1
Q
Achondroplasia
A
- impaired cartilage proliferation at the growth plate
- due to an autosomal dominant activating mutation in FGFR3, which inhibits growth
- most mutations are sporadic and related to increased paternal age; mutations are autosomal dominant with full penetrance; homozygosity is incompatible with life
- presents with short extremities but normal-sized head and chest since endochondral, but not intramembranous, bone formation is impaired
- mental function, life span, and fertility are all unaffected
- the most common cause of dwarfism
2
Q
What is the difference between endochondral and intramembranous bone formation?
A
- endochrondral bone formation utilizes a cartilage skeleton and is the process through which long bones grow
- intramembranous does not involve a cartilage intermediate and is the process through which flat bones grow
3
Q
Osteogenesis Imperfecta
A
- a congenitally defect resulting in structurally weak bone
- usually due to an autosomal dominant defect in COL1A1 or COL1A2, involved in type I collagen synthesis
- presents with multiple fractures, blue sclera because thinning of the scleral collagen reveals underlying choroidal veins, hearing loss because the ossicles fracture easily, and opalescent teeth that wear easily due to lack of dentin
- may be confused with child abuse, but in this case, bruising is absent
4
Q
How can osteogenesis imperfecta be distinguished from child abuse upon examination?
A
osteogenesis imperfecta will present with fractures but bruises will be absent
5
Q
Why does osteogenesis imperfecta present with blue sclera?
A
because thinning of the scleral collagen reveals the underlying choroidal veins
6
Q
Osteopetrosis
A
- an inherited defect of bone resorption, which results in thick, heavy bone that fractures easily
- due to poor osteoclast function, most commonly because of a carbonic anhydrase II mutation, which impairs the ability of osteoclasts to form the acidic microenvironment necessary for resorption
- presents with bone fractures; anemia, thrombocytopenia, and leukopenia with extramedullar hematopoiesis because marrow is replaced by growing bone; vision and hearing impairment as bone growth impinges on cranial nerves; hydrocephalus as bone growth narrows the foramen magnum, and renal tubular acidosis
- x-rays show a “bone-in-bone” appearance
- treatment is a HSCT because osteoclasts are derived from monocytes
7
Q
Which bone disease can be cured with a hematopoietic stem cell transplant? Why?
A
osteopetrosis because it is due to osteoclast malfunction and osteoclasts are derived from the monocyte lineage
8
Q
Osteoclasts are derived form what cell lineage?
A
monocytes
9
Q
Rickets
A
- vitamin D deficiency in children, with resulting hypophosphatemia and hypocalcemia, which leads to defective mineralization of osteoid
- deficiency is most often due to decreased sun exposure, poor diet, malabsorption, liver failure, or renal failure
- typically seen in children under the age of 1
- presents with pigeon-breast deformity (anterior protrusion of the sternum), frontal bossing, rachitic rosary, and bowing of the legs in ambulating children
- labs reveal hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated alkaline phosphatase
- x-rays demonstrate “looser zones” also known as pseudofractures, epiphyseal widening, and metaphysical cupping/fraying
10
Q
Osteoblasts produce what bone product?
A
osteoid
11
Q
What is a Rachitic rosary?
A
- palpable osteoid deposition at the costochondral junction
- a feature of childhood Rickets
12
Q
Osteomalacia
A
- vitamin D deficiency in adults, with resulting hypophosphatemia and hypocalcemia, which leads to defective mineralization of osteoid
- deficiency is most often due to decreased sun exposure, poor diet, malabsorption, liver failure, or renal failure
- osteoclast activity is fine so bone is resorbed and replaced by osteoid, increasing risk for fracture
- labs reveal hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated alkaline phosphatase
- x-rays demonstrate “looser zones” also known as pseudofractures
13
Q
What is alkaline phosphatase?
A
the enzyme expressed by osteoblasts that creates an alkaline microenvironment necessary for the precipiation and deposition of calcium in bone
14
Q
Describe the synthesis of Vitamin D and it’s actions.
A
- normally vitamin D is derived form sun exposure and the diet- it is activated in the liver via 25-hydroxylation and then by 1-a-hydroxylation in the proximal tubule cells of the kidney
- it functions to increase serum calcium and phosphate by increasing absorption from the intestine, reabsorption in the kidney, and resorption of bone
15
Q
Why does liver disease impair vitamin D activity?
A
because the liver is the site of 25-hydroxylation of vitamin D, the first step in activation of vitamin D
16
Q
Why does renal disease impair vitamin D activity?
A
- 1-a-hydroyxlation, the final step of vitamin D activation, is performed by cells in the PCT of the kidney
- additionally, vitamin D acts on the kidney to increase calcium and phosphate reabsorption
- so damage impairs both the activation of and activity of vitamin D
17
Q
Osteoporosis
A
- a reduction in trabecular bone mass defined by a DEXA more than 2.5 SD below normal or by a fragility fracture of the hip or vertebra
- risk is based on peak bone mass around age 30 and the rate of bone loss that follows (based on genetics, weight-bearing exercise, diet, and estrogen); most common in old age and post-menopause
- presents with bone pain and fractures in weight-bearing areas such as the vertebrae, hips, and distal radius
- labs are normal, which helps distinguish osteoporosis from osteomalacia
- treat with exercise, vitamin D, and calcium to limit further bone loss as well as bisphosphates to induce apoptosis of osteoclasts; can also use teriparatide, SERMS, denosumab, and rarely calcitonin
- estrogen therapy is currently not recommended and glucocorticoids are contraindicated
18
Q
How can osteoporosis be distinguished from osteomalacia?
A
- via histology for one
- secondly, labs are normal in those with osteoporosis but abnormal in those with osteomalacia
19
Q
How is bone density measured?
A
via a DEXA scan
20
Q
At what point in our lives is peak bone mass achieved? What determines the level of this peak?
A
- peak is reached in early adulthood around age 30
- determined by genetics, such as vitamin D receptor variants; diet; and exercise
21
Q
At what rate does bone loss after the age of 30 generally occur? What factors modify this rate?
A
- typically loss 1% of bone mass each year
- faster with lack of weight-bearing exercise, poor diet, or decreased estrogen
22
Q
What effect does estrogen have on bone density?
A
it has a protective effect
23
Q
Paget’s Disease of Bone
A
- a localized process that involves one or more bones, but not the entire skeleton, through an imbalance between osteoclast and osteoblast activity
- there are three distinct stages: first there is hyperactivity of osteoclasts and loss of bone; then there is a mixed phase in which both osteoclasts and osteoblasts are hyperactive as osteoblasts realize the bone loss and quickly lay down bad bone to try to make up for it; finally, the osteoclasts burn out and we have an osteoblastic phase
- the end result is thick, sclerotic bone that fractures easily
- presenting with bone pain (micro fractures), increasing hat size, hearing loss, lion-like facies, and an isolated elevated alkaline phosphatase
- complications include high-output cardiac failure, secondary to the formation of AV shunts in bone, and increased risk for osteosarcoma
- histology reveals a mosaic pattern of lamellar bone with frequent cement lines
- treat with calcitonin, which inhibits osteoclast activity, and bisphosphonates, which induce osteoclast apoptosis
24
Q
What is the most common cause of isolated elevated alkaline phosphatase in patients over 40?
A
Paget disease of bone
25
Osteomyelitis
- an infection of the bone and marrow
- S. aureus is the most common cause in general, N. gonorrhoeae (young, sexually active), Salmonella (Sickle cell), Pseudomonas (diabetics or IV drug use), Pasteurella (dog/cat bite/scratch), and M. tuberculosis (Pott disease)
- more common in children for whom the metaphysics is seeded by a transient bacteremia; in adults it usually occurs from seeding of the epiphysis from an open-wound bacteremia
- presents with bone pain and signs of systemic infection
- x-ray reveals a lytic focus surrounded by a ring of reactive bone (i.e. sclerosis), called the sequestrum and involucrum, respectively
- diagnose using blood culture
26
What are the most common organisms that cause osteomyelitis?
- S. aureus is the most common cause in general
- N. gonorrhoeae is seen in sexually active young adults
- Salmonella is seen in those with Sickle cell
- Pseudomonas is seen in diabetics or IV drug abusers
- Pasteurella is associated with cat/dog bites/scratches
- M. tuberculosis spreads to the vertebrae and is known as Pott disease
27
What is the difference between childhood osteomyelitis and osteomyelitis affecting adults?
- in children, the metaphysis is generally seeded during a transient bacteremia
- in adults, the epiphysis is usually seeded by an open-wound bacteremia
28
What is a sequestrum and an involucrum?
- sequestrum is the central, lytic lesion of osteomyelitis
| - the involucrum is a region of sclerotic or reactive bone surrounding it
29
Aseptic Necrosis of Bone
- aka avasulcar necrosis of bone
- a very painful infarction of bone and marrow due to ischemia
- causes include trauma or fracture, steroids, sickle cell, caisson disease (the Bend's), Gaucher disease, and slipped capital femoral epiphysis
- Legg-Calve-Perthes disease is the idiopathic form
- most often involves the femoral head due to insufficiency of medial circumflex femoral artery
- major complications are osteoarthritis and fracture
30
Osteoma
- a benign tumor of bone
- most often arising on the surface of facial bones
- associated with Gardner syndrome (of FAP, fibromatosus in the retroperitoneum, and osteomas of the face)
31
What is Gardner syndrome?
- FAP
- fibromatosus in the retroperitoneum
- osteomas of the face
32
Osteoid Osteoma
- a benign tumor of osteoblasts, which produce osteoid, surrounded by a rim of reactive bone
- occurs mostly in males under the age of 25 in the cortex of long bones (most often the diaphysis)
- classically presents as bone pain that resolves with aspirin
- imaging will reveal a bony mass < 2 cm with a radiolucent core of osteoid
33
How does an osteoblastoma compare to an osteoma?
similar to osteoid osteoma but...
- greater than 2 cm in size
- arises most often in the vertebrae
- and presents as bone pain that does not respond to aspirin
34
Osteoblastoma
- a benign tumor of osteoblasts, which produce osteoid, surrounded by a rim of bone
- occurs predominantly in the vertebrae
- imaging typically reveals a bony mass > 2 cm with a radiolucent core of osteoid
- presents as bone pain that does not respond to aspirin
35
Osteochondroma
- a tumor of bone with an overlying cartilage cap
- arises from a lateral projection of the metaphysis, which then continues growing outward with bone being deposited beneath
- as a result, the bone is continuous with the normal marrow space
- the most common benign tumor of bone
- rarely, the overlying cartilage can transform into a chondrosarcoma
36
What is the most common benign tumor of bone?
osteochondroma
37
Osteosarcoma
- a malignant proliferation of osteoblasts
- greatest incidence is in teenagers, with another rise in prevalence in the elderly (bimodal); risk factors include familial retinoblastoma, Paget disease, radiation exposure, and Li Fraumeni syndrome
- arises in the metaphysis of long bones, most often the distal femur or proximal tibia around the region of the knee
- imaging reveals a destructive mass with a sunburst appearance that lifts the periosteum off the edge of the bone, creating Codman's triangle
- presents with pathologic fractures or bone pain with swelling
- histology reveals pleomorphic cells that produce osteoid
38
What is Codman's triangle?
the angle between the surface of a long bone and the periosteum at the site of an osteosarcoma where the periosteum has been pushed away from the length of the diaphysis
39
Giant Cell Tumor
- a bone tumor composed of multinucleate giant cells and stromal cells
- the only significant tumor that arises in the epiphysis of long bones
- most often in the distal demure or proximal tibia of young adults
- has a soap-bubble appearance on x-ray
- locally aggressive and may recur
40
Which primary bone tumor arises in the epiphysis of bones?
giant cell tumor
41
Ewing Sarcoma
- a malignant proliferation of poorly-differentiated cells derived from neuroectoderm
- arises in the diaphysis of long bones, typically in males less than 15 years of age
- characteristic (11;22) translocation causing fusion protein EWS-FLI 1
- has an "onion-skin" appearance on x-ray since tumor grows in the medullary cavity, pushing on the surface and triggering the periosteum to produce layers of new bone
- biopsy reveals small, round blue cells that resemble lymphocytes; as such it may be confused with lymphoma or osteomyelitis since it may present with fever
- often presents with metastasis but is responsive to chemotherapy
42
What is a t(11;22) mutation indicative of?
Ewing Sarcoma
43
What is a chondroma?
a benign tumor of cartilage that usually arises in the medulla of small bones of the hands and feet
44
What is a chondrosarcoma?
a malignant, cartilage-forming tumor that most often arises in the medulla of the pelvis or central skeleton
45
Where are chondromas and chondrosarcomas most likely to arise?
- chondroma: medulla of small bones in the hands and feet
| - chondrosarcoma: medulla of the pelvis or central skeleton
46
Which cancers classically metastasize to the bone?
PB KTL
- prostate
- breast
- kidney
- thyroid
- lung
47
Which metastatic cancers to the bone are most likely to cause a blastic lesion?
- prostate is classically blastic
| - breast is said to be mixed
48
What type of cartilage forms the articular surface of synovial joints?
hyaline
49
What type of collagen is found in the hyaline cartilage of synovial joints?
type II (car"two"lage)
50
What is the purpose of the synovium lining joint capsules?
secrete a fluid rich in hyaluronic acid to further lubricate the joint
51
Where does synovial fluid come from? What compound is highly concentrated within it for the purpose of additional lubrication?
the synovium produces a fluid rich in hyaluronic acid
52
Osteoarthritis
- the most common type of arthritis, it is a progressive degeneration of articular cartilage due to "wear and tear"
- risk factors include age, obesity, and trauma
- most often affects weight bearing joints and notably affects both DIPs and PIPs but not the MCPs
- presents with joint stiffness in the morning that worsens during the day; can often feel "joint mice" which are fragments of cartilage floating in the joint space
- histology shows disruption of cartilage, eburnation of the subchondral bone ("polishing"), and osteophyte formation, particularly in the DIPs and PIPs
- treat with acetaminophen, NSAIDs, and intra-articular glucocorticoids
53
What are Heberden nodes?
osteophytes of the DIPs
54
What are Bouchard nodes?
osteophytes of the PIPs
55
Rheumatoid Arthritis
- a chronic, systemic autoimmune disease that predominantly affects the joints
- HLA-DR4 haplotype is a risk factor
- joint destruction arises from synovitis causing granulation tissue formation, contributing to a pannus
- that pannus destroys the joint and causes joint fusion and deviation
- joint symptoms are worse in the morning/improve with activity, are symmetric, and spare the DIPs and first CMC
- non-joint signs include malaise, weight loss, myalgia, rheumatoid nodules, lung interstitial fibrosis, pleural effusion, and Baker cysts behind the knee
- rheumatoid factor (IgM against the Fc portion of IgG) is specific but anti-citrullinated peptide is more specific
- synovial fluid contains neutrophils and elevated protein; x-ray will show narrowing of joints, loss of cartilage, and osteopenia
- complications include anemia of chronic disease and secondary amyloidosis
- treat with NSAIDs glucocorticoids, disease-modifying agents (methotrexate, sulfasalazine, hydroxycholoroquine, and leflunomide), and biologics like TNFa inhibitors
56
What is a pannus?
- a form of synovitis in which the synovium becomes thickened by granulation tissue
- responsible for the joint destruction of rheumatoid arthritis
57
Which joints in the fingers are affected by rheumatoid arthritis?
the PIPs; DIPs are usually spared
58
What are the signs & symptoms of rheumatoid arthritis.
- symmetric involvement of the joints with sparing of the DIPs
- morning stiffness that improves with activity
- fever, malaise, weight loss, and myalgias
- rheumatoid nodules (central necrosis surrounded by epithelioid histiocytes on the skin or visceral organs)
- vasculitis
- baker cysts (swelling of bursa behind the knee)
- pleural effusions, LAD, and interstitial lung fibrosis
- joint space narrowing, loss of cartilage, and osteopenia on x-ray
- positive rheumatoid factor
- complications include anemia of chronic disease and secondary amyloidosis
59
What are rheumatoid nodules?
areas of central necrosis surrounded by epithelioid histiocytes on the skin or visceral organs
60
What are Baker cysts?
- a collection of popliteal fluid in the gastrocnemius-semimembranous bursa, commonly in communication with the synovial space
- related to chronic joint disease, especially rheumatoid arthritis
61
What is rheumatoid factor?
IgM against the Fc portion of IgG, which serves as a marker of tissue damage and disease activity in rheumatoid arthritis
62
What are seronegative spondyloarthropathies?
- a group of joint disorders characterized by a lack of rheumatoid factor, axial skeleton involvement, and an association with HLA-B27
- often associated with IBD
63
Ankylosing Spondyloarthritis
- a seronegative spondyloarthropathy (negative rheumatoid factor, axial skeleton involvement, and HLA-B27 association)
- arises in young adult males with low back pain as well as uveitis and aortitis leading to aortic regurgitation
- often see fusion of the vertebrae known as "bamboo spine"
64
Reactive Arthritis
- a seronegative spondyloarthropathy (negative rheumatoid factor, axial skeleton involvement, and HLA-B27 association)
- characterized by a triad of conjunctivitis, urethritis, and arthritis ("can't see can't pee, can't climb a tree")
- most often in young males weeks after a GI, Chlamydia trachomatis, or Campylobacter infection
65
Psoriatic Arthritis
- a seronegative spondyloarthropathy (negative rheumatoid factor, axial skeleton involvement, and HLA-B27 association)
- involves axial and peripheral joints with the DIPs of the hands and feet most commonly affected, leading to "sausage" fingers or toes
66
Infectious Arthritis
- that due to an infectious agent, usually bacterial
- causes include N. gonorrhoeae in young adults (most common) and S. aureus in older children and adults
- classically involves just a single joint, particularly the knee
- presents as a warm joint with limited range of motion, fever, increased white count, and elevated ESR
67
Describe uric acid biosynthesis. How is it eliminated from the body?
- AMP is converted to hypoxanthine and GMP to guanine
- these metabolites are then converted to xanthine and xanthine is converted to uric acid via xanthine oxidase
- uric acid is then moved into the blood and excreted by the kidney
68
Gout
- deposition of monosodium rate crystals in tissue, especially the joints due to hyperuricemia
- primary gout is the most common, but it can also arise in the setting of leukemia or myeloproliferative disorders in which there is increased cell turnover, Lesch-Nyhan syndrome (HGPRT reduces shunting of uric acid precursors through the purine salvage pathway), or renal insufficency (poor elimination)
- acute gout may be precipitated by consumption of alcohol or excessive amounts of meat and presents with painful arthritis of the great toe from crystal deposition and the resulting acute inflammatory reaction
- chronic gout leads to formation of tophi (white, chalky aggregates of uric acid crystals with fibrosis and giant cell reaction in the soft tissue joints) and renal failure due to rate crystal deposition in the tubules
- synovial fluid shows neutrophils and needle-shaped crystals with negative birefringence under polarized light; yellow under parallel light
- treat acute incidents with NSAIDs, glucocorticoids, and colchicine; use xanthine oxidase inhibitors like allopurinol or febuxostat as preventative treatment
69
What is the function of HGPRT?
it is an enzyme, named hypoxanthine-guanine phosphoribosyltransferase, that moves hypoxanthine (from AMP) and guanine (form GMP) into the purine salvage pathway
70
What is Lesch-Nyhan syndrome?
arises from a deficiency of HGPRT, an enzyme in the purine salvage pathway, which presents with gout, mental retardation, and self-mutilation
71
What two things are known to precipitate cases of acute gout? Why?
- alcohol competes with uric acid for excretion
| - dietary meat adds lots of purine precursors that must be eliminated as uric acid
72
What is the name for the painful arthritis of the big toe that is seen in gout?
podagra
73
Chronic gout leads to what two symptoms/complications?
- formation of tophi
| - deposition in renal tubules and renal failure
74
What are tophi? Where are they most likely?
- white, chalky aggregates of uric acid crystals with fibrosis and giant cell reaction in the soft tissue and joints, secondary to chronic gout
- most often on the external ear, olecranon bursa, or Achilles tendon
75
Pseudogout
- a disease that resembles the clinical features of gout but is instead due to the deposition of calcium pyrophosphate dihydrate
- these are rhomboid-shaped crystals with weakly positive birefringence under polarized right; blue under parallel light
- knee is most often affected
- x-ray often demonstrates cartilage calcification (chonedrocalcinosis)
- treat with NSAIDs, colchicine, and glucocorticoids for acute attacks; colchicine is also used for prophylaxis
76
What crystals are found in cases of pseudogout?
rhomboid-shaped, weakly positive birefringent calcium pyrophosphate dihydrate crystals
77
Dermatomyositis
- an inflammatory disorder of the skin and skeletal muscle
- etiology is unknown but there is an association with carcinoma, particularly gastric carcinoma
- presents with bilateral proximal muscle weakness as well as three types of rash: affecting the upper eyelids (heliotrope), malar rash, and red papule on the elbows, knuckles, and knees known as Gottron papules
- labs find positive ANA and elevated creatine kinase but most important is anti-Jo-1 antibody; also anti-SRP and anti-Mi-2 antibodies
- histology demonstrates perimysial inflammation (CD4) with perifascicular muscle fiber atrophy
- treat with corticosteroids followed by long-term immunosuppression like methotrexate
78
What are Gottron papule?
red papule on the knuckles, elbows, and knees in those with dermatomyositis
79
What is anti-Jo-1 antibody a feature of?
dermatomyositis
80
Malar rash and positive ANA can be seen in those with lupus as well as what MSK disorder?
dermatomyositis
81
Polymyositis
- an inflammatory disorder of skeletal muscle
- resembles dermatomyositis clinically in that there is proximal muscle weakness but there is no skin involvement
- most often involves the shoulders
- histology reveals endomysial inflammation (CD8) with necrotic muscle fibers
82
How can dermatomyositis and polymyositis be differentiated clinically and histologically?
- clinically: polymyositis doesn't present with skin involvement like dermatomyositis does
- histologically: polymyositis is characterized by endomysial inflammation by CD8 cells with atrophy whereas dermatomyositis is characterized by perimysial inflammation by CD4 cells with atrophy
83
X-Linked Muscular Dystrophy
- a degenerative disorder characterized by muscle wasting and replacement of skeletal muscle by adipose
- due to an X-Linked recessive defect in the dystrophin gene, which encodes a protein important for anchoring the muscle cytoskeleton to the ECM
- mutations are often spontaneous and relatively common because the dystrophin gene is incredibly large; often a frameshift mutation that causes truncation of the protein product
- Duchenne presents with proximal muscle weakness at 1 year of age (begins in pelvic girdle and progresses superiorly), calf pseudo hypertrophy, and elevated creatinine kinase and aldolase
- Gower maneuver often seen, in which patients use upper extremities to help them stand, as is a waddling gait
- diagnosis is confirmed by Western blot
- those with Duchenne die due to cardiac (dilated cardiomyopathy) or respiratory failure secondary to replacement of the necessary muscles, including myocardium, with adipose
84
What do most with Duchenne's muscular dystrophy die of?
cardiac or respiratory failure after the necessary muscles for either system are replaced by adipose
85
Myasthenia Gravis
- a disease characterized by autoantibodies against the post-synaptic ACh receptor at the neuromuscular junction and inhibit activation
- presents with muscle weakness, particularly affecting the eyes, that worsens with use and improves with rest; ptosis and diplopia are classic signs
- associated with thymus hyperplasia or thymoma, and in these cases a thymectomy improves the symptoms of myasthenia gravis
- use an edrophonium test for diagnosis and to determine if functional decline during treatment is due to too big or too small a dose of long-acting acetylcholinesterase inhibitors
- more common in women
86
Lipoblasts are characteristic of what pathology?
liposarcoma
87
What are the most common benign and malignant soft tissue tumors in adults? What is the most common malignant soft tumor in children?
- adult benign: lipoma
- adult malignant: liposarcoma
- child malignant: rhabdomyosarcoma
88
Cardiac rhabdomyoma is associated with what disease?
tuberous sclerosis
89
Rhabdomyosarcoma?
- a malignant tumor of skeletal muscle and the most common malignant soft tissue tumor in children
- characteristic cell is desman-positive rhabdomyoblasts
- commonly seen in the head or neck; and in the vagina of young girls ("grape-like" mass)
90
Lambert-Eaton syndrome
- a disease characterized by antibodies against pre-synaptic calcium channels of the NMJ, leading to impaired ACh release
- arises as a paraneoplasic syndrome in cases of small cell carcinoma of the lung
- presents with proximal muscle weakness that usually spares the eyes and that improves with use
- acetylcholinesterase agents do not improve symptoms
- resolves with resection of the cancer
91
How does Lambert-Eaton syndrome differ from myasthenia gravis?
- Lambert-Eaton is the result of antibodies against presynaptic calcium channels at the NMJ instead of post-synaptic ACh receptors
- Lambert-Eaton won't improve with acetylcholinesterase inhibitors but will improve with use
- Lambert-Eaton usually spares the eyes
92
What is the anterior drawer sign?
an anterior gliding of the tibia indicative of ACL injury
93
What is the posterior drawer sign?
a posterior gliding of the tibia indicative of PCL injury
94
Where is the ACL located?
it extends from the lateral femoral condyl to the anterior tibia
95
How are the ACL and PCL named?
according to their relative position where they insert on the tibia
96
Where is the PCL located?
it extends form the medial femoral condyl to the posterior tibia
97
What sort of knee injury does abnormal passive abduction indicated?
it indicates an MCL tear
98
How would you identify a LCL tear of the knee during a physical exam?
it would show up as abnormal/excessive passive adduction of the knee
99
Describe the McMurray test and how it should be interpreted.
- a test used to identify a tear in either the medial or lateral meniscus
- the foot or tibia is rotated during flexion and extension of the knee while the patient is on his back
- pain or popping with external rotation indicates a medial meniscal tear
- pain or popping with internal rotation indicates a lateral meniscal tear
100
How would you test for a medial meniscal tear?
with external rotation during the McMurray test
101
What is the "unhappy triad" of knee injury?
- classically involves damage to the ACL, MCL and medial meniscus following a lateral force applied to a planted leg
- however, lateral meniscus tear is more common
- presents with knee pain and signs of instability
102
Prepatellar Bursitis
- inflammation of the knee's largest sac of synovial fluid
| - caused by repeated trauma or pressure from excessive kneeling
103
What muscles make up the rotator cuff?
SItS- superspinatus- infraspinatus- teres minor- subscapularis
104
What is the location, function, and innervation of the superspinatus muscle.
- it originates from the supraspinatous fossa of the scapula and inserts on the superior facet of the greater tubercle of the humerus (it is the superior muscle of the rotator cuff)
- it functions to abduct the arm until the deltoid takes over
- it is innervated by the suprascapular nerve off the upper trunk of the brachial plexus (C5,C6)
105
Which rotator cuff muscle is most often injured? Why?
the supraspinatous because it is commonly impinged upon while running through the subacromial space, leading to tendinopathy and tear
106
The empty/full can test is used to assess what muscle?
the supraspinatus of the rotator cuff
107
What is the location, function, and innervation of the infraspinatus muscle.
- it originates from the infraspinatus fossa of the scapula and inserts on the middle facet of the greater tubercle of the humerus (it is a posterior muscle of the rotator cuff)
- it laterally rotates the arm
- it is innervated by the suprascapular nerve off the upper trunk of the brachial plexus (C5,C6)
108
Pitching injuries often damage which portion of the rotator cuff?
the infraspinatus, responsible for laterally rotating the arm
109
What is the location, function, and innervation of the teres minor muscle.
- it originates from the lateral border of the inferior scapula and inserts on the inferior facet of the greater tubercle of the humerus (it is a posterior muscle of the rotator cuff)
- it adducts and laterally rotates the arm
- it is innervated by the axillary nerve
110
What is the location, function, and innervation of the subscapularis muscle.
- it originates from the subscapular fossa (anterior surface) and inserts on the lesser tubercle of the humerus (it is the anterior muscle of the rotator cuff)
- it adducts and medially rotates the arm
- it is innervated by the upper and lower sub scapular nerves
111
The rotator cuff primarily receives it's innervations from where?
C5 and C6
112
Medial Epicondylitis
- aka golfer's elbow
- it is an inflammation of the wrist flexor tendons that connect to the medial epicondyle
- due to repetitive flexion (forehand)
- presents with pain near the medial epicondyle
113
Lateral Epidondylitis
- aka tenis elbow
- it is an inflammation of the wrist extensor tendons that connect to the lateral epicondyle
- due to repetitive extension
- presents with pain near the lateral epicondyle
114
Name the wrist bones and their order.
So Long To Pinky, Here Comes The Thumb (towards pinky then towards thumb)
- Scaphoid, Lunate, Triquetrum, Pisiform (thumb to pinky)
- Hamate, Capitate, Trapezoid, Trapezium (pinky to thumb)
115
Which carpal bone is located in the anatomic snuff box?
the scaphoid
116
Which carpal bone is most commonly fractured?
the scaphoid
117
Scaphoid Fracture
- the most common carpal to be fractured
- usually from a fall onto an outstretched hand
- retrograde blood supply means that the bone is prone to avascular necrosis following a fracture
118
Which carpal bone may dislocate and cause an acute carpal tunnel syndrome?
the lunate
119
Which carpal bone, if damaged, can also injure the ulnar nerve?
the hook of the hamate
120
What runs beneath the hook of the hamate bone?
the ulnar nerve
121
Carpal Tunnel Syndrome
- entrapment of the median nerve in the carpal tunnel, which compresses the nerve
- presents with paresthesia, pain, and numbness in the distribution of the median nerve (i.e. palmar surface of lateral 3.5 fingers and hand plus dorsal surface of those same 3.5 fingers) as well thenar eminence atrophy without loss of sensation
- associated with repetitive use, pregnancy, rheumatoid arthritis, hypothyroidism, diabetes, and dialysis-related amyloidosis
122
Why does the thenar eminence atrophy without loss of sensation in those with carpal tunnel syndrome?
the motor nerve supplying the thenar eminence (recurrent branch of the median) arises after the median nerve passes through the carpal tunnel but the palmar cutaneous branch of the median nerve enters the hand external to the carpal tunnel to supply sensory innervation of the thenar eminence
123
Guyon Canal Syndrome
- compression of the ulnar nerve at the wrist or hand
- classically seen in cyclists due to pressure from the handlebars
- presents with paresthesia, pain, and numbness in the distribution of the median nerve
124
What would cause axillary nerve injury and how would it present?
- most likely damaged by a fracture of the surgical neck of the humerus or anterior dislocation of the humerus
- presents with flattened deltoid, loss of arm abduction past 15 degrees, and loss of sensation over the deltoid muscle and lateral arm
125
Which nerves and arteries would most likely be injured by the following humeral fractures:- surgical neck- midshaft- supracondylar- medial epicondyle
- surgical neck: axillary nerve and posterior circumflex humeral artery
- midshaft: radial nerve and deep brachial artery
- supracondylar: median nerve and brachial artery
- medial epicondyle: ulnar nerve and ulnar collateral artery
126
What would cause musculocutaneous nerve injury and how would it present?
- caused by compression of the upper trunk in the brachial plexus
- presents with loss of forearm flexion and supination, since is supplies motor innervation for the anterior arm, and a loss of sensation over the lateral forearm
127
What would cause radial nerve injury and how would it present?
- most likely caused by a midshaft fracture of the humerus or compression of the axilla (e.g. Saturday night palsy)
- presents with wrist drop, reduced grip strength, and loss of sensation over the posterior arm and forearm as well as over the dorsal hand
128
Why does ulnar nerve injury cause a reduction in grip strength?
because wrist extension is necessary for maximal action of flexors
129
What would cause median nerve injury and how would it present?
- proximal injury from supracondylar fracture of the humerus or distal injury from carpal tunnel or wrist laceration
- "Pope's blessing" and from loss of wrist flexion, flexion of the lateral fingers, thumb opposition, and lumbricals of the 2nd and 3rd digits when trying to make a fist
- loss of sensation over the dorsal and palmar aspects of the later 3.5 fingers as well as thenar eminence with a proximal lesion
- positive Tinel sign (tingling to percussion)
130
What is the Tinel sign?
a tingling to percussion, especially in the distribution of the median nerve in those with carpal tunnel syndrome
131
What would cause ulnar nerve injury and how would it present?
- fracture of the medial epicondyle of the humerus or hook of the hamate are most likely
- presents with an "ulnar claw" when trying to extend the digits and radial deviation of the wrist upon flexion
- loss of wrist flexion, flexion of the medial fingers, abduction and adduction of the fingers, actions of medial 2 lumbical muscles
- loss of sensation over medial 1.5 fingers including hypothenar eminence
132
What would cause damage to the recurrent branch of the median nerve and how would it present?
- most likely from a superficial laceration of the palm
- presents with "ape hand" with loss of thenar muscle group preventing opposition, abduction, and flexion of the thumb
- no loss of sensation
133
Describe the cutaneous innervation of the arm as seen on page 419 of FA.
- axillary nerve supplies the lateral shoulder
- radial nerve supplies the lateral arm just above the elbow
- musculocutaneous nerve supplies the lateral forearm
- intercostobrachial nerve supplies the medial arm just distal to the axilla
- medial brachial cutaneous supplies the medial arm distal to the intercostobrachial to just above the elbow
- medial antebrachial cutaneous supplies the medial forearm
134
Describe the cutaneous innervation of the hand as seen on page 419 of FA.
- the ulnar nerve supplies the medial 1.5 fingers as well as the palm and dorsal surface
- the median nerve supplies the lateral 3.5 fingers and the lateral palmar surface
- the radial nerve supplies the dorsal surface of the lateral hand
135
Erb Palsy
- also known as "waiter's tip"
- due to traction or tear of the upper trunk damaging the C5 and C6 roots
- caused in infants by lateral traction on the neck during delivery and in adults by trauma that bends the head away toward the opposite shoulder
- presents with weakness in the deltoid, supraspinatus, infraspinatus, and biceps brachii
- unable to abduct, laterally rotate, flex, or supinate the arm, so the arm hands by their side, medially rotate, extended, and protonated)
136
Describe the nerve roots that contribute to the axillary, musculocutaneous, radial, median, and ulnar nerves.
pneumonic: A, MU, all
- axillary: 5, 6
- musculocutaneous: 5, 6, 7
- radial: all (C5-T1)
- median: all (C5-T1)
- ulnar (C8-T1)
137
Klumpke Palsy
- due to traction or tear of the lower trunk damaging the C8 and T1 roots
- caused in infants by upward force on the arm during delivery and in adults by trauma as if grabbing a tree branch to break one's fall
- presents with weakness in the intrinsic muscles of the hand (lumbricals, interossei, thenar, and hypothenar)
- result is total claw hand since lumbricals normally flex MCP joints and extend DIPs and PIPs
138
Thoracic Outlet Syndrome
- a compression of the lower trunk and subclavian artery
- caused by a cervical rib or Pancoast tumor
- has the same muscle defects of Klumpke palsy with weakness in the intrinsic muscles of the hand (lumbricals, interossei, thenar, and hypothenar)
- presents with "total claw hand" as well as atrophy of the intrinsic hand muscles plus ischemia, pain, and edema due to vascular compression
139
Winged Scapula
- caused by lesion to the long thoracic nerve during axillary node dissection or stab wound
- results in a defect of the serratus anterior muscle
- which presents as the inability to anchor one's scapula to the thoracic cage; and therefore cannot abduct arm above a horizontal position
140
Describe "ulnar claw" and what causes it.
can't extend the fourth and fifth digits due to distal ulnar nerve injury
141
Which nerves supply the thenar and hypothenar eminences?
- thenar: median nerve
| - hypothenar: ulnar
142
What is the function of the lumbrical muscles?
they flex the MCP and extend the DIP and PIP
143
Describe "pope's blessing" hand and what causes it.
inability to flex the first three digits because of proximal median nerve injury
144
Describe "median claw" hand and what causes it.
inability to flex the first three digits because of distal median nerve injury
145
What would cause the "OK gesture" hand?
inability to flex the fourth and fifth digits because of proximal ulnar nerve injury
146
What are the hypothenar muscles?
- muscles in the medial palm, which are supplied by the ulnar nerve
- includes opponens digiti minimi, abductor digiti minimi, and flexor digiti minimi brevis
147
What are the thenar muscles?
- muscles in the lateral palm which are supplied by the median nerve
- includes the opponens pollicis, abductor pollicis brevis, and the flexor pollicis brevis
148
What is the function of the dorsal and palmar interossei muscles?
the dorsal muscles abduct the fingers and the palmar muscles adduct the fingers
149
What would lead to an injury of the obturator nerve and how would it present?
- most likely damaged during pelvic surgery
- originates from L2-L4 and therefore presents with decreased sensation of the medial thigh and impaired adduction of the leg
150
What would lead to an injury of the femoral nerve and how would it present?
- most likely damaged during a pelvic fracture
| - originates from L2-L4 and would present with poor flexion of the thigh and impaired leg extension
151
What would lead to an injury of the common peroneal nerve and how would it present?
- caused by trauma or compression of the lateral aspect of the leg or by a fibular neck fracture
- originates from L4-S2 and would present with foot drop, "steppage gait," and loss of sensation on the dorsal of the foot
- Peroneal Everts and Dorsiflexes; if injured, foot dropPED
152
What would lead to an injury of the tibial nerve and how would it present?
- most likely from knee trauma, Baker cyst, or tarsal tunnel syndrome (more distally)
- originates from L4-S3 and would therefore present its an inability to curl toes and loss of sensation on sole of foot
- the more proximal injuries in the knee would also results in a foot that was everted at rest with loss of inversions and plantarflexion
- Tibial Inverts and Plantarflexes; if injured can't stand on TIP toes
153
What would lead to an injury of the superior gluteal nerve and how would it present?
- most likely iatrogenic during an intramuscular injection to the upper medial gluteal region
- originates from L4-S1 and would therefore present with a positive Trendelenburg sign: pelvis tilt because weight-bearing leg cannot maintain alignment through hip abduction with drop arising on the contralateral side
154
What nerve is most likely damaged by doing the course of an intramuscular injection to the upper medial gluteal region?
the superior gluteal nerve (L4-S1)
155
What is a positive Trendelenburg sign?
- also known as hip drop
- it arises from an injury to the superior gluteal nerve in the upper medial gluteal region
- presents with pelvic tilt because weight-bearing leg cannot maintain alignment of the pelvis through hip abduction
- hip drops to the side contralateral the injury
156
What would lead to an injury of the inferior gluteal nerve and how would it present?
- most likely arising from posterior hip dislocation
- arises from L5-S2 and presents with difficulty climbing stairs or rising from a seated position due to loss of hip extension
157
What muscles do the superior and inferior gluteal nerves innervate?
- superior: gluteus medius, gluteus minimus, and tensor fascia latae
- inferior: gluteus maximus
158
Describe innervation of the posterior thigh and leg.
the sciatic nerve, arising from L4-S3 innervates the posterior thigh, and then splits into the common perineal and tibial nerves
159
What is the clinical significance of the pudendal nerve?
- arising from S2-S4, it innervates the perineum
- as such, it is often blocked with local anesthetic during childbirth, using the ischial spine as a landmark for injection
160
Where should intramuscular gluteal injections be given to avoid nerve injury?
given in the superolateral gluteal quadrant, avoiding the superior gluteal nerve
161
What nerve and artery pair extends from the axilla down the lateral thorax?
- long thoracic nerve
| - lateral thoracic artery
162
What nerve and artery pair is grouped at the surgical neck of the humerus?
- axillary nerve
| - posterior circumflex humeral artery
163
What nerve and artery pair runs through the cubital fossa?
- median nerve
| - brachial artery
164
What nerve and artery pair runs through the popliteal fossa?
- tibial nerve
| - popliteal artery
165
What nerve and artery pair runs behind the medial malleolus?
- tibial nerve
| - posterior tibial artery
166
In which direction do intervertebral discs usually herniate? Why?
- they typically herniate posterolaterally
- this is due to the thin posterior longitudinal ligament and thicker anterior longitudinal ligament along the middling of the vertebral bodies
167
How do radiculopathies generally present?
paresthesia and weakness in the distribution of the specific lumbar or sacral spinal nerves
168
Herniation of the L3-L4 disc causes deficits in the pattern of which spinal nerve?
L4; disc herniations tend to affect the nerve associated with the inferior vertebral body
169
What are the signs of an L3-L4 radiculopathy?
weakness of knee extension and diminished patellar reflex
170
What are the signs of an L4-L5 radiculopathy?
weakness of dorsiflexion with difficulty in heel-walking
171
What are the signs of an L5-S1 radiculopathy?
weakness of plantarflexion with difficulty in toe-walking and a poor achilles reflex
172
What are T-tubules?
deep invaginations of the plasma membrane of skeletal and cardiac muscle cells, which are in association with terminal cisternae (enlarged areas of sarcoplasmic reticulum)
173
What is the sarcoplasmic reticulum?
a membrane-bound structure in skeletal and cardiac muscle cells with the primary purpose of storing calcium
174
What is a skeletal muscle triad? What is the equivalent in cardiac muscle cells?
- a triad is the collection of 1 t-tubule in association with two terminal cisternae of the sarcoplasmic reticulum
- in cardiac muscle, the t-tubule is associated with only one terminal cisternae and this unit is referred to as a dyad
175
How many terminal cisternae are in association with one t-tubule in skeletal and cardiac muscle cells?
- triad of skeletal muscle: 1 t-tubule + 2 terminal cisternae
- dyad of cardiac muscle: 1 t-tubule + 1 terminal cisternae
176
What is a myofibril?
the functional unit of a muscle cell with is formed predominantly by actin and myosin
177
Describe the events that lead to muscle contraction?
- an action potential depolarizes presynaptic voltage-gated calcium channels, inducing release of acetylcholine
- acetylcholine binds to the postsynaptic nicotinic receptors at the NMJ and depolarize the motor end plate
- this depolarization travels along the muscle cell and down the t-tubule, associated with terminal cisternae
- this causes depolarization of voltage-sensitive dihydropyridine receptors, mechanically coupled to ryanodine receptors on the sarcoplasmic reticulum
- both receptors experience a conformational change, allowing calcium release from the sarcoplasmic reticulumm
- the calcium that is released, binds troponin C, causing a conformational change that moves tropomyosin out of the myosin-binding groove on actin filaments
- myosin releases bound ADP and Pi, and this displacement leads to the power stroke
- myosin then binds a new ATP molecule, which triggers detachment of the myosin head form the actin filament
- with hydrolysis of ATP to ADP + Pi, the myosin adopts a high-energy position for the next contraction cycle
178
What are ryanodine receptors?
voltage-gated calcium channels in the membrane of the sarcoplasmic reticulum, responsible for releasing calcium when muscle cells are depolarized
179
What event is associated with the myosin power stroke?
release of ADP and Pi
180
What even is associated with detachment of the myosin head from the actin filament?
binding of a new ATP molecule
181
What is troponin?
a calcium-sensitive protein that inhibits the interaction between myosin and actin during times of muscle relaxation
182
What are the specific functions of troponin T, I, and C?
- troponin C is the calcium sensor
- troponin I inhibits cross-bridging
- troponin T binds tropomyosin
183
What is the dihydropyridine receptor?
a voltage-sensitive receptor in the T-tubule that is mechanically coupled to ryanodine receptors
184
Describe the following components of the sarcomere:
- A band
- H band
- I band
- M line
- Z line
- A band: the enter length of the thick filaments, centered on the M-line
- H band: the area, near the m-line, of thick filaments not superimposed by thin filaments
- I band: the area, near the z-line, of actin filaments not superimposed by thick filaments
- M line: the line in the center of the sarcomere where myosin tails are cross-linked
- Z line: the dark line that defines the bounds of the sarcomere, where actin filaments are anchored
185
How does muscle contraction affect the length of the A, H, and I bands of the sarcomere?
- the A band is always the same length, regardless of contraction
- the H and I bands, shorten during contraction
186
What are the characteristics of type I muscle fibers?
- they are also known as slow twitch fibers
- they are red from increased mitochondria and myoglobin concentration; as such, they rely on oxidative phosphorylation
- they are important for sustained contraction
- the proportion of type I fibers increases with endurance training
187
What are the characteristics of type II muscle fibers?
- they are also known as fast twitch fibers
- they are white because they have less mitochondria and less myoglobin; this is because they rely on anaerobic glycolysis
- they are important for maximal strength
- the proportion of type II fibers increases with weight/resistance training
188
Describe the mechanism for smooth muscle relaxation.
- agonist binds a receptor on the endothelial cell and induces an increase in intracellular calcium
- this calcium activates or increases expression of NOS, which converts L-arginine to nitric oxide
- NO diffuses into the surrounding smooth muscle and causes an increase in cGMP levels
- cGMP then activates myosin-light-chain phosphatase, which dephosphorylates the myosin regulatory chain and impairs contraction
189
What is the precursor to nitric oxide?
L-arginine
190
Describe the mechanism for smooth muscle contraction..
- an action potential arrives and depolarizes the cell membrane
- this opens L-type voltage-gated calcium channels
- there is an associated rise in calcium-calmodulin complexes, which active the myosin-light-chain kinase
- phosphorylation of myosin, then allows for contraction
191
What is the myosin-light-chain kinase?
an enzyme, activated by the calcium-calmodulin complex, which phosphorylates the regulatory light-chain of myosin and allows for muscle contraction
192
What is the myosin-light-chain phosphatase?
an enzyme, activated by cGMP, that dephosphorylates the regulatory light-chain of myosin and allows for muscle relaxation
193
What are woven and lamellar bone?
- woven bone is that first laid down by osteoblasts
| - lamellar bone is reorganized, stronger bone that replaces the woven bone
194
Osteoblasts and osteoclasts are derived from what stem cell population?
- osteoblasts differentiate from mesenchymal stem cells in the periosteum
- osteoclasts differentiate from fusion of monocyte and macrophage lineage precursors
195
Osteoclasts use primarily what two proteins for bone resorption?
carbonic anhydrase II to create an acidic microenvironment and collagenases
196
What is the effect of pulsatile PTH and continuous PTH?
- pulsatile exerts an anabolic effect on bone
| - continuous causes catabolism of bone
197
Through what mechanism is estrogen protective of bone mass?
it inhibits apoptosis of osteoblasts and induces apoptosis in bone-resorbing osteoclasts
198
How does PTH stimulate osteoclast activity?
it activates osteoblasts, which then release RANK-L, a protein that binds RANK receptors expressed by osteoclasts, promoting reabsorption
199
What is osteoprotegrin?
a decoy receptor for RANK-L secreted by osteocytes
200
What is RANK-L?
a protein released by osteoblasts in response to PTH, which then induces differentiation and activation of osteoclasts
201
What are Haversian and Volkmann's canals?
- Volkmann's canals are those that penetrate the bone from the periosteum and supply Haversian canals
- Haversian canals are located at the center of an osteon, surrounded by lamellar bone and supply that bone
202
What are the lacunae and canaliculi of bone?
- canaliculi are the small channels through which osteocytes project and connect with one another
- lacunae are the small cavities in which osteocyte soma reside
203
What is denosumab?
a monoclonal antibody against RANKL, used for the treatment of osteoporosis
204
Vertebral Compression Fracture
- an indicator of osteoporosis
| - presents with acute back pain, loss of height, and kyphosis
205
What three fractures are most common in those with osteoporosis?
- vertebral compression fracture
- colles fracture of the distal radius
- fracture of the femoral neck
206
Hypervitaminosis D
- caused by over supplementation or granulomatous disease
| - labs show elevated serum calcium and phosphate with low PTH
207
What is the most specific marker for rheumatoid arthritis?
anti-cyclic citrullinated peptide antibody
208
How is osteoarthritis treated?
acetaminophen, NSAIDs, and intra-articular glucocorticoids
209
What is Felty syndrome?
a triad of neutropenia, splenomegaly, and rheumatoid arthritis
210
What are the layers of the epidermis and their defining features?
- basalis: stem cell population
- spinosum: desmosomes between keratinocytes
- granulosum: granules in keratinocytes
- corneum: keratin in anucleated cells
211
Atopic Dermatitis
- aka eczema
- a type I hypersensitivity reaction associated with asthma and allergic rhinitis
- characterized by a pruritic, erythematous, oozing rash with vesicles and edema
- usually appears on the face in infancy and then migrates to the antecubital fossae
- most often affects the face and flexor surfaces
212
Contact Dermatitis
- a type IV hypersensitivity
- induced by irritant chemicals, drugs, and substances like poison ivy and nickel jewelry
- presents with a pruritic, erythematous, oozing rash with vesicles and edema
- treat by removing the offending agent and applying topical glucocorticoids
213
Acne Vulgaris
- a skin condition characterized by a progression or collection of comedones, pustules, and nodules
- comedones are colloquially referred to as white and black heads; they arise from androgen-induced upregulation of sebum production by sebaceous glands, which causes an excess of keratin, blocking follicles
- Propionibacterium acnes infection produces lipases, which break down the sebum and release pro-inflammatory fatty acids, resulting in pustule formation
- scarring of pustules lead to nodules
- treat with benzoylperoxide (an antimicrobial) and vitamin A derivatives, which reduce keratin production
214
What causes comedones formation during puberty?
sebaceous glands express androgen receptors, and up regulate sebum production in response to rising estrogen levels, which then leads to a keratin blockage and buildup of sebum
215
What is Propionibacterium acnes?
a bacteria that infects comedones, expresses lipases, and releases pro-inflammatory fatty acids to form pustules from comedones
216
Psoriasis
- due to excessive keratinocyte proliferation
- associated with HLA-C and often arises in areas of trauma, suggesting an environmental trigger
- characterized by well-circumscribed, salmon-colored plaques with a silvery scale, classically on extensor surfaces and the scalp; may also present with pitting of nails
- histology reveals acanthosis, parakeratosis, collections of neutrophils in the stratum corneum called Munro micro abscesses, and a thinning of epidermis above elongated dermal papillae
- because of this epidermal thinning, bleeding occurs when the scale is picked off, known as the Auspitz sign
- treat with corticosteroids, UV light + psoralen, or immune modulating therapy
217
What is PUVA?
- a combination of psoralen and UVA light used to treat psoriasis
- psoralen increases the absorption of the UVA light by the keratinocytes
218
Why is UV light used to treat psoriasis?
because the disease process is defined by excessive keratinocyte proliferation and UV light will damage keratinocytes
219
What is an Auspitz sign?
bleeding when a psoriatic scale is picked off
220
What is a Munro microabscess?
a collection of neutrophils in the stratum corneum of patients with psoriasis
221
What is acanthosis?
another name for epidermal hyperplasia
222
What is parakeratosis?
a term used to describe hyperkeratosis with retention of keratinocyte nuclei in the stratum corneum
223
Lichen Planus
- a pruritic, planar, polygonal, purple, papular rash, often with reticular white lines on the surface, called Wickham striae
- commonly involves the oral mucosa, wrists, and elbows
- histology shows inflammation of the dermal-epidermal junction with a "saw-tooth" appearance and lymphocytic infiltration
- etiology is unknown but there is an association with chronic HCV infection
- 6 P's: pruritic, purple, polygonal, planar papules and plaques
224
What are Wickham striae?
the reticular white lines on the surface of lichen planus papules
225
Pemphigus Vulgaris
- autoimmune destruction of desmosomes between keratinocytes in the stratum spinosum
- a type II hypersensitivity mediated by IgG against desmoglein which causes a separation of the spinosum from the basalis; the basalis remains attached to the BM via intact hemidesmosomes
- presents with skin AND oral mucosa bullae which are thin-walled, weak, and easily rupture, leading to shallow erosions with dried crust
- positive nikolsky sign
- immunofluorescence highlights IgG surrounding keratinocytes in a "net-like" pattern
226
Bullous Pemphigoid
- autoimmune destruction of hemidesmosomes that attach the stratum basalis to the basement membrane
- mediated by IgG against a hemidesmosome component known as BP180 in the BM
- the basalis separates form the basement membrane
- blisters spare the oral mucosa and are thick, so the bullae do not rupture easily
- negative nikolsky sign
- immunofluorescence highlights IgG in a linear pattern following the basement membrane
227
What are the differences between pemphigus vulgarisms and bulls pemphigoid?
- PV results from IgG against demosomes, whereas BP results form IgG against hemidesmosomes
- PV results in blisters with separation between the basalis and spinosum whereas BP is between the basalis and basement membrane
- PV bullae are thin-wall, easily ruptured, and affect the oral mucosa whereas BP bullae are thick-walled, difficult to rupture, and spare the oral mucosa
- PV demonstrates a "net-like" pattern of immunofluorescence whereas BP demonstrates a linear pattern
228
Dermatitis Herpetiformis
- groups of pruritic vesicles and bullae
- due to autoimmune deposition of IgA at the tips of dermal papillae
- have a strong associated with celiac disease and in those cases, will resolve with diet restriction
- treat with dapsone
229
Erythema Multiforme
- a hypersensitivity reaction characterized by a targetoid rash and bullae
- targetoid because they represent areas of central epidermal necrosis surrounded by erythema
- associated most often with HSV, but also mycoplasma, drugs (PCN and sulfonamides), autoimmune diseases like SLE, and malignancy
- if it involves the oral mucosa or lip and is accompanied by a fever, it is known as Stevens Johnson syndrome with diffuse sloughing of skin, resembling a large burn
230
What is do we call the milder form of SJS and the more severe form of SJS? How are they all differentiated?
- milder: erythema multiform (no oral/mucosal involvement and no fever)
- more severe: toxic epidermal necrolysis (greater percentage of skin affected)
231
Seborrheic Keratosis
- a benign squamous proliferation
- presents as a raised, discolored plaque on the extremities or face and has a "stuck on" appearance
- histology demonstrates keratin pseudocysts
- the sudden onset of multiple is known as Leser-Trelat sign and is suggestive of an underlying carcinoma, particularly of the GI tract
- more common in the elderly
232
What is the Leser Trelat sign?
the sudden onset of multiple seborrheic keratoses, which is suggestive of carcinoma, especially in the GI tract
233
Acanthosis Nigricans
- an epidermal hyperplasia with darkening of the skin
- sometimes described as a "velvet-like" skin and most often involves the axilla or groin
- associated with insulin resistance (e.g. non-insulin-dependent diabetes) and malignancy, particularly gastric carcinoma
234
Which two skin conditions are strongly associated with GI tract malignancy?
- seborrheic keratosis (Leser-Trelat sign)
| - acanthosis nigricans
235
Basal Cell Carcioma
- a malignant proliferation of the basal cells in the epidermis
- risk factors stem from greater UVB-mediated DNA damage (e.g. sunlight, albinism, xeroderma pigementosum)
- presents as an elevated nodule with a central, ulcerated crater surrounded by dilated, telangiectatic vessels; classically involves the upper lip
- may also present as non healing ulcers with infiltrating growth or as a scaling plaque
- often described as a "pink, pearl-like papule"
- histology demonstrates nodules of basal cells with peripheral palisading
- metastasis is rare; treat with surgical excision; prognosis is good
- the most common cutaneous malignancy
236
Which cutaneous cancer classically involves the upper lip? The lower lip?
- upper lip: basal cell carcinoma
| - lower lip: squamous cell carcinoma
237
What is xeroderma pigementosum?
an AR defect in the enzymes needed for nucleotide excision repair, which are responsible for repairing UV-mediated pyrimidine dimers in the DNA; therefore, these individuals have a much higher incidence of cutaneous malignancy
238
Squamous Cell Carcinoma of the Skin
- a malignant proliferation of squamous cells characterized by the formation of keratin pearls
- risk factors stem from UVB-medaited DNA damage, immunosuppressive therapy, arsenic exposure, and chronic inflammation
- presents as an ulcerated, nodular mass, classically on the face and especially the lower lip
- may arise from an actinic keratosis, which is a precursor lesion
- metastasis is uncommon; use surgical excision to treat
239
Actinic Keratosis
- a precursor lesion to squamous cell carcinoma
| - presents as a hyperkeratotic, scaly plaque, often on the face, back, or neck
240
Keratoacanthoma
- a well-differentiated squamous cell carcinoma that develops rapidly and regresses spontaneously
- presents as a cup-shaped tumor filled with keratin debris
241
From what cell population are melanocytes derived?
neural crest
242
Melanin is derived from what precursor?
tyrosine
243
Describe how keratinocytes become pigmented.
- melanocytes in the basalis convert tyrosine to melanin
| - they then pass melanosomes to the keratinocytes they are in contact with
244
Vitiligo
- a localized loss of skin pigmentation
- due to autoimmune destruction of melanocytes
- not as obvious in light-skinned individuals until they attempt to tan
245
Albinism
- a congenital lack of pigmentation
- due to a defect in the tyrosinase enzyme, which impairs melanin production in melanocytes (importantly, not due to a lack of melanocytes)
- may involve only the eyes (known as the ocular form) or the eyes and skin (oculocutaneous form)
- increases the risk of basal cell carcinoma, squamous cell carcinoma, and melanoma because they have less protection against UVB
246
Ephelis
- aka freckle
- it is a small, tan-to-brown macule that darkens with sun exposure
- due to an increased number of melanosomes (note: there is not an increase in melanocytes)
247
What is melasma?
a mask-like hyperpigmentation of the cheeks associated with pregnancy and oral contraceptives
248
Nevus
- aka a mole, it is a benign neoplasm of melanocytes
- they are flat macule or raised papule with symmetry, sharp borders, evenly distributed color, and small diameter (< 6 mm)
- those that are congenital are usually associated with hair
- acquired arise later in life and move through three stages: junctional, compound, and intradermal; junctional nevi are benign nests of melanocytes at the dermal-epidermal junction that grow horizontally; compound are those that begin to grow into the dermis; intradermal are compound nevi that eventually lose their junctional component
- junctional are most common in children and intradermal are most common in adults because of this progression
- may give rise to dysplasia and serve as a precursor to melanoma
249
What are melanoma ABCDs?
- asymmetry
- borders are irregular
- color is not uniform
- diameter is more than 6 mm
250
What size is typical of moles and melanomas?
moles tend to be less than 6 mm and melanomas tend to be more
251
What is dysplastic nevus syndrome?
an autosomal dominant disorder characterized by formation of dysplastic nevi that may progress to melanoma
252
Melanoma
- a malignant proliferation of melanocytes
- defined by the ABCDs: asymmetry, border irregularity, color variation, and diameter > 6 mm
- go through a radial (horizontal) growth phase along the epidermis and superficial dermis during which the risk of metastasis is low
- this is followed by a vertical growth phase, which increases the risk of metastasis
- in fact, the most important prognostic factor is the depth of invasion (known as Breslow thickness)
- variants include superficial, which is most common and characterized by early radial growth with a good prognosis; lentigo maligna with radial growth and a good prognosis; nodular with early vertical growth and a poor prognosis; and sacral lentiginous which is unrelated to UV exposure and arises on the palms or soles of dark-skinned individuals
- S-100 positive is a distinguishing feature
- often driven by activating mutations in BRAF kinase; as such patients with unresectable melanoma may benefit from vemurafenib, a BRAF kinase inhibitor
253
What is Breslow thickness?
- the degree to which a melanoma has grown vertically
| - the most important prognostic indicator for melanomas
254
What is unique about the superficial, lentigo maligna, nodular, and acral lentiginous forms of melanoma?
- superficial is the most common subtype and is dominated by early radial growth with a good prognosis
- lentigo maligna is characterized by radial growth and a good prognosis as well
- nodular is characterized by early vertical growth and a poor prognosis
- sacral lentiginous is not related to UV damage and tends to arise on the soles and palms of people with dark skin
255
Impetigo
- a superficial bacterial skin infection
- most often due to S. aureus or S. pyogenes
- presents as an erythematous macule, usually on the face, that progress to a postule, which ruptures, resulting in an erosion with a dry, crusted, honey-colored serum
- can also take a bullous form, usually caused by S. aureus
- highly contagious
- commonly affecting children
256
Cellulitis
- a deeper (dermal and subcutaneous) infection
- usually caused by S. aureus or S. pyogenes
- presents as a red, tender, swollen rash with fever
- can progress to necrotizing fasciitis with necrosis of sub tissue if the infection is by an anaerobic "flesh-eating" bacteria; in these cases the bacteria produce CO2 in the tissue, which can be heard as crepitus
- risk factors are recent surgery, trauma, or insect bite
257
What is necrotizing fasciitis?
- cellulitis with an anaerobic "flesh-eating bacteria"
| - those bacteria produce CO2, which gets trapped in the tissue and can be heard as crepitus
258
Staph Scalded Skin Syndrome
- a sloughing of skin with erythematous rash and fever, leading to significant skin loss
- usually seen in newborns and children as well s adults with renal insufficiency
- due to S. aureus exfoliative A and B toxins, which result in epidermolysis of the stratum granulosum only
- positive nikolsky sign
- distinguished histologically from toxic epidermal necrolysis by the level of skin separation since TEN occurs at the dermal-epidermal junction
- heals completely
259
How do we distinguish Staph Scladed Skin Syndrome from TEN?
- histologically by the level of separation
- TEN involves separation at the dermal-epidermal junction whereas Staph Scalded Skin Syndrome involves separation within the stratum granulosum
260
Verruca
- also known as a wart
- it is caused by HPV infection of keratinocytes
- presents as a flesh-colored papule with a rough surface, most often on the hands and feet
- histology reveals koilocytic change
261
Molluscum Contagiosum
- a firm, pink, umbilicated papule
- due to poxvirus infection
- most often in children, sexually active adults (as an STI), and immunocompromised individuals
- can see molluscum bodies on histology
262
Polymyalgia Rheumatica
- pain and stiffness in the shoulders and hips, often with fever, malaise, and weight loss; without muscle weakness
- most common in women over 50 and associated with giant cell (temporal) arteritis-
- labs reveal elevated ESR and CRP but normal CK
- demonstrate a rapid response to low-dose corticosteroids
263
Fibromyalgia
- characterized by chronic, widespread MSK pain associated with stiffness, paresthesias, poor sleep, fatigue, and cognitive disturbances know as the "fibro fog"
- most common in females 20-50 y.o.
- treat with regular exercise, antidepressants (TCAs and SNRIs), and anticonvulsants
264
Myositis Ossificans
- a heterotypic ossification of skeletal muscle following muscular trauma
- usually in the extremities
- may present as a suspicious mass at the site of known trauma or as incidental finding on radiography
265
Raynaud Phenomenon
- reduced blood flow to the skin due to arteriolar vasospasm in response to cold or stress
- fingers first turn white with ischemia, blue with hypoxia, and then red with reperfusion
- can be primary, known as Raynaud disease, or secondary, known as Raynaud syndrome
- most often in the context of mixed connective tissue disease, SLE, and CREST
- may cause digital ulceration
- treat with calcium channel blockers
266
Define hyperkeratosis.
a thickening of the stratum corneum
267
Define parakeratosis.
a thickening of the stratum corneum with retention of nuclei
268
Define hypergranulosis.
an increased thickness of the stratum granulosum
269
Define spongiosis.
an accummulation of edematous fluid in the intercellular spaces of the epidermis
270
Define acantholysis.
a separation of epidermal cells
271
Define acanthosis.
an epidermal hyperplasia, particularly in the spinosum
272
Cadherins compose which cell type of epithelial junction?
zonula adherens
273
What sort of proteins form gap junctions between epithelial cells?
connexons
274
What are zonula adherens junctions?
- those primarily composed fo cadherins
| - form a belt connecting actin cytoskeletons of adjacent cells below the tight junctions
275
What are the primary components of tight junctions?
claudins and occludins
276
What is the purpose of the desmosomes?
they provide structural support via intermediate filament interactions between cells
277
What is the function of hemidesmosomes?
connect keratin in basal cells to the underlying basement membrane
278
What is the function of integrins in the epidermis?
they are membrane proteins that maintain the integrity of the basolateral membrane by binding to collagen and laminin in the basement membrane
279
Erythema Nodosum
- painful inflammatory lesions of subq fat, usually on the anterior chins
- can be associated with sarcoidosis, coccidioidomycosis, histoplasmosis, TB, streptococcal infection, leprosy, and IBD
280
Pityriasis Rosea
- a "herald patch" followed days later by other scaly erythematous plaques, that typically follow a "christmas tree" distribution on the trunk
- self-resolving in 6-8 weeks
281
What kind of UV radiation is responsible for sunburns?
UVB for burns, UVA for tanning and photoaging
282
Stevens-Johnson Syndrome
- usually associated with an adverse drug reaction
- manifests as fevere, bullae formation and necrosis, sloughing of skin at the dermal-epidermal junction; targetoid lesions may appear as in erythema multiforme
- has a high mortality rate
- TEN is defined as SJS with more than 30% body surface involvement
283
Erysipelas
- an infection of the upper dermis and superficial lymphatics
- usually from S. pyogenes
- presents with a well-defined demarcation between the infected and normal skin
- equate it to somewhere between impetigo and cellulitis
284
Abscess
- a collection of pus from a walled-off infection within the deeper layers of skin
- almost always due to S. aureus
285
What is herpes whitlow?
a herpes infection of the skin on the finger
286
Urticaria
- also known as hives
- pruritic wheals that form after mast cell degranulation
- characterized by superficial dermal edema and lymphatic channel dilation
287
Rosacea
- an inflammatory skin disorder characterized by erythematous papules and pustules but no comedones
- may be associated with facial flushing in response to external stimuli such as alcohol and heat
- phymatous rosacea can cause rhinophyma (a bulbous deformation of the nose)
288
Angiosarcoma
- a malignancy of blood vessels
- typically occurring in the head, neck, or breast area in the elderly on sun-exposed areas
- associated with radiation therapy and chronic post-mastectomy lymphedema
- hepatic angiosarcoma in particular is associated with vinyl chloride and arsenic exposure
- very aggressive and difficult to resect
289
Bacillary Angiomatosis
- benign capillary skin papules found in AIDS patients
- caused by Bartonella henselae infections
- commonly mistaken for Kaposi sarcoma but has a neutrophilic infiltrate
290
What is the difference between a cherry hemangioma and a strawberry hemangioma?
- cherry: a benign capillary hemangioma of the elderly, which does not regress
- strawberry: a benign capillary hemangioma of infancy that grows rapidly and regresses spontaneous by 5-8 years of age
291
What is a cystic hygroma?
a cavernous lymphangioma of the neck associated with Turner syndrome
292
Glomus Tumor
a benign, painful, red-blue tumor commonly found in the fingernails that arises from modified smooth muscle cells of the thermoregulatory glomus body
293
Pyogenic Granuloma
a polypoid lobulated capillary hemangioma associated with trauma and pregnancy that can ulcerate and bleed
294
Describe the mechanism, clinical use, and side effect profile of acetaminophen.
- it reversibly inhibits COX, primarily in the CNS
- as such it is an antipyretic and analgesic although it has no anti-inflammatory action
- indicated as an alternative to aspirin in children with viral illnesses to avoid Eye syndrome
- overdose produces hepatic necrosis as the toxic metabolite NAPQI depletes glutathione and forms toxic tissue byproducts in the liver
295
What is the antidote for acetaminophen toxicity?
N-acetylcystein, a precursor for glutathione that helps regenerate glutathione
296
Through what mechanisms do glucocorticoids have an anti-inflammatory effect?
they inhibit PLA2 and activate inhibitor of kB, which inhibits NF-kB, a transcription factor that up regulates inflammatory mediators like COX-2
297
What is epoprostenol?
a PGI2 analog that reduces vascular tone and impairs platelet aggregation
298
What is alprostadil?
a PGE1 analog that reduces vascular tone
299
What is dinoprostone?
a PGE2 analog that increases uterine tone
300
What is carboprost?
a PGF2a analog that increases uterine tone
301
Describe the mechanism, clinical use, and side effect profile of aspirin.
- it irreversibly inhibits COX-1 and COX2 by covalent acetylations, which reduces synthesis of TXA2 and prostaglandins
- used at low dose (<300 mg/day) to inhibit platelet aggregation and lower the risk of thrombotic events; used at intermediate dose (300-2400 mg/day) for its antipyretic and analgesic effects; used at high dose (2400-4000 mg/day as an anti-inflammatory
- may cause gastric ulceration or tinnitus; chronic use can lead to acute renal failure, interstitial nephritis, or GI bleeding
- should not be used in the setting of children with viral infection because of the risk for Reye syndrome
- causes a respiratory alkalosis early, but transitions to a mixed metabolic acidosis-respiratory alkalosis
302
What effect does aspirin have on bleeding time, PT, and PTT?
- it does not affect PT and PTT
| - but it increases bleeding time because it impairs synthesis of TXA2, an important platelet agonist
303
At what dose is aspirin prescribed to inhibit platelet aggregation?
< 300 mg/day
304
Describe the mechanism, clinical use, and side effect profile of celecoxib.
- reversibly inhibits COX-2, sparing COX-1; because of this it has the added benefit of not inhibiting platelet aggregation
- used for rheumatoid arthritis and osteoarthritis
- increases the risk of thrombosis and may cause a sulfa allergy
305
What is the only COX-2 selective inhibitor still on the market?
celecoxib
306
What is the difference between COX-1 and COX-2?
COX-1 is more or less constitutively expressed and serves as a protective agent in the GI tract and produces TXA2; COX-2 is inducible in the setting of inflammation and mediates that process while damaging the GI tract
307
Which cyclooxyrgenase is responsible for producing TXA2? Why does this matter?
it is produced by COX-1, which means that celecoxib sprees platelet function should you need anti-inflammatory effects with retained platelet aggregation
308
Describe the mechanism, clinical use, and side effect profile of NSAIDs.
- includes ibuprofen, naproxen, indomethacin, ketorolac, diclofenac, meloxicam, and piroxicam
- function by reversibly inhibiting both COX-1 and COX-2 to inhibit prostaglandin synthesis
- used as antipyretics, analgesics, and anti-inflammatory agents; indomethacin in particular is used to close a PDA
- may cause interstitial nephritis, gastric ulcer, or renal ischemia
309
Why do the NSAIDs sometimes cause renal ischemia?
because prostaglandins are an important for vasodilation of the afferent arteriole
310
Describe the mechanism, clinical use, and side effect profile of leflunomide.
- reversibly inhibits dihydroorotate dehydrogenase and thus prevents pyrimidine synthesis to suppress T-cell proliferation
- used in rheumatoid arthritis and psoriatic arthritis
- may cause diarrhea, hypertension, hepatotoxicity, and teratogenesis
311
Describe the naming convention, mechanism, clinical use, and side effect profile of bisphosphonates.
- end in the suffix "-dronate"
- serve as pyrophosphate analogs, bind hydroxyapatite in bone, and inhibit osteoclast activity
- used for osteoporosis, hypercalcemia, Paget disease of bone, metastatic bone disease, and osteogenesis imperfecta
- may cause esophagitis so take with lots of water and remain standing for 30 minutes; other side effects are osteonecrosis of the jaw or atypical stress fractures
312
Describe the mechanism, clinical use, and side effect profile of teriparatide.
- recombinant PTH given subq daily to increase osteoblastic activity
- used in the treatment of osteoporosis; causes more bone growth than anti-resorptive therapies like bisphosphonates
- may cause a transient hypercalcemia
313
Describe the mechanism and clinical uses of allopurinol.
- it is a competitive inhibitor of xanthine oxidase which reduces conversion of hypoxanthine and xanthine to rate
- used in the treatment of gout as well as in lymphoma and leukemia to prevent tumor lysis-associated urate nephropathy
314
Describe the mechanism and clinical uses of febuxostat.
it inhibits xanthine oxidase for the treatment of gout
315
What is pegloticase?
a recombinant uricase that catalyzes metabolism of uric acid to allantoin, which is more water-soluble, for the treatment of gout
316
Describe the mechanism of action and major side effect of probenecid in the treatment of gout.
it inhibits reabsorption of uric acid in the proximal tubule but may precipitate uric acid calculi
317
What sort of COX inhibitors are useful in treating gout? Which are not and why?
- use naproxen or indomethacin
| - do not use salicylates because they impair uric acid clearance
318
What is colchicine?
a drug used for the prophylactic and acute treatment of gout because it binds and stabilizes tubules to inhibit microtubule polymerization and impair neutrophil chemotaxis/degranulation (may have GI side effects)
319
Describe the mechanism, clinical use, and side effect profile of etanercept.
- it is a fusion protein produced by recombinant DNA which serves as a TNFa decoy receptor
- used for rheumatoid arthritis, psoriasis, and ankylosing spondylitis
- may cause reactivation of latent TB or predispose one to infection
320
Describe the mechanism, clinical use, and side effect profile of infliximab.
- an anti-TNFa monoclonal antibody
| - used for the treatment of IBD, rheumatoid arthritis, ankylosing spondylitis, and psoriasis
321
Describe the mechanism, clinical use, and side effect profile of adalimumab.
- an anti-TNFa monoclonal antibody
| - used for the treatment of IBD, rheumatoid arthritis, ankylosing spondylitis, and psoriasis
322
Describe the mechanism and clinical use of rasburicase.
- a recombinant uricase that catalyzes metabolism of uric acid to allantoin
- used to prevent and treat tumor lysis syndrome, particularly urate nephropathy
323
How does Becker muscular dystrophy compare to Duchenne?
- Becker is due to some mutation (usually a non-frameshift insertion) that leaves a partially functional gene product rather than a truncated one as in Duchenne's
- Becker presents as a milder form with later onset in adolescence or early adulthood
STEP1
flashcards
Decks in class (24)
# Cards
-
Behavioral Sciences98
-
Immunology275
-
Hematology224
-
Basics of Pathology104
-
Neoplasia112
-
Renal162
-
Endocrine171
-
Cardiology299
-
Pharmacology237
-
Pulmonology251
-
GI322
-
GU484
-
Neuro404
-
Psych259
-
Neuro Part 2181
-
MSK323
-
Biochemistry334
-
Bacteriology129
-
GI and Endocrine Drugs49
-
Fungi8
-
ANS Drugs69
-
Blood and Inflammation Drugs52
-
Cardio & Renal Drugs41
-
UWorld Test Questions26
