def, s/s
Loss of trabecular (spongy) bone mass resulting in porous bone with risk for fracture. Based on peak bone mass (age 30) and loss of bone mass afterward.
bone pain and fractures in weight-bearing areas
*vertebral crush fractures: acute back pain, loss of height,kyphosis
Is estrogen protective or detrimental to peak bone mass? What can ^ peak bone mass? What drug can decrease it?
genetics (Vit D receptor variances), exercise, diet increase.
List the 2 most common forms of osteoporosis.
type 1: postmenopausal; ↑ bone resorption due to ↓ estrogen levels
type 2: senile osteoporosis; affects men and women > 70 years of age
Describe the levels of the following in osteoporosis:
- use this to differentiate from osteomalacia
Osteoporosis monitoring, Rx (3/6)
monitor bone density using DEXA scan
bisphosphonates (attach to bone, osteoclasts eat and apoptose)
- glucocorticoids are contraindicated
Paget's disease of bone
Imbalance between osteoclast and osteoblast function- infection of the osteoclasts making them crazy, doesn't need to be activated by osteoblast
*usually seen in late adulthood, localized in one bone*. May be d/t infection by paramyxovirus.
-> thick, sclerotic bone that fx easily
Paget's disease of bone etiology
unknown; possibly viral (paramyxovirus)
*infection of the osteoclasts making them crazy, doesn't need to be activated by osteoblast
Do osteoblasts or osteoclasts have PTH receptors?
List the 3 stages of Paget's disease of bone.
osteoblastic (osteoclast burns out)
*note that cement lines have not been fused → mosaic pattern
Paget's disease of bone s/s (3/5)
bone pain (microfracture)
increasing hat size (skull commonly affected)
hearing loss (cranial nerve impingement due to auditory foramen narrowing)
isolated elevated alkaline phosphatase* (Ca, PO4, PTH normal)- osteoblasts lay down bone in end-stage disease
Paget's disease of bone drug Tx (2)
calcitonin: inhibits osteoclasts
bisphosphonates: inhibits osteoclasts
List 2 complications of Paget's disease of the bone.
high-output cardiac failure- *remodeling of bone leads to formation of A-V shunts
osteosarcoma- *osteoblasts are producing a large amount of bone and can become mutated->malignant tumor
Infection of the marrow space and bone- usually d/t bacteria via hematogenous spread (kids) or open wound (adults)
What part of the bone is affected in children with osteomyelitis? adults?
metaphysis in children
epiphysis in adults
List 6 causes of osteomyelitis.
S. aureus- most common
N. gonorrhoeae- sexually active young adults
Salmonella- sickle cell disease
Pseudomonas- diabetics or IV drug abuse
Pasteurella- dog or cat bite/scratch
TB- Pott disease of the vertebra
bone pain with fever and leukocytosis
Describe the X-ray of osteomyelitis. Dx?
lytic focus (liquefactive necrosis) surrounded by sclerosis (reactive bone)
- diagnosis made by blood culture
avascular (aseptic) necrosis- def., causes, complications
ischemic necrosis of bone and bone marrow.
d/t trauma, fx, steroids, sickle cell (dactylitis), caisson disease (gas emboli (N2) lodges in bone.
comp: osteoarthritis and fracture
What bone tumor is associated with Gardner syndrome? Benign or malignant? What is Gardner's syndrome?
- MC in craniofacial bones
- FAP + fibromatosis of retroperitoneum+osteomas
benign tumor of bone. MC on surface of facial bones. A/W Gardner syndrome (- FAP + fibromatosis of retroperitoneum+osteomas)
Benign tumor of osteoblasts laying down osteoid surrounded by rim of reactive bone.
- young adults (< 25 years)
- arises in cortex of diaphysis of long bones
Bone pain resolves with aspirin*.
on x-ray- bony mass with radiolucent core (core is osteoid)
Similar to osteoid osteoma but bigger (>2cm). MC assoc. w/vertebrae*
- presents as bone pain that does not respond to aspirin*
benign Tumor of bone with an overlying cartilage cap. MC benign tumor of bone. d/t lateral projection of growth plate (little mushroom growing off bone)- contiguous with marrow*
overlying cartilage can txform to chondrosarcoma
What is the most common benign tumor of bone?
*but overlying cartilage can transform to chondrosarcoma
Which bone lesions show up in metaphysis?
osteomyelitis in kids, osteochondroma, osteosarcoma,
Which bone lesions show up in epiphysis?
osteomyelitis in adults, giant cell tumor
Which bone lesions show up in diaphysis?
osteoid osteoma, osteoblastoma, Ewing's Sarcoma
How is vitamin D activated?
25-OHase in liver, then 1-alpha OHase in proximal tubules.
(exostosis)Malignant proliferation of osteoblasts- presents as path. fx with swelling and bone pain.
*peak incidence is seen in teenagers (men 10-20 years of age), also elderly.
MC in metaphysis on long bones around knee.
radiograph: sunburst appearance and lifting of periosteum (Kodman's angle)* (be careful with myositis ossificans)
histo: large pleomorphic cells producing osteoid.
List 4 risk factors for osteosarcoma.
familial Rb (RFfor bilat. retinoblastoma and OS)
Paget's disease (elderly)
Ischemic necrosis of bone and marrow. D/t trauma/fx (MC), steroids, sickle cell anemia (dactylitis), caisson disease (N2 bubbles). Complications- osteoarthritis and fx.
Giant cell tumor
Multinucleated giant cells and stromal cells. Soap bubble on x-ray.
epiphysis around knee!!
. locally aggressive, recurrent.
Locally aggressive and recurrent.
Histology shows pleiomorphic cells producing osteoid
Giant cell tumor (osteoclastoma) bone location
epiphysis around knee
X-ray shows a "double bubble" or "soap-bubble" appearance.
giant cell tumor
*reactive bone formation creates the soap-bubble appearance
*locally aggressive tumor
Malignant proliferation of poorly-differentiated cells derived from neuroectoderm
*extremely aggressive with early metastases, but responsive to chemotherapy.
X-ray: onion skin (tumor pushes out, periosteum lays down new layers).
Histo: small blue cells like lymphs (looks like osteomyelitis or lymphoma.
Can present with fever, so it looks like osteomyelitis.
Ewing's sarcoma bone location
diaphysis of long bones
*usually in male children < 15 years of age
*other sites include pelvis, scapula, ribs
X-ray of a long bone shows an onion-skin appearance.
*growth within the medullary cavity leads to layering of new bone on the periosteum
<i>Going out for Ewing's and onion rings
What bone tumor has a t(11;22) translocation?
<i>Patrick Ewing's jersey number
benign tumor of cartilage- medulla of small bones in hands or feet.
malignant cartilage-forming tumor. In medulla of pelvis or central skel.
Do cartilage tumors arise in the cortex or medulla?
Are metastatic or primary tumors of the bone more common?
What type of lesions are produced by metastatic tumors of the bone? What is an exception?
osteolytic (punched-out) lesions
prostatic carcinoma classically produces osteoblastic lesions (sclerotic)
Describe the normal anatomy of a synovial joint.
2 bones have articular cartilage made of type 2 collagen. Capsule surrounds joint. Capsule lined by synovium- secretes hyaluronic acid.
Degenerative joint disease- def., s/s., risk factors (3)
osteoarthritis. Progressive degeneration of articular cartilage (type 2 collagen) d/t Wear and tear. Fragments fall off into joint space (joint mice), eburnation (polishing) of subchondral bone, osteophyte outgrowths (bouchard nodes)
RF: age (major), obesity, trauma
Hips, low sine, knees, DIP AND PIP*. Joint stiffness worsens during day*. Osteophyte outgrowths in DIP and PIP (bouchard nodes)
Rheumatoid arthritis gene association
What is the hallmark of rheumatoid arthritis?
synovitis (inflamm. of synovium) leading to formation of pannus (inflamed granulation tissue- myofibroblasts contract in healing- fuse joint and pull joint out of alignment)-> destr. of cartilage and ankylosis (fusion) of joint (bilat joints- elbows/knees/wrist/fingers (DIP spared)). Morning stiffness that improves with use.
What type of arthritis presents as morning stiffness that improves with activity?
Which interphalangeal joint is usually spared in rheumatoid arthritis?
Rheumatoid arthritis s/s (3/7)
joint space narrowing
loss of cartilage
osteopenia (wears away at bone)
fever, malaise, weight loss, myalgias (d/t inflamm.)
rheumatoid nodules (fibrinoid necrosis surr. by palisading histiocytes)
Baker cyst (behind the knee)
interstitial lung fibrosis
Describe the lab findings in rheumatoid arthritis. Describe the synovial fluid.
Rheumaoid factor- IgM autoantibody against the Fc portion of IgG.
SF: neutrophils, ^protein, slightly cloudy.
List 2 complications of rheumatoid arthritis.
anemia of chronic disease
secondary amyloidosis (SAA is an acute phase reactant)
seronagative arthropathies- general, types
lack rheumatoid factor, involve axial skeleton, HLA-B27 assoc.
ankylosing spondyloarthritis, reiter syndrome, psoriatic arthritis
young adult males
Low back pain- involves sacroiliac joints and spine that leads to fusion of the vertebrae (bamboo spine). Seronegative.
HLA B27 assoc.
*aortic regurgitation due to aortitis->aneurysm
*uveitis (red eyes- blurry vision-> blindness)
seronegative spondyloarthropathy presents in young male adults weeks after a GI or C. trachomatis infection. Triad: Can't see, Can't pee, can't climb a tree (arthritis, urethritis, conjunctivitis)
associated with "sausage" fingers or toes?
- 10% of cases of psoriasis
- involves axial and peripheral joints, esp. DIP
What is the most common overall cause of infectious arthritis? Second most common cause? Description?
- young adults
- older children and adults
Single warm joint with limited ROM
fever and ^ WBC, ^ESR
Describe the normal physio of uric acid and what leads to hyperuricemia
Food has DNA/RNA. Purines broken down to uric acid.
AMP -> hypoxanthine
hypoxanthine and guanine can be recycled using HGPRT (hypoxanthine guanine phosphoribotransferase
hypoxanthine and guanine both-> xanthine
Xanthine --(xanthine oxidase)--> uric acid
Uric acid goes into blood and is filtered by kidney.
hyperuricemia can be d/t too much uric acid in blood or dec. excretion.
Deposition of monosodium urate (MSU- from uric acid) crystals in tissues, especially the joints- classic in acute gout attack is painful big toe (podagra)- crystals activate neutros*.
-exacerbated by ETOH or meat.
Can be primary (unknown cause) or secondary.
Chronic gout can cause tophi and renal failure.
List 3 causes of secondary gout.
-leukemia and myeloproliferative disorders (high cell turnover breaks more purines into UA)
-Lesch-Nyhan syndrome - HGPRT required for purine salvage pathway (x-linked deficiency)- MR and self-mutilation (biting lips and fingers)
-renal insufficiency (dec. excretion of uric acid)
How does alcohol consumption cause gout?
byproducts compete with uric acid for excretion
Uric acid crystals in soft tissue or joints
tophi- white, chalky aggregates of UA. Seen in chronic gout.
- associated with fibrosis and giant cell reaction
How does chronic gout cause renal failure?
uric acid deposits in the tubules
Describe the laboratory findings of gout
polarized light- needle-shaped crystals with NEGATIVE birefringence in SF
- yellow when parallel to ray
What deposits cause pseudogout?
Describe the laboratory findings of pseudogout under polarized light.
basophilic rhomboid-shaped crystals in SF with weak POSITIVE birefringence
dermatomyositis- desc., presentation, labs, histo, tx, assoc.
Inflammatory disorder of the skin and skeletal muscle
bilateral PROXIMAL weakness- *can't comb hair, can't climb stairs- *distal involvement can develop late in disease
rash of upper eyelids (heliotrope rash) malar rash**, red papules on elbows, knuckles, knees (Grotton's lesions)
^CK, ^ANA, ^Anti-jo-1 Ab*,
biopsy- perimysial inflamm. with Tcells, perifascicular atrophy (closer to skin) (contrast with polymyositis)
Assoc. with gastric carcinoma*
Hallmark lab findings for dermatomyositis
Perimysial inflammation (CD4+ T cells) with perifascicular atrophy
Inflammatory disorder of skeletal muscle that does not involve the skin. Prox. mm weakness. biopsy- Endomysial inflammation (CD8+ T cells) with necrotic muscle fibers
Disorder characterized by replacement of skeletal muscle by adipose tissue
X-linked muscular dystrophy
Gene defects associated with x-linked muscular dystrophy
dystrophin (needed to anchor mm cells to basement membranes).
Largest gene in body, so can be spontaneous mutation/deletion
X-linked muscular dystrophy presentation, lab
Child presents with proximal muscle weakness at 1 year of age, Calf pseudohydrophy, ^CK
Cause of death in X-linked muscular dystrophy
cardiac or respiratory failure (myocardium often involved).
Autoantibodies against the postsynaptic Ach receptor at the NMJ
*more commonly seen in women
myasthenia gravis def. presentation, tx.
Ab against ACh receptor at NMJ.
Muscle weakness that worsens with use and improves with rest;
classically involves eyes leading to ptosis and diplopia*.
assoc. with thymic hyperplasia/thymoma** - remove the thymus and s/x improve.
tx- symptoms improve with anticholinesterase
Which NMJ disorder is associated with thymic hyperplasia and thymoma?
*****myasthenia gravis*****- thymectomy improves s/s
Antibodies against presynpatic calcium channels at the NMJ
Lambert-Eaton syndrome-> impaired Ach release.
Which NMJ disorder is associated with small cell carcinoma of the lung?
*resolves with resection of cancer
Lambert-Eaton syndrome presentation- tx
Ab against presynaptic Ca channels-> dec. Ach release.
Usually paraneoplastic syndrome- MCC is small cell carcinoma
Proximal muscle weakness that improves* with use; eyes are usually spared. Anticholinesterase doesn't help. Resect Ca.
Benign tumor of adipose tissue- MC benign soft tissue in adults
Most common benign soft tissue tumor in adults
Malignant tumor of adipose tissue- lipoblasts are characteristic cell. MC malignant tumor in adults
Most common malignant soft tissue tumor in adults
rhabdomyoma- def, special ex. and assoc
Benign tumor of skeletal muscle
cardiac rhabdomyoma assoc. tuberous sclerosis
rhabdomyosarcoma- histo, MCC sites
Malignant tumor of skeletal muscle- rhabdomyoblast is characteristic cell.- desmin positive*.
MC in vagina of young girls**, head and neck overall.
MC malignant soft tissue tumor in kids
Most common malignant soft tissue tumor in children
Primary bone tumor with spindle-shaped cells with multinucleated giant cells
giant cell tumor (osteclastoma)
Giant cell tumor (osteoclastoma) age
20-40 years of age
men < 25 years of age
2nd most common primary malignant bone tumor
osteosarcoma (osteogenic sarcoma)
Codman's triangle or sunburst pattern on X-ray
*elevation of periosteum
Most common primary malignant bone tumor
Anaplastic small blue cell malignant tumor
Chondrosarcoma age and sex
men 30-60 years of age
Chondrosarcoma location (3/6)
Malignant cartilaginous tumor
Expansile glistening mass within the medullar cavity
In what disease can osteoclasts have up to 100 nuclei?
*markedly increased bone turnover
Describe the following in Paget's disease (osteitis deformans):
↑ alkaline phosphatase
Compartment syndrome treatment
List 3 common organisms that cause septic arthritis.
<i>STD = Synovitis (e.g. knee), Tenosynovitis (e.g. hand), and Dermatitis (e.g. pustules)
List 2 causes of chronic infectious arthritis.
TB (mycobacterial dissemination)
Most common cause of septic arthritis in patients with prosthetic joints
STD that presents as monoarticualr, migratory arthritis with asymmetrical pattern
What is the most common body part affected by polymyositis?
"Mechanic's hand", "shawl and face" rash
List 2 enzymes elevated in dermatomyositis and polymyositis.
Which type of osteoporosis is associated with femoral neck fracture and distal radius (Colles') fractures?
Prophylaxis for type 2 osteoporosis
exercise and calcium ingestion before age 30
Which cells are implicated in osteopetrosis?
osteoclasts (abnormal function)
Describe the following in osteopetrosis:
Why does osteopetrosis cause anemia, thrombocytopenia, infection, and extramedullary hematopoiesis?
primary spongiosa fills medullary cavity, causing decreased marrow space
"Erlenmeyer flask" bones
osteopetrosis (marble bone disease)
Describe the following in osteitis fibrosa cystica:
↑ serum Ca2+
↓ serum phosphate
Bone replaced by fibroblasts, collagen, and irregular bony trabeculae
polyostotic fibrous dysplasia
Form of polyostotic fibrous dysplasia characterized by multiple unilateral bone lesions associated with endocrine abnormalities (precocious puberty) and cafe-au-lait spots
Wear and tear of joints leads to destruction of articular cartilage, subchondral cysts, sclerosis, osteophytes (bone spurs), eburnation
What disorder is associated with Heberden's and Bouchard's nodes?
What disorder is associated with eburnation?
*polished, ivory-like appearance of bone
Osteoarthritis predisposing factors (3)
Does cartilage loss in osteoarthritis begin on the lateral or medial aspect?
medial aspect → bowlegged
Name an autoantibody that is less sensitive but more specific than rheumatoid factor.
Rheumatoid arthritis Rx (4)
DMARDs (methotrexate, sulfasalazine, hydroxychloroquine)
Rheumatoid arthritis hypersensitivity type
Diuretics that can cause gout
Lysosomal storage disease that can cause gout
von Gierke's disease
Is gout more often a result of uric acid overproduction or underexcretion?
What disorder is associated with PRPP excess?
List 3 classic sites of tophus formation.
Acute gout Rx (2)
NSAIDs (e.g. indomethacin)
Chronic gout Rx (3)
uricosurics (e.g. probenecid)
What is the classic site of pseudogout?
knee (large joints)
Is gout more common in men or women?
Is pseudogout more common in men or women?
Crystals are yellow when parallel and blue when perpendicular to the light.
Crystals are blue when parallel and yellow when perpendicular to the light.
List 3/4 causes of osteonecrosis (infarction of bone and marrow)
Dactylitis and "pencil-in-cup" deformity on X-ray
*seen in fewer than 1/3 of patients with psoriasis
Reactive arthritis (Reiter's syndrome) classic triad
conjunctivitis and anterior uveitis
What does Vitamin D do?
^serum Ca and PO4 by ^ absorption in intestine, ^ resorption in kidney, ^resorption from bone.
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