Musculoskeletal Pathology Flashcards Preview

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Flashcards in Musculoskeletal Pathology Deck (179):
1

Stages of pagets

  • Osteoclastic
  • Mixed osteoclastic-osteoblastic
  • Osteoblastic

2

_________ inflammation in dermatomyositis. ________ inflammation in polymyositis.

Perimysial; Endomysial

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

3

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

Anti-CCP (anti-cyclic citrullinated peptide) antibodies

4

mechanism of osteopetrosis

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

5

What are the types of Ehler Danlos Syndrome?

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)

6

Why is hepatosplenomegaly seen in osteopetrosis?

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

7

Laboratory findings of RA

  • Rheumatoid factor; marker of tissue damage and disease activity
  • Neutrophils and high protein in synovial fluid

8

  • Bilateral proximal muscle weakness
  • Rash of the upper eyelids
  • Red papules on the elbows, knuckles, and knees

Dermatomyositis

9

What is the affected molecule in achondroplasia?

FGFR3 (receptor)

10

Long, tapering fingers and toes called ____________.

Arachonodactyly

11

Another name for hyperparathyroidism

von Recklinghausen's disease of bone

12

Tamoxifen

  • 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

13

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

Wormian bones

14

Symptoms of multiple myeloma

  • Elevated calcium
  • Renal failure
  • Anemia
  • Bone lesions

15

  • Low back pain
  • Bamboo spine
  • Aortic regurgitation

Ankylosing spondyloarthritis

  • Vertebrae bodies fuse
  • Uveitis and aortitis

16

Components of hyaline cartilage

Water

Type II collagen

17

Activation of _________ on osteoclast precursor stimulates tyrosine kinase cascade.

M-CSF (Monocyte colony stimulating factor)

18

cause of primary gout

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

19

Transcient bacteremia (children) seeds _________.

Metaphysis

 

20

Mechanism by which CA2 defect leads to osteopetrosis

  • 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

21

osteoprotegerin

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

22

Synoviocytes function

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

23

Causes of avascular necrosis

  • Trauma or fracture
  • Steroids
  • SCA
  • Caisson disease

24

Why does carbonic anhydrase type II defeciency result in osteopetrosis?

Acidic environment required for osteoclast activity is loss

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

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