PATH - General Flashcards
Achondroplasia
autosomal dominant with full penetrance
Failure of longitudinal bone growth (endochondral ossification)–>short limbs
activation of fibroblast
growth factor receptor (FGFR3)
Osteoporosis
Trabecular (spongy) and cortical bone *lose mass and interconnections despite normal bone mineralization and lab values (serum Ca2+ and
PO43−).
Can lead to *vertebral compression fractures
- Most commonly due to INC bone resorption related to DEC estrogen levels (Type I-postmenopausal) and old age (Type II-Senile).
- Can be secondary to drugs or other medical conditions
*bone mineral density scan with a T-score of ≤ −2.5 or by a fragility fracture of hip or vertebra.
Osteopetrosis (marble bone disease)
Failure of normal bone resorption due to defective osteoclasts–>thickened, *dense bones that are prone to fracture.
X-rays show bone-in-bone (“stone” bone) appearance
Mutations (eg, *carbonic anhydrase II) impair ability of osteoclast to generate acidic environment necessary for bone resorption
Osteomalacia/Rickets
Most commonly due
to *vitamin D deficiency
Defective mineralization of osteoid (osteomalacia) or cartilaginous growth plates
(rickets, only in children)
Children with rickets have bow legs, bead-like costochondral junctions (rachitic rosary), craniotabes (soft skull).
X-rays show osteopenia and “Looser zones” (pseudofractures) in osteomalacia, epiphyseal
widening and metaphyseal cupping/fraying in
rickets.
DEC vitamin D–>DEC serum Ca2+–>INC PTH secretion–>DEC serum PO43−.
Hyperactivity of osteoblasts–>INC ALP
Paget disease of bone
osteitis deformans
Common, localized disorder of bone remodeling caused by INC osteoclastic activity
followed by INC osteoblastic activity that forms poor-quality bone.
Mosaic pattern of woven and lamellar bone
-*Hat size can be increased due to skull thickening
-hearing loss is common due to
auditory foramen narrowing
INC Risk
- long bone chalk-stick fractures
- osteogenic sarcoma
INC ALP
Stages of Paget disease: -Lytic—osteoclasts -Mixed—osteoclasts+osteoblasts -Sclerotic—osteoblasts -Quiescent—minimal osteoclast/osteoblast activity
Osteonecrosis (avascular necrosis)
Infarction of bone and marrow, usually very painful.
Most common site is *femoral
head
Osteoarthritis
Mechanical—wear and tear destroys articular cartilage (“degenerative joint disease”).
Chondrocytes mediate degradation and inadequate repair.
- Pain in weight-bearing joints *after use, improving with rest
- Asymmetric joint involvement
- Knee cartilage loss begins medially (“bowlegged”)
- *No systemic symptoms.
- Osteophytes (bone spurs)
- joint space narrowing
- subchondral sclerosis and cysts
- Involves DIP (Heberden nodes) and PIP (Bouchard nodes), and 1st CMC; not MCP.
Rheumatoid arthritis
Autoimmune—inflammatory cytokines and cells induce *pannus formation, which erodes articular cartilage and bone
-Pain, swelling, and morning stiffness lasting > 1 hour, improving with use
-Symmetric joint involvement
-*Systemic symptoms
(fever, fatigue, weight loss)
-Extraarticularmanifestations common
-Deformities include subluxation, fingers with ulnar deviation, swan neck, and boutonniere
-Synovial fluid inflammatory
-Involves MCP, PIP,
wrist; not DIP or 1st CMC.
*HLA-DR4
smoking, silica exposure
- ⊕ rheumatoid factor (anti-IgG antibody; in 80%)
- anti-cyclic citrullinated peptide antibody (more specific).
Gout
Acute inflammatory monoarthritis caused by precipitation of *monosodium urate crystals in joints
Associated with hyperuricemia
Crystals are needle shaped and ⊝ birefringent under polarized light (yellow under parallel light,
blue under perpendicular light
-painful MTP joint of big toe (podagra)
-Tophus formation (often on external ear, olecranon bursa, or
Achilles tendon)
Pseudogout
Deposition of *calcium pyrophosphate crystals within the joint space
Crystals are *rhomboid and weakly ⊕ birefringent under polarized light (blue when parallel to light)
Pain and swelling with acute inflammation (pseudogout) and/or chronic degeneration (pseudoosteoarthritis).
Knee most commonly affected joint
Sjögren syndrome
Autoimmune disorder characterized by destruction of exocrine glands (especially
lacrimal and salivary)
Findings:
- Inflammatory joint pain
-Keratoconjunctivitis sick (DEC tear production and subsequent corneal damage)
-Xerostomia (DEC 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 parotid enlargement).
Predominantly affects females
40–60 years old.
Septic arthritis
Medical Emergency!
S aureus, Streptococcus, and Neisseria gonorrhoeae are common causes.
Affected joint is swollen, red, and painful.
Synovial fluid purulent (WBC > 50,000/mm3).
*Gonococcal arthritis—STI that presents as either purulent arthritis (eg, knee) or triad of
polyarthralgias, tenosynovitis (eg, hand), dermatitis (eg, pustules).
Ankylosing spondylitis
Symmetric involvement of spine and sacroiliac joints–>ankylosis (joint fusion), uveitis, aortic
regurgitation
*Bamboo spine (vertebral fusion)
Arthritis *without rheumatoid factor (no anti-IgG antibody).
Strong association with *HLA-B27 (MHC class I serotype)
Reactive arthritis
AKA Reiter syndrome
Classic triad:
Conjunctivitis
Urethritis
Arthritis
“Can’t see, can’t pee, can’t bend my knee.”
Systemic Lupus Erythematous
RASH OR PAIN: Rash (malar or discoid) Arthritis (nonerosive) Serositis Hematologic disorders (eg, cytopenias) Oral/nasopharyngeal ulcers Renal disease Photosensitivity Antinuclear antibodies Immunologic disorder (anti-dsDNA, anti-Sm, antiphospholipid) Neurologic disorders (eg, seizures, psychosis)
Common causes of death in SLE:
*Cardiovascular disease
-Libman-Sacks Endocarditis—nonbacterial, verrucous thrombi usually on mitral or aortic
valve ("LSE in SLE").
*Infections
*Renal disease
-Lupus nephritis can be nephritic
or nephrotic (hematuria or proteinuria).
Sarcoidosis
Characterized by immune-mediated, widespread *noncaseating granulomas
Often asymptomatic except for enlarged lymph nodes
*Schaumann and asteroid bodies
Findings on CXR of *bilateral adenopathy and *coarse reticular opacities
elevated serum ACE levels
elevated CD4+/CD8+ ratio in bronchoalveolar lavage fluid
Polymyalgia Rheumatica
Pain and stiffness in shoulders and hips, often with fever, malaise, weight loss
associated with *giant cell (temporal) arteritis.
INC ESR
INC CRP
normal CK
Polymyositis
Progressive symmetric proximal muscle weakness, characterized by endomysial inflammation with *CD8+ T cells
Most often involves shoulders
INC CK ⊕ ANA ⊕ anti-Jo-1 ⊕ anti-SRP ⊕ anti-Mi-2 antibodies
Dermatomyositis
Similar to polymyositis, but also involves malaria rash, Gottron papules, heliotrope (erythematous periorbital) rash, “shawl and face” rash, “mechanic’s hands.”
Perimysial inflammation and atrophy with *CD4+ T cells
INC CK ⊕ ANA ⊕ anti-Jo-1 ⊕ anti-SRP ⊕ anti-Mi-2 antibodies
Myasthenia gravis
Most common NMJ disorder
Autoantibodies to *postsynaptic ACh receptor
Ptosis, diplopia, weakness
*Worsens with muscle use
Ass. w/ **Thymoma, thyme hyperplasia
AchE Reverses symptoms (edrophonium to diagnose,
pyridostigmine to treat)
Lambert-Eaton myasthenic syndrome
Autoantibodies to presynaptic Ca2+ channel–>DEC ACh release
Proximal muscle weakness, autonomic symptoms (dry mouth, impotence)
*Improves with muscle use
Ass w/ **Small cell lung cancer
Myositis ossificans
Heterotopic ossification of skeletal muscle following muscular trauma
Most often seen in upper
or lower extremity
May present as suspicious “mass” at site of known trauma or as incidental finding on radiography.
Scleroderma (systemic sclerosis)
Triad of autoimmunity, noninflammatory vasculopathy, and collagen deposition with fibrosis
- Commonly sclerosis of skin, manifesting as puffy, taut skin without wrinkles, fingertip pitting
- Also sclerosis of renal, pulmonary (most common cause of death), cardiovascular, GI systems.
Diffuse scleroderma
widespread skin involvement, rapid progression, early visceral
involvement.
Associated with *anti-Scl-70 antibody (anti-DNA topoisomerase I antibody).
