Musculoskeletal - Pathoma Flashcards
The driving etiology for achondroplasia is an ________expression of ________.
The driving etiology for achondroplasia is an overexpression of FGFR3.
True/False.
Most cases of achrondoplasia are sporadic and related to advanced paternal age.
True.
Identify which (if any) of the following are affected by achrondroplasia:
Mental function
Lifespan
Fertility
No effects on mental function, lifespan, or fertility
What are the three common features of osteogenesis imperfecta?
Multiple fractures (absent bruising can distinguish from child abuse)
Blue sclera (increased exposure of choroidal veins)
Hearing loss (easy fracture of middle ear bones)
Osteo_________ is a disorder of bone mineralization.
Osteo_________ is a disorder of bone mass.
Osteo_________ is a disorder of bone resorption.
Osteomalacia is a disorder of bone mineralization.
Osteoporosis is a disorder of bone mass.
Osteopetrosis is a disorder of bone resorption.
Osteopetrosis is a(n) _____________ (sporadic/inherited) defect of bone _____________ (formation/mineralization/resorption).
Osteopetrosis is an inherited defect of bone resorption.
What is the main result of the lack of bone resorption seen in osteopetrosis?
Abnormally thick, heavy bone which fractures easily
Osteopetrosis occurs due to poor ____________ function.
Osteopetrosis occurs due to poor osteoclast function.
Osteopetrosis often occurs due to a mutation in ________________, leading to a loss of the ________ microenvironment needed for bone resorption.
Osteopetrosis often occurs due to a mutation in carbonic anhydrase II, leading to a loss of the acidic microenvironment needed for bone resorption.
Name some of the major presenting S/Sy of osteopetrosis:
F______________
A______________, T______________, L______________
V______________ and H______________ impairment
H______________
R________________________
Name some of the major presenting S/Sy of osteopetrosis:
Fractures**
Anemia, **Thrombocytopenia, Leukocytopenia**
Visual** and Hearing** impairment
Hydrocephalus
Renal tubular acidosis(type 2)
Why is osteopetrosis associated with hydrocephalus?
Narrowing of the foramen magnum
Why is osteopetrosis associated with type 2 RTA?
Lack of carbonic anhydrase
(leading to decreased tubular HCO3- reabsorption)
What is the treatment for osteopetrosis?
Bone marrow transplant
(osteoclasts derive from monocytes)
A defect in mineralization of osteoid in children is called ___________.
A defect in mineralization of osteoid in adults is called ___________.
A defect in mineralization of osteoid in children is called Rickets.
A defect in mineralization of osteoid in adults is called osteomalacia.
Osteoblasts normally produce ________, which is then mineralized with calcium and phosphate to form bone.
Osteoblasts normally produce osteoid, which is then mineralized with calcium and phosphate to form bone.
Osteomalacia/Rickets results due to a lack of ________.
Osteomalacia/Rickets results due to a lack of vitamin D.
Vitamin D deficiency can lead to osteo_________.
Vitamin D deficiency can lead to osteomalacia.
Rickets most commonly arises in children of what age?
< 1 year
What are some of the S/Sy of Rickets?
Pigeon-breast deformity (inward bend of the ribs + sternal protrusion)
Frontal bossing (osteoid deposition in skull)
Rachitic rosary (osteoid deposition at costochondral junction)
Genu varum (in ambulating children)
What are some of the clinical S/Sy of osteomalacia in relation to the bones?
Weak bones;
pathologic fractures
What are some of the laboratory S/Sy of osteomalacia?
Decreased: calcium, phosphate
increased PTH, alkaline phosphate
Peak bone mass is achieved at ____ years of age and is based on genetics (___________ receptor variants), diet, and exercise.
Peak bone mass is achieved at 30 years of age and is based on genetics (vitamin D receptor variants), diet, and exercise.
After peaking at 30 years of age, ____% is typically lost each year.
After peaking at 30 years of age, 1 % is typically lost each year.
How can bone density be measured?
DEXA scanning
What are some of the laboratory S/Sy of osteoporosis?
Normal: Ca2+, PO43-, PTH, ALP
How can osteoporosis and osteomalacia be easily distinguished, despite similar presentation of weak bones and pathologic fractures?
Lab values
(normal in osteoporosis; elevated PTH and ALP + decreased Ca2+ and PO43- in osteomalacia)
True/False.
Osteoporosis treatment includes exercise, vitamin D, calcium, bisphosphonates, estrogen replacement, and glucocorticoids.
False.
Osteoporosis treatment includes exercise, vitamin D, calcium, and bisphosphonates.
Estrogen replacement is not currently recommend** and glucocorticoids **are contraindicated (as they worsen osteoporosis).
How do bisphosphonates treat osteoporosis?
By inducing osteoclast apoptosis
(by binding hydroxyapatite at the pyrophosphate-binding site)
Among the following, identify which produce an elevation in ALP:
Achondroplasia
Osteoporosis
Osteomalacia
Osteopetrosis
Osteomyelitis
Paget disease of the bone
Osteogenesis imperfecta
Osteomalacia (+ elevated PTH)
Paget disease of the bone
What is the underlying cause of Paget disease of the bone?
Imbalance between osteoblast and osteoclast function
(though we don’t know why - may be a viral cause)
What is the most common cause of an isolated elevation of ALP in patients over 40?
Paget disease of the bone
True/False.
Paget disease of the bone is a systemic process involving multiple bones (sometimes widespread skeletal involvement).
False.
Paget disease of the bone is a localized process involving one or more bones.
How is Paget disease of the bone treated?
Calcitonin
+
Bisphosphonates
What are the three distinct phases of Paget disease of the bone?
(1) O____________
(2) M________________________
(3) O____________
What are the three distinct phases of Paget disease of the bone?
(1) Osteoclastic**
(2) M_ixed osteoclastic-osteoblastic_
(3) Osteoblastic**
The end result of Paget disease of the bone is _______, _______ bone that ________ easily.
The end result of Paget disease of the bone is thick, sclerotic bone that fractures easily.
Name some of the clinical features of Paget disease of the bone:
Bone ____________
Increasing H____________
H____________ loss
L____________
Name some of the clinical features of Paget disease of the bone:
Bone pain
Increasing Hat size
Hearing loss
L_ion-like facies_
What is the lab finding of Paget disease of the bone?
Isolated ALP elevation
What does bone biopsy reveal in Paget disease of bone?
Mosaic pattern of lamellar bone
Name two major complications of Paget disease of the bone.
High-output cardiac failure (due to formation of AV shunts in bone)
Osteosarcoma
Osteomyelitis most commonly occurs in _________ (age group), is _________ (general etiology), and results due to _________ spread.
Osteomyelitis most commonly occurs in children, is bacterial, and results due to hematogenous spread.
Transient bacteremia (often in _________) often seeds the ______physis.
Open-wound bacteremia (often in _________) often seeds the ______physis.
Transient bacteremia (often in children) often seeds the metaphysis.
Open-wound bacteremia (often in adults) often seeds the epiphysis.
Name the etiology associated with osteomyelitis in each of the following scenarios:
Most common cause (90% of cases)
Sexually active young adults
Sickle cell disease
Diabetes
IVDUs
Cat or dog bites
Involving the vertebral column
- E. coli*
- N. gonorrhoeae*
- Salmonella spp.*
- Pseudomonas spp.*
- Pseudomonas spp.*
- Pasturella multocida*
- Mycobacterium tuberculosis*
How is the diagnosis of osteomyelitis made?
Blood culture
What are the clinical features of osteomyelitis?
Bone pain + systemic signs of infection (fever/leukocytosis)
lytic focus surrounded by sclerotic bone (abcess/sequestrum surrounded by involucrum)
Avascular bone necrosis is typically ischemic necrosis of what?
Bone and bone marrow
What are the most common causes of avascular necrosis of bone?
Trauma and/or fracture
Besides trauma/fracture, name two other causes of avascular necrosis.
Sickle cell disease
Caisson disease
Where do osteomas most commonly arise?
The facial bones
(most commonly associated with Gardner syndrome)
What are osteoid osteomas?
Benign osteoblast tumors surrounded by a rim of reactive bone
What demographic is more commonly affected by osteoid osteomas?
Males < 25 years of age
Where do osteoid osteomas typically arise?
Cortex of long bones
Osteoid osteomas present as bone _______ that resolves with _______.
Osteoid osteomas present as bone pain that resolves with aspirin.
How do osteoid osteomas present on imaging?
Bony mass (< 2 cm) with a lucent core (osteoid)
What tumor is similar to an osteoid osteoma but is larger (>2 cm), arises in the vertebrae (as opposed to the long bones), and does not respond to aspirin?
Osteoblastomas
What is the most common benign tumor of bone?
Osteochondroma
Osteochondromas are tumors of ________ with an overlying ________ cap.
Osteochondromas are tumors of bone with an overlying cartilage cap.
Osteochondromas arise from ________ projections of the _____physis and are continuous with the ______________.
Osteochondromas arise from lateral projections of the metaphysis and are continuous with the marrow space.
Osteosarcomas are malignant proliferations of ___________.
Osteosarcomas are malignant proliferations of osteoblasts.
Osteosarcomas typically arise in what demographic?
Teenagers
(sometimes the elderly)
Osteosarcomas typically arise in what area(s) of the skeleton?
The knee metaphyses
(distal femur or proximal tibia)
Name some risk factors for osteosarcoma development.
Familial RB
Paget disease of the bone
Radiation exposure
How do osteosarcomas typically present?
Pathologic fracture
or
bone pain with swelling
What does imaging reveal in an osteosarcoma?
Destructive mass + ‘sunburst’ appearance + Codman triangle (lifting of the periosteum)
Biospy of an osteosarcoma would reveal what?
Osteoid-producing pleomorphic cells
Giant cell tumors are comprised of what cell(s)?
Multinucleated giant cells
+
stromal cells
Giant cell tumors are __________ (benign/malignant) tumors of ________ (organ).
Giant cell tumors are malignant tumors of bone.
True/False.
Giant cell tumors are locally aggressive
True.
Giant cell tumors typically arise in what demographic?
Young adults
How do giant cell tumors appear on X-ray?
Soap-bubble appearance
Where do giant cell tumors arise?
The epiphysis of long bones
(especially around the knee - distal femur or proximal tibia)
Which bone malignancies often arise in the metaphyses of the distal femur or proximal tibia around the knee?
Which bone malignancies often arise in the epiphyses of the distal femur or proximal tibia around the knee?
Osteosarcomas
Giant cell tumors
Ewing sarcoma are ____________ (benign/malignant) proliferations of _________-differentiated _______________ cells.
Ewing sarcoma are malignant proliferations of poorly-differentiated neuroectodermal cells.
How do Ewing sarcomas appear on X-ray?
‘Onion-skin’ appearance
True/False.
Ewing sarcomas typically arise in the diaphysis of long bones in male children.
True.
Ewing sarcomas are associated with a _______ translocation and can be confused with _______ or chronic osteomyelitis due to the presence of small, round, blue cells (which look similar to lymphocytes).
Ewing sarcomas are associated with a 11:22 translocation and can be confused with lymphoma or chronic osteomyelitis due to the presence of small, round, blue cells (which look similar to lymphocytes).
Ewing sarcomas often present with ____________ and ________ (are/are not) responsive to chemotherapy.
Ewing sarcomas often present with metastases and are responsive to chemotherapy.
Where do chondromas most commonly arise?
The medulla of small bones in the hands or feet
______________ are malignant cartilage-producing tumors that often arise in the medulla of the pelvis or central skeleton.
Chondrosarcomas are malignant cartilage-producing tumors that often arise in the medulla of the pelvis or central skeleton.
Chondrosarcomas are malignant cartilage-producing tumors that often arise in the _________ of the _________ or central skeleton.
Chondrosarcomas are malignant cartilage-producing tumors that often arise in the medulla of the pelvis or central skeleton.
What is the most common type of bone tumor?
Metastases
How do metastases to the bone typically present?
As osteolytic lesions
(prostatic metastases to bone classically appear as osteoblastic lesions)
The synovium lining joint capsules secretes a fluid rich in _____________ acid (in order to lubricate the joint and facilitate smooth motion).
The synovium lining joint capsules secretes a fluid rich in hyaluronic acid (in order to lubricate the joint and facilitate smooth motion).
What are the major risk factors for osteoarthritis?
Age (> 60);
obesity, trauma
Osteoarthritis is characterized by joint stiffness in the morning that ________ throughout the day.
Osteoarthritis is characterized by joint stiffness in the morning that worsens throughout the day.
In osteoarthritis, there is a burnishing/polishing of the subchondral bone. This is called ____________.
In osteoarthritis, there is a burnishing/polishing of the subchondral bone. This is called eburnation.
Osteoarthritis osteophytes are classically found in which joints?
The PIP (Bouchard nodes) and DIP (Heberden nodes)
True/False.
Rhematoid arthritis is strongly associated with HLA-B27.
False.
Rhematoid arthritis is strongly associated with HLA-DR4.
True/False.
Rheumatoid arthritis is associated with intra-articular pannus formation.
True.
Note: a pannus is a proliferation of granulation tissue.
What term refers to fusion of a joint?
Ankylosis
Rheumatoid arthritis is characterized by joint pain in the morning that __________ throughout the day.
Rheumatoid arthritis is characterized by joint pain in the morning that improves throughout the day.
Which joint of the hands is typically affected in osteoarthritis but spared in rheumatoid arthritis?
The DIP joints
Patients with rheumatoid arthritis will sometimes show ________ drift in their fingers and ________ deviation in their wrists.
Patients with rheumatoid arthritis will sometimes show ulnar drift in their fingers and radial deviation in their wrists.
List some of the systemic S/Sy associated with rheumatoid arthritis.
Fever
Malaise
Myalgias
Weight loss
Describe the histology of the rheumatoid nodules seen in rheumatoid arthritis.
Central zones of necrosis surrounded by epithelioid histiocytes
Where do rheumatoid nodules arise in patients with rheumatoid arthritis?
The skin and visceral organs
A patient with rheumatoid arthritis presents with a mass behind their knee. What is the likely diagnosis?
A Baker cyst
True/False.
Rheumatoid arthritis is associated with vasculitis (possibly of multiple organs), pleural effusions, lymphadenopathy, and interstitial lung fibrosis.
True.
Rheumatoid factor is an Ig____ against the ____ portion of Ig____.
Rheumatoid factor is an IgM against the Fc portion of IgG.
True/False.
Rheumatoid arthritis is associated with polycythemia and primary amyloidosis.
False.
Rheumatoid arthritis is associated with anemia and secondary amyloidosis.
True/False.
Synovial fluid in affected joints of patients with rheumatoid arthritis will show a high lymphocyte count and high glucose count.
False.
Synovial fluid in affected joints of patients with rheumatoid arthritis will show a high neutrophil count and high protein count.
What makes the seronegative spondyloarthropathies serum negative?
They are rheumatoid factor negative
The seronegative spondyloarthropathies are associated with HLA-_____ and typically involve the _________ skeleton.
The seronegative spondyloarthropathies are associated with HLA-B27 and typically involve the axial skeleton.
Name the four major seronegative spondyloarthropathies.
Psoriatic arthritis
Ankylosing spondylitis
Irritable bowel syndrome
Reactive arthritis
True/False.
Psoriatic arthritis is seen in up to 90% of cases of psoriasis.
False.
Psoriatic arthritis is seen in ~10% of cases of psoriasis.
Psoriatic arthritis often involves the _____ skeleton and the ______ joints of the hands and feet (leading to ‘_________’ fingers or toes).
Psoriatic arthritis often involves the axial skeleton and the DIP joints of the hands and feet (leading to ‘sausage’ fingers or toes).
Name two extra-articular manifestations of ankylosing spondylitis.
Uveitis
Aortitis (leading to aortic regurgitation)
What are the three major components of reactive arthritis?
Conjunctivitis
Urethritis
Arthritis
Reactive arthritis is most commonly seen in ________ ________ (demographic) weeks after a GI or chlamydial infection.
Reactive arthritis is most commonly seen in young males weeks after a GI or chlamydial infection.
What is the most common etiology of infectious arthritis?
And the second most common?
N. gonorrhoeae (often in young adults)
E. coli (typically older children and adults)
What are some of the clinical and/or laboratory findings in a patient with infectious arthritis?
Single joint affected (often the knee);
decreased range of motion in that joint;
fever, leukocytosis;
elevated ESR
In gout, ________ crystals deposit in tissues.
In pseudogout, ________ crystals deposit in tissues.
In gout, monosodium urate crystals deposit in tissues.
In pseudogout, calcium pyrophosphate dihydrate crystals deposit in tissues.
In gout, synovial fluid shows ________-shaped crystals.
In pseudogout, synovial fluid shows ________-shaped crystals.
In gout, synovial fluid shows needle-shaped crystals.
In pseudogout, synovial fluid shows rhomboid-shaped crystals.
In gout, synovial fluid shows needle-shaped crystals that show _______ _______ under polarized light.
In pseudogout, synovial fluid shows rhomboid-shaped crystals that show _______ _______ _______ under polarized light.
In gout, synovial fluid shows needle-shaped crystals that show negative birefringence under polarized light.
In pseudogout, synovial fluid shows rhomboid-shaped crystals that show weakly positive refringence under polarized light.
Which is the more common cause of gout, primary hyperuricemia or secondary hyperuricemia?
Primary hyperuricemia
(etiology often unknown)
Name a few causes of secondary hyperuricemia associated with gout development.
Leukemia / myeloproliferative disorders (high cell turnover)
Lesch-Nyhan syndrome (HGPRT deficiency)
Renal insufficiency (decreased uric acid excretion)
What are gout tophi?
White, chalky aggregates of uric acid crystals with fibrosis and giant cell reaction in the soft tissue and joints
What term refers to acute gout presenting as an exquisitely painful arthritis of the great toe?
Podagra
True/False.
Renal insufficiency can lead to hyperuricemia and gout. Hyperuricemia can then precipitate urate nephropathy and renal failure.
True.
What do we know about the inciting etiology of dermatomyositis?
Typically idiopathic;
also associated with some carcinomas (e.g. gastric carcinomas)
What are some of the characteristic dematologic findings of dermatomyositis?
Heliotrope and malar rashes
+
Red papules on elbows, knuckles, and knees
What are the laboratory findings of dermatomyositis?
Elevated creatine kinase
Positive anti-nuclear and anti-Jo-1 antibodies
What are the muscle biopsy findings in patients with dermatomyositis?
Perimysial inflammation (CD4+ T cells)
+
perifascicular atrophy
True/False.
Polymyositis is very similar to dermatomyositis, just without the dematologic clinical findings.
True.
Polymyositis is characterized by muscle _______mysial infiltration with CD__+ T cells.
Dermatomyositis is characterized by muscle _______mysial infiltration with CD__+ T cells.
Polymyositis is characterized by muscle endomysial infiltration with CD8+ T cells.
Dermatomyositis is characterized by muscle perimysial infiltration with CD4+ T cells.
Duchenne muscular dystrophy is caused by a(n) __________ in the dystrophin gene.
Becker muscular dystrophy is caused by a(n) __________ in the dystrophin gene.
Duchenne muscular dystrophy is caused by a deletion in the dystrophin gene.
Becker muscular dystrophy is caused by an in-frame mutation in the dystrophin gene.
True/False.
Duchenne muscular dystrophy typically only involves the skeletal muscle.
False.
The myocardium is commonly involved.
Duchenne muscular dystrophy commonly results in death due to what complications?
Cardiac or respiratory failure
Which form of muscular dystrophy results due to a mutation in the dystrophin gene and leads to a later/milder course of disease than Duchenne muscular dystrophy?
Becker muscular dystrophy
Duchenne muscular dystrophy follows what inheritance pattern?
Becker muscular dystrophy follows what inheritance pattern?
X-linked
X-linked
Identify which of the following (or both) classically involves the eyes:
Myasthenia gravis
Lambert-Eaton syndrome
Myasthenia gravis
Identify in which of the following (or both) the muscle weakness associated with the disease should improve with muscle use:
Myasthenia gravis
Lambert-Eaton syndrome
Lambert-Eaton syndrome
Identify which of the following (or both) can be treated with acetylcholinesterase agents:
Myasthenia gravis
Lambert-Eaton syndrome
Myasthenia gravis
(may also be treated with thymectomy if associated with thymoma)
How is Lambert-Eaton syndrome treated?
Resection of the malignancy
(typically small cell carcinoma of the lung)
Lambert-Eaton syndrome is associated with _________ muscle weakness.
Lambert-Eaton syndrome is associated with proximal muscle weakness.
True/False.
Myasthenia gravis is equally common in men and women.
False.
Myasthenia gravis is more common in women.
What is the most common malignancy of soft tissue in adults?
(Which cell type is indicated?)
Liposarcoma
(Lipoblasts are the characteristic cells.)
What is the most common malignancy of soft tissue in children?
(Which cell type is indicated?)
Rhabdomyosarcoma
(Rhabdomyloblasts are the characteristic cells.)
What are the common sites of rhabdomyosarcomas in children?
The head and neck;
the vagina
What is the most common benign soft tissue tumor in adults?
Lipomas
