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
MUSC1_1- 12
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
MUSC1_1- 17
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