Musculoskeletal Pathology Flashcards
Achondroplasia is due to an _________ mutation in ________. This leads to _______.
activating mutation in FGFR3 (Fibroblast Growth Factor Receptor 3). overexpression of FGFR3 leads to impaired cartilage proliferation in the growth plate.
What impact does achondroplasia have on development?
leads to short extremities with normal sized head and chest. mental function, life span, and fertility are not effected
What causes the pattern of short extremities but normal head and chest with achondroplasia?
the activating mutation of FGFR3 leads to impaired endochondral bone formation, while intramembranous bone formation remains unaffected. this is due to embryological development.
what is endochondral bone formation?
formation of a cartilage matrix, which is then replaced by bone. it is the mechanism by which long bones grow. this is affected with achondroplasia.
what is intramembranous bone formation?
characterized by formation of bone without preexisting cartilage matrix. it is the mechanism by which flat bones, such as the skulls and rib cage, develop. this is not affected with achondroplasia
osteogensis imperfecta is a congenital defect of…
bone formation resulting in structurally weak bone
osteogenesis imperfecta is most commonly due to an…
autosomal dominant defect in COLLAGEN TYPE I synthesis. (bONE has ONE in it_
what are the clinical features of osteogenesis imperfecta
- multiple fractures, which can mimic child abuse, but bruising is absent
- Blue sclera, which is due to thining of scleral collagen
- hearing loss due to the bones of the inner ear easily fracturing.
what is the cause of blue sclera with osteogenesis imperfecta
thinning of the scleral collagen, which reveals underlying CHOROIDAL VEINS
Osteopetrosis is due to…
inherited defect of bone resorption resulting in abnormally thick, heavy bone that fractures easily. it is due to poor osteoclast function
there are multiple genetic variants with osteopetrosis, which lead to mutations in…
carbonic anhydrase II
what is the outcome of loss of carbonic anhydrase II with osteopetrosis
inability to convert H2O + CO2 to H2CO3. H2CO3 would then normally be converted to H+ and HCO3- and the H+ would be used to create the acidic environment essential for bone resorption. without this, you cant break down bone
what are the clinical features of osteopetrosis
bone fractures anemia, thrombocytopenia, leukopenia vision and hearing impairment hydrocephalus renal tubular acidosis
why can anemia, thrombocytopenia, and leukopenia be seen with osteopetrosis?
it results in bony replacement of medullary (bone marrow) space, a myelophthisis process (process that replaces marrow space). extramedullary hematopoeisis is also seen due to the loss in medullary space
why is there visual impairment and hearing impairment with osteopetrosis?
impingement of cranial nerves by increased bone size
why is there hydrocephalus with oseopetrosis?
narrowing of the foramen magnum due to increased bone thickness
how can osteopetrosis cause renal tubular acidosis?
the loss of carbonic anhydrase II leads to inability to convert H20 + CO2 to H2CO3, which then becomes H+ and HCO3-. without creating H+ and HCO3-, there will be no bicarb to pump into the blood, leading to acidosis.
what is the treatment for osteopetrosis?
bone marrow transplant. this allows for the creation of functional monocytes, which are the precursors to functional osteoclasts.
Rickets and Osteomalacia result from
defective mineralization of osteoid. this is due to a low vitamin D level. in children- rickets; in adults- osteomalacia
what is the role of vitamin D
raises serum calcium and phosphate by:
- increasing absorption of calcium and phosphate from intestines
- increasing reabsorption of calcium and phosphate from kidneys
- increasing reabsorption of calcium and phosphate from bone
what is the result of abnormal bone mineralization in children with rickets
- pigeon breasted deformity- inward bending ribs with anterior protrusion o the sternum
- frontal bossing (enlargement of the forehead- due to osteiod deposition on the skull
- rachitic rosary- due to osteoid deposition in the costochondral junction
- bowing of the legs
what are lab finding of osteopetrosis
decreased serum calclium, decreased serum phosphate, increase PTH and increased alk phos.
Osteoporosis is due to a decrease in _______ bone mass
trabecular
risk of Osteoporosis is based on peak bone mass. what 3 factors determine peak bone mass
- diet
- Exercise
- vitamin D receptor
it is achieved by age 30
rate of bone loss is determined by
- diet
- exercise
- estrogen, which serves to protect bones
what are lab finding with osteomalacia
decreased serum calcium
decreased serum phosphate
increased PTH
increased alkaline phosphatase
why is there an increased alkaline phosphatase with osteomalacia?
if there are active osteoblasts, there will be increased alkaline phosphatase because a basic/ alkaline environment is needed to deposit calcium. osteoblasts are active with osteomalacia
what do osteoblasts due and how does this impact osteomalacia and rickets
osteoblasts lay down osteoid, which is then is converted to bone with calcium and phosphate mineralization. with osteomalation and rickets, there is osteoid deposition, but defective mineralization
what are the clinical features of Osteoporosis
- bone pain and fractures in weight bearing areas such as vertebrae, hip, and distal radius
- bone density decrease, which is measured by DEXA scan
- serum calcium, phosphate, PTH, and alkaline phosphatase are normal, which helps to differentiate from osteomalacia
how do lab tests differ with osteomalacia and osteoporosis
with Osteoporosis, serum calcium, phosphate, PTH, and alkaline phosphatase are normal.
with osteomalacia, serum calcium and phosphate are decreased, and PTH and alkaline phosphatase are elevated
what are the treatments for osteoporosis
- exercise, vitamin D, and calcium to limit bone loss
- bisphosphonates, which induce apoptosis of osteoclasts.
- estrogen replacement therapy is debated
- glucocorticoids are contraindicated
Paget’s disease of bone is caused by an imbalance between…
osteoblast and osteoclast function
Paget’s disease is a _______ process that involves _______ bones.
localized process that involves one or more bones, not the entire skeleton
what are the three phases of Paget’s disease
- osteoclastic: osteoclasts go crazy
- mixed osteoblastic-osteoclastic: osteoblasts also kick in to try and help
- osteoblastic: osteoclasts burn out and osteoblasts continue, which results in thick, sclerotic bone that fractures easy.
what is the relationship between osteoclasts and osteoblasts
osteoblasts manage osteoclasts. osteoblasts have the PTH receptor, so osteoclasts shouldn’t work without being told to by osteoblasts, which receive PTH
what will biopsy reveal with Paget’s disease
mosaic pattern of lamellar bone that looks like puzzle pieces
what are the clinical features of Paget’s disease
- bone pain due to microfractures
- increasing HAT SIZE due to skull being affected
- hearing loss due to impingment of cranial nerves
- LION LIKE FACIES due to involvment of cranial facial bones
- isolated elevated ALK PHOS.
Paget’s disease is the most common cause of isolated elevated ________ in patients over 40
alkaline phosphatase
treatment of Paget’s disease of bone includes
calcitonin to inhibit osteoclast function
bisphosphonates to induce apoptosis of osteoclasts
what are two complications of Paget’s disease (HIGH YIELD)
- HIGH OUTPUT CARDIAC FAILURE DUE TO FORMATION OF AV SHUNTS
2. OSTEOSARCOMA
osteomyelitis is an infection of the ______ and ______ that usually arises in ________ and is most commonly caused by ____
bone and marrow, children, bacteria
osteomyelitis is usually caused by bacteria through ________ spread. it typically seeds in which areas for children and adults?
hematogenous spread. transient bacteremia in children seeds in the METAPHYSIS. open round bacteremia in adults seeds in the EPIPHYSIS. HIGH YIELD
bacterial causes of osteomyelitis include (6)
- S. aureus: most common, 90%
- N gonorrhoeae: sexually active young adults
- Salmonella: most common with sickle cell
- Pseudomonas: diabetics and IV drug users
- Pasteurella: cat or dog bites or scratches
- Mycobacterium Tuberculosis: usually involves vertebrae
clinical features of osteomyelitis
- bone pain with systemic findings like fever and leukocytosis
- Lytic focus (abscess) surrounded by SCLEROSIS of bone of X ray.
- - lytic focus is called SEQUESTRUM
- - sclerosis is called INVOLCRUM
diagnosis of osteomyelitis is made by _______
blood culture
avascular (aseptic) necrosis is
ischemic necrosis of the bone and bone marrow
what are the causes of avascular necrosis, as well as the complications
trauma of fracture (most common). steroids, sickle cell anemia (dactylitis), and caisson disease (nitrogen emboli).
complications include osteoarthritis and fractures
Osteoma is a ______ tumor of bone
benign (oma)
osteoma most commonly arises on the _________ and is associated with ________ syndrome
surface of facial bones; Gardner Syndrome
Osteoid osteoma is a _______ tumor of ______ surrounded by a rim of ________
benign tumor of osteoblasts (that produce osteoid) surrounded by a rim of reactive bone.
Osteoid osteoma arises in the ________ and occurs in what age?
CORTEX of long bones and occurs at age <25, more commonly in males
Osteoid osteoma presents as….
bone pain that RESOLVES WITH ASPIRIN
What are the three main differences between Osteoid osteoma and osteoblastoma
- osteoblastoma has a bone mass >2 cm, which Osteoid osteoma is <2cm
- osteoblastoma arises in the vertebrae, while Osteoid osteoma is in the cortex of long bones
- osteoblastome arises as bone pain that DOES NOT RESOLVE WITH ASPIRIN
Osteochondroma is ….
tumor of bone with an overlying cartilage cap. it is the MOST COMMON BENIGN TUMOR OF BONE
Osteochondroma arises from a _______ of the growth plate (metaphysis) and the bone is _______ with the marrow space
lateral projection of metaphysis and is continuous with the marrow space
a complication of osteochondroma is….
the overlying cartilage can transform into chondrosarcoma
Osteosarcoma is a …
malignant proliferation of osteoblasts. MALIGNANT = SARCOMA
Peak incidence of osteosarcoma is seen in _____ and _______
teens and elderly
what are the risk factors for osteosarcoma (3)
- familial retinoblastoma (Teens)
- Paget disease (elderly)
- radiation exposure (elderly)
where does osteosarcoma typically present
arises in the metaphysis of long bones, usually the distal femur and proximal tibia (region of the knee) HIGH YIELD
how does osteosarcoma present
as a pathological fracture or bone pain with swelling
what does imaging of osteosarcoma reveal
destructive mass with “sun burst” appearance and lifting of the periosteum, which is called CODMAN’S TRIANGLE/ ANGLE
biopsy of osteosarcoma reveals
pleomorphic cells that produce osteoid. this is the hallmark biopsy
Giant cell tumor is the only relevant tumor occurring in the
epiphysis. typically occurs in young adults in the epiphysis
why can giant cell tumor and osteosarcoma have a similar presentation
because they both occur in the distal femur or proximal tibia (region of the knee)
what is the x ray appearance of Giant Cell Tumor
“soap bubbles” in the epiphysis
Ewing sarcoma is a _______ proliferation of poorly differentiated cells derived from _______
malignant, neuroectoderm
where does Ewing sarcoma arise
in the diaphysis of the long bones, usually in male children less than 15 years of age
and “onion skin” appearance on x ray is indicative of…
Ewing sarcoma
what mutation is characteristic of Ewing sarcoma
translocation 11;22
biopsy of Ewing sarcoma reveals
small, round blue cells that resemble lymphocytes. can be confused with lymphoma or chronic osteomyelitis
chondrosarcoma is a ________, ________ forming tumor that arises in ________
malignant cartilage forming tumor that arises in medulla of pelvis or central skeleton
chondroma is a _____ tumor of ______ that arises in _______
benign tumor of cartilage that arises in medulla of small bones of hands and feet
what are the three main points of cartilage tumors
- both commonly arise in the medulla
- benign tumors occur in small bones of hands and feet (chondroma)
- malignant tumors arise in pelvis or central skeleton (chondrosarcoma)
metastatic bone tumors usually results in ______ lesions. what is the main exception
punch out lesions. prostatic carcinoma classically produces osteoblastic lesions (sclerosis of bone)
degenerative joint disease (osteoarthritis) is most often due to ______. how common is it?
wear and tear. most common form of arthritis.
what are the three main risk factors for degenerative joint disease (osteoarthritis)
age, obesity, trauma
what is the classical presentation of degenerative joint disease (osteoarthritis)
joint stiffness in the mornings that worsens throughout the day HIGH YIELD
does degenerative joint disease (osteoarthritis) include the DIP, PIP, or both
both
what are the pathologic features of degenerative joint disease (osteoarthritis) (3)
- disruption of the cartilage that lines the articular surfaces, with fragments of cartilage floating in joint space (joint mice)
- eburnation/ polishing of the subchondral bone
- osteophyte formation (reactive bony outgrowths)
with degenerative joint disease (osteoarthritis), what are the names of osteophytes in the DIP and PIP
DIP: HEBERDEN NODES
PIP: BOUCHARD NODES
Rheumatoid Arthritis is a ___________ disease
chronic, systemic autoimmune disease
Rheumatoid Arthritis is assocaited with….
HLA-DR4
Rheumatoid Arthritis is characterized by involvement of joints. what is the hallmark joint involvement
synovitis leading to formation of pannus (inflamed granulation tissue). the contraction of the granulation tissue leads to destruction of cartilage and ankylosis (fusion) of the joint
what are the 6 clinical features of Rheumatoid Arthritis
- symmetric involvement of PIP joints of fingers (Swan neck deformity), wrists (radial deviation), elbows, ankles, and knees. DIP spared
- fevers, malaise, weight loss, and myalgias
- rheumatoid nodules (central zone of necrosis surrounded by epithelial histiocytes)
- vasculitis
- baker cyst: swelling of bursa behind the knee
- pleural effusions, lymphadenopathy, and interstitial lung fibrosis
what are the lab findings with Rheumatoid Arthritis
IgM autoantibody against the Fc portion of IgG (rheumatoid factor); marker of tissue damage and disease activity.
neutrophils and high protein in the synovial fluid
what are two complications of Rheumatoid Arthritis
anemia of chronic disease and secondary amyloidosis
seronegative spondyloarthropathies are a group of joint disorders characterized by (3)
- lach of rheumatoid factors (seronegative)
- axial skeleton involvement (spondylo)
- HLA-B27 associated
seronegative spondyloarthropathies include which three conditions
- ankylosing spondyloarthritis
- reiter syndrome
- psoriatic arthritis
Ankylosing Spondyloarthritis involves ______ and ______.
sacroiliac joints and spine
Ankylosing Spondyloarthritis presentation
arises in oung adults, most often males
presents with low back pain, involvement of the vertebral bodies can eventually arise, leading to fusion of the vertebrae (bamboo spine)
extra articular manifestations include uveitis and aortitis, leading to aortic regurgitation
Reiter Syndrome is characterized by what triad and what is the presentation
Arthritis, urethritis, and conjuctivitis. “cant pee, can’t see, cant climb a tree.”
arises in young adults, typically males, weeks after a GI or chlamydia infection
psoriatic arthritis is seen in ____ of psoriasis cases and presents…
involves the axial and peripheral joints. DIP joints of the hands and feet are the most commonly effected, leading to SAUSAGE FINGERS AND TOES.
Infectious arthritis is typically due to bacterial infections, most commonly which two etiologies
N. Gonorrhoeae with young adults
S aureus with older children and adults
infectious arthritis typically involves how many joints and what is the presentation?
single joint, usually the knee. presents as a warm joint with imited ROM, fevers, increased white count, and elevated ESR are common.
Gout is due to deposit of ______ in tissues, especially joints, with is a result of _______
monosodium urate (MSU); hyperuricemia (related to overproduction or decreased production of uric acid
uric acid is derived from….
purine metabolism. it is excreted by the kidneys
primary gout is how common? what is the etiology of the hyperuricemia?
the most common form of gout. etiology unknown
secondary gout is seen with which three conditions
- leukemia and myeloproliferative disorders
- Lesch-Nyhan syndrome
- renal insufficiency
how does leukemia and myeloproliferative disorders lead to secondary gout?
increased cell turnover leads to hyperuricemia
how does Lesch-Nyhan Syndrome lead to secondary gout? what does this condition present like?
x linked deficiency of HYPOXANTHINE-GUANINS PHOSPHORIBOSYLTRANFERASE (HGPRT), which typically salvages xanthine and guanine. lack of this leads to increased production of uric acid. presents with mental retardation and self mutilation.
how does renal insufficiency lead to secondary gout?
decreased excretion of uric acid
How does acute gout present and what is a brief explanation of the pathophysiology? what two conditions may precipitate arthritis?
presents as exquisitely painful arthritis of the great toe (podagra). it is due to MSU crystals depositing in the joint, triggering and acute inflammatory reaction. alcohol or consumption of meat may precipitate arthritis.
what two conditions does chronic gout lead to?
development of TOPHI (white chalky aggregates of uric acid crystals with fibrosis and giant cell reactions in the soft tissues and joints)
renal failure - urate crystals may deposit in kidney tubules.
what are the lab findings with gout
hyperuricemia. synovial fluid shows NEEDLE SHAPED CRYSTALS WITH NEGATIVE BIFRINGENCE upon polarized light. HIGH YIELD
pseudogout resembles gout clinically, but is due to _______
calcium pyrophosphate dihydrate (CPPD). synovial fluid will show RHOMBOID SHAPED CRYSTALS WITH WEAKLY POSITIVE BIFRINGENCE, while gout will show NEEDLE SHAPED CRYSTALS WITH NEGATIVE BIFRINGENCE
what is a lipoma
benign tumor of adipose tissue. MOST COMMON BENIGN SOFT TISSUE TUMOR IN ADULTS
what is liposarcoma and what is the characteristic cell?
malignant tumor of adipose tissue. MOST COMMON MALIGNANT SOFT TISSUE TUMOR IN ADULTS. LIPOBLAST is the characteristic cell
what is rhabdomyoma?
benign tumor of skeletal muscle.
cardiac rhabdomyoma is associated with…
tuberous sclerosis
what is rhabdomyosarcoma
malignant tumor of skeletal muscle and the MOST COMMON MALIGNANT SOFT TISSUE TUMOR IN CHILDREN
what is the characteristic cell of rhabdomyosarcoma
rhabdomyoblast, which is DESMIN POSITIVE
what are the most common sites of rhabdomyosarcoma
head and neck; vagina is classic site in young girls (known as Sarcoma Botryoides Variant)
dermatomyositis is an inflammatory disorder of the ______ and ______. it has an unknown etiology, byt some cases are associated with ________
skin and skeletal muscle. carcinoma, especially gastric carcinoma.
what are the clinical features of dermatomyositis?
- bilateral PROXIMAL MUSCLE WEAKNESS (HALLMARK) with potential distal involvement late in the disease.
- rash of the UPPER EYELIDS (HELITROPE RASH), with potential MALAR RASH (must differentiate from lupus)
- RED PAPULES on elbows, knuckles, and knees (GOTTRAN PAPULES)
what are the laboratory findings with dermatomyositis?
- increased creatine kinase
- POSITIVE ANA AND ANTI JO-1 ANTIBODY (HALLMARK)
- perimysial inflammation (CD4+ T cells) with perifasicular atrophy on biopsy (HIGH YIELD)
what is the treatment for dermatomyositis?
corticosteroids.
what is polymyositis? what does it resemble?
inflammatory disorder of skeletal muscle. resembles dermatomyositis clinically, but SKIN IS NOT INVOLVED.
how do dermatomyositis and polymyositis differ on biopsy?
dermatomyositis: PERImysial inflammation (CD4+ T cells) with perifasicular atrophy on biopsy (HIGH YIELD)
polymyositis: ENDOmysial inflammation (CD8+ T cells) with necrotic muscle fibers seen on biopsy
X linked muscular dystrophy (Duchenne) is…
degenerative disorder characterized by muscle wasting and REPLACEMENT OF SKELETAL MUSCLE BY ADIPOSE TISSUE (HIGH YIELD)
X linked muscular dystrophy is due to defects in what gene? what is the role of the protein formed by this gene?
dystrophin gene. dystrophin is important in anchoring muscle to cytoskeleton extracellular matrix. mutations are often spontaneous and the large gene predisposes it to a high rate of mutation
how does dystrophin vary with X linked muscle dystrophy and duchenne
with duchenne, the dystrophy is due to the deletion of the dystrophin gene
with x linked, the dystrophy is due to defects in the dystrophin gene
how does duchenne muscular dystrophy present?
presents as proximal muscle weakness at 1 year of age, which progresses to involve the distal muscles
What is the characteristic finding of Duchenne muscular dystrophy
calf pseudohypertrophy. will have an elevated CK
what is the cause of Becker Muscular dystrophy
mutated dystrophin that results in more mild disease
what is the cause of myasthenia gravis
autoantibodies against the post synaptic ACETYLCHOLINE RECEPTOR and the neuromuscular junction
what are the clinical feature of myasthenia gravis?
- muscle weakness that WORSENS with use and improves with rest, classically involving eyes, leading to ptosis and diplopia.
- symptoms improve with anticholinesterase agents
myasthenia gravis is associated with what?
thymic hyperplasia and thymoma. thymectomy improves symptoms
what is the cause of Lambert-Eaton Syndrome?
antibodies against the presynaptic calcium channels of the neuromuscular junction. arises as a paraneoplastic syndrome, most commonly due to small cell carcinoma of the lung. leads to IMPAIRED ACETYCHOLINE RELEASE, as firing of the presynaptic calicium channels is required for release
what are the clinical features of Lambert-Eaton Syndrome?
- proximal muscle weakness that IMPROVES WITH USE, EYES ARE USUALLY SPARED
- Anticholinesterase agents do not improve symptoms
- resolves with resection of cancer
what are the clinical differences between myasthenia gravis and lambert-eaton syndrome?
- both involve muscle weakness, but myasthenia gravis is WORSE with use. Lambert- Eaton is improved with use
- anticholinesterase agents improve Myasthenia Gravis, but have no impact on Lambert- Eaton
how does the involvement of the neuromuscular junction with Myasthenia Gravis and Lambert-Eaton syndrome differ?
myasthenia gravis: antibodies againts the POST SYNAPTIC acetylcholine receptor. ACH is in cleft, which is why antichoinesterase agents work
Lambert-Eaton: antibodies against the PRE SYNAPTIC calcium channels, which prevents release of ACH into the synaptic cleft. this is why anticholinesterase agents do not work.
