Pathoma Musculoskeletal Pathology

Question 1

What are the clinical features associated with osteogenesis imperfecta? What might it be confused with?

Answer 1

BITE
B = Bones - multiple fractures
I = Eye -> blue sclera from choroidal veins showing (translucent connective tissue)
T = Teeth, - abnormal dentin
E = Ears- hearing loss, due to abnormal ossicles

Confused with child abuse -> look for ITE signs

Question 2

What does the growth plate look like in osteopetrosis? Why?

Answer 2

Growth plate has lots of residual cartilage which should have been resorbed but has not
-> overgrowth of atypical, malformed bone

This is due to osteoclast dysfunction, most commonly due to an autosomal dominant abnormality in carbonic anhydrase 2.

Question 3

What are the consequences of bone overformation in osteopetrosis?

Answer 3

1. Increased susceptibility to fractures with thick woven bones (Erlenmeyer flash deformity of ulna / radius)
2. Narrowing of skull foramina -> cranial nerve deficits and hydrocephalus (foramen magnum narrowing)
3. Obliteration of marrow space due to bone overgrowth
   - > myelophthisic process

Question 4

What will occur due to obliteration of marrow space in osteopetrosis? What is the treatment for this condition?

Answer 4

Anemia and pancytopenia, leading to increased susceptibility for infections.

Extramedullary hematopoiesis will cause hepatosplenomegaly.

Treatment is hematopoietic stem cell transplant -> osteoclasts are derived from monocytes.

Question 5

What are the physical features of achondroplasia? Why?

Answer 5

Short limbs -> lack of endochondral ossification

Large head (macrocephaly) with flat nose -> intramembranous ossification is not affected (does not require a cartilage precursor)

Question 6

Why is rickets different than osteomalacia? What process is occurring in endochondral ossification?

Answer 6

In children, the epiphyseal cartilage which is forming the physis has not closed up.

Lack of calcification of cartilage -> overgrowth of chondrocytes / wild cartilage formation, contributing to pathology of rickets

Question 7

What are the findings of rickets typically seen in infancy? define: craniotabes, rachitic rosary, pigeon breast deformity, harrison groove

Answer 7

Typically they are head / rib cage abnormalities since they aren’t walking around (no weightbearing)

Craniotabes - head is soft and compressible
Frontal bossing - head is overgrown and protruding
Rachitic rosary - overgrowth of costal cartilage
Pigeon-breast deformity - sternum protrudes (pectus carinatum)
Harrison groove -> groove can be seen below costal margin because ribs are so weak they get pulled in

Question 8

How does vitamin D deficiency present in adulthood?

Answer 8

Osteomalacia, which is osteopenia with loss of bone density and cortical thickness, with increased susceptibility to fractures, weakness, and bone pain.

Looser zones - pseudofractures which are linear areas of unmineralized osteoid seen in bone.

Question 9

How does the third stage of Paget disease appear radiographically?

Answer 9

Sclerotic stage -> osteoblasts only. Bone enlargement with abnormally increased density and course bone thickening

Question 10

What labs will be elevated in serum and urine in Paget disease?

Answer 10

1. Increased collagen breakdown products (i.e. hydroxyproline) in urine / serum -> due to increased osteoclast activity (in osteolytic / first stage)
2. Increased serum ALP -> very high osteoblast activity (especially third stage) - isolated finding

Question 11

What are you at increased risk for due to chronic Paget disease?

Answer 11

1. High-output cardiac failure due to increased vascularity and AV malformations in the affected bones - LOL ehab
2. Osteosarcoma -> increased osteoblast activity makes this a possibility in adults

Question 12

With what symptoms does osteoporosis typically present?

Answer 12

Typically presents with acute back pain and loss of height as the osteopenia will lead to increased fracture risk -> formation of microfractures within vertebral bodies.

Also commonly cause kyphosis, loss of height, and fractures of femoral head and distal radius

Question 13

What is the risk of osteoporosis ultimately based on and when is this achieved? How can this value be increased?

Answer 13

Based on peak bone mass determined by age 30

• > increased by diet and exercise
• > somewhat determined genetically by vitamin D receptor variants

Question 14

What is the most common way that osteomyelitis occurs / infection spreads to bone? Common spot in bone?

Answer 14

Minor skin or mucosal injury leads to a bacteremia which seeds bone (hematogenously spread)

Commonly seeds metaphysis, especially in children if the growth plate is open (lots of blood flow to growing growth plate, with decreased blood flow rate)

Question 15

Are children or adults more likely to get septic arthritis from osteomyelitis?

Answer 15

Adults -> bacteria can cross the growth plate after it closes, allowing bacterial access to epiphysis
-> explains why N. gonorrhea osteomyelitis is common in sexually active young adults

Question 16

What is an important cause of osteomyelitis in diabetics and IV drug abusers?

Answer 16

Pseudomonas aeruginosa

• > enters diabetic wounds
• > IV drug users -> directly seeds bloodstream

Question 17

What is the involucrum vs sequestrum?

Answer 17

Sequestrum - abscess which needs to be sequestered off

InvOlucrum - new bOne formation.

Question 18

What is an osteoma and where does it typically occur?

Answer 18

A benign, slowly enlarging tumor of cortical bone, usually arising on flat bones of skull.

Also occurs as part of Gardner syndrome (also with FAP + retroperitoneal fibromatosis).

Question 19

How does an osteoid osteoma appear radiologically? How does it appear clinically?

Answer 19

Osteoblastic tumor of diaphysis of longbone in adolescent males, prevents with pain at night which is relieved by aspirin.

Small (<2cm), well-circumscribed, intracortical mass

The center is radiolucent -> composed of osteoid and woven bone made by osteoblasts

The outside is radiodense -> margin is formed by reactive lamellar bone

Question 20

**What condition is most similar to osteoid osteoma and how do you tell them apart?

Answer 20

OsteoBLASToma - almost exactly the same as osteoid osteoma, except:

• Osteoblastoma is larger (>2 cm)
• Arises in vertebrae (rather than diaphysis of long bones)
• Does NOT respond to aspirin

Question 21

What is an osteochondroma also called? Is it common? When does it arise? What is the feared complication?

Answer 21

Exostosis = “bone growing out”

It is the most common benign tumor of bone

It commonly arises sporadically in males <25. It can be multiple in younger children a hereditary autosomal dominant form

Complication: Cap can become chondrosarcoma

Question 22

What is a enchondroma and who tends to get them?

Answer 22

Benign tumor of cartilage.

Cartilage tumors are rule-breakers -> tend to occur in young to middle-aged adults (20s-30s)

Question 23

Where do enchondromas tend to appear and what do they look like on X-ray?

Answer 23

Tend to appear in the medulla of small tubular bones of hands and feet, contiguous with metaphysis.

They appear as well-circumscribed, mostly radioLUCENT masses made of hyaline cartilage, surrounded by a thin bony rim.

Question 24

What is the most common primary non-hematopoietic bone malignancy? What syndromes is it associated with?

Answer 24

Osteosarcoma

Associated with mutations in Rb and TP53, which are cell cycle regulators:

1. Familial Retinoblastoma
2. Li Fraumeni syndrome

Question 25

Where does osteosarcoma tend to arise and what age groups are susceptible?

Answer 25

Tends to arise in METAPHYSIS of the long bones, especially the knees 1. Teenagers - teenage boys during their growth spurt 2. Older adults - >65 years old, with predisposing bone disease -> i.e. Paget disease

Question 26

How does osteosarcoma often appear radiologically?

Answer 26

Codman triangle - from malignancy lifting the periosteum off the surface of the bone Sunburst pattern on X-ray - from reactive subperiosteal bone formation leading to fragmented densities

Question 27

How does osteosarcoma appear histologically? Where does it spread?

Answer 27

Pleomorphic cells that produce osteoid | -> spreads to the lungs early since it's a sarcoma

Question 28

What is giant cell tumor caused by and is it benign or malignant?

Answer 28

Caused by neoplastic osteoblast precursors which stimulate osteoclast proliferation -> osteoclasts are the reactive giant cells to the malignancy "osteoclastoma" It is a very aggressive benign entity, which can be classed as malignant, but rarely metastasizes.

Question 29

Who gets giant cell tumors? What is the growth pattern of giant cell tumors? What can be seen on X-ray?

Answer 29

Tumor in the EPIphysis of young ADULTS (20-40) Soap bubble appearance on X-ray: Hemorrhagic, cystic mass which is osteolytic. often hemorrhagic, with prominent giant cells. Tumor remains localized in epiphysis of long bones, causing considerable destruction and frequently recurring after conservative excision.

Question 30

What bone tumor is related to a primitive neuroectodermal tumor? Who is it diagnosed in? What causes it?

Answer 30

Ewing sarcoma: t(11;22), fusion protein encoding EWS transcription factor Diagnosed in white male children <15 years old

Question 31

What is seen microscopically and radiographically in Ewing sarcoma?

Answer 31

Microscopically - sheets of small round blue cells (neuroectodermal tumor) -> looks alot like lymphoma too Radiographically - "Onion-skin" proliferation of subperiosteal bone as it pushes outward. Also Codman's triangle triangle can be seen.

Question 32

What is the prognosis of Ewing sarcoma, and what condition could it mimic?

Answer 32

Since it is so destructive, it causes lots of inflammation and may cause fever -> similar to osteomyelitis It responds well to chemo / radiation since it is so aggressive

Question 33

How aggressive is chondrosarcoma typically, and what is the treatment?

Answer 33

Typically a low-grade, indolent malignancy which makes it difficult to treat with chemotherapy. Thus, treatment is complete excision, which often requires radical pelvic or shoulder excision with wide margins taken. -> occurs in older man usually

Question 34

What tumors frequently metastasize to bone?

Answer 34

Lead Kettle: PB KTL Prostate Breast Kidney Thyroid Lung

Question 35

What is the pattern of joint involvement in primary osteoarthritis? Men vs women?

Answer 35

Oligoarticular, affecting especially the weight-bearing joints. Knees and hands - affected in women. Hands are very familial. Hips - affected in men Cervical and lower lumbar vertebrae - affected in both First tarso-metatarsal joint -> from stepping off of foot

Question 36

What pathologic features characterize the joint in general in osteoarthritis?

Answer 36

1. Joint space narrowing -> cartilage thinning leads to less radiolucent space between bones 2. Joint mice (loose bodies) - sloughed cartilage +/- bone into joint

Question 37

What are osteophytes? Do they have cartilage on them?

Answer 37

Bone spurs -> reactive bony outgrowths at the margins of the articular surface They are capped by cartilage (like osteochondroma). They grow laterally because they can't make bone on the weightbearing surface (they would get crushed).

Question 38

What genetic markers are associated with development of rhuematoid arthritis?

Answer 38

1. HLA-DRB1 - common epitope for presentation in MHC Class II 2. HLA-DR4 - 4 walls in a rheum 3. PTPN22 - protein tyrosine phosphatase - plays a role in inhibition of T cell activation. Increased risk if lost.

Question 39

What are the sensitive and specific antibodies for RA?

Answer 39

Sensitive: anti-CCP (cyclic citrullinated peptides) + rheumatoid factor (IgM or IgA antibodies against the Fc portion of IgG - unclear if involved) Specific: anti-CCP most specific CCPs are arginine residues which are post-translationally converted to citrulline.

Question 40

What type of inflammatory infiltrate characterizes the synovium and the joint fluid proper in RA?

Answer 40

Synovium: chronic inflammatory infiltrate with T cells and B cells responding and presenting CCP antigens Synovial fluid: Neutrophilic infiltrate -> immune complex deposition in joint (ultrafiltrate of plasma) activates complement. C5a attracts neutrophils and promotes cell lysis, which allows further exposure of citrullinated peptides.

Question 41

How do the bone changes in RA distinctively differ from OA?

Answer 41

RA -> T cell expression of RANKL leads to bone thinning and destruction OA -> subchondral sclerosis is characteristic, the exact opposite (eburnated bone surface becomes thickened to deal with the articular cartilage being lost)

Question 42

What is the pannus which is formed in RA? How does it invade?

Answer 42

The edematous, thickened synovial tissue with a villous transformation -> it is thickened by chronic inflammation and secretes many inflammatory factors, invading from the periphery of the joint capsule onto the articular surface (vs OA which is solely articular surface involvement)

Question 43

What can the pannus due to two adjacent bones that makes them highly immobile and decreases their range of motion?

Answer 43

Fibrous and bony ankylosis - Fusion of joint and fibrous tissue -> pannus is granulation tissue and can fuse bones together like a scar. Can happen in any inflammatory arthritis.

Question 44

Give an example of a synovial herniation in RA and why it happens?

Answer 44

Inflammation and edema into the synovial joint causes a synovial herniation. Commonly happens behind the knee -> popliteal fossa. This is called a "Baker cyst"

Question 45

Where are rheumatoid nodules and what is their histology?

Answer 45

They are usually found in areas of tissue damage -> i.e. on hands and elbows where damage would occur and allow citrullinated peptides to be exposed. Histology: Fibrinoid necrosis with palisading histiocytes

Question 46

What can RA cause in the lungs?

Answer 46

It is known to cause interstitial lung fibrosis. Can be caused when rheumatoid nodules appear in lungs. Some people think this often happens before joint involvement. Nodules can also be found in lung in combination with pneumoconiosis -> Caplan syndrome Endstage: honeycomb lung

Question 47

How is joint involvement of RA distinctively different from OA?

Answer 47

Affects MCP (not affected in OA unless secondary to hemochromatosis), wrist, shoulders, cervical spine (not affected unless secondary OA).

Question 48

What are the cardiovascular complications of rheumatoid arthritis?

Answer 48

Immune-mediated pericarditis Accelerated atherosclerosis due to chronic inflammation Small vessel leukocytoclastic vasculitis

Question 49

What are the eye and lung manifestations of rheumatoid arthritis?

Answer 49

Lungs - pleuritis, pulmonary nodules (identical to cutaneous rheumatoid nodules) which can lead to progressive fibrosis and honeycombing Eyes - scleritis -> diffuse or nodular. The sclera is the layer which is continuous with the cornea in the fibrous tunic.

Question 50

What is the general treatment scheme for RA?

Answer 50

NSAIDs and corticosteroids as rapid onset bridging therapy while the DMARDs and biologics come online. DMARDs: MTX, sulfasalazine, hydroxychloroquine, leflunomide Biologics: i.e. TNFalpha inhibitors, costimulation inhibitors, etc

Question 51

What drugs are used in the treatment of fibromyalgia?

Answer 51

Neuropathic pain! Do not use corticosteroids or narcotics. 1. Pregabalin and Gabapentin 2. SNRIs - duloxetine and milnacipran 3. Tricyclics - amitriptyline

Question 52

What is the normal nucleated cell count in synovial fluid and what is the minimum threshold for inflammatory joint disease? What conditions can cause extremely elevated counts?

Answer 52

Normal: <200 cells/uL Inflammatory: >2,000 cells / uL ``` Extremely inflammatory: >50,000 cells /uL 4 conditions: 1. Acute rheumatoid flares 2. Septic arthritis 3. Acute crystal arthritis 4. Reactive arthritis ``` These are mostly PMNs

Question 53

What is the most common cause of septic arthritis overall and in young adults?

Answer 53

Overall - Staph aureus, especially common in children even tho it cannot spread thru growth plate Young adults - if sexually active, Neisseria gonorrhea

Question 54

What is gonococcal dermatitis-arthritis syndrome? Who is at greatest risk?

Answer 54

Triad of pustules, migratory polyarthritis, and tenosynovitis Greatest risk are sexually active women, especially those with terminal complement deficiencies (C5-C9)

Question 55

Who tends to get gout, men or women, and why?

Answer 55

Tends to occur in men, because estrogen has a uricosuric effect Women can start getting gout after menopause Happens most commonly in blacks in their 30s-50s

Question 56

Give the breakdown pathway of adenine to uric acid and the rate limiting step.

Answer 56

Purine breakdown pathway: Adenine -> Hypoxanthine via adenosine deaminase. HX -> Xanthine via xanthine oxidase (XO) Xanthine -> uric acid via XO Note that hypoxanthine is the purine base of inosine. Aka Adenosine -> Inosine via adenosine deaminase.

Question 57

What is the cause of hyperuricemia in most patients and give a few examples of what can cause this?

Answer 57

90% of patients have hyperuricemia due to underexcretion Causes: renal insufficiency, keto or lactic acidosis, ethanol, thiazide diuretics, lead nephropathy, pyrazinamide (all complete for uric acid excretion in the kidney).

Question 58

What are the causes of hyperuricemia due to overproduction?

Answer 58

10% of patients: HGPRT deficiency (Lesch-Nyhan) PRPP synthetase overactivity (overproduction of purines) G6PD deficiency (too much hemolysis) Myeloproliferative disorders, cytotoxic chemotherapy, sickle cell anemia (cell turnover and tumor lysis syndromes)

Question 59

How does von Gierke disease cause gout?

Answer 59

von Gierke -> Glucose-6-phosphatase deficiency Lack of phosphate leads to ATP -> AMP -> adenine -> broken down to uric acid more readily. Furthermore, glucose is forced to be used in glycolysis -> high blood lactate levels. Lactic acidosis compete with uric acid transporter

Question 60

What are the characteristics of the birefringence of monosodium urate crystals?

Answer 60

Negative birefringence ParaLLel to polarized light = YeLLow Perpendicular = blue

Question 61

What is CPPD disease and what are the two clinical conditions on its spectrum?

Answer 61

Calcium pyrophosphate deposition disease 1. Chondrocalcinosis - radiographic evidence of calcification of cartilage -> many will not have pseudogout. (equivalent to hyperuricemia in gout) 2. Pseudogout - mono or polyarticular arthritis -> many patients with chondrocalcinosis never get this, and chondrocalcinosis is not required for diagnosis.

Question 62

What conditions are associated with CPPD disease?

Answer 62

1. Familial - ANKH gene - defect in phosphate transport 2. Hyperparathyroidism -> trying desperately to clear the phosphate out, also the calcium is building up. Associated with low phosphate levels in the blood because of this. Also associated with hypomagnesemia -> constitutive action of PTH. 3. Hemochromatosis - MCPs especially 4. Trauma / surgery

Question 63

What are the shared features of the seronegative spondyloarthropathies?

Answer 63

1. No rheumatoid factor (anti-IgG antibody) -> seronegative 2. Associated with HLA-B27 3. Insidious onset beginning before age 40 4. Inflammatory back pain -> associated with morning stiffness >1 hour, improves with exercise 5. Peripheral arthritis is also associated 6. Enthesitis - shared pathology of inflammation where ligaments / tendons insert onto bone 7. Dactylitis 8. Uveitis

Question 64

What peripheral joints are commonly involved in Ankylosing spondylitis and what problems can this cause? How does this tie into why the patients should quit smoking?

Answer 64

Commonly involves hips, shoulders, and joints of the chest wall: i.e. AC or sternoclavicular joints Involvement of costochondral and costovertebral joints can contribute to the development of restrictive lung disease -> loss of chest expansion is common in late-stage disease Apical pulmonary fibrosis and mechanical restrictive lung disease are very common -> another reason why these patients are advised to quit smoking

Question 65

What are the eye and cardiovascular complications common in AS?

Answer 65

Eye -> acute anterior uveitis is common, which is marked by painful eye redness and blurred vision. Cardiovascular -> Aortitis of ascending aorta leads to distortion of aortic ring -> aortic regurgitation is relatively common.

Question 66

How can AS be confused with OA?

Answer 66

There will be joint-space narrowing, cystic / erosive changes, and subchondral sclerosis. Note however: involvement of shoulders which can occur in AS would not happen in osteoarthritis unless it was secondary.

Question 67

What bacteria are implicated in reactive arthritis? -> remember that this is one of the seronegative spondyloarthropathies

Answer 67

GI: Shigella, Salmonella, Campylobacter, Yersinia -> all cause infectious diarrhea GU: Chlamydia

Question 68

Is psoriatic arthritis always seen in people with psoriasis? What type of arthritis is typically seen very characteristically?

Answer 68

Seen in about 30% of people Arthritis has varying presentations. Most characteristic: Asymmetric oligoarthritis which involves the DIP joints of the hands and feet. Dactylitis "sausage fingers" are also commonly seen. More rarely, joint involvement could be extensive enough to become polyarticular and symmetrical, mimicking RA.

Question 69

What are the radiographic characteristics of psoriatic arthritis?

Answer 69

1. Ray phenomenon - all joints in one digit can be involved (unique) 2. Bony ankylosis - loss of joint space with fusion. 3. Asymmetric erosive arthritis with no periarticular osteopenia (vs RA) 4. Pencil-in-cup deformity - > Distal part of the more proximal phalanx is sharpened via marginal erosion (due to synovitis) while the proximal part of the distal phalanx is widened (cup).

Question 70

What causes Marfan syndrome?

Answer 70

Autosomal dominant disorder of fibrillin-1 gene causing defective sheath around elastin -> chromosome 15

Question 71

What is the most common superficial fibromatosis and what will the clinical symptom commonly be?

Answer 71

Palmar fibromatoses. This thickening can frequently result in finger contraction, especially the 4th and 5th fingers = "Dupuytren contracture" -> due to collagen / myofibroblast contracture

Question 72

How do plantar and penile fibromatoses present?

Answer 72

Plantar - thickened nodules of fibroblasts on plantar fascia of feet Penile - thickening of tunica albuginea, leading to curvature of the shaft -> Peyronie disease

Question 73

Where do deep fibromatoses usually arise, in a broad sense?

Answer 73

Extra-abdominal - typically in large proximal muscle groups, very deep (i.e. thigh) Abdominal - anterior abdominal wall muscles, associated with pregnancy Intra-abdominal - often in the mesentery and the pelvis -> can cause volvulus. Especially associated with Gardner syndrome.

Question 74

What is the defining clinical characteristic of dermatofibroma and who gets it? What's the other name for it?

Answer 74

Benign fibrous histiocytoma - Tends to be on the legs of young to middle-aged women. Looks a bit like a melanoma, but DIMPLES with lateral compression

Question 75

What are the two growth patterns within a schwannoma? Does the tumor mass intermingle? What syndrome is it associated with?

Answer 75

Tumor mass is well demarcated and can be easily removed from the nerve (i.e. vestibular schwannoma) Associated with NF-2, loss of merlin. Two growth patterns characterize it histologically: Antoni A - Associated with Verocay bodies Antoni B - Hypocellular regions with myxoid stroma

Question 76

What is the single most common soft tissue malignancy of adults, and what cells are characteristic? Where does it arise? What mutation is associated?

Answer 76

Liposarcoma - a yellowish mass which contains lipoblasts -> cells composed of tiny vacuoles rather than large fat droplets Arises where all soft tissues malignancies tend to: retroperitoneum or deep proximal muscles (i.e. thigh) Associated with upregulation of p53 inhibitor

Question 77

What is the cell of derivation of synovial sarcoma and who gets it?

Answer 77

Occurs in young adults (in between children and normal older adults you see for sarcomas) Cell of differentiation is UNKNOWN -> called synovial because it arises near synovial joints (especially the knee)

Question 78

What are the mechanisms of polymyositis vs dermatomyositis?

Answer 78

Polymyositis - autoinvasive CD8+ T cells with endomysial inflammation due to direct attack of muscles Dermatomyositis - Antibody or immune-complex mediated microangiopathy (affects blood vessels) with secondary muscle damage

Question 79

Which inflammatory myositis presents more acutely and is associated with systemic symptoms? What are its symptoms?

Answer 79

Dermatomyositis - erythematous dermatitis over upper trunk, neck, and extensor surfaces of fingers, elbows, and knees - heliotrope rash - purple discolatoration with periorbital edema - rash on fingers gives look of calloused 'mechanics hands' with nailbed infarcts

Question 80

What is seen in the serum in patients with dermatomyositis and how does this relate to treatment?

Answer 80

Circulating antibodies to myosin and nuclear antigens -> plasmapheresis is a good treatment, more helpful in DM than PM anti-Jo-1 = anti-tRNA synthetase

Question 81

What will biopsy show for autoimmune myositis and how do you differentiate between dermatomyositis and polymyositis?

Answer 81

Both show segmental myonecrosis and regeneration with mononuclear inflammatory infiltrates -> CPK elevations Dermatomyositis - vasculopathic changes Polymyositis - CD8+ T cells

Question 82

What is the most typical treatment regimen for DM/PM?

Answer 82

Prednisone, which should be gradually tapered as symptoms improve. - > Add azathioprine, MTX, cyclosporin as needed - > rituximab if refractory

Question 83

What is the most common form of muscular dystrophy in adults? What causes it?

Answer 83

Myotonic dystrophy type 1 | - expanded CTG repeat in DMPK gene

Question 84

What are the relevant symptoms of myotonic dystrophy type 1?

Answer 84

CTG - cataracts, toupee (frontal balding), gonadal atrophy Myotonia - inability to relax muscles after vigorous effort - i.e. handshake Muscular dystrophy EKG changes - heart block leads to arrhythmias

Question 85

How do patients with myotonic dystrophy look? What is a common treatment required in this condition?

Answer 85

They have a "hatchet face" appearance -> muscle loss in temporal face + frontal balding makes face look elongated Need for pacemaker is common -> PR interval elongation progresses to heartblock

Question 86

What therapy is specifically indicated for ALS and what is its mechanism of action?

Answer 86

Riluzole - prolongs life in ALS by 4-6 months -think RiLOUzole as in Lou Gehrig's disease -Mechanism of action: anti-glutamate excitotoxicity

Question 87

What are common conditions which dermatomyositis is a paraneoplastic syndrome for?

Answer 87

Ovarian carcinoma, gastric carcinoma | -> remember this because of the Krukenburg tumor relationship

Question 88

Where does the inflammation occur in dermatomyositis vs polymyositis?

Answer 88

Dermatomyositis - Perimysial inflammation (CD4+ T cells) with perifascicular atrophy (inflammation at the EDGE of the muscle fascicle) Polymyositis - ENDOmysial inflammation -> CD8+ T cell inflammation INSIDE the muscle fascicile

Question 89

What is the genetic difference between Duchenne and Becker muscular dystrophy?

Answer 89

Duchenne - typically due to a frameshift mutation or nonsense mutation which leads to absent or truncated protein -> almost completely absent dystrophin so more severe. Sattar says Duchenne = Deletion. Becker - non-frameshift mutations, leading to reduced dystrophin or abnormal dystrophin, but still partially functional. Often due to exon deletions.

Question 90

What causes death in Duchenne Muscular Dystrophy?

Answer 90

Heart / Diaphragm become involved Death occurs due to respiratory compromise / infection / dilated cardiomyopathy

Question 91

What are the characteristic physical features of achondroplasia?

Answer 91

1. Rhizomelia - shortened proximal extremities 2. Brachydactyly with trident configuration - shorted digits with space between 3rd and 4th fingers 3. Macrocephaly - intramembranous bone formation not impaired 4. Midface hypoplasia 5. Frontal bossing 6. Lordosis, kyphosis, spinal stenosis