Pathoma - Musculoskeletal Pathology Flashcards
1
Q
What is Achondroplasia?
A
Disorder of cartilage proliferation in the growth plate
2
Q
What causes achondroplasia?
A
activating sporadic mutation in FGFR3 –> turning on receptor inhibits the growth of the cartilage
3
Q
inheritance of achondroplasia
A
- autosomal dominant
- related to increase paternal age
4
Q
clinical features of achondroplasia
A
- short extremities with normal sized head and chest
- mental function, life span and fertility are not affected
5
Q
Why does achondroplasia only affect the short extremities?
A
- two ways of bone formation: intramembranous from CT forms bones of skull, chest and flat bones of wrists. Endochondral forms from cartilage matrix that mineralizes and forms bone = growth of long bone
6
Q
what is osteogenesis imperfecta?
A
congenital defect of imperfect formation of bone
7
Q
inheritance of osteogenesis imperfecta
A
autosomal dominant
8
Q
clinical features of osteogenesis imperfecta
A
- weak bone –> multiple fractures
- multiple fractures
- blue sclera
- hearing loss
9
Q
cause of osteogenesis imperfecta
A
defect in formation of type 1 collagen synthesis
10
Q
why do patients with osteogenesis imperfect have hearing loss and blue sclera?
A
- hearing loss = small bones in ear lacking type 1 collagen
- blue sclera = sclera has type 1 collagen. loss of that exposes choroid veins
11
Q
what is osteopetrosis?
A
inherited defect of bone resorption
12
Q
cause of osteopetrosis
A
- due to poor osteoclast fxn.
- multiple genetic variants
- E.g. carbonic anhydrase 2 mutation = lack of acidic environment needed to remove calcium in order to resorb bone.
- CA joins water and CO2 to form bicarbonate acid. This splits into acid and bicarb.
13
Q
clinical features of osteopetrosis?
A
thick, heavy bone that fractures easily = no balance between osteoblasts and osteoclasts
- anemia, thrombocytopenia, leukopenia with EMH
- vision and hearing impairment
- hydrocephalus
- renal tubular acidosis
14
Q
xray of osteopetrosis
A
see a completely thickened bone = white instead of having a middle dark space where the medulla would be seen
15
Q
any do you get pancytopenia with osteopetrosis
A
myelophthisic process = thickening of the bone which replaces out medullary space which knocks out hematopoiesis with estramedullary hematopoiesis in the spleen and the liver
16
Q
why do patients with osteopetrosis get hydrocephalus, vision and hearing impairment?
A
- hydrocephalus = thickening of the bone at the foramen magnum
- thickening of the skull compresses cranial nerves as they exit the skull
17
Q
why do patients get renal tubular acidosis?
A
lack of CA = no formation and split of bicarb acid. You do not excrete acid and you do not get a net gain of bicarb sent back into the blood to balance acid. So people get acidemia as a result of a proximal tubular defect of not having CA.
18
Q
Treatment of osteopetrosis?
A
bone marrow transplant –> give back ability to make normal monocytes from hematopoesis = make normal osteoclasts.
19
Q
Rickets and osteomalacia
A
Defective mineralization of osteoid
- due to low levels of vitamin D
- NB: osteoblasts lay down osteoid which is then mineralized by calcium and phosphate. Because there is not vitamin D which works of the kidney, intestine and bone to maintain the calcium and phosphate in the blood.
20
Q
how does a vitamin D deficiency develop?
A
decreased sun exposure, poor diet, malabsorption (fat soluble), liver failure and renal failure (needed for activating vitamin D)
21
Q
clinical features of rickets
A
- in children - usually by age 1
- pigeon breast deformity, frontal bossing from osteoid deposition on the skull, rachitic rosary from osteoid deposition at the costo-chondro junction which feels like beeds (rosary) and bowing of legs as they grow from the growth plate
- all caused by abnormal mineralization and depositon of osteoid
22
Q
clinical features of osteomalacia
A
- in adults
- results in weak bone with increased risk of fracture
- low serum calcium, low serum phosphate, high PTH and high alkaline phosphate
23
Q
pathogenesis of weak bone in osteomalacia
A
weak bone = osteoclasts remove bone, the blasts lay down osteoid but it cannot be mineralized. Leads to increase risk of fracture in weight bearing areas like the vertebral bodies or the hip
24
Q
pathogenesis of abnormal lab values in osteomalacia
A
- calcium and phos are low because of lack of vit. D
- PTH is up because there is low calcium
- alkaline phosphate = active when osteoblasts need to lay down bone because it created an alkaline environment so the calcium can be incorporated
25
what is osteoporosis
- loss/reduction of trabeculae bone mass
| - resulting in porous bone with risk of fracture
26
How is the risk of osteoporosis related to bone mass?
risk of osteoporosis is based on peak bone mass achieved by the age of 30 (early adulthood) and the rate of bone loss thereafter.
27
What are the determinants of peak bone mass?
1) genetic e.g. variants of vitamin D receptor 2) diet 3) exercise
28
What determines the loss of bone mass?
Bone mass is lost after age 30 at slightly less than 1% per year. Bone mass is lost more quickly with lack of weight bearing exercise (eg space travel), poor diet or decreased estrogen (postmenopausal).
29
What are the most common forms of osteoporosis?
senile and postmenopausal
30
What are the clinical features of osteoporosis?
1. bone pain and fractures in weight bearing areas like vertebra, hip and distal radius. See loss of height and kyphosis.
2. bone density loss (studied by DEXA scan)
3. serum calcium, phosphate, PTH and alkaline phosphate are normal
31
How do labs distinguish between osteoporosis and osteomalacia?
Calcium, phosphate, alkaline phosphate and PTH are normal in osteoporosis. Calcium and phosphate are low in osteomalacia but PTH and alkaline phosphate are high.
32
What is the treatment for osteoporosis?
exercise, vitamin D, calcium --> limit bone loss
bisphophonates --> induce apoptosis of osteoclasts
estrogen replacement therapy is debated and not recommended.
Glucocorticoids are contraindicated.
33
What is paget disease of the bone?
imbalance between osteoclast and osteoblast function
| - usually seen in late adulthood (greater than 60 years)
34
what is the etiology of paget disease?
unknown, possibly viral
35
what is the pattern of involvement of paget disease?
localized process involving one or more bones; does not involve the entire skeleton
36
What are the stages of paget disease?
1. osteoclastic 2. mixed osteoblastic and osteoclastic 3. osteoblastic.
End result if a thick, sclerotic bone that fractures easily
37
Describe the bone biopsy of a patient with paget disease?
mosaic pattern of lamellar bone
38
What are the clinical features of paget disease of the bone?
1. bone pain due to microfractures
2. hearing loss due to impingement of cranial nerves
3. increasing size of hat --> skull is commonly involved
4. lion like faces --> involved craniofacial bones
5. isolated elevation of alkaline phosphate --> paget disease is the most common cause of isolated elevation of alkaline phosphate in adults over age 40.
39
What is the treatment for paget disease?
1. calcitonin - inhibits osteoclast function
| 2. bisphophonates - induces apoptosis of osteoclasts
40
What are the potential complication of paget disease?
1. high output cardiac failure - due to formation of AV shunts in bone
2. osteosarcoma
41
What is osteomyelitis?
infection of the marrow and bone
| usually occurs in children
42
What are the most common etiology of osteomyelitis?
- most commonly bacterial; arises via hematogenous spread
= transient bacteremia (children) seeds metaphysis of long bones in the region of most rapid growth and vascularity. Involves, in order of frequency, the lower end of the femur, the upper end of the tibia and humerus, and the radius.
= open-wound bacteremia (adults) seeds epiphysis; e.g. vertebrae which are generally highly vascular. Hematogenous spread can occur by way of the nutrient branches of the spinal artery or by flow from the pelvic veins to the lumbar veins and, under conditions of increased abdominal pressure, retrograde flow through the paravertebral venous plexus of Batson
43
What are the common causes of osteomyelitis?
- Staph. aureus - most common cause (90%)
- N. gonorrhoeae - sexually active young adults
- salmonella - sickle cell disease
- pseudomonas - diabetics or IV drugs abusers
- pasteurella - associated with cat or dog bite/scratches
- mycobacterium tuberculosis - usually involves vertebrae (pott disease)
44
what are the clinical features of osteomyelitis?
1. bone pain with systemic signs of infection (e.g. fevere and leukocytosis)
2. lytic focus (abscess) surrounded by sclerosis of bone on x-ray; lytic focus is called sequestrum, and sclerosis is called involucrum
45
How is diagnosis of osteomyelitis made?
by blood culture
46
what is avascular (aseptic) necrosis?
ischemic necrosis of bone and marrow
47
what are the causes of avascular necrosis?
trauma; fracture (most common); steroids; sickle cell anemia and caisson disease (decompression sickness)
48
what are the major complications of avascular necrosis?
osteoarthritis and fracture
49
Give an overview list of bone tumors?
osteoma; osteoid osteoma; osteochondroma; osteosarcoma; giant cell tumor; ewing sarcoma; chondroma; chondrosarcoma; metastatic tumors
50
What is osteoma?
a benign bone tumor that most commonly arises in the facial bones.
associated with gardner syndrome --> subset of familial adenomatous polyposis, autosomal dominant, polyps in colon and tumors outside - skull, thyroid, fibroma and epidermoid.
51
What is osteoid osteoma?
- benign tumor of osteoblasts (that produce osteoid) surrounded by a rim of reactive bone
- occurs in young adults <25 years, more common in males
52
How does osteoid osteoma present?
- arises in cortex of long bones e.g. femur
| - bone pain that resolves with aspirin
53
What does imaging of osteoid osteoma show?
imaging shows a bony mass less that 2cm with a radioluscent core (osteoid)
54
How does osteoblastoma compare to osteoid osteoma?
osteoblastoma is similar to osteoid sarcoma but is larger (>2cm), arises in vertebrae, and presents as bone pain that does not respond with aspirin
55
What is osteochondroma?
- this is a tumor of bone with an overlying cartilage cap
| - this is the most common benign tumor of bone
56
How does osteochondroma arise?
arises from a lateral projection of the growth plate (metaphysis), bone is continuous with the marrow space
- the overlying cartilage can transform (rarely) to chondrosarcoma
57
What is osteosarcoma?
- this is malignant proliferation of osteoblasts
| - arises in the metaphysis of long bones, usually the distal femur or proximal tibia (region of the knee)
58
How does osteosarcoma present?
- presents as pathologic fracture or bone pain with swelling
59
What is the peak incidence and risk factor for osteosarcoma?
- peak incidence in teenagers; less commonly seen in the elderly
- risk factors = familial retinoblastoma, paget disease and radiation exposure
60
what does imaging of osteosarcoma reveal?
- imaging reveals a destructive mass with a sunburst appearance and lifting of the periosteum (codman triangle)
61
what do you see on a biopsy of osteosarcoma
pleomorphic cells that produce osteoid
62
What are giant cell tumors?
tumors comprised of multinucleated giant cells and stromal cells
- locally aggressive tumor, may recur
- occur in young adults
- arises in the epiphysis of long bones, usually distal femur or proximal tibia (knee)
63
what do you see on imaging of giant cell tumors?
soap-bubble appearance on x-ray
64
what is ewing sarcoma?
malignant proliferation of poorly-differentiated cells derived from neuroectoderm
- arises in diaphysis of long bones
- 11:22 translocation is characteristic
- can be confused with lymphoma or chronic osteomyelitis
65
what do you see on imaging and biopsy of ewing sarcoma?
```
x-ray = onion-skin appearance
biopsy = small round blue cells that resemble lymphocytes
```
66
Presentation and treatment of ewing sarcoma
often presents with metastasis; responsive to chemotherapy
67
what is chrondroma?
benign tumor of cartilage
| - usually arises in the medulla of small bones of the hands and feet
68
what is chondrosarcoma?
malignant cartilage-forming tumor
| - arises in medulla of the pelvis or central skelton
69
how do metastatic bone tumors present?
more common than primary tumors
- usually result in osteolytic (punched-out) lesions
- prostatic carcinoma classically produces osteoblastic lesions
70
What are the two types of joints present?
- solid joints = tightly connected to provide structural strength (cranial sutures)
- synovial joints = have joint space to allow for motion
- Articular surface of adjoining bones is made of hyaline cartilage (type 2 collagen) that is surrounded by a joint capsule
- synovium lining the joint capsule secretes fluid rich in hyaluronic acid to lubricate the joint and facilitate smooth motion
71
What are the classic presentation of osteoarthritis?
- joint stiffness in the morning that worsens during the day
72
What are the pathologic features of osteoarthritis?
- pathologic features:
1) disruption of the cartilage that lines the articular surface; fragments of cartilage floating in the joint space are called "joint mice"
2) eburnation of the subchondral bone
3) osteophyte formation (reactive bony outgrowths); classically arises in the DIP (heberden nodes) and PIP (bouchard nodes) joints of the finger
73
What are the major risk factors of osteoarthritis?
age (common after 60 years); obesity; trauma
74
what joints are affected by osteoarthritis?
- affects a limited number of joints (oligoarticular); hips, lower lumbar spine, knees, and the distal interphalangeal joints (DIP) and proximal interphalangeal joints (PIP) of fingers are common sites
75
what is osteoarthritis?
- progressive degeneration of articular cartilage; most common type of arthritis
- most often due to wear and tear
76
what is rheumatoid arthritis?
- chronic, systemic autoimmune disease
- classically arises in women of late child-bearing age
- associated with HLA-DR4
77
what is the hallmark of rheumatoid arthritis?
- involvement of joints
- synovitis leading to formation of a pannus (inflamed granulation tissue)
- leads to destruction of cartilage and ankylosis (fusion) of the joint
78
What are the clinical features of rheumatoid arthritis?
- arthritis with morning stiffness that improves with activity
- symmetric involvement of PIP joints of the fingers (swan-neck deformity), wrists (radial deviation), elbows, ankles, knees
- DIP is usually spared (unlike OA)
79
How does rheumatoid arthritis appear on x-ray
- joint space narrowing, loss of cartilage, osteopenia
80
What other clinical features show up with rheumatoid arthritis?
- fever, malaise, weight loss, myalgias
- rheumatoid nodules - central zone of necrosis surrounded by epitheloid histiocytes; arise in skin and visceral organs
- vasculitis - multiple organs may be involved
- baker cyst - swelling of bursa behind the knee
- pleural effusions, lymphadenopathy, and interstitial fibrosis
81
what laboratory findings are seen in rheumatoid arthritis?
- IgM autoantibody against Fc portion of IgG (rheumatoid arthritis); marker of tissue damage and disease activity
- neutrophils and high protein in synovial fluid
82
Complications of rheumatoid arthritis?
anemia of chronic disease and secondary amyloidosis
83
What are seronegative spondyloarthropathies?
These are a group of joint disorders characterized by:
- lack of rheumatoid arthritis
- Axial skeleton involvement
- HLA-B27 association
84
What are the three types of seronegative spondyloarthropathies?
Ankylosing spondyloarthritis
Reactive arthritis
Psoriatic arthritis
85
What are the features of ankylosing spondyloarthritis?
- involves sacroiliac joints and spine
- arises in young adults, most often male
- presents with low back pain; involvement of vertebral bodies eventually arises leading to fusion of the vertebrae (bamboo spine)
- extra-articular manifestations = uveitis, aortitis (leading to aortic regurge)
86
What are the features of reactive arthritis?
- type of seronegative spondylarthropathy
- characterized by
- arises in young adults (usually males) weeks after a GI or chlamydia trachomatis infection
87
What are the features of psoriatic arthritis
- type of seronegative arthropathu
- seen in 10% of cases of psoriasis
- involves the axial and peripheral joints; DIP joints of the hands and feet are most commonly affected, leading to sausage finger or toes
88
What are the features of infectious arthritis?
- arthritis due to infectious agent, usually bacterial
- causes include: N. gonorrheae = in young adults (most common cause); S. aureus = older children and adults; second most common cause
- classically involves a single joint, usually the knee
- presents as warm joint with limited range of motion; fever, increased white count and elevated ESR
89
What are the laboratory findings associated with gout?
- hyperuricemia
| - synovial fluid shows needle shaped crystals with negative birefringence under polarized light
90
what are the features of pseudogout?
- resembles gout clinically, but is due to deposition of calcium pyrophosphate dihydrate (CPPD)
- synovial fluid shows rhomboid-shaped crystals with weakly positive birefringence under polarized light
91
What is gout?
- deposition of monosodium urate (MSU) crystals in tissues, especially the joints
- there are multiple forms: primary, secondary, acute and chronic gout
92
What is the cause of gout?
due to hyperuricemia; related to overproduction or decreased excretion of uric acid - derived from purine metabolism and is excreted in the kidney
93
what are the features of primary gout?
most common form; etiology of hyperuricemia is uknown
94
Secondary gout is seen with...
Secondary gout is seen with:
- leukemia and myeloprolifertaive disorders - increased cell turnover leads to hyperuricemia
- lesch-nyahn syndrome - x-linked deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT); presents with mental retardation and self mutilation
- renal insufficiency - decreased renal excretion of uric acid
95
What are the features of acute gout?
presents as extremely painful arthritis of the great toe (podagra)
- MSU cyrstals deposit in the joint, triggering an acute inflammatory reaction
- alcohol or consumption of meat may precipitate arthritis
96
Chronic gout leads to...
Chronic gout leads to: development of tophi - white, chalky aggregates or uric acid crystals with fibrosis and giant cell reaction in the soft tissue and joints
- renal failure - urate crystals may deposit in kidney tubules (urate nephropathy)
97
The following laboratory findings are associated with which skeletal muscle disease?
- increased creatinine kinase
- positive ANA and anti-jo-1 antibody
- perimysial inflammation (CD4-T cells) with perifascicular atrophy on biopsy
dermatomyositis
98
what are the features of demratomyositis?
inflammatory disorder of the skin and skeletal muscle
| - unknown etiology; same cases are associated with carcinoma (e.g. gastric carcinoma)
99
The following clinical features are associated with which skeletal muscle disease?
- bilateral proximal muscle weakness; distal involvement can develop late in disease
- rash of the upper eyelids (heliotrope rash); malar rash
- red papules on the elbows, knuckles and knees (Gottron papules)
Dermatomyositis
100
The following clinical features are associated with which skeletal muscle disease?
- bilateral proximal muscle weakness; distal involvement can develop late in disease
- red papules on the elbows, knuckles and knees (Gottron papules)
Polymyositis
101
What are the features of polymyositis?
inflammation of skeletal muscle
- involves endomysial inflammation (CD 8 T-cells) with necrotic muscle fibers seen on biopsy
- endomysial means within connective tissue outlining each myocyte
102
What is the treatment of dermatomyositis?
corticosteroids
103
What is x-linked muscular dystrophy?
- degenerative disorder characterized by muscle wasting and replacement of skeletal muscle by adipose tissue
104
What is the cause of x-linked muscular dystrophy?
- due to defects of dystrophin gene
- dystrophin is important for anchoring the muscle cytoskeleton to the extracellular matrix
- mutations are often spontaneous; large gene size predisposes to high rate of mutation
- two types --> duchenne and becker
105
What are the features of duchenne muscular dystrophy?
- x-linked muscular dystrophy
- presents as proximal muscle weakness at 1 year of age; progresses to involve distal muscles
- calf pseudohypertrophy is a characteristic finding
- serum creatinine kinase is elevated
Death results from cardiac or respiratory failure; myocardium is commonly involved
106
What are the features of becker muscular dystrophy?
- x-linked muscular dystrophy
- due to mutated dystrophin
- clinically results in milder disease than duchenne
107
- muscle weakness that worsens with use and improves with rest; classically involves the eyes, leading to ptosis and diplopia
- symptoms improve with anticholinesterase agents
- associated with thymic hyperplasia or thymoma
- thymectomy improves symptoms
Myasthenia gravis
108
Disease caused by autoantibodies against postsynaptic acetylcholine receptor at the neuromuscular junction
- more commonly seen in women
- myasthenia gravis
109
Disease caused by autoantibodies against presynaptic calcium channels of the NMJ
lambert-eaton syndrome
110
What is the most common etiology of lambert-eaton syndrome?
arises as a paraneoplastic syndrome, most commonly due to small cell carcinoma of the lung
- leads to impaired acetylcholine release => firing of presynaptic calcium calcium channels is required for acetylcholine release
111
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 the cancer
112
Lipoma, liposarcoma, rhabdomyoma and rhabdomyosarcoma are all...
soft tissue tumors
113
most common benign tumor of adipose tissue in adults
lipoma
114
most common malignant tumor of adipose tissue in adults with a characteristic cell of precursor cells of adipocytes
liposarcoma
| - with a lipoblast is the cell
115
benign tumor of skeletal muscle which can be associated with tuberous sclerosis
cardiac rhabdomyoma
116
most common malignant tumor of skeletal muscle in children; a desmin positive cell is the characteristic cell type
- most common site is the head and neck; vagina is the most common site in young girls
rhabdomyosarcoma
| - rhabdomyoblast is the cell
117
triad of arthritis, urethritis and conjunctivitis =
reactive arthritis
