MSI Path Flashcards
Stratum Corneum
- Outermost layer comprised mostly of keratin that is attached to each other at desmosomal jct
- Provides the majority of the barrier function of skin
Stratum Lucidum
-Extra layer that is only found on the palms and soles
Stratum Granulosum
- Keratinocytes lose their nuclei in this level
- Secrete lipids
Startum Spinosum
- Desmosomal attachments cause spinous appearance as cells dehydrate
- Still contain nucleus
- Langerhans cells are here, polar lipids
Stratum Basale
- Basal regenerative layer
- Connected to BM via basement membrane
- Contain melanocytes and also merkel cells
Sebacous Gland
- Holocrine secretion of waterproofing fluid
- Most concentrated in hair areas and face
- Can cause acne
Eccrine Gland
- Secrete Na/Cl into a duct that is then reabsorbed
- Found throughout the body and function to cool
- Sympathetic cholinergic inervation (postganglionic)
Apocrine Glands
- Release a sugar, oil, and watery mixture
- Blebs off membrane
- Located in axilla and genetalia
- Are responsible for smell
Tight Junctions
-Occludins and claudins form a water tight barrier
Zonula Adherens
- Connects the cytoskeleton of neighboring cells
- Functions through cadherins (Ca dependent binding proteins)
- Loss of cadherins can promote metastasis
Macula Adherens (desmosomes)
- Function as spot welds and provide sheer force stabilization
- Desmogleins/solins in homotypic interactions
- Ab to desmogleins leads to pemphigous vulgaris
- Also form connections between myocytes and have been implicated in some congenital arrythmias
Hemidesmosome
- Attach keratin and intracellular to Collagen, laminin etc
- Integrins bind to lamanin: Cell signaling
- Ab Attack leads to bullous pemphigoid
Epidermolysis Bulosa
-Mutation in keratin genes that are important for hemidesmosome function leads to “Skin falling off”
Knee Anatomy
- Names refer to sites of tibial attachment
- Fibula is on the lateral leg, so use as landmark
- ACL is anterior lateral tibia and PCL is posterior medial tibia
Pudendal Nerve block
- Lateral to Ischial spine
- S2-4 somatic sensory loss of genital and anal region
- Childbirth
Supraspinatus
-15 degrees of abduction
Infraspinatus
Lateral rotation and abduction
-Commonly torn in pitchers
Teres Minor
Lateral rotation
-Adduction
Subscapularis
Medial rotation
adduction
Rotator Cuff Innervation
C5-6
-Erb Duschene palsy leads to arm that lies in medial rotation and at side due to paralysis of rotator cuff
Scaphoid
Makes connection with radius and is the most commonly fractured wrist bone
-Needs attention becase of risk of avascular necrosis
Lunate
-Dislocation leads to acute carpal tunnel syndrome and paralysis of distal median nerve.
Hamate
- Ulnar Nerve goes under
- Fracture leads to loss of sensation to medial palmar hand and medial flexors
Axillary Nerve
- Damage from surgical head fracture (runs with circumflex humeral)
- Also can be lesioned by dislocation of humerus
- Leads to paralysis of deltoid and loss of sensation in that area
Radial Nerve
- Runs in the radial groove with the deep brachial artery
- Fracture of the midshaft of the humerus
- Dislocation of the radius
- Saturday night palsy with compression in the axilla
- Controls Triceps, brachioradialis, supinator, wrist extensors
- Also sensory to the back of the hand
Median Nerve
- Supracondylar fracture
- Compression through pronator teres
- Compression in carpal tunnel
- Controls muscles flexion of muscles on the lateral aspect of the hand including the thumb
- Controls sensation on the palmar aspect of the lateral hand
- Also runs in interosseus nerve
Recurrent Median Nerve
- Branch post carpal tunnel that controls thumb movements
- Damage by superficial laceration
Ulnar Nerve
- Muscles on the medial hand (C8, T1) and sensation on the palmar and dorsal medial hand
- Damage with hook of hamate
- Fracture of medial epicondyle
- Also will get radial deviation on wrist flexion
Erbs Palsy
Damage to upper trunk C5-6
- Childbirth or from rapid pushing of head to other side
- Causes waiters tip (damage to rotator cuff and some biceps)
Klumpkes Palsy
- Damage to lower trunk
- From reaching or outstrectched arm
- Total claw hand with damage to all intrinsic hand muscles
Obturator
-Controls muscles of the medial thigh and causes adduction L2-L4
Femoral
-L2-4 controls thigh flexion and leg extension (quads)
Common Peroneal
Commonly injured because of superficial location on the lateral aspect of the leg (Near the fibula)
- Causes an inabilty to dorsiflex and evert the foot leading to foot slap and foot drop
- Loss of sensation from dorsum of foot
Tibial Nerve
- Damaged with knee trauma
- Causes loss of plantar flexion and inversion
- Loss of sensation over sole of foot
Superior Gluteal
- Controls the gluteus minimus and medius which raise the hip
- Positive trendelenberg sign, contralateral hip drops when standing on one leg
Inferior Gluteal
Gluteus maxiums
-Can’t jump, run, raise from a chair
Endochondral Ossification
- Occurs in appendicular and axial skeleton
- Cartilagenous frame laid by chondrocytes, replaced by woven bone by clasts and blasts and finally remodeled into lamellar bone
- Woven bone seen in fractures and Pagets disease
Membranous Ossification
- Occurs in facial bones and calvarium
- No cartillage structure, blasts and clasts lay down woven bone directly
Osteoblasts
- Mesenchymal origin
- Build bone with collagen and ossification
- Secrete ALKP to keep alkaline environment for ossification
Osteoclasts
- Monocyte lineage, contain RANK-R that respond to RANK-L on blasts
- Secrete acids and collagenases
- TARP is a marker
PTH
- Increases RANKL expression on blasts and increase clast activity to resorb bone.
- When Ca is present low level PTH will maintain bone remodelling, but when calcium is deficient elevted PTH leads to Ca extraction
Estrogen
- Causes apoptosis of clasts and maintains blasts
- Menopause leads to reversal of effect and causes osteoporosis
Achondroplasia
- AD activating mutation in FGFR3 leading to impaired chondrocyte proliferation. Associated with advanced paternal age
- Causes impaired endochondral ossification because of improper cartilalge skeleton
- Epiphysis will be disorganized
- Shortened limbs and long bones with normal intramembraneous ossification. Normal Head, chest, wrist, etc
- Normal fertility and other functions.
Osteoporosis
- Loss of trabechular bone with porous appearnace on X Ray
- Does not have unmineralized osteoid like osteomalacia because the fundamental problem is an aging/estrogen induced decrease in blast function and decrease in clast function
- All labs will be normal
- Estrogen normally helps to activate blasts and inhibit clasts (IL-1,6, osteoprotegrin) Loss at menopause shifts balance
- Senile occurs in men and women equally and comes from falling off after peak bone density is reached at the age of 30 or so.
- Can be aided with exercise, proper diet including vitamin D, and vitamin D Receptor polymorphisms
- Tx: Raloxifen/HRT, Bisphosphenates which cause apoptosis in clasts, vitamin D, Ca, Diet
- Symptoms include femoral, hip fracuters and vertebral fractures.
- Pulsatile PTH can keep blasts functiononing in the face of adequate calcium
- Gluococorticoids are contraindicated
Glucocorticoids
-Contraindicated in osteoporosis
Osteopetrosis
- Impaired osteoclast function most commonly due to mutation in carbonic anhydrase 2. Leads to inability to acidify the local environment and resorb bone
- Increased deposition leads to thickened hypermineralized bone that is prone to fracture
- Extra bone can also compress nerves leading to carpal tunnel or deafness
- Labs will show a decrease in Ca and increase in ALP
- Bone marrow would be currative because clasts are from monocyte lineage
RTA
-RTA can be seen with osteopetrosis because of CA mutation leading to impaired acid secreition and bicarb resporption in PCT (type 1)
Osteopetrosis complications
-Myelpphthesis can cause pancytopenia and EMH
Osteomalacia and Rickets
- Low vitamin D levels leads to a reduction in Ca and P in the blood leading to decreased bone mineralization
- Will stimulate PTH to increase blast activity leading to increase in ALP
- Prolieration and hypeactivity of blasts leads to the classic unmineralized osteoid proliferation
- Rickets, kids: Osteoid commonly seen at ribs (rossettes) and forehead. Bowing legs
Paget’s Disease
- Etiology unnown, possibly viral. Focal (Not sytemic) increase in clast activity that is opposed by blast activity leads to increase deposition of woven bone and weak mosaic pattern.
- Clasts will burn out and blasts will continue leading to increasing deposition. Commonly in skull with increased head size or wrist for carpal tunel
- Labs: Everything is normal except for an isolated increase ALP because of increase osteoid and mineralization.
- Can lead to osteosarcoma of the adult
- Can also create AV shunts that leads to high output cardiac failure.
Pituitary Dwarfism
- Lack of response to GH
- WIll be shortened in all bones
Polyostotic FIbrosa Cystica
- Increase in PTH signalling leads to increased bone resportion
- WIll be replaced by fibroblasts and will appear as radiolucent portions in bone that is surrounded by normal or sclerotic bone
- Can also be seen in mccune albright
- Tx: Bisphosphenates can impede resportion
McCune Albright
- Defect in regulation of Gs signalling leading to increase cAMP and overactivity
- Post zygotic mutation, so patients demonstrate mosacism
- Causes Shortened digits and PTH hyperresponsiveness
- Short stature, Polyositis FIbrosa Cystica
- Also causes precocious puberty and cafe-au-lait spots
Osteomyelitis
- Most common in kids and shows up with fever and systemic symptoms and a unifocal inflammatory joint arthtitis
- Lytic focus with surrounding sclerosis
- Most often in metaphysis
- S AUreus most common
- Pseudomonas in Diabetics and drug users
- Salmonella in sickle cell
- Pasturella in bites
- Nisseria
- TB
Avascular Necrosis
- Loss of blood supply leads to cell death and risk of fracture
- GLucocorticoids can cause, especially in large joints
- Sickle cell get vaso-occlusive crisis in hands (dactylitis)
- Scaphoid fracture that is not properly treted (proximal protion has weak “retrograde” flow from radial artery
- Can also occur in alcholics
Femoral Head Fracture
-Avascular necrosis can occur because of disruption of supply from medial circumflex artery
Giant Cell Tumor
- Tumor of spindle cell, pleiomorphic giant cells that arises in the epiphysis of long bones (only tumor in epiphysis)
- Stains CD56+, monocyte lineage
- Locally aggressiv tumor that has soap bubble appearance on X-Ray, but is not malignant
Osteochondroma
- Tumor of bone cells that grow out from growth plate of metaphysis
- Surrounded by chondrocyte covering that can rarely become malignant
- Very common and seen in males under 25
Osteoid Osteoma
- Osteoblastic tumor leading to dpeosition of osteoid that is not mineralized, appears radiolucent on x-ray
- Seen in the cortex of long bones
- Often surrounded by an area of sclerosis
- Pain improves with aspirin
Osteoma
- Extra bone growht, commonly in the head/sinuses
- May be related to trauma
- Benign but can cause local mass effect
Osteosarcoma
- Tumor of the metaphysis and of osteoblasts. Occurs near the cortex
- Creates Codman’s angle by pushing the periosteum out of the surface
- X ray may show “Sunburst sign”
- Associated with Rb mutations
- In adults can be secondary to paget’s disease and also radiation
- Pain does not respond to ASA
- Resection is definitive cure.
Ewings Sarcoma
- Tumor of primitive neuroectoderm cells
- Occurs most commonly in young males
- Occur in the diaphysis of long bones
- May cause onion skinning and proliferation outward
- Caused by transolatcion (11:22)
- Aggressive and highly metastatic, but responds well to chemo
Chondrosarcoma
- Cartillage tumors arise in the medulla and appear as radiolucent tumors
- Medulla of diaphysis in long bones (fingers commonly)
- Seen most commonly in middle aged men
- Glistening collagen producing tumor
Bone Metastasis
- By far more common
- Most often are lytic metastasis
- Are osteoblastic sclerotic metastasis in prostate cancer
Alkaptonuria
- Defect in tyrosine and phenylalanine metabolism leads to accumulation of homogentisic acid
- Causes joint pain, dark urine, heart disease
- Urine will be black
Osteoarthritis
- Wear and tear destruciton of cartillage (Col 2 and GAGs/HA from synovium).
- Age is the biggest predisposing factor, also trauma and obesity
- Joint space narrowing, eburnation, osteophytes of subcondral bone.
- Minimal inflammatory debris in joint
- Involves the PIP and DIP (Heuberdens nodes) and not the MCP
- Also commonly involves large weight bearing joints
- Tx is NSAIDs
- Improves with rest and gets worse with use
Rheumatoid Arthritis
- Systemic autoimmune disese most characterizd by joint inflammation
- RF is IgM to Fc protion of IgG and can correlate with disease severity but not dx. Not all RA have, and many other non RA disease do
- Use Citrullinated peptide to diagnose
- Highly associated with HLA-DR4 (MHC2)
- Inflammation of synovium and increase in lymphocytes and macrophages in joints
- Eventually panes of granulation tissue and fibroblasts form
- Pannes cause akylosis of joints and myofibroblast traction and deviation
- Involves the PIP and MP but not the DIP joints, also stiff in morning gets better with use. Can easily distinguish RA from OA
- Systemic illness with other manifestations
- Can cause pulmonary fibrosis and effusions
- Can cause secondary amyloidosis from (SAA-AA formation (nephrotic syndrome))
- Anemia of chronic disease
- Fatigue, LAD
- Subcutaneous nodes, vasculitis (Fibrnioid necrosis)
- Bakers cyst
- Tx: MTX, Infliximab (don’t give if pt has TB)
Juvenile RA
- RA symptoms in childhood
- May cause uveitis and blindness as feared complications
Sjogrenns
- Caused by autoimmune lympocytic infiltration of exocrine glands. Most commonly the salivary and lacrimal
- Positive anitbody test to riboneucleoptide proteins (SS-A and B, Ro and La) also very commonly RA positive
- Symptoms are Xerostomia which predisposes to carries, xerophthalmia which predisposes to infection, and arthritis.
- Associated with HLA-DR/DQ (MHC2 like RA)
- Lymphoctic infiltration and germinal center formation predispose to MALT lymphoma in exocrine glands (Hashimotos and H pylori)
- Ab can cross placenta and cause neonatal heart block
- Parotid Gland Enlargment
- Also patients often have cryoglobulins
Gout
- Cause by deposition of monosodium urate crystals in joints.
- MSU crystals cause neutrophilic activiation and episodes of acute gout
- MSU deposits because of elevated uric acid levels caused by increased production or decreased excretion
- Production from diet (AMP, GMP in meats) also from leukemia and increased cell turnover
- More commonly from impaired excretion. Excreted via anion transporter in kidney.
- Competes with lactate (Von GIerke disease), Alchohol
- Thiazides and loop diuretics also increase risk of gout attack
- Produced from purine pathway via xanthine oxidase
- Tx: Colchicine, NSAIDS
- Chronic can use allopurinol inhibits xanthine oxidase
- Probenacid can increase secretion, uricase analogs can break it down
Chronic Gout
- Tophi deposit (Ear, elbow, etc)
- Can cause uric acid stone and urate nephropahty leading to acute renal failure
Lesch Nyhan
XR defect in HGPRT meaning less Purine salvage and more purine loss leading to increased uric acid and gout
Tumor Lysis Syndrome
- Seen when treating leukemias etc
- Spill eveything that was inside into the ECF
- Increase uric acid and lactic acidosis may cause gout
- Hyperkalemia, hyperphosphatemia, hypocalcemia
Pseudogout
- Deposition of calcium pyrophophate crystals into large joints
- Most commonly effects the knee (assymetrical)
- Common in elderly
- Pyrophosphate comes from ATP breakdown and Ca from elevated Ca levels (hyper PTH, cancer, etc)
- Positively birefringent rhomboid crystals
- Tx: NSAIDs
Von Gierke Disease
- Dysfunctional glucose 6 phosphatase in muslce prevents glycogen usage leading to lactic acidosis and exercise intolerance in kids
- Lactate competes with uric acid for excretion and can preciptate and attack of acute gout
Infectous Arthritis
- Purulent inflammation of joints, assymetric
- S Aureus is most commont
- Classically is Gonorrhea following STD
- Can also be lyme disease (molecular mimicry)
- Synovitis, Tenosynovitis, Dermatitis
Seronegative Spondyloarthropathies
- RF negative but HLA-B27 positive
- MHC class I and seen more commonly in men
Ulcertive Colitis (maybe crohns)
-Ankylosing spondyloarthtis and other seronegative arthropathies are commonly seen in inflammatory bowel disease
Psoriatic Arthritis
- Occurs in 1/3 of patients with psoriasis
- DIP is always involved creaing a sausage finger
- Pencil in cup deformitiy is also often seen
- Can involve nearly any joint in the body and commonly involves nail changes
Ankylosing Spondylitis
- Fusion of sacroiliac joints and lumbar spine
- Seen as pain, stiffness, and inflexability in young adult men
- Fusion of joints
- Can be associated with uveitis
- Aortitis can also be seen that will lead to aortic anyeurism and aortic regurgitation
- Can also show a restrictive lung disease pattern because of mechanical obstruction of ventilation
Reactive Arthritis
- Arthritis, conjunctivitis, and urethritis following GI or STD infection
- Can also involve a rash on the palms and soles
- Chronically may lead to ossification of the achilies tendon
Dermatomyositis
- CD4 mediated inflammation and atrophy of perimyseal (apical fascicel)
- Associated with dermato findings: Heliotrope rash of eyelids, malar rash similiar to lupus, rash on knuckles and knees
- ANA positive, anti-Jo-1 positive (tRNA synthetase)
- CK will be increased
- Often a paraneoplastic syndrome so always look for a GI malignancy when diagnosed
- Differentiate from lupus because there is overlap in many lab and physical findings
Polymyositis
- CD8 mediated inflamation and necrosis of endomysial myocytes
- Proximal muscle weakness with similiar presentation to dermatomyositis other than the skin findings
- CK will be elevated, ANA and anti Jo-1.
- Proximal leads to inabilty to comb hair and rise from chair
Inclusion body myositis
- Identical presentation to dermato and polymyositis but there will be no response to steroid treatment
- T Cell mediated, increases with age,
- Progressive muscle weakness with dysphagia and foot drop
- Aspiration pneumonia is a common cause of death
- May be related to amyloid deposits
Myasthenia Gravis
- Most common NMJ disorder
- Ab to AchR leads to muscle weakness that gets worse with use
- Patient often complains of diplopia and ptosis that are worse at the end of the day
- Associated with thymoma and often thymoma removal will lead to resolution
- Dx with edrophonium and treatment with neostigmine
Lambert Eaton
- Ab to presynaptic Ca channels
- Proximal limb weakness that gets better with use
- Paraneoplatic syndrome of small cell carcinoma of lung
- Rare
Myositis ossificans
- Trauma can cause fibroblasts in muscle to differentiate into bone
- May present as odd mass on X-Ray or post injury.
Atopic Dermatitis
- IgE mediated type 1 hypersentivity commonly seen with eczema and asthma
- Most commonly involves flexor surfaces and face
Contact Dermatitis
- Contact to specfic iritant
- Type 4 hypersensitivity
- Poison Ivy
Acne Vulgaris
- Keratin plugs cause backup of sebacous gland leading to accumulation of sebum (holocrine secretions)
- P acnes can breakdown lipid and cause inflammation
- Inflammation leads to pimples
- Tx: DEcrease P Acnes or decrease keratin (vitamin A)
Psoriasis
-Hyperproliferation of keratinocytes is fundamental problem
-Increased number of basal cell layer
-Nucleated cells in the stratum corneum
-Dermal papillae will come close to epidermis and pinpoint bleeding can occur
-Clinically will appear as salmon colored scaly rashes most commonly at the knee/extensor surfaces and the scalp
-Associated with HLAC (Type 1)
-Can also have reactive arthritis
-Tx: steroids,
UVA and psoralen can also cause death to keratinocytes and prevent their proliferation
Lichen Planus
- Polygonal pink, scaly rashes
- Sawtooth infiltrate at dermal epidermal junction
- Associated with hep C
- Commonly see dystrophic nails
Pemphigus Vulgaris
- Ab to desmoglein of desmosomes, appears as a reticular pattern on immunoflourescence
- Causes acantholysis
- Blisters are weak because lack basal layer and are easily ruptured
- Rupture can lead to significant skin barrier loss and fluid loss
- Involvment of oral mucousa and easy breakage are how to clinically differentiate from bullous pemphigoid
Bullous Pemphigoid
- Ab to basement membrane (Collagen 4 or lamanin)
- Lead to linear type 2 hypersensitivity
- Blisters will be thicker and will be harder to rupture
- Clinically is more mild than pemphigous vulgaris
- Does not involve oral mucousa
Dermatitis Herpetiformis
-Deposition of IgA Ab that cross react with proteins at top of dermal papillae
-Leads to vesicular and pruritic lesios thus herpetiformis
-Caused essentially by celiacs disease, if celiacs is
controlled so will blisters
-HLADQ (MHCII)
Eryhtema Multiforme
- Pink variable shaped rash marks with a central area of necrosis
- Caused by a number of things including drugs and infections
- Most commonly mycoplasma and HSV
- Drugs are usually sulfa and beta lactams
- Necrotic center
Stevens Johnsons
- Eryhtema Multiforme that will involve the oral mucousa and one other mucous membrane
- Can be severe sqequale and is fatal in some cases
- More commonly drugs than infection
Toxic Epidermal Necrolysis
- Extreme form of stevens johnsons with greter than 30% of body desquamated
- Death is a high possibility
- Treat patients like burn pateints
- Commonly associated with drugs
- Occurs at the Dermal/Epidermal Junction, more devastating than scalded skin syndrome
Scalded skin syndrome
- Staph Aureus A and B exfoliative toxin causes dissociation of desmosomes and leads to disintegration of the granulosum
- Not as serious as TEN
Albinism
- Decrease in melanocyte number and quality.
- Neural Crest origin
- OFten defect in tyrosinase which converts DOPA to melanin
Melasma
-Hyperpigmentation of the face associated with elevated progesterone, estrogen levels
Vilitigo
-Autoimmune destruction of melanocytes leading to localized depigmentation
Seborrheic Keratosis
- Stuck on appearing plaques. Contain keratin coils
- By themselves are benign
- Leser Trelat sign is massive increase in number due to GI malignancy or lymphoma
Icthyosis
-Loss of granulosum
Pyoderma Gangrenosum
-Necrotic lesion of the leg that is associated with hematologic malignancy or autoimmunity
Acanthosis Nigricans
Hyperplasia of epidermis leading to a velvety skin appearance
-Associated with insulin resistance or GI malignancy
Actinic Keratosis
- Premalignant condition that can lead to SCC
- Often seen on face, hands, neck, related to UVB sunrays (pyrimidine dimers)
- Scaly plaque
- Often treated with topical 5-FU
Erythema Nodosum
-Inflammation of the subutaneous fat in granulomatous diseases (Fungal, TB, sarcoid, etc)
Lichen Planus
- Pruriitc, purple, polygonal. Dysplastic nails are also commonly seen
- Associated with saw tooth infiltration at dermal/epidermal junction
- Commonly seen with hepatitis C infection
Pytariasis Rosea
- Herald patch that looks like ringworm and is often misdiagnosed
- Shortly after there is massive increase in number of lesions throughout body
- Self Resolves and often occurs after URI
UVA and UVB damage
- UVA causes DNA DS breaks
- UVB causes Pyrimidine Dimer formation
Basal Cell Carcinoma
- Tumor of the basal cell layer
- Associated with sunlight and UVB radiation
- More common on the upper face than the lower face
- Ulcerated center with peripheral telangectasia, pearly white nodules
Squamous Cell Carcinoma
- Tumor of SC, keratin pearls
- Can come as a consequence of actinic keratosis
- Rarely metastasizes
- Associated with immunosupression, arsenic and chronic inflammation
Keratoacanthoma
Variety of SCC that appears rapidly and then rapidly disapears
-Has scooped out central portion
Melanoma
- S-100 positive neural crest cells
- Caused by sun exposure
- Depth of invasion is the primary prognostic factor and metastasis are possible
- Associated with V600E Brafkinase mutation that can be treated with veruzumab (TKI)
- Most common location for dark colored individuals is on the hands and feet
Dysplastic Nevus syndrome
- Hereditery increased propensity for nevi
- CDNK2A mutation
