MSK

Question 1

Achondroplasia

Answer 1

• 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

Question 2

What is the difference between endochondral and intramembranous bone formation?

Answer 2

• 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

Question 3

Osteogenesis Imperfecta

Answer 3

• 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

Question 4

How can osteogenesis imperfecta be distinguished from child abuse upon examination?

Answer 4

osteogenesis imperfecta will present with fractures but bruises will be absent

Question 5

Why does osteogenesis imperfecta present with blue sclera?

Answer 5

because thinning of the scleral collagen reveals the underlying choroidal veins

Question 6

Osteopetrosis

Answer 6

• 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

Question 7

Which bone disease can be cured with a hematopoietic stem cell transplant? Why?

Answer 7

osteopetrosis because it is due to osteoclast malfunction and osteoclasts are derived from the monocyte lineage

Question 8

Osteoclasts are derived form what cell lineage?

Answer 8

monocytes

Question 9

Rickets

Answer 9

• 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

Question 10

Osteoblasts produce what bone product?

Answer 10

osteoid

Question 11

What is a Rachitic rosary?

Answer 11

• palpable osteoid deposition at the costochondral junction

- a feature of childhood Rickets

Question 12

Osteomalacia

Answer 12

• 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

Question 13

What is alkaline phosphatase?

Answer 13

the enzyme expressed by osteoblasts that creates an alkaline microenvironment necessary for the precipiation and deposition of calcium in bone

Question 14

Describe the synthesis of Vitamin D and it’s actions.

Answer 14

• 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

Question 15

Why does liver disease impair vitamin D activity?

Answer 15

because the liver is the site of 25-hydroxylation of vitamin D, the first step in activation of vitamin D

Question 16

Why does renal disease impair vitamin D activity?

Answer 16

• 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

Question 17

Osteoporosis

Answer 17

• 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

Question 18

How can osteoporosis be distinguished from osteomalacia?

Answer 18

• via histology for one

- secondly, labs are normal in those with osteoporosis but abnormal in those with osteomalacia

Question 19

How is bone density measured?

Answer 19

via a DEXA scan

Question 20

At what point in our lives is peak bone mass achieved? What determines the level of this peak?

Answer 20

• peak is reached in early adulthood around age 30

- determined by genetics, such as vitamin D receptor variants; diet; and exercise

Question 21

At what rate does bone loss after the age of 30 generally occur? What factors modify this rate?

Answer 21

• typically loss 1% of bone mass each year

- faster with lack of weight-bearing exercise, poor diet, or decreased estrogen

Question 22

What effect does estrogen have on bone density?

Answer 22

it has a protective effect

Question 23

Paget’s Disease of Bone

Answer 23

• 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

Question 24

What is the most common cause of isolated elevated alkaline phosphatase in patients over 40?

Answer 24

Paget disease of bone

Question 25

Osteomyelitis

Answer 25

- 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

Question 26

What are the most common organisms that cause osteomyelitis?

Answer 26

- 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

Question 27

What is the difference between childhood osteomyelitis and osteomyelitis affecting adults?

Answer 27

- in children, the metaphysis is generally seeded during a transient bacteremia - in adults, the epiphysis is usually seeded by an open-wound bacteremia

Question 28

What is a sequestrum and an involucrum?

Answer 28

- sequestrum is the central, lytic lesion of osteomyelitis | - the involucrum is a region of sclerotic or reactive bone surrounding it

Question 29

Aseptic Necrosis of Bone

Answer 29

- 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

Question 30

Osteoma

Answer 30

- 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)

Question 31

What is Gardner syndrome?

Answer 31

- FAP - fibromatosus in the retroperitoneum - osteomas of the face

Question 32

Osteoid Osteoma

Answer 32

- 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

Question 33

How does an osteoblastoma compare to an osteoma?

Answer 33

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

Question 34

Osteoblastoma

Answer 34

- 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

Question 35

Osteochondroma

Answer 35

- 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

Question 36

What is the most common benign tumor of bone?

Answer 36

osteochondroma

Question 37

Osteosarcoma

Answer 37

- 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

Question 38

What is Codman's triangle?

Answer 38

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

Question 39

Giant Cell Tumor

Answer 39

- 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

Question 40

Which primary bone tumor arises in the epiphysis of bones?

Answer 40

giant cell tumor

Question 41

Ewing Sarcoma

Answer 41

- 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

Question 42

What is a t(11;22) mutation indicative of?

Answer 42

Ewing Sarcoma

Question 43

What is a chondroma?

Answer 43

a benign tumor of cartilage that usually arises in the medulla of small bones of the hands and feet

Question 44

What is a chondrosarcoma?

Answer 44

a malignant, cartilage-forming tumor that most often arises in the medulla of the pelvis or central skeleton

Question 45

Where are chondromas and chondrosarcomas most likely to arise?

Answer 45

- chondroma: medulla of small bones in the hands and feet | - chondrosarcoma: medulla of the pelvis or central skeleton

Question 46

Which cancers classically metastasize to the bone?

Answer 46

PB KTL - prostate - breast - kidney - thyroid - lung

Question 47

Which metastatic cancers to the bone are most likely to cause a blastic lesion?

Answer 47

- prostate is classically blastic | - breast is said to be mixed

Question 48

What type of cartilage forms the articular surface of synovial joints?

Answer 48

hyaline

Question 49

What type of collagen is found in the hyaline cartilage of synovial joints?

Answer 49

type II (car"two"lage)

Question 50

What is the purpose of the synovium lining joint capsules?

Answer 50

secrete a fluid rich in hyaluronic acid to further lubricate the joint

Question 51

Where does synovial fluid come from? What compound is highly concentrated within it for the purpose of additional lubrication?

Answer 51

the synovium produces a fluid rich in hyaluronic acid

Question 52

Osteoarthritis

Answer 52

- 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

Question 53

What are Heberden nodes?

Answer 53

osteophytes of the DIPs

Question 54

What are Bouchard nodes?

Answer 54

osteophytes of the PIPs

Question 55

Rheumatoid Arthritis

Answer 55

- 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

Question 56

What is a pannus?

Answer 56

- a form of synovitis in which the synovium becomes thickened by granulation tissue - responsible for the joint destruction of rheumatoid arthritis

Question 57

Which joints in the fingers are affected by rheumatoid arthritis?

Answer 57

the PIPs; DIPs are usually spared

Question 58

What are the signs & symptoms of rheumatoid arthritis.

Answer 58

- 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

Question 59

What are rheumatoid nodules?

Answer 59

areas of central necrosis surrounded by epithelioid histiocytes on the skin or visceral organs

Question 60

What are Baker cysts?

Answer 60

- 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

Question 61

What is rheumatoid factor?

Answer 61

IgM against the Fc portion of IgG, which serves as a marker of tissue damage and disease activity in rheumatoid arthritis

Question 62

What are seronegative spondyloarthropathies?

Answer 62

- 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

Question 63

Ankylosing Spondyloarthritis

Answer 63

- 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"

Question 64

Reactive Arthritis

Answer 64

- 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

Question 65

Psoriatic Arthritis

Answer 65

- 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

Question 66

Infectious Arthritis

Answer 66

- 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

Question 67

Describe uric acid biosynthesis. How is it eliminated from the body?

Answer 67

- 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

Question 68

Gout

Answer 68

- 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

Question 69

What is the function of HGPRT?

Answer 69

it is an enzyme, named hypoxanthine-guanine phosphoribosyltransferase, that moves hypoxanthine (from AMP) and guanine (form GMP) into the purine salvage pathway

Question 70

What is Lesch-Nyhan syndrome?

Answer 70

arises from a deficiency of HGPRT, an enzyme in the purine salvage pathway, which presents with gout, mental retardation, and self-mutilation

Question 71

What two things are known to precipitate cases of acute gout? Why?

Answer 71

- alcohol competes with uric acid for excretion | - dietary meat adds lots of purine precursors that must be eliminated as uric acid

Question 72

What is the name for the painful arthritis of the big toe that is seen in gout?

Answer 72

podagra

Question 73

Chronic gout leads to what two symptoms/complications?

Answer 73

- formation of tophi | - deposition in renal tubules and renal failure

Question 74

What are tophi? Where are they most likely?

Answer 74

- 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

Question 75

Pseudogout

Answer 75

- 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

Question 76

What crystals are found in cases of pseudogout?

Answer 76

rhomboid-shaped, weakly positive birefringent calcium pyrophosphate dihydrate crystals

Question 77

Dermatomyositis

Answer 77

- 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

Question 78

What are Gottron papule?

Answer 78

red papule on the knuckles, elbows, and knees in those with dermatomyositis

Question 79

What is anti-Jo-1 antibody a feature of?

Answer 79

dermatomyositis

Question 80

Malar rash and positive ANA can be seen in those with lupus as well as what MSK disorder?

Answer 80

dermatomyositis

Question 81

Polymyositis

Answer 81

- 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

Question 82

How can dermatomyositis and polymyositis be differentiated clinically and histologically?

Answer 82

- 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

Question 83

X-Linked Muscular Dystrophy

Answer 83

- 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

Question 84

What do most with Duchenne's muscular dystrophy die of?

Answer 84

cardiac or respiratory failure after the necessary muscles for either system are replaced by adipose

Question 85

Myasthenia Gravis

Answer 85

- 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

Question 86

Lipoblasts are characteristic of what pathology?

Answer 86

liposarcoma

Question 87

What are the most common benign and malignant soft tissue tumors in adults? What is the most common malignant soft tumor in children?

Answer 87

- adult benign: lipoma - adult malignant: liposarcoma - child malignant: rhabdomyosarcoma

Question 88

Cardiac rhabdomyoma is associated with what disease?

Answer 88

tuberous sclerosis

Question 89

Rhabdomyosarcoma?

Answer 89

- 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)

Question 90

Lambert-Eaton syndrome

Answer 90

- 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

Question 91

How does Lambert-Eaton syndrome differ from myasthenia gravis?

Answer 91

- 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

Question 92

What is the anterior drawer sign?

Answer 92

an anterior gliding of the tibia indicative of ACL injury

Question 93

What is the posterior drawer sign?

Answer 93

a posterior gliding of the tibia indicative of PCL injury

Question 94

Where is the ACL located?

Answer 94

it extends from the lateral femoral condyl to the anterior tibia

Question 95

How are the ACL and PCL named?

Answer 95

according to their relative position where they insert on the tibia

Question 96

Where is the PCL located?

Answer 96

it extends form the medial femoral condyl to the posterior tibia

Question 97

What sort of knee injury does abnormal passive abduction indicated?

Answer 97

it indicates an MCL tear

Question 98

How would you identify a LCL tear of the knee during a physical exam?

Answer 98

it would show up as abnormal/excessive passive adduction of the knee

Question 99

Describe the McMurray test and how it should be interpreted.

Answer 99

- 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

Question 100

How would you test for a medial meniscal tear?

Answer 100

with external rotation during the McMurray test

Question 101

What is the "unhappy triad" of knee injury?

Answer 101

- 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

Question 102

Prepatellar Bursitis

Answer 102

- inflammation of the knee's largest sac of synovial fluid | - caused by repeated trauma or pressure from excessive kneeling

Question 103

What muscles make up the rotator cuff?

Answer 103

SItS- superspinatus- infraspinatus- teres minor- subscapularis

Question 104

What is the location, function, and innervation of the superspinatus muscle.

Answer 104

- 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)

Question 105

Which rotator cuff muscle is most often injured? Why?

Answer 105

the supraspinatous because it is commonly impinged upon while running through the subacromial space, leading to tendinopathy and tear

Question 106

The empty/full can test is used to assess what muscle?

Answer 106

the supraspinatus of the rotator cuff

Question 107

What is the location, function, and innervation of the infraspinatus muscle.

Answer 107

- 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)

Question 108

Pitching injuries often damage which portion of the rotator cuff?

Answer 108

the infraspinatus, responsible for laterally rotating the arm

Question 109

What is the location, function, and innervation of the teres minor muscle.

Answer 109

- 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

Question 110

What is the location, function, and innervation of the subscapularis muscle.

Answer 110

- 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

Question 111

The rotator cuff primarily receives it's innervations from where?

Answer 111

C5 and C6

Question 112

Medial Epicondylitis

Answer 112

- 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

Question 113

Lateral Epidondylitis

Answer 113

- 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

Question 114

Name the wrist bones and their order.

Answer 114

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)

Question 115

Which carpal bone is located in the anatomic snuff box?

Answer 115

the scaphoid

Question 116

Which carpal bone is most commonly fractured?

Answer 116

the scaphoid

Question 117

Scaphoid Fracture

Answer 117

- 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

Question 118

Which carpal bone may dislocate and cause an acute carpal tunnel syndrome?

Answer 118

the lunate

Question 119

Which carpal bone, if damaged, can also injure the ulnar nerve?

Answer 119

the hook of the hamate

Question 120

What runs beneath the hook of the hamate bone?

Answer 120

the ulnar nerve

Question 121

Carpal Tunnel Syndrome

Answer 121

- 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

Question 122

Why does the thenar eminence atrophy without loss of sensation in those with carpal tunnel syndrome?

Answer 122

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

Question 123

Guyon Canal Syndrome

Answer 123

- 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

Question 124

What would cause axillary nerve injury and how would it present?

Answer 124

- 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

Question 125

Which nerves and arteries would most likely be injured by the following humeral fractures:- surgical neck- midshaft- supracondylar- medial epicondyle

Answer 125

- 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

Question 126

What would cause musculocutaneous nerve injury and how would it present?

Answer 126

- 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

Question 127

What would cause radial nerve injury and how would it present?

Answer 127

- 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

Question 128

Why does ulnar nerve injury cause a reduction in grip strength?

Answer 128

because wrist extension is necessary for maximal action of flexors

Question 129

What would cause median nerve injury and how would it present?

Answer 129

- 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)

Question 130

What is the Tinel sign?

Answer 130

a tingling to percussion, especially in the distribution of the median nerve in those with carpal tunnel syndrome

Question 131

What would cause ulnar nerve injury and how would it present?

Answer 131

- 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

Question 132

What would cause damage to the recurrent branch of the median nerve and how would it present?

Answer 132

- 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

Question 133

Describe the cutaneous innervation of the arm as seen on page 419 of FA.

Answer 133

- 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

Question 134

Describe the cutaneous innervation of the hand as seen on page 419 of FA.

Answer 134

- 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

Question 135

Erb Palsy

Answer 135

- 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)

Question 136

Describe the nerve roots that contribute to the axillary, musculocutaneous, radial, median, and ulnar nerves.

Answer 136

pneumonic: A, MU, all - axillary: 5, 6 - musculocutaneous: 5, 6, 7 - radial: all (C5-T1) - median: all (C5-T1) - ulnar (C8-T1)

Question 137

Klumpke Palsy

Answer 137

- 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

Question 138

Thoracic Outlet Syndrome

Answer 138

- 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

Question 139

Winged Scapula

Answer 139

- 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

Question 140

Describe "ulnar claw" and what causes it.

Answer 140

can't extend the fourth and fifth digits due to distal ulnar nerve injury

Question 141

Which nerves supply the thenar and hypothenar eminences?

Answer 141

- thenar: median nerve | - hypothenar: ulnar

Question 142

What is the function of the lumbrical muscles?

Answer 142

they flex the MCP and extend the DIP and PIP

Question 143

Describe "pope's blessing" hand and what causes it.

Answer 143

inability to flex the first three digits because of proximal median nerve injury

Question 144

Describe "median claw" hand and what causes it.

Answer 144

inability to flex the first three digits because of distal median nerve injury

Question 145

What would cause the "OK gesture" hand?

Answer 145

inability to flex the fourth and fifth digits because of proximal ulnar nerve injury

Question 146

What are the hypothenar muscles?

Answer 146

- muscles in the medial palm, which are supplied by the ulnar nerve - includes opponens digiti minimi, abductor digiti minimi, and flexor digiti minimi brevis

Question 147

What are the thenar muscles?

Answer 147

- muscles in the lateral palm which are supplied by the median nerve - includes the opponens pollicis, abductor pollicis brevis, and the flexor pollicis brevis

Question 148

What is the function of the dorsal and palmar interossei muscles?

Answer 148

the dorsal muscles abduct the fingers and the palmar muscles adduct the fingers

Question 149

What would lead to an injury of the obturator nerve and how would it present?

Answer 149

- 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

Question 150

What would lead to an injury of the femoral nerve and how would it present?

Answer 150

- most likely damaged during a pelvic fracture | - originates from L2-L4 and would present with poor flexion of the thigh and impaired leg extension

Question 151

What would lead to an injury of the common peroneal nerve and how would it present?

Answer 151

- 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

Question 152

What would lead to an injury of the tibial nerve and how would it present?

Answer 152

- 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

Question 153

What would lead to an injury of the superior gluteal nerve and how would it present?

Answer 153

- 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

Question 154

What nerve is most likely damaged by doing the course of an intramuscular injection to the upper medial gluteal region?

Answer 154

the superior gluteal nerve (L4-S1)

Question 155

What is a positive Trendelenburg sign?

Answer 155

- 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

Question 156

What would lead to an injury of the inferior gluteal nerve and how would it present?

Answer 156

- 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

Question 157

What muscles do the superior and inferior gluteal nerves innervate?

Answer 157

- superior: gluteus medius, gluteus minimus, and tensor fascia latae - inferior: gluteus maximus

Question 158

Describe innervation of the posterior thigh and leg.

Answer 158

the sciatic nerve, arising from L4-S3 innervates the posterior thigh, and then splits into the common perineal and tibial nerves

Question 159

What is the clinical significance of the pudendal nerve?

Answer 159

- 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

Question 160

Where should intramuscular gluteal injections be given to avoid nerve injury?

Answer 160

given in the superolateral gluteal quadrant, avoiding the superior gluteal nerve

Question 161

What nerve and artery pair extends from the axilla down the lateral thorax?

Answer 161

- long thoracic nerve | - lateral thoracic artery

Question 162

What nerve and artery pair is grouped at the surgical neck of the humerus?

Answer 162

- axillary nerve | - posterior circumflex humeral artery

Question 163

What nerve and artery pair runs through the cubital fossa?

Answer 163

- median nerve | - brachial artery

Question 164

What nerve and artery pair runs through the popliteal fossa?

Answer 164

- tibial nerve | - popliteal artery

Question 165

What nerve and artery pair runs behind the medial malleolus?

Answer 165

- tibial nerve | - posterior tibial artery

Question 166

In which direction do intervertebral discs usually herniate? Why?

Answer 166

- 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

Question 167

How do radiculopathies generally present?

Answer 167

paresthesia and weakness in the distribution of the specific lumbar or sacral spinal nerves

Question 168

Herniation of the L3-L4 disc causes deficits in the pattern of which spinal nerve?

Answer 168

L4; disc herniations tend to affect the nerve associated with the inferior vertebral body

Question 169

What are the signs of an L3-L4 radiculopathy?

Answer 169

weakness of knee extension and diminished patellar reflex

Question 170

What are the signs of an L4-L5 radiculopathy?

Answer 170

weakness of dorsiflexion with difficulty in heel-walking

Question 171

What are the signs of an L5-S1 radiculopathy?

Answer 171

weakness of plantarflexion with difficulty in toe-walking and a poor achilles reflex

Question 172

What are T-tubules?

Answer 172

deep invaginations of the plasma membrane of skeletal and cardiac muscle cells, which are in association with terminal cisternae (enlarged areas of sarcoplasmic reticulum)

Question 173

What is the sarcoplasmic reticulum?

Answer 173

a membrane-bound structure in skeletal and cardiac muscle cells with the primary purpose of storing calcium

Question 174

What is a skeletal muscle triad? What is the equivalent in cardiac muscle cells?

Answer 174

- 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

Question 175

How many terminal cisternae are in association with one t-tubule in skeletal and cardiac muscle cells?

Answer 175

- triad of skeletal muscle: 1 t-tubule + 2 terminal cisternae - dyad of cardiac muscle: 1 t-tubule + 1 terminal cisternae

Question 176

What is a myofibril?

Answer 176

the functional unit of a muscle cell with is formed predominantly by actin and myosin

Question 177

Describe the events that lead to muscle contraction?

Answer 177

- 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

Question 178

What are ryanodine receptors?

Answer 178

voltage-gated calcium channels in the membrane of the sarcoplasmic reticulum, responsible for releasing calcium when muscle cells are depolarized

Question 179

What event is associated with the myosin power stroke?

Answer 179

release of ADP and Pi

Question 180

What even is associated with detachment of the myosin head from the actin filament?

Answer 180

binding of a new ATP molecule

Question 181

What is troponin?

Answer 181

a calcium-sensitive protein that inhibits the interaction between myosin and actin during times of muscle relaxation

Question 182

What are the specific functions of troponin T, I, and C?

Answer 182

- troponin C is the calcium sensor - troponin I inhibits cross-bridging - troponin T binds tropomyosin

Question 183

What is the dihydropyridine receptor?

Answer 183

a voltage-sensitive receptor in the T-tubule that is mechanically coupled to ryanodine receptors

Question 184

Describe the following components of the sarcomere: - A band - H band - I band - M line - Z line

Answer 184

- 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

Question 185

How does muscle contraction affect the length of the A, H, and I bands of the sarcomere?

Answer 185

- the A band is always the same length, regardless of contraction - the H and I bands, shorten during contraction

Question 186

What are the characteristics of type I muscle fibers?

Answer 186

- 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

Question 187

What are the characteristics of type II muscle fibers?

Answer 187

- 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

Question 188

Describe the mechanism for smooth muscle relaxation.

Answer 188

- 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

Question 189

What is the precursor to nitric oxide?

Answer 189

L-arginine

Question 190

Describe the mechanism for smooth muscle contraction..

Answer 190

- 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

Question 191

What is the myosin-light-chain kinase?

Answer 191

an enzyme, activated by the calcium-calmodulin complex, which phosphorylates the regulatory light-chain of myosin and allows for muscle contraction

Question 192

What is the myosin-light-chain phosphatase?

Answer 192

an enzyme, activated by cGMP, that dephosphorylates the regulatory light-chain of myosin and allows for muscle relaxation

Question 193

What are woven and lamellar bone?

Answer 193

- woven bone is that first laid down by osteoblasts | - lamellar bone is reorganized, stronger bone that replaces the woven bone

Question 194

Osteoblasts and osteoclasts are derived from what stem cell population?

Answer 194

- osteoblasts differentiate from mesenchymal stem cells in the periosteum - osteoclasts differentiate from fusion of monocyte and macrophage lineage precursors

Question 195

Osteoclasts use primarily what two proteins for bone resorption?

Answer 195

carbonic anhydrase II to create an acidic microenvironment and collagenases

Question 196

What is the effect of pulsatile PTH and continuous PTH?

Answer 196

- pulsatile exerts an anabolic effect on bone | - continuous causes catabolism of bone

Question 197

Through what mechanism is estrogen protective of bone mass?

Answer 197

it inhibits apoptosis of osteoblasts and induces apoptosis in bone-resorbing osteoclasts

Question 198

How does PTH stimulate osteoclast activity?

Answer 198

it activates osteoblasts, which then release RANK-L, a protein that binds RANK receptors expressed by osteoclasts, promoting reabsorption

Question 199

What is osteoprotegrin?

Answer 199

a decoy receptor for RANK-L secreted by osteocytes

Question 200

What is RANK-L?

Answer 200

a protein released by osteoblasts in response to PTH, which then induces differentiation and activation of osteoclasts

Question 201

What are Haversian and Volkmann's canals?

Answer 201

- 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

Question 202

What are the lacunae and canaliculi of bone?

Answer 202

- canaliculi are the small channels through which osteocytes project and connect with one another - lacunae are the small cavities in which osteocyte soma reside

Question 203

What is denosumab?

Answer 203

a monoclonal antibody against RANKL, used for the treatment of osteoporosis

Question 204

Vertebral Compression Fracture

Answer 204

- an indicator of osteoporosis | - presents with acute back pain, loss of height, and kyphosis

Question 205

What three fractures are most common in those with osteoporosis?

Answer 205

- vertebral compression fracture - colles fracture of the distal radius - fracture of the femoral neck

Question 206

Hypervitaminosis D

Answer 206

- caused by over supplementation or granulomatous disease | - labs show elevated serum calcium and phosphate with low PTH

Question 207

What is the most specific marker for rheumatoid arthritis?

Answer 207

anti-cyclic citrullinated peptide antibody

Question 208

How is osteoarthritis treated?

Answer 208

acetaminophen, NSAIDs, and intra-articular glucocorticoids

Question 209

What is Felty syndrome?

Answer 209

a triad of neutropenia, splenomegaly, and rheumatoid arthritis

Question 210

What are the layers of the epidermis and their defining features?

Answer 210

- basalis: stem cell population - spinosum: desmosomes between keratinocytes - granulosum: granules in keratinocytes - corneum: keratin in anucleated cells

Question 211

Atopic Dermatitis

Answer 211

- 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

Question 212

Contact Dermatitis

Answer 212

- 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

Question 213

Acne Vulgaris

Answer 213

- 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

Question 214

What causes comedones formation during puberty?

Answer 214

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

Question 215

What is Propionibacterium acnes?

Answer 215

a bacteria that infects comedones, expresses lipases, and releases pro-inflammatory fatty acids to form pustules from comedones

Question 216

Psoriasis

Answer 216

- 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

Question 217

What is PUVA?

Answer 217

- a combination of psoralen and UVA light used to treat psoriasis - psoralen increases the absorption of the UVA light by the keratinocytes

Question 218

Why is UV light used to treat psoriasis?

Answer 218

because the disease process is defined by excessive keratinocyte proliferation and UV light will damage keratinocytes

Question 219

What is an Auspitz sign?

Answer 219

bleeding when a psoriatic scale is picked off

Question 220

What is a Munro microabscess?

Answer 220

a collection of neutrophils in the stratum corneum of patients with psoriasis

Question 221

What is acanthosis?

Answer 221

another name for epidermal hyperplasia

Question 222

What is parakeratosis?

Answer 222

a term used to describe hyperkeratosis with retention of keratinocyte nuclei in the stratum corneum

Question 223

Lichen Planus

Answer 223

- 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

Question 224

What are Wickham striae?

Answer 224

the reticular white lines on the surface of lichen planus papules

Question 225

Pemphigus Vulgaris

Answer 225

- 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

Question 226

Bullous Pemphigoid

Answer 226

- 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

Question 227

What are the differences between pemphigus vulgarisms and bulls pemphigoid?

Answer 227

- 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

Question 228

Dermatitis Herpetiformis

Answer 228

- 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

Question 229

Erythema Multiforme

Answer 229

- 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

Question 230

What is do we call the milder form of SJS and the more severe form of SJS? How are they all differentiated?

Answer 230

- milder: erythema multiform (no oral/mucosal involvement and no fever) - more severe: toxic epidermal necrolysis (greater percentage of skin affected)

Question 231

Seborrheic Keratosis

Answer 231

- 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

Question 232

What is the Leser Trelat sign?

Answer 232

the sudden onset of multiple seborrheic keratoses, which is suggestive of carcinoma, especially in the GI tract

Question 233

Acanthosis Nigricans

Answer 233

- 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

Question 234

Which two skin conditions are strongly associated with GI tract malignancy?

Answer 234

- seborrheic keratosis (Leser-Trelat sign) | - acanthosis nigricans

Question 235

Basal Cell Carcioma

Answer 235

- 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

Question 236

Which cutaneous cancer classically involves the upper lip? The lower lip?

Answer 236

- upper lip: basal cell carcinoma | - lower lip: squamous cell carcinoma

Question 237

What is xeroderma pigementosum?

Answer 237

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

Question 238

Squamous Cell Carcinoma of the Skin

Answer 238

- 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

Question 239

Actinic Keratosis

Answer 239

- a precursor lesion to squamous cell carcinoma | - presents as a hyperkeratotic, scaly plaque, often on the face, back, or neck

Question 240

Keratoacanthoma

Answer 240

- a well-differentiated squamous cell carcinoma that develops rapidly and regresses spontaneously - presents as a cup-shaped tumor filled with keratin debris

Question 241

From what cell population are melanocytes derived?

Answer 241

neural crest

Question 242

Melanin is derived from what precursor?

Answer 242

tyrosine

Question 243

Describe how keratinocytes become pigmented.

Answer 243

- melanocytes in the basalis convert tyrosine to melanin | - they then pass melanosomes to the keratinocytes they are in contact with

Question 244

Vitiligo

Answer 244

- a localized loss of skin pigmentation - due to autoimmune destruction of melanocytes - not as obvious in light-skinned individuals until they attempt to tan

Question 245

Albinism

Answer 245

- 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

Question 246

Ephelis

Answer 246

- 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)

Question 247

What is melasma?

Answer 247

a mask-like hyperpigmentation of the cheeks associated with pregnancy and oral contraceptives

Question 248

Nevus

Answer 248

- 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

Question 249

What are melanoma ABCDs?

Answer 249

- asymmetry - borders are irregular - color is not uniform - diameter is more than 6 mm

Question 250

What size is typical of moles and melanomas?

Answer 250

moles tend to be less than 6 mm and melanomas tend to be more

Question 251

What is dysplastic nevus syndrome?

Answer 251

an autosomal dominant disorder characterized by formation of dysplastic nevi that may progress to melanoma

Question 252

Melanoma

Answer 252

- 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

Question 253

What is Breslow thickness?

Answer 253

- the degree to which a melanoma has grown vertically | - the most important prognostic indicator for melanomas

Question 254

What is unique about the superficial, lentigo maligna, nodular, and acral lentiginous forms of melanoma?

Answer 254

- 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

Question 255

Impetigo

Answer 255

- 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

Question 256

Cellulitis

Answer 256

- 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

Question 257

What is necrotizing fasciitis?

Answer 257

- cellulitis with an anaerobic "flesh-eating bacteria" | - those bacteria produce CO2, which gets trapped in the tissue and can be heard as crepitus

Question 258

Staph Scalded Skin Syndrome

Answer 258

- 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

Question 259

How do we distinguish Staph Scladed Skin Syndrome from TEN?

Answer 259

- 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

Question 260

Verruca

Answer 260

- 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

Question 261

Molluscum Contagiosum

Answer 261

- 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

Question 262

Polymyalgia Rheumatica

Answer 262

- 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

Question 263

Fibromyalgia

Answer 263

- 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

Question 264

Myositis Ossificans

Answer 264

- 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

Question 265

Raynaud Phenomenon

Answer 265

- 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

Question 266

Define hyperkeratosis.

Answer 266

a thickening of the stratum corneum

Question 267

Define parakeratosis.

Answer 267

a thickening of the stratum corneum with retention of nuclei

Question 268

Define hypergranulosis.

Answer 268

an increased thickness of the stratum granulosum

Question 269

Define spongiosis.

Answer 269

an accummulation of edematous fluid in the intercellular spaces of the epidermis

Question 270

Define acantholysis.

Answer 270

a separation of epidermal cells

Question 271

Define acanthosis.

Answer 271

an epidermal hyperplasia, particularly in the spinosum

Question 272

Cadherins compose which cell type of epithelial junction?

Answer 272

zonula adherens

Question 273

What sort of proteins form gap junctions between epithelial cells?

Answer 273

connexons

Question 274

What are zonula adherens junctions?

Answer 274

- those primarily composed fo cadherins | - form a belt connecting actin cytoskeletons of adjacent cells below the tight junctions

Question 275

What are the primary components of tight junctions?

Answer 275

claudins and occludins

Question 276

What is the purpose of the desmosomes?

Answer 276

they provide structural support via intermediate filament interactions between cells

Question 277

What is the function of hemidesmosomes?

Answer 277

connect keratin in basal cells to the underlying basement membrane

Question 278

What is the function of integrins in the epidermis?

Answer 278

they are membrane proteins that maintain the integrity of the basolateral membrane by binding to collagen and laminin in the basement membrane

Question 279

Erythema Nodosum

Answer 279

- painful inflammatory lesions of subq fat, usually on the anterior chins - can be associated with sarcoidosis, coccidioidomycosis, histoplasmosis, TB, streptococcal infection, leprosy, and IBD

Question 280

Pityriasis Rosea

Answer 280

- 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

Question 281

What kind of UV radiation is responsible for sunburns?

Answer 281

UVB for burns, UVA for tanning and photoaging

Question 282

Stevens-Johnson Syndrome

Answer 282

- 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

Question 283

Erysipelas

Answer 283

- 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

Question 284

Abscess

Answer 284

- a collection of pus from a walled-off infection within the deeper layers of skin - almost always due to S. aureus

Question 285

What is herpes whitlow?

Answer 285

a herpes infection of the skin on the finger

Question 286

Urticaria

Answer 286

- also known as hives - pruritic wheals that form after mast cell degranulation - characterized by superficial dermal edema and lymphatic channel dilation

Question 287

Rosacea

Answer 287

- 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)

Question 288

Angiosarcoma

Answer 288

- 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

Question 289

Bacillary Angiomatosis

Answer 289

- benign capillary skin papules found in AIDS patients - caused by Bartonella henselae infections - commonly mistaken for Kaposi sarcoma but has a neutrophilic infiltrate

Question 290

What is the difference between a cherry hemangioma and a strawberry hemangioma?

Answer 290

- 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

Question 291

What is a cystic hygroma?

Answer 291

a cavernous lymphangioma of the neck associated with Turner syndrome

Question 292

Glomus Tumor

Answer 292

a benign, painful, red-blue tumor commonly found in the fingernails that arises from modified smooth muscle cells of the thermoregulatory glomus body

Question 293

Pyogenic Granuloma

Answer 293

a polypoid lobulated capillary hemangioma associated with trauma and pregnancy that can ulcerate and bleed

Question 294

Describe the mechanism, clinical use, and side effect profile of acetaminophen.

Answer 294

- 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

Question 295

What is the antidote for acetaminophen toxicity?

Answer 295

N-acetylcystein, a precursor for glutathione that helps regenerate glutathione

Question 296

Through what mechanisms do glucocorticoids have an anti-inflammatory effect?

Answer 296

they inhibit PLA2 and activate inhibitor of kB, which inhibits NF-kB, a transcription factor that up regulates inflammatory mediators like COX-2

Question 297

What is epoprostenol?

Answer 297

a PGI2 analog that reduces vascular tone and impairs platelet aggregation

Question 298

What is alprostadil?

Answer 298

a PGE1 analog that reduces vascular tone

Question 299

What is dinoprostone?

Answer 299

a PGE2 analog that increases uterine tone

Question 300

What is carboprost?

Answer 300

a PGF2a analog that increases uterine tone

Question 301

Describe the mechanism, clinical use, and side effect profile of aspirin.

Answer 301

- 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

Question 302

What effect does aspirin have on bleeding time, PT, and PTT?

Answer 302

- it does not affect PT and PTT | - but it increases bleeding time because it impairs synthesis of TXA2, an important platelet agonist

Question 303

At what dose is aspirin prescribed to inhibit platelet aggregation?

Answer 303

< 300 mg/day

Question 304

Describe the mechanism, clinical use, and side effect profile of celecoxib.

Answer 304

- 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

Question 305

What is the only COX-2 selective inhibitor still on the market?

Answer 305

celecoxib

Question 306

What is the difference between COX-1 and COX-2?

Answer 306

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

Question 307

Which cyclooxyrgenase is responsible for producing TXA2? Why does this matter?

Answer 307

it is produced by COX-1, which means that celecoxib sprees platelet function should you need anti-inflammatory effects with retained platelet aggregation

Question 308

Describe the mechanism, clinical use, and side effect profile of NSAIDs.

Answer 308

- 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

Question 309

Why do the NSAIDs sometimes cause renal ischemia?

Answer 309

because prostaglandins are an important for vasodilation of the afferent arteriole

Question 310

Describe the mechanism, clinical use, and side effect profile of leflunomide.

Answer 310

- 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

Question 311

Describe the naming convention, mechanism, clinical use, and side effect profile of bisphosphonates.

Answer 311

- 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

Question 312

Describe the mechanism, clinical use, and side effect profile of teriparatide.

Answer 312

- 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

Question 313

Describe the mechanism and clinical uses of allopurinol.

Answer 313

- 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

Question 314

Describe the mechanism and clinical uses of febuxostat.

Answer 314

it inhibits xanthine oxidase for the treatment of gout

Question 315

What is pegloticase?

Answer 315

a recombinant uricase that catalyzes metabolism of uric acid to allantoin, which is more water-soluble, for the treatment of gout

Question 316

Describe the mechanism of action and major side effect of probenecid in the treatment of gout.

Answer 316

it inhibits reabsorption of uric acid in the proximal tubule but may precipitate uric acid calculi

Question 317

What sort of COX inhibitors are useful in treating gout? Which are not and why?

Answer 317

- use naproxen or indomethacin | - do not use salicylates because they impair uric acid clearance

Question 318

What is colchicine?

Answer 318

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)

Question 319

Describe the mechanism, clinical use, and side effect profile of etanercept.

Answer 319

- 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

Question 320

Describe the mechanism, clinical use, and side effect profile of infliximab.

Answer 320

- an anti-TNFa monoclonal antibody | - used for the treatment of IBD, rheumatoid arthritis, ankylosing spondylitis, and psoriasis

Question 321

Describe the mechanism, clinical use, and side effect profile of adalimumab.

Answer 321

- an anti-TNFa monoclonal antibody | - used for the treatment of IBD, rheumatoid arthritis, ankylosing spondylitis, and psoriasis

Question 322

Describe the mechanism and clinical use of rasburicase.

Answer 322

- a recombinant uricase that catalyzes metabolism of uric acid to allantoin - used to prevent and treat tumor lysis syndrome, particularly urate nephropathy

Question 323

How does Becker muscular dystrophy compare to Duchenne?

Answer 323

- 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