Musculoskeletal/Skin/CT- Pathology Flashcards
1
Q
What is achondroplasia?
A
failure of longitudinal bone growth resulting in short limbed dwarfism with normal membranous ossification (large head relative to body)
2
Q
What causes achondroplasia?
A
activation of FGFR3 which inhibits chondrocyte proliferation
85% of cases are sporadic mutations and the MOI of the hereditary pattern is AD will full penetrance (homozygous is lethal)
3
Q
How is osteoporosis diagnosed?
A
DEXA with a T-score less than -2.5
4
Q
Describe Type I osteoporosis
A
post-menopausal, with increased bone resorption as estrogen levels decline
5
Q
Describe Type II osteoporosis
A
Senile, common in 70+ yo
6
Q
What are the main tx options of osteoporosis?
A
bisphosphonates
PTH analogs
SERMs
denosumab (MAb against RANKL)
7
Q
What is osteopetrosis?
A
failure of normal bone resorption due to defective osteoclasts resulting to thickned, dense bones that are prone to fracture
8
Q
What causes osteopetrosis?
A
Osteopetrosis is caused by underlying mutations that interfere with the acidification of the osteoclast resorption pit, for example due to a deficiency of the carbonic anhydrase enzyme encoded by the CA2 gene. Carbonic anhydrase is required by osteoclasts for proton production. Without this enzyme hydrogen ion pumping is inhibited and bone resorption by osteoclasts is defective, as an acidic environment is needed to dissociate calcium hydroxyapatite from the bone matrix. As bone resorption fails while bone formation continues, excessive bone is formed
9
Q
What are the symptoms of osteopetrosis?
A
- bone breaks
- pancytopenia as bone fills marrow space
- It can also result in blindness, facial paralysis, and deafness, due to the increased pressure put on the nerves by the extra bone
- erlenmeyer flask bones
10
Q
Lack of vitD in osteomalacia and rickets causes what?
A
failure of osteoid mineralization
11
Q
What is Paget disease of bone?
A
common, localized disorder of bone remodeling caused by increase in both osteoblastic and osteoclastic activity resulting in partially sclerotic and lytic bone
12
Q
Paget Disease
A
13
Q
Paget disease increases the risk of _______
A
osteogenic sarcoma
14
Q
What are the symptoms of Paget disease?
A
bone fractures/breaks
- hearing loss
- head enlargement (hat wont fit)
15
Q
How does osteonecrosis present?
A
infarction of bone and marrow is very painful
16
Q
What are the most common causes of avascular necrosis (aka osteonecrosis)?
A
femoral head (#1)- due to insufficiency of medial circumflex femoral a.
scaphoid bone (#2)
17
Q
What are the major causes of avasular necrosis?
A
ASEPTIC
Alcoholism
Sickle cell disease
Exogenous/endogenous corticosteroids
Pancreatitis
Trauma
Idiopathic (Legg-Calve Perthes disease)
Caisson (‘the bends’)
18
Q
Describe Legg-Calve Perthes
A
a childhood hip disorder initiated by a disruption of blood flow to the ball of the femur called the femoral head. Due to the lack of blood flow, the bone dies (osteonecrosis or avascular necrosis) and stops growing. Over time, healing occurs by new blood vessels infiltrating the dead bone and removing the necrotic bone which leads to a loss of bone mass and a weakening of the femoral head.
19
Q
How does osteoporosis present in labs?
A
all normal, just low DEXA
20
Q
How does osteopetrosis present in labs?
A
all normal, with dense, brittle bones. Ca2+ decresed in severe disease
21
Q
How does Paget disease present in labs?
A
ISOLATED increased ALP leading to ‘mosaic’ bone architecture
22
Q
How does osteomalacia/rickets present in labs?
A
decreased Ca2+, PO43-
increased ALP and PTH
23
Q
How does hypervitaminosis D present in labs?
A
increased Ca and Po4
decreased PTH
24
Q
What causes hypervitaminosis D?
A
oversupplementation or granulomatous disease like sarcoidosis
25
What is osteitis fibrosa cystica?
Osteitis fibrosa cystica abbreviated OFC, also known as osteitis fibrosa, osteodystrophia fibrosa, and Von Recklinghausen's disease of bone, is a skeletal disorder **caused by hyperparathyroidism**.
This surplus stimulates the activity of osteoclasts.
The hyperparathyroidism can be triggered by a parathyroid adenoma, hereditary factors, parathyroid carcinoma, or renal osteodystrophy.
Osteoclastic bone resorption releases minerals, including calcium, from the bone into the bloodstream. In addition to elevated blood calcium levels, over-activity of this process results in a loss of bone mass, a weakening of the bones as their calcified supporting structures are replaced with fibrous tissue (peritrabecular fibrosis), and **the formation of cyst-like brown tumors in and around the bone**.
The symptoms of the disease are the consequences of both the general softening of the bones and the excess calcium in the blood, and include bone fractures, kidney stones, nausea, moth-eaten appearance in the bones, appetite loss, and weight loss.
26
How do OFC and primary hyperPTHism present in labs?
increased serum Ca2+, ALP, and PTH
decreased PO43-
27
How does 2ndary hyperPTHism present in labs?
decreased Ca2+
increased PO43-, ALP, and PTH
28
What are some benign bone tumors?
Giant cell tumors
Osteochondroma
29
What is this?
Giant cell tumor of bone with 'soap bubble' appearance
30
Where are giant cell tumors found?
epiphyseal end of long bones, in 20-40 yo
31
What is this?
osteochondroma, with cauliflower extension
32
What is the 2nd most common primary malignant bone tumor after MM?
Osteosarcoma
33
Who typically gets osteosarcomas?
bimodal: 10-20 yo and 65+
34
What are the predisposing factors for osteosarcoma?
Paget disease of bone
bone infarcts
radiation
familial retinoblastoma
Li-Fraumeni syndrome
35
Where are osteosarcomas found?
metaphysis of bone, often around knee
36
A Codman triangle is seen in what?
osteosarcoma
37
What mutation is seen in Ewing Sarcoma?
t(11,22) causing a EWS-FLI 1 fusion
38
How does Ewing sarcoma act?
extremely aggressive withe arly METS, but responisve to chemo
39
Osteoarthritis is the mechanical degradation of joint cartilage due to wear and tear. What are some of the classic joint findings?
subchondral cysts
sclerosis
osteophytes (bone spurs)
eburnation (polished, ivory-like appearance of bone) (Below)
synovitis
Heberden nodes (DIP) and Bouchard nodes (PIP). No MCP involvement
40
41
What are the predisposing factors for osteoarthritis?
age, obesity, joint trauma
42
How does osteoarthritis present?
pain after use (eg. end of day), improving with rest
Noninflammatory
43
How is osteoarthritis tx?
acetaminophen, NSAIDs, and intra-articular glucocorticosteroids
44
What causes rheumatoid arthritis?
autoimmune rxn causing inflammatory destruction of synovial joints mediated by cytokines and type III and IV hypersensitivity rxns
45
What are the joint findings of rheumatoid arthritis?
-pannus (inflammatory grnaulation tissue) formation in proximal joints (MIP, PIP)
subQ rheumatoid nodules
ulnar deviation of fingers and/or subluxation
swan necking or boutnniere deformities
46
What are the predisposing factors for RA?
female
+ rheumatoid IgG factor or anti-cyclic citrullinated peptide Ab (more specific)
-HLA-DR4
47
How does RA present?
morning stiffness lasting 30+ min and improving with use
symmetric joint involvemnet
fever, fatigue, weight loss,
pleuritis, pericarditis
48
How is RA tx?
NSAIDs
glucocorticoids
DMARDS (methotrexate, sulfasalazine)
TNF-a inhibitors
49
Sjogrens= autoimmune disorder characteristized by destruction of exocrine glands (especially lacrinal and salivary) by lymphocytic infiltrates
50
What Abs are seen in Sjogrens?
antinuclear SS-A (anti-Ro) and SS-B (anti-La)
51
What causes gout?
acute inflammatory monoarthritis caused by precipitation of monosodium urate crystals (more common males)
52
What are the main patho causes of gout?
- 90% underexcretion of uric acid - largely idiopathic; can be exacerbated by certain meds (thiazides)
- overproduction of uric acid (10%)-Lesch Nyhan syndrome, PRPP excess, cell turnover (tumor lysis syndrome), von Gierke disease
53
Gout
Gout- NEGATIVELY birefringent under polarized light
54
Gout crystals are _____ under para**ll**el light and _____ under perpendicular light
yellow- parallel
blue- perp
55
How does gout present?
monoarthritis swelling (MTP joint in big toe)
Tophus formation (often on external ear, olecranon bursa, or Achilles tendon)
56
Why would alcohol use lead to gout?
alcohol metabolites compete for the same excretion sites in the kidney as uric acid, decreasing uriac acid secretion and subsequent buildup
57
How is acute gout tx?
NSAIDs (indomethacin), glucocorticoids, colchicine
58
How is gout prevented?
xanthine oxidase inhibitors (e.g. allopurinol, febuxostat)
59
What causes pseudogout?
pain and effusion in a joint, caused by deposition of calcium pyrophosphate crystals with joint spaces forming weakly basophilic, rhomboid crystals
60
What joints does pseudogout commonly affect?
large joints like the knee in 50+ yo (both sexes equally affected)
61
What are some diseases associated with pseudogout?
hemochromatosis, hyperPTHism, osteoarthritis
62
What are some common causes of infective arthritis?
S. aureus, Streptococcus, and Neisseria gonorrhoeae
63
What are seronegative spondylathropathies?
arthritis w/out rheumatoid factor, with a strong association with HLA-B27 (codes for MHC class I)- occurs more in males
64
What are the seronegative spondylathropathies?
**PAIR**
**P**soriatic arthritis
**A**nkylosing spondylitis
**I**BD
**R**eactive arthritis
65
Describe psoriatic arthritis (seen in less than 1/3 of pts with psoriasis)
joint pain and stiffness associated with psoriasis
asymmetric involvement
dactylitis (sausage fingers); 'pincil in cup' deformity on xray (below)
66
What things are seen with ankylosing spondylitis?
bamboo spine (below)
uveitis
aortic regurg
67
What is the classic triad of reactive arthritis (Reiter syndrome)?
Conjunctivitis and anterior uveitis
urethritis
arthritis
"cant see, cant pee, cant climb a tree
68
What are some common causes of Reiter Syndrome?
Post-Gi infection (Shigella, Salmonella, Yersinia, Campylobacter)
Chlamydia
69
Who commonly gets Lupus?
AA female of reproductive age
70
What are the symptoms of Lupus?
**RASH OR PAIN**
**R**ash (malar or discoid)
**A**rthritis
**S**oft tissues/serositis
**H**eme disorders (e.g. cytopenias
**O**ral/nasopharyngeal ulcers
**R**enal disease, **R**aynaud phenomenon
**P**hotosensitivity, Positive VDRL/RPR
**A**NAs
**I**mmunosuppressants
**N**eurologic disorders (e.g. seizures, phychosis)
71
what are the most common causes of death with lupus?
CV disease
Infection
Renal disease
72
What is Libman-Sacks endocarditis?
a nonbacterial, wart-like vegetation on both sides of valves seen in SLE
73
What Abs are seen in SLE?
ANA (not specific)
Anti-dsDNA Abs (specific, poor prognosis)
Anti-Smith Abs
Antihistone (sensitive for drug-induced lupus)
decreased C3, C4, and CH50
74
Tx of lupus
NSAIDs, steroids, immunosuppressants, hydroxychloroquine
75
What is antiphospholipid syndrome?
Autoimmune disorder diagnosed on clinical criteria including a hx of thrombosis or spontaneous abortion along with anticardiolipin and/or anti-B2 glycoprotein Abs
76
What is sarcoidosis characterized by?
immune-mediated, widespread **noncaseating** grnaulomas, elevated serum ACE levels, and elevated CD4+/CD8+ ratio commonly in black females
77
How does sarcoidosis present?
often asymptomatic except for some LAD
78
How would a CXR of sarcoidosis present?
bilateral hilar adenopathy, reticular opacities
79
What are some associations of sarcoidosis?
restrictive lung disease (interstitial fibrosis)
erythea nodosum
lupus
Bell palsy
80
What is PMR?
pain and stiffness in shoulders and hip, often with fever, malaise, and weight loss, but not muscle weakness
81
Who gets PMR?
more common in women 50+ yo, associated with giant cell arteritis
82
Lab findings of PMR?
elevated ESR and CRP
normal CK
83
How is PMR tx?
rapid response to low-dose steroids
84
Describe fibromyalgia?
Most commonly seen in females 20-50 yo and marked by chronic, widespread MS pain associated with stiffness, poor sleep, fatigue, and paresthesias.
Tx with exercise, antidepressants (TCAs, SSRIs), anticonsulvants
85
What are the lab findings of polymyositis/dermatomyositis?
elevated CK
positive ANA, anti-Jo-1, anti-SRP, anti-Mi-2 ABs
86
What is polymyositis?
A type of chronic inflammation of the muscles (inflammatory myopathy) related to dermatomyositis and inclusion body myositis. The inflammation is predominantly of the **endomysium** in polymyositis (below), whereas dermatomyositis is characterized by primarily _perimysial inflammation_
87
88
Polymyositis
progressive symmetric proximal muscle weakness, characterized by endomysial inflammation with CD8 T cells. Most often involves the shoulders
89
Dermatomyositis
also involves a malar rsh, Gottron papules, heliotrope rash, 'shawl and face' rash, and mechanic's hands
90
Dermatomyositis rash on joints (aka Gottron papules)
SLE hand rash in between joints
91
What is the main inflammatory cell in polymyositis? dermatomyositis?
PM- CD8
DM- CD4
92
What is Myastenia gravis?
An autoimmune disorder marked by Abs against postsynaptic ACh receptors resulting in ptosis, diplopia, and muscle weakness
93
What are some associations of MG?
thymoma, thymic hyperplasia
94
What is Lambert-Eaton myasthenic syndrome?
autoantibodies to presynaptic Ca2+ channels, inhibiting ACh release resulting in proximal muscle weakness, autonomic symptoms (dry mouth, impotence)
Improves with muscle use
95
What is myositis ossificans?
metaplasia of skeletal muscle into bone following **muscular trauma**
96
What is the classic triad of scleroderma (aka systemic sclerosis)?
autoimmunity, noninflammatory vasculopathy, and collagen deposition with fibrosis common in women
97
What are the main types of scleroderma?
Diffuse and limited
98
Described diffuse scleroderma
widespread skin involvemetn, rapi progression, early visceral involvement
99
What Abs are associated with diffuse scleroderma?
anti-DNA topoisomerase I antibody
100
Describe limited scleroderma?
lmited skin involvement confined to fingers and face. Also with CREST syndrome.
101
What is CREST syndrome
syndrome associated with limited scleroderma with **c**alcinosis, **r**aynaud phenomenon, **e**sophageal dysmotility, **s**clerodactylyl (a localized thickening and tightness of the skin of the fingers or toes), and **t**elangiectasia
102
Limited scleroderma is associated with what Abs?
anti-centromere
103
104
What prevents paracellular movement of solutes?
tight junctions (aka zonula occludens), composed of claudins and occludins
105
What is located below tight junctions, forming belts connecting actin cytoskeletons of adjacent cells with Ca2+-dependent adhesion proteins (aka CADherins)?
adherens junction (zonula adherens)
Loss of E-cadherins promotes metastasis
106
What forms structural support among cells via keraton interactions?
desmosomes (aka macula adherens)
AutoABs= pemphigus vulgaris
107
What are gap junctions composed of?
channel proteins called connexons (permit electrical and chemical communication between cells)
108
What do integrins do?
these are membrane proteins that maintain the integrity of BM by binding to collagen and laminin in the BM
109
What do hemidesmosomes do?
they connect keratin in basal cells to underlying BM
AutoABs= bullous pemphigoid
110
What would this be classified as?
A macule (flat lesion with well-circumscribed change in skin color less than 1 cm)
Ex: freckle, labial macule (front)
111
What would this be classified as?
A patch (a macule 1+ cm)
Ex. large birthmark (congenital nevus)
112
What would this be classified as?
A macule (elevated solid lesion less than 1cm)
Ex. Mole (nevus), acne
113
What would this be classified as?
plaque (papule 1+ cm)
ex. psoriasis
114
What would this be classified as?
A vesicle (small fluid-containing blister less than 1 cm)
Ex. chickenpox (varicella), shingles
115
What would this be classified as?
a bulla (large fluid-containing blister 1+ cm)
Ex. bullous pemphigoid
116
What is hyperkeratosis?
increased thickness of the straum corneum as seen in psoriasis and calluses
117
What is parakeratosis?
hyperkeratosis with retention of nuclei in straum corneum (as seen in psoriasis)
118
What is spongiosis?
epidermal accumulation of edematous fluid in intercellular spaces
119
What is acantholysis?
seperation of epidermal cells (as seen in pemphigus vulgaris)
120
What is acanthosis?
epidermal hyperplasia (especially in the spinosum)
121
What causes albinism?
normal melanocyte no. with decreased melanin production due to decrease tyrosinase activity or defectiv tyrosine transport. Can also be due to failure of neural crest cell migration during development
122
What is melasma (cholasma)?
a characteristic hyperpigmentation associated with pregnancy (aka the 'mask of pregnancy') or OCP use
123
What is vitiligo and what causes it?
irregular areas of complete digmentation caused by autoimmune destruction of melanocytes
124
