Steve Tyler's Screaming Skin MS Stuff Flashcards
Name the Epidermis layers from outer layer to inner layer
Stratum Corneum (keratin), Stratum Lecidum, Stratum Granulosum, Stratum Spinosum (spines=desmosomes), Stratum Basale (Stem cell site); Californians Like Girls in String Bikinis
Tight junction
Zona Occludens: prevent paracellular movement of solutes; composed of claudins and occludins
Adherens Junction
Zona adherens; below tight junction forms belt connection actin cytoskeletans of adjacent cells with CADherins (Ca dependent ADhesion proteins) Loss of E cadherin promotes metastasis
Desmosome
Macula adherens; structural support via keratin interactions. Autoantibodies against desmosomes lead to pemphigus Vulgaris;
Gap Junctions
Channel proteins call connexons permit electrical and chemical communication between cells.
Integrins
Membrane proteins that maintain the integrity of basolateral membrane by binding to collagen and laminin in basement membrane;
Hemidesmosome
Connects keratin in basal cells to underlying basement membrane. Autoantibodies against hemidesmosomes leads to bullos pemphigoid (hemidesmosomes are down bullow)
Knee Injury exam methods and what they mean
Anterior drawer sign is ACL injury;
Posterior drawer sign is PCL injury;
Abnormal passive abduction (Valgus stress) is MCL injury;
Abnormal passive adduction (Varus stress) is LCL;
McMurray test: pain on external rotation is medial meniscus and pain on internal rotation is lateral meniscus
Unhappy triad
Common injury in contact sports due to lateral force applied to a planted leg. Classically consists of damage to the ACL, MCL, and medial meniscus (Attached to MCL); However, lateral meniscus injury is more common
What landmark do you look for when doing a Pudendal nerve block (relieve pain of delivery)
ischial spine
Where do you palpate for the appendix
2/3 distance between the umbilicus and the anterior superior iliac spine (ASIS), just proximal to the ASIS (McBurney point)
If you want to do a lumbar puncture what landmark do you look for
Iliac crests
Rotator Cuff muscles, their nerves, and function
SITS;
supraspinatus (suprascapular nerve): abducts the arm initially, most common rotator cuff injury;
Infraspinatus (suprascapular nerve): laterally/external rotates arm, common pitching injury;
Teres Minor (axillary nerve): adducts and laterally/external rotates arm;
Subscapularis (subscapular nerve): medially/internally rotates and adducts arm;
SITS are mostly innervated by C5 and C6
Name the wrist bones
Scaphoid, Lunate, Triquetrum, Pisiform, Hamate, Capitate, Trapezoid, Trapezium;
So Long To Pinky, Here Comes The Thumb
Special stuff about the scaphoid
Palpated in anatomical snuff box;
Is the most commonly fractured carpal bone and is prone to avascular necrosis owing to retrograde blood supply
Dislocation of Lunate can cause what acute symptoms
can cause acute carpal tunnel syndrome
A fall on an outstretched hand that damages the hook of the hamate can cause what
ulnar nerve injury
Carpal Tunnel Syndrome
Entrapment of median nerve in carpal tunnel: nerve compression leading to paresthesia, pain, and numbness in distribution of median nerve; more common in pregnant women
Guyon Canal Syndrome
Compression of the ulnar nerve at the wrist or hand, classically seen in cyclists due to pressure form handlebars
What supplies the cells that differentiate into osteoblasts after a fracture?
Periosteum
Erb’s Palsy
Waiter’s tip;
Injury: traction or tear of the upper (Erber) trunk (C5, 6 roots);
Caused by: infants due to lateral traction on neck during delivery and adults get it form trauma;
Causes deficits in deltoid (abduction), Infraspinatus (lateral rotation), Biceps brachii (flexion and supination)
Klumpke Palsy
Traction of tear of Lower trunk: C8-T1 root;
Caused by: infants get it from upward force on arm during delivery, Adults form trauma;
Causes deficits in intrinsic hand muscles, lumbricals, interossei, thenar, hypothenar (get claw hand, lumbricals normally flex MCP joints and extend DIP and PIP joints)
Thoracic outlet syndrome
Compression of the lower trunk and subclavian vessels;
Caused by cervical rib injury or pancoast tumor;
Causes deficits in intrinsic hand muscles, lumbricals, interossei, thenar, hypothenar (with atrophy of hand muscles, edema, pain, and ischemia due to vascular compression);
Treat with incision of anterior scalene muscle
Winged scapula
Lesion of the long thoracic nerve;
Caused by axillary node dissection after mastectomy, stab wounds;
Deficit in Serratus anterior causing the inability to anchor scapula to thoracic cage so you cannot abduct arm above horizontal position
Injury to the axillary nerve
C4-C6;
Can be caused by fractured surgical neck of humerus or anterior dislocation of humerus;
Presents as Flattened deltiod, loss of arm abduction at shoulder (>15 degrees), loss of sensation over deltoid muscle and lateral arm
Injury to Musculocutaneous nerve
C5-C7;
Caused by upper trunk compression;
Presents as loss of forearm flexion and supination, loss of sensation over lateral forearm
Injury to Radial Nerve
C5-T1;
Caused by Midshaft fracture of humerus, compression of axilla (due to crutches or sleeping with arm over chair);
Presents as wrist drop (loss of elbow, wrist, and finger extension, Decreased grip strength (wrist extension necessary for maximal action of flexors), Loss of sensation over posterior arm/forearm and dorsal hand
Injury to Median Nerve
C5-T1;
Caused by supracondylar fracture of humerus (proximal lesion), carpal tunnel and wrist laceration (distal lesion);
Presents as “Ape hand” and “Pope’s blessing,” Loss of wrist and lateral finger flexion, thumb opposition, lumbricals of 2nd and 3rd digits, Proximal lesion causes loss of sensation over thenar eminence and dorsal and palmar aspects of lateral 3 1/2 fingers (but not with carpal tunnel)
injury to Ulnar
C8-T1;
Caused by fracture of medial epicondyle of humerus “funny bone” (proximal lesion), fractured hook of hamate (Distal);
Presents as ulnar claw on digit extension, proximal lesion shows radial deviation of wrist upon flexion, loss of flexion of wrist and medial fingers, abduction and adduction of fingers (interossei will waste), actions of medial 2 lumbrical muscles, loss of sensation over medial 1 1/2 fingers including hypothenar eminence.
Recurrent branch of median nerve
C5-T1;
Caused by superficial laceration of palm;
Get Ape Hand, loss of thenar muscle group (opposition, abduction, and flexion of thumb), no loss of sensation
What are the thenar muscles
By the thumb Opponens pollicis (Opposes), Abductor pollicis brevis (abducts), Flexor pollicis brevis (Flexes)
What are the hypothenar muscles
By the pinky;
Opponens digiti minimi (opposes), Abductor digiti minimi (abducts), Flexor digiti minimi brevis (flexes)
Dorsal interosseous muscles do what
Abduct the fingers (DAB=Dorsal ABduct)
Palmar interosseous muscles do what
Adducts the fingers (PAD=Palmars ADducts
Lumbrical muscles do what
Flex at the MCP joint, extend PIP and DIP joints
Injury to Obturator nerve
L2-L4;
Cause of injury: pelvic surgery;
Presents as: decreased sensation of medial thigh and decreased abduction (adductor longus, adductor brevis, adductor magnus, gracilis)
Injury to Femoral nerve
L2-L4;
Cause of the injury is likely pelvic fracture;
Presents as decreased thigh flexion and leg extension
Injury to Common peroneal nerve
L4-S2;
Cause of injury is trauma or compression of lateral aspect of leg, fibular neck fracture;
Presents as foot drop (inverted and plantarflexed at rest, loss of eversion and dorsiflexion. “steppage gate.” loss of sensation on dorsum of foot;
PED=Peroneal Everts and Dorsiflexes foot (injury causes foot to be dropPED)
Injury to tibial nerve
L4-S3;
Caused by knee trauma, baker cyst (proximal lesion), tarsal tunnel syndrome (distal lesion);
Presents as inability to curl toes and loss of sensation on sole of foot. In proximal lesions, foot everted at rest with loss of inversion and plantarflexion;
TIP=Tibial Inverts and Plantarflexes (injury means you can’t stand on your TIP toes)
Injury to Superior gluteal nerve
L4-S1;
Posterior hip dislocation or polio are common causes;
Presents as Trendelenburg gait
What is trendelenburg gait
Common in superior gluteal nerve damage;
Pelvis tilts because weight bearing leg cannot maintain aligment of pelvis through hip abduction (superior nerve innverates medius and minimus). Lesion is contralateral to the side of the hip that drops, ipsilateral to extremity on which the patient stands
Inferior gluteal nerve damage
L5-S2;
Posterior Hip Dislocation is common cause;
Presents as difficulty climbing stairs, rising from seated position, loss of hip extension (inferior nerve innervated maximus)
What nerve and artery run in the axilla and lateral thorax
Long thoracic nerve and lateral throracic artery
What nerve and artery run by the surgical neck of humerus
Axillary nerve, posterior circumflex artery
What nerve and artery run in the midshaft of humerus
Radial nerve, deep brachial artery
What nerve and artery run in the distal humerus and cubital fossa
Median nerve and the popliteal artery
What nerve and artery run in the Posterior to medial malleolus
Tibial nerve and Posterior tibial artery
What bands get smaller and which ones stay the same during muscle contraction
Contraction results in shortening of H and I bands, and Z lines come closer together (HIZ shrinkage); but the A band stays the same (A is Always the same)
Type 1 muscle fibers
Slow twitch; red fibers resulting from increased mitochondria and myoglobin concentration (increased oxidative phosphorylation) leading to sustained contraction (1 slow red ox);
Decreased amount of glycogen
Type 2 Muscle fibers
Fast twitch;
white fibers resulting from decreased mitochondria and myoglobin concentrations (increased anaerobic glycolysis); weight training results in hypertrophy of fast twitch muscles.;
increased amount of glycogen
Endochondral ossification
bones of axial and appendicular skeleton, and base of the skull. Cartilaginous model of bone is first made by chondrocytes. Osteoclasts and osteoblasts later replace with woven bone and then remodel to lamellar bone. In adults, woven bone occurs after fractures and in Paget disease.
Membranous ossification
Bone of calvarium and facial bones. Woven bone formed directly without cartilage. Later remodeled to lamellar bone.
Osteoblasts
Build Bone by secreting collagen and catalyzing mineralization. Differentiate from mesenchymal stem cells in periosteum.
Osteoclasts
Multinucleated cells that dissolve bone by secreting acid and collagenases. Differentiate from monocytes/macrophages.
Parathyroid and its effect on bones
at low and intermittent levels it exerts anabolic effects (builds bones) on osteoblasts (directly) and osteoclasts (indirectly). Chronic high PTH levels cause catabolic effects (osteitis fibrosa cystica)
Estrogen and its effect on bones
Estrogen inhibits apoptosis in osteoblasts and induces apoptosis in osteoclasts. When estrogen deficient, excess remodeling cycles and bone resorption lead to osteoporosis.
Achondroplasia
Failure of longitudinal bone growth (endochondral ossification) causing short limbs. Membranous ossification is not affected leading to large head relative to limbs. Constitutive action of fibroblast growth factor receptor (FGFR3) actually inhibits chondrocyte proliferation. >85% of mutations occur sporadically and are associated with increased paternal age, but there is some autosomal dominant inheritance. Common cause of dwarfism. Normal life span and fertility.
Osteoporosis
Trabecular (spongy) bone loses mass and interconnections despite normal bone mineralization and lab values (Ca and PO) Diagnosis by a bone mineral density test (DEXA) with a T score of
Type 1 osteoporosis
Postmenopausal; increased bone resorption due to decreased estrogen levels. Commonly get a femoral neck fracture, distal radius (Colles) fracture
Type 2 osteoporosis
Senile osteporosis; affects men and women >70 years old. Prophylaxis: regular weight bearing exercise and adequate calcium and vitamin D intake throughout adulthood.
Treat with Bisphosphonates, PTH, SERMs, rarely calcitonin; denosumab (antibody against RANKL)
Osteopetrosis
AKA marble bone disease;
Failure of normal bone resorption due to defective osteoclasts leading to thickened, dense bones that are prone to fracture. Bone fills marrow space leading to pancytopenia, extramedullary hematopoiesis. Mutations (e.g. carbonic anhydrase II) impair ability of osteoclasts to create an acidic environment necessary for bone resorption. X rays show bone in bone appearance. Can result in CN impingement and palsies as a result of narrowing foramina. Bone marrow transplant is potentially curative as osteoclasts are derived from monocytes.
Osteomalacia/rickets
Vitamin D deficiency. Osteomalacia in adults, rickets in kids. Due to defective mineralization/calcification of osteoid leading to soft bones that bow out. Decreased Vit D leads to decreased Ca leads to increased PTH secretion leading to decreased PO4. Hyperactivity of osteoblasts leads to increased ALP (osteoblasts need alkaline environment);
Look for vegan diet low in vitamin D
Paget disease of bone (osteitis deformans)
Common, localized disorder of bone remodeling caused by increase in both osteoblastic and osteoclastic activity. Serum Calcium, phosphorus, and PTH levels are normal. Increase ALP. Mosaic pattern of woven and lamellar bone, long bone chalk-stick fractures. Increased blood flow from increased arteriovenous shunts may cause high output cardiac failure. Increased risk of osteogenic sarcoma. Hat size will be increased. Hearing loss common due to narrowing foramen. Associated with paramyxovirus infection
Stages of Paget
Lytic stage-osteoclasts;
Mixed stage-osteoclasts and osteoblasts;
Sclerotic stage-osteoblasts;
Quiescent stage- minimal osteoclast/osteoblast activity
Osteonecrosis
AKA avascular necrosis;
Infarction of bone and marrow, usually very painful. Caused by trauma, high dose corticosteroids, alcoholism, sickle cell. Most common site is femoral head (due to insufficiency of medial circumflex femoral artery)
What will labs look like in osteoporosis
Everything is normal here, just decreased bone mass
What will labs look like in Osteoporosis
usually normal calcium unless severe malignant disease, dense brittle bones
What will labs look like in Paget Disease
Increased ALP and abnormal mosaic bone architecture, everything else is normal
What will labs look like in Osteomalacia/Rickets
decreased serum Ca, decreased PO4, Increased ALP, Increased PTH; See soft bones that bow out
What will labs look like in Hypervitaminosis D
Increased serum Ca, increased PO4, normal ALP, decreased PTH; Caused by over supplementation or granulomatous disease (e.g. sarcoidosis)
What will labs look like in Osteitis Fibrosa Cystica due to primary hyperparathyroidism
Increased serum Ca, Decreased PO4, Increased ALP, Increased PTH
What will labs look like in osteitis fibrosa cystica due to secondary hyperparathyroidism
decreaed serum Ca, Increased PO4, Increased ALP, Increased PTH
Giant Cell tumor
20-40 year olds get it; In the epiphyseal end of long bones; locally aggressive benign tumor around the knee; Soap bubble appearance on X ray; Multinucleated giant cells
Osteochondroma
Most common benign tumor;
Males
Osteosarcoma (osteogenic sarcoma)
2nd most common primary malignant bone tumor after multiple myeloma;
Bimodal distribution of 10-20year olds and >65 year olds;
Predisposing factors are Paget disease, bone infarcts, radiation, familial retinoblastoma, Li-Fraumeni syndrome (germline p53 mutation);
Usually in the metaphysis of long bones often around knee;
Codman triangle (from elevation of periosteum) or sunburst pattern on x ray;
Aggressive and treated with surgical en bloc resection and chemo
Ewing Sarcoma
Think boys less than 15;
Commonly appears in diaphysis of long bones, pelvis, scapula, and ribs;
anaplastic small blue cell malignant tumors (histology looks like a crap load of blue cells);
Extremely aggressive with early metastases, but responsive to chemo;
onion appearance in bone;
Associated with 11;22 translocation
Chondrosarcoma
Rare, malignant cartilaginous tumor;
Men 30-60 years old, usually located in the pelvis, spine, scapula, humerus, tibia and femur;
May be of primary origin or form osteochondroma;
Is an expansile glistening mass within medullary cavity
Osteoarthritis: what is it, what are the exam findings
Mechanical-joint wear and tear destroys articular cartilage;
Findings: Subchondral cysts, sclerosis, osteophytes, eburnation (polished, ivory like appearance of bone), Heberden nodes (DIP), and Bouchard nodes (PIP), NO MCP;
Osteoarthritis: predisposing factors
Predisposing factors: age, obesity, joint deformity, trauma;
Osteoarthritis: Presentation
Presents as: pain in weight bearing joints after use (e.g. end of the day pain), improving with rest, Knee cartilage usually lost medially (bow legged). Non inflammatory, No systemic symptoms
Osteoarthritis: Treatment
NSAIDs, Intra-articular glucocorticoids
Rheumatiod arthritis: Etiology
Autoimmune: inflammatory destruction of synovial joints. Mediated by cytokines, type III and 4 hypersensitivity reactions (lymphocytes and plasma cells)
Rheumatiod arthritis: Joint findings
Pannus formation in the joints of MCP and PIP, subcutaneous rheumatoid nodules (fibrinoid necrosis), ulnar deviation of fingers, subluxation, Baker cysts (in popliteal fossa). No DIP involvement
Rheumatiod arthritis: Predisposing factors
Female > Males;
80% have + rheumatoid factor (anti-IgG antibody);
anti-cyclic citrullinated peptide antibody is more specific;
Strong association with HLA-DR4
Rheumatiod arthritis: Classic presentation
Morning stiffness > 30 minutes; Improves with use of joints; Symmetric joint involvement; Systemic symptoms (fever, fatigue, pleuritis, pericarditis)
Rheumatiod arthritis: Treatment
NSAIDs like indomethacin;
glucocorticoids;
Disease modifying agents (methotrexate is the big one!, sulfasalazine, TNF-alpha inhibitors)
Sjogrens syndrome
Autoimmune disorder that destroys exocrine glands (lacrimal and salivary);
Predominantly affects females 40-60 years old;
Findings: Xerophthalmia (decreased tear production leading to corneal damage), Xerostomia (Decreased saliva production), Presence of anti-nuclear antibodies SS-A (anti-Ro) and SS-B (anti-La), bilateral parotid enlargement;
can be primary or secondary to other diseases (rheumatoid);
Complications include dental carries, mucosa associated lymphoid tissue lymphoma (MALT) which presents as unilateral parotid enlargement
Findings in Gout
Acute inflammatory monoarthritis caused by precipitation of monosodium urate crystals in joints. Associated with hyperuricemia;
More common in males
Gout is associated with hyperuricemia which can be caused by
1) Underexcretion of uric acid (90%), largely idiopathic, can be exacerbated by certain medications (like thiazides);
2) Overproduction of of uric acid (10%), Lesch-Nyhan syndrome, PRPP excess, increase cell turnover (tumor lysis syndrome), von Gierke syndrome;
Crystals in Gout
Crystals are needle shaped and negative birefringent (yellow under parallel light, blue under perpendicular light),
Symptoms of Gout
Asymetric joint distribution, Joint is red, swollen and painful; Podagra (MTP joint of big toe); Tophus formation (external ear, olecranon bursa, or achilles tendon); Acute attacks tend to come on after large meal or alcohol consumption (made metabolic acidosis and competes for same excretion sites in kidney as uric acid, causing decreased uric acid excretion)
Treatment of Gout
Acute: NSAIDs (indomethacin), glucocorticoids, colchicine;
Chronic (preventative): xanthine oxidase inhibitors (allopurinol, febuxostat)
Psuedogout
Present with pain and effusion in a joint;
caused by deposition of calcium pyrophosphate crystals within the joint space (chondrocalcinosis on x ray);
forms basophilic, rhomboid crystals that are weakly positively birefringent. Usually affects large joints (classically the knee);
>50 years old, both sexes;
Disease associated with Psuedogout: hemochromatosis, hyperparathyroidism, and hypoparathyroidism;
Treat: NSAIDs for sudden severe attacks, Steroids, Colchicine;
Crystals are blue when parallel to light
Infectious arthritis
S. aureus, Streptococcus, N. gonorrhoeae are common causes;
Gonococcal arthritis is an STD that presents as a migratory arthritis with an asymmetric pattern;
Affected joint is swollen, red, and Painful;
STD=synovitis (e.g. knee), Tenosynovitis (e.g. hand), and Dermatitis (e.g. pustule);
What are the Seronegative spondyloarthropathies and what does that mean
Arthritis with rheumatoid factor (no anti-IgG antibodies). Strong association with HLA-B27 (codes for HLA MHC class I). Occurs more often in males PAIR= Psoriatic arthritis, Ankylosing spondylitis, Inflammatory bowel disease, Reactive arthritis (Reitier syndrome)
Psoriatic arthritis
Joint pain and stiffness associated with psoriasis;
Asymetric and patchy involvement;
Dactylitis (sausage fingers), “pencil in cup” deformity on x ray;
Seen in
Ankylosing Spondylitis
Chronic Inflammatory Disease of spine and sacroiliac joints leading to ankylosis (stiff spine due to fusion of joints), uveitis, and aortic regurgitation; Bamboo spine (vertebral fusion)
Inflammatory Bowel disease: associated with what?
Crohn disease and ulcerative colitis are often accompanied by ankylosing spondylitis or peripheral arthritis
Reactive Arthritis (Reiter Syndrome)
Classic triad: Conjunctivitis and anterior uveitis, Urethritis, Arthritis;
Often Post GI (shigella, salmonella, Yersinia, campylobacter) or chlamydia infections;
Can’t See, Can’t Pee, Can’t bend my knee
SLE: symptoms, exam findings
Presents with Rash, joint pain and fever; most commonly a woman of reproductive age and african descent; Libman Sacks Endocarditis: wart like vegetations on both sides of valve (get insufficiency or stenosis of valves); Lupus nephritis (type III hypersensitivity): Nephritic (diffuse proliferative glomerulonephritis), Nephrotic (membranous glomerulonephritis)
SLE: Findings in labs
ANA: sensitive, not specific;
Anti-dsDNA antibodies: specific, poor prognosis (means you have renal disease);
Anti-smith antibodies: specific, not prognostic (directed against snRNPs);
Antihistone antibodies: sensitive for drug induced lupus;
Anticardiolipin antibodies: false positive on tests for syphilis, prolonged PTT (paradoxically increased risk of arterivenous thrombosis);
Decreased C3, C4, and CH50 due to immune complex deposition
SLE: treatment
NSAIDs, steroids, immunosuppressants, hydroxychloroquine
Sarcoidosis
Characterized by immune-mediated, widespread noncaseating granulomas and elevated serum ACE levels. Common in black females. often asymptomatic expect for enlarged lymph nodes. Incidental findings on CXR of bilateral hilar adenopathy and/or reticular opacities.
Treat with Steroids
What diseases is sarcoidosis associated with
Associated with restrictive lung disease (interstitial fibrosis), erythema nodosum, lupus pernio, Bell palsy, epithelioid granulomas containing mircoscopic Schaumann and asteriod bodies, uveitis, and hypercalcemia (due to increased 1aplha hydroxylase mediated vitamin D activation in macrophages).
Polymyalgia Rheymatica
Pain and stiffness in shoulders and hips, often with fever, malaise, and weight loss. Does not cause muscle weakness. More common in women > 50 years old; associated with temporal (giant cell) arteritis.
Findings: Increased CRP and ESR, normal CK;
treatment: give lose dose corticosteroids (rapid response)
Fibromyalgia
Most commonly seen in females 20-50 years old;
Chronic, widespread musculoskeletal pain associated with stiffness, paresthesias, poor sleep, and fatigue. Treat with regular exercise, antidepressants (TCAs and SNRIs), and anticonvulsants
Polymyositis
Progressive symmetric proximal muscle weakness, characterized by endomysial inflammation with CD8+ T cells. Most often involves shoulders
Dermatomyositis
Similar polymyositis, but also involves malar rash (similar to SLE), Gottron papules, heliotrope (erythematous periorbital) rash, “shawl and face” rash, mechanic’s hands. Increased risk of occult malignancy. Perimysial inflammation and atrophy with CD4+ T cells.
Myasthenia gravis
Most common NMJ disorder;
Autoantibodies to postsynaptic ACh receptor;
Presents with Ptosis, diplopia, weakness, Worsens with muscular use;
Associated with Thymoma, thymic hyperplasia;
Give AChE inhibitors to reverse symptoms
Lambert Eaton Myasthenic syndrome
Very uncommon;
Autoantibodies against presynaptic Calcium channels leading to decreases ACh release;
Proximal muscle weakness, autonomic symptoms (Dry mouth, impotence), improves with muscle use;
Associated with small cell lung cancer;
AChE inhibitors do littel to nothing to relieve symptoms
Myositis ossificans
Metaplasia of skeletal muscle to bone following muscular trauma. Most often seen in upper and lower extremity. May present as suspicious mass at site of known trauma or as incidental finding on radiography.
Scleroderma (systemic sclerosis)
Excessive fibrosis and collagen deposition throughout the body. Commonly sclerosis of the skin, manifesting as taut puffy skin with no wrinkles. Also get sclerosis of renal, pulmonary (cause of death), cardiovascular, and GI system. 75% female;
2 types: Diffuse scleroderma, Limited scleroderma
Diffuse scleroderma
Widespread skin involvement, rapid progression, early visceral involvement. Associated with anti-Scl-70 antibodies (anti-DNA topoisomerase I antibody)
Limited scleroderma
Limited skin involvement confined to fingers and face. Also with CREST symptoms;
Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia. More benign clinical course. Associated with antiCentromere antibody (C for CREST)
Macules
Flat lesion with well circumscribed change in skin color
Patch
Macule > 1 cm;
Examples would be large birthmark (congenital nevus)
Papules
Elevated solid skin lesion
Plaque s
Papules > 1 cm;
Examples are Psoriasis
Vesicles
Small fluid-containing blister
Bulla
Large fluid-containing blisters > 1 cm;
example Bullous pemphigoid
Pustule s
Vesicle containing pus;
examples: Pustular psoriasis
Wheal s
Transient smooth papule or plaque;
Examples: Hives (urticaria)
Scales
Flaking off of stratum corneum;
Examples: Eczema, psoriasis, SCC
Crusts
Dry exudate;
Examples of impetigo
Hyperkeratosis is what
Increased thickness of stratum corneum;
Examples Psoriasis, calluses
Parakeratosis is what
Hyperkeratosis with retention of nuclei in stratum corneum;
Examples: psoriasis
Spongiosis
Epidermal accumulation of edematous fluid in intercellular spaces;
Examples: Eczematous dermatitis
Acantholysis
Separation of epidermal cells;
Examples: Pemphigus vulgaris
Acanthosis
Epidermal hyperplasia (increased spinosum); Examples: Acanthosis nigricans
Albinism
Normal melanocyte number with decreased melanin production due to decreased tyrosinase activity or defective tyrosine transport. Can also be caused by failure of neural crest cell migration during development. Increased risk of skin cancer.
Melasma (chloasma)
Hyperpigmentation associated with pregnancy (mask of pregnancy) or OCP use.
Vitiligo
Irregular areas of complete depigmentation Caused by autoimmune destruction of melanocytes.
Verrucae
Warts; Caused by HPV. Soft, tan-colored, cauliflower-like papules. Epidermal hyperplasia, hyperkeratosis, koilocytosis. Condyloma acuminatum on genitals.
Melanocytic nevus
Common mole. Benign, but melanoma can arise in congenital or atypical moles. Intradermal nevi are papular. Junction nevi are flat macules.
Urticaria
Hives. Pruritic wheals that form after mast cell degranulation. Characterized by superficial dermal edema and lymphatic channel dilation.
Ephelis
Freckle. Normal number of melanocytes, increased melanin pigment
Atopic dermatitis (Eczema)
Pruritic eruption, commonly skin flexures. Often associated with other atopic disease (Asthma, allergic rhinitis). Usually starts on the face in infancy and often appears in the antecubital fossae thereafter.
Allergic contact dermatitis
Type IV hypersensitivity reaction that follows exposure to allergen. Lesions occur at site of contact (e.g. nickel, poisin ivy, neomycin)
Psoriasis
Papules and plaques with silvery scaling, especially on knees and elbows. Acanthosis with parakeratotic scaling (nuclei still in stratum corneum). Increased stratum spinosum, decreased stratum granulosum. Auspitz sign which is pinpoint bleeding spots from exposure of dermal papillae when scales are scraped off. Can be associated with nail pitting and psoriatic arthritis.
Seborrheic keratosis
Flat, greasy, pitmented squamous epithelial proliferation with keratin-filled cysts (horn cysts). Looks “stuck on.” Lesions occur on head, trunk, and extremities. Common benign neoplasm of older persons.
Leser-Trelat sign
Sudden appearance of multiple seborrheic keratoses. Indicating an underlying malignancy.
Impetigo
Very superficial skin infection. Usually from S aureus or S pyogenes. Highly contagious. Honey-colored crusting. Bullous impetigo has bullae and is usually caused by S. aureus
Cellulitis
Acute, painful, spreading infection of dermis and subcutaneous tissues. Usually from S pyogenes or S aureus. Often starts with a break in skin from trauma or another infection.
Necrotizing fasciitis
Deeper tissue injury, usually form anaerobic bacteria or S pyogenes. Results in crepitus from methane and CO2 production. “Fleshing eating bacteria.” Causes bullae and a purple color to the skin.
Staphylococcal scalded skin syndrome
Exotoxin destroys keratinocyte attachments in the stratum granulosum only (vs. Toxic epidermal necrolysis, which destroys the epidermal-dermal junction). Characterized by fever and generalized erythematous rash with sloughing of the upper layers of the epidermis that heals completely. Seen in newborns and children.
Hairy leukoplakia
White, painless plaques on the tongue that cannot be scraped off. EBV mediated. Occurs in HIV positive patients.
Pemphigus vulgaris
Potentially fatal autoimmune skin disorder with IgG antibody against desmoglein (component of desmosomes);
Flaccid intraepidermal bullae cause by acantholysis (keratinocytes in stratum spinosum are conncected by desmosomes);
Oral mucosa is involved;
Immunofluoresence shows antibodies around epidermal cells in a reticular (net-like) pattern;
Nikolsky sign + (separation of epidermis upon manual stroking of skin)
Bullous pemphigoid
Less severe than pemphigus vulgaris. Involves IgG antibodies against hemidesmosome (epidermal basement membrane, antibodies are “bullow” the epidermis);
Tense blisters filled with eosinophils affect skin but not the oral mucosa;
Immunofluorescence shows linear pattern at epidermal-dermal junction;
Nikolsky sign negative (no seperation of epidermis upon manual stroking of skin)
Dermatitis herpetiformis
Pruritic papules, vesicles, and bullae (often found on elbows). Deposits of IgA at the tips of dermal pappillae. Associated with celiac disease.
Erythema multiforme
Associated with infections (e.g. mycoplasma pneumoniae, HSV), drugs (sulfa drugs, beta-lactams, phenytoin), cancers, and autoimmune disease. Presents with multiple types of lesions-macules, papules, vesicles, and target lesions (looks like targets with multiple rings and a dusky center showing epitheleal disruption)
Steven johnson syndrome
Characterized by fever, bulla formation and necrosis, sloughing of skin, and a high mortality rate. Typically 2 mucous membranes are involved, and skin lesions may appear like targets as seen in erythemia multiforme. Usually associated with adverse drug reaction. A more severe form of steven johnson syndrome with > 30% of the body surface area involved is toxic epidermal necrolysis.
Acanthosis nigricans
Epidermal hyperplasia causing symmetrical, hyperpigmented, velvety thickening of skin, especially on neck or in axilla. Associated with hyperinsuliinemia (e.g. diabetes, obesity, cushings syndrome) and visceral malignancy (e.g. gastric adenocarcinoma)
Actinic Keratosis
Premalignant lesions caused by sun exposure. Small, rough, erythematous or brownish papules or plaques. Risk of squamous cell carcinoma is proportional to degree of epithelial dysplasia
Erythema nodosum
Painful inflammatory lesions of subcutaneous fat, usually on anterior shins. Often idiopathic, but can be associated with sarcoidosis, coccidioidomycosis, histoplasmosis, TB, Strep infections, leprosy, and crohn disease.
Lichen Planus
6 P’s: Pruritic, Purple, Polygonal, Planar, Papules, and Plaques;
Mucosal involvement manifests as Wickham striae (reticular white lines). Sawtooth infiltrate of lymphocytes at dermal-epidermal junction. Associated with Hep C
Pityriasis rosea
Herald patch followed days later by christmas tree distribution. Multiple plaques with collarette scale. Self resolving in 6-8 weeks.
Sunburn
Acute cutaneous inflammatory reaction due to excessive UV irradiation. Causes DNA mutations, inducing apoptosis of keratinocytes. UVA is dominant in tanning and photoaging, IVB in sunburn Can lead to impetigo and skin cancers (basal cell carcinoma, squamous cell carcinoma, and melanoma)
Basal cell carcinoma
Most common skin cancer. Found in sun exposed areas of the body. Locally invasive, but almost never metastasizes. Pink early nodules commonly with telangiectasias, rolled borders, and central crusting or ulceration. BCCs also appear as non healing ulcers with infiltrating growth or as a scaling plaque (superficial BCC);
BCCs usually have palisading nuclei
Squamous cell carcinoma
Second most common skin cancer;
Associated with excessive sun exposure, immunosuppression, and occasionally arsenic exposure. Commonly appears on the face, lower lips, ears, hands. Locally invasive, but may spread to lymph nodes and will rarely metastasize. Ulcerative red lesions with frequent scale. Associated with chronic draining sinuses .Histopathology: keratin “pearls”
Actinic keratosis
A scaly plaques that is a precursor to squamous cell carcinoma
Keratoacanthoma
is a variant of actinic keratosis that grows rapidly for 4-6 weeks and may regress spontaneously over months.
Melanoma
common tumor with significant risk of metastasis. S-100 tumor marker. Associated with sunlight exposure;
fair skinned persons are at increased risk;
Depth of tumor correlates with risk of metastasis;
Look for the ABCDEs: Asymmetry, Border irregularity, Color variation, Diameter >6mm, and Evolution over time.
Often driven by activating mutation in BRAF kinase.
Primary treatment is excision with appropriately wide margins;
If metastatic or unresectable patients with BRAF V600E mutation may benefit from verurafenib, a BRAF kinase inhibitor
Function of LTB4
Is a neutrophil chemotactic agent (neutrophils arrive B4 everyone else);
Function of LTC4, D4, E4
function in bronchoconstriction, vasoconstriction, contraction of smooth muscle, and increased vascular permeability
Function of PGI2
Inhibits platelet aggregation and promotes vasodilation;
Platelet-Gathering Inhibitor
Aspirin: mechanism
Irreversibly blocks cyclooxygenase by covalent acetylation, which decreases synthesis of TXA2 and prostaglandins Increases bleeding time until new platelets are produced (7 days). No effect on PT, PTT. a type of NSAID
Aspirin: clinical use
Low dose (
Aspirin: toxicity
Gastic ulceration, tinnitus (CN VIII). Chronic use can lead to acute renal failure, interstitial nephritis, and upper GI bleeding. Risk of Reye syndrome in children treated with aspirin for viral infection. Also stimulates respiratory centers, causing hyperventilation and respiratory alkalosis
NSAIDs
Names: ibuprofen, naproxen, indomethacin, ketorolac, diclofenac;
Clinical use: antipyretic, anti-inflammatory, indomethacin used to close PDA;
Toxicity: Interstitial nephritis, gastic ulcers (PGs protect gastric mucosa), renal ischemia (PGs vasodilate afferent arteriole)
COX-2 inhibitors: mechanism
Celecoxib;
reversibly inhibits specifically COX-2 which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain;
spares COX-1, which helps maintain the gastric mucosa. This, should not have the corrosive effects of other NSAIDs on the GI lining. Spares platelet function as TXA2 production goes through COX1
COX-2 inhibitors: Clinical use
Rheumatoid arthritis, osteoarthritis; patients with gastritis or ulcers
COX-2 inhibitors: Toxicity
Increased risk of thrombosis, Sulfa allergy in celecoxib
Acetaminophen: Mechanism
Reversibly inhibits cyclooxygenase, mostly in CNS, inactivated peripherally
Acetaminophen: Clinical uses
Antipyretic, analgesic, but NOT anti-inflammatory. Used instead of aspirin to avoid Reye syndrome in kids with viral infections
Acetaminophen: Toxicity
Overdose produces hepatic necrosis; Acetaminophen metabolite (NAPQ1) depletes glutathione and forms toxic tissue adducts in liver. N-acetylcysteine is antidote-regenerates glutathione
Bisphosphonates: names
Aldronate, riserdronate, -dronates
Bisphosphonates: mechanism
Pyrophosphate analogs;
bind hydroxyapatite in bone, inhibiting osteoclast activity
Bisphosphonates: clinical use
Osteoporosis, hypercalcemia, paget disease of bone
Bisphosphonates: toxicity
Corrosive esophagitis (patients are advised to take with water and remain upright for 30 minutes), osteonecrosis of the jaw
Allopurinol
inhibits xanthine oxidase which decreases conversion of xanthine to uric acid. Also used in lymphoma and leukemia to prevent tumor lysis associated urate nephropathy. Increased concentrations of azathioprine and 6-MP (both normally metabolized by xanthine oxidase);
Do not give salicylates, all but the highest doses depress uric acid clearance. Even high doses (5-6g/day) have obly minor uricosuric activity
Febuxostat
inhibits xanthine oxidase
Probenicid
inhibits reabsorption of uric acid in PCT (also inhibits secretion of penicillin)
Drugs used in gouty attacks
NSAIDs: Naproxen and indomethacin;
Glucocorticoids: oral and intraarticular;
Colchicine: binds and stabilized tubulin to inhibit microtubule polymerization, impairing leukocyte chemotaxis and degranulation. Acute and prophylactic use. GI side effects
TNF-alpha inhibitor drugs: predispose you to what
predispose to infection, including reactivation of latent TB, since TNF blockade prevents activation of macrophages and destruction of phagocytosed microbes.
Etanercept
TNF-alpha inhibitor;
Fusion protein (receptor for TNF-alpha + IgG1 Fc), produced by recombinant DNA;
EtanerCEPT is a TNF decoy reCEPTor;
Used for rheumatoid arthritis, psoriasis, ankylosing spondylitis
Infliximab, Adalimumab
anti-TNF-alpha monoclonal antibody;
used for IBD, rheumatoid arthritis, ankylosing spondylitis, psoriasis
Baker cyst
benign swelling, commonly seen in the popliteal fossa as a result of the build up of bursal fluid; will reduce active and passive movement of knee;
Can burst and be painful;
Associated with Rheumatoid arthritis
corticosteroids effect on bones
decreased absorption of Calcium in the intestine;
increase Calcium excretion in kidney;
Decreased serum Calcium increases PTH and bone is broken down to try to compensate for decreased Calcium levels.
Troponin
In cardiac and skeletal muscles;
binds calcium and mediates Calcium activated muscle contraction
Calmodulin
in smooth muscle;
calcium binding protein that mediates calcium activated smooth muscle contraction
