MSI Flashcards
Macula Adherens
Desmosomes attached to keratin
Zonula Dherens
Cadherins homotypic
ACL/PCL
Named for their location on the tibia
- ACL is anterior drawer test. Normally prevents anteior displacement of the tibia on the femur
- PCL is posterior drawer prevents posterior movement of the tibia on the femur
Achondroplasia
- AD FGFR3 activating mutation that inhibits chondrocyte proliferation in the epiphysis leading to disorganized epiphysis
- Impaired endochondral ossification and shortening of long bones. Other bones are fine
- Usually associated with advanced paternal age
Osteoporosis
Normal labs and caused by an age related increase in clastic activity and a decreae in blastic activity
- IL-1 and 6 cause decrease clasts and estrogen increases protegrin
- One type is in post menopausla women and can respond to SERMs like raloxifen
- Type 2 is in everybody
- Treat with vitamin D, Ca, excercise, bisphosphonates, SERM
- Avoid corticosteroids
- Thinned trabechulae is histologic halmark
- Can also give pulsatile PTH that will increase the activity of blasts (RANK-L is expressed by blasts in response to PTH adn RANK is on clasts)
Osteopetrosis
- AR dysfucntion in Carbonic Anhydrase 2 which leads to an inability to generate acidic environment for clasts to degrade bone
- Results in an increase in ALP activity and a decrease in Ca
- Sclerotic thickened bone that is easy to break
- Can present as hearing and neural impingment
- Can be cured with a BM transplant that regenerates calsts
- Can also get a myelophtisic process that causes pancytopmenia and EMH
Osteomalacia and Rickets
Caused by a decrease in vitamin D that impairs Ca and P metabolism
- Low Ca and P with icnreased ALP and PTH
- There will be unmineralized osteoid (collagen)
- Rickets is short stature, bowing of legs and head, ribs that have beads
- Malacia is weak bendy bones that are prone to fracutre
- Deficent dietary or malabsorption
Pagets
- Cause is unknown, but there is an initial increae in blastic activity that degrades bone that is then followed by an increae in clastic activity that increases bone lay down
- Leads to a disorganized lamellar structure histologically and enlarging or changing bones grossly
- Increase in ALP with all other lab values normal. The priamry defect is with the clasts and does not involve Ca metabolism
- Increaed risk of osteosarcoma, especially in the older population
- Can also have high output heart failure because of AV malformations.
Osteotits Fibrosis Cystica
- Increase in PTH leads to subperiosteal resporption of bone that is then replaced by fibroblasts and collagen
- Can be seen secondary to primary PTH or renal disease
- Labs are variable, but 1 is increase in PTH and ALP and Ca with a decrease in phosphate
McCune Albright
- Hereditery increase in GPCR signalling that elads to overactivation of a numbr of hormone pathways, most often PTH
- Fibrosa cystica, unilateral cafe au lait spot and possible precocious puberty
- Shortened 4th and 5th digits is classic
Labs
- Osteoporosis all normal
- Osteopetrosis: Increase in ALP and decrease in Ca
- Pagets: Increase in ALP isolated
- Osteomalacia: increase in PTH and ALP decrease in Ca and P
- Osteotitis: Decrease in P increase in PTH, ALP and Ca
Giant Cell Tumor
Osteoclastic benign tumor most commonly located in the epiphysis
- Will have osteoclastic markers, CD68, will be of monocyte lineage
- Will have a soap bubble appearance on X Ray
- Multinucleated giant cells and spindle cells
Osteoma
-Will improve with NSAIDs
Osteochondroma
- Exophytic process from epiphyseal plate leads to chondrocyte cap
- Generally occurs in young men
- Pain is relieved by NSAIDs
Osteosarcoma
- Malignant tumor of the metaphysis
- Classically appears as Codmans triangle with a sunburst pattern
- Is osteoblastic in origin
- Asslocated with Rb, Pagets, Radiation
Ewings Sarcoma
- Small blue cell neuroendocrine tumor in the diaphysis of long bones, small blue cells
- translocation of 11;22
- Onion skin appearance that can take up the entire bone laterally
- Highly malignant, but generally responsive to radiation
Chondrosarcoma
- Tumor of cartilage cells that leads to a radiolucent image in the diaphysis
- Generally occurs in older males
- Meddullary cavity
Avascular Necrosis
-Necrosis of scaphoid following fracture
-Pathologic fracture of femur head without osteoporosis
Associated with alcohol and steroids
-Sickle cell is aslo a common cause (dactylitis)
OA
Chronic wear and tear inflammation that leads to breakdown of collagen covering of bone, generally in large weight bearing jounts. Cartillage is normally type 2 collagen and PG
- DIP is often involved (not in RA, but MCP is spared)
- Osteophytes
- Treat with NSAIDS adn intrajoint steroids
RA
- Systemic type 3 hypersensitivity immune response
- CCP is more specific, but RA is also likely
- IgM to Fc IgG is RA
- Deposition in joints and inflammation elads to pannus formation and deviation
- Fibrnioid necrosis below teh skin is a common complaint (Rheumatoid nodules)
- Systemic illness that can cause pleuritis, pericarditis, amyloidosis (AA)
- Treat with DMARDs (MTX, Steroids, Sulfasalazine)
- HLADR4
- Invovment of PIP and MCP with sparing of DIP
Juvenile RA
- Generally presents as a mores systemic illness and can present with fevers
- OFten get associated uveitis
- Systemic is predominant feature
Sjogrenna
- Lymphocytic infiltrate into exocrine glands
- Salivary leads to xerostomia and lacrimal to xeroopthalmia
- Leads to infections and cavities
- Also causes arthritis
- RA is commonly positive
- Ribonucleptide ssRA and ssLA are more specific. Can cross placenta and cause neonatal heart block
- Tx: steroids and symptoms
- Risk of marginal zone lymphoma from lyphoid aggregates
- Can also treat with muscarinic agonist to increase eyeflow
- Can also see cryoglobulins as you can in RA
- Associated with HLADR/Q
Alkaptonuria
- Defect in homogentisic oxidase that metabolizes tyrosine
- Leads to arthritis, black urine, and heart disease
Gout
- MSU preco[itates in joints that are then phagocytosed by nneutrohils leading to inflammatin
- Most commonly big toe
- Due to increase in purine breakdown
- HGPRT in lesch nyhan
- Inhibitors of xanthine oxidase are treatment (fuboxistat and allopurinoll
- Causes can be destruction of leukemia cells and decreased excretion
- Decreased excretion from competition for organic anion transporter (lactate and alcohol)
- Thiazides also cause gout
- Tophus formation possible
Pseudogout
Larger joints with calcium pyrophosphate crystals
- Basophilic on stain (like psammoma bodies)
- Usually knees
- Hypercalcemia is a risk factor
Osteonecrosis
Infarction of marrow space due to alcoholism, sickle cell, and high dose steroids
Seronegative Spondyloarthropathies
- are all RF negative
- Associated with HLA B27 (MHC1)
- IBD
Psoriatic Arthritis
- Occurs in fewer than 1/3 of patients
- Pencil in cup deformity always involving DIP and has pencil in cup appearance
Ankylosing spondylitis
Pannus and fusion of the sacro illiac joints
- Leads to restrictive lung diseas due to kyphosis
- Uveitis can cause blindness
- Aoritis can cause regurg
Reactive arthritis
Urethritis, Conjunctivitis, and arhtritis that is sometimes accompanied by a rash
Osteomyleitis
-Hematogenous spread
-A Aureus
-Salmonella
-Psuedomonas
TB
Ankylosis Spndylitis
- Fusion of sacroiliac joints
- Aortitis can cause death
- Uveitis can cause blindness
Infectous Arthritis
Gonorrhea
-S Aureus, Lyme, pastuerulla
SLE
-Type 3 hypersensitvity to post apoptotic nuclear fragments
-Defect in early compliment leads to inabilty to clear via C3b
-Deposition in tissue throughout the body
-Most common presenting symtoms are arthritis and macular facial rash
-Basal cell degeneration and dermal atrophy
-Also discid rash
-Pericarditis and pleuritis are possible
-Liebman sacks aeseptic endocarditis
-Antiphospholipids give false positive VDRL and also lead to hypercoagulable state that commonly causes abortions
-Mucocytis
-Neurologic symptoms
-Renal disease is the most common cause of death
Membranous leads to nephrotic syndrome early in disease course
-Diffuse proliferative gives rise to nephritis syndrome late in course and is common cause of death
-ANA and Anti-smith/anti DSDNA
-Hilar adenopathy and raynauds are common
-Hemolytic anemia
Drug induced lupus
- Antihistone antibodies
- Commonly seen with hydralazline and procaimamide
Sarcoidosis
- Noncasseating granulomas
- Most common is restrictive lunf disease with bilateral hilar adenopathy
- Can effect any organ
- Commonly effects GI and Eyes, may lead to blindness
- Eryhthema nodosum is common skin complaint (subq fat, commonly on shins)
- Increased ACE expression in lung tissue
- Also elevated vitamin D levels leads to incrase in Ca levels
- Bells Palsy
- Ca depsoits are shumman bodies and asteroid bodies are classic
Polymyalgia Rheumatica
- Inflammation in joints and bones that involves multiple
- Older patients with massively elevated ESR, commonly seen with temporal arteritis
- Normal CK
- Treat with steroids
Fibromyalgia
female in middle age that has musculoskeletal compaints
-Treat with SSRI
Polymyositis
- CD8 driven endomysial inflammation
- A component of mixed connective tissue disease
- Elevated CK and Anti-Jo-1 antibody
- Treat with steroids
- Morning stiffness that most commonly effects the shoulders
- On differential for RA
Dermatomyositis
- CD4 driven TH2 inflammation of epimysial muscle and face/hands
- Heliotrope rash that involves area around eyes and sometimes looks like lupus rash
- Mechanics hands
- Commonly associated with a visceral malignancy and may be a paraneoplastic syndome
- Anti-Jo-1 antibodies to tRNA synthase
- Treat with steroids
Inclusion body byositis
Similiar presentation with muscle pain and an elvetated CK
- Incluision bodies will be seen and does not respond to steroids
- Commonly seen in elderly
MG
Anitbody to AchR leads to muscle weakness
- Most commonly in small muscles and occurs at the end of the day and is worse with movement
- Thymoma is almost always found
- Treat with neostygmine and pyridostigmine
Lambert Eaton
- Ab to Ca Channels that are V gated
- Leads to muscle weakness in proximal msucles commonly that gets better with exercise
- Small Cell lung paraneoplastic
Myositis Ossificans
- Fibroblasts turn into osteoblasts
- Most commonly seen around sites of trauma, but can occur genetically
Scleroderma
- Vascular injury that leads to TH2 mediated activation of fibroblasts that leads to collagen and PG depostion in tissues
- Most noticible in the skin that leads to thickened skin that is not wrinkled
- Can occur in any organ
- Lungs is the most common cause of death leading to a restrictive disease picture
- Heart can also be invlolved
- Kidney can also be involved, interlobular artery, change is myxoid
- Can be diffuse that commonly has visceral involvment, characterized by anti scl-70 antibody to topoisomerase
- CREST is characterized by anti centromere antibody
- Calcinosis, Esophageal dysmotility, Raynauds, sclerodactyly, tel;angectasia. Minimal sclerosis of internal organs, therefore more benign presentation
Mixed connective tissue
- Has facets of SLE, Scelroderma, and Polymyositis
- U1 riboneucleotide positive
Parakaratosis
Epidermal cells retain nuclei into stratum granulosum layer
-Seen along with acanthosis in psoriasis
Albinism
- Can be due to decrease in melanocyte number (s-100)
- Or decrease melanin prouction from tyrosine
Vitiligo
Autoimmune destruciton of melanocytes in a particular pattern, seen in
Melasma
-Change in color due to elevated estrogens (OCP) or pregnancy
Psoriasis
Increase gworht of epidermis and cells retain theri nuclei
- Acanthosis and parakeratosis
- If scraped, ther ewill be pinpoint hemorrhages at the point of dermal papilae entry
- Salmon coloerd plaques
- Can treat with UVA sunlight and soralen to destory cells
- Nuclei still present in stratum corenum
- Increase in spinosum and decrease in granularum, more immature cells in spinosum
Seborheic Keratosis
- Lipid filled, stuck on lesions that are benign
- Can occur all at once in leser trelaut sign which signals visceral malignancy like pancreatic cancer
- Keratin cyst with keratin horns
Pemphigus Vulgaris
- IgG antibodies to desmoglein 3 which leads to acanthlolysis and classic reticular pattern
- Will break easily and can be deadly, treat like burns
- Will involve mucous membranes
- Macula Adherens (Desmosomes) intercellular attachments to keratin
Bullous Pemphigoud
- Ab to hemidesmososes at D/E junction leads to blisters that don’t rupture easily and not acanthlysis
- Does not involve mucosa and is less severe
Dermatitis Herpetiformis
- IgA antibodies to gliadin that lead to accumulation at derrmal papipllae
- Pruritic vesicualr lesions on extensor surfaces
- Celiac is HLA DR2/8
Eryhtema Multiforme
- Many causes including indcetion (HSV adn mycoplasma) drugs (beta lactams and sulfa) and cancer
- Leads to a irregular targetoid lesion and epithelial disruption
- There is no consistent morpholgy (Multiforme)
- Does not involve mucous membrans and is a precursosr to stevens johnsons
Stevens Johnsons
- Continution of EM, usually due to drugs (Sulfa)
- Widespread CD8 mediated necrosis and destruction at D/E junction leading to massiv sheding of skin
- Involves mucous membranes
- If greater than 30% of body involved then is TEN
Acanthosis Nigricans
- IGF mediated increase in epithelial proloferation and also collagen deposition leads to a velvety thick skin
- Usually bilateral and commonly located at armpits
- Sign of inuslin resistance or visceral malignancy
Actinic Keratosis
- Crusty scaly plaque that is a precursor to SCC
- Associated with UVB exposure
- UVA is more energy and causes burns
- UVB is lower energy and causes thymidine dimers
Eryhtema Nodosum
- Small nodules of subq necrosis of fat, commonly presenting in skin
- Associated with all kinds of granulomatous reactions
- TB, Sarcoid, Fungal
Lichen Planus
- Purple Pruritic papules,polygonal commonly presenting onshings, but can present anywehre
- Highly associated with Hep C infection
- Sawtooth at DE junction
- Lymphocytic infiltrate
- Commonly invovles oral mucosa
- Also see dystrophic naiils
Pitarysis Rosea
- Herald patch that is often misdiagnosed as RIngworm
- Followed later by christmas tree distribution extensive rash
- Do not treat and goes away on its own
- Commonly occurs following a URI
Sunburn
Burns and tanning are commonly associated with UVA light and UVB light is thymidine dimers
-Can lead to infections and impetigo
Impetigo
Infection of the epidermis, msot commonly by S Aureus and S Pyogenes
-S Aurues may cause bullae
Cellulitis
Infection of the dermis
-Pyogenes and aureus
Necrotizing fascitis
- S Pyogenes
- Clostridium perfringens - gas gangrene
Scalded skin synddomre
S Aureus exotoxin to desomsomes leads to acanthllyssis and skin shedding
- Different from TEN because doesn’t involve the DE junction just the
- Involves the stratum granulosum
Hairy Oral Leukoplakia
Associated with EBV occurs on the lateral tongue in immunocompromised individuals
Basal Cell Carcinoma
- Upper lip
- Pearly white plaques with ulcerations and rolled edges
- Histologically will show nests of cells with pallisading nuclei
- Locally aggressive but rarely metastasize
- 5-FU is a common topical treatment
SCC
- Kertin pearls, associated with UVB expsore
- Commonly forms out of actinic keratosis
- Scaly red, gross appearing
- Can be keratoacanthoma that has an ulcerated keratin filled pit
- Local invasion and may get to nodes, but mets are rare
- Can also occur at sites of chronic inflammation such as draining sinuses
- Increased risk with arsenic exposure and immunosupresion
Melanoma
- S-100 neural crest cells
- ABCDE
- BRAF kinase activtin mutaiton
- Spread is a function of depth
- Treat with vemerafanib
AA pathway
- AA goes to lipoxygenase that leads to leukotrienes
- LTB4 is NO tactic
- LTBC-E are vasodilation, leakage and bronchoconstrictin
- COX pathway
- 1: TXA2 and PGE, 2: PGI and Pain
- E2 important for renal flow, gut flow and uterine contraction
Glucocoriticouds
Lipocortin inhibits clevage of AA
-Also causes hypocalcemia and death to blasts and increase in clast activity leading to osteoporosis. Some effect is blurred by PTH and hypocalcemia (decrease absorption in gut)
Aspirin
- Irreversible acetylation of COX
- Low dose is antiplatelt med is anitpain and fever, and high dose is antiinflammatory
- Reyes
NSAIDs
Reversible Cox inhibitors
- Ulcers
- Intersitial Nephritis
Celecoxib
Specific for reversible cox 2
-Has minimal GI effect but also dose not decreae platelts
Acetomenaphin
Does not effect GI and effects cox in CNS
- Does not cause Reye’s syndrome
- Causes toxic oxygen radical mediated necorsis of hepatocytes in response to overdose.
- N acetlycystein will regenerate glutathione to get rid of it
- NAPQI matabolite
BisP
- Pyrophosphate analog that binds to hydroxyappetite and decrease ability to resororb
- Pagets, osteoporosis, hyperclacemia
- Can cause corrosive esophagitits and osteonecrosis of the jaw
Caliptriol
Vitamin D analog that can be used for psoriasis
Allopurinol, Febuxostat
Inhibits Xanthine oxidase to decrease production of uric acid
-Can be used in gout and tumor lysis syndrome
-Will increase toxic concentration of 6MP
-Can also decrease rate of gout excretion
-
Probenacid
- Prevents Uric acid reabsoprtion in PCT
- Also prevents peniclin secretinon in PCT
Colchicine
- Stabalizes MT and prevents degranulation and chemotaxis of neutrophils
- Causes GI upset
Etanercept
-Decoy IgG receptor for TNF alpha
Adalimnuab, infliximab
TNF Ab
-RA, ankylosing, psoriasis, crohns
Uztezumimab
Ab to IL-12 and 23 that decreases differntiation into TH1 cells
-Used to treat psoriasis
