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Flashcards in Derm/Musculoskeletal Deck (63)
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1

Epidermis Layers

Corneum
Lucidum
Granulosum
Spinosum
Basale
"Californians Like Girls in String Bikinis"

2

Adherens junction

Below tight junction (between epithelial cells)
- Belt connecting actin cytoskeletons via Cadherins (Ca+2- dependent adhesion proteins
- Loss of E-cadherin= metastases

3

Desmosomes

Macula adherens providing structural support via keratin
- Autoantibodies--> pemphigus vulgaris*

4

Gap junction

Channel proteins= connexons
- Central channel= electrical, chemical communication

5

Integrins

Membrane proteins maintaining basement membrane
- Bind laminin in BM

6

Hemidesmosome

Connects Keratin in basal cell to underlying basement membrane
- Autoantibodies--> bullous pemphgoid*

7

Endochondrial ossification

Axial and appendicular skeleton
1. Cartilaginous model laid down by chondrocytes
2. Osteoblasts/clasts replace with woven bone
3. Remodel to lamellar bone

**Woven bone in fractures, Paget's disease

8

Membranous ossification

Calvarium, facial bones
1. No cartilage model- woven bone directly formed
2. Remodeled to woven bone

9

Cytokine stimulation of osteoblasts/clasts

TGF= increase osteoblasts, collagen synthesis
- Induce osteoclast apoptosis

IGF-1= osteoblast replication, collagen synthesis
- Inhibits MMP-13 (metalloprotease)--> decreased collagen breakdown

IL-1= stimulates osteoclast activity

RANK-L= receptor for activated nuclear factor Kappa-beta Ligand
- PTH--> Osteoblasts produce RANK-L--> stimulate osteoclast activity

M-CSF= macrophage colony stimulating factor
- Secreted by osteoblasts to activate osteoclast formation/differentiation

10

Osteoblast activity

Alkaline Phosphatase levels (differentiate from liver Alk-Phos vis gel electrophoresis)

11

Osteoclast activity

Urinary deoxypyridinoline

Urinary hydroxyproline (also caused by meat consumption)

Tartrate-resistant acid phosphatase (breaks down bone)

12

Achondroplasia

Failure of longitudinal bone growth (endochondrial ossification)
--> short limbs
* Membranous ossification NOT affected (Head disproportionately large)

Constitutive activation of FGFR3--> inhibit chondrocyte proliferation

85% sporadic, advanced paternal age
15% autosomal dominant inheritance

13

Albright's hereditary osteodystrophy

Pseudohypoparathyroidism 1A= end organ resistance to PTH (+ TSH, LH, FSH)
- Short stature
- short metatarsal, metacarpals

14

Osteopetrosis

Failure of normal bone resorption d/t defective osteoclasts
- Thickened, dense bone
- Bone fills marrow--> pancytopenia, extramedullary hematopoiesis

Mutation in osteoclasts- can't generate acidic environment (ex: carbonic anhydrase II)

Symptoms:
- Cranial nerve impingement, palsies d/t narrow foramina
- Bone fractures

Bone marrow transplant= curative

15

Osteomalacia/rickets

Vitamin D deficiency (poor diet, low sun, GI malabsorption)
- Defective mineralization (calcification) of osteoid (osteoid matrix accumulation around trabeculae)
- Soft bones--> bow out

Hyperactivity of osteoblasts--> see elevated Alk phos
- Secondary hyperparathyroidism (low Ca+2, phosphate)

16

Paget's disease

Disordered bone remodeling:
1) Osteoclast activity increased (RANK-L, M-CSF increased)
2) Osteoblast activity increases
3) Fibroblasts, endothelial cells activated-> vascularization

Labs:
- Elevated alk-phos

Symptoms:
- Mosaic "woven" bone
- Increased blood flow d/t AV shunting (increased blood demand from bones--> high output heart failure
- Increased hat size
- Hearing loss (auditory foramina narrowing)
** Increased risk of osteogenic sarcoma (persistant bone pain unresponsive to OTC analgesics)

17

McCune-Albright syndrome

Form of polyostic fibrous dysplasia:
- Bone replaced by fibroblasts, collagen, irregular bony trabeculae

PLUS:
- Multiple bone lesions
- Endocrine abnormalities (precocious puberty)
- Cafe-au-lait spots

18

Rheumatoid arthritis

Type III hypersensitivity reaction: inflammatory destruction of synovial joints (pannus formation):
- MCP, PIP--> ulnar deviation (no DIP involvement)
- Baker's cyst

80% positive Rheumatoid Factor (anti-IgG antibody, Fc portion)
** Anti-cyclic citrullinated peptide antibody most specific

Associated with HLA-DR4

Systemic involvement:
- Fever
- Fatigue
- Pleuritis
- Pericarditis

19

Infectious arthritis

S. aureus, Streptococcus, Neisseria gonorrhoeae

- Synovitis
- Tenosynovitis
- Dermatitis (pustules)

20

Psoriatic arthritis

Seronegative spondylarthropathy (no RF)
- HLA-B27 (HLA MHC class I)

Joint pain, stiffness associated with psoriasis
- Asymmetric, patchy
- Dactylitis (sausage fingers)
- Pencil in cup deformity

Seen in < 1/3 patients with psoriasis

21

Ankylosing spondylitis

HLA-B27 association

Ankylosis (stiff spine d/t fusion of joints
Uveitis
Aortic regurgitation

22

Reactive arthritis= Reiter's syndrome

HLA-B27 association

Conjunctivitis, anterior uveitis
Urethritis
Arthritis

May also see:
- Mouth ulcerations, circinate balanitis, keratoderma blennorrhagicum (vesicles and scale)
- axial involvement in ~20%= sacroilitis

23

Digital clubbing

Drumstick fingers with flattened nail folds, shininess of nail distal end
- Spongy, flutuant nail beds

Due to:
- Lung disease (hypoxia): lung cancer, TB, CF, bronchiectasis, pulm HTN, empyema, chornic lung disease
- Heart disease: congenital cyanotic disease, bacterial endocaditis
- Other: IBD, Crohn/UC, hyperthyroidism, malabsorption

Pathophys:
- Increased peripheral megakaryocytes, platelet clumps--> PDGF--> vascularization
- Prostaglandin E2--> platelet EP3 receptor

24

Systemic Lupus erythematosus

90% female, 14-45
Most severe in black women
C1-complement component deficiency

Presentation:
- Fever, fatigue, weight loss
- Libman-Sacks endocarditis
- Hilar adenopathy
- Raynaud's phenomenon
- Nephritis (diffuse proliferative= nephritic or membranous= nephrotic)

Screen:
- False postivie RPR/VDRL d/t APL (antiphospholipid antibodies)
- ANA (antinucelar antibodies): sensitive
- Anti-dsDNA: specific, poor prognosis
- Anti-Smith (anti-SM): specific, not prognostic
- Antibodies against RBCs (Type II hypersensitvity)--> autoimmune hemolysis (warm IgG, direct Coomb's, spherocytosis)
- Anti-histone antibodies: seen in drug-induced lupus (slow acetylators: phase II in liver; seen with hydralazine, procainamide, INH)
- Anti snRNPs (spliceosome): seen in multiple connective tissue diseases

25

Sarcoidosis

Mostly black females
Immune-mediated widespread noncaseating granulomas
- Elevated serum ACE

Symptoms:
- Enlarged lymph node
- CXR: bilateral hilar lymphadenopathy, reticular opacities

Associated with:
- Restrictive lung disease (interstitial fibrosis)
- Erythema nodosum
- Bell's palsy
- Epithelial granulomas (microscopic Schaumann and asteroid bodies)
- Uveitis
- Hypercalcemia ** due to epithelioid macrophages--> 1-alpha-hydroylase mediated vitamin D activation

Treatment: Steroids

26

Polymyalgia rheumatica

Women > 50 years:
- Pain, stiffness in shoulders and hips
- fever, malaise, weight loss
- No muscle weakness

associated with temporal (giant cell) arteritis

Elevated ESR, normal CK

Treatment: rapid response to low-dose corticosteroids (vs GCA that requires high dose steroids)

27

Dermatomyositis

- Symmetric proximal weakness (shoulders)
- Malar rash
- Grotton's papules
- Heliotrope rash

Histo:
- Perimysial inflammation
- Atrophy
- CD4+ infiltration

Labs:
- Elevated CK, ANA+, Jo-1 antibodies

** associated with malignancy

Tx: steroids

28

Polymyositis

- progressive symmetric proximal weakness in shoulders
- Endomysial inflammation
- CD8+ cells

Labs:
- Elevated CK, ANA+, Jo-1 antibodies

Treatment: steroids

29

Lambert-Eaton Myasthenic syndrome

Autoantibodies to presynaptic Ca+2 channels--> decreased Ach release

Clinical: proximal muscle weakness IMPROVING with use (vs MG)

Associated with SCLC

No effect on course with AchE-I (vs MG)

30

Crises in Myasthenia Gravis

MG= autoantibodies to postsynaptic Ach receptor
- decreased EPP (end-plate potential)

Myasthenic crisis= not enough AChE-I administered (edrophonium tx will reverse symptoms)

Cholinergic crisis= excess AChE-I administered
--> refractory depolarization--> weakness NOT responsive to edrophonium
- Treatment: Pralidoxime= reactivates AchE (diazempam, atropine)

Side-effects of MG treatment= cholinergic overdose (GI symptoms, excess lacrimation)
- Treat with Scopalamine