Nerve injury - Kaplan Test Prep

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Composed of keratin filled anucleate cells. • Calluses: stratum corneum hypertrophy. Stratum basalis. Basement membrane. Kaplan Pathology 2010: Figure 11- ...

Musculoskeletal and Connective Tissue Stephen Bagley, M.D Resident Physician, University of Pennsylvania

MUSC1_1MS01- 1

Musculoskeletal System: Dermatology Anatomy, physiology, and disease of: – – – – –

Skin Muscles and ligaments Peripheral nerves Bones Connective tissue

MUSC1_1MS01- 2

Musculoskeletal and Connective Tissue Lecture 1 - Dermatology

MUSC1_1MS01- 3

Skin layers from surface to base Epidermal layers:

Basement membrane

C. – Stratum corneum L. – Stratum lucidum G. – Stratum granulosum S. - Stratum spinosum

Stratum basalis

B. – Stratum basalis

Mnemonic: Californians Like Girls in String Bikinis

Kaplan Pathology 2010: Figure 11-1

FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451

MUSC1_1- 4

Skin layers from surface to base Epidermal layers:

Basement membrane

C. – Stratum corneum •

Top layer



Continuously sloughed off Stratum basalis



Composed of keratin filled anucleate cells



Calluses: stratum corneum hypertrophy

Kaplan Pathology 2010: Figure 11-1

FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451

MUSC1_1- 5

Skin layers from surface to base Epidermal layers:

Basement membrane

L. – Stratum lucidum

• This layer is only found in thick skin (e.g. palms and soles) Stratum basalis

Kaplan Pathology 2010: Figure 11-1

FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451

MUSC1_1- 6

Skin layers from surface to base Epidermal layers:

Basement membrane

G. – Stratum granulosum

Stratum basalis

Kaplan Pathology 2010: Figure 11-1

FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451

MUSC1_1- 7

Skin layers from surface to base Epidermal layers:

Basement membrane

S. - Stratum spinosum

Stratum basalis

Kaplan Pathology 2010: Figure 11-1

FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451

MUSC1_1- 8

Skin layers from surface to base Epidermal layers:

Basement membrane

B. – Stratum basalis •

Home to stem cells

Stratum basalis

Kaplan Pathology 2010: Figure 11-1

FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451

MUSC1_1- 9

Skin layers from surface to base Basement membrane: • Separates the epidermis from the dermis

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

FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451

MUSC1_1- 10

Skin layers from surface to base Epidermal layers:

Basement membrane

C. – Stratum corneum L. – Stratum lucidum G. – Stratum granlosum S. - Stratum spinosum

Stratum basalis

B. – Stratum basalis

Kaplan Pathology 2010: Figure 11-1

FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451

MUSC1_1- 11

Epithelial Cell Junctions

Kaplan Anatomy: Figure I-1-10

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2 ME 3e: 82 • ME 4e: 82

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Zona Occludens

Zona occludens (tight junctions): • • •

Kaplan Anatomy: Figure I-1-10

Determines cell polarity Prevents diffusion across paracellular space Composed of: • Claudins: Adhesive proteins • Occludins: Block diffusion in between cells

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2 ME 3e: 82 • ME 4e: 82

MUSC1_1- 13

Zona Adherens

Kaplan Anatomy: Figure I-1-10

Zona adherens (intermediate junctions): •

Composed of: • Cadherins: pericellular adhesive molecules responsible for cell to cell connection • Cadherins connect the intracellular actin filaments of adjacent cells • CADherins are Ca2+ dependent ADhesion molecule

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2 ME 3e: 82 • ME 4e: 82

MUSC1_1- 14

Zona Occludens Vs. Zona Adherens

Kaplan Anatomy: Figure I-1-10

Name

Zona occludens

Zona adherens

Contain

Claudins and occludins

Cadherins

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2 ME 3e: 82 • ME 4e: 82

MUSC1_1- 15

Macula Adherens (Desmosome)

Kaplan Anatomy: Figure I-1-10

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

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2 ME 3e: 82 • ME 4e: 82

MUSC1_1- 16

Macula Adherens (Desmosome)

Kaplan Anatomy: Figure I-1-10

Macula adherens (desmosome): Clinical correlate •

Pemphigus vulgaris: • Auto-antibodies developed against the desmosome • Clinical manifestation: Epithelial sloughing

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2 ME 3e: 82 • ME 4e: 82

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Gap Junction

Kaplan Anatomy: Figure I-1-10

Gap junctions: •

Open channels which allow electric and metabolic communication between two cells • Composed of connexons • Connexons have a central channel which allows flow between two cells

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2 ME 3e: 82 • ME 4e: 82

MUSC1_1- 18

Basement Membrane

Kaplan Anatomy: Figure I-1-10

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)

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2 ME 3e: 82 • ME 4e: 82

MUSC1_1- 19

Basement Membrane

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

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)

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2 ME 3e: 82 • ME 4e: 82

MUSC1_1- 20

Hemidesmosome

Kaplan Anatomy: Figure I-1-10

Hemidesmosome: •

Anchors epithelial cells to the basement membrane

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2 ME 3e: 82 • ME 4e: 82

MUSC1_1- 21

Hemidesmosome

Kaplan Anatomy: Figure I-1-10

Hemidesmosome: Clinical correlate •

Bullous pemphigoid • Auto-antibodies developed against the hemidesmosomes

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2 ME 3e: 82 • ME 4e: 82

MUSC1_1- 22

Integrin

Integrin

Integrin: •

Protein molecules used by hemidesmosomes to connect epithelial cells to the extracellular matrix

Kaplan Anatomy: Figure I-1-10

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 370.2 ME 3e: 82 • ME 4e: 82

MUSC1_1- 23

Macule versus patch

Macule: Flat discoloration < 1cm • Example: Tinea versicolor

Patch: Macule > 1cm

FA 2013: 395.2 • FA 2012: 423.2 • FA 2011: 387.2 ME 3e: n/a • ME 4e: n/a

Macule and Patch, commons.wikimedia.org. Used with permission.

MUSC1_2- 1

Papule versus plaque

Papule: Raised skin lesion < 1cm • Example: Acne vulgaris Papule and Plaque.svg, commons.wikimedia.org. Used with permission.

Plaque: Papule > 1cm • Example: Psoriasis FA 2013: 395.2 • FA 2012: 423.2 • FA 2011: 387.2 ME 3e: n/a • ME 4e: n/a

MUSC1_2- 2

Vesicles Vesicle: Small fluid-filled blister < 1cm • Examples: See in Chickenpox and Herpes

Wheal: Transient vesicles • Example: Hives

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

FA 2013: 395.2 • FA 2012: 423.2 • FA 2011: 387.2 ME 3e: n/a • ME 4e: n/a

MUSC1_2- 3

Bulla Bulla: Large fluid-filled vesicle > 1cm

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

FA 2013: 395.2 • FA 2012: 423.2 • FA 2011: 387.2 ME 3e: n/a • ME 4e: n/a

MUSC1_2- 4

Keloid 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

FA 2013: 395.2 • FA 2012: 423.2 • FA 2011: 387.2 ME 3e: 157 • ME 4e: 157

MUSC1_2- 5

Pustule Name

Description

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

FA 2013: 395.2 • FA 2012: 423.2 • FA 2011: 387.2 ME 3e: n/a • ME 4e: n/a

Examples

MUSC1_2- 6

Callus

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

Hyperkeratosis

Increased thickness of stratum corneum

FA 2013: 395.2 • FA 2012: 423.2 • FA 2011: 387.2 ME 3e: n/a • ME 4e: n/a

Calluses

MUSC1_2- 7

Parakeratosis Name

Description

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

FA 2013: 395.2 • FA 2012: 423.2 • FA 2011: 387.2 ME 3e: n/a • ME 4e: n/a

Examples

MUSC1_2- 8

Psoriasis

Kaplan Pathology 2010: Figure 11-4

Parakeratosis

Hyperkeratosis with retention of nuclei in stratum corneum

FA 2013: 395.2 • FA 2012: 423.2 • FA 2011: 387.2 ME 3e: 452 • ME 4e: 452

Psoriasis

MUSC1_2- 9

Acantholysis Name

Description

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

FA 2013: 395.2 • FA 2012: 423.2 • FA 2011: 387.2 ME 3e: n/a • ME 4e: n/a

Examples

MUSC1_2- 10

Common Diseases Of The Skin

FA 2012: 424.1



FA 2011: 388.1 • ME 3e 451



FA 2010: 384

MUSC1_3- 1

Verrucae •

Common warts



Appearance: soft, tan-colored, cauliflower-appearing lesions



Histology: Epidermal hyperplasia, hyperkeratosis, koilocytosis (vacuolated cells)



Etiology: Human papiloma virus



Clinical manifestation: Common warts and genital warts (condyloma acuminatum) Dornwarzen.jpg, commons.wikimedia.org. Used with permission.

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 456 • ME 4e: 456

MUSC1_3- 2

Nevus •

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 melanoma

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 452 • ME 4e: 452

Copyright Richard Usatine, M.D. Used with permission

MUSC1_3- 3

Nevus

Dysplastic nevus

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 452 • ME 4e: 452

Kaplan S2 Internal Medicine 2008: page 431

MUSC1_3- 4

Urticaria •

Common Hives



Intensely pruitic wheals that form during an allergic reaction



Pathophysiology: Mast cell degranulation with histamine release

Copyright Richard Usatine, M.D. Used with permission

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 453 • ME 4e: 453

MUSC1_3- 5

Atopic dermatitis •

Also known as eczema



Found on flexure skin surfaces



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

Copyright Richard Usatine, M.D. Used with permission FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 451 • ME 4e: 451

MUSC1_3- 6

Allergic Contact Dermatitis •

Type IV hypersensitivity reaction



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



Categorized as: • Acute: Presents with ulcers and vesicle • Chronic: Skin thickening or lichenification

Allergic contact dermatitis following poison ivy exposure Kaplan S2 Internal Medicine 2008: page 430 FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 452 • ME 4e: 452

MUSC1_3- 7

Psoriasis •

Autoimmune condition



Clinical manifestation: •

Papules and plaques with characteristic silvery scaling.

Copyright Richard Usatine, M.D. Used with permission

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 452 • ME 4e: 452

MUSC1_3- 8

Psoriasis •

Histology Review: •

Parakeratonic scaling •

Nucleated cells of the stratum corneum



Acanthosis



Increased stratum spinosum layer



Decreased stratum granulosum layer

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

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 452 • ME 4e: 452

MUSC1_3- 9

Psoriasis •

Clinical manifestation: •

Papules and plaques with characteristic silvery scaling



Auspitz sign – Exam finding that’s considered positive when scraping of psoriatic lesions produces bleeding

Copyright Richard Usatine, M.D. Used with permission

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 452 • ME 4e: 452

MUSC1_3- 10

Psoriasis: Histology review Epidermal findings Acanthosis with parakeratotic scaling Increased stratum spinosum layer Decreased stratum granulosum layer

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 452 • ME 4e: 452

MUSC1_3- 11

Psoriasis •

Clinical manifestation: •

Papules and plaques with characteristic silvery scaling



Auspitz sign – Exam finding that’s considered positive when scraping of psoriatic lesions produces bleeding



Arthritis



Nail pitting

Copyright Richard Usatine, M.D. Used with permission

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 4562 • ME 4e: 452

MUSC1_3- 12

Psoriasis

Copyright Richard Usatine, M.D. Used with permission

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 452 • ME 4e: 452

MUSC1_3- 13

Seborrheic keratosis •

Clinical manifestation: •

Benign, fat, greasy, pigmented lesions



Brown, scaly, “pasted on” appearance



Appear on the head, trunk



Histology •



Epithelial proliferation with keratin-filled cysts

Epidemiology •

Common in elderly Copyright Richard Usatine, M.D. Used with permission

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 452 • ME 4e: 452

MUSC1_3- 14

Albinism •

Characteristics: •

Decreased melanin production



Histology: •

Normal number of melenocytes Etiology: 2 causes

• •

Inherited defect of tyrosinase



Failure of neural crest migration during embryologic development

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

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 46 • ME 4e: 46

MUSC1_3- 15

Albinism •

Two types: •

Occular albinism •

X-linked disorder



Albinism limited to the eyes



Oculocutaneous albinism •

Eye, skin, and hair albinism



Increased risk of all skin cancer types

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

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 46 • ME 4e: 46

MUSC1_3- 16

Vitiligo •

Characteristics: •

Autoimmune attack on melanocytes



Decreased melanin production



Clinical manifestation: •

White pigmented lesions throughout the body

Copyright Richard Usatine, M.D. Used with permission

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 453 • ME 4e: 453

MUSC1_3- 17

Melasma (chloasma) •

Characteristics: •

Skin hyperpigmentation



Commonly seen in pregnancy or with oral contraceptive use



No clinical significance



Clinical manifestation: •

Facial involvement called the “mask of pregnancy”

Copyright Richard Usatine, M.D. Used with permission FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 452 • ME 4e: 452

MUSC1_3- 18

Impetigo •

Characteristics: •

Superficial skin infection



Contagious



Etiology: •



S. aureus or S. pyogenes

Clinical manifestation: •

Honey-colored, crusting Copyright Richard Usatine, M.D. Used with permission

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 453 • ME 4e: 453

MUSC1_3- 19

Cellulitis •

Characteristics: •



Acute infection of the skin with dermis and subcutaneous tissue involvement

Etiology: •



Staphylococcus or Streptococcus

Clinical manifestation: •

Erythema, warmth, pain, induration Copyright Richard Usatine, M.D. Used with permission

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 454 • ME 4e: 454

MUSC1_3- 20

Necrotizing Fasciitis (“Flesh-eating” bacteria) •

Characteristics: •



Acute infection of the fascia and muscle

Etiology: •

Anaerobes (e.g. Clostridium perfringens)



Toxin-producing bacteria (e.g. S. pyogenes



Clinical manifestation: •



Crepitus due to methane and CO2 production Dark, purple-looking, mottled, and painful skin lesions

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: n/a • ME 4e: n/a

Necrotizing fasciitis of the leg

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

MUSC1_3- 21

Staphylococcal scalded skin syndrome •

Characteristics: • Due to an exotoxin-producing strain of Staphylococcus



Histology: • Destroys keratinocyte attachments of the stratum granulosum



Clinical manifestation: • Skin exfoliation • Fever and erythema followed weeks later by sloughing of the upper epidermis • Epidemiology: Newborns and children

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 457 • ME 4e: 457

MUSC1_3- 22

Hairy leukoplakia •

Characteristics: •



Seen usually in HIV patients

Etiology: •



Epstein-Barr virus

Clinical manifestation: •

White, painless plaques



Found on the bottom and sides of the tongue



Cannot be scraped off Copyright Richard Usatine, M.D. Used with permission

FA 2013: 397.1 • FA 2012: 424.1 • FA 2011: 388.1 ME 3e: 355 • ME 4e: 355

MUSC1_3- 23

Pemphigus vulgaris

Kaplan Anatomy: Figure I-1-10



Characteristics: •

IgG antibodies against desmosomes



Weakened cell to cell connections

FA 2013: 402 • FA 2012: 425 • FA 2011: 388 ME 3e: 82 • ME 4e: 82

MUSC1_3- 24

Pemphigus vulgaris •

Etiology: •

IgG antibodies against desmosomes



Histology:



Epithelial cell sloughing

Copyright Richard Usatine, M.D. Used with permission

FA 2013: 402 • FA 2012: 425 • FA 2011: 388 ME 3e: 82 • ME 4e: 82

MUSC1_3- 25

Pemphigus vulgaris •

Etiology: •



IgG antibodies against desmosomes

Histology: •

Epithelial cell sloughing



Immunofluorescence shows



Reticular, lace-like pattern of antibody surrounded by epithelial cells

en.wikipedia. commons.wikimedia.org. Used with permission.

FA 2013: 402 • FA 2012: 425 • FA 2011: 388 ME 3e: 82 • ME 4e: 82

MUSC1_3- 26

Pemphigus vulgaris •

Clinical manifestation: •

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. FA 2013: 402 • FA 2012: 425 • FA 2011: 388 ME 3e: 82 • ME 4e: 82

MUSC1_3- 27

Bullous pemphigoid

Kaplan Anatomy: Figure I-1-10



Characteristics: •

IgG antibodies against hemidesmosomes

FA 2013: 398 • FA 2012: 425 • FA 2011: 389 ME 3e: 82 • ME 4e: 82

MUSC1_3- 28

Bullous pemphigoid •

Characteristics: •



Similar, less severe phenotype compared with pemphigus vulgaris

Etiology: •



IgG antibodies against hemidesmosomes

Histology: •



Immunofluorescence shows linear patter antibodies aligning the epithelial basement membrane

Clinical manifestation: • • •

Negative Nikolsky’s sign Skin involvement No mucosal involvement • Mucosal involvement is seen in pemphigus vulgaris

FA 2013: 398 • FA 2012: 425 • FA 2011: 389 ME 3e: 82 • ME 4e: 82

Copyright Richard Usatine, M.D. Used with permission

MUSC1_3- 29

Dermatitis herpetiformis •

Characteristics: • •



Etiology: •

• •

Resembles a herpes infection Associated with Celiac disease

IgA antibodies seen at dermal papillae tips

Histology: Immunofluorescence shows • Linear patter antibodies aligning the epithelial basement membrane



Clinical manifestation: • •

Pruitic papules and vesicles Extensor surfaces (e.g. elbows)

FA 2013: 398 • FA 2012: 425 • FA 2011: 389 ME 3e: 452 • ME 4°:452

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

MUSC1_3- 30

Erythema multiforme •

Characteristics: •

Autoimmune reaction seen in: •

Infections:



Mycoplasma



Herpes simplex



Drugs



Sulfa drugs



Beta-lactam antibiotics



Phenytoin



Cancers



Autoimmune diseases

FA 2013: 398 • FA 2012: 425 • FA 2011: 389 ME 3e: 452 • ME 4°:452

Copyright Richard Usatine, M.D. Used with permission

MUSC1_3- 31

Erythema multiforme •

Clinical manifestation: •

Non-specific rash



Target lesions



Bull’s eye appearing papules with a pale center

Copyright Richard Usatine, M.D. Used with permission FA 2013: 398 • FA 2012: 425 • FA 2011: 389 ME 3e: 452 • ME 4e: 452

MUSC1_3- 32

Stevens-Johnson syndrome •

Characteristic: •

Drug reaction



High mortality rate



Clinical manifestations: •

Fever



Severe bulla formation



Necrosis and skin sloughing



Mucosa involvement (e.g. oral and genital)

http://www.dermnet.com/Stevens-JohnsonSyndrome/picture/14975.en.wikipedia. commons.wikimedia.org. Used with permission. FA 2013: 398 • FA 2012: 425 • FA 2011: 389 ME 3e: 452 • ME 4e: 452

MUSC1_3- 33

Toxic epidermal necrolysis •

Characteristic: •

More severe form of Stevens-Johnson syndrome (> 30% of body involvement) •

< 30% in Stevens-Johnson syndrome

http://www.dermnet.com/Toxic-EpidermalNecrolysis/picture/14991.en.wikipedia. commons.wikimedia.org. Used with permission. FA 2013: 398 • FA 2012: 425 • FA 2011: 389 ME 3e: 453 • ME 4e: 453

MUSC1_3- 34

Lichen planus •

Characteristics: •

The four Ps •

Pruritic



Purple appearance



Polygonal •

• • •

Different shapes

Papules Associated with Hepatitis C infection

Histology •

Saw-tooth appearing T-cell infiltrate of the epidermaldermal junction Copyright Richard Usatine, M.D. Used with permission

FA 2013: 398 • FA 2012: 425 • FA 2011: 389 ME 3e: 452 • ME 4e: 452

MUSC1_3- 35

Actinic keratosis •

Characteristics: •

Premalignant lesion



Precursor to squamous cell carcinoma (skin)



Seen in elderly, in longterm sun exposed areas (ear or scalp of a bald head)

Copyright Richard Usatine, M.D. Used with permission

FA 2013: 378.3 • FA 2012: 404.3 • FA 2011: 389 ME 3e: 451 • ME 4e: 451

MUSC1_3- 36

Acanthosis nigricans •

Characteristics: •

Hyperpigmented, thick, velvety appearance



Commonly seen on the underarms and neck



Associated with:





Hyperinsulinemia (e.g. type 2 diabetics)



Visceral malignancies

Histology: •

Epithelial hyperplasia of the stratum spinosum

Copyright Richard Usatine, M.D. Used with permission

FA 2013: 398 • FA 2012: 425 • FA 2011: 389 ME 3e: 451 • ME 4e: 451

MUSC1_3- 37

Erythema nodosum •

Characteristics: •

Inflammatory lesions of the subcutaneous fat



Associated with infections and autoimmune diseases





Coccidioidomycosis



Histoplasmosis



Tuberculosis



Leprosy



Streptococcal infections



Sarcoidosis

Clinical manifestation: • •

Commonly seen on the anterior shins

Copyright Richard Usatine, M.D. Used with permission

Painful nodules

FA 2013: 398 • FA 2012: 425 • FA 2011: 389 ME 3e: 452 • ME 4e: 452

MUSC1_3- 38

Pityriasis rosea •

Characteristics: •



Common benign condition

Clinical manifestation: •

Circular herald patch appears on the trunk days before general rash eruption



Christmas tree pattern rash of the chest, shoulder, and back



Macules and papules



Remits spontaneously

Copyright Richard Usatine, M.D. Used with permission

FA 2013: 398 • FA 2012: 425 • FA 2011: 389 ME 3e: 452 • ME 4e: 452

MUSC1_3- 39

Strawberry hemangioma •

Characteristics: •



Appears in the first few weeks of life

Clinical manifestation: •

Large, bright red lesion of the face



Spontaneous regression by 5-8 years old

Copyright Richard Usatine, M.D. Used with permission FA 2013: 398 • FA 2012: 425 • FA 2011: 389 ME 3e: 266 • ME 4e: 266

MUSC1_3- 40

Cherry hemangioma •

Characteristics: •

Similar and smaller than strawberry hemangiomas



Common in the elderly



Benign lesions that occur with aging



Clinical manifestation: •

Found throughout the body



Do not regress

Copyright Richard Usatine, M.D. Used with permission

FA 2013: 398 • FA 2012: 425 • FA 2011: 389 ME 3e: 266 • ME 4e: 266

MUSC1_3- 41

Squamous cell carcinoma Characteristics: •

Associated with: • Lifetime of sun exposure • Arsenic exposure and liver angiosarcoma • Rarely metastasize • Locally invasive

Clinical manifestation: • • •



Actinic keratosis presents initially Erythematous, ulcerated appearance Commonly on the lower face

commons.wikimedia.org. Used with permission.



Copyright Richard Usatine, M.D. Used with permission



Treatment: •

Surgical removal

FA 2013: 403.1 • FA 2012: 428.1 • FA 2011: 390 ME 3e: 453 • ME 4e: 453

MUSC1_4- 1

Squamous cell carcinoma •

Histology: •

Keratin pearls •

Characteristic of all squamous cell carcinomas

© Katsumi M. Miyai, M.D., Ph.D., Regents of the University of California. Used with permission.

FA 2013: 403.1 • FA 2012: 428.1 • FA 2011: 390 ME 3e: 453 • ME 4e: 453

MUSC1_4- 2

Basal cell carcinoma Characteristics: •



Associated with chronic sun exposure

Clinical manifestation: •

Rolled edges with central umbilication/clearing



Pearly papule appearance



Telangiectasia overlying papules



Common on the upper face



Copyright Richard Usatine, M.D. Used with permission



Histology: •

Palisading nuclei

FA 2013: 403.1 • FA 2012: 428.1 • FA 2011: 390 ME 3e: 451 • ME 4e: 451

commons.wikimedia.org. Used with permission.

MUSC1_4- 3

Melanoma •

Characteristics: •

Skin cancer most likely to metastasize



Associated with chronic sun exposure



Risk factors:





Fair skin



Dysplastic nevus

Clinical manifestation: •

Large, dark, multicolored lesion with irregular borders



Post resection follow up with the tumor marker S-100

FA 2013: 403.1 • FA 2012: 428.1 • FA 2011: 390 ME 3e: 452 • ME 4e: 452

Copyright Richard Usatine, M.D. Used with permission.

MUSC1_4- 4

Musculoskeletal and Connective Tissue Lecture 2 – Anatomy and physiology of muscles and ligaments Stephen Bagley, M.D Resident Physician, University of Pennsylvania MUSC2_1MS02- 1

Skeletal Muscle Cell Membrane

Dyhydropyridine receptors

Kaplan Pathology 2010: Figure III-1-2

FA 2013: 385.1 • FA 2012: 412.1 • FA 2011: 377.1 ME 3e: 425 • ME 4e: 425

MUSC2_1- 2

Skeletal Muscle Cell Membrane •

Transverse tubules (T-tubule)

Ryanodine receptor Kaplan Pathology 2010: Figure I-4-5

FA 2013: 385.1 • FA 2012: 412.1 • FA 2011: 377.1 ME 3e: 425 • ME 4e: 425

MUSC2_1- 3

Skeletal Muscle Cell Membrane •

Dihydropyridine and ryanodine receptor are calcium channels



Sarcoplasmic reticulum: intracellular calcium storage space Sarcoplasmic reticulum

Dihydropyridine receptor

Calcium

(ryanodine receptor)

T-tubule

FA 2013: 385.1 • FA 2012: 412.1 • FA 2011: 377.1 ME 3e: 425 • ME 4e: 425

Kaplan Pathology 2010: Figure III-1-5

MUSC2_1- 4

Skeletal Muscle Cell Contractile Apparatus •

H zone: • •



Contains myosin thick filament Length changes with contraction

A band: • •



Length of the myosin thick filament Length remains constant

I band: • •



Contains actin thin filament Length changes with contraction

Z lines: •

Demarcate sarcomere borders

FA 2013: 385.1 • FA 2012: 412.1 • FA 2011: 377.1 ME 3e: 425 • ME 4e: 425

Kaplan Pathology 2010: Figure III-1-1

MUSC2_1- 5

Skeletal Muscle Cell Contraction •

Acetycholine (Ach)

Action potential

(Muscle cell depolarization)T-tubule

(Nicotinic receptor) Kaplan Pathology 2010: Figure II-2-5

FA 2013: 385.1 • FA 2012: 412.1 • FA 2011: 377.1 ME 3e: 425 • ME 4e: 425

MUSC2_1- 6

Skeletal Muscle Cell Contraction •

Dihydropyridine receptor: •

Voltage gated L-type Ca2+ channel



Functions as a voltage sensor



When activated, pulls junctional foot processes away from the ryanodine calcium-release channels

Cell depolarization

Dihydropyridine receptor opening



Calcium-induced calcium release from the sarcoplasmic reticulum

(ryanodine receptor)

T-tubule Kaplan Pathology 2010: Figure III-1-5

FA 2013: 385.1 • FA 2012: 412.1 • FA 2011: 377.1 ME 3e: 425 • ME 4e: 425

MUSC2_1- 7

Skeletal Muscle Cell Contraction •

Calcium binds to a binding site on the troponin protein known as troponin C



Tropomyosin moves



Myosin-Actin binding site (actin cross-bridge) is revealed



Myosin cross-bridge binds to actin cross-bridge

Troponin C

Kaplan Pathology 2010: Figure III-1-3 FA 2013: 386.1 • FA 2012: 413.1 • FA 2011: 378.2 ME 3e: 425 • ME 4e: 425

MUSC2_1- 8

Skeletal Muscle Cell Contraction

Power stroke

Kaplan Pathology 2010: Figure III-1-4

FA 2013: 386.1 • FA 2012: 413.1 • FA 2011: 378.2 ME 3e: 425 • ME 4e: 425

MUSC2_1- 9

Skeletal Muscle Cell Contractile Apparatus •

I band: • •



Contains actin thin filament Length shortens with contraction

H zone: • •



Contains myosin thick filament Length shortens with contraction

A band: • •

Length of the myosin thick filament Length remains constant

Kaplan Pathology 2010: Figure III-1-1

FA 2013: 385.1 • FA 2012: 412.1 • FA 2011: 377.1 ME 3e: 425 • ME 4e: 425

MUSC2_1- 10

Skeletal Muscle Cell Contractile Apparatus

Kaplan Pathology 2010: Figure III-1-1

FA 2013: 385.1 • FA 2012: 412.1 • FA 2011: 377.1 ME 3e: 425 • ME 4e: 425

MUSC2_1- 11

Skeletal Muscle Cell Contraction •

Calcium binds to troponin C



Tropomyosin moves Troponin C



Myosin-Actin binding site (actin cross-bridge) is revealed



Myosin cross-bridge binds to actin cross-bridge

Kaplan Pathology 2010: Figure III-1-3 FA 2013: 386.1 • FA 2012: 413.1 • FA 2011: 378.2 ME 3e: 425 • ME 4e: 425

MUSC2_1- 12

Skeletal Muscle Cell Contraction

Myosin in a cocked state

Power stroke

Kaplan Pathology 2010: Figure III-1-4

FA 2013: 386.1 • FA 2012: 413.1 • FA 2011: 378.2 ME 3e: 425 • ME 4e: 425

MUSC2_1- 13

Skeletal Muscle Cell Contraction •

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

Myosin in a cocked state

1

FA 2013: 386.1 • FA 2012: 413.1 • FA 2011: 378.2 ME 3e: 425 • ME 4e: 425

Power stroke Kaplan Pathology 2010: Figure III-1-4

MUSC2_1- 14

Skeletal Muscle Cell Contraction - Slow twitch fibers

- Fast twitch fibers

. Hypertrophies with weight training

FA 2013: 385.2 • FA 2012: 412.2 • FA 2011: 378.1 ME 3e: 425 • ME 4e: 425

MUSC2_1- 15

Skeletal Muscle Denervation Atrophy •

Muscle tissue atrophies following denervation



Muscle fiber type grouping seen on histology and occurs with reinnervation

FA 2013: 214.2 • FA 2012: 246.1 • FA 2011: 221.3 ME 3e: 156 • ME 4e: 156

MUSC2_1- 16

Skeletal Muscle Disuse Atrophy •

Occurs with prolonged disuse



Angular atrophy seen on histology and occurs primarily in type 2 fibers

FA 2013: 214.2 • FA 2012: 246.1 • FA 2011: 221.3 ME 3e: 156 • ME 4e: 156

MUSC2_1- 17

Smooth Muscle Contraction Kaplan MedEssentials 3e p426

• 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

MUSC2_1- 18

Muscle Cell Contraction Review

Kaplan Physiology 2010: Figure III-13

FA 2013: 380 • FA 2012: 407 • FA 2011: 372.2 ME 3e: 424 • ME 4e: 424

MUSC2_1- 19

Smooth Muscle Contraction

(By myosin phosphatase)

Kaplan MedEssentials 3e p426

FA 2013: n/a

• FA 2012: 413.2 • FA 2011: 378.3 ME 3e: 424 • ME 4e: 424

MUSC2_1- 20

Smooth Muscle Contraction: Pharmocologic consequences

• cGMP activates myosin phosphatase

Kaplan MedEssentials 3e p85, 426

FA 2013: 380 • FA 2012: 407 • FA 2011: 372.2 ME 3e: 424 • ME 4e: 424

MUSC2_1- 21

Thenar Eminence Thenar Eminence Function Muscles

Control thumb movement Opponens pollicis Abductor pollicis brevis Flexor pollicis brevis

FA 2013: 383.3 • FA 2012: 411.2 • FA 2011: 376.2 ME 3e: 437 • ME 4e: 437

MUSC2_2- 1

Hypothenar Eminence Hypothenar Eminence Function Muscles

Control of 5th digit movement Opponens digiti minimi Abductor digiti minimi Flexor digiti minimi

FA 2013: 383.3 • FA 2012: 411.2 • FA 2011: 376.2 ME 3e: 436 • ME 4e: 436

MUSC2_2- 2

Thenar Eminence Innervation Thenar Eminence Function Muscles

Control thumb movement Opponens pollicis Abductor pollicis brevis Flexor pollicis brevis

Innervation

FA 2013: 383.3 • FA 2012: 411.2 • FA 2011: 376.2 ME 3e: 436 • ME 4e: 436

Median nerve

MUSC2_2- 3

Hypothenar Eminence Innervation Hypothenar Eminence Function Muscles

Control of 5th digit movement Opponens digiti minimi Abductor digiti minimi Flexor digiti minimi

Innervation

FA 2013: 383.3 • FA 2012: 411.2 • FA 2011: 376.2 ME 3e: 436 • ME 4e: 436

Ulnar nerve

MUSC2_2- 4

Interosseous muscles Muscle Dorsal interosseous muscle

Function Abducts the fingers

Palmar interosseous muscle Adduct the fingers

FA 2013: 383.3 • FA 2012: 411.2 • FA 2011: 376.2 ME 3e: 436 • ME 4e: 436

Position Between the metacarpal bones Between the metacarpal bones

MUSC2_2- 5

Interosseous muscles Muscle DAB

Dorsal interosseous muscle

PAD

Palmar interosseous muscle

Function Abducts the fingers

Adduct the fingers

FA 2013: 383.3 • FA 2012: 411.2 • FA 2011: 376.2 ME 3e: 436 • ME 4e: 436

Position Between the metacarpal bones Between the metacarpal bones

MUSC2_2- 6

Lumbrical muscles Muscle Lumbrical muscles

Function Flex the fingers at the metacarpal joint Extend the fingers at the interphalangeal joints

FA 2013: 383.3 • FA 2012: 411.2 • FA 2011: 376.2 ME 3e: 436 • ME 4e: 436

MUSC2_2- 7

Interosseous muscle innervation Muscle

Function

Dorsal interosseous muscle

Abducts the fingers

Between the intercarpal bones

Ulnar nerve

Palmar interosseous muscle

Adduct the fingers

Between the intercarpal bones

Ulnar nerve

FA 2013: 383.3 • FA 2012: 411.2 • FA 2011: 376.2 ME 3e: 436 • ME 4e: 436

Position

Innervation

MUSC2_2- 8

Lumbrical muscle innervation Muscle Lumbrical muscles

Function

Innervation

Flex the fingers at the metacarpal joint

Median nerve supplies the 1st and 2nd lumbricals

Extend the fingers at the interphalangeal joints

Ulnar nerve supplies the 3rd and 4th lumbricals

FA 2013: 383.3 • FA 2012: 411.2 • FA 2011: 376.2 ME 3e: 436 • ME 4e: 436

MUSC2_2- 9

Rotator Cuff Muscles • • • • •

Rotator cuff (Shoulder) Muscles Supraspinatus Infraspinatus Teres Minor Subscapularis



Function: Shoulder movement and rotation



Supraspinatus muscle



Function: •

Kaplan Anatomy Figure III-4-5



Abducts the arm for the initial 10 -15

FA 2013: 379.3 • FA 2012: 405.3 • FA 2011: 371.2 ME 3e: 434 • ME 4e: 434

MUSC2_3- 1

Deltoid Muscle In Abduction •

Deltoid muscle



Function: •

Supraspinatus muscle abducts the arm for the initial 10 -15



The deltoid muscle controls the remainder of abduction

Kaplan Anatomy Figure III-6-1

FA 2013: 379.3 • FA 2012: 405.3 • FA 2011: 371.2 ME 3e: 434 • ME 4e: 434

MUSC2_3- 2

Infraspinatus Muscles •

Infraspinatus muscle • Function: •



Lateral arm rotation

Teres minor muscle





Lateral arm rotation



Adduction of the arm Kaplan Anatomy Figure III-4-5

• Function:

Subscapularis muscle • Function: •

Medial arm rotation



Adduction of the arm

FA 2013: 379.3 • FA 2012: 405.3 • FA 2011: 371.2 ME 3e: 434 • ME 4e: 434

MUSC2_3- 3

Knee Ligaments

Kaplan Anatomy Figure III-5-5

FA 2013: 379.1 • FA 2012: 405.1 • FA 2011: 370.3 ME 3e: 440 • ME 4e: 440

MUSC2_4- 1

Collateral Ligaments

Lateral

Medial

Kaplan Anatomy Figure III-5-5

FA 2013: 379.1 • FA 2012: 405.1 • FA 2011: 370.3 ME 3e: 440 • ME 4e: 440

MUSC2_4- 2

Lateral Collateral Ligaments •

Lateral collateral ligament: •

Attaches the femur to the fibula laterally

Lateral

Medial

Kaplan Anatomy Figure III-5-5

FA 2013: 379.1 • FA 2012: 405.1 • FA 2011: 370.3 ME 3e: 440 • ME 4e: 440

MUSC2_4- 3

Anterior and posterior cruciate ligaments

Kaplan Anatomy Figure III-5-5

FA 2013: 379.1 • FA 2012: 405.1 • FA 2011: 370.3 ME 3e: 440 • ME 4e: 440

MUSC2_4- 4

Anterior Cruciate Ligament (ACL)



Two attachment sites: •

Lateral condyle of the femur



Anterior tibial plateau

Lateral

Medial

Kaplan Anatomy Figure III-5-5

FA 2013: 379.1 • FA 2012: 405.1 • FA 2011: 370.3 ME 3e: 440 • ME 4e: 440

MUSC2_4- 5

Anterior Cruciate Ligament - 2 •

Two attachment sites: •

Lateral condyle of the femur



Anterior tibial plateau



Posterior Crutiate Ligament (PCL)



Two attachment sites: •

Posterior tibial plateau



Medial condyle of the femur Kaplan Anatomy Figure III-5-5

FA 2013: 379.1 • FA 2012: 405.1 • FA 2011: 370.3 ME 3e: 440 • ME 4e: 440

MUSC2_4- 6

Posterior Cruciate Ligament (PCL) •

Two attachment sites: •

Posterior tibial plateau



Medial condyle of the femur

Lateral

Medial

Kaplan Anatomy Figure III-5-5

FA 2013: 379.1 • FA 2012: 405.1 • FA 2011: 370.3 ME 3e: 440 • ME 4e: 440

MUSC2_4- 7

Four Major Knee Ligaments

Lateral

Medial

Kaplan Anatomy Figure III-5-5

FA 2013: 379.1 • FA 2012: 405.1 • FA 2011: 370.3 ME 3e: 440 • ME 4e: 440

MUSC2_4- 8

Knee menisci •

Meniscus •



Cartilaginous tissue

Function: • • •

Structural integrity Reduce friction Disperse upper body weight

Lateral

Medial

Kaplan Anatomy Figure III-5-5

FA 2013: 379.1 • FA 2012: 405.1 • FA 2011: 370.3 ME 3e: 440 • ME 4e: 440

MUSC2_4- 9

Knee Injuries: Unhappy Triad •

Unhappy triad: •

Etiology: •



Lateral force

Injured ligaments: • • •

MCL ACL Meniscus tear (80% are lateral, 20% are medial)

Lateral Medial

Kaplan Anatomy Figure III-5-5 FA 2013: 379.1 • FA 2012: 405.1 • FA 2011: 370.3 ME 3e: 440 • ME 4e: 440

MUSC2_4- 10

Anterior Cruciate Ligament Injury On Exam •

Anterior Cruciate Ligament Injury On Exam: •

Anterior drawer sign: • • •



Grab the shin Hold the femur stable Pull the leg forward

Medial Collateral: Ligament Injury On Exam •

Physical exam test: •



Passive abduction of the knee joint

Lateral Collateral: Ligament Injury On Exam •

Physical exam test: •

Passive adduction of the knee joint

FA 2013: 379.1 • FA 2012: 405.1 • FA 2011: 370.3 ME 3e: 440 • ME 4e: 440

Vectorized and colorized in Inkscape, based on Image:Knee diagram.png.commons.wikimedia.org. Used with permission.

MUSC2_4- 11

Repetitive Elbow Injury •

Etiology: • Due to chronic repetitive damage to the elbow and its tendons

Grays 13:27, 19 September 2003 Magnus Manske 313x650 (51,410 bytes) (From ((:en:Gray\’s Anatomy))).commons.wikimedia.org. Used with permission. FA 2013: n/a

• FA 2012: n/a • FA 2011: 376.3 ME 3e: n/a • ME 4e: n/a

MUSC2_5- 1

Repetitive Elbow Injury: Lateral Epicondylitis •

Etiology: • Due to chronic repetitive damage to the elbow and its tendons

Lateral collateral ligament

Grays 13:27, 19 September 2003 Magnus Manske 313x650 (51,410 bytes)(From ((:en:Gray\’s Anatomy))).commons.wikimedia.org. Used with permission.

FA 2013: n/a

• FA 2012: n/a • FA 2011: 376.3 ME 3e: n/a • ME 4e: n/a

MUSC2_5- 2

Repetitive Elbow Injury: Medial Epicondylitis •

Etiology: • Due to chronic repetitive damage to the elbow and its tendons

Medial collateral ligament

Grays 13:27, 19 September 2003 Magnus Manske 313x650 (51,410 bytes)(From ((:en:Gray\’s Anatomy))).commons.wikimedia.org. Used with permission.

FA 2013: n/a

• FA 2012: n/a • FA 2011: 376.3 ME 3e: n/a • ME 4e: n/a

MUSC2_5- 3

Repetitive Elbow Injury: Lateral Epicondylitis •

Etiology: • Due to chronic repetitive damage to the elbow and its tendons



Lateral collateral ligament

Also known as “Tennis elbow”

Grays 13:27, 19 September 2003 Magnus Manske 313x650 (51,410 bytes)(From ((:en:Gray\’s Anatomy))).commons.wikimedia.org. Used with permission.

FA 2013: n/a

• FA 2012: n/a • FA 2011: 376.3 ME 3e: n/a • ME 4e: n/a

MUSC2_5- 4

Repetitive Elbow Injury: Medial Epicondylitis •

Etiology: • Due to chronic repetitive damage to the elbow and its tendons



Medial collateral ligament

Also known as “Golfer’s elbow”

Grays 13:27, 19 September 2003 Magnus Manske 313x650 (51,410 bytes)(From ((:en:Gray\’s Anatomy))).commons.wikimedia.org. Used with permission.

FA 2013: n/a

• FA 2012: n/a • FA 2011: 376.3 ME 3e: n/a • ME 4e: n/a

MUSC2_5- 5

Musculoskeletal and Connective Tissue Lecture 3 – Innervation of the extremities

MUSC3_1MS03- 1

The Brachial Plexus

Kaplan Anatomy Figure III-6-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_1- 2

The Brachial Plexus Uln

Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_1- 3

The Brachial Plexus Plexus Divisions: R. T. D. C. B.

roots trunks divisions cords branches

Uln

Mnemonic: Randy Travis Drinks Cold Beer

Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_1- 4

Antebrachial Cutaneous Nerves Lateral Antebrachial Cutaneous Nerve •

Branches off the musculocutaneous nerve



Sensory innervation to the forearm

Uln

lateral

Medial Antebrachial Cutaneous Nerve •

Branches off the medial cord



Sensory innervation to medial forearm

Lateral antebrachial cutaneous nerve

Medial antebrachial cutaneous nerve Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_1- 5

The Brachial Plexus Review Branches: • • • • •

Musculocutaneous n. Axillary n. Radial n. Median n. Ulnar n.

Cutaneous sensory nerves: •

Lateral antebrachial cutaneous n.



Medial antebrachial cutaneous n.

Uln

Lateral antebrachial cutaneous nerve

Medial antebrachial cutaneous nerve Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_1- 6

The Brachial Plexus Uln

Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_1- 7

Upper Trunk Injuries Upper Trunk injuries: •

Etiology: violent stretch of the upper brachial plexus Uln



Shoulder dystocia: Neonatal injury during delivery



Sports injury: Following a fall, landing onto the area between the head and shoulder

Lateral antebrachial cutaneous nerve

Medial antebrachial cutaneous nerve Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_1- 8

Lower Trunk Injuries Lower Trunk injuries: •

Cervical rib: Congenital extra rib which compresses the lower trunk

Own work, commons.wikimedia.org. Used with permission FA 2013: 382.3 • FA 2012: 410.2 • FA 2011: 375.2 ME 3e: 432 • ME 4e: 432

MUSC3_1- 9

Lower Trunk Injuries Lower Trunk injuries: •

Pancoast tumor: A tumor at the apex of the lung that compresses the lower trunk of the brachial plexus

Own work, commons.wikimedia.org. Used with permission FA 2013: 382.3 • FA 2012: 410.2 • FA 2011: 375.2 ME 3e: 432 • ME 4e: 432

MUSC3_1- 10

Axillary nerve Uln

Lateral antebrachial cutaneous nerve

Medial antebrachial cutaneous nerve Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_2- 1

Axillary nerve •

Found along the lateral area of the shoulder



Etiology of injury: 1. Humerus neck fracture 2. Needle puncture

Grays anatomy, commons.wikimedia.org. Used with permission FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 433 • ME 4e: 433

MUSC3_2- 2

Radial Nerve Uln

Lateral antebrachial cutaneous nerve

Medial antebrachial cutaneous nerve Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_2- 3

Radial Nerve Proximal injury: •

Axilla injury due to compression from crutches

Distal injury: 1. Due to mid-shaft humeral fracture 2. Aggressive stretching of the forearm with radial subluxation and radial n. injury

Gray1235.svg, commons.wikimedia.org. Used with permission FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 433 • ME 4e: 433

MUSC3_2- 4

Median Nerve Uln

Lateral antebrachial cutaneous nerve

Medial antebrachial cutaneous nerve Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_2- 5

Median Nerve Proximal nerve injury: • Supracondylar humerus fracture • Pronator teres syndrome

Supracondylar fracture

Median nerve

Gray1235.svg, commons.wikimedia.org. Used with permission FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 432 • ME 4e: 432

MUSC3_2- 6

Median Nerve: Anterior Interosseous Nerve Distal nerve injury •

Anterior interosseous nerve compression from hemorrhage or hematoma, following radius or ulnar fracture

Anterior interosseous nerve

Grays anatomy, commons.wikimedia.org. Used with permission FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 432 • ME 4e: 432

MUSC3_2- 7

Median Nerve: Carpal Tunnel Carpal tunnel syndrome: •

Median nerve injury

Carpal tunnel

Grays anatomy, commons.wikimedia.org. Used with permission

FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 432 • ME 4e: 432

MUSC3_2- 8

Ulnar Nerve Common ulnar nerve injury: • Repetitive minor trauma (funny bone) • Fracture

Ulnar nerve

Medial epicondylar fracture

Gray1235.svg, commons.wikimedia.org. Used with permission FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 433 • ME 4e: 433

MUSC3_2- 9

Sensory Innervation Of Upper Extremity Dermatomes: C4 – Shoulder C5 – Shoulder C6 – Lateral forearm T1 – Medial forearm T2 – Axilla

File:Gray797.png, commons.wikimedia.org. Used with permission FA 2013: 380.1 • FA 2012: 407.1 • FA 2011: 372.1 ME 3e: 431 • ME 4e: 431

File:Gray798.png, commons.wikimedia.org. Used with permission

MUSC3_2- 10

Sensory Innervation Of Upper Extremity Dermatome innervation: C5 – Axillary n. C6 – Lateral antebrachial cutaneous n. T1 – Medial antebrachial cutaneous n.

File:Gray812.png and File:Gray814.png, commons.wikimedia.org. Used with permission FA 2013: 380.1 • FA 2012: 407.1 • FA 2011: 372.1 ME 3e: 431 • ME 4e: 431

MUSC3_2- 11

Sensory Innervation Of Upper Extremity Dermatomes: C4 – Shoulder C5 – Shoulder C6 – Lateral forearm T1 – Medial forearm T2 – Axilla

File:Gray797.png, commons.wikimedia.org. Used with permission FA 2013: 380.1 • FA 2012: 407.1 • FA 2011: 372.1 ME 3e: 431 • ME 4e: 431

MUSC3_2- 12

Sensory Innervation Of Upper Extremity

Kaplan Anatomy Figure III-4-2

FA 2013: 380.1 • FA 2012: 407.1 • FA 2011: 372.1 ME 3e: 431 • ME 4e: 433

MUSC3_2- 13

Clinical Signs And Symptoms of Axillary Nerve Injury Uln

Lateral antebrachial cutaneous nerve

Medial antebrachial cutaneous nerve Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_3- 1

Clinical Signs And Symptoms of Axillary Nerve Injury Etiology of injury: 1. Humerus neck fracture 2. Humeral head dislocation

Motor deficit: 1. Loss of deltoid muscle innervation 2. Loss of arm abduction at the shoulder joint •

Patient can still initiate abduction with the supraspinatus muscle.

Sensory deficit: 1. Loss of sensation over the deltoid muscle

Grays anatomy, commons.wikimedia.org. Used with permission FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 433 • ME 4e: 433

MUSC3_3- 2

Clinical Signs And Symptoms of Radial Nerve Injury Uln

Lateral antebrachial cutaneous nerve

Medial antebrachial cutaneous nerve Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_3- 3

Clinical Signs And Symptoms of Radial Nerve Injury Proximal injury: •

Saturday night palsy: • Extended axilla area compression (e.g. crutches)

Motor deficit: 1. Wrist drop 2. Tricep weakness

Distal injury: 1. Due to mid-shaft humeral fracture

Motor deficit: 1. Wrist drop 2. No tricep weakness

Sensory deficit: 1. Loss of sensation over the posterior arm and dorsum of the hand and thumb Grays anatomy, commons.wikimedia.org. Used with permission FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 432 • ME 4e: 432

MUSC3_3- 4

Median Nerve Injury Uln

Lateral antebrachial cutaneous nerve

Medial antebrachial cutaneous nerve Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_3- 5

Median Nerve Injury Proximal nerve injury: •

Supracondylar humerus fracture



Pronator teres syndrome

Motor deficit: 1. Loss of flexion of the lateral three digits (“hand of benediction”)

Supracondylar fracture

2. Wrist flexion Median nerve

3. Thumb opposition (“Ape hand”) a) Seen in proximal and distal median n. injury Gray1235.svg, commons.wikimedia.org. Used with permission FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 432 • ME 4e: 432

MUSC3_3- 6

Ape hand injury

1. Lateral finger flexion 2. Wrist flexion 3. Thumb opposition (“Ape hand”) a) Seen in proximal and distal median n. injury

FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 432 • ME 4e: 432

Eeb11288(talk), commons.wikimedia.org. Used with permission

Motor deficit:

Eeb11288(talk), commons.wikimedia.org. Used with permission

Nerve injury: proximal or distal median nerve

MUSC3_3- 7

Median Nerve Injury: Proximal Injury Proximal injury: •

Sensory deficit: 1. Palmar lateral 3 ½ digits 2. Thenar eminence a) Innervated by a median n. branch which takes off before the carpal tunnel

Kaplan Anatomy Figure III-4-2

FA 2013: 380.1 • FA 2012: 407.1 • FA 2011: 372.1 ME 3e: 433 • ME 4e: 433

MUSC3_3- 8

Median Nerve Injury: Distal Injury Distal injury: •

Sensory deficit: 1. Palmar lateral 3 ½ digits 2. Sensation of the palm is spared

Kaplan Anatomy Figure III-4-2

FA 2013: 380.1 • FA 2012: 407.1 • FA 2011: 372.1 ME 3e: 433 • ME 4e: 433

MUSC3_3- 9

Median Nerve Injury: Carpal Tunnel Carpal tunnel syndrome: • Median nerve injury

Kaplan Anatomy Figure III-4-4

FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 432 • ME 4e: 432

MUSC3_3- 10

Ulnar Nerve Injury Uln

Lateral antebrachial cutaneous nerve

Medial antebrachial cutaneous nerve Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_3- 11

Ulnar Nerve Injury Proximal ulnar nerve injury: •

Medial epicondylar humerus (“funny bone”) fracture



Motor deficit: 1. Medial finger flexion 2. Medial ulnar wrist flexion a) Radial deviation noted with wrist flexion

Gray1235.svg, commons.wikimedia.org. Used with permission

Ulnar nerve

FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 433 • ME 4e: 433

Medial epicondylar fracture

MUSC3_3- 12

Ulnar Nerve Injury Proximal injury: • Sensory deficit: 1. Medial 1 ½ digits 2. Hypothenar eminence

Kaplan Anatomy Figure III-4-2

FA 2013: 380.1 • FA 2012: 407.1 • FA 2011: 372.1 ME 3e: 433 • ME 4e: 433

MUSC3_3- 13

Ulnar Nerve Injury Distal injury: •

Etiology of injury: •

Hamate hook fracture (e.g. falling onto an outstretched hand)

Kaplan Anatomy Figure III-4-8

FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 433 • ME 4e: 433

MUSC3_3- 14

Ulnar Nerve Injury Distal injury: •

Motor deficit 1. Extension of the 4th and 5th digits. a) Lumbrical muscle impairment

Image:Gray427.png, commons.wikimedia.org. Used with permission FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 433 • ME 4e: 433

MUSC3_3- 15

Ulnar Nerve Injury Distal injury: •

Motor deficit 1. Extension of the 4th and 5th digits a) Lumbrical muscle impairment b) Also known as: I. “Ulnar claw hand” II. “Pope’s blessing”



On exam: 1. Ulnar claw is similar in appearance to the hand of benediction.

Own work, commons.wikimedia.org. Used with permission

2. The two are distinguished by whether flexion or extension of the interphalangeals causes the deficit. FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 433 • ME 4e: 433

MUSC3_3- 16

Musculocutaneous Nerve Injury Uln

Lateral antebrachial cutaneous nerve

Medial antebrachial cutaneous nerve Kaplan Anatomy Figure III-4-1

FA 2013: 381.1 • FA 2012: 408.1 • FA 2011: 373.1 ME 3e: 431 • ME 4e: 431

MUSC3_3- 17

Musculocutaneous Nerve Injury Etiology of injury: •

Upper trunk brachial plexus injury



Shoulder dystocia Uln

Kaplan Anatomy Figure III-4-1

FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 431 • ME 4e: 431

MUSC3_3- 18

Musculocutaneous Nerve Motor innervation: •

Biceps



Brachialis



Coracobrachialis



Flexors of the forearm at the elbow flexors (at the elbow) Coracobrachialis Biceps

Grays anatomy, commons.wikimedia.org. Used with permission

FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 433 • ME 4e: 433

Brachialis

MUSC3_3- 19

Brachial Plexus Injury •

Upper Trunk: Erb-Duchenne Palsy (“waiter’s tip”) Uln

• Loss of arm abduction: held by the side • Due to rotator cuff loss • Paralysis of the lateral rotators (supinator muscle) • Arm held medially rotated • Loss of biceps function • Forearm held in pronation • Injury to C5 to C6 • Musculocutaneous, axillary, and radial nerve injury



Lower Trunk: Klumpke’s palsy • Injury to C8 to T1 • Etiology of injury: • Cervical rib • Pancoast tumor • Abduction injury •

Seen in thoracic outlet syndrome Kaplan Anatomy Figure III-4-1

FA 2013: 382.2 • FA 2012: 410.1 • FA 2011: 375.1 ME 3e: 432 • ME 4e: 432

MUSC3_3- 20

Thoracic outlet syndrome •

Compression of the neurovascular bundle entering the thoracic cavity • Components affected: •

C8 & T1 roots



Subclavian artery

Neurovascular bundle at risk

Kaplan Anatomy Figure III-6-1

FA 2013: 382.2 • FA 2012: 410.1 • FA 2011: 375.1 ME 3e: 432 • ME 4e: 432

MUSC3_3- 21

Thoracic Outlet Syndrome: Klumpke’s palsy Thoracic outlet syndrome •

Signs/Symptoms of Klumpke’s palsy: 1. Thenar and hypothenar eminence atrophy (median and ulnar n.) 2. Interosseous muscle atrophy (ulnar n.) 3. Sensory deficits of medial forearm and hand (ulnar n.) Uln

Kaplan Anatomy Figure III-4-1 FA 2013: 382.2 • FA 2012: 410.1 • FA 2011: 375.1 ME 3e: 432 • ME 4e: 432

MUSC3_3- 22

Thoracic Outlet Syndrome Thoracic outlet syndrome •

Signs/Symptoms: 1. 2. 3. 4.

Thenar and hypothenar eminence atrophy (median and ulnar n.) Interosseous muscle atrophy (ulnar n.) Sensory deficits of medial forearm and hand (ulnar n.) Radial pulse disappears with ipsilateral head turn (subclavian artery)

Neurovascular bundle at risk

Kaplan Anatomy Figure III-6-1

FA 2013: 382.2 • FA 2012: 410.1 • FA 2011: 375.1 ME 3e: 432 • ME 4e: 432

MUSC3_3- 23

Thoracic Outlet Syndrome Lower trunk brachial plexus injury: C8 and T1 1. Klumpke’s palsy

Uln

Kaplan Anatomy Figure III-4-1 FA 2013: 382.2 • FA 2012: 410.1 • FA 2011: 375.1 ME 3e: 432 • ME 4e: 432

MUSC3_3- 24

Lumbrical Muscles Lumbrical muscles •

Function: •

Act upon digits 2-5



Flexion the metacarpal phalangeal (MCP) joint



Extend the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints

Kaplan Anatomy Figure III-4-1

Image:Gray427.png, commons.wikimedia.org. Used with permission

FA 2013: 382.1 • FA 2012: 409.1 • FA 2011: 374.1 ME 3e: 433 • ME 4e: 433

MUSC3_3- 25

Ulnar claw injury Nerve injury: Distal ulnar nerve •

Motor deficit (“Pope’s blessing”): •

Loss of lumbrical function of the 4th and 5th digits • •



Loss of flexion at the MCP Loss of flexion and extension at the PIP and DIP

Function preserved of the 1st-3rd digits

Own work, commons.wikimedia.org. Used with permission FA 2013: 383.1 • FA 2012: 410.3 • FA 2011: 375.3 ME 3e: 433 • ME 4e: 433

MUSC3_3- 26

Median claw injury Nerve injury: Distal median nerve (post carpal tunnel) •

Motor deficit: •

Loss of lumbrical function of the 2nd and 3rd digits • • •



Loss of flexion at the MCP Loss of flexion and extension at the PIP and DIP Thenar weakness

Function preserved of the 4th and 5th digits

Gray817.png, commons.wikimedia.org. Used with permission FA 2013: 383.1 • FA 2012: 410.3 • FA 2011: 375.3 ME 3e: 432 • ME 4e: 432

MUSC3_3- 27

Ape hand injury Nerve injury: Proximal or distal median nerve •

Motor deficit: •

Loss of the opponens pollicis (unopposable thumb)

Eeb11288(talk), commons.wikimedia.org. Used with permission

FA 2013: 383.1 • FA 2012: 410.3 • FA 2011: 375.3 ME 3e: 432 • ME 4e: 432

Eeb11288(talk), commons.wikimedia.org. Used with permission

MUSC3_3- 28

Klumpke’s total claw Nerve injury: Lower trunk of the brachial plexus (C8 and T1 roots) •

Motor deficit: • •

Loss of function of all lumbrical and interosseous muscles (2nd-5th digits) Loss of extension (clawing) of all digits

Image:Gray427.png, commons.wikimedia.org. Used with permission

FA 2013: 383.1 • FA 2012: 410.3 • FA 2011: 375.3 ME 3e: 432 • ME 4e: 432

MUSC3_3- 29

Long Thoracic Nerve Injury •

Receives innervation from the C5, C6, and C7 roots Uln

Kaplan Anatomy Figure III-4-1 FA 2013: 383.2 • FA 2012: 411.1 • FA 2011: 376.1 ME 3e: 433 • ME 4e: 433

MUSC3_3- 30

Long Thoracic Nerve Injury •

Receives innervation from the C5, C6, and C7 roots



Innervates the serratus anterior muscle



Serratus anterior muscle: •

Connects the scapula to the thoracic cage



“Boxer’s muscle”



Injury results in a “winged scapula” Winged Scapula

肩胛骨突起 Winging scapula, commons.wikimedia.org. Used with permission

FA 2013: 383.2 • FA 2012: 411.1 • FA 2011: 376.1 ME 3e: 433 • ME 4e: 433

MUSC3_3- 31

Lumbosacral Plexus •

Ventral rami of the lumbar and sacral spine

Kaplan Anatomy Figure III-5-1

FA 2013: 384.1 • FA 2012: 411.3 • FA 2011: 376.4 ME 3e: 438 • ME 4e: 438

MUSC3_4- 1

Superior Gluteal Nerve Injury •

Motor deficit: • Gluteus medius and gluteus minimus muscles • ê Thigh abduction • Positive Trendelenburg sign

De.wikipedia, commons.wikimedia.org. Used with permission

FA 2013: 384.1 • FA 2012: 411.3 • FA 2011: 376.4 ME 3e: 438 • ME 4e: 438

MUSC3_4- 2

Inferior Gluteal Nerve Injury •

Etiology of injury: • Posterior hip dislocation

Kaplan Anatomy Figure III-5-1

FA 2013: 384.1 • FA 2012: 411.3 • FA 2011: 376.4 ME 3e: 438 • ME 4e: 438

MUSC3_4- 3

Inferior Gluteal Nerve Injury •

Motor deficit: • Gluteus maximus • Difficulty jumping, climbing stairs, and rising from a seated position

Kaplan Anatomy Figure III-5-1

FA 2013: 384.1 • FA 2012: 411.3 • FA 2011: 376.4 ME 3e: 438 • ME 4e: 438

MUSC3_4- 4

Lower extremity sensory dermatomes

File:Gray798.png, commons.wikimedia.org. Used with permission FA 2013: 384.1 • FA 2012: 411.3 • FA 2011: 376.4 ME 3e: 438 • ME 4e: 438

File:Gray797.png, commons.wikimedia.org. Used with permission

MUSC3_4- 5

Ankle anatomy

Kaplan Anatomy Figure III-5-7

FA 2013: 384.1 • FA 2012: 411.3 • FA 2011: 376.4 ME 3e: 438 • ME 4e: 438

MUSC3_4- 6

Ankle anatomy

Medial

Lateral

File:Gray360.png, commons.wikimedia.org. Used with permission FA 2013: 384.1 • FA 2012: 411.3 • FA 2011: 376.4 ME 3e: 438 • ME 4e: 438

MUSC3_4- 7

Ankle anatomy

Medial

Lateral

File:Gray360.png, commons.wikimedia.org. Used with permission FA 2013: 384.1 • FA 2012: 411.3 • FA 2011: 376.4 ME 3e: 438 • ME 4e: 438

MUSC3_4- 8

Ankle injury Inversion injury: • Anterior talofibular ligament involved

Kaplan Anatomy Figure III-5-7

FA 2013: 384.1 • FA 2012: 411.3 • FA 2011: 376.4 ME 3e: 438 • ME 4e: 438

MUSC3_4- 9

Ankle injury Inversion injury: • Anterior talofibular ligament involved • Associated with: • Fibula fracture • 5th metatarsal avulsion

Kaplan Anatomy Figure III-5-7

FA 2013: 384.1 • FA 2012: 411.3 • FA 2011: 376.4 ME 3e: 438 • ME 4e: 438

MUSC3_4- 10

Ankle injury Eversion injury: • Less common than inversion due to a strong deltoid ligament

Kaplan Anatomy Figure III-5-7

FA 2013: 384.1 • FA 2012: 411.3 • FA 2011: 376.4 ME 3e: 438 • ME 4e: 438

MUSC3_4- 11

Ankle injury Eversion injury: • Medial malleolus bone avulsion • Fibular fracture

File:Gray357.png, commons.wikimedia.org. Used with permission

FA 2013: 384.1 • FA 2012: 411.3 • FA 2011: 376.4 ME 3e: 438 • ME 4e: 438

MUSC3_4- 12

Calcaneus Fracture Etiology of injury: • Fall onto the heels

Calcaneus

Kaplan Anatomy Figure III-5-7

FA 2013: 384.1 • FA 2012: 411.3 • FA 2011: 376.4 ME 3e: 438 • ME 4e: 438

MUSC3_4- 13

Musculoskeletal and Connective Tissue Lecture 4 – Disorders of the bones Stephen Bagley, M.D Resident Physician, University of Pennsylvania

MUSC4_1MS04- 1

Histology of bone formation

FA 2013: 386.2

• FA 2012: 413.3 • FA 2011: 379.1 ME 3e: n/a • ME 4e: n/a

MUSC4_1- 2

Woven bone Woven bone: •

Immature bone or that seen in diseases



Disorganized structure



Irregular osteocyte arrangement

Original work of Robert M. Hunt, commons.wikimedia.org. Used with permission.

FA 2013: 386.2

• FA 2012: 413.3 • FA 2011: 379.1 ME 3e: n/a • ME 4e: n/a

MUSC4_1- 3

Lamellar bone Lamellar bone: •

Bone is organized into osteons



Osteons: • A haversian canal with surrounding osteocytes arranged in rings called lamellae

Lamellae

Haversian canal

Kaplan Anatomy Figure I-3-8 FA 2013: 386.2

• FA 2012: 413.3 • FA 2011: 379.1 ME 3e: n/a • ME 4e: n/a

MUSC4_1- 4

Lamellar bone Haversian canal: • •

Contains blood vessels that supply osteons Lined by osteoprogenitor cells and osteoblasts

Kaplan Anatomy Figure I-3-3 FA 2013: 386.2

• FA 2012: 413.3 • FA 2011: 379.1 ME 3e: n/a • ME 4e: n/a

MUSC4_1- 5

Lamellar bone Haversian canal: •

Contains blood vessels that supply osteons



Communicates with surrounding osteocytes via canaliculi • Canaliculi are tiny channels in wihtin the osteoid that form gap junctions with processes of other osteocytes.

Haversian canal

Canal iculi

Osteoc ytes

Kaplan Anatomy Figure I-3-4 FA 2013: 386.2

• FA 2012: 413.3 • FA 2011: 379.1 ME 3e: n/a • ME 4e: n/a

MUSC4_1- 6

Bone Histology Review Woven bone: •

Irregular disorganized structure



No pattern of osteocyte arrangement

Lamellar bone: •

Organized into osteons



Osteons contain a haversian canal, connected to osteocytes by canaliculi



Osteocytes arranged into rings called lamellae

Original work of Robert M. Hunt, commons.wikimedia.org. Used with permission.

Kaplan Anatomy Figure I-3-3 FA 2013: 386.2

• FA 2012: 413.3 • FA 2011: 379.1 ME 3e: n/a • ME 4e: n/a

MUSC4_1- 7

Spongy versus compact bone Spongy bone Also called trabecular or cancellous bone

FA 2013: 386.2

• FA 2012: 413.3 • FA 2011: 379.1 ME 3e: n/a • ME 4e: n/a

Compact bone Also called cortical bone

MUSC4_1- 8

Bone characteristics Spongy bone: Characteristics Compact bone



Thinner



Trabecular or reticular Pattern

Spongy bone

Compact bone: Characteristics •

Hard, long, and smooth



Contains osteons



Examples: Humerus or femur, at the diaphysis U.S. National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program, commons.wikimedia.org. Used with permission. FA 2013: 386.2

• FA 2012: 413.3 • FA 2011: 379.1 ME 3e: n/a • ME 4e: n/a

MUSC4_1- 9

Spongy bone Spongy bone: Location •

Epiphyses of long bones



Vertebral bodies

http://training.seer.cancer.gov/module_anatomy/unit3_4_bone_class ification.html, commons.wikimedia.org. Used with permission. FA 2013: 386.2

• FA 2012: 413.3 • FA 2011: 379.1 ME 3e: n/a • ME 4e: n/a

MUSC4_1- 10

Endochondral ossification •

Longitudinal bone growth



Chondrocytes initially form a cartilaginous model



Osteoclasts and osteoblasts follow, replacing cartilage with woven bone



Woven bone is later remodeled into lamellar bone

FA 2013: 386.2

• FA 2012: 413.3 • FA 2011: 379.1 ME 3e: n/a • ME 4e: n/a

Zone of proliferating chondrocytes

Zone of hypertrophying chondrocytes

Kaplan Anatomy Figure I-3-7

MUSC4_1- 11

Membranous ossification •

Seen in flat bone growth • Examples: Skull and facial bones



Woven bone is formed by the osteoblasts and osteoclast without precursory cartilage formation



Woven bone is later remodeled into lamellar bone

Kaplan Anatomy Figure I-3-6

FA 2013: 386.2

• FA 2012: 413.3 • FA 2011: 379.1 ME 3e: n/a • ME 4e: n/a

MUSC4_1- 12

Source Of Osteoblasts Osteoblasts: •

Bone-producing cells



Source: Mesenchymal stem cells in the periosteum

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

FA 2013: 386.2

• FA 2012: 413.3 • FA 2011: 379.1 ME 3e: n/a • ME 4e: n/a

MUSC4_1- 13

Disorders of bones

FA 2013: 386.2 • FA 2012: 413.3 • FA 2011: 379.1 ME 3e: 442 • ME 4e: 442

MUSC4_2- 1

Achondroplasia •

Characteristics: • Failure of endochondrial ossification (longitudinal bone growth) • Membranous ossification not affected • Common cause of dwarfism



Clinical manifestation: • Short limbs • Normal sized heads



Etiology: • Fibroblast growth factor receptor (FGFR3): • Constitutive activation inhibits chondroctye prolideration • Thus ↓ cartilage formation and ↓ endochondrial ossification of the long bones

FA 2013: 387.1 • FA 2012: 414.1 • FA 2011: 379.2 ME 3e: 442 • ME 4e: 442

en.wikipedia, commons.wikimedia.org. Used with permission.

MUSC4_2- 2

Achondroplasia •

Epidemiology: • 85% sporatic mutation • 15% autosomal dominantly inherited • Normal lifespan • Normal fertility

en.wikipedia, commons.wikimedia.org. Used with permission. FA 2013: 387.1 • FA 2012: 414.1 • FA 2011: 379.2 ME 3e: 442 • ME 4e: 442

MUSC4_2- 3

Osteoporosis •

Characteristics: • Reduction of spongy bone density • Decreased bone mass despite normal mineralization (i.e. hardness) • Easily fractured

Kaplan Pathology Figure 27-1

FA 2013: 387.2 • FA 2012: 414.2 • FA 2011: 379.3 ME 3e: 443 • ME 4e: 443

MUSC4_2- 4

Type 1 Osteoporosis •

Epidemiology: • Postmenopausal women



Etiology: • ↓ estrogen leads to ↑ bone resorption

FA 2013: 387.2 • FA 2012: 414.2 • FA 2011: 379.3 ME 3e: 443 • ME 4e: 443

MUSC4_2- 5

Type 1 Osteoporosis Etiology •

Etiology: • RANK ligands are found on osteoblasts • RANK receptors are found on osteoclasts • RANK ligand and receptor interaction promotes osteoclast activity • ↓ estrogen promotes ↑ RANK receptor expression • This leads to ↑ RANK ligand and receptor interaction and ↑ bone resorption

FA 2013: 387.2 • FA 2012: 414.2 • FA 2011: 379.3 ME 3e: 443 • ME 4e: 443

MUSC4_2- 6

Type 2 (Senile) Osteoporosis Epidemiology: Man or woman > 70 years of age

FA 2013: 387.2 • FA 2012: 414.2 • FA 2011: 379.3 ME 3e: 443 • ME 4e: 443

MUSC4_2- 7

Osteoporosis Clinical Manifestations •

Fractures: • Compression fracture • Can occur from normal weight-bearing • Femoral neck fracture • Hip fracture • Distal radius (Colles’ fracture) • Commonly due to a fall onto an outstretched hand



Signs/symptoms: • Acute back pain • Loss of height • Kyphosis

FA 2013: 387.2 • FA 2012: 414.2 • FA 2011: 379.3 ME 3e: 443 • ME 4e: 443

Kaplan Pathology Patho_27-SB1

MUSC4_2- 8

Osteoporosis Management •

Prophylaxis: • Exercise • Weight-bearing exercise • Calcium diet and supplementation, especially < 30 years old

Radpod.org, commons.wikimedia.org. Used with permission. FA 2013: 387.2 • FA 2012: 414.2 • FA 2011: 379.3 ME 3e: 443 • ME 4e: 443

MUSC4_2- 9

Osteoporosis Management •

Treatment: • Selective Estrogen Receptor Modulators • Blocks estrogen from binding to receptors in the bone, not elsewhere

Radpod.org, commons.wikimedia.org. Used with permission. FA 2013: 387.2 • FA 2012: 414.2 • FA 2011: 379.3 ME 3e: 443 • ME 4e: 443

MUSC4_2- 10

Osteoporosis Management •

Treatment: • Calcitonin • Causes less bone resorption

Radpod.org, commons.wikimedia.org. Used with permission. FA 2013: 387.2 • FA 2012: 414.2 • FA 2011: 379.3 ME 3e: 443 • ME 4e: 443

MUSC4_2- 11

Osteoporosis Management •

Treatment: • Pulsatile parathyroid hormone treatment • For severe cases

• Do not use steroids in osteoporosis patients

• Bisphosphonates (main treatment)

Radpod.org, commons.wikimedia.org. Used with permission. FA 2013: 387.2 • FA 2012: 414.2 • FA 2011: 379.3 ME 3e: 443 • ME 4e: 443

MUSC4_2- 12

Osteoporosis Management: Bisphosphonates •

All in the class end with –dronate • Etidronate • Pamidronate • Alendronate • Risedronate • Zoledronate



Mechanism: • A structural analog of pyrophasphate that reduces osteoclast activity • Reduce the formation and resorption of hydroxyapatite

FA 2013: 405.4 • FA 2012: 430.4 • FA 2011: 392.3 ME 3e: 385 • ME 4e: 385

Radpod.org, commons.wikimedia.org. Used with permission.

MUSC4_2- 13

Osteoporosis Management: Bisphosphonates •

Other indications for use: • Paget’s disease (bone) • Malignancy-associated hypercalcemia

Radpod.org, commons.wikimedia.org. Used with permission.

FA 2013: 405.4 • FA 2012: 430.4 • FA 2011: 392.3 ME 3e: 385 • ME 4e: 385

MUSC4_2- 14

Osteoporosis Management: Bisphosphonates •

Drug toxicities: • Corrosive esophagitis • Drug should be taken while in an an upright position • Nausea and diarrhea • Jaw osteonecrosis

Jaw osteonecrosis En.wikipedia, commons.wikimedia.org. Used with permission.

FA 2013: 405.4 • FA 2012: 430.4 • FA 2011: 392.3 ME 3e: 385 • ME 4e: 385

MUSC4_2- 15

Osteopetrosis (marble bone disease) •

Characteristics: •



Etiology: •



Failure of normal bone resorption

Abnormal osteoclast function due to a genetic deficiency of carbonic anhydrase II

Clinical manifestation:

Rare causes of scoliosis and spine deformity: experience and particular features, commons.wikimedia.org. Used with permission.



Thick, dense bones that are prone to fracture



Normal serum calcium, phosphate, and alkaline phosphotase (similar lab profile to osteoporosis)



Symptoms of decreased marrow (anemia, thrombocytopenia, leukopenia)



Symptoms of extramedullary hematopoiesis (hepatomegaly and splenomegaly)

FA 2013: 387.3 • FA 2012: 414.3 • FA 2011: 379.4 ME 3e: 443 • ME 4e: 443

MUSC4_2- 16

Osteopetrosis (marble bone disease) •

Imaging: • X-ray: “Erlenmeyer flask” bones (flare out)

http://www.radswiki.net, commons.wikimedia.org. Used with permission.

“Erlenmeyer flask” bones FA 2013: 387.3 • FA 2012: 414.3 • FA 2011: 379.4 ME 3e: 443 • ME 4e: 443

MUSC4_2- 17

Osteopetrosis (marble bone disease) •

Clinical manifestation: • Cranial nerve impingement due to narrowed skull foramina

Rare causes of scoliosis and spine deformity: experience and particular features, commons.wikimedia.org. Used with permission.

FA 2013: 387.3 • FA 2012: 414.3 • FA 2011: 379.4 ME 3e: 443 • ME 4e: 443

MUSC4_2- 18

Osteomalacia Versus Osteoporosis Osteomalacia

Osteoporosis

Normal bone mass

Reduced bone mass

Defective bone mineralization

Normal bone mineralization

FA 2013: 387.4 • FA 2012: 414.4 • FA 2011: 379.5 ME 3e: 443 • ME 4e: 443

MUSC4_2- 19

Osteomalacia/rickets •

Characteristics • Normal bone mass • Defective bone mineralization



Histology: • Normal osteoid matrix accumulation around trabeculae • Absent mineralization

FA 2013: 387.4 • FA 2012: 414.4 • FA 2011: 379.5 ME 3e: 443 • ME 4e: 443

MUSC4_2- 20

Osteomalacia/rickets •

Etiology: • Adult: • Vitamin D deficiency, thus decreased calcium absorption, increased parathyroid hormone, and decreased serum phosphate En wikipedia, commons.wikimedia.org. Used with permission.

• Child (Rickets): • Vitamin D deficiency •

Treatment: • Vitamin D supplementation (adults)

Decreased bone opacity seen in osteomalacia

FA 2013: 387.4 • FA 2012: 414.4 • FA 2011: 379.5 ME 3e: 443 • ME 4e: 443

MUSC4_2- 21

Osteomalacia/rickets •

Clinical manifestations: • Children: • Cranial Tabes • Failure of fontanelles closure • Rachitic rosary • Due to thickened costochondral junctions

FA 2013: 387.4 • FA 2012: 414.4 • FA 2011: 379.5 ME 3e: 443 • ME 4e: 443

MUSC4_2- 22

Paget’s disease (osteitis deformans) •

Characteristics: • Abnormal bone architecture due to ↑ osteoblastic and osteoclastic activity • ↑ bone formation and resorption

Radpod.org, commons.wikimedia.org. Used with permission.

FA 2013: 387.5 • FA 2012: 414.5 • FA 2011: 380.1 ME 3e: 443 • ME 4e: 443

MUSC4_2- 23

Paget’s disease (osteitis deformans) •

Etiology: • Paramyxovirus is the suspected cause

Radpod.org, commons.wikimedia.org. Used with permission.

FA 2013: 387.5 • FA 2012: 414.5 • FA 2011: 380.1 ME 3e: 443 • ME 4e: 443

MUSC4_2- 24

Paget’s disease (osteitis deformans) •

Clinical manifestations: • Normal serum calcium, phosphorus, and parathyroid hormone levels • Increased alkaline phosphatase

Radpod.org, commons.wikimedia.org. Used with permission.

FA 2013: 387.5 • FA 2012: 414.5 • FA 2011: 380.1 ME 3e: 443 • ME 4e: 443

MUSC4_2- 25

Paget’s disease (osteitis deformans) •

Two stages • Morphologic phase • Osteolytic processes followed by osteoblastic processes • Mosaic bone pattern • Increased hat size Own work, commons.wikimedia.org. Used with permission.

• Hearing loss • Late phase • Arteriovenous malformations and shunting within the bone • High output cardiac failure (CHF) • Osteogenic sarcoma FA 2013: 387.5 • FA 2012: 414.5 • FA 2011: 380.1 ME 3e: 443 • ME 4e: 443

Characteristic jigsaw-puzzle pattern seen on H&E in Paget’s disease of bone

MUSC4_2- 26

Polyostotic fibrous dysplasia •

Characteristics:



Associated with McCune-Albright syndrome (most common cause) • A form of polyostotic fibrous dysplasia •

Clinical triad: • Multiple unilateral bone lesions • Other endocrine abnormalities (e.g. precocious puberty) • Café’-au-lait spots (“coast of Maine” spots) of the skin



Histology: • Bone is replaced with fibroblasts, collagen, and irregular bony trabeculae

FA 2013: 388.2 • FA 2012: 415.2 • FA 2011: 380.3 ME 3e: 442 • ME 4e: 442

MUSC4_2- 27

Expected Lab Values In Bone Disorders

FA 2013: 388.1 • FA 2012: 415.2 • FA 2011: 380.2 ME 3e: 443 • ME 4e: 443

MUSC4_2- 28

Labs: Osteoporosis And Osteopetrosis Disorder

Osteoporosis

Osteopetrosis

Bone mass

Reduced

Increased

Bone mineralization

Normal

Normal

Labs

Normal labs

Normal labs

FA 2013: 388.1 • FA 2012: 415.2 • FA 2011: 380.2 ME 3e: 443 • ME 4e: 443

MUSC4_2- 29

Labs: Osteomalacia And Osteoporosis Disorder Bone mass

Osteomalacia Normal

Bone mineralization Reduced Labs

Hypocalcemia, Hypophosphatemia, Elevated parathyroid hormone, Normal alkaline phosphatase

FA 2013: 388.1 • FA 2012: 415.2 • FA 2011: 380.2 ME 3e: 443 • ME 4e: 443

Osteoporosis Reduced Normal Normal

MUSC4_2- 30

Osteitis fibrosa cystica •

Characteristics: • Bone disease associated with chronic kidney disease • Also known as brown tumors of the bone



Etiology: • Chronic kidney disease → Decreased Vitamin D production • Compensatory increased in parathyroid hormone (PTH) • Elevated alkaline phosphatase also seen due to elevated osteoblastic activity Disorder Labs

Osteitis fibrosa cystica Elevated PTH, Hypercalcemia, Hypophosphatemia, Elevated alkaline phosphatase

FA 2013: 388.1 • FA 2012: 415.2 • FA 2011: 380.2 ME 3e: 442 • ME 4e: 442

MUSC4_2- 31

Paget’s disease of bone Disorder Labs

Paget’s disease of bone Normal PTH, calcium, and phosphate Elevated alkaline phosphatase

FA 2013: 388.1 • FA 2012: 415.2 • FA 2011: 380.2 ME 3e: 442 • ME 4e: 442

MUSC4_2- 32

Primary Bone Tumors

FA 2013: 389.1 • FA 2012: 416.1 • FA 2011: 381.1 ME 3e: 445 • ME 4e: 445

MUSC4_3- 1

Osteoma •

Characteristics: • Benign • Associated with Gardner’s syndrome (Familial Adenomatous Polyposis) • Characterized by: • Numerous colonic polys • Jaw osteoma

FA 2013: 389.1 • FA 2012: 416.1 • FA 2011: 381.1 ME 3e: 445 • ME 4e: 445

MUSC4_3- 2

Osteoid Osteoma •

Characteristics: • Benign • < 2cm • Location: proximal tibia and femur • Most commonly in men < 25 years of age



Histology: • Interlacing trabeculae of woven bone, surrounded by osteoblasts

Source: Tylan A. Muncy

FA 2013: 389.1 • FA 2012: 416.1 • FA 2011: 381.1 ME 3e: 445 • ME 4e: 445

MUSC4_3- 3

Osteoblastoma •

Characteristics: • Benign • Morphologically the same as osteoid osteoma • Larger than osteoid osteoma • Location: vertebral column



Histology: • Interlacing trabeculae of woven bone, surrounded by osteoblasts

Osteoblastoma - high mag.jpg, commons.wikimedia.org. Used with permission.

FA 2013: 389.1 • FA 2012: 416.1 • FA 2011: 381.1 ME 3e: 445 • ME 4e: 445

MUSC4_3- 4

Giant Cell Tumor •

Characteristics: • Location: Epiphyseal end of long bones • Peak incidence: 20-40 years of age • Men > Women • Benign, yet locally aggressive



X-ray: • “Double bubble” or “soap bubble” appearance

Source: Boma O. Afiesimama

FA 2013: 389.1 • FA 2012: 416.1 • FA 2011: 381.1 ME 3e: 445 • ME 4e: 445

MUSC4_3- 5

Giant Cell Tumor •

Histology: • Spindle shaped cells • Multi-nucleated giant cells

Multi-nucleated giant cells

Giant cell tumor of bone – high mag.jpg, commons.wikimedia.org. Used with permission.

FA 2013: 389.1 • FA 2012: 416.1 • FA 2011: 381.1 ME 3e: 445 • ME 4e: 445

MUSC4_3- 6

Osteochondroma (exostosis) •

Characteristics: • Exostosis with a cartilaginous cap • Typically in men < 25 years of age • Location: Metaphysis of long bones • Malignant transformation (chondrosarcoma) is rare

FA 2013: 389.1 • FA 2012: 416.1 • FA 2011: 381.1 ME 3e: 445 • ME 4e: 445

MUSC4_3- 7

Enchondroma •

Characteristics:

Enchondroma

• Benign, cartilaginous tumor • Location: Small bones within the intramedullary space (e.g. hand and feet)

Own work, commons.wikimedia.org. Used with permission. FA 2013: 389.1 • FA 2012: 416.1 • FA 2011: 381.1 ME 3e: 445 • ME 4e: 445

MUSC4_3- 8

Malignant Bone Tumors

FA 2013: 389.1 • FA 2012: 416.1 • FA 2011: 381.1 ME 3e: 445 • ME 4e: 445

MUSC4_3- 9

Osteosarcoma (osteogenic sarcoma) •

Characteristics: • •

Malignant 2nd most common bone malignancy (melanoma is 1st) Typically men, ages 10-20 Location: Metaphysis of long bones (e.g. distal femur, proximal tibia)

• •



Risk factors: • • • •



Paget’s disease of bone Bone infarcts History of bone radiation Familial retinal blastoma

X-ray: •

Sunburst pattern (periosteal elevation due to inflammation)

FA 2013: 389.1 • FA 2012: 416.1 • FA 2011: 381.1 ME 3e: 445 • ME 4e: 445

Kaplan Pathology Figure 27-4

MUSC4_3- 10



Characteristics: • Aggressive, fast-growing • Typically in teenage boys, < 15 years of age • Location: Diaphysis of long bones, pelvis, scapula, and ribs • 11;22 translocation



Histology: • Anaplastic, small, blue cells



Treatment: • Good response to chemotherapy



X-ray: • “Onion-skin” appearance

FA 2013: 389.1 • FA 2012: 416.1 • FA 2011: 381.1 ME 3e: 445 • ME 4e: 445

Kaplan Pathology Figure 274

EN:Wikipedia. IMG EwingSarcomaTibia.jpg, commons.wikimedia.org. Used with permission.

Ewing’s sarcoma

MUSC4_3- 11

Chondrosarcoma •

Characteristics: • Malignant tumor of cartilage

• Typically in men, ages 30-60

• Location: Pelvis, spine, scapula, humerus, tibia, and femur • Spine involvement is unusual in Ewing’s

Kaplan Pathology Figure 274

Mrichondrosarcoma.jpg, commons.wikimedia.org. Used with permission. FA 2013: 389.1 • FA 2012: 416.1 • FA 2011: 381.1 ME 3e: 445 • ME 4e: 445

MUSC4_3- 12

Primary Bone Tumors

FA 2013: 389.1 • FA 2012: 416.1 • FA 2011: 381.1 ME 3e: 445 • ME 4e: 445

MUSC4_3- 13

Musculoskeletal and Connective Tissue Lecture 5 – Arthritis Stephen Bagley, M.D Resident Physician, University of Pennsylvania MUSC5_1MS05- 1

Osteoarthritis •

Characteristics: •



Not an inflammatory condition

Etiology: • •



Chronic wear and tear of joints with destruction of articular cartilage Articular cartilage loss leads to increased bone on bone friction

Risk factors: •



Age / Previous joint injuries

Characteristic joint findings: • • • •

Subchondral cysts Sclerosis Osteophytes (bone spurs) Eburnation (polished, irory-like appearance of bone)

FA 2013: 390.1 • FA 2012: 417.1 • FA 2011: 382.1 ME 3e: 446 • ME 4e: 446

MUSC5_1- 2

Osteoarthritis •

Physical exam: • Heberden’s nodes at the distal interphalangeal joint • Bouchard’s nodes at the proximal interphalangeal joint



Patient presentation: • Exertional pain in weight-bearing joints • Pain relieved with rest (distinguishes from Rheumatoid arthritis) • Medial knee pain • No systemic systems

Heberden’s nodes Kaplan Pathology Figure 27-1

FA 2013: 390.1 • FA 2012: 417.1 • FA 2011: 382.1 ME 3e: 446 • ME 4e: 446

MUSC5_1- 3

Rheumatoid arthritis •

Characteristics • Autoimmune inflammatory condition • Systemic manifestations present • Pannus formation in the synovial joints



Histology: • Hyperplasia and hypertrophy of the synovium

Kaplan Pathology Figure Patho_28-SB1

FA 2013: 390.1 • FA 2012: 418.1 • FA 2011: 383.1 ME 3e: 446 • ME 4e: 446

MUSC5_2- 1

Rheumatoid arthritis •

Characteristics • Systemic manifestations • Felty’s syndrome: • Rheumatoid arthritis • Splenomegaly • Neutropenia • Symmetric joint involvement • Arthritis location: • Metacarpal phalangeal joint • Morning stiffness

FA 2013: 390.1 • FA 2012: 418.1 • FA 2011: 383.1 ME 3e: 446 • ME 4e: 446

MUSC5_2- 2

Rheumatoid arthritis •

Systemic manifestations: • Felty’s syndrome: • Rheumatoid arthritis • Splenomegaly • Neutropenia • Fever • Fatigue • Pleuritis • Pericarditis • Interstitial lung disease • Vasculitis Copyright Richard Usatine, M.D. Used with permission

FA 2013: 390.1 • FA 2012: 418.1 • FA 2011: 383.1 ME 3e: 446 • ME 4e: 446

MUSC5_2- 3

Rheumatoid arthritis •

Etiology: • Type III hypersensitivity disorder • Damage due to immune complex formation • Positive Rheumatoid factor, an anti-IgG antibody



Labs: • Rheumatoid factor (sensitive but not specific) • Anti-CCP antibody • HLA-DR4

Rheumatoid nodule Copyright Richard Usatine, M.D. Used with permission

FA 2013: 390.1 • FA 2012: 418.1 • FA 2011: 383.1 ME 3e: 446 • ME 4e: 446

MUSC5_2- 4

Rheumatoid arthritis •

Characteristic lesions: • Ulnar deviation • Deviated in the ulnar direction

Kaplan Pathology Figure 28.2

Ulnar deviation at the MCP joint FA 2013: 390.1 • FA 2012: 418.1 • FA 2011: 383.1 ME 3e: 446 • ME 4e: 446

MUSC5_2- 5

Rheumatoid arthritis •

Characteristic lesions: • Boutonnier deformity

Kaplan Pathology Figure 28.2

RA_hand_deformity.jpg, commons.wikimedia.org

Boutonnier deformity of the PIP joint FA 2013: 390.1 • FA 2012: 418.1 • FA 2011: 383.1 ME 3e: 446 • ME 4e: 446

MUSC5_2- 6

Rheumatoid arthritis •

Characteristic lesions: • Swan Neck deformity • Involved fingers bend in the wrong direction at the PIP joints

Kaplan Pathology Figure 28.2

FA 2013: 390.1 • FA 2012: 418.1 • FA 2011: 383.1 ME 3e: 446 • ME 4e: 446

MUSC5_2- 7

Gout •

Etiology: • Due to hyperuricemia and precipitation of monosodium urate crystals into joints • IgG-mediated inflammation



Signs/symptoms: • Erythema, warmth, and pain classically at the 1st metatarsal joint • Asymmetrical involvement of other joints

Kaplan Pathology 2011: Figure 28-4

FA 2013: 391.2 • FA 2012: 419.1 • FA 2011: 384.1 ME 3e: 446 • ME 4e: 446

MUSC5_3- 1

Gout •

Histology: • Needle-shaped, negatively birefringent crystals • Crystals turn yellow under a parallel light

Fluorescent uric acid.jpg, commons.wikimedia.org

Uric acid crystals under polarized light FA 2013: 391.2 • FA 2012: 419.1 • FA 2011: 384.1 ME 3e: 446 • ME 4e: 446

MUSC5_3- 2

Gout •

Etiology: •

Idiopathic, decreased ability to excrete uric acid in the urine •

Precipitants: •

Large protein meals



Alcohol binges



Thiazide diuretics



Large cell turn over (e.g. acute leukemia or following chemotherapy)



Lesch-Nyhan syndome •

Purine salvage deficiency



Purines degraded into uric acid



Patients develop gout at an early age

Kaplan Pathology 2011: Figure 28-4



Other signs/symptoms: •

Tophi: a painful granulomatous foreign body reaction occurring near a joint space •

FA 2013: 391.2 • FA 2012: 419.1 • FA 2011: 384.1 ME 3e: 446 • ME 4e: 446

Common locations: •

External ear



Elbow



Achilles tendon MUSC5_3- 3

Gout •

Treatment: • Acute: • NSAIDs • Colchicine

• Chronic • Allopurinol • Probenecid

GoutTophiElbow.jpg, commons.wikimedia.org

FA 2013: 391.2 • FA 2012: 419.1 • FA 2011: 384.1 ME 3e: 446 • ME 4e: 446

MUSC5_3- 4

Pseudogout •

Characteristics: •



Calcium pyrophosphate crystals deposit in the joints

Signs/symptoms: •



Pain, erythema, and inflammation

Histology: •

Needle-shaped, positively birefringent crystals •



Crystals turn yellow under a perpendicular light and blue under a parallel light

Treatment: •

Acute: •

NSAIDS



Colchicine Source: Boma O Afiesimama

FA 2013: 391.3 • FA 2012: 419.2 • FA 2011: 384.2 ME 3e: 446 • ME 4e: 446

MUSC5_3- 5

Infectious arthritis •

Etiology: • Staph aureus • Streptococcus • Neisseria gonorrhoeae



Gonococcal arthritis: • Arthritis characteristics: • Co-symptom of urethritis • Monoarticular • Migratory • Asymmetrical • Synovitis • Tenosynovitis • Dermatitis

FA 2013: 392.1 • FA 2012: 420.1 • FA 2011: 384.3 ME 3e: 447 • ME 4e: 447

MUSC5_4- 1

Chronic Infectious arthritis •

Etiology: • Tuberculosis • Lyme disease • Chronic arthritis can develop due to untreated infection

Erythema migrans FA 2013: 392.1 • FA 2012: 420.1 • FA 2011: 384.3 ME 3e: 447 • ME 4e: 447

Kaplan Pathology 2010 Figure 28-5

MUSC5_4- 2

Seronegative spondyloarthropathies •

Characteristics: • Arthritis without rheumatoid factor • Strong association with HLA-B27

FA 2013: 392.3 • FA 2012: 420.3 • FA 2011: 385.1 ME 3e: 446 • ME 4e: 446

MUSC5_5- 1

Psoriatic arthritis •

Characteristics: • Associated with psoriasis • Signs/symptoms • Asymmetric arthritis • Typically involves the fingers • Dactylitis (“sausage fingers”)



X-ray: • “Pencil-in-cup” deformity

Psoriatic-arthritis-003.jpg, commons.wikimedia.org. Used with permission.. FA 2013: 392.3 • FA 2012: 420.3 • FA 2011: 385.1 ME 3e: 446 • ME 4e: 446

MUSC5_5- 2

Ankylosing spondylitis •

Characteristics: • Inflammatory condition of the spine and sacroiliac joint • Typically affects young men



Signs/symptoms: • Morning back stiffness • Difficulty with bending forward



X-ray: • Bamboo spine appearance due to joint fusion Kaplan Pathology 2010 Figure 28-3

FA 2013: 392.3 • FA 2012: 420.3 • FA 2011: 385.1 ME 3e: 446 • ME 4e: 446

MUSC5_5- 3

Ankylosing spondylitis •

Associated with: • Uveitis • Aortic regurgitation • Inflammatory bowel disease • Crohns’ disease • Ulcerative colitis

Kaplan Pathology 2010 Figure 28-3 FA 2013: 392.3 • FA 2012: 420.3 • FA 2011: 385.1 ME 3e: 446 • ME 4e: 446

MUSC5_5- 4

Reactive arthritis •

Characteristics: • An autoimmune reaction to a pathogen • Gastrointestinal (e.g. Campylobacter) • Genitourinary (e.g. Chlamydia)



Etiology: • Autoimmune reaction develops during the immune response to the primary pathogen infection

FA 2013: 392.3 • FA 2012: 420.3 • FA 2011: 385.1 ME 3e: 446 • ME 4e: 446

MUSC5_5- 5

Reactive Arthritis – Reiters Syndrome •

Reiter’s syndrome • Classic triad: • Conjunctivitis and uveitis • Urethritis • Arthritis

FA 2013: 392.3 • FA 2012: 420.3 • FA 2011: 385.1 ME 3e: 446 • ME 4e: 446

MUSC5_5- 6

Reactive Arthritis – Review •

Associated with HLA-B27



Prone to developing uveitis

FA 2013: 392.3 • FA 2012: 420.3 • FA 2011: 385.1 ME 3e: 446 • ME 4e: 446

MUSC5_5- 7

Treatment Of Arthritis: Eicosanoids •

Eicosanoids: Arachidonic acid products

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 1

Arachidonic Acid Products

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 2

Arachidonic Acid Products •

COX 1: • Location: • GI system • Platelets

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 3

Arachidonic Acid Products

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 4

Arachidonic Acid Products: Prostacyclin •

Prostacyclin (PGI2): •

Anti-platelet properties •





↓ platelet aggregation Vasodilation

Prostaglandin: •

Proinflammatory mediator



PGE2





↓ vascular tone



↑ pain



↑ urterine tone



↑ temperature

Thromboxane (TXA2): •

Pro-platelet •



↑ platelet aggregation Vasoconstriction

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

Kaplan Pharmacology 2010 Figure VI-4-1

MUSC5_6- 5

Cox enzyme review

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 6

Arachidonic Acid Products: Leukotrienes •

LTB4 • Function: • Neutrophil chemotaxis



Other leukotrienes • Function: • Bronchoconstriction

LTB4

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 7

Arachidonic Acid Pathway: Pharmacology Corticosteroids •

Inhibit phospholipase A2



Inhibits protein synthesis and thus COX production

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 8

Zileuton •

Inhibits lipoxygenase, decreasing leukotrienes

LTB4

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 9

Leukotriene receptor blockers •

Medications: • Montelukast • Zafirlukast



Mechanism: • Block leukotriene receptors (lung) therefore decrease bronchconstriction



Indication: • Asthma

LTB4

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 10

Non-steroidal anti-inflammatory drugs (NSAIDs) •

Medications: • Acetaminophen • Aspirin



Mechanism: • COX 1 and COX 2 blocker

LTB4

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 11

COX 2 inhibitors •

Medications: • Acetaminophen • Aspirin



Mechanism: • Selective COX 2 blocker

LTB4

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 12

Aspirin •

Mechanism: •

Covalently binds to and irreversibly inhibits cyclooxygenase 1 and 2



↓ Thromboxane and prostaglandin synthesis



Indications: •

Low dose (baby aspirin): < 300mg day •



Heart disease: ↓ platelet aggregation Intermediate dose: (300-2400mg/day)



Anti-pyretic



Analgesic



High dose: (2400-4000 mg/day) •

LTB4

Anti-inflammatory Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.2

• FA 2012: 429.2 • FA 2011: 391.2 ME 3e: 54 • ME 4e: 54

MUSC5_6- 13

Aspirin •

Side effects: • •

Gastric upset Upper gastrointestinal bleeding and ulceration •

• • •

Acute renal failure Interstitial nephritis Reye’s syndrome (children) •





Due to inhibition of gastric COX 1 (prostaglandin synthesis is important for maintenance of the gastric mucosal lining)

May occur when aspirin is used for symptom relief during a viral illness Associated with: • Liver failure • Encephalopathy

Aspirin induced asthma (due to loss of prostaglandin induced bronchodilation)

FA 2013: 404.2

• FA 2012: 429.2 • FA 2011: 391.2 ME 3e: 54 • ME 4e: 54

LTB4

Kaplan Pharmacology 2010 Figure VI-4-1

MUSC5_6- 14

Other NSAIDs •

Medications: • • • •



Ibuprofen Naproxen Indomethacin Ketorolac

Mechanism: • •



Reversibly block COX ↓ prostaglandin and ↓ inflammation

Indications: • • • •

Anti-pyretic Analgesic Anti-inflammatory Patent ductus arteriosus closure (indomethacin)

LTB4

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 15

Other NSAIDs •

Side effects: • Renal damage • Fluid retention and CHF • Aplastic anemia • GI distress (bleeding and ulcers)

LTB4

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 391.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 16

NSAIDs: Selective COX 2 inhibitors •

Medications: •



Celecoxib

Mechanism: • •



Blocks COX 2 (only) ↓ prostaglandin and ↓ inflammation

Indications: • •



Patients with a history of GI bleeding Rheumatoid and osteoarthritis (celecoxib)

Side effects: • •

Thrombosis (e.g. acute MI) Contraindicated in patients with sulfa allergies

FA 2013: 404.1

• FA 2012: 429.1 • FA 2011: 392.1 ME 3e: 54 • ME 4e: 54

LTB4

Kaplan Pharmacology 2010 Figure VI-4-1

MUSC5_6- 17

NSAIDs: Acetaminophen •

Mechanism: •

Reversibly inhibits COX in the CNS



No anti-inflammatory properties (due to absent effect in the periphery)



Indications: •

Analgesic



Anti-pyretic



Viral symptom management in children (instead of aspirin)



Side effects: •

Hepatic necrosis with overdosage •

Due to hepatic glutathione depletion by a tylenol metabolite)



↓ glutathione leads to free radical accumulation and hepatocyte destruction

FA 2013: 404.2

• FA 2012: 429.2 • FA 2011: 391.2 ME 3e: 54 • ME 4e: 54

LTB4

Kaplan Pharmacology 2010 Figure VI-4-1

MUSC5_6- 18

NSAIDs: Acetaminophen •

Treatment of overdose: • N-acetylcysteine • Regenerates glutathione

LTB4

Kaplan Pharmacology 2010 Figure VI-4-1

FA 2013: 404.2

• FA 2012: 429.2 • FA 2011: 392.1 ME 3e: 54 • ME 4e: 54

MUSC5_6- 19

Gout Treatment: •

Acute: •



NSAIDS / Colchicine

Chronic •

Allopurinol / probenecid

Colchicine: •

Mechanism: •



Binds to and stabilizes tubulin

Side effects: •



GI (e.g. diarrhea)

Indications: •

Used in acute gout, following failed aspirin therapy •

GoutTophiElbow.jpg, commons.wikimedia.org

Aspirin is 1st line due to a better side effect profile

FA 2013: 391.2 • FA 2012: 419.1 • FA 2011: 384.1 ME 3e: 446 • ME 4e: 446

MUSC5_6- 20

Probenecid •

Mechanism: • Inhibits uric acid reabsorption in the proximal convoluted tubule



Side effects: • Inhibited penicillin secretion



Indications: • Used in chronic gout

Kaplan Pathology 2011: Figure 28-4

FA 2013: 406.1 • FA 2012: 431.1 • FA 2011: 392.4 ME 3e: 449 • ME 4e: 449

MUSC5_6- 21

Allopurinol

Kaplan Pharmacology 2010 Figure VI-6-1



Mechanism: • Inhibits xanthine oxidase • Xanthine oxidase is required for uric acid production



Indications: • Used in chronic gout • Tumor lysis syndrome prophylaxis, given to cancer patients prior to administering chemotherapy

FA 2013: 406.1 • FA 2012: 431.1 • FA 2011: 392.4 ME 3e: 449 • ME 4e: 449

MUSC5_6- 22

Allopurinol •

Contraindicactions: • Azathioprine and 6-mercaptopurine use •

Blocking xanthine oxidase blocks the metabolism of these drugs, leading accumulation and toxicity

• Concurrent salicylate use (e.g. aspirin) •

Depresses uric acid clearance

Fluorescent uric acid.jpg, commons.wikimedia.org

FA 2013: 406.1 • FA 2012: 431.1 • FA 2011: 392.4 ME 3e: 449 • ME 4e: 449

MUSC5_6- 23

Musculoskeletal And Connective Tissue Lecture 6 – Autoimmune and connective tissue disease Stephen Bagley, M.D Resident Physician, University of Pennsylvania MUSC6_1MS06- 1

Sjögren’s syndrome •

Characteristics: • ↑ risk of B cell lymphoma (due to lymphocyte dysfunction) • History of dental caries • Antibodies • Anti-SSA (Ro) • Anti-SSB (La)



Signs /symptoms: • Clinical triad: • Xerophthalmia (dry eyes, conjunctivitis, and a granular, “sand in my eyes” feeling • Xerostomia (dry mouth, dysphagia) • Arthritis • Parotid gland enlargement

FA 2013: 391.1 • FA 2012: 418.2 • FA 2011: 383.2 ME 3e: 106 • ME 4e: 106

MUSC6_1-

2

Sjögren’s syndrome •

Characteristics: • Typically affects females ages 40-60 • Associated with rheumatoid arthritis

FA 2013: 391.1 • FA 2012: 418.2 • FA 2011: 383.2 ME 3e: 106 • ME 4e: 106

MUSC6_1-

3

Sicca syndrome •

Characteristics: • Related to Sjögren’s syndrome, but without arthritis



Signs/symptoms: • Dry eyes • Dry mouth • Nasal and pharyngeal dryness • Vaginal dryness • Chronic bronchitis • Reflux esophagitis

FA 2013: 391.1 • FA 2012: 418.2 • FA 2011: 383.2 ME 3e: 106 • ME 4e: 106

MUSC6_1-

4

Systemic lupus erythematosus Characteristics: •

Systemic inflammatory condition



Typically among females (90% of cases), ages 14-45



SLE is most common and severe in African American females



© Katsumi M. Miyai, M.D., Ph.D., Regents of the University of California. Used with permission.



Signs/symptoms: •

Fever



Fatigue



Weight loss



Nonbacterial verrucous (Libman-Sacks) endocarditis •

Due to immune complex deposition onto heart valves



Hilar adenopathy



Raynaud’s phenomenon

FA 2013: 393.1 • FA 2012: 421.1 • FA 2011: 385.2 ME 3e: 106 • ME 4e: 106

Malar rash MUSC6_2-

1

SLE: Diagnostic Criteria •

Diagnostic criteria: •



4 of 11 characteristic signs/symptoms must be present

Characteristic signs/symptoms: •

Immunoglobulins •

Anti-double stranded DNA (anti-dsDNA) – very specific



Anti-Smith (anti-Sm) – very specific



Anti-nuclear antibody (ANA) – sensitive, NOT specific



Anti-phospholipid antibody •

Directed against phospholipids of •

Cells membranes



Clotting cascade proteins



Protein C and thrombin are affected, leading to hypercoagulable state, yet a prolonged PTT



Referred to as:





Lupus anticoagulant



Anti-cardiolipin antibody

Assess with a mixing study: absence of PTT correction is diagnostic

FA 2013: 393.1 • FA 2012: 421.1 • FA 2011: 385.2 ME 3e: 106 • ME 4e: 106

MUSC6_2-

2

SLE: Diagnostic Criteria •

Diagnostic criteria: •



4 of 11 characteristic signs/symptoms must be present

Characteristic signs/symptoms: •

Malar rash (butterfly rash)



Discoid rash



Antinuclear antibody



Mucositis (oropharyngeal ulcers)



Neurologic disorders (lupus cerebritis)



Serositis (pleuritis and pericarditis)



Hematologic disorders •

Thrombocytopenia



Leukopenia



Anemia



Arthritis (any joint)



Renal disorders (lupus nephritis) •



Discoid rash

Causes the majority of SLE patient morbidity

Photosensitivity

FA 2013: 393.1 • FA 2012: 421.1 • FA 2011: 385.2 ME 3e: 106 • ME 4e: 106

Copyright Richard Usatine, M.D. Used with permission.

MUSC6_2-

3

SLE: Lupus Nephritis •

Lupus nephritis: •

Causes most SLE patient morbidity



Usually a nephritic syndome •



May have components of nephrotic syndrome

Etiology: •

Immune complex deposition in the kidney •

Wire-loop glomerular lesions seen on histology

Copyright Richard Usatine, M.D. Used with permission

Discoid rash FA 2013: 393.1 • FA 2012: 421.1 • FA 2011: 385.2 ME 3e: 106 • ME 4e: 106

MUSC6_2-

4

SLE: Lab Findings •

False positive syphilis tests (RPR or VDRL assays) • Caused by the presence of anti-phospholipid antibodies

Copyright Richard Usatine, M.D. Used with permission.

Malar rash FA 2013: 393.1 • FA 2012: 421.1 • FA 2011: 385.2 ME 3e: 106 • ME 4e: 106

MUSC6_2-

5

SLE: Antibodies •

Immunoglobulins: • Anti-double stranded DNA (anti-dsDNA) – very specific • Anti-Smith (anti-Sm) – very specific • Anti-nuclear antibody (ANA) – sensitive, NOT specific • Anti-phospholipid antibody • Lupus anticoagulant • Anti-cardiolipin antibodies • Anti-histone antibody: • Associated with drug-induced lupus • SLE that develops due to specific drug exposure • Drugs: • Hydralazine • Procainamide

FA 2013: 393.1 • FA 2012: 421.1 • FA 2011: 385.2 ME 3e: 106 • ME 4e: 106

MUSC6_2-

6

Sarcoidosis •

Characteristics: •

Immune mediated, widespread, noncaseating (non-necrotic) granulomatous inflammation



Granuloma infiltration causes ongoing inflammation and organ dysfuction



Most common in African American females

A noncaseating granuloma, seen in the large, poorly circumscribed nodule in the center of the field

Kaplan Pathology 2010 Figure 3-6

FA 2013: 393.2 • FA 2012: 421.2 • FA 2011: 386.1 ME 3e: 177, 293 • ME 4e: 177, 293

MUSC6_3-

1

Sarcoidosis •

Signs/symptoms: •

Restrictive/interstitial lung disease



Bilateral hilar adenopathy



Erythema nodosum



Bell’s palsy



Hypercalcemia (due to elevated vitamin D)

Copyright Richard Usatine, M.D. Used with permission.

Erythema nodosum

FA 2013: 393.2 • FA 2012: 421.2 • FA 2011: 386.1 ME 3e: 177, 293 • ME 4e: 177, 293

MUSC6_3-

2

Sarcoidosis •

Labs: •

Elevated vitamin D levels



Hypergammaglobulinemia



↑ Angiotensin converting enzyme (ACE)



↓ Decreased sensitivity to skin tests (e.g. PPD)

Sarcoidosis nose flare Copyright Richard Usatine, M.D. Used with permission.

FA 2013: 393.2 • FA 2012: 421.2 • FA 2011: 386.1 ME 3e: 177, 293 • ME 4e: 177, 293

MUSC6_3-

3

Sarcoidosis •

Histology: •

Granulomas with giant cells



Schaumann bodies and asteroid bodies

A noncaseating granuloma, seen in the large, poorly circumscribed nodule in the center of the field

FA 2013: 393.2 • FA 2012: 421.2 • FA 2011: 386.1 ME 3e: 177, 293 • ME 4e: 177, 293

Kaplan Pathology 2010 Figure 3-6

MUSC6_3-

4

Sarcoidosis •

Histology: •

Granulomas with giant cells



Schaumann bodies and asteroid bodies



Treatment: •

Steroids

Kaplan Pathology 2010 Figure 3-6

Asteroid body

Asteroid bodies high mag cropped.jpg, commons.wikimedia.org. Used with permission.

Two asteroid bodies FA 2013: 393.2 • FA 2012: 421.2 • FA 2011: 386.1 ME 3e: 177, 293 • ME 4e: 177, 293

MUSC6_3-

5

Polymyalgia rheumatica •

Characteristics: • • •



A systemic inflammatory disorder No muscle inflammation Typically occurs in patients > 50 years old

Signs and symptoms: •

Pain and stiffness in the shoulders and hips • Feels like proximal muscle pain, muscle weakness is absent • Fever • Malaise • Weight loss



Labs: • •



Normal creatinine kinase (CK) levels ↑ Erythrocyte sedimentation rate (ESR)

Treatment: Prednisone

FA 2013: 393.3

• FA 2012: 421.3 • FA 2011: 386.2 ME 3e: n/a • ME 4e: n/a

MUSC6_4-

1

Myositis Disorders •

Characteristics: • Ongoing inflammation of the muscles



Labs: • ↑ Creatinine kinase levels

FA 2013: 394.2 • FA 2012: 422.2 • FA 2011: 386.3 ME 3e: 450 • ME 4e: 450

MUSC6_4-

2

Polymyositis •

Characteristics: •

Inflammation of multiple muscle groups



Progressive and symmetric



Proximal muscle groups affected the most (e.g. hips and shoulders)



Etiology: •



CD8+ T-cell injury to myofibers

Histology: •



Endomysial inflammation, within muscle fibers

Labs: •

↑ Creatinine kinase levels

Muscle biopsy on H&E showing endomysial inflammation Polymyositis HE.jpg, commons.wikimedia.org. Used with permission.

FA 2013: 394.2 • FA 2012: 422.2 • FA 2011: 386.3 ME 3e: 450 • ME 4e: 450

MUSC6_4-

3

Dermatomyositis •

Characteristics: •

Inflammation of multiple muscle groups



Proximal muscle groups affected the most (e.g. hips and shoulders)



Histology: •



Perivascular (perimysial) inflammation, within muscle fibers

Labs: •

↑ Creatinine kinase levels



↑ Aldolase levels

Perimysial inflammation Dermatomyositis – high mag.jpg, commons.wikimedia.org. Used with permission.

FA 2013: 394.2 • FA 2012: 422.2 • FA 2011: 386.3 ME 3e: 450 • ME 4e: 450

MUSC6_4-

4

Dermatomyositis: Signs and symptoms Signs/symptoms: •

Heliotrope rash (periorbital)



“Shawl and face” rash



Gottron’s papules develop on the dorsal fingers, over joints



“Mechanic’s hands” (i.e callused hands)

Other characteristics: •

↑ Risk of malignancy (e.g. colon and ovarian cancer)



Antibodies: •

ANA (sensitive yet non-specific)



Anti-Jo-1 (very specific)



Copyright Richard Usatine, M.D. Used with permission.



Copyright Richard Usatine, M.D. Used with permission.



Treatment: •

Steroids to reduce inflammation Heliotrope rash

FA 2013: 394.2 • FA 2012: 422.2 • FA 2011: 386.3 ME 3e: 450 • ME 4e: 450

MUSC6_4-

5

Neuromuscular junction diseases

Kaplan Pathology 2010 Figure 29.2

Neuromuscular Junction Physiology FA 2013: 394.3 • FA 2012: 422.3 • FA 2011: 386.4 ME 3e: 450 • ME 4e: 450

MUSC6_5-

1

Myasthenia gravis •

Etiology: •

Antibodies against the post-synaptic acetylcholine receptors of the NMJ Bind to and inactivates the receptor





Signs/symptoms: • •

Muscle weakness that worsens with prolonged use Typically affects the facial muscles •

Ptosis



Extraocular muscles



Double vision





Respiratory muscle involvement

Diagnostic tests: •

Electromyography: repetitive nerve stimulation testing •





Progressive decrease in action potential size of affected muscle groups

Edrophonium (an achetylcholinesterase inhibitor) improves symptoms

Other characteristics: •

Associated with thymoma

FA 2013: 394.3 • FA 2012: 422.3 • FA 2011: 386.4 ME 3e: 450 • ME 4e: 450

Kaplan Immunology-Microbiology 2010 Figure I-13-5

MUSC6_5-

2

Lambert-Eaton syndrome •

Etiology: •

Antibodies against the presynaptic calcium channels of the neuromuscular junction Antibody mediated attack





Decreased acetylcholine release with neuronal transmission

Signs/symptoms: •



Proximal muscle weakness that improves with repeated use

Other characteristics: •

Associated with malignancy, occurring as a paraneoplastic syndrome (e.g. small cell lung cancer)

FA 2013: 394.3 • FA 2012: 422.3 • FA 2011: 386.4 ME 3e: 450 • ME 4e: 450

Kaplan Pathology 2010 Figure 29.2

MUSC6_5-

3

Lambert-Eaton syndrome •

Diagnostic tests: • Electromyography: repetitive nerve stimulation testing • Progressive increase in action potential size of affected muscle groups

Antibody mediated attack

• Edrophonium does not improve symptoms

Kaplan Pathology 2010 Figure 29.2

FA 2013: 394.3 • FA 2012: 422.3 • FA 2011: 386.4 ME 3e: 450 • ME 4e: 450

MUSC6_5-

4

Scleroderma (progressive systemic sclerosis – PSS) •

Two types • Diffuse scleroderma •

Excessive fibrosis and collagen deposition throughout the body



Rapidly progressive



Sites of involvement: • Skin involvement (thick and leathery) • Visceral organ involvement • Lungs involvement (interstitial lung fibrosis) is usually the cause of death



Etiology: • Anti Scl-70 antibodies against topoisomerase 1

FA 2013: 395.1 • FA 2012: 423.1 • FA 2011: 387.1 ME 3e: 107, 264 • ME 4e: 107, 264

Perioral Scleroderma Involvement Copyright Richard Usatine, M.D. Used with permission.

MUSC6_6-

1

Scleroderma (progressive systemic sclerosis – PSS) •

Two types 1. Diffuse scleroderma: 2. CREST syndrome: • Sites of involvement: • • • • •

Calcinosis Raynaud’s phenomenon Esophageal dysmotility (associated with GERD) Sclerodactyly Telangiectasia

• Limited skin involvement • More benign course • Etiology: •

Telangiectasias fingers scleroderma

Copyright Richard Usatine, M.D. Used with permission.

Anti centromere antibodies

FA 2013: 395.1 • FA 2012: 423.1 • FA 2011: 387.1 ME 3e: 107, 264 • ME 4e: 107, 264

MUSC6_6-

2

Tumor Necrosis Factor Alpha (TNF-α) Inhibitor: •

General characteristics: • A class of drugs that inhibit the affects of TNF-α • TNF-α is an important inflammatory mediator

FA 2013: 406.2 • FA 2012: 432.1 • FA 2011: 393.1 ME 3e: 448 • ME 4e: 448

MUSC6_7-

1

Etanercept •

Mechanism: • Recombinant form of the human TNF receptor that binds TNF • Decreases the net effect of TNF-α



Clinical Use: • Rheumatoid arthritis • Psoriasis • Ankylosing spondylitis

FA 2013: 406.2 • FA 2012: 432.1 • FA 2011: 393.1 ME 3e: 448 • ME 4e: 448

MUSC6_7-

2

Infliximab •

Mechanism: • Anti-TNF antibody • Decreases the net effect of TNF-α



Clinical use: • Crohn’s disease • Rheumatoid arthritis • Ankylosing spondylitis



Adverse effects: • Predisposition to infections • Particularly latent tuberculosis reactivation • It’s important to assess for signs of TB prior to initiating Infliximab

FA 2013: 406.2 • FA 2012: 432.1 • FA 2011: 393.1 ME 3e: 448 • ME 4e: 448

MUSC6_7-

3

Adalimumab •

Mechanism: • Anti-TNF antibody • Decreases the net effect of TNF-α



Clinical use: • Rheumatoid arthritis • Psoriasis • Ankylosing spondylitis

FA 2013: 406.2 • FA 2012: 432.1 • FA 2011: 393.1 ME 3e: 448 • ME 4e: 448

MUSC6_7-

4

Musculoskeletal and Connective Tissue: Summary •

Anatomy, physiology, and disease of: • Skin • Muscles and ligaments • Peripheral nerves • Bones • Connective tissue

MUSC6_8-

1