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Bone, Joint & Muscle Pathology Flashcards

1
Q

What is Achondroplasia?

A
  • Failure of longitudinal bone growth (endochonrdal ossification)→ short limbs
  • Membranous ossification is not affected→ large head & chest relative to limbs
  • Common cause of dwarfism
  • Normal life span & fertility
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2
Q

**Growth Factor involved in Achondroplaisa **

A

Constitutive activation of fibroblast GF receptor (FGFR3) acutally inhibits chondrocyte proliferation

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3
Q

Pattern of Inheritance of Achondroplaisa

A
  • AD inheritance
  • 85% occur sporadically & assoc w/ advanced paternal age
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4
Q

What is Osteoporosis?

A

Trabecular (spongy) bone loses mass & interconnections despite normal bone mineralization & lab values ( serum Ca2+ & PO43-)

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5
Q

What is Type I Osteoporosis?

A
  • Postmenopausal: inc bone resportion d/t dec estrogen levels
  • Femoral neck fracture, distal radius (Colles’) fractures
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6
Q

What is Type II Osteoporosis?

A
  • Senile osteoporosis
  • Affects men & women >70 years of age
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7
Q

Prophylaxis for Type II Osteoporosis

A
  • Regular wt bearing exercise
  • Sdequate Ca & Vit D intake throughout adulthood
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8
Q

Tx for Osteoporosis Type II

A
  • Estrogen (SERMs) &/or calcitonin
  • Bisphosphonates (induce osteoclast apoptosis)
  • Pulsatile PTH for severe cases
  • Glucocorticoids are contraindicated
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9
Q

What is Osteopetrosis?

A

Failure of normal bone resorption d/t defective osteoclasts→ thickened, dense bones that are prone to fracture

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10
Q

What does Osteopetrosis look like?

A

Bone fills marrow space, causing pancytopenia, extramedullary hematopoiesis

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11
Q

What mutations are involved w/ Osteopetrosis?

A

Carbonic anyhydrase II→ loss of the acidic microenvironment required for bone resorption

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12
Q

Look of Osteopetrosis on X-ray

A

Bone-in-bone appearance

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13
Q

What are the clinical features of Osteopetrosis?

A
  • Bone fractures
  • Anemia, thrombocytopenia & leukopenia w/ extramedullar hematopoiesis
  • Hydrocephalus d/t narrowing of foramen magneum
  • Renal tubular acidosis
  • Cranial nerve impingement→ vision & hearing impairment
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14
Q

Tx for Osteopetrosis

A

BM transplant is potentialy curative as osteoclasts are derived from monocytes

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15
Q

What can Vit D deficiency cause?

A
  • Rickets in children
  • Osteomalacia in adults
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16
Q

Pathway of Vit D Deficiency

A
  • dec Vit D→ dec serum Ca→ Inc PTH secretion → dec serum phosphate
  • Hyperactivity of osteoclasts→ inc alk phos
  • Defective mineralization/ calcification of osteoid→ soft bones that bow out
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17
Q

What is Paget dz of bone (Osteitis deformans)?

A

Common, localized disorder of bone remodeling caused by an imbalance in osteoblastic & osteoclastic activity

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18
Q

Lab Values of Osteitis deformans

A

Normal serum Ca, P & PTH levels w/ inc ALP

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19
Q

What does osteitis deformans look like?

A
  • Mosaic (“woven”) bone pattern
  • Long bone chalk-stick fractures
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20
Q

What can Osteitis deformans cause?

A
  • Inc blood flow from inc arteriovenous shunts may cause high-output HF
  • Inc risk of osteosarcoma
  • Hat size can be Inc
  • Hearing loss is common d/t auditory foramen narrowing
  • Bone pain
  • Lion-like face
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21
Q

What is osteitis fibrosa cystica?

A
  • “Brown tumors” of hyperparathyroidism
  • Inc serum Ca, ALP, PTH & dec P
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22
Q

What is Polyostotic fibrous dysplasia?

A

Bone replaced by fibroblasts, collagen & irregular bony trabeculae

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23
Q

What is McCune-Albright Syndrome?

A

Form of polycystic fibrous dysplasia char by mulitple unilateral bone lesions assoc w/ endocrine ABN (precocious puberty) & café-au-lait spots

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24
Q

What are the 1º benign bone tumors?

A
  • Giant cell tumor (osteoclastoma)
  • Osteochondroma (exostosis)
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25
What age group osteoclastoma occur?
20-40yo
26
What is Giant Cell tumor?
Locally aggressive benign tumor that arises in the epiphysis of long bones, us. the distal femur or proximal tibial region (knee)
27
What is the appearance of Giant Cell tumor on X-ray?
"Double bubble" or "soap bubble"
28
Histo of Giant cell tumor
Spindle-shaped cells w/ multinucleated giant cells & stromal cells
29
Who does Osteochonroma occur in?
Males \<25yo
30
What is Osteochondroma?
* Most common benign tumor * Mature bone w/ cartilagenous cap
31
Where does Osteochondroma commonly originate?
Arise from a lateral projection of the growth plate (metaphysis); bone is continous w/ marrow space
32
What does Osteochondroma transform to?
Rare transformation to chondrosarcoma
33
What are the 1° malignant bone tumors?
* Osteosarcoma (osteogenic sarcoma) * Ewing's sacroma * Chondrosarcoma
34
Who gets Osteosacroma?
* Males\> females * 10-20 yo
35
What are the predisposing factors to Osteosarcoma?
* Paget's dz of bone * Bone infarcts * Radiation * Familial retinoblastoma
36
Characteristics of Osteosarcoma
* Metaphysis of long bones, often around distal femur, proximal tibial region (knee) * Codman's triangle (from elevation of periosteum or 'sunburst pattern' on X-ray
37
Tx of Osteosarcoma
Aggressive, tx w/ surgical en bloc resection (w/ limb salvage) & chemotherapy
38
Who gets Ewing's Sarcoma?
Boys \<15yo
39
Where does Ewing's Sarcoma occur?
Commonly appears in diaphysis of long bones, pelvis, scapula & ribs
40
Histo of Ewing's Sarcoma
* Anaplastic small blue cells that resemble lymphocytes * "Onion skin" appearance on X-ray
41
Prognosis of Ewing's Sarcoma
Extremely aggressive w/ early mets but responsive to chemo
42
What translocation is Ewing's Sacroma assoc w/?
t(11;22) translocation | (11+22=33 Patrick Ewing's jersey #)
43
Who gets Chonrosarcoma?
Men 30-60yo
44
Where is Chondrosarcoma located?
Pelvis, spine, scapula, humerus, tibia or femur
45
What is Chondrosarcoma?
* Malignant cartilaginous tumor * May be of 1° origin or from osteochondroma * Expansile glistening mass w/in the medullary cavity
46
Cause of Osteoarthritis
Mechanical- joint wear & tear destroys articular cartilage
47
Joint findings of Osteoarthritis
* Subchondral cysts * Sclerosis * Osteophytes (bone spurs) * Eburnation (polished ivory-like appearance of bone) * Bouchard's nodes (PIP) * Heberden nodes (DIP) * No MCP involvement
48
Predisposing factors of Osteoarthritis
* Age (\>60yo) major RF * Obesity * Joint deformity * Trauma
49
Clinical Presentation of Osteoarthritis
* Joint stiffness in the morning that worsens during the day & improves w/ rest * Knee CT loss begins medially ("bowlegged") * Noninflammatory * No systemic sx
50
Tx of Osteoarthritis
NSAIDs & Intra-articular glucocorticoids
51
Cause of Rheumatoid arthritis
* Autoimmune- inflammatory destruction of synovial joints * Type III hypersensitivity * IgM auto-Ab against Fc portion of IgG (rheumatoid factor)
52
Joint findings in RA
* Synovitius→ Pannus (inflam granulation tissue) * Rheumatoid nodules: central zone of necrosis surrounded by epi histiocytes * Radial deviation of wrists * Ulnar deviation of fingers * Boutonniere deformity of thumb * Baker's cysts (in politeal fossa) * No DIP involvement\* * Swan-neck deformity of fingers
53
Predisposing Factors of RA
* Classically women of childbearing age * 80% have + Rheumatoid factors (anti-IgG Ab) * Anti-cyclic citrullinated peptide Ab is more specific * Strong assoc w/ HLA-DR4\*\*
54
Clinical Presentation of RA
* Morning stiffness lasting \>30 min & improving w/ use * Symmetric joint involvement * Systemic sx- fever, fatigue, pleuritis, pericarditis, vasculitis, lymphadenopathy, interstitial lung fibrosis
55
Tx of RA
* NSAIDs * Glucocorticoids * Dz-modifying agents (methotrexate, sulfasalazine, TNF-alpha inhibitors)
56
What is Sjögren's Syndrome?
Lymphocytic infiltration of exocrine glands, especially lacrimal & salivary
57
Classic Triad of Sjögren's Syndrome
* Xerophthalamia- dry eyes, conjuctivitis, "sand in my eyes" * Xerostomia- dry mouth, dysphagia * Arthritis
58
Characteristics of Sjögren's Syndrome
* Parotid enlargement * inc risk of B-cell lymphoma * Dental Caries * Auto-Ab to ribonucleoprotein Ag: SS-A (Ro), SS-B (La) * Assoc w/ rehumatoid arthritis
59
What is Gout?
Precipitation of monosodium urate crystals into joints d/t hyperuricemia from overy production or dec excretion of uric acid
60
What does Gout look like?
Crystals are needle shaped & negatively birefringemant= yellow crystals under parallel light
61
Sx of Gout
* Asymmetric joint distribution * Joint is swollen, red & painful * Classic manifestation is painful MTP joint of the big toe (podagra) * Tophus formation (often on external ear, olecranon bursa or Achilles tendon) * Acute attack tends to occur after a large meal or alcohol consumption (alcohol metabolites compete for same excretion sites in kindney as uric acid, causing dec uric acid sec & subsequent bulidup in blood)
62
Tx of Gout
* _Acute_: NSAIDs (indomethacin), glucocorticoids * _Chronic_: xanthine oxidase inhibitors (allopurinol, febuxostat)
63
Cause of Pseudogout
* Depostions of Ca pyrophosphate dihydrate (CPPD) crystals w/in the joint space * Usuallly affects large joints (classically the knee)
64
What does Pseudogout look like?
* Forms basophilic, rhomoid crystals that are weakly + birefringement * Crystals are blue when parallel to the light
65
Who gets Pseudogout?
* \>50yo * Effects both sexes equally
66
Tx of Pseudogout
* NSAIDs for sudden severe attacks * Steroids * Colchicine
67
Causes of Infectious Arthritis
* *S. aureus* * *Streptococcus* * *Niesseria gonorrheaoeae*
68
What is Infectious Arthritis?
* Arthritis d/t an infectious agent * Gonococcal arthritis is an STD that presents as a migratory arthritis w/ an asymmetric pattern
69
Sx of Infectious Arthritis
* Affected joint is swollen, red & painful * **S**ynovitis (knee) * **T**enosynovitis (hand) * **D**ermatitis (pustules) * Fever, Inc WBC & inc ESR
70
What is Osteonecrosis?
* Avascular necrosis * Infarction of bone & marrow * Pain assoc w/ activity * MC site is femoral head
71
Causes of Osteonecrosis
* Trauma * High-dose corticosteroids * Alcoholism * Sickle cell
72
What are Seronegative spondyloarthropathies?
* Arthritis w/o rheumatoids factor (no IgG Ab) * Psoriatic arthritis * Ankylosing spondylitis * IBS * Reactive arthritis (Reiter's synd)
73
What seronegative spondyloarthropathies asoc w/?
* HLA-B27 (gene that codes for HLA- MHC class I) * Occurs more often in males * Axial skeleton involvement * Lack of rheumatoid factor
74
What is Psoriatic arthritis?
* Joint pain & stiffness seen in hands & feet * Asymmetric & patchy involvement * Dactylitis "sausage fingers" * Pencil-in-cup deformity on X-ray
75
What is Ankylosing spondylitis?
* Chronic inflam dz of spine & sacroiliac joints→ ankylosis * Bamboo spine (vertebral fusion) * Uveitis & aoritic regurg
76
What is IBS?
Chron's dz & UC are often accompanied by ankylosing spondylitis or peripheral arthritis
77
Reactive arthritis (Reiter's Synd) Triad
* **C**onjunctivitis & anterior uveitis * **U**rethritis * **A**rthritis * "Can't see, can't pee, can't climb a tree" * Post GI or *chlamydia* infections
78
Who gets SLE?
* 90% are female * 14-45yo * MC & severe in black females
79
Clinical presentation of SLE
* Fever, fatigue, wt loss * **Libman-sacks endocarditis** (verrucous war-likem sterile vegetations on both sides of valve) * Hilar adenopathy * Raynaoud's phenomenon
80
What is the common COD in SLE?
Nephritis→ Diffuse proliferative glomerulonephritis
81
What causes false + on the syphillis test (RPR/VDRL)?
Antiphospolipid Ab's which cross-react w/ cardiolipin used in tests
82
What do SLE lab tests detect?
* **Antinuclear Ab's** (ANA)- sensitive, (1° screening) but not specific for SLE * **Ab's to ds-DNA** (anti-dsDSA)- very specific, poor prognosis, * **Anti-Smith Ab's** (anti-Sm)- very specific, but not prognostic * **Antihistone Ab's**- more sensitive for drug-induced lupus
83
I'M DAMN SHARP (SLE characteristics)
* **I**g's (anti-dsDNA, anti-Sm, antiphospholipid) * **M**alar rash * **D**iscoid rash * **A**ntinuclear Ab * **M**ucositis (oropharyngeal ulcers) * **N**eurologic disorders * **S**erositis (pleuritis, pericarditis) * **H**ematologic disorders * **A**rthritis * **R**enal disorders * **P**hotosensitivity
84
Characteristics of Sacroidosis
* Immune-mediated, widesspread noncaseating granulomas & elevated serum ACE levels * Often asx except for enlarged LN * Common in black females
85
What is Sarcoidosis assoc w/?
* Restrictive lung dz (interstitial fibrosis) * Erythema nodosum * Bell's palsy * Epi granulomas containing microscopic Schaumann & asteroid bodies * Uveitis * Hyper-Ca (d/t elevated 1-alpha-med vit D activation in epitheloid macro)
86
Tx of Sarcoidosis
Steroids
87
Sx of Polymyalgia rheumatica
* Pain & stiffness in shoulds & hips * Fever * Malaise * Wt loss * Does not cause muscle weakness
88
Who gets Polymyalgia rheumatica?
MC in women \>50yo
89
What is associated with Polymyalgia rheumatica?
Temporal (giant cell) arteritis
90
Findings in Polymyalgia rheumatica
Inc ESR & normal CK
91
Tx of Polymyalgia rheumatica
Rapid response to low-dose corticosteroids
92
Who gets Fibromyalgia?
MC seen in women 20-50yo
93
What is Fibromyalgia?
Chronic, widespread MSS pain assoc w/ stiffness, paresthesia, poor sleep & fatigue
94
What is Polymyositis?
* Progressive symmetric proximal muscle weakness * Char by endomysial inflam w/ CD8+ T cells w/ necrotic muscle fibers * Most often involves shoulders but NOT skin
95
What are the characteristics of Dermatomyositis?
* Similar to polymyositis except it involves the skin * Bilateral proximal muscle weakness * Malar rash (similar to SLE) * Gottron's lesions→ red papules on elbows, knuckles & knees * Heliotrope rash (upper eyelids) * "Mechanic hands"
96
What is found on muscle biopys in dermatomyositis?
Perimysial inflam (CD4+ T cells) w/ perifasciular atrophy on bx
97
What does Dermatomyositis inc the risk of?
Occult Malignancy
98
Lab findings in Polymyositis/Dermatomyositis
* Inc creatine kinase * + ANA * + anti-Jo-1 Ab's\*\*\*
99
Tx of Polymyositis/dermatomyositis
Corticosteroids
100
What is the freq of Myasthenia gravis?
MC NMJ disorder MC in women
101
What is the cause of Myasthenia gravis?
Auto-Ab's to postsynaptic ACh receptors at NMJ
102
What does AChE inhibitor admin do in Myasthenia gravis?
Reversal of sx
103
Clinical characterisitics of Myastenia gravis
* Ptosis * Diplopia * Weakness * Worsens w/ muscle use
104
What is Myasthenia gravis assoc w/?
Thymoma & thymic hyperplasia→ thyectomy improves sx
105
Freq of Lmabert-Eaton myasthenic synd
Uncommon
106
Cause of Lamber-Eaton myasthenic synd
Auto-Ab's to presynaptic Ca2+ channel at NMJ→ dec ACh release
107
Clinical sx of Lamber-Eaton Synd
Proximal muscle weakness that improves w/ muscle use. Eyes are spared
108
What is Lamber-Eaton synd assoc w/?
Small cell lung cancer→ paraneoplastic synd
109
What does AChE inhibitor admin in Lamber-Eaton Synd do?
No effect
110
What is Myositis ossificans?
Metaplasia of skm to bone following muscular trauma
111
Where is Myositis ossificans most often seen?
Upper or lower extremity
112
How does Myositis ossificans present?
Suspicous "mass" at site of known trauma or as incidental finding on radiography
113
What is Scleroderma (systemic sclerosis)?
Excessive fibrosis & collagen deposition throughout the body
114
How does Scleroderma of skin commonly present?
Sclerosis of skin, manifesting as puffy & taut skin w/ absence of wrinkles
115
What organ systems does slceroderma affect?
* Renal * Pulmonary (most likely COD) * CV * GI system
116
Who gets scleroderma?
75% female
117
What is Diffuse scleroderma?
Widespread skin involvement, rapid progression, early visceral involvement
118
What is Diffuse scleroderma assoc w/?
anti-Scl-70 Ab (anti-DNA topoisomerase I Ab)
119
Clinical sx of CREST synd
* **C**alcinosis * **R**eaynaud's phenomenon * **E**sophageal dysmotility * **S**clerodactyly * **T**elangiectasia * Limited skin involvement often confined to fingers & face
120
What is the clincial course of CREST synd?
More benign clinical course
121
What is CREST synd assoc w/?
Anti-**C**entromere Ab ( **C** fo **C**REST)
122
What is Osteogenesis Imperfecta?
Cogenital defect of bone resorption resutling in structurally weak bone
123
What causes Osteogenesis Imperfecta?
AD defect in collagen type I synthesis (used to make bone)
124
What are the clinical features of Osteogenesis Imperfecta?
* Multiple fractures of bone * Blue sclera d/t thinning sclera collagen that reveals underlying choroidal veins * Hearing loss
125
What causes Vit D def?
* Decreased sun exposure * Poor diet * Malabsorption * Liver failure * Renal failure
126
What are the clinical features of Rickets
* Pigeon-breast deformity: inward bending of ribs * Frontal bossing * Rachitic rosary d/t osteoid dep @ costochondral junction * Bowing of legs
127
Who gets Rickets?
MC arises in children \<1 yo
128
What are the clinical features of Osteomalacia?
* Inc risk of bone fracture d/t inadequate mineralization * Dec serum Ca, dec P, inc PTH & Inc alk phos
129
What is Osteomyelitis?
Infection of marrow & bone. MC bacterial arising by hematogenous spread
130
How does Osteomyletis arise in children?
Tranisent bacteremia that seeds metaphysis
131
How does osteomyelitis arise in adults?
Open-wound bacteremia that seeds epiphysis
132
What are the causes of Osteomyelitis?
* S. aureus→ MCC (90%) * N. gonorrhoeae→ sexually active young adults * Salmonella→ sickle cell dz * Pseudomonas→DM or IV drug abusers * TB→ vertebrae (Potts dz)
133
Whare are the clinical features of osteomyelitis?
* Bone pain w/ systemic signs of infection * Lytic focus (abscess) surrounded by sclerosis of bone on x-ray * Lytic focus→ sequestrum * Sclerosis→ involucrum * Dx made by blood culture
134
What is avascular (aseptic) necrosis?
Ischemic necrosis of bone & BM
135
What are the causes of avascular (aseptic) necrosis?
* Trauma or fracture (MC) * Steroids * Sickle cell anemia (dactylitis) * Caisson dz (gas emboli, us N, in bone)
136
What are the complications of avascular (aseptic) necrosis?
Osteoarthritis & fracture
137
What are Osteomas?
Benign tumor of bone
138
Where do osteomas commonly arise?
Surface of facial bones
139
What are osteomas assoc w/?
Gardner synd: Familial adenomatous polyposis w/ fribomatosis in retroperitoneum & osteomas of facial bone
140
What is Osteoid Osteoma?
Benign tumor of osteoblasts (that produce osteoid) surrounded by a rim of reactive bone (osteoma)
141
Who do osteoid osteomas occur in?
young adults \<25 yo (MC in males)
142
Where do osteoid osteomas arise?
cortex & diaphysis of long bones (femur)
143
What resolves the bone pain in oteoid osteoma?
Aspirin
144
What does imaging of an osteoid osteoma reveal?
Bony mass (\<2cm) w/ a radiolucent core (osteoid)
145
What is an osteoblastoma?
Similar to osteoid osteoma but larger (\>2cm), arise in vertebrae & presents as bone pain that does NOT respond to aspirin
146
What is a Chondroma?
Benign tumor of cartilage that arises in the medulla of small bones of hands & feet
147
What are the char of metastatic tumors of bone?
* MC than 1° tumors * Osteolytic (punched-out) lesions * Prostatic CA classically produces osteoblastic lesions
148
What are causes of 2° Gout?
* Leukemia & myeloproliferative disorders (inc cell turn over) * Lesch-Nyhan synd
149
What is Lesch-Nyhan synd?
* X-linked def of hyoxanthine-guanine phosphoribosyltransferase (HGPRT) * Presents w/ mental retardation & self-mutilation (bite fingers & lips)
150
What is a Lipoma?
MC benging soft issue tumor in adults. Benign tumor of adipose tissue
151
What is a liposarcoma?
MC malignat soft tissue tumor in adults. Malignant tumor of adipose tissue. Lipoblasts are the char cell\*\*
152
What are Rhabdomyomas?
Benign tumor of skm
153
What is cardiac rhabdomyoma assoc w/?
Tuberous sclerosis
154
What are Rhabdomyosarcomas?
Malignant tumor of skm. MC malignant soft tissue tumor in children
155
What are the char cells of Rhabdomyosarcomas?
Rhabdomyoblasts; desmin +
156
What are the common locations of Rhabdomyosarcomas?
* MC site is the head & neck * Vagina is the classic site in girls \<5yo
157
What is X-linked muscular dystrophy?
Degenerative disorder of skm char by muscle wasting & replacement of skm by adipose tissue
158
What mutations are involved in X-linked muscular dystrophy?
Dystrophin→ anchors muscle cytoskeleton to the extracellular matrix; mut are often spon d/t large gene size
159
What is the cause of Duchenne muscular dystrophy?
Deletion of dystrophin
160
How does Duchenne muscular dystrophy present?
* Proximal muscle weakness at 1 year of age, progresses to involve distal muscles * Calf pseudohypertophy (lage d/t fat) * Serum creatinine kinase is elevated
161
What is the COD in Duchenne muscular dystrophy?
Cardiac or resp failure (myocardium commonly involved)
162
What is Becker muscular dystrophy?
Caused by mutated dystrophin→ clincially results in milder dz

MSS, Skin & CT (5 decks)

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