5 musculoskeletal high yield

MUSC1_1- Stratum basalis Basement membrane Kaplan Pathology 2010: Figure 11-1... MUSC1_1- 7 Skin layers from surface to base Stratum basalis Basement membrane Kaplan Pathology 2010: F

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MS01- MUSC1_1-

Musculoskeletal and Connective

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MS01- MUSC1_1-

Anatomy, physiology, and disease of:

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MS01- MUSC1_1-

Lecture 1 - Dermatology

Musculoskeletal and Connective

Tissue

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Stratum basalis Basement membrane

Kaplan Pathology 2010: Figure 11-1

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FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1

ME 3e: 451 • ME 4e: 451

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MUSC1_1- 6

Skin layers from surface to base

Epidermal layers:

L – Stratum lucidum

• This layer is only found in

thick skin (e.g palms and

soles)

FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1

ME 3e: 451 • ME 4e: 451

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MUSC1_1- 7

Epidermal layers:

G – Stratum granulosum

FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1

ME 3e: 451 • ME 4e: 451

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FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1

ME 3e: 451 • ME 4e: 451

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FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1

ME 3e: 451 • ME 4e: 451

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Zona occludens (tight junctions):

• Determines cell polarity

• Prevents diffusion across paracellular space

• Composed of:

• Claudins: Adhesive proteins

• Occludins: Block diffusion in between cells

Kaplan Anatomy: Figure I-1-10

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Zona Occludens

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2

ME 3e: 82 • ME 4e: 82

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• Cadherins connect the intracellular actin filaments of adjacent cells

• CADherins are Ca2+ dependent ADhesion molecule

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Name Zona occludens Zona adherens

Contain Claudins and occludins Cadherins

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Zona Occludens Vs Zona Adherens

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2

ME 3e: 82 • ME 4e: 82

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Macula adherens (desmosome): The most important junction

• Composed of Cadherins

• Cadherins connect the intracellular intermediate filaments of adjacent cells

• Desmoplakin attaches to the intermediate filaments

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Macula Adherens (Desmosome)

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2

ME 3e: 82 • ME 4e: 82

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Macula adherens (desmosome): Clinical correlate

• Pemphigus vulgaris:

• Auto-antibodies developed against the desmosome

• Clinical manifestation: Epithelial sloughing

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Macula Adherens (Desmosome)

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2

ME 3e: 82 • ME 4e: 82

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MUSC1_1-

Basement membrane:

• A sheet-like structure underlying virtually all epithelia, which consists of basal lamina and

reticular lamina

• A barrier between the epithelial cell layer and the connective tissue (e.g dermis)

en:wp, commons.wikimedia.org Used with permission

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Basement Membrane

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2

ME 3e: 82 • ME 4e: 82

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Macule: Flat discoloration < 1cm

• Example: Tinea versicolor

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Papule: Raised skin lesion < 1cm

• Example: Acne vulgaris

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Vesicle: Small fluid-filled blister < 1cm

• Examples: See in Chickenpox and

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Bulla: Large fluid-filled vesicle > 1cm

Vesicles and Bulla.svg, commons.wikimedia.org Used with permission

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Keloid: Abnormal scar tissue hypertrophy that occurs at a site of injury

• Common in African American patients

Copyright Richard Usatine, M.D Used with permission

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Keloid

FA 2013: 395.2 • FA 2012: 423.2 • FA 2011: 387.2

ME 3e: 157 • ME 4e: 157

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MUSC1_2-

Name Description Examples

Pustule Blister containing pus

Crust Dried exudate from a vesicle or

bulla

Chickenpox Impetigo

Hyperkeratosis Increased thickness of stratum

corneum

Calluses

Parakeratosis Hyperkeratosis with retention of

nuclei in stratum corneum

Psoriasis

Acantholysis Separation of epidermal cells from

one another

Pemphigus vulgaris

Acanthosis Epidermal hyperplasia (increased

number of cells in the spinosum layer of the epithelium)

Dermatitis Inflammation of the skin

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bulla

Chickenpox Impetigo

corneum

Calluses

Psoriasis

one another

Pemphigus vulgaris

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bulla

Chickenpox Impetigo

corneum

Calluses

Psoriasis

one another

Pemphigus vulgaris

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• Etiology: Human papiloma virus

• Clinical manifestation: Common

warts and genital warts (condyloma

acuminatum)

Dornwarzen.jpg, commons.wikimedia.org Used with permission

2

Verrucae

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1

ME 3e: 456 • ME 4e: 456

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MUSC1_3-

• The common mole

• Numerous types

• Nevocellular nevus: most

common type Benign lesion

• Blue nevus: Blue colored,

congenital, intradermal lesion

• Spitz nevus: Benign,

congenital lesion seen in

children Also known as a

juvenile melinoma due to the

presence of spindle cells

• Dysplastic nevus: Any nevus

that contains atypical cells

If untreated, may progress to

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MUSC1_3-

• Common Hives

• Intensely pruitic wheals that form during an allergic reaction

• Pathophysiology: Mast cell degranulation with histamine release

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Urticaria

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1

ME 3e: 453 • ME 4e: 453

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MUSC1_3-

• Also known as eczema

• Found on flexure skin surfaces

• Associated with other atopic disorders (e.g asthma or other allergies)

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Atopic dermatitis

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1

ME 3e: 451 • ME 4e: 451

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MUSC1_3-

• Type IV hypersensitivity reaction

• Etiology: T-cell mediated reaction following contact with allergens (e.g poison ivy)

Allergic contact dermatitis following poison ivy exposure

Kaplan S2 Internal Medicine 2008:

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MUSC1_3-

• Autoimmune condition

• Clinical manifestation:

• Papules and plaques with characteristic silvery scaling

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Psoriasis

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1

ME 3e: 452 • ME 4e: 452

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Normal epidermal layers

File: WVSOM Meissner’s corpuslce.JPG by Wbensmith, commons.wikimedia.org Used with permission

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Psoriasis

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1

ME 3e: 452 • ME 4e: 452

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• Papules and plaques with characteristic silvery scaling

• Auspitz sign – Exam finding that’s considered positive when scraping

of psoriatic lesions produces bleeding

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Epidermal findings

Acanthosis with parakeratotic scaling

Increased stratum spinosum layer

Decreased stratum granulosum layer

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Psoriasis: Histology review

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1

ME 3e: 452 • ME 4e: 452

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Copyright Richard Usatine, M.D

Used with permission

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Seborrheic keratosis

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1

ME 3e: 452 • ME 4e: 452

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• Inherited defect of tyrosinase

• Failure of neural crest

migration during embryologic development

Albinistic man portrait, commons.wikimedia.org Used with permission

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Albinism

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1

ME 3e: 46 • ME 4e: 46

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MUSC1_3-

• Characteristics:

• Skin hyperpigmentation

• Commonly seen in pregnancy or

with oral contraceptive use

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• Acute infection of the

skin with dermis and

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• Acute infection of the

fascia and muscle

Necrotizing fasciitis of the leg

Necrotizing fasciitis left leg.JPEG, commons.wikimedia.org Used with permission

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• White, painless plaques

• Found on the bottom and

sides of the tongue

• Cannot be scraped off

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Hairy leukoplakia

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1

ME 3e: 355 • ME 4e: 355

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MUSC1_3-

• IgG antibodies against desmosomes

• Weakened cell to cell connections

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FA 2013: 402 • FA 2012: 425 • FA 2011: 388

ME 3e: 82 • ME 4e: 82

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MUSC1_3-

• Etiology:

• IgG antibodies against desmosomes

• Histology:

• Epithelial cell sloughing

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FA 2013: 402 • FA 2012: 425 • FA 2011: 388

ME 3e: 82 • ME 4e: 82

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FA 2013: 402 • FA 2012: 425 • FA 2011: 388

ME 3e: 82 • ME 4e: 82

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MUSC1_3-

• Epithelial cell sloughing

• Nikolsky’s sign: positive when manual

pressure or movement of the skin causes

epithelial separation and sloughing

Pemphigus.jpg, commons.wikimedia.org Used with permission

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FA 2013: 402 • FA 2012: 425 • FA 2011: 388

ME 3e: 82 • ME 4e: 82

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• Immunofluorescence shows linear

patter antibodies aligning the

epithelial basement membrane

• Negative Nikolsky’s sign

• Skin involvement

• No mucosal involvement

• Mucosal involvement is seen in pemphigus vulgaris

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Bullous pemphigoid

FA 2013: 398 • FA 2012: 425 • FA 2011: 389

ME 3e: 82 • ME 4e: 82

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MUSC1_3-

http://www.dermnet.com/Dermatitis-Herpetiformis/picture/13646 commons.wikimedia.org Used with permission

• Resembles a herpes infection

• Associated with Celiac disease

• Linear patter antibodies aligning

the epithelial basement

membrane

• Pruitic papules and vesicles

• Extensor surfaces (e.g elbows)

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Dermatitis herpetiformis

FA 2013: 398 • FA 2012: 425 • FA 2011: 389

ME 3e: 452 • ME 4°:452

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• Severe bulla formation

• Necrosis and skin

sloughing

• Mucosa involvement (e.g

oral and genital)

Syndrome/picture/14975.en.wikipedia commons.wikimedia.org Used with permission

http://www.dermnet.com/Stevens-Johnson-33

Stevens-Johnson syndrome

FA 2013: 398 • FA 2012: 425 • FA 2011: 389

ME 3e: 452 • ME 4e: 452

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MUSC1_3-

• Characteristic:

• More severe form of Stevens-Johnson

syndrome (> 30% of body involvement)

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• Saw-tooth appearing T-cell

infiltrate of the

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• Premalignant lesion

• Precursor to squamous

cell carcinoma (skin)

• Seen in elderly, in

long-term sun exposed areas

(ear or scalp of a bald

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MUSC1_3-

• Hyperpigmented, thick,

velvety appearance

• Commonly seen on the

underarms and neck

the stratum spinosum

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Acanthosis nigricans

FA 2013: 398 • FA 2012: 425 • FA 2011: 389

ME 3e: 451 • ME 4e: 451

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MUSC1_3-

• Inflammatory lesions of the

subcutaneous fat

• Associated with infections

and autoimmune diseases

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• Common benign condition

• Circular herald patch appears

on the trunk days before

general rash eruption

• Christmas tree pattern rash

of the chest, shoulder, and

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• Similar and smaller than

strawberry hemangiomas

• Common in the elderly

• Benign lesions that occur

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MUSC1_4-

• Associated with:

• Lifetime of sun exposure

• Arsenic exposure and liver

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• Large, dark, multicolored lesion

with irregular borders

• Post resection follow up with

the tumor marker S-100 Copyright Richard Usatine, M.D

Used with permission

4

Melanoma

FA 2013: 403.1 • FA 2012: 428.1 • FA 2011: 390

ME 3e: 452 • ME 4e: 452

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MS02- MUSC2_1-

Lecture 2 – Anatomy and physiology of

muscles and ligaments

Musculoskeletal and Connective

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MUSC2_1-

Ryanodine receptor

Kaplan Pathology 2010: Figure I-4-5

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Skeletal Muscle Cell Membrane

FA 2013: 385.1 • FA 2012: 412.1 • FA 2011: 377.1

ME 3e: 425 • ME 4e: 425

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Calcium (ryanodine receptor) Dihydropyridine receptor

T-tubule

• Sarcoplasmic reticulum: intracellular calcium storage space

Kaplan Pathology 2010: Figure III-1-5

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• H zone:

• Contains myosin thick filament

• Length changes with contraction

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• When activated, pulls

junctional foot processes

away from the ryanodine

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Troponin C

site on the troponin protein

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• I band:

• Contains actin thin filament

• Length shortens with

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MUSC2_1- 13

Skeletal Muscle Cell Contraction

Power stroke

Myosin in a cocked state

FA 2013: 386.1 • FA 2012: 413.1 • FA 2011: 378.2

ME 3e: 425 • ME 4e: 425

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MUSC2_1- Power stroke

Myosin in a cocked state

• Myosin binds to ATP

• Myosin hydrolyzes ATP into

ADP and an inorganic

phosphate

• Myosin is bound to ADP and

an inorganic phosphate in

the cocked state

• Myosin binds to actin

Power stroke

• Loss of ADP with the power

stroke

• Myosin binds to ATP causing

a dissociation of actin and

myosin (myosin recocks)

• Rigor mortis is due to the

absence of ATP in the

deceased

1

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FA 2013: 386.1 • FA 2012: 413.1 • FA 2011: 378.2

ME 3e: 425 • ME 4e: 425

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MUSC2_1-

- Slow twitch fibers - Fast twitch fibers

Hypertrophies with weight training

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FA 2013: 385.2 • FA 2012: 412.2 • FA 2011: 378.1

ME 3e: 425 • ME 4e: 425

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Skeletal Muscle Denervation Atrophy

FA 2013: 214.2 • FA 2012: 246.1 • FA 2011: 221.3

ME 3e: 156 • ME 4e: 156

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Skeletal Muscle Disuse Atrophy

FA 2013: 214.2 • FA 2012: 246.1 • FA 2011: 221.3

ME 3e: 156 • ME 4e: 156

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Kaplan MedEssentials 3e p426

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Smooth Muscle Contraction

• Smooth muscle cells can also transmit action potentials directly to other

smooth muscle cells, by way of electrical synapses

• Cells with electrical synapses are joined by gap junctions

• These synapses are also found between cardiac cells and some neurons

FA 2013: n/a • FA 2012: 413.2 • FA 2011: 378.3

ME 3e: 424 • ME 4e: 424

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