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Musculoskeletal Pathology Flashcards

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1
Q

Stages of pagets

A
  • Osteoclastic
  • Mixed osteoclastic-osteoblastic
  • Osteoblastic
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2
Q

_________ inflammation in dermatomyositis. ________ inflammation in polymyositis.

A

Perimysial; Endomysial

NOTE: perimysial inflammation is characterized by CD4 cells, while endomysial inflammation is characterized by CD8 cells

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3
Q

__________ is more specific than rheumatoid factor in early and fully established rheumatoid arthritis

A

Anti-CCP (anti-cyclic citrullinated peptide) antibodies

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4
Q

mechanism of osteopetrosis

A
  • Defective metaphyseal remodeling
  • Small neural foramina compress exiting nerves
  • Primary spongiosa fills medullary cavity
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5
Q

What are the types of Ehler Danlos Syndrome?

A

I/II- Classic

  • Skin and joint hypermobility, atrophic scars, easy bruising
  • Autosomal dominant
  • COL5A1, COL5A2

III- Hypermobility

  • Joint hypermobility, pain, and dislocation
  • Autosomal dominant

IV- Vascular

  • Thin skin, arterial or uterine rupture, bruising, small joint hyperextensibility
  • Autosomal dominant
  • COL3A1

VI- Kyphoscoliosis

  • Hypotonia, joint laxity, congenital scoliosis, ocular fragility
  • Autosomal recessive
  • Lysyl hydroxylase (PLOD1)
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6
Q

Why is hepatosplenomegaly seen in osteopetrosis?

A

Bone growth in the medullary cavity prevents hematopoiesis in the bone marrow. This leads to extramedullar hematopoiesis (i.e. in liver)

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7
Q

Laboratory findings of RA

A
  • Rheumatoid factor; marker of tissue damage and disease activity
  • Neutrophils and high protein in synovial fluid
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8
Q
  • Bilateral proximal muscle weakness
  • Rash of the upper eyelids
  • Red papules on the elbows, knuckles, and knees
A

Dermatomyositis

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9
Q

What is the affected molecule in achondroplasia?

A

FGFR3 (receptor)

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10
Q

Long, tapering fingers and toes called ____________.

A

Arachonodactyly

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11
Q

Another name for hyperparathyroidism

A

von Recklinghausen’s disease of bone

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12
Q

Tamoxifen

A
  • SERM
  • Binds to estrogen receptor
  • Antiestrogenic on mammary epithelium, hence its use in both the prevention and treatment of breast cancer
  • Proestrogenic on uterine epithelium
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13
Q

___________ are extra bone pieces that occur within a suture in the cranium.

A

Wormian bones

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14
Q

Symptoms of multiple myeloma

A
  • Elevated calcium
  • Renal failure
  • Anemia
  • Bone lesions
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15
Q
  • Low back pain
  • Bamboo spine
  • Aortic regurgitation
A

Ankylosing spondyloarthritis

  • Vertebrae bodies fuse
  • Uveitis and aortitis
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16
Q

Components of hyaline cartilage

A

Water

Type II collagen

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17
Q

Activation of _________ on osteoclast precursor stimulates tyrosine kinase cascade.

A

M-CSF (Monocyte colony stimulating factor)

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18
Q

cause of primary gout

A

Hyperuricemia related to overproduction or decreased excretion of uric acid (derived from purine metabolism).

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19
Q

Transcient bacteremia (children) seeds _________.

A

Metaphysis

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20
Q

Mechanism by which CA2 defect leads to osteopetrosis

A
  • CA2 required by osteoclasts and renal tubule cells to generate protons from carbon dioxide and water
  • Absent CA2 prevents osteoclasts from acidyfing resorption pit and solubilizing hydroxyapatite
  • Absent CA2 blocks acidification of urine by renal tubule cells causing renal tubular acidosis
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21
Q

osteoprotegerin

A

“Decoy” RANKL receptor that binds RANKL to prevent RANK-RANKL interaction, which leads to decreased osteoclast activity

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22
Q

Synoviocytes function

A

Produce proteins, hyaluronic acid (lubricant, nutrition for cartilage)

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23
Q

Causes of avascular necrosis

A
  • Trauma or fracture
  • Steroids
  • SCA
  • Caisson disease
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24
Q

Why does carbonic anhydrase type II defeciency result in osteopetrosis?

A

Acidic environment required for osteoclast activity is loss

NOTE: Renal tubular acidosis is also seen, due to decreased tubular reabsorption of HCO3-.

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25
What is the characteristic cell of liposarcoma?
Lipoblast
26
What is the cause of the ankylosis of joints seen in RA?
Myoblasts
27
Hereditary multiple osteochondromatois
* Mutations in EXT1 (more severe) and EXT2 genes * Rarely give rise to chondrosarcoma * Growth after puberty * Increasing pain * Associated with thickening of cartilagenous cap * Overal diameter \>8cm
28
Complications of RA
Anemia of chronic disease Secondary amyloidosis
29
treatment for septic arthritis
* methicillin resistant S. Aureus * Vancomycin * Pseudomonas aeruginoa * Ceftazidime
30
Benign tumor associated with Gardener's syndrome
Osteoma
31
histology of avascular necrosis osteonecrosis
Dead bone with epty lacunae Fat necrosis
32
Pseudogout is due to deposits of \_\_\_\_\_\_\_\_\_\_.
calcium pyrophosphate dihydrate (CPPD) **NOTE:** Synovial fluid shows rhomboid-shaped crystals with weakly positive birefringence under polarized light
33
Acute treatment for gout?
Colchicine NSAIDs Corticosteroids
34
What soft tissue tumors are associated with Li-Fraumeni syndrome?
Breat CA, OS, RBS, glioblastoma
35
Another name for reactive arthritis
Reiter syndrome
36
Causes of von Reckinghausen's disease of bone
* Excessive or inappropriate PTH levels due to autonomous PTH secretion * Primary due to parathyroid adenoma * Hypercalcemia * Secondary due to underlying renal disease * Hypocalcemia due to renal failure stimulates PTH hypersecretion * Nodular parathyoid hyperplasia in all 2 pathathyroid glands
37
How does one get osteomyelitis from Brucella?
Unpasteurized goat's milk
38
* Radiology * Pseudofracture diagnostic (looser's zone) * Generalized osteopenia, rarefied pale bone
Osteomalacia
39
What is the affected molecule in osteogenesis imperfecta (types 1-4)?
COL1A1, COL1A2 (Type 1 collagen)
40
Raloxifene
* Selective estrogen receptor modulator * Produces estrogen-agonistic effects on bone and lipid metabolism * Produces estrogen-antagonistic effects on uterine endometrium and breast tissue * FDA-approved SERM for treatment/prevention of postmentopausal OP
41
What are the characteristics of seronegative spondyloarthropathies?
* Lack of rheumatoid factor * Axial skeleton involvement * HLA-B27
42
FGF3
inhibits chondrocyte proliferation and aids chondrocyte differentiation **\*Activating** mutation in this gene in achondroplasia
43
What factors upregulate M-CSF and RANKL?
PTH, PGE2, activate vitamin D
44
Histology * Increased unmineralized osteoid, widened osteoud seams
osteomalacia
45
Risk factors for osteosarcoma
Familial RB Paget Radiation exposure
46
Sequestrum
Lytic focus
47
Dysostosis
disorder of the development of bone, in particular affecting ossification
48
Characteristics of parvovirus in adults
* Acute tenderness of joints/arthitis hands, wrists, and knees for 2 wk; in 10% months * Chronic anemia/RBC aplasia * Sickle cell anemia, HIV+
49
Bine morphogenic proteins (BMP)
TGF-Beta family, chondropcyte proliferation/hypertrophy
50
Gout is the deposition of ___________ crystals in tissues, especially the joints.
Monosodium urate
51
What soft tissue tumors are associated with Maffucci syndrome?
* Spindle cell hemangioma * Multiple enchrondomas * 15% risk of chondrosarcoma
52
Degenerative disorder characterized by muscle wasting and replacement of skeletal muscle by adipose tissue
Dystrophy
53
Cardio problems in Marfan syndrome
* Dilated aortic root/ascending aorta * Cystic medial necrosis * Aortic dissection * Dilated aortic root * Blood in false lumen * Occulsion of carotid artery * Hemorrphage rupturing through aortic wall into pericardium * Fatal cardiac tamponade * Cause of death in 30-45%
54
How does Vitamin D raise serum calcium and phosphate?
* Acts on: * Intestines * Kidney * Bone
55
\_\_\_\_\_\_\_\_\_\_ is due to defective mineralization of osteoid.
Rickets/ Osteomalacia
56
Causes of secondary gout
* Leukemia and myeloproliferative disorders * Increased cell turnorver leads to hyperuricemia * Lesh-Nyhan syndrome * X-linked deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) * Renal insufficiency
57
Gain of function mutations seen in achondroplasia
* Point mutation (Arg for Gly375) in FGFR3 on 4p16.13 * Constitutive activation of FGFR3 suppressing growth
58
Biopsy that reveals amosaic pattern of lamellar bone, would indicate what?
Paget's disease
59
How is Vitamin D activated?
* 25-hydroxylation by the liver * 1-alpha- hydroxylation by the proximal tubule of the kidney
60
Bracydatyly with trident hand
Achondroplasia
61
Cardiac rhabdomyoma is associated with \_\_\_\_\_\_\_\_\_.
Tuberous sclerosis
62
Synovial fluid anaylsis in Rheumatoid arthritis
* Inflammatory with neutrophils * High protein content * Low viscocity * Poor mucin clot
63
Histologic hallmark of chronic osteomyelitis
Dead bone (sequestrum)
64
Fibrillin
* Glycoprotein, major component of microfibrils in extracellular matrix * Makes a sheath around elastin * Abundant in microfibrils in aorta, ligaments, and lens
65
In Marfan syndrome, elastic aortic wall is replaced by structurally weak \_\_\_\_\_\_\_.
Glycosaminoglycans * Consequence: Aortic dilation
66
Adult forms of osteopetrosis have an increased risk of \_\_\_\_\_\_\_.
Osteomyelitis, especially jaw
67
Site of hematogenous acute ostomyelitis
**Metaphysis because it has increased nutrient rich arteries and relatively fewer phagocytic cells** than the physis or diaphysis
68
Lab findings of rhabdomyosarcoma
Desmin positive
69
First work up in swollen painful joint
Arthrocentesis
70
Angioid streaks on retina
Paget Disease of Bone
71
Unmineralized bone formed during remodeling.
Osteomalacia
72
treatment for methiciliin sensitive S.Aureus
Naficillin/Oxacillin or Cefazolin
73
What is the affected molecule in oteopetrosis?
* Autosomal dominant (adult) * LRP5 (receptor) * Infantile form * Autosomal recessive * RANKL (receptor ligand) * Renal tubular acidosis * CA2 * Autosomal recessive * Late onset, type 2 * CLCN7
74
Histology: Cortex of stalk merges with cortex of host bone so medulalry cavities is continuous
Osteochondroma
75
How is diagnosis of osteomyelitis made?
Blood culture
76
Outcomes of chronic gout
* Development of tophi * White chalky aggregates of uric acid crystals with fibrosis and giant cell reaction in the soft tissue and joints * Renal failure * Urate crystas may deposit in kidney tubules
77
Benign tumor of osteoblasts surrounded by a rim of reactive (sclerotic) bone
Osteoid osteoma
78
Laboratory finding of gout
* Synovial fluid shows needle-shaped crystals with negative birefrigence under polarized light
79
Characteristics of Reactive arthritis
* Arthritis * Urethretis * Conjunctivitis
80
RUNX2
Osteoblast differentiation
81
Types of OI
I- Normal life span, childhood fractures * Normal stature II- Fatal in utero or perinatal, intrauterine fractures III- Progressive, deforming * Growth retardation IV- Compatible with survival
82
Denosumab is a ________ inhibitor.
RANKL
83
What role of TGF-b play in marfan Syndrome?
* Fibrillin-1 directly binds a latent form of TGF-β, keeping it sequestered and unable to exert its biological activity. * reduced levels of fibrillin-1 allow TGF-β levels to rise due to inadequate sequestration. * an inflammatory reaction releasing proteases that slowly degrade the elastic fibers and other components of the extracellular matrix is known to occur.
84
How is bone density measured?
DEXA scan
85
Open-wound bacteremia (adults) seeds \_\_\_\_\_\_\_.
Epiphysis
86
* Chalky white friable deposits * Oval granular blue-gray aggreagtes * Blocky shor crystals with blunt ends measuring 0.5-5 microns
Pseudogout
87
PTH and PTHrP
Osteoclast activation
88
Treatment of osteoid osteoma and osteoblastoma
Radiofrequency ablation, complete excision **NO** radiation (could transform into osteosarcoma)
89
Clinical presentations of Ehler Danlos Syndrome
* Joint dislocations, joint hypermobility * Hyperextensible highly stretchable skin * Fragile thin skin with "cigarette paper" texture * Poor wound healing with atrophic scars * Easy bruising with ecchymoses
90
What soft tissue tumors are associated with Gardner syndrome?
Colon polyps, colon CA, desmoid
91
When are disseminated conococcal infections exacerbated in women?
During menses
92
Defect in Ehler Danlos Syndrome
Abnormal collagen
93
Ankylosing spondyloartiritis involves the ___________ and the \_\_\_\_\_\_\_\_\_\_.
Sacroiliac joint; spine
94
* Rhabdomyoblast large cells with abundant pink striated cytoplasm * +IHC: * Desmin * Myogenin, MYOD1
Embroyonal RMS **NOTE:** Alveolar RMS is also positive for desmin
95
Most of the OI mutations are autosomal dominant except?
OI II
96
Best outcome of osteosarcoma
100% necrosis at limb-salvage resection
97
Cause of mutations in achondroplasia
Sporadic and related to increased paternal age
98
migratory arthritis involves which locations?
Knees\> shoulders\> elbows\> ankles
99
Lineage of giant cell tumor of bone
Probably monocyte-macrophage
100
Key feature of psoriatic arthritis
Pitting and/or ridging of nails
101
OA chondrocytes produce ______ and \_\_\_\_\_\_\_.
IL-1 AND TNF-a * IL-1 and TNF-a stimulate production of catabolic metalloproteinases and inhibit the synthesis of type II collagen and proteoglycans
102
What dysplasia/neoplasia is associated with MG?
Thymic hyperplasia or thymoma
103
Classic location of avascular necrosis
Convex ends of long bones
104
Presentation of rickets
* Pigeon-breast deformitity- inward bending of the ribs with anterior protrusion of the sternum * Frontal bossing * Rachitic rosary * Bowing of legs in ambulating (walking) children
105
Most common forms of ostoporosis
Senile and postmenopausal
106
3 routes of spread for osteomyelities
* Hematogenous spread * Extension from contiguous site * Direct implantation (trauma/surgery)
107
Juvenile Idiopathic Arthritis
* Heterogenous group of disorders * unknown cause/pathogenesis * Arthtitis before age of 16 * peristence for at least 6 weeks
108
Compare woven bone to lamellar bone
**Woven bone** * Produced quickly * More cellular and disorganized * Haphazard, less strong than lamellar bone * pathologic: near osteomyelitis, fracture callus **Lamellar bone** * Produced slowly so stronger * Outer cortex thicker * Central medulla * Bony trabeculae * Richest in vertebrae and femoral neck
109
X-ray: Diffuse osteopenia
OI
110
Why is AKP elevated in osteomalacia?
Due to activation of osteoblasts
111
What causes the blue sclera seen in osteogenesis imperfecta?
Thinning of sclera collagen reveals underlying **choroidal veins**
112
Common cause of septic arthritis in children less than 2 yrs?
H. influenzae
113
What components of complement are activated by crystals in gout?
C3a, C5a
114
Which cytokines are necessary for the maturation of osteoclasts?
IL-1, IL-3, il-6, IL-11, TNF, Monocyte-Colony stimulation factor (CSF)
115
What factors lead to decreased bone resorption?
TGF-beta * Decreases RANKL and increases osteoprotegrin Estrogen * Decreases M-CSF and increases osteoprotegrin Bone morphogenetic proteins Testosterone LDL receptor related proteins 5 and 6 Oral calcium Calcitonin
116
Receptors of _____ detect increased PTH.
OSTEOBLASTS \*Osteoblasts release mediators that stimulate osteoclast activity
117
Clinical features of osteogenesis imperfecta
* Multiple fractures of bone (can mimic child abuse) * Blue sclera * Hearing loss (bones of middle ear are easily fractured)
118
Albright syndrome
* Precocious sexual development * Large irregular ("coast of Maine") serpiginous macules on neck, chest, back, shoulder, pelvis
119
RANKL is secreted by \_\_\_\_\_\_\_\_\_\_.
Osteoblasts **REMEMBER:** Osteoblasts regulate osteoclasts
120
* Endochondomatosis plus * Cutaneous, subcutaneous, and cavernous hemangiomas, often bilateral extensive with calcified thrombi in x-ray
Maffucini Syndrome **NOTE:** Ollier disease presents with enchrondromatosis
121
What role does PTH play in Vitamin D activation?
* PTH activates a-1-hydroxylase in proximal tubules of the kidneys * a-1-hydroxylase converts 25-hydroxyvitamin D to active metabolite, 1,25-dihydroxyvitamin D3 **NOTE:** In chronic renal failure loss of a-1-hydroxylase contributes the inability to make active Vitamin D, SO LOW 1,25 dihydroxycholecalciferol (active vitamin D) AND CONSEQUENT **OSTEOMALACIA**
122
Clinical features of Lambert-Eaton syndrome
* Anticholinesterases do not improve symptoms * Resolves with resection of cancer * proximal muscle weakness that improves with use * Eyes are usually spared
123
Histologic variation of osteosarcoma
* Osteoblastic * Chondroblastic * Fibroblastic * Parosteal * Better prognosis * Periostal
124
Function of osteocytes
Control calcium phosphorus homeostasis
125
Location of osteomas
Surfaces of facial bones
126
End result of paget disease
Thick, sclerotic bone that fractures easily
127
Joint stiffness that worsens during the day
Osteoarthritis
128
X-ray: * Destructive, motheaten, permeative * Lamellated "onionskin" periosteal reaction
Ewing Sarcoma
129
Paraneoplastic disorder associated with lambert-eaton syndrome?
Small cell carcinoma of the lung
130
X-ray: Well- circumscribed oval lucencies with thin rim of radiodense bone (O ring sign), "popcorn" calcifications
Enchondroma
131
Characteristics of congenital syphyllis
* Saber shin * Notched incisors * "Mulberry" molers
132
Labs of osteomalacia
* Decreased Ca, phosphate * Increased PTH, AKP
133
Sausage fingers or toes
Psoriatic arthritis
134
Gene involved in polyostic fibrous dysplasia
GNAS: Alpha subunit of the Gs protein receptor \*Associated with Albright Syndrome
135
Cause of achondroplasia
Activating mutation in FGFR3, leading to inhibition of cartilage growth **NOTE:** Intramembranous bone formation is not affected**.**
136
Tick must be attached for greater than _______ hrs in lyme disease.
24
137
X-ray: juxta-articular osteopenia and mirrar image symmetry with marginal erosions
Rheumatioid arthritis
138
major causes of osteonecrosis
Trauma/fracture Corticosteroids Alcohol SCA
139
Clinical characteristics of Rheumatoid arthritis
* Morning stiffness improves with activity * Symmetric involvement of PIP joints of the fingers (swan neck deformity), wrists (radial deviation), elbows, ankles, and kneess * DIP is usually spared
140
What sites are affected by osteoarthritis?
* Hips * Lower lumbar spine * Knees * DIP * PIP
141
What lab work should be gathered for septic arthritis?
* CBC * ESR * CRP **NOTE:** Arthrocentesis ( a needle can be inserted into the joint and joint fluid aspiration obtained for evaluation)
142
X-ray reveals abony mass with a radiolucent core
Osteoid osteoma
143
Chronic papillary synovitis (synoviocyte hyperplasia) is associated with which disease?
lyme
144
Clinical features of Paget's disease
* Bone pain * Increasing hat size * Hearing loss * Lion-like facies * Isolated elevated alkaline phosphatase
145
Common sites of osteomyelitis
* Children- long bones * Adults- vertebrae/discs
146
Characteristics of X-linked muscuar dystrophy
* Calf pseudohypertrophy * Serum creatine kinase is elevated
147
Dentinogensis imperfecta
Opalescent blue gray yellow teeth
148
\_\_\_\_\_\_\_\_\_\_\_\_ due to fibrous replacement of bone, subperiosteal thinning.
Brown tumors
149
Secondary causes of OA
Obesity Recurrent injury Alkaptonuria * Accumulation of homogenestic acid Sickle Cell Anemia Avascular necrosis Diabetes
150
Albers-Schonberg disease
* Absent/reduced bone resorption * Failure of osteoclast development or function * Diffuse symmetric skeletal scleoris \*Associated with Osteopetrosis
151
Marfan Syndrome is the result of what type of mutation?
Defective fibrillin-1 (FBN-1) missense or splice site mutations on Chromosome 15
152
Chronic treatment to prevent acute gout
* probenecid- for underexcretors * Allopurinol- for overproducers
153
Laboratory findings in dermatomyositis
* Increased creatine kinase * Positive ANA anti-Jo-1 antibody * Perimysial inflammation (CD4 cells) with perifascular atrophy on biopsy
154
Ewing sarcoma is a malignant proliferation of poorly-differentiated cells derived from \_\_\_\_\_\_\_\_\_\_.
Neuroectoderm
155
Because Marfan Syndrome affects connective tissue, skeleton, eyes, and cardio. It is said to exhibit \_\_\_\_\_\_\_\_\_.
Pleiotropy
156
treatment for dermatomyositis
Corticosteriods
157
Findings of infectious arthritis
* Warm joint * Limitied range of motion * Fever * Increased WBC * Elevated ESR
158
Multinucleated macrophages with 6-12 nuclei that originate from circulating monocytes.
Osteoclasts
159
In adults, woven bone occurs after _______ and in \_\_\_\_\_\_\_\_\_.
Fractures; Paget's disease
160
What caused an increased rick for chrondrosarcoma?
Ollier Disease, Maffucini syndrome \*Mutation in isocitrate dehydrogenase 1 (IDH1) or IDH2
161
What drugs can precipitate gout?
Thiazides and lead toxicity
162
\_\_\_\_\_\_\_\_\_\_\_ are contraindicated with osteoporosis.
Glucocorticoids \*Worsen prognosis
163
Treatment for Paget's disease
* Calcitonin- inhibits osteoclast function * Bisphosphonates- induces apoptosis of osteoclasts
164
How do people with dystrophin defect usually die?
Cardiac or respiratory failure; myocardium is commonly involved
165
Treatment for osteomyelitis
* Drainage via needle aspiration * Prolonged IV antibiotics * Splinting and cast immobilization * Surgery debridement/ removal of dead bone
166
90% of osteosarcomas metastses to \_\_\_\_\_\_\_\_\_.
Lungs
167
Most common extra-articular manifestation RA
Rheumatoid nodule * •Central fibrinoid necrosis, palisading rim CD68+ epithelioid histiocytes, lymphocytes
168
In sodium urate gout, blue color is ______ to the axis of compensation and yellow color is _______ to the axis of compensation.
Perpendicular; parallel
169
What factors lead to an increase in bone resorption?
* RANKL * IL-1, TNF- alpha * PTH AND PTHrP * Sclerostin * Monocyte-Colony Stimulating Factor (M-CSF) * Glucocorticoids **REMEMBER:** Glucocorticoids are contraindicated in osteoporosis and may worsen prognosis
170
X-ray of Polyostic fibrous dysplasia
* Shaft expanded with a "Shepherd's crook" deformity * Trabecular pattern is replaced by a ground glass appearance
171
X-Ray: Lytic focus (abcess) surrounded by sclerosis of bone
Osteomyelitis
172
Common sites of rhabdomyosarcoma
Head and neck; vagina in young girls
173
Which drugs are bisphosphates?
Alendronate Ibandronate Risedronate Zoledronate
174
\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is due to an autosomal dominant defect in collagen type I synthesis.
Osteogenesis imperfecta
175
Complications of pagets
* High output cardiac failure * Osteosarcoma
176
True or false. Paget disease is a localized process involving one or more bones but does not involve the entire skeleton.
True
177
Patient presents with: * Anemia * Thrombocytopenia * Leukopenia * Vision and hearing impairment * Hydrocephalus
Osteopetrosis
178
Osteocyte surrounded by matrix
Osteocytes **NOTE:** Osteocytes are conected via canaliculi and receive nutrient blood supply via Haversian canal
179
Synovitis leading to formation of a pannus
Rheumatouid arthritis

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