USMLE - Musculoskeletal and Connective Tissue Part 2

↓Ca

No change in PO4

↑ ALP

No change in PTH

Thickened, dense bones

↓ Ca

↓ PO4

↑ ALP

↑ PTH

Soft Bones

↑ Ca

↓ PO4

↑ ALP

↑ PTH

"Bone tumors" of hyperparathyroidism

No change in Ca

No change in PO4

↑ ALP

No change in PTH

Abnormal bone architecture

Bone replaced by fibroblasts, collagen, and irregular bony trabeculae
McCune-Albright Syndrome characterized by multiple unilateral bone lesions associated with endocrine abnormalities (precocious puberty) and cafe-au-lait spots

Osteoclastoma

20-40 year olds

Epiphyseal end of long bones: distal femur, proximal tibial region (knee)

Locally aggressive benign tumor

Double bubble or soap bubble appearance

Spindle-shaped cells with multinucleated giant cells

Exostosis

Most common benign tumor

Males < 25

Originates from long Metaphysis

Mature bone w/ cartilaginous cap

Malignant transformation into chondrosacroma is rare

Osteogenic sarcoma
2nd most common primary malignant bone tumor (after multiple myeloma)
Male > female, 10-20 years old
Aggressive
Surgical en bloc resection (with limb salvage) and chemotherapy

Wider portin of long bone adjacent to epiphyseal plate

Paget's disease of bone, Bone infarcts, Radiation, Familial Retinoblastoma
Metaphysis of long bone often around distal femur and proximal tibial region (knee)
Codman's Triangle (from elevation of periosteum) or sunburnt pattern

Boys < 15 years old
Diaphysis of long bones, pelvis, scapula, and ribs
Anaplastic small blue cell tumor
Malignant

Onion skin appearance in bone
t(11;22) translocation
Extremely aggressive with early mets
Responsive to chemotherapy

Men 30 - 60
Diaphysis. Pelvis, Spine, Scapula, Humerus, Tibia, Femur
Malignant
Cartilaginous
Primary or from osteochondroma
Expansive glistening mass within medullary cavity

Mechanical (wear and tear) destruction of articular cartilage
Age, Obesity, Joint deformity
NSAIDs, Intra-articular glucocorticoids

Pain in weight-bearing joints after use (at end of day), Improves with rest, Knee cartilage loss begins medially (bowlegged), No systemic symptoms, Not inflammatory
Subchondral cysts, Sclerosis, Joint narrowing, Osteophytes (bone spurs)
Eburnation (polished, ivory like appearance of bone), Ulcerated cartilage, Thickened capsule, Synovial hypertrophy, Bouchard's nodes (PIP), No MCP involvement

Autoimmune - inflammatory destruction of synovial joints. Type III hypersensitivity reaction
Pannus formation in joints (MCP and PIP), Increased synovial fluid, Bone and Cartilage erosion
Subcutaneous rheumatoid nodules (fibrinoid necrosis), Ulnar deviation in fingers, Subluxation, Baker's Cyst (in popliteal fossa)
MCP and PIP, No DIP

Females > Males
80% have RF+ (anti IgG Ab), Anti-cyclic citrullinated peptide Ab (specific)
HLA-DR4
Morning stiffness lasting >30 minutes and improving with use. Systemic joint involvement and systemic symptoms (fever, fatigue, pleuritis, pericarditis)
NSAIDs, Glucocorticoids, Disease modifying agents (Methotrexate, Sulfasalazine, TNFα inhibitors)

Lymphocytic infiltration of exocrine glands
Especially lacrimal and salivary glands
Xerophthalmia (dry eyes, conjunctivitis, "sand in my eyes"), Xerostomia (dry mouth, dysphagia), Arthritis, Parotid enlargement
Risk of B cell lymphoma, dental caries
Auto Abs to ribonucleoprotein antigens: SS-A (Ro), SS-B (La)
Females between 40 and 60
Rheumatoid Arthritis

Precipitation of monosodium Urate Crystals into joints due to hyperuricemia
Lesch-Nyhan syndrome, PRPP excess, ↓ excretion of uric acid (thiazide diuretics), ↑ cell turnover, von Gierke's disease. 90% due to underexcretion, 10% due to overproduction.
More common in men
Crystals are needle shaped and negatively birefringent (yellow crystals under parallel light)

Asymmetric joint distribution

Joints are swollen, red, and painful

Painful MTP (metatarsophalangeal) joint of the big toe (podagra)

Tophus formation (external ear, olecranon bursa, achilles tendon)

Acute attacks tend to occur after a large meal or EtOH consumption

EtOH metabolites compete for same excretion sites in kidney as uric acid causing ↓ uric acid secretion

Deposition of Ca pyrophosphate crystals w/in joint space
Basophilic rhomboid crystals that are weakly positively birefringent
Large joints (knee)
Older than 50, male and female equal
NSAIDs (sudden severe attacks), Steroids, Colchicine

Gout: yellow when parallel to light
Pseudogout: blue when parallel to light

S. aureus, Streptococcus, Neisseria gonorrhoeae
Joints are swollen, painful, and red
"STD"
Synovitis (knee), Tenosynovitis (hand), Dermatitis (pustules)

STD that presents as a migratory arthritis with an asymmetric pattern

Avascular necrosis

Infarction of bone and marrow

Pain associated with activity

Trauma, high-dose corticosteroids, alcoholism, sickle cell

Femoral head

Arthritis w/o RF

HLAB27

Males

"PAIR"

Psoriatic arthritis, Ankylosing spondylitis, IBD, Reactive arthritis

Joint pain and stiffness associated with psoriasis

Asymmetric and patchy involvement

Dactylitis (sausage fingers)

Pencil in cup deformity on XR

1/3 of pts with psoriasis get it

Chronic inflammatory disease of spine and sacroiliac joints

Ankylosis (stiff spine due to fusion of joints), Uveitis, Aortic Regurgitation

Bamboo spine (vertebral fusion)

Reiter's Syndrome
"Can't see, Can't Pee, Can't Climb a Tree"
Conjunctivitis and anterior uveitis, Urethritis, Arthritis, Palm and Sole Rash
Post GI or Chlamydia infection

Pain and stiffness in shoulders and hips often with fever, malaise, and wt loss. Does not cause muscular weakness
More common in women > 50
Associated with Temporal Giant Cell Arteritis
↑ ESR. Normal CK
Rapid response to low-dose corticosteroids

Women 20-50
Chronic, widespread musculoskeletal pain
Associated with stiffness, paresthesia, poor sleep, and fatigue

Progressive symmetric proximal muscle weakness
Endomysial inflammation with CD8+ T cells
Shoulders
↑ CK, ANA+, +anti Jo1 Abs
Steroids

Progressive symmetric proximal muscle weakness with malar rash, Gottron's papules, Heliotrope rash, Shawl and Face rash, Mechanic hands
Perimysial inflammation and atrophy with CD4+ T cells
↑ risk of occult malignancy
↑ CK, ANA+, +anti Jo1 Abs
Steroids

Myasthenia gravis

| Lambert-Eaton Myasthenic Syndrome

Most common NMJ disorder

AutoAbs to postsynaptic ACh receptors

Ptosis, Diplopia, Weakness, Worsens with muscle use

Thymoma, Thymic hyperplasia

AChE inhibitors

Uncommon
AutoAbs to presynaptic Ca channels --> ACh release
Proximal muscle weakness that improves with muscle use
Small cell lung cancer
No effect with AChE inhibitors

Metaplasia of skeletal muscle to bone following muscular trauma
Most often seen in upper and lower extremity
May present as suspicious mass at site of known trauma or as incidental finding on radiography

Leukotrienes

"Neutrophils Arrive Before Others"

| Neutrophil chemotactic

Bronchoconstriction, Vasoconstriction, Contraction of Smooth Muscle, ↑ Vascular permeability

Prostacyclin
"Platelet Gathering Inhibitor"
Inhibits platelet aggregation and promotes vasodilation. ↓ Bronchial tone, ↓ Uterine tone
Membrane lipids (eg phosphatidylinositol) --> [PLA2] --> Arachidonic Acid --> [COX] --> Endoperoxides (PGG2, PGH2) --> Prostacyclin (PGI2)

Membrane lipids (eg phosphatidylinositol) --> [PLA2] --> Arachidonic Acid --> [Lipoxygenase] --> Hydroperoxides (HPETEs) --> Leukotrienes

PGE2, PGF2α
↑ Uterine tone, ↓ Vascular tone, ↓ Bronchial tone
Membrane lipids (eg phosphatidylinositol) --> [PLA2] --> Arachidonic Acid --> [COX] --> Endoperoxides (PGG2, PGH2) --> Prostaglandins

TXA2
↑ Platelet aggregation, ↑ Vascular tone, ↑ Bronchial tone
Membrane lipids (eg phosphatidylinositol) --> [PLA2] --> Arachidonic Acid --> [COX] --> Endoperoxides (PGG2, PGH2) --> Thromboxane

Irreversibly inhibits COX1 and COX2 by acetylation
↓ synthesis of both TXA2 and Prostaglandins, ↑ bleeding time, No effect on PT of PTT
NSAID

Low dose (less than 300mg): ↓ platelet aggregation.

Intermediate dose (300-2400): antipyretic and analgesic.

High dose (2400-4000): anti-inflammatory

Gastric ulcers, Tinnitus (CNVIII), Chronci use can lead to acute renal failure, interstitial nephritis, upper GI bleed. Reyes syndrome in children. Stimulates respiratory centers leading to hyperventilation and respiratory alkalosis

Ibuprofen, Naproxen, Indomethacin, Ketorolac, Diclofenac
Reversibly inhibits COX1 and COX2. Blocks Prostaglandin synthesis
Antipyretic, analgesic, anti-inflammatory. Indomethacin used to close PDA
Interstitial nephritis, Gastric ulcer, Renal ischemia

Celecoxib
Reversibly inhibits COX2 which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain.
Spares COX1 and thus doesn't affect gastric mucosa. Also spares TXA2 and spares platelet function

RA and Osteoarthritis in pts with gastritis or ulcers

| ↑ risk of thrombosis. Sulfa allergy

Reversibly inhibits COX, mostly in CNS. Inactivated peripherally
Antipyretic, analgesic, not anti-inflammatory. Used instead of aspirin to avoid Reyes Syndrome in children w/ viral infection
OD produces hepatic necrosis. Metabolite depletes glutathione and forms toxic tissue adducts in liver

N-acetylcysteine regenerates Glutathione

Alendronate, other -dronates
Pyrophosphate analog
Bind hydroxyapatite in bone and inhibits osteoclast activity
Osteoporosis, hyperCa, Paget's disease of bone
Corrosive esophagitis, Osteonecrosis of the jaw

Allopurinol, Febuxostat, Probenecid, Colchicine

Inhibits xanthine oxidase thus ↓ conversion of xanthine to uric acid
Gout, Lymphoma and Leukemia (to prevent tumor lysis and associated urate nephropathy).
↑ concentrations of azathioprine and 6MP (both normally metabolized by xanthine oxidase)
Do not give salicylates
All but highest doses depress uric acid clearance. Even high doses have only minor uricosuric activity

Inhibits xanthine oxidase

| Gout

Inhibits reabsorption of uric acid in PCT
Gout
inhibits secretion of penicillin

Binds and stabilizes tubulin to inhibit polymerization thus impairing leukocyte chemotaxis and degranulation (decreases LTB4)
Gout
GI side effects, especially if given orally: diarrhea, abdominal pain, nausea
Myelosuppression

NSAIDs (Naproxen and Indomethacin)

| Oral or Intramuscular Glucocorticoids

Predispose to infection including TB since TNF blockade prevents activation of macrophages and destruction of phagocytosed microbes

"etanerCEPT is a TNF decoy reCEPTor"
TNFα inhibitors
Fusion protein: receptor for TNFα and IgG1 Fc produced by recombinant DNA
RA, Psoriasis, Ankylosing Spondylitis

TNFα inhibitors
Anti TNFα monoclonal Ab
RA, Psoriasis, Ankylosing Spondylitis, Crohn's Disease

A membrane that lines the outer surface of all bones, except at the joints of long bones.

Unmineralized bone

Posterior to anterior: Calcaneus and Cuboid

Posterior to anterior: Talus and Navicular bones

| Medial, Intermediate, and Lateral Cuneiforms

Deep Peroneal nerve: In between big toe and 2nd toe
Superficial Peroneal nerve: Top of foot and Lateral Leg
Sural Nerve: Lateral foot
Saphenous nerve (L3-L4): Medial leg and medial knee
Femoral nerve: Anterior and lateral thigh
Obturator nerve: Medial thigh

Tibial nerve: plantar surface of foot

Sural nerve: lateral leg

Saphenous nerve: Medial leg

Femoral nerve: Lateral thigh

Sciatic nerve: Posterior thigh