Derm and MSK

Question 1

Trinucleotide repeats

Answer 1

Huntington’s - CAG (caudate has less Ach and GABA)

Friedrichs ataxia - GAA

myotonic dystrophy - CTG –> abnormality in myotonin protein kinase

• frontal bladding
• muscle weakness in face - will see a teenager with mouth dropped open
• can’t relax muscle grip
• diabetes
• cardiac abnormality

Fragile X syndrome - CGG (chin, giant gonads)

• hypermethylation
• autism, MVP

scenario: couple is told their kid will be very abnormal
-couple has kid anyway and dies in 1 mo
= triple repeat

Question 2

myasthenia gravis

Answer 2

Type 2 HSR
IgG against AchR - affects striated muscle

ptosis, diplopia, dysphagia

eventually, all the receptors go

will see germinal follicles (B cells) in the thymus - they are making the antibodies
- thymectomy - 1/3 total cure, 1/3 partial cure, 1/3 no effect (all receptors are gone)

end plate potential affected - this is different from an AP
- sufficient end plate potential will trigger an AP

finding - decreased compound muscle AP amplitude with repeated excitation (summed APs of all muscle fibers in a motor unit)

ddx with edrophonium
treat with ACHe inhibitor = pyridostigmine
- use scopolamine/hyoscyamine in times of cholingeric excess - muscarinic Ach receptor antagonist

contrast to Eaton-Lambert - here you will also see dry mouth, impotence (autonomic symptoms)

Question 3

lupus

Answer 3

autoimmunity due to loss of self-tolerance

fever, migratory arthritis, hypocomplementemia, proteinuria

morning stiffness, photophobia, malar rash, pericarditis (serositis), oral ulcers, neuro disturbances

positive ANA - 99% sensitivity
+ anti-Smith (100% specificity) + anti-DSDNA (98% specificity, + indicates that pt has kidney disease)
- antihistone antibodies - specific for drug-induced

warm IgG antibodies against erythrocytes - cytopenias

libman-sacks endocarditis - on undersurface of valve

common causes of death - CVD, infections, renal disease

treat with NSAIDS, steroids, hydroxychloroquine

side note - antiphospholipid syndrome - long PTT
- lupus anticoag, anticardiolipid, anti-b2 glycoproteins

Question 4

dermatomyositis

Answer 4

general - increased CK, ANA, anti-Jo, anti-SRP, anti-Mi2-antibodies
- steroids and methotrexate

poliomyositis - endomysium, CD8, shoulders
……………………
dermatomyositis - like poliomyositis + rash

highest association of underlying cancer - it is a paraneoplastic syndrome
- ovarian, lung, CRC, NHL

photosensitive, raccoon eyes (heliotrope), myositis –> elevated serum CK

Goitron’s patches - over IP joints

perifascicular muscle inflammation and patchy necrosis - proximal muscle weakness

Question 5

Sjogren’s syndrome

Answer 5

inflammatory joint pain +

antibodies that destroy salivary glands (dry mouth, bilateral parotid enlargement) and lacrimal glands (dry eyes)
- can have MALT lymphoma - presents as parotid enlargement

biopsy of lower lip - confirmatory ddx, will see lymphocytes destroying the salivary glands

anti-SSA (anti-rho) and anti-SSB (anti-La) = antibodies
[- side note about anti-rho antibodies - pts with lupus can have it, it can cross the placenta and destroy the baby’s conduction system –> baby with complete heart block)]

Question 6

seborrheic dermatitis

Answer 6

Malassezia furfur = fungus

pre-AIDS defining lesion

Question 7

microsporum canis

Answer 7

bald spot on head

black light (UVA light aka Wood’s light) causes lesion to fluoresce

microsporum canis - used to be most common cause of tinea capitis

now the most common cause is trichophyton tonsurans - fluorescent metabolites are on the other side of the hair shaft, so Woods lamp negative
-ring worm - scrape the outside - do a KOH prep, will see hyphae

all other superficial dermatophyte infections are due to trichophyton rubrum

Question 8

Pityriasis rosea

Answer 8

non-pruritic oblong patch (herald patch) –> KOH prep shows nothing –> you prescribe topical steroids

3 days later, pt returns - rash with lines of Langer and christmas tree distribution on trunk

NOT infectious, NOT a fungus

self-resolving

Question 9

nevus

Answer 9

precursor lesion for melanoma

100+ = dysplastic nevus syndrome

first step in management - excision

superficial spreading malignant melanoma is most common

on elderly - lentigomalignant melanoma - seen on face, least likely to met

black population dont get malignant melanomas - pigment in skin prevents UV light penetration

• but they do get - acral lentiginous malignant melanoma, most aggressive melanoma
• scenario: black person comes in with dyspnea - CT shows melanoma mets in lung - where is the primary?
  
  • under the nails, palms, or soles of the feet = acral lentiginous malignant melanoma
  • has nothing to do with radiation

nodular malignant melanoma - also aggressive

prognosis - depth of invasion!, < 0.76 mm - no way there will be mets

Question 10

poisonous spiders

Answer 10

black widow spider - neurotoxin –> produces spasm of the muscles of the upper thigh and abdomen
- painful bite - scenario, person goes to their basement…sharp pick… located in Oklahoma
- anti-venom
“black widow will drive you crazy”

brown recluse - violin spider

• no pain
• necrotoxin - ulcer in skin

Question 11

in the skin, where is the receptor for androgen receptors

Answer 11

in the sebaceous glands - DHT!

athletes - consider steroid use
- methyltestosterone

acne

1) follicular epidermal hyperproliferation
2) excessive sebum production
3) inflammation
4) P. acnes

other causes of acne - EGFR inhibitors, Li

Question 12

pseudogout

Answer 12

rhomboid crystals, but can also have needle-shaped crystals

• blue in parallel light = positive birefringence
• chondrocalcinosis

v. s. gout: negative birefringence - yellow under parallel light
- alcoholics get gout because kidneys excrete lactic acid (and b-hydroxybutyrate) instead of uric acid
- tophus - MSU in soft tissue –> can erode away joints
- can be exacerbated by diuretics (thiazides)
- initially, treat with anti-inflammatory (indomethacin, NSAID)
- colchicine is second-line (impairs neutrophil migration and phagocytosis by interfering with microtubule formation, ADR is GI upset)
- allopurinol, febuxostat for overproducers and pts with tophi
- probenicid (and high dose salicylates, inhibits uric acid reabsorption in PCT, also inhibits secretion of penicillin), sulfinpyrazone (both inhibits uric acid reabsorption at PCT) for underexcretiors
- pegloticase - recombinant uricase
- note - salicylates and diuretics inhibit tubular secretion)

Question 13

arthritis

Answer 13

osteoarthritis - asymmetric

• wearing down articular cartilage –> narrow joint space
• osteophyte - bone spur at end of joint due to continuous wearing down of articular cartilage (mediated by chrondocytes)
• subchondral sclerosis and cysts
• knee cartilage loss begins medially - bow legged
• Bouchard’s nodes and Heberdens nodes
• DIP and PIP involved (think old lady who does needle work

RA (HLA-DR4, smoking, silica exposure) - IgM against IgG in synovial fluid –> complement is activated –> neutrophils comes in –> damage to joint

• synovial issue grows over articular cartilage (pannus) and destroying it –> fibrosis –> fixing/ankylosis of joints
• have to move joints, symmetric joint involvement
• ulnar deviation of joints
• rheumatoid nodules - pallisading histiocytes around central necrosis
• long-standing RA involves the cervical spine –> joint destruction and subluxation (esp C1 against C2)
  - chronic subluxation - neck pain/stiffness, neuro findings
  - endotracheal intubation can WORSEN subluxation and cause compression of SC –> quadriplegia –> which progresses to spastic paralysis
• anti-CCP are more specific
• treat with DMARDs, TNFa inhibitors, etanercept (decoy receptor protein)
• scenario - pt having trouble eating crackers, and in my eyes –> pt with RA has developed Sjogren’s syndrome (autoimmune destruction of lacrimals and minor salivary glands)
• scenario 2 - pt with rheumatoid nodules + pneumoconiosis = Caplan syndrome
• methotrexate treatment (folate deficiency, interstitial fibrosis of lungs)
• can add etanercept - TNF-a inhibitor to methotrexate if needed, etanercept is a TNF-a decoy receptor (that is linked to human IgG)
• hydroxychloroquine - used in mild RA and SLE, tox is irreversible retinopathy

…………………………………………………………………..
seronegative spondyloarthritis (no RF) - HLA-B27, PAIR
Psoriatic arthritis - dactylitis (sausage fingers), nail findings, pencil in cup DIP

AK - HLA-B27, young men

• wake up in the morning with severe lower back, pain in SI joints - inflammatory reaction
• improves throughout the day, relieved with exercise
• bamboo spine, costovertebral/costosternal fusion (restrictive lung disease)
• aortitis, uveitis, iritis

IBD - UC, Crohns

Reiter’s syndrome

• pt with HLA-B27 + gets chlamydia infection –> progresses to AK (occurs more commonly in men)
• other triggers in HLA-B27 pts - Shigella, psoriasis, UC, yersnia, campy, salmonella
• Achilles tendonitis - inflammatory reaction
• conjunctivitis, urethritis, arthritis - cant see, cant pee, cant bend my knee

……………………………………………………………………….
Alkaptonuria - AR
- degenerative arthritis due to homogentisate dioxygenase deficiency –> homogentisate acid accumulates in the urine and intervertebral cartilages (black pigment in spine)
- urine turns black upon exposure to sunlight

Question 14

osteogenesis imperfecta

Answer 14

cant make type 1 collagen

mechanism of blue sclera - sclera becomes thin and see-through, can see underlying choroidal veins

Question 15

DMD

Answer 15

XR - absent dystrophin (due to frameshift mutation)
elevated serum CK
pseudohypertrophy of calves - calves filled with adipose tissue

BMD - abnormal dystrophin protein

Question 16

cromoyln sodium

Answer 16

inhibits mast cell degranulation

Question 17

thyroidectomy

Answer 17

recurrent laryngeal, weakness of posterior cricoarytenoid muscles, hoarseness with impaired breathing

Question 18

come lets get sunburned

Answer 18

Corneum - anucleate
Lucidum
Granulosum -
Spinosum - desmosomes connect neighboring cells (edema will show cells connected by spines)
Basal layer
BM
dermis - blood vessels, hair shafts, glands

Question 19

inflammatory dermatoses

Answer 19

dermatitis (flexors), acne, psoriasis (extensor), lichen planus

atopic dermatitis aka eczema
- pruritic, erythematous, oozing rash with vesicles and edema
- face (infants) and flexors
- type 1 HSR (so IgE, mast cells) - associated with asthma and allergic rhinitis
….vs contact dermatitis (nickel, chemicals, PENICILLIN)
- epidermal spongiosis
- topical steroids

acne vulgaris

• comedones, pustules, nodules
  1) excess keratinization of hair shaft
  2) excess production of sebum (androgen sensitive)
  3) P acnes –> produces lipases –> breakdown sebum –> pro-inflammatory fatty acids –> pustule –> nodule
• treat with benzoyl peroxide to kill P acnes, vitamin A derivatives will reduce keratinization

psoriasis

• due to excessive keratinocyte proliferation - autoimmune, HLA-C, trigger (trauma)
  - hyperplasia of epidermis = acanthosis (specifically spinosum)
• well-circumscribed salmon-colored plaques with silvery scale (keratin will have nuclei = parakeratosis)
• extensors and scalps
• pitting of nails may also be present
• neutrophils in s. corneum - microabcesses
• increased stratum spinosum, decreased stratum granulosum
• elongation of dermal papillae with thinning of overlying dermis - pulling away silvery scale will lead to pinpoint bleed (Auspitz sign)
• treat with corticosteroids and immune-modulating therapy
• UVA + psoralen (increases absorption of UVA light) - UVA light damages keratinocytes – they cant proliferate
• can also treat with calcipotriene (vitamin D analog)

lichen planus (Ps)

• pruritic, planar, polygonal in shape, purple papules
• increased thickness of stratum granulosum
• reticular white lines on surface (Wickham striae)
• wrists, elbows, and oral mucosa
• inflammation at dermal epidermal junction –> sawtooth appearance
• associated with chronic HCV

Question 20

blistering dermatoses

Answer 20

separating layers of skin –> VESICLES

Pemphigus vulgaris - autoimmune destruction of desmosomes

• due IgG antibody against desmoglien3
• IF highlights IgG around keratinocytes = fish-net appearance
• acantholysis of stratum spinosum - occurs when you separate keratinocytes
• tombstone appearance along dermis - basal cells poke out like tombstones
• thin epidermis - easily ruptured blisters (and you can have separation of epidermis upon manual stroking of skin)
• can also involve oral mucosa

Bullous pemphigoid (think B for Basal)

• autoimmune destruction of hemidesmosomes
• IgG antibody against BM - linear IF
• presents as subepidermal blisters of skin - oral mucosa spared
• tensee bullae do not rupture easily (contain eos)

dermatitis herpetiformis

• IgA (IgA against gluten) deposition at tips of dermal papillae - on extensor surfaces
  - overlying basal cells become vacuolated and coalescing blisters form over papillae
• celiacs! - increased intrapepithelial lymphocytes, villus destruction, crypt hyperplasia
• treat with dapsone

erythema multiforme

• HSR with targetoid rash (due to central necrosis) and bullae
• HSV, myoplasma, lupus, malignancy, penicillin, sulfa drugs
• erythema multiforme involves skin - if it involves 2 mucosa and fever –> SJS/TEN
  - diffuse sloughing of skin resembling a large burn - sloughing at dermal-epidermal junction
  - TEN is a medical emergency

Question 21

epithelial tumors

Answer 21

seborrheic keratosis

• benign squamous proliferation, common in elderly
• stuck-on-plaque
• circular spaces with abundant pink keratin = pseudocysts (look like onion-ringed inclusions)
• Leser-Trelat sign

acanthosis nigricans - insulin resistance or malignancy

basal cell - most common

• risk factors include prolonged exposure to sunlight, albinism, xeroderma pigmentosum (AR, defect in DNA endonuclease)
• elevated nodule - central ulceration - surrounded by telangiectasias (dilated blood vessels)
• upper lip
• appearance is variable - waxy nodules, ulceration
• nodules of basal cells with peripheral palisading
• surgical excision - rarely mets, excellent prognosis

squamous cell carcinoma

• risk factors include prolonged exposure to sunlight, albinism, xeroderma pigmentosum
• additional risk factors - immunosuppressive therapy (transplant pts), arsenic poisoning, chronic inflammation (burn scar, draining sinus tract)
• presents as ulcerated, nodular mass on lower lip with scale
• locally invasive, may spread to LNs
• excise - mets uncommon

actinic keratosis = precursor to squamous cell carcinoma (but less than 1% actually progress)

• presents as hyperkeratotic, scaly plaque on face, back, or neck (increased stratum corneum)
• whitish scale - felt more than seen
• can have cutaneous horns

keratoacanthoma

• well-differentiated SCC
• develops rapidly and regresses spontaneously
• cup-shaped tumor filled with keratin debris

Question 22

disorders of pigmentation and melanocytes

Answer 22

melanocytes - present in basal layer

• tyrosine –> melanin in melanosomes –> melanosomes are passed off to keratinocyes
• from neural crest

vitiligo

• autoimmune destruction of melanocytes
• in a light skinned individual - failure to TAN

albinism - defective tyrosinase

• ocular form, oculocutaneous form
• increased risk of skin cancer - basal cell, squamous cell, melanoma

freckle - due to increased numbers of melanosomes
- darkens when exposed to sunlight

melasma

• mask-like hyperpigmentation of cheeks
• associated with pregnancy and OCPs

nevus - benign neoplasm of melanocytes
- hair grows from it
melanoma
acquired nevus
- junctional (kids, flat), into dermis (compound nevus), intradermal nevus (adults, papule)

MELANOMA - malignant neoplasm, BRAF kinase mutation (can treat with vemurafenib)

• most common cause of death from skin cancer
• risk factors is increased UVB
• dysplastic nevus syndrome - AD
• ABCDs (D > 6mm)

1) radial growth in epidermis - low risk for mets
2) vertical growth into deep dermis - depth prop to mets
- lentigo maligna melanoma - lentiginous proliferation (radial growth) - good prognosis
- superficial spreading (most common) - dominant early radial phase, good prognosis
- nodule - early vertical phase, poor prognosis
- acral lentiginous melanoma - arises on palms or soles often in dark-skinned individuals
- not related to UV light exposure

Question 23

infectious skin disorders

Answer 23

impetigo - S. pyogenes, S. aureus
- erythematous macules –> pustules

erysipelas - upper dermis and superficial lymphatics, S pyogenes

cellulitis - dermal infection

• S. pyogenes (hyaluronidase), S. aureus
• presents as red, tender, swollen rash with fever
• can progress to nec fasc (subQ tissue) –> CO2, crepitus, medical emergency

Staph scalded skin syndrome = S. aureus

• sloughing of skin with erythematous rash and fever
• leads to sig skin loss, heals completely
• see in kids and adults with renal insufficien9cy
• exfoliative A and B toxins - separates stratum granulosum (toxin cleaves desmoglein)
  v. s. TEN - separation at dermal-epidermal junction

verruca - HPV, rough surface, hands and feet
- cauliflower-like epidermal hyperplasia

molluscum contagiosum

• firm, pink umbilicated papules due to POXvirus (enveloped, dsDNA, linear)
• most often arise in kids - but also in sexually active adults and immunocompromised individuals
• molluscum bodies in keratinocytes = viral inclusions (eosinophilic)
• sandy-like material in the center of the crater –> self-innoculate –> repeated infection

hairy leukoplakia - EBV, HIV, cant scrape off, precancerous

Question 24

back pain ddx

Answer 24

degenerative, inflammatory (autoimmune), infectious, mets (constant pain, worse at night, not responsive to position changes)

prostate cancer
- androgen receptor blockers - spironolactone, cyproterone, flutamide

spinal stenosis - pain with standing, relieved by spine flexion

radiculopathy eg disk herniation - radiates to leg, positive straight leg raise test

• discs herniate posteriorly because of thick anterior longitudinal ligament
• L3-L4 - knee extension
• L4-L5 - dorsiflexion
• L5- S1 - achilles, plantar flexion

Question 25

cell-ECM connections

Answer 25

actin - integrin, traverses cell membrane - fibronectin - collagen
- fibronectins are produced by fibroblasts, call bind to GAGs

decreased integrin expression - melanoma

Question 26

knee exam

Answer 26

ACL
- will be anterior on tibial plateau

PCL - looks almost entirely posterior
- originates on anterolateral medial condyle –> inserts on posterior intercondylar area

abnormal passive abduction - MCL tear (lower leg abducts out)

McMurray - pain on external rotation, medial meniscus tear

common pediatric fractures - greenstick fracture, torus fracture (axial force –> buckle fracture of cortex)

unhappy triad - sports injury –> ACL, MCL, medial meniscus damaged
- but lateral meniscus injury is more common

suprapatellar bursitis - trauma, running

pre-patellar bursitis - housemaids knee

anserine bursitis - pain on medial knee below joint margin
- due to obesity or overuse in athletes

Baker cyst - popliteal fluid collection, related to chronic joint disease (extrusion of fluid from joint into bursa)

Question 27

rotator cuff

Answer 27

SITS - C5-C6
supraspinatus, suprascapular nerve - abducts arm initially (then deltoid jumps in)
- most common rotator cuff tear –> can lead to tendinopathy
- empty can test

infraspinatus, suprascapular nerve - laterally rotates arm, pinching injury

teres minor, axillary nerve - adducts and lateral rotates arm

subscapularis, subscapular nerves - medially rotates and adducts arm

side note- muscles that abduct the arm

• supraspinatus (suprascapular), deltoid (axillary)
• 100deg (+) - trapezius (accessory), serratus anterior (long thoracic

Question 28

elbow

Answer 28

medial epicondylitis - repeated flexion, golfers elbow

lateral - extension, tennis elbow

Question 29

wrist

Answer 29

scaphoid - FOOSH, avascular necrosis

dislocation of lunate can cause acute carpal tunnel

carpal tunnel - median nerve compression

• thenar atrophy, sensation spared (palmar cutaneous branch enters above carpal tunnel)
• associated with pregnancy, RA, hypothyroid, DM, acromegaly, dialysis-related amyloidosis

Guyon canal syndrome - compression of ulnar nerve, cyclists

Question 30

upper extremity nerves

Answer 30

humerus fractures follow the A-R-M (proximal to distal)

axillary (C5-6) - head/neck of humerus

• flattened deltoid, loss of arm abduction
• loss of sensation over deltoid muscle and lateral arm
• posterior circumflex artery

musculocutaneous (C5-C7) - upper trunk compression
- loss of forearm flexion and supination, loss of sensation over lateral forearm

radial (C5-T1) - runs with deep brachial artery

• midshaft fracture of humerus or compression of axilla (crutches)
• wrist drop - loss of elbow, wrist, and finger extension
• loss of grip strength
• loss of posterior arm sensation

median (C5-T1) - runs with brachial artery

• supracondylar fracture of humerus, carpal tunnel
• loss of flexion in pope’s blessing region (palmar surface)

recurrent branch of median (C5-T1)
- superficial laceration of palm - loss of thenar muscle group (cant oppose thumb), sensation intact

ulnar (C8-T1)

• fracture of medial epicondyle of humerus or hook of hamate
• ulnar claw on digit extension

dorsum of hand = fingers (median nerve), back of hand (radial and ulnar nerves)

brachial artery (starts behind the M)

• -> deep brachial at mid-humerus (posterior) –> radial collateral and middle collateral arteries
• -> brachial artery (anterior, runs with radial nerve) –> radial and ulnar arteries
• supracondylar fractures may injury brachial artery

Question 31

brachial plexus lesions

Answer 31

Erbs palsy - waiters tip

• traction of upper trunk C5-C6 (musculocutaneous and suprascapular) - trauma, lateral traction on neck during delivery
• affected muscles - deltoid, supraspinatus, infraspinatus, biceps brachii

Klumpke palsy - traction tear of lower trunk (C8-T1 root)
- upward force on arm during delivery, adult grabs a tree branch to break a fall
- claw hand (due to damage to lumbricals)
AND related - thoracic outlet syndrome - compression of lower trunk and subclavian vessels
- cervical rib, pancoast tumor
- atrophy of intrinsic hand muscles - due to vascular compression

winged scapula - cant abduct arm above horizontal

Question 32

hand

Answer 32

claw - with distal lesions of median or ulnar nerves

• loss of balance between flexors and extensors - MCPs extend, flexion at DIP and PIP
• here distal is close to the shoulder?

deficits are less pronounced with proximal lesions - voluntary flexion of digits

DAB PAD - dorsals abduct, palmars adduct
lumbricals flex at MCP, extend at IPs

Question 33

muscle conduction and contraction

Answer 33

skeletal muscle - 1 tubule, 2 cisternae (of SR)
cardiac muscle - 1 tubule, 1 cisternae
1) AP opens Ca2+ channels –> NT release –> depolarization of motor end plate
2) depolarization travels down T tubule –> depolarization of dihydropyridine receptor
- which is MECHANICALLY coupled to RyR
3)… binding of ATP causes detachment of myosin head from actin filament, hydrolysis of ATP cocks head, release of ADP and Pi causes power stroke

type 1 muscle - slow twitch, red fibers (mitochondria, myoglobin), sustained contraction

type 2 - fast twitch, anaerobic glycolysis

smooth muscle contraction:

• Ca2+ enters and bind Ca-calmodulin complex –> activates myosin light chain kinase –> contraction
• remember - NO activates myosin-light chain phosphatase

Question 34

bone formation

Answer 34

endochondral ossification - cartilage –> woven bone (haphazard organization of collagen sheets) –> lamellar bone

• woven bone occurs after fractures and in Padget’s disease
• defective in achondroplasia (AD, fully penetrant) - failure of longitudinal bone growth
  - constitutive activation of FGFR3 - inhibits chondrocyte proliferation (normally bone growth relies on chondrocyte apoptosis, upon which mineralization occurs)

membranous ossification
- woven bone without cartilage (direct deposition of new bone on old bone) - calvarium, facial bones, clavicle

osteoblast - mesenchymal

• estrogen inhibits osteoblast apoptosis, promotes osteoclast apoptosis
  - causes closure of epiphyseal plate during puberty
• osteoblastoma, osteoid osteoma - benign, bone pain worse at night

osteoclast - monocyte origin, secretes H+ and collagenases to dissolve bone

………………………………………………………..
osteoporosis
- non-modifiable - age, sex, White/Hispanic/Asia, FH
- AAs have greater bone density
- modifiable - decreased physical activity/low body weight, poor Ca and vit D intake, excessive alcohol and tobacco use, premature menopause, glucocorticoid use
-estrogen inhibits IL1 - low estrogen –> increased IL1, TNFa, increased expression of RANKL (–> NF-kB)
- fracture - vertebral body, hip, sometimes femoral neck or distal radius (Colles fracture)
-CYP inducers, aromatase inhibitors, medroxyprogesterone, GnRH agonists (decrease estrogen and testosterone), PPIs (decrease Ca2+ absorption), decreased bone formation (glucocorticoids, unfractionated heparin, thiazolidinediones), tobacco, low body weight are other risk factors
- weight training and walking puts the stress on bones - increases bone mass
- 1500 mg Ca and 400 units of vitamin D/daily - primary prevention things that a lady in reproductive age should be taking
- treat with bisphosphonates, teriparatide, SERMs, denosumab (anti-RANKL)
- bisphosphonates - pyrophosphate analogs –> inhibit osteoclast activity, ADRS (esophagitis if taken orally, osteonecrosis of jaw, atypical stress fractures)
- teriparatide - PTH analog, increases osteoblastic activity, avoid in pts who have had prior cancers/radiation therapy, increased risk of osteosarcoma
- thiazides have been associated with higher mineral bone density and reduced fracture risk

osteopetrosis - failure of normal bone resorption due to defective osteoclasts - osteoclasts cant generate an acidic environment (CA2 mutation)

• thickened bones are prone to fracture
• bone fills marrow space… and other spaces (cranial nerve impingement)
• marrow transplant (osteoclasts are derived from monocytes)

osteomalacia - pseudofractures, epiphyseal widening
- increased PTH and activity of osteoblasts (increased ALP)

Padget’s disease - localized increased osteoclastic and then osteoblastic activity –> poor quality bone
- issue is excessive RANK and NFkB activation –> osteoclast differentiation
phases - 1) lytic, 2) mixed (disorganized woven and lamellar bone), 3) sclerotic (osteoblasts only), 4) quiescent
- in the sclerotic phase - you will see a mosaic pattern of lamellar bone with prominent cement lines
- features are of accelerated bone remodeling and eventual bony overgrowth: pt has increasing hat size, hearing loss (auditory foramen has narrowed)
- new bone is weaker
- increased ALP, all else normal
- AV shunts - occurs in the early stages, osteoclasts are releasing cytokines –> stromal proliferation. High output cardiac failure
- increased risk of osteogenic carcinoma
- treat with bisphosphonates

avascular necrosis - very painful

• due to insufficiency of medial femoral circumflex
• corticosteroids, alcoholism, sickle cell, trauma, bends, Gaucher

Question 35

bone tumors

Answer 35

benign
osteochondroma - males <25
- bony exostosis with cartilaginous cap, rarely transforms to chondrosarcoma
- Ollier’s disease - osteochondromas all over body (develop close to the growth plates of the humerus), increased risk for becoming malignant (chondrosarcoma)

giant cell tumor - 20-40 yo

• knee, epiphysis region - osteoclastoma, soap bubble appearance on xray
• multinucleated giant cells that express RANK-L

malignant
osteosarcoma - bimodal dist
- risk factors - Padget disease, bone infarcts, radiation, familial RB, Li-Fraumeni
- metaphysis of long bones - again around knee, invades through periosteum and into muscle
- sunburst pattern on XR, codman triangle

Ewing sarcoma - boys < 15

• diaphysis of long bones, pelvis, scapula, ribs
• anaplastic, small blue cell tumor - early mets but responds to chemo
• onion skin reaction of periosteum
• associated with t(11;22)

Question 36

septic arthritis

Answer 36

S. aureus, Streptococcus, N. gono (dermatitis, tenosynovitis, knee arthritis)

leukocytes > 100,000 (v.s. gout will present with a much lower leukocyte count)

Question 37

aspirin and NSAIDs

Answer 37

low dose - decreased platelet aggregation
intermediate - antipyretic and analgesic
high - anti-inflam

ADRs - ….tinnitus (CN8), ARF/interstitial nephritis
- early resp alk, later mixed metabolic acid-resp alk

note- celecoxib - sulfa allergy

Question 38

leflunomide

Answer 38

reversibly inhibits dihydroorotate dehydrogenase –> prevents pyrimidine synthesis
- suppresses T cell proliferation

ADRs - diarrhea, HTN, hepatotox, teratogenicity

Question 39

sunburn

Answer 39

inflammatory reaction to UVB

Question 40

tumors

Answer 40

angiosarcoma - head, neck, breast, usually in eldery on sunexposed areas

• associated with radiation therapy and post-mast lymphedema
• side note - breast cancer itself will met to bone, liver, lungs
• dermis will be infiltrated with slit-like abnormal vascular spaces

superficial/strawberry hemangioma - will affect an infant, will spontaneously involute
cavernous hemangioma - dilated vascular space, skin, viscera, brain (associated with VHL)

cherry hemangioma - congested capillaries in papillary dermis

glomus tumor - blue tumor, under fingernails, from modified smooth muscle from thermoregulatory body

• afferent arteriole –> innervated muscular AV anastomosis –> efferent arteriole
• glomus bodies shunt blood away from skin surface in cold temps to prevent heat loss vv

pyogenic granuloma - polypoid lobulated capillary hemangioma –> can ulcerate and bleed, associated trauma and pregnancy

Kaposi - can also affect GI and lungs

Question 41

other skin conditions
rosacea
pseudofolliculitis barbae
urticaria

Answer 41

pseudofolliculitis barbae - looks like razor bumps, primary on AA
- painful, pruritic papules/pustules

rosacea - can sometimes cause rhinophyma or bulbous deformation of nose
- can be associated with external stimuli

urticaria - hives - superficial dermal edema and lymphatic channel dilation

Question 42

epithelial cell junctions

Answer 42

tight junctions - claudins, occludins

adherins - actin and cadherins, Ca2-dep adhesion
- connect cells

desmosome-IF - structural support

gap junctions - connexons

Question 43

scleroderma

Answer 43

autoimmunity, noninflam vasculopathy, collagen deposition with fibrosis

• taught face, fingertip pitting
• sclerosis of organ systems - sclerosis of pulmonary system is the most common cause of death

diffuse - anti-Scl-70 (anti-DNA topo1)
limited - to fingers and face = CREST
- calcinosis, anti-centromere antibody
- Raynaud
- esophageal dysmotility
- sclerodactyl
- telangeictasia

Question 44

lower extremity nerves

Answer 44

iliohypogastric T12-L1 - can be injured in abdominal surgery

• sensory - suprapubic region
• motor - transversus abdominis and internal oblique

genitofemoral - L1-L2 - can be injured in laparoscopic surgery

• sensory - scrotum/labia majora, medial thigh
• motor - cremaster

lateral femoral cutaneous - L2-L3
- anterolateral thigh - can be injured by tight clothing, obesity, pregnancy

obturator - L2-L4, can be injured in pelvic surgery

• sensory for medial thigh
• motor - adduction

femoral L2-L4 - pelvic facture

• sensory for anterior thigh
• motor - thigh flexion, leg extension (quads, psoas)
• saphenous nerve (branch of femoral) - loss of medial leg sensation

sciatic - L4-S3, herniated disk

• sensory - posterior thigh
• motor - hams
• -> common peroneal (L4-S2) - dorsiflexes (deep) and Everts foot (superficial branch) –> injury leads to foot drop
  - sensory of dorsum of foot, motor is foot extensors
  - can be damaged in fibular neck fracture
• -> tibial (L4-S3), runs with popliteal and post tibial - damaged in knee trauma, Baker cyst, tarsal tunnel syndrome
  - sensory of sole of foot, motor is flexors and inversion (damage leads to inability to curl toes)

superior gluteal L4-S1 - can be injured during IM injection to superomedial quadrant

• Trendelenburg gait - pelvis tilts on normal side (weight bearing, injured leg cant maintain pelvic alignment)
  - ipsilateral lesion when pt is standing
  - always inject in superolateral quadrant - to avoid this nerve

inferior gluteal L5-S2 - glut max!

• injured in posterior hip dislocation
• difficulty climbing stairs, rising from a seated position, cant extend hip

pudenal S2-S4 - sensory perineum, motor sphincters
- stretched during childbirth

Question 45

actions of hip muscles

Answer 45

abductors - glut med and min

extensors - glut max, hams

flexors - iliopsoas, rectus fem, TFL
- sit up from supine - also using abdominal muscles

internal rotation - gluts, TFL

external - iliopsoas, glut max, piriformis, obturator

Question 46

McArdle disease

Answer 46

glycogen storage disease - where muscle glycogen cant be broken down due to a defect in myophosphorylase

–> muscle weakness and cramping during exercise –> impaired energy production during muscle contraction

Question 47

xanthelasma

Answer 47

lesion on eyelid - contains lipid-laden macrophages

associated with hyperlipidemia - chronic cholestatic processes result in hypercholesterolemia

Question 48

mixed CT disease

Answer 48

associated with anti-U1 RNP antibodies (speckled ANA)

Question 49

sarcoidosis

Answer 49

elevated ACE, Ca2+, and CD4/CD8 ratio

hilar and mediastinal adenopathy

associated with restrictive lung disease, erythema nodosum, skin lesions that look like lupus, Bells palsy

treat with steroids if symptomatic

Question 50

polymyalgia rheumatica

Answer 50

pain and stiffness in shoulders and hips + fever/malaise
- does not cause muscle weakness, normal CK

elevated CRP, ESR, associated with temporal arteritis - rapid response to low dose steroids

Question 51

fibromyalgia

Answer 51

tender points, stiffness, paresthesia, fibro fog

treat with regular exercise, anti-depressants, anticonvulsants

Question 52

vertebral osteomyelitis

Answer 52

localized back pain, fever, previous staph bacteremia from an IV catheter = vertebral osteomylelitis

hematogenous spread is the most common (vertebral bone has a very rich and vascular marrow), other spreading methods can occur

staph, some gram negatives (pseudomonas)

initial eval = blood cultures, MRI of spine