Pathoma CH. 18 Musculoskeletal Pathology Flashcards
1
Q
Impaired cartilage proliferation in the growth plate…
A
Achondroplasia
2
Q
What is a common cause of dwarfism that involves abnormal cartilage growth within the growth plate?
A
Achondroplasia
3
Q
What is the mutation present in patient with achondroplasia?
A
Activating mutation in fibroblast growth factor receptor 3 (FGFR3)
4
Q
What is the pattern of inheritance for achondroplasia?
A
Autosomal dominant
5
Q
Overexpression in what inhibits growth in the disease achondroplasia?
A
Fibroblast growth factor receptor 3 (FGFR3)
6
Q
What bone formation is affected in achondroplasia and which is not? What clinical features are present because of this?
A
Poor endochondral (formation of cartilage matrix then replaced by bone—long bone growth) bone formation with normal intramembranous (formation of bone without a preexisting cartilage matrix—mechanism for flat bone development) bone formation
Short extremities with normal-sized head and chest
7
Q
A congenital defect of bone formation→ structurally weak bone, commonly due to an autosomal dominant defect in collagen type I synthesis…
A
Osteogenesis Imperfecta
8
Q
A 4 year old patient presents with a history of multiple bone fractures. Upon physical exam blue scleras are present and the child has mild hearing loss. What is the most likely diagnosis in this patient?
A
Osteogenesis Imperfecta
9
Q
What causes the appearance of the blue sclera seen in patient with osteogenesis imperfect?
A
Thinning of scleral collagen revealing the underlying choroidal veins
10
Q
An inherited defect of bone resorption that results in abnormally thick, heavy bone that fractures easily…
A
Osteopetrosis
11
Q
What is the cause of osteopetrosis?
A
Poor osteoclast function
12
Q
What mutation leads to a loss of the acidic microenvironment required for bone resorption resulting in osteopetrosis?
A
Carbonic anhydrase II mutation
13
Q
Patient presents with multiple bone fractures, anemia, thrombocytopenia, and leukopenia, vision and hearing impairment, hydrocephalus, and renal tubular acidosis. What is the most likely diagnosis in this patient?
A
Osteopetrosis
14
Q
Why are anemia, thrombocytopenia, and leukopenia with extramedullary hematopoiesis seen in patients with osteopetrosis?
A
Bone replaces marrow
15
Q
Vision and hearing impairment are seen in osteopetrosis, why?
A
Impingement of cranial nerves
16
Q
Why is hydrocephalus seen in patients with osteopetrosis?
A
Narrowing of the foramen magnum
17
Q
Renal tubular acidosis is seen in osteopetrosis, what is the mechanism for this?
A
Carbonic anhydrase II mutation—results in decreased tubular reabsorption of HCO3 leading to metabolic acidosis
18
Q
What is the treatment for osteopetrosis?
A
Bone marrow transplant—osteoclasts are derived from monocytes
19
Q
Defective mineralization of osteoid due to low levels of Vit D causing low serum calcium and phosphate, which are used to form the osteoid from osteoblasts…
A
Rickets-children
Osteomalacia- adults
20
Q
What is required for the activation of Vit D?
A
25-hydroxylation in the liver &
1-a-hydroxylation in the proximal tubule cells of the kidney
21
Q
What are the 3 organs acted upon by Vitamin D to raise serum calcium and phosphate?
A
Intestine
Kidney
Bone
22
Q
What are some causes of Vitamin D deficiency?
A
Decreased sun exposure Poor diet Malabsorption Liver failure Renal failure
23
Q
What is the cause of Rickets and what patient population is it seen in?
A
Low Vit D in children, resulting in abnormal bone mineralization
24
Q
What are the clinical presentations for rickets?
A
Most common in children
25
What causes frontal bossing seen in patients with rickets?
Osteoid deposition on the skull
26
What causes rachitic rosary seen in patients with rickets?
Osteoid deposition at the costochondral junction
27
What causes osteomalacia and in what patient population is it seen?
Low vitamin D in adults
28
What are the laboratory findings seen in patients with osteomalacia?
Decreased calcium
Decreased phosphate
Increased PTH—due to low calcium
Increased alkaline phosphatase
29
A disease where there is a reduction in trabecular bone mass…
Osteoporosis
30
Osteoporosis results in an increase risk of ______ due to porous bone.
Bone fractures
31
At what age is peak bone mass achieved and what is it based on?
```
Age 30
Based on:
-Genetics
-Diet
Exercise
```
32
What increases the rate at which individual’s loss bone mass after they hit their peak bone mass?
Lack of weight-bearing exercise
Poor diet
Decreased estrogen
33
What are the two most common forms of osteoporosis?
Senile
| Postmenopausal
34
What are the clinical features of osteoporosis and how is it distinguished from osteomalacia, which has a similar presentation?
Bone pain and fractures in weight-bearing areas such as:
Vertebrae
Hip
Distal radius
Distinguished from osteomalacia with labs→ calcium, phosphate, PTH, and alkaline phosphate are all normal
In osteomalacia→ calcium and phosphate decreased and PTH and alkaline phosphate are elevated
35
How is bone density measured?
DEXA scan
36
What treatment options for osteoporosis will limit bone loss?
Exercise
Vitamin D
Calcium
37
What treatment option for osteoporosis will induce apoptosis of osteoclasts?
Bisphosphonates
38
What drugs are contraindicated for patients at a high risk of osteoporosis or patient with osteoporosis?
Glucocorticoids—worsen osteoporosis
39
What bone disease is characterized by an imbalance between osteoclast and osteoblast function and is usually seen in late adulthood?
Paget disease of bone
40
What are the three stages of Paget disease of bone and what is the end result?
Osteoclastic
Mixed osteoblastic-osteoclastic
Osteoblastic
End result—thick, sclerotic bone that fractures easily
41
What is seen on biopsy of patients with Paget disease of bone?
Mosaic pattern of lamellar bone—puzzle like
42
A 65 year old male patient presents with bone pain and complaining of increased hat size. Upon physical exam, hearing impairment is found as well as lion-like facies. Labs are drawn and an isolated elevated alkaline phosphatase is found. What is the most likely diagnosis for this patient?
Paget disease of bone
43
What causes the bone pain seen in Paget disease of bone?
Microfractures
44
What causes the increasing hat size seen in Paget disease of bone?
Skull is commonly affected—bone will thicken
45
What causes the hearing loss seen in Paget disease of bone?
Impingement on cranial nerve
46
What cause the Lion-like facies seen in Paget disease of bone?
Involvement of craniofacial bones
47
What disease is the most common cause of isolated elevated alkaline phosphatase in patients who are over the age of 40?
Paget disease of bone
48
Name the two treatment options for Paget disease of bone and the mechanism of each…
Calcitonin—inhibits osteoclast function
| Bisphosphonates—induces apoptosis of osteoclasts
49
What are 2 complications that can occur in patients with Paget disease of bone?
High-output cardiac failure—due to formation of AV shunts in bone
Osteosarcoma—mutation occurs in osteoblasts causing overgrowth
50
Infection of the bone marrow and bone, most often seen in children and commonly caused by bacteria…
Osteomyelitis
51
Where does bacteria seed in children with osteomyelitis?
Metaphysis—transient bacteremia
52
Where does bacteria seed in adults with osteomyelitis?
Epiphysis—open wound bacteremia
53
What is the most common bacteria that causes osteomyelitis?
Staphylococcus aureus
54
Sexually active young adults can contract osteomyelitis through what bacterium?
N. gonorrhoeae
55
Patients who have sickle cell disease can contract osteomyelitis through what bacterium?
Salmonella
56
Diabetics or IV drug users can contract osteomyelitis through what bacterium?
Pseudomonas
57
Osteomyelitis caused by the bacterium Pasteurella is associated with _________.
Car or dog bite/scratches
58
Mycobacterium tuberculosis can cause osteomyelitis involving a specific body part. What is this body part and what is the disease involved?
Vertebrae—Pott disease
59
What are the clinical signs and symptoms of a patient who presents with osteomyelitis?
Bone pain with systemic signs of infection
-fever
-leukocytosis
Lytic focus (sequestrum) surrounded by sclerosis (involucrum) of bone on X-ray
60
How is the diagnosis of osteomyelitis made?
Blood culture
61
Ischemic necrosis of bone and bone marrow caused by trauma, fracture, steroids, sickle cell anemia or caisson disease (Nitrogen gas emboli)…
Avascular necrosis
62
What are the 2 most common complications of avascular necrosis of bone?
Osteoarthritis and fracture
63
Benign tumor of bone…
Osteoma
64
Where is the most common site of an osteoma?
Surface of facial bones
65
What syndrome is associated with osteoma formation?
Gardner syndrome (familial colorectal polyposis)?
66
A Benign tumor of osteoblasts with a rim of reactive bone, seen in patient
Osteoid Osteoma
67
A benign tumor of osteoblasts, arises in the cortex of long bones, and presents as bone pain that resolves with aspirin… What is the significance of knowing the bone pain is controlled with aspirin?
Osteoid Osteoma
Bone pain caused by an osteoblastoma can not be resolved with the use of aspirin
68
What is seen on imaging studies when an osteoid osteoma is present?
Bony mass with a radiolucent core (osteoid)
69
What is similar to an osteoid osteoma but is larger, arises in vertebrae, and presents as bone pain that does NOT respond to aspirin?
Osteoblastoma
70
The most common benign tumor of the bone that presents with an overlying cartilage cap…
Osteochondroma
71
Where does an osteochondroma arise from?
Lateral projection of the growth plate (metaphysis)
72
What can the overlying cartilage of an osteochondroma transform into?
Chondrosarcoma
73
A malignant proliferation of osteoblasts…
Osteosarcoma
74
Age what age range is an osteosarcoma most likely to be present?
Teenagers
75
What are the risk factors from the development of an osteosarcoma?
Familial retinoblastoma
Paget disease
Radiation exposure
76
Where does an osteosarcoma arise from and where are the most common sites of development?
Metaphysis
Distal femur or proximal tibia
77
What are the signs and symptoms upon presentation of an osteosarcoma?
Pathologic fracture or bone pain with swelling
78
What is seen on imaging of a patient with osteosarcoma?
Destructive mass with a sunburst appearance and lifting of the periosteum→ Codman triangle
79
What is seen upon biopsy of an osteosarcoma?
Pleomorphic cells that produce osteoid
80
The only bone tumor that arises form the epiphysis of long bones?
Giant cell tumor
81
What is comprised within a Giant cell tumor?
Multinucleated giant cells and stromal cells
82
What appearance is present upon xray of a giant cell tumor?
Soap-bubble appearance
83
A malignant proliferation of poorly-differentiated cells derived from neuroectoderm…
Ewing sarcoma
84
Where does an Ewing sarcoma arise from and who is most often affected by an Ewing sarcoma?
Arises in the diaphysis of long bones
Male children
85
What appearance is seen on xray of an Ewing sarcoma?
Onion-skin appearance→ due to the layers of periosteum
86
What is seen on biopsy of an Ewing sarcoma and how can it be differentiated from lymphoma or chronic osteomyelitis?
Small, round blue cells that resemble lymphocytes
11:22 translocation is what differentiates it
87
A benign tumor of cartilage…
Chondroma
88
A tumor of cartilage that arises in the medulla of small bones of the hands and feet…
Chondroma
89
A malignant cartilage-forming tumor…
Chondrosarcoma
90
A malignant cartilaginous tumor that arises in the medulla of the pelvis or central skeleton…
Chondrosarcoma
91
What type of carcinoma classically produces osteoblastic lesions?
Prostatic carcinoma
92
What is the most common type of arthritis most often due to wear and tear?
Degenerative joint disease (osteoarthritis)
93
What are the major risk factors for the development of osteoarthritis?
Age (>60)
Obesity
Trauma
94
What are the most common joint affected by osteoarthritis?
```
Hips
Lower lumbar spine
Knees
Distal interphalangeal joints
Proximal interphalangeal joints
```
95
What is the classic presentation for osteoarthritis?
Joint stiffness in the morning that WORSENS during the day—different from rheumatoid arthritis because that gets better with activity
96
What are Heberden and Bouchard nodes?
Pathologic features of osteoarthritis—osteophyte formation that arise in the DIP and PIP, respectively
97
Chronic, systemic autoimmune disease involving the joints and is associated with HLA DR4…
Rheumatoid Arthritis
98
Who are the most common individuals to develop rheumatoid arthritis?
Women of late childbearing age
99
What are the hallmarks of rheumatoid arthritis?
Synovitis leading to the formation of a pannus (inflamed granulation tissue)→ destruction of cartilage and ankylosis of the joint
100
Morning stiffness that improves with activity is a characteristic of what type of arthritis?
Rheumatoid Arthritis
101
What are the common sites of involvement of rheumatoid arthritis and is it usually asymmetric or symmetric?
```
PIP
Wrists
Elbows
Ankles
Knees
```
Symmetric disease
DIP joints are spared unlike with osteoarthritis
102
What are 3 abnormalities found on xray with rheumatoid arthritis?
Joint-space narrowing
Loss of cartilage
Osteopenia
103
Fever, malaise, weight loss, and myalgias are all symptoms of ________ arthritis.
Rheumatoid
104
Seen in rheumatoid arthritis—central zone of necrosis surrounded by epitheliod histiocytes, arise in skin and visceral organs
Rheumatoid nodules
105
Vasculitis, Baker cyst, pleural effusions, lymphadenopathy and interstitial lung fibrosis are all symptoms that can arise from _______ arthritis.
Rheumatoid
106
What autoantibodies are found with rheumatoid arthritis?
IgM autoantibody against Fc portion of IgG
107
What two abnormal substances are found in the synovial fluid of a patient with rheumatoid arthritis?
Neutrophils
| High protein
108
Group of joint disroders characterized by:
Lack of rheumatoid factor
Axial skeleton involvement
HLA-B27 association…
Seronegative Spondyloarthropathies
109
What does Ankylosing spondyloarthritis involve?
Sacroiliac joints and spine
110
A 31 year old male presents with low back pain involving the vertebral bodies which have fused (bamboo spine). Upon physical examination uveitis (inflammation of the middle layer of eye) and aortitis. Echocardiogram is performed and aortic regurgitation is present. What is the most likely diagnosis in this patient?
Ankylosing spondyloarthritis
111
What are the three characteristics of Reiter syndrome?
Arthritis
Urethritis
Conjunctivitis
Cant Pee/Cant See/ Cant climb a tree
112
What two infections are common precursors for Reiter syndrome?
GI or Chlamydia trachomatis infection
113
Disease involving axial and peripheral joints. DIP joints of the hands and feet are most commonly affected→ sausage fingers and toes…
Psoriatic arthritis
114
Arthritis due to N gonorrhoeae or S aureus infection.
Infectious arthritis
115
What is the most common cause of infectious arthritis in young adults?
N gonorrhoeae
116
What is the 2nd most common caused of infectious arthritis in older children and adults?
S aureus
117
Infectious arthritis usually involves just one joint, which is usually the ______.
Knee
118
A 24 year old male patient presents with a warm knee joint that has limited range of motion. Upon exam, patient is found to have fever, increased white count, and elevated ESR. Cultures are performed and the patient is found to have an N gonorrhoeae infection. What is the most likely diagnosis in this patient.
Infectious arthritis
119
A disease characterized by deposition of monosodium urate (MSU) crystals in tissues, especially joints.
Gout
120
What causes gout?
Hyperuricemia→ overproduction or decreased excretion of uric acid
121
What are the 3 diseases associated with secondary gout?
Leukemia and myeloproliferative disorders
Lesch-Nyhan syndrome
Renal insufficiency
122
How does Lesch-Nyhan syndrome cause secondary gout?
X-linked deficiency of hypoxanthine-quanine phosphoribosyltransferase (HGPRT)—used for salvage pathway of purine metabolism products
Presents with mental retardation and self mutilation (bite lips and fingers)
123
What is the mechanism for secondary gout caused my leukemia and myeloproliferative disorders?
Increased cell turnover→ hyperuricemia
124
How does renal insufficiency lead to secondary gout?
Decreased renal excretion of uric acid
125
What is the usual presentation for acute gout? What are the two most common causes of acute gout?
Exquisitely painful arthritis of the great toe(podagra)
Consumption of Alcohol or Meat
126
What can chronic gout lead to?
Development of tophi—white, chalky aggregates of uric acid crystals with fibrosis and giant cell reaction in the soft tissue of joints
Renal failure—urate crystals may deposit in kidney tubules
127
What are the laboratory findings seen with gout?
Hyperuricemia
| Synovial fluid→ needle-shaped crystals with negative birefringence
128
What is pseudogout?
Resembles gout clinically but is due to deposition of calcium pyrophosphate dehydrate (CPPD)
129
What is seen within the synovial fluid with pseudogout?
Rhomboid-shaped crystals with weakly positive birefringenece
130
Patient presents with bilateral proximal muscle weakness, a rash of the upper eyelids, a malar rash, red papules on the elbows, knuckles, and knees. Lab results shoes increased creatine kinase, positive ANA and anti-Jo-1 antibody and perimysial inflammation with perifascicular atrophy on biopsy. What is the most likely diagnosis for this patient?
Dermatomyositis→ inflammatory disorder of the skin and skeletal muscle
131
What is used for the treatment of dermatomyositis?
Corticosteroids
132
Inflammatory disorder of skeletal muscle that does NOT involve the skin?
Polymyositis
133
What are the clinical features of polymyositis?
Resembles dermatomyositis but skin is not involved
| Endomysial infllmmation with necrotic muscle fibers seen on biopsy
134
A degenerative disorder that is characterized by wasting and replacement of skeletal muscle by adipose tissue.
X-linked muscular dystrophy
135
What causes X-linked muscular dystrophy?
Defects of dystrophin gene
136
What is the cause of Duchenne’s muscular dystrophy?
Deletion of dystrophin
137
What is the presentation of Duchenne muscular dystrophy?
Proximal muscle weakness at 1 year of age
Calf pseudohypertrophy
Elevated creatine kinase
138
What are the two most common causes of death with Duchenne muscular dystrophy?
Cardiac or respiratory failure
139
Why does Becker muscular dystrophy present with much milder disease?
Its due to a mutated dystrophin gene and not an absent one, therefore there is still some structural support.
140
Benign tumor of adipose tissue…
Lipoma
141
Malignant tumor of adipose tissue…
Liposarcoma
142
What is the characteristic cell of a liposarcoma?
Lipoblasts
143
Benign tumor of skeletal muscle…
Rhabdomyoma
144
Cardiac rhabdomyoma is associated with what?
Tuberous sclerosis→ genetic disease that causes benign tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin.
145
Malignant tumor of skeletal muscle…
Rhabdomyosarcoma—most common malignant soft tissue tumor in childten
146
What is the characteristic cell of Rhabdomyosarcoma and what is this disease positive for?
Rhabdomyoblasts and is desmin positive
147
What is the most common site for Rhabdomyosarcoma to occur?
Head and neck
Vagina is the classic site in young girls
