MSK pathology

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  1. Knee injury
    (unhappy triad)
    Common football injury. Force from the lateral side → "unhappy triad"

    • 1. Medial collateral ligament (MCL)
    • 2. Anterior Cruciate ligament (ACL)
    • 3. Lateral (not medial) meniscus

    • PCL - posterior cruciate ligament
    • LCL - lateral collateral ligament

    "Anterior" and "posterior" in ACL/PCL refer to site of tibial attachment

    • Tests: 
    • -Positive anterior drawer sign indicates tearing of ACL
    • -Abnormal passive abduction indicates torn MCL

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  2. McBurney's point
    • Appendix
    • 2/3rds the way from the umbilicus to the anterior superior iliac spine
  3. Rotator cuff muscle
    SItS (small t for teres minor)

    • -Supraspinatus - abducts arm initially (before deltoid; most common rotator cuff injuryI
    • -Infraspinatus - laterally rotates arm; pitching injury
    • -Teres minor - adducts and lateral rotates arm
    • -Subscapularis - medially rotates and adducts arm

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  4. Bones of the hand and wrist
    Some Lovers Try Positions That They Can't Handle

    Scaphoid, Lunate, Triquetrum, Pisiform, Trapezium, Trapezoid, Capitate, Hamate

    • DIP Joint
    • PIP Joint
    • MP Joint

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  5. Achondroplasia
    Failure of longitudinal bone growth (endochondral ossification). Intramembranous ossification not effected.

    Result: Short limbs, normal (large) head

    Constitutive activation of fibroblast growth factor receptor (FGFR3) actually inhibits chondrocyte proliferation

    >85% occur sporadically; associated with advanced paternal age, Autosomal dominant inheritance.

    Common cause of dwarfism; normal life span and fertility
  6. Osteogenesis Imperfecta
    Congenital defect of bone resorption that results in structurally weak bone; most common defect in collagen type I synthesis

    Remember: bone has "one" in it

    • Presentation:
    • 1. Multiple fractures of bone 
    • 2. Blue sclera - thinning of the scleral collagen reveals underlying choroidal veins
    • 3. Hearing loss - bone of middle ear easily fractured
  7. Osteoporosis
    Trabecular (spongy) bone loses mass and interconnections despite normal bone mineralization and lab values

    Presentation: Vertebral crush fractures - acute back pain, loss of height, kyphosis

    • Type I - Postmenopausal; ↑ bone resorption due to ↓ estrogen levels
    • - Femoral neck fracture, distal radius (Colles') fracture

    • Type II - Senile osteoporosis - Affects men and women > 70 yrs of age
    • -Prophylaxis exercise and calcium ingestion before age 30

    Prognosis: ~1% bone mass loss each year

    Tx: estrogen (SERMs) and/or calcitonin; bisphosphonates (induce apoptosis of osteoclasts) or pulsatile PTH for severe cases. Glucocorticoids are contraindicated

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  8. Osteopetrosis
    marble bone disease
    • Failure of normal bone resorption; leads to thickened, dense bones that are prone to fracture
    • -Abnormal function of osteoclasts

    Labs: Serum calcium, phosphate, and alkaline phosphatase (ALP) are normal

    Primary spongiosa fills medullary cavity, causing decrease in marrow space --> anemia, thrombocytopenia, infection. Increased extramedullary hematopoiesis.

    Cause: Genetic deficiency of carbonic anhydrase II → loss of acidic environment required for bone resorption

    *Acid removes calcium from bone

    X-ray shows "Erlenmeyer flask" bones that flare out. Can result in cranial nerve impingement and palsies due to narrowed foramina (vision and hearing impairment)

    hydrocephalus due to narrowing of the foramen magnum

    Renal tubular acidosis - seen with carbonic anhydrase II mutation (decreased tubular reabsorption of HCO3-, leading to metabolic acidosis

    Tx:  bone marrow transplant: Osteoclasts are derived from monocytes

    *Osteoclasts are the macrophages of the bone
  9. Carbonic anhydrase II

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  10. Osteomalacia/rickets
    • Defective mineralization/calcification of osteoid (what osteoblasts lay down) → soft bones.
    • Vitamin D deficiency in adults → ↓ calcium levels →↑ secretion of PTH, ↓ in serum phosphate. ↑ ALP

    • Vit D deficiency:
    • 1. sunlight exposure (85%), diet (15%)
    • 2. Activation requires 25-hydroxylation by the liver followed by 1-alpha-hydroxylation by proximal tubule cells of the kidney
    • 3. Active vit D raises serum calcium and phosphate by acting on 
    •     a. Intestines - increases absorption
    •     b. Kidney - increases reabsorption
    •     c. Bone - increases resorption

    Reversible when Vit D is replaced

    • Adults:
    • -weak bones with increased risk for fracture (weight bearing bones)

    • Vitamin D deficiency in childhood causes rickets 
    • -if child has started walking → you may see bowed legged kids
    • -Frontal bossing (enlarged forehead)
    • -Rachitic rosary - osteoid deposition at the costrochondral junction
    • -Pigeon-breast deformity
  11. Paget's disease
    (osteitis deformans)
    Abnormal bone architecture caused by ↑ in both osteoblastic and osteoclastic activity. Result is thick, sclerotic bone that fractures easily

    Possible viral in origin (paramyxovirus is suspected)

    • Phase 1: ↑ Osteoclasts (go bonkers)
    • Phase 2: ↑ both
    • Phase 3: ↑ Osteoblasts (osteoclasts tire out)

    Labs: Serum calcium, phosphorus, and PTH levels are normal. ↑ ALP

    Mosaic bone pattern; long bone chalk-stick fractures.

    ↑ blood flow from ↑ AV shunts (arteriovenous shunts) may cause high-output heart failure

    Can lead to osteosarcoma - osteoblast malignancy

    Presentation: ↑ hat size; hearing loss is common due to auditory foramen narrowing; lion-like faces; bone pain; isolated elevated ALP

    Tx: Calcitonin - (inhibits osteoclast function); Bisphosphonates - (induces apoptosis of osteoclasts)
  12. Lab values in bone disorders
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    • -Osteoporosis: normal labs; decreased bone mass
    • -Osteopetrosis: normal labs; thickened, dense bones
    • -Osteomalacia/rickets: ↓ Ca, ↓ Phosphate, nl ALP, ↑ PTH; Soft bones
    • -Osteitis fibrosa cystica: ↑ Ca, ↓ Phosphate, ↑ ALP, ↑ PTH; "Brown tumors"
    • -Paget's disease: nl Ca, nl Phosphate, ↑ ALP, nl PTH; Abnormal bone architecture
  13. Polyostotic fibrous dysplasia
    Bone is replaced by fibroblasts, collagen, and irregular bony trabeculae. McCune-Albright syndrome is a form of polyostotic fibrous dysplasia characterized by multiple unilateral bone lesions associated with endocrine abnormalities (precocious puberty) and cafe-au-lait spots

  14. Osteomyelitis
    Infection of marrow and bone - usually in children

    • Bacterial (most common); hematogenous spread
    • 1. Transient bacteremia (children) seeds metaphysis
    • 2. Open-wound bacteremia (adults) seeds epiphysis

    • Causes:
    • -Staphylococcus aureus (90% of cases)
    • -N gonorrhoeae - sexually active young adults
    • -Salmonella - sickle cell disease
    • -Pseudomonas - diabetics or IV drug abusers
    • -Pasteurella - associated with cat or dog bite/scratches
    • -Mycobacterium tuberculosis - involves vertebrae (Pott disease)

    • Clinical:
    • 1. Bone pain with systemic signs of infection
    • 2. Lytic focus (abscess) surrounded by sclerosis of bone on x-ray.

    Focus = sequestrum, sclerosis = involucrum
  15. Avascular (aseptic) necrosis
    Ischemic necrosis of bone and bone marrow

    Presentation: Pain associated with activity

    Causes: trauma, fracture, steroids, sickle cell anemia, alcoholism, caisson disease (gas emboli)

    Complications: osteoarthritis and fracture
  16. Primary bone tumors
    • 1. Giant cell tumor (osteoclastoma)
    • 2. Osteochondroma (exostosis)
    • 3. Osteoma
    • 4. Osteoid osteoma
    • 5. Chondroma
  17. Osteoma
    Benign tumor of bone

    Most commonly arises on surface of facial bones

    Associated with Gardner syndrome (FAP + Fibromatosis (retroperitoneum) + osteoma)
  18. Osteoid osteoma
    Benign tumor of osteoblasts (which produce osteoid), surrounded by rim of reactive, sclerotic bone

    • Presentation:
    • -young adults <25yrs; Males > females
    • -cortex of long bones (diaphysis)
    • -Bone pain that resolves with aspirin
    • -Imaging: bony mass (<2cm) with radiolucent core (osteoid)

    -Osteoblastoma is similar, but is larger (>2cm) and arises in vertebrae, presents as bone pain that does not respond to aspirin
  19. Osteochondroma
    Tumor of bone with overlying cartilage cap; most common benign tumor

    • Presentation: young men (<25yrs)
    • -Arises from a lateral projection of the growth plate (metaphysis); bone is continuous with marrow space

    Malignant transformation to chondrosarcoma is rare
  20. Giant cell tumor
    Tumor comprised of multinucleated giant cells and stromal cells

    • Presentation: young adults (20-40yrs)
    • -Arises in the epiphysis of long bones, usually the distal femur or proximal tibia (region of the knee)
    • -locally aggressive tumor; may recur
    • -"soap bubble" or "double bubble" appearance on X-ray
  21. Chondroma
    Benign tumor of cartilage

    Usually arisis in the medulla of small bones of the hands and feet
  22. Osteosarcoma
    (osteogenic sarcoma)
    Malignant proliferation of osteoblasts; 2nd most common primary malignant bone tumor (after malignant myeloma)

    • Epidemiology: Peak incidence in teens, less commonly seen in elderly
    • -Risk factors: familial retinoblastoma, Paget disease, radiation exposure
    • -Arises in the metaphysis of long bones, usually distal femur or proximal tibia

    • Presentation: Pathologic fracture or bone pain with swelling
    • -X-ray shows "sunburst" pattern and lifting of the periostium (Codman triangle)

    Prognosis: poor
  23. Ewing's sarcoma
    Malignant proliferation of poorly-differentiated cells derived from neuroectoderm

    • Presentation: Male children (<15 yrs)
    • -Arises in the diaphysis of long bones, pelvis, scapula, and ribs
    • -"onion-skin" appearance on X-ray (periosteum layers new bone) "going out for Ewings and onion rings
    • -Extremely aggressive: often presents with metastasis
    • -responsive to chemotherapy

    • Biopsy: small, round blue cells that resemble lymphocytes
    • 1. Can be confused with lymphoma or chronic osteomyelitis (swelling)
    • 2. (11;22) translocation is characteristic
    • (11 + 22 = 33 ... Patrick Ewing's jersey number)
  24. Chondrosarcoma
    Malignant cartilage-forming tumor

    • Presentation: Men age 30-60.
    • -Arises in medulla of the pelvis or central skeleton (and spine, scapula, humerus, tibia, femur)
    • -Expansive glistening mass within the medullary cavity

    May be primary in origin, or from osteochondroma
  25. Bone anatomy and location of bone tumors
    Image Upload 8
  26. Metastatic bone tumors
    More common that primary tumors

    • Usually result in osteolytic (punched-out) lesions
    • -exception: Prostate carcinoma classically produces osteoblastic lesions
  27. Dermatomyositis
    Inflammatory disorder of the skin and skeletal muscles

    Unknown etiology; some cases are associated with gastric carcinoma (increase risk of malignancy)

    • Presentation:
    • -bilateral proximal muscle weakness; distal involvement later in disease
    • -Rash of upper eyelids (heliotrope rash); malar rash may also be seen
    • -Red papules on the elbows, knuckles, knees (Grotton lesion)
    • -"shawl and face" rash, "mechanics hands"

    • Labs
    • -Increased creatinine kinase
    • -Positive ANA and anti-Jo-1 antibody (B cell mediated)
    • -Increased aldolase

    • Bx:
    • -Perimysial inflammation (CD4+ T cells) with perifascicular atrophy on biopsy
    • -perimysium is closer to the skin (than endomysium): dermatomyositis

    Tx: corticosteroids
  28. Polymyositis
    Inflammatory disorder of skeletal muscle

    • Presentation: progressive symmetric, proximal weakness caused by CD8+ T cell-induced injury to myofibers.
    • -Most often involves sholders

    Bx: endomysial inflammation with necrotic muscle fibers

    Similar to dermatomyositis, but T cell (not B cell) mediated, and endomysium (not perimysium) involvement
  29. Neuromuscular junctional disease
    • Myasthenia gravis
    • Lambert-Eaton syndrome
  30. Myasthenia gravis
    Autoantibodies against the postsynaptic ACh receptor at the NMJ; most common NMJ disorder

    • Presenation: Women > men
    • - Muscle weakness that worsens with use (decrimenting) and improves with rest
    • -classically involves eyes leading to ptosis and diploplia

    • Tx:
    • -symptomatic: anticholinesterase agent (AChE inhibitors)
    • -Associated with thymic hyperplasia or thymoma: Thymectomy improves sx
  31. Lambert-Eaton Syndrome
    Autoantibodies to presynaptic Ca channel of the NMJ; results in decreased Ach release and muscle weakness

    Paraneoplastic syndrome; most commonly due to small cell lung cancer

    • Presentation:
    • -Proximal muscle weakness that improves with use (Incrementing response); eyes are usually spared
    • -Anticholinesterase agents do not improve symptoms
    • -Resolves with resection of the cancer
  32. X-linked muscular dystrophy
    DMD, BMD
    Degenerative disorder characterized by muscle wasting and replacement of skeletal muscle by adipose tissue

    • Cause: mutations of dystrophin (one of the largest genes)
    • -Dystrophin is used to anchor muscle cytoskeleton to ECM
    • -Mutations are spontaneous, large gene size predisposes to high rate of mutation

    Duchenne muscular dystrophy is due to deletion of dystrophin

    • Presentation: proximal muscle weakness at 1 year of age; progresses to involve distal muscles
    • 1. Calf pseudohypertrophy is characteristic finding (but really just adipose tissue)
    • 2. Serum creatinine kinase is elevated (muscle breakdown)

    Death from cardiac or respiratory failure; myocardium is commonly involved

    • Becker muscular dystrophy is due to mutated dystrophen
    • -clinically milder disease
  33. Rhabdomyomoa
    Benign tumor of skeletal muscle

    Cardiac rhabdomyoma is associated with tuberous sclerosis
  34. Rhabdomyosarcoma
    Malignant tumor of skeletal muscle

    Most common malignant soft tissue tumor in children

    Rhabdomyoblast is characteristic cell; desmin positive

    Presentation: Head and neck (most common); vagina is classic site in young girls
  35. Bisphosphonates
    Etidronate, pamidronate, alendronate, risedronate, zoledronate (IV)

    Mechanism: Inhibit osteoclastic activity. Reduce both bone formation and resorption of hydroxyapatite

    Indications: malignancy-associated hypercalcemia, Paget's disease, postmenopausal osteoporosis

    Toxicity: corrosive esophagitis (except IV), nausea, diarrhea, osteonecrosis of the jaw
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MSK pathology

MSK pathology from 1st AID & Pathoma
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