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First Aid > Musculoskeletal, Skin, and Connective Tissue - Pathology (1) > Flashcards

Musculoskeletal, Skin, and Connective Tissue - Pathology (1) Flashcards

1
Q

Achondroplasia

A
  • Failure of longitudinal bone growth (endochondral ossification) –>Ž short limbs.
  • Membranous ossification is not affected –>ŽŽ large head relative to limbs.
  • Constitutive activation of fibroblast growth factor receptor (FGFR3) actually inhibits chondrocyte proliferation.
  • > 85% of mutations occur sporadically and are associated with advanced paternal age, but the condition also demonstrates autosomal dominant inheritance.
  • Common cause of dwarfism.
  • Normal life span and fertility.
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2
Q

Osteoporosis

  • Definition
  • Type I
  • Type II
    • Senile osteoporosis
    • Prophylaxis
    • Treatment
A
  • Definition
    • Trabecular (spongy) bone loses mass and interconnections despite normal bone mineralization and lab values (serum Ca2+ and PO43-).
    • Diagnosis by a bone mineral density test (DEXA) with a T-score of ≤ -2.5.
    • Can be caused by long-term exogenous steroid use.
    • Can lead to vertebral crush fractures—acute back pain, loss of height, kyphosis.
  • Type I
    • Postmenopausal
      • Increased bone resorption due to decreased estrogen levels.
    • Femoral neck fracture, distal radius (Colles) fracture.
  • Type II
    • Senile osteoporosis
      • Affects men and women > 70 years old.
    • Prophylaxis
      • Regular weight-bearing exercise and adequate calcium and vitamin D intake throughout adulthood.
    • Treatment
      • Bisphosphonates, PTH, SERMs, rarely calcitonin
      • Denosumab (monoclonal antibody against RANKL).
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3
Q

Osteopetrosis (marble bone disease)

  • Definition
  • Findings
  • Treatment
A
  • Definition
    • Failure of normal bone resorption due to defective osteoclasts Ž–> thickened, dense bones that are prone to fracture.
    • Mutations (e.g., carbonic anhydrase II) impair ability of osteoclast to generate acidic environment necessary for bone resorption.
  • Findings
    • Bone fills marrow space –>Ž pancytopenia, extramedullary hematopoiesis.
    • X-rays show bone-inbone appearance [A].
    • Can result in cranial nerve impingement and palsies as a result of narrowed foramina.
  • Treatment
    • Bone marrow transplant is potentially curative as osteoclasts are derived from monocytes.
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4
Q

Osteomalacia/rickets

  • Definition
  • Caused by…
  • Causes…
A
  • Definition
    • Decreased vitamin D Ž–> decreased serum calcium –> increased PTH secretion –> decreased serum PO43-.
  • Caused by…
    • Vitamin D deficiency.
    • Defective mineralization / calcification of osteoid Ž–> soft bones that bow out.
  • Causes…
    • Osteomalacia in adults
    • Rickets in children.
    • Hyperactivity of osteoblasts Ž–> increased ALP (osteoblasts require alkaline environment).
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5
Q

Paget disease of bone (osteitis deformans) (420)

  • Definition
  • Findings
  • Stages of Paget disease:
A
  • Definition
    • Common, localized disorder of bone remodeling caused by increases in both osteoblastic and osteoclastic activity.
    • Increased blood flow from increased arteriovenous shunts may cause high-output heart failure.
    • Increased risk of osteogenic sarcoma.
  • Findings
    • Serum Ca2+, phosphorus, and PTH levels are normal. 
    • Increased ALP.
    • Mosaic pattern of woven and lamellar bone [A]
      • Long bone chalk-stick fractures. 
    • Hat size can be increased [B]
      • Hearing loss is common due to auditory foramen narrowing.
  • Stages of Paget disease:
    • Lytic—osteoclasts
    • ƒƒMixed—osteoclasts + osteoblasts
    • Sclerotic—osteoblasts
    • ƒƒQuiescent—minimal osteoclast/osteoblast activity
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6
Q

Osteonecrosis (avascular necrosis)

A
  • Infarction of bone and marrow, usually very painful.
    • Most common site is femoral head (due to insufficiency of medial circumflex femoral artery).
  • Caused by trauma, high-dose corticosteroids, alcoholism, sickle cell.
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7
Q

Lab values in bone disorders

  • For each (increased/decreased)
    • Serum Ca2+
    • PO43-
    • ALP
    • PTH
    • Comments
  • Osteoporosis
  • Osteopetrosis
  • Paget disease
  • Osteomalacia/rickets
A
  • Osteoporosis
    • Serum Ca2+: —
    • PO43-: —
    • ALP: —
    • PTH: — 
    • Comments: Decreased bone mass
  • Osteopetrosis
    • Serum Ca2+: — / decreased
    • PO43-: —
    • ALP: —
    • PTH: —
    • Comments: Dense, brittle bones.
      • Ca2+ decreased in severe, malignant disease
  • Paget disease
    • Serum Ca2+: —
    • PO43-: — 
    • ALP: Increased
    • PTH: —
    • Comments: Abnormal “mosaic” bone architecture
  • Osteomalacia/rickets    
    • Serum Ca2+: Decreased
    • PO43-: Decreased
    • ALP: Increased
    • PTH: Increased
    • Comments: Soft bones
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8
Q

Lab values in bone disorders

  • For each (increased/decreased)
    • Serum Ca2+
    • PO43-
    • ALP
    • PTH
    • Comments
  • Hypervitaminosis D
  • Osteitis fibrosa cystica
    • 1° hyperparathyroidism
    • 2° hyperparathyroidism
    • General comments
A
  • Hypervitaminosis D  
    • Serum Ca2+: Increased
    • PO43-: Increased
    • ALP: — 
    • PTH: Decreased
    • Comments: Caused by over-supplementation or granulomatous disease (e.g., sarcoidosis)
  • Osteitis fibrosa cystica
    • 1° hyperparathyroidism
      • Serum Ca2+: Increased
      • PO43-: Decreased
      • ALP: Increased
      • PTH: Increased
      • Comments: Idiopathic or parathyroid hyperplasia, adenoma, carcinoma
    • 2° hyperparathyroidism
      • Serum Ca2+: Decreased
      • PO43-: Increased
      • ALP: Increased
      • PTH: Increased
      • Comments: Often as compensation for ESRD (decreased PO43- excretion and production of activated vitamin D)
    • General comments
      • “Brown tumors” due to fibrous replacement of bone, subperiosteal thinning
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9
Q

Giant cell tumor

  • Type of tumor
  • Epidemiology / location
  • Characteristics
A
  • Type of tumor
    • Benign primary bone tumor
  • Epidemiology / location
    • 20–40 years old.
    • Epiphyseal end of long bones.
  • Characteristics
    • Locally aggressive benign tumor often around knee.
    • “Soap bubble” appearance on x-ray [A]
    • Multinucleated giant cells.
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10
Q

Osteochondroma (exostosis)

  • Type of tumor
  • Epidemiology / location
  • Characteristics
A
  • Type of tumor
    • Benign primary bone tumor
  • Epidemiology / location
    • Most common benign tumor.
    • Males < 25 years old.
  • Characteristics
    • Mature bone with cartilaginous cap.
    • Rarely transforms to chondrosarcoma.
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11
Q

Osteosarcoma (osteogenic sarcoma)

  • Type of tumor
  • Epidemiology / location
  • Characteristics
A
  • Type of tumor
    • Malignant primary bone tumor
  • Epidemiology / location
    • 2nd most common 1° malignant bone tumor (after multiple myeloma).
    • Bimodal distribution: 10–20 years old (1°), > 65 (2°).
    • Predisposing factors: Paget disease of bone, bone infarcts, radiation, familial retinoblastoma, Li-Fraumeni syndrome (germline P53 mutation).
    • Metaphysis of long bones, often around knee [B] [C].
  • Characteristics
    • Codman triangle (from elevation of periosteum) or sunburst pattern on x-ray.
    • Aggressive.
    • Treat with surgical en bloc resection (with limb salvage) and chemotherapy.
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12
Q

Ewing sarcoma

  • Type of tumor
  • Epidemiology / location
  • Characteristics
A
  • Type of tumor
    • Malignant primary bone tumor
  • Epidemiology / location
    • Boys < 15 years old.
    • Commonly appears in diaphysis of long bones, pelvis, scapula, and ribs.
  • Characteristics
    • Anaplastic small blue cell malignant tumor [D].
    • Extremely aggressive with early metastases, but responsive to chemotherapy.
    • “Onion skin” appearance in bone.
    • Associated with t(11;22) translocation.
      • 11 + 22 = 33 (Patrick Ewing’s jersey number).
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13
Q

Chondrosarcoma (423)

  • Type of tumor
  • Epidemiology / location
  • Characteristics
A
  • Type of tumor
    • Malignant primary bone tumor
  • Epidemiology / location
    • Rare, malignant, cartilaginous tumor.
    • Men 30–60 years old.
    • Usually located in pelvis, spine, scapula, humerus, tibia, or femur.
  • Characteristics
    • Malignant cartilaginous tumor.
    • May be of 1° origin or from osteochondroma.
    • Expansile glistening mass within the medullary cavity.
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14
Q

Osteoarthritis

  • Etiology
  • Joint findings
  • Predisposing factors
  • Classic presentation
  • Treatment
A
  • Etiology
    • Mechanical—joint wear and tear destroys articular cartilage.
  • Joint findings
    • Subchondral cysts, sclerosis [A], osteophytes (bone spurs), eburnation (polished, ivory-like appearance of bone), Heberden nodes (DIP), and Bouchard nodes (PIP).
    • No MCP involvement.
  • Predisposing factors
    • Age, obesity, joint deformity, trauma.
  • Classic presentation
    • Pain in weight-bearing joints after use (e.g., at the end of the day), improving with rest.
    • Knee cartilage loss begins medially (“bowlegged”).
    • Noninflammatory.
    • No systemic symptoms.
  • Treatment
    • NSAIDs, intra-articular glucocorticoids.
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15
Q

Rheumatoid arthritis

  • Etiology
  • Joint findings
  • Predisposing factors
  • Classic presentation
  • Treatment
A
  • Etiology
    • Autoimmune—inflammatory destruction of synovial joints.
    • Mediated by cytokines and type III and type IV hypersensitivity reactions.
  • Joint findings
    • Pannus formation in joints (MCP, PIP), subcutaneous rheumatoid nodules (fibrinoid necrosis), ulnar deviation of fingers, subluxation [B], Baker cyst (in popliteal fossa).
    • No DIP involvement.
  • Predisposing factors
    • Females > males.
    • 80% have (+) rheumatoid factor (anti-IgG antibody)
    • Anti–cyclic citrullinated peptide antibody is more specific.
    • Strong association with HLA-DR4.
  • Classic presentation
    • Morning stiffness lasting > 30 minutes and improving with use, symmetric joint involvement, systemic symptoms (fever, fatigue, pleuritis, pericarditis).
  • Treatment
    • NSAIDs, glucocorticoids, disease-modifying agents (methotrexate, sulfasalazine, TNF-α inhibitors).
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16
Q

Sjögren syndrome

  • Definition
  • Findings
  • Complications
A
  • Definition
    • Autoimmune disorder characterized by destruction of exocrine glands (especially lacrimal and salivary).
    • Can be a 1° disorder or a 2° syndrome associated with other autoimmune disorders (e.g., rheumatoid arthritis).
    • Predominantly affects old.
  • Findings
    • Xerophthalmia (decreased tear production and subsequent corneal damage)
    • Xerostomia (decreased saliva production)
    • Presence of antinuclear antibodies: SS-A (anti-Ro) and/or SS-B (anti-La)
    • Bilateral parotid enlargement
  • Complications
    • Dental caries
    • Mucosa-associated lymphoid tissue (MALT) lymphoma (may present as unilateral parotid enlargement).
17
Q

Gout

  • Definition
  • Findings
  • Symptoms
  • Treatment
    • Acute
    • Chronic (preventive)
A
  • Definition
    • Acute inflammatory monoarthritis caused by precipitation of monosodium urate crystals in joints [A].
  • Findings
    • Associated with hyperuricemia, which can be caused by:
      • Underexcretion of uric acid (90% of patients)
        • Largely idiopathic
        • Can be exacerbated by certain medications (e.g., thiazide diuretics).
      • ƒƒOverproduction of uric acid (10% of patients)
        • Lesch-Nyhan syndrome, PRPP excess, increased cell turnover (e.g., tumor lysis syndrome), von Gierke disease.
    • Crystals are needle shaped and (-) birefringent
      • Yellow under parallel light, blue under perpendicular light).
      • More common in males.
  • Symptoms
    • Asymmetric joint distribution.
      • Joint is swollen, red, and painful [B].
    • Classic manifestation is painful MTP joint of the big toe (podagra).
    • Tophus formation (often on external ear, olecranon bursa, or Achilles tendon).
    • Acute attack tends to occur after a large meal or alcohol consumption (alcohol metabolites compete for same excretion sites in kidney as uric acid, causing decreased uric acid secretion and subsequent buildup in blood).
  • Treatment
    • Acute: NSAIDs (e.g., indomethacin), glucocorticoids, colchicine.
    • Chronic (preventive): xanthine oxidase inhibitors (e.g., allopurinol, febuxostat).
18
Q

Pseudogout

  • Findings
  • Diseases that may be associated with pseudogout
  • Treatment
  • Gout vs. pseudogout
A
  • Findings
    • Presents with pain and effusion in a joint, caused by deposition of calcium pyrophosphate crystals within the joint space (chondrocalcinosis on x-ray).
    • Forms basophilic, rhomboid crystals that are weakly positively birefringent [A].
    • Usually affects large joints (classically the knee).
    • > 50 years old; both sexes affected equally.
  • Diseases that may be associated with pseudogout
    • Hemochromatosis, hyperparathyroidism, and hypoparathyroidism.
  • Treatment
    • NSAIDs for sudden, severe attacks; steroids; and colchicine.
  • Gout vs. pseudogout
    • Gout—crystals are yellow when parallel (||) to the light.
    • Pseudogout—crystals are blue when parallel (||) to the light.
19
Q

Infectious arthritis

  • Definition
  • Common causes
  • Gonococcal arthritis
A
  • Definition
    • Affected joint is swollen, red, and painful.
  • Common causes
    • S. aureus, Streptococcus, and Neisseria gonorrhoeae
  • Gonococcal arthritis
    • An STD that presents as a migratory arthritis with an asymmetric pattern.
    • STD = Synovitis (e.g., knee), Tenosynovitis (e.g., hand), and Dermatitis (e.g., pustules).
20
Q

Seronegative spondyloarthropathies

  • Definition
  • Conditions
A
  • Definition
    • Arthritis without rheumatoid factor (no anti-IgG antibody).
    • Strong association with HLA-B27 (gene that codes for HLA MHC class I).
    • Occurs more often in males.
  • Conditions (PAIR)
    • ​Psoriatic arthritis
    • Ankylosing spondylitis
    • Inflammatory bowel disease
    • Reactive arthritis (Reiter syndrome)
21
Q

Psoriatic arthritis

A
  • Seronegative spondyloarthropathy
  • Joint pain and stiffness associated with psoriasis.
  • Asymmetric and patchy involvement.
  • Dactylitis (“sausage fingers” [A]), “pencil-incup” [B] deformity on x-ray.
  • Seen in fewer than 1 ⁄3 of patients with psoriasis.
22
Q

Ankylosing spondylitis

A
  • Seronegative spondyloarthropathy
  • Chronic inflammatory disease of spine and sacroiliac joints –>Ž ankylosis (stiff spine due to fusion of joints), uveitis, and aortic regurgitation.
  • Bamboo spine (vertebral fusion) [C].
23
Q

Inflammatory bowel disease

A
  • Seronegative spondyloarthropathy
  • Crohn disease and ulcerative colitis are often accompanied by ankylosing spondylitis or peripheral arthritis.
  • Bamboo spine (vertebral fusion) [C].
24
Q

Reactive arthritis (Reiter syndrome)

A
  • Seronegative spondyloarthropathies
  • Post-GI (Shigella, Salmonella, Yersinia, Campylobacter) or Chlamydia infections.
  • Classic triad:
    • ƒƒConjunctivitis and anterior uveitis
    • ƒƒUrethritis
    • Arthritis
    • “Can’t see, can’t pee, can’t climb a tree.”
25
Q

Systemic lupus erythematosus:
Symptoms

  • Classic presentation
  • Libman-Sacks endocarditis
  • Lupus nephritis
    • Nephritic
    • Nephrotic
  • Common causes of death in SLE:
  • Symptoms
A
  • Classic presentation
    • Rash, joint pain, and fever, most commonly in a female of reproductive age and African descent.
  • Libman-Sacks endocarditis
    • Wart-like vegetations on both sides of valve.
  • Lupus nephritis (type III hypersensitivity reaction):
    • ƒƒNephritic—diffuse proliferative glomerulonephritis.
    • ƒƒNephrotic—membranous glomerulonephritis.
  • Common causes of death in SLE:
    • Cardiovascular disease
    • Infections
    • Renal disease
  • Symptoms (RASH OR PAIN)
    • Rash (malar [A] or discoid)
    • Arthritis
    • Soft tissues/serositis
    • Hematologic disorders (e.g., cytopenias)
    • Oral/nasopharyngeal ulcers
    • Renal disease, Raynaud phenomenon
    • Photosensitivity, Positive VDRL/RPR
    • Antinuclear antibodies
    • Immunosuppressants
    • Neurologic disorders (e.g. seizures, psychosis)
26
Q

Systemic lupus erythematosus

  • Findings
  • Treatment
A
  • Findings
    • Antinuclear antibodies (ANA)—sensitive, not specific.
    • Anti-dsDNA antibodies—specific, poor prognosis (renal disease).
    • Anti-Smith antibodies—specific, not prognostic (directed against snRNPs).
    • Antihistone antibodies—sensitive for drug-induced lupus.
    • Anticardiolipin antibodies—false positive on tests for syphilis, prolonged PTT (paradoxically, increased risk of arteriovenous thromboembolism).
    • Decreased C3, C4, and CH50 due to immune complex formation.
  • Treatment
    • NSAIDs, steroids, immunosuppressants, hydroxychloroquine.
27
Q

Sarcoidosis

  • Definition
  • Findings
  • Associated with/
  • Treatment
A
  • Definition
    • Characterized by immune-mediated, widespread noncaseating granulomas [A] and elevated serum ACE levels.
    • Common in black females.
  • Findings
    • Often asymptomatic except for enlarged lymph nodes.
    • Incidental findings on CXR of bilateral hilar adenopathy and/or reticular opacities [B].
  • Associated with restrictive lung disease (interstitial fibrosis), erythema nodosum, lupus pernio, Bell palsy, epithelioid granulomas containing microscopic Schaumann and asteroid bodies, uveitis, and hypercalcemia (due to increased 1α-hydroxylase–mediated vitamin D activation in macrophages).
  • Treatment: steroids.
28
Q

Polymyalgia rheumatica

  • Symptoms
  • Findings
  • Treatment
A
  • Symptoms
    • Pain and stiffness in shoulders and hips, often with fever, malaise, and weight loss.
    • Does not cause muscular weakness.
    • More common in women > 50 years old
    • Associated with temporal (giant cell) arteritis.
  • Findings
    • Increased ESR, increased C-reactive protein, normal CK.
  • Treatment
    • Rapid response to low-dose corticosteroids.
29
Q

Fibromyalgia

  • Findings
  • Treatment
A
  • Findings
    • Most commonly seen in females 20–50 years old.
    • Chronic, widespread musculoskeletal pain associated with stiffness, paresthesias, poor sleep, and fatigue.
  • Treatment
    • Treat with regular exercise, antidepressants (TCAs, SNRIs), and anticonvulsants.
30
Q

Polymyositis/dermatomyositis

  • Symptoms
    • Polymyositis
    • Dermatomyositis
  • Findings
  • Treatment
A
  • Symptoms
    • Polymyositis
      • Progressive symmetric proximal muscle weakness
      • Characterized by endomysial inflammation with CD8+ T cells.
      • Most often involves shoulders.
    • Dermatomyositis
      • Similar to polymyositis, but also involves malar rash (similar to SLE), Gottron papules [A], heliotrope (erythematous periorbital) rash, “shawl and face” rash [B], “mechanic’s hands.” 
      • Increased risk of occult malignancy.
      • Perimysial inflammation and atrophy with CD4+ T cells.
  • Findings
    • Increased CK, (+) ANA, (+) anti-Jo-1, (+) anti-SRP, (+) anti-Mi-2 antibodies.
  • Treatment
    • Steroids.
31
Q

Myasthenia gravis

  • Type of disease
  • Frequency
  • Pathophysiology
  • Clinical
  • Associated with…
  • AChE inhibitor administrator
A
  • Type of disease
    • Neuromuscular junction disease
  • Frequency
    • Most common NMJ disorder
  • Pathophysiology
    • Autoantibodies to postsynaptic ACh receptor
  • Clinical
    • Ptosis, diplopia, weakness
    • Worsens with muscle use
  • Associated with…
    • Thymoma, thymic hyperplasia
  • AChE inhibitor administrator
    • Reversal of symptoms
32
Q

Lambert-Eaton myasthenic syndrome

  • Type of disease
  • Frequency
  • Pathophysiology
  • Clinical
  • Associated with…
  • AChE inhibitor administrator
A
  • Type of disease
    • Neuromuscular junction disease
  • Frequency
    • Uncommon
  • Pathophysiology
    • Autoantibodies to presynaptic Ca2+ channel –> decreased ACh release
  • Clinical
    • Proximal muscle weakness, autonomic symptoms (dry mouth, impotence)
    • Improves with muscle use
  • Associated with…
    • Small cell lung cancer
  • AChE inhibitor administrator
    • Minimal effect
33
Q

Myositis ossificans

A
  • Metaplasia of skeletal muscle to bone following muscular trauma [A].
  • Most often seen in upper or lower extremity.
  • May present as suspicious “mass” at site of known trauma or as incidental finding on radiography.

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