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Actinic Keratoses (AK)
Hypertrophic AK (thickened), pigmented AK, actinic chelitis (lips)
small, raised scaly spots on chronically sun-exposed skin; scattered, thick erythematous patches
UV induced mutations in p53 cause unrestrained growth and damage to repair genes prevents tumor rejection
sun exposure immunosuppression genetic conditions
skin type I, age > 70, field disease on upper limbs/ head/ neck
Histology? Surface changes at epidermis
cryosurgery, topicals (5-FU, imiquimod, PDT w/ photosensitizer ALA, chemical peel, reduction of immunosuppressants to safe levels
Most common precursor to SCC
Nodular (can be pigmented in darker pts) Basal Cell Carcinoma (BCC) Superficial (more scaly, less thick) Morpheaform (scarring, loss of pigment; MORE AGGRESSIVE)
UVB causes direct DNA damage to p53 and overexpression of originate from keratinocytes from epidermis or follicular bcl-2, which prevents apoptosis; carcinoma of follicular epithelium; unlikely to metastasize; most common skin cancer keratinocytes & found above clavicle
Chronic UVB exposure, immunosuppression, inherited conditions (Gorlin Goltz basal cell nevus syndrome, XP), chronic arsenism, patch mutations, previous BCC
750,000 new cases/yr, growing incidence among younger ages (30-40s)
male, older age, fair complexion, tendency to burn, outdoor occupation
surgical excision, Moh's, PDT w/ ALA, radiation tx (for non-operable), topical tx for field dz (5-FU, imiquimod), reduction of immunosuppressants to safe levels
Basal Cell Nevus Syndrome (BCNS)
TONS of BCCs as child, megaloblastomas, palmar pits, bifid ribs, frontal bossing of scalp
Deficiency in patch (negative regulator of Shh) causes constitutive action of positive regulator (Shh), increasing incidence of BCC Shh binds and inhibits patch; without patch, smoothened causes increased transcription of GLI-1,2,3, causing increased cell proliferation Chronic UVB exp Originates from interfollicular keratinocytes following direct DNA chem carcinogens damage to p53 from UVB; SCC make VEGF so highly genetic disorders angiogenic immunosuppression HPV Apoptosis loss possibly due to ROS resistance of SCC chronic inflam (leg ulcers, DLE, Genetic predisposition for loss of p53 (XP, HPV) osteomyelitis)
Vismodegib (targets Shh to decrease tumor size; but still residual tumor so perhaps development of resistance)
Loss of taste (and ultimately anorexia) is a side effect of tx
Squamous Cell Carcinoma (SCC)
Worrisome when recurrent, location on forehead / temple/ ear/ lip, large size (>2cm), poor differentiation, invasion (in-transit met to lymphatic channels), perineural invasion
Asymptomatic until fast growing --> painful, grows faster than BCC, ulceration/ verruca-like, common in transplant pts, metastatic potential
250,000 new cases/yr; growing incidence among younger ages (30-40s)
Heart/lung transplant recipients Chronic lymphocytic leukemia XP
surgical excision, Moh's, PDT w/ ALA, radiation tx (for non-operable), topical tx for field dz (5-FU, imiquimod, cryosurgery), reduction of immunosuppressants to safe levels
genetic mutations (MC1R mutations- red hair & predispose to B-raf mut; familial loss of p16) less common than other skin cancers (BCC>SCC>>MM) SSMM (common, pagetoid - migration to place not typically found, trunk of men, legs of female; regression = loss of pigment/scarring) - NM (no radial growth- often ulcerated, rapidly growing, can lack pigment; trunk of men, invades through dermal/epidermal jx); - LMM (sun exposed areas; slowest growth rate and longest radial growth stage); usually appears as growing freckle, freckle in unusual place, or freckle that crosses anatomic boundaries - ALM (palms, soles, subungal; Hutchinson's sign, melanonychia striata, abnl nail) Malignant tumor arising spontaneously from melanocytes in basal epidermis or from dysplastic nevi; dysplastic nevi then undergoes radial growth where it becomes invasive until able to grow vertically; once vertical growth phase reached, the tumor has high metastatic potential young adults FH of MM or DN UV light rptd childhood sunburns # (>50) & size (>5mm) of nevi CN PMH of MM high SES Skin types 1&2 latitude DNA repair defects immunosuppression NM in middle-aged men; LMM in older pts w/ chronic UVB exposure & age spots; ALM more common in dark/Asian pts uniform pigmentation, symmetrical shape, sharply demarcated borders, wide distribution and colors Dysplastic nevus syndrome (DN) - multiple benign with characteristics of precursor melanoma: irregular family members w/ melanoma and multiple DN growth, variation in color/size, multiple asymmetric lesions in pt (also have only one copy of p16)
Superficial spreading melanoma (SSMM) Nodular melanoma (NM) Malignant Melanoma (MM) "know your ABCDEs" Lentigo maligna melanoma (LMM) Acral lentiginous melanoma (ALM) - hands, feet, mouth, genitals Mucosal melanoma (very rare!)
ALM can sometimes occur in conjuction with 4% of cancer cases, but vitiligo (autoimmune more than 75% of skin dz); associated with cancer deaths; 5th & mutations in C-kit 7th most common Associated with oxidative damage from UVA cancers in men & Melanoma in sunwomen; 70,000 new protected areas can Staging depends on Breslow's depth, ulceration, # mitotic cases/yr; primarily result from mutations in figures, lymphatic/ vasculature entry younger adults; b-raf or N-ras increased incidence B-raf mutation --> loss of PTEN --> activation of oncogene Akt - oncogenes due to recreational -> transformation of radial/noninvasive melanoma to habits vertical/invasive MM LACK MUTATIONS IN p53 N-ras mutation --> activation of oncogene Akt
Evaluation includes history, TBSE, LN exam, CXR, routine labs, & MRI brain/CT of chest (for late-stage) HIGH risk for metastasis Histology? Sun exposure signs (loss of elastin fibers, solar Surgical removal/ excisional bx elastosis - abnl elastin in upper dermis) Sentinel LN bx to stage metastasis Excisional (or incisional punch) bx for Breslow's depth to LNs (used for melanomas >1.0mm in depth) Braf inhibitors (PLX4032) prolongs survival but not curative later detection and higher stage associated with higher mortality Pts with p16 mutations have increased risk of pancreatic cancer too!
Arise from melanocytes
can be sporadic or familial
Giant Melanocytic Nevus
Present at birth or within first year of life; important to monitor changes in size/color/symmetry
Relative risk for melanoma depends on size of CN
Prophylactic removal during teen years; staged surgical removals if large New tx include mimics of photolyases (enzymes in other organisms that repair CPDs) Histology? Endothelial swelling, decreased langerhans, neutrophil recruitment, apoptotic keratinocytes (bright pink) areas of hyperplasia (thickened stratum corneum, epidermis, dermis)
Xeroderma pigmentosum (XP)
marked increase in skin malignancies at young age, photosensitivity, impaired DNA damage repair systems
Defective NER (nucleotide excision repair); accumulation of oxidative and DNA damage Determined by total UVB energy absorbed (ind of duration)
At least 10 DNA repair defects Failed or incomplete repair of thymine dimers --> mutations in p53 (higher risk for nonmelanoma skin cancers)
High rate of MM, SCC, freckles
Inflammation (cytokines, histamine, prostaglandins, serotonin) cause redness; increased adhesion protein expression --> immune cell recruitment Change in existing melanin (immediate pigment darkening caused by redistribution of melanin - IPD, persistent pigment darkening- PPD)
Major risk factor for nonmelanoma and melanoma skin cancers
N/A New melanin (delayed tanning) formed when keratinocytes release MSH in response to UVR; MSH binds MC1R on melanocytes --> increased melanin production and proliferation mutations in filaggrin (which binds to keratin) causes bundling/collapsing of keratin fibers
Inherited disease causing generalized scaling and thickened skin
Excess stratum corneum due to altered epidermal differentiation
Localized scaly plaques, can be raised; less prone to infections (abundant AMPs)
Excess stratum corneum from low epidermal turnover
Epidermolysis bullosa (EB) (General)
blisters on hands and feet
Inherited disorder w/ defects in cellular attachments, causing epidermis to no longer stick to dermis Superficial blistering within the epidermis caused by disorganization of keratin intermediate filament network
Less severe bc blistering in higher skin layers EB Simplex Dominant mutation causes complete disruption of the keratin more superficial (but painful blisters), non-scarring, localized to polymer (even if you have one nl K14) hands/ feet/ extremities, no mucus membrane involvement Recessive mutation causes truncated protein or loss of protein but not as problematic Very serious bc blistering in middle skin layers Junctional Generalized blisters at birth, periorificial granulation tissue, nail shedding/dystrophy, denuded areas, enamel defects, growth retardation, anemia, epithelial blistering of mucosal membranes (Resp, GI, GU) Subepidermal blistering w/ scarring Dystrophic (Recessive-RDEB or DominantDDEB) milia (cysts on newborns) that scar upon healing, Subepidermal blistering absent/dystrophic nails, Mitten deformities (fusion of finger scar tissue (RDEB)); mucosal surfaces involved, malnutrition, growth retardation, anemia Autoimmune-mediated blistering disease caused by antibody deposition against collagen VII blistering disease where epidermis is lifting off of basement membrane; usually on lower extremities of older patients Itchy, tense blisters (do not break easily!), Autoimmune blistering disorder where antibodies are directed at hemidesmosomes (sub-basal) so loss of epidermal attachment to basement membrane Blistering in the lamina lucida
Genetic defects w/ keratin (arginine at position G of alpha-helix heptad is mutated)
Histology? Cytolytic fracture / cleavage plane below the nuclei of basal cells --> aggregation of keratin fibers
premature stop codon in laminin 5 genes sometimes defects w/ collagen 17 or B4/a6 integrins Can be lethal in early childhood
Premature stop codon in collagen VII genes
Epidermolysis bullosa acquisita Bullous pemphigoid (BP) Bullous pemphigoid
Autoantibodies against Collagen VII Histology? Subepidermal blister (white space btwn epidermis & dermis) (sub-basal split), healthy epidermis, +eosinophils (pink) Dx confirmed w/ immunofluorescent Abs binding to basement membrane Histology? Subepidermal blister (white space btwn epidermis & dermis) (sub-basal split), healthy epidermis, +eosinophils (pink) Dx confirmed w/ immunofluorescent Abs
Autoantibodies against BPAG1 and/or BPAG2
Mucus membrane pemphigoid
red line along gingivial sulcus (white picket fence), no scarring
Autoimmune blistering disorder where antibodies are directed at hemidesmosomes (sub-basal) so loss of epidermal attachment to basement membrane Severe inflammation of the eye causes thick & fibrous scarring that fuses with the eye conjunctiva as symblepharon
Autoantibodies against BPAG2, laminins, integrins
Ocular cicatricial pemphigoid Pemphigus Pemphigus vulgaris
severe ocular disease, symblepharon (fibrous bands where eyelid fuses to conjunctiva) Inter-epidermal blisters, jagged & flaccid blisters w/ positive Nikolsky sign (easy to deform w/ slight pressure), hyperpigmentation in healing areas, not too much scarring, severe nail disease, oral lesions
Possible blindness as skin covers cornea if no aggressive treatment Histology? Basal epidermis still attached to BM, and rete ridges still visible but huge white space above represents blister (suprabasal split) Chicken wire appearance w/ direct immunofluorescence Immunosuppressants, corticosteroids; new therapies (tyrosine kinase inhibitors to increase resistance to pemphigus IgG) Immunosuppressants, corticosteroids
Autoimmune blistering disorder where antibodies (IgG) are Autoantibodies against attacking intra-epidermal (suprabasal) proteins of desmosome, desmoglein 3 and/or resulting in compromised cell-cell adhesion [basal layer splits desmoglein 1 from spinous layer]
side effects of steroids; high fatality w/o tx
Pemphigus foliaceus Ectodermal Dysplasia N/A
Albinism Vitiligo Keloid Panniculitis onychomycosis Dermatitis
N/A N/A N/A N/A N/A General Acute dermatitis (eczema) Chronic dermatitis Subacute dermatitis
Autoimmune blistering disoder where antibodies (IgG) attack Autoantibodies against intra-epidermal (suprabasal) proteins of the desmosome, resulting in compromised cell-cell adhesion [basal layer splits desmoglein 1 from spinous layer] Mutation in Loss of desmosomal cadherin organization and mediation of desomosomal Fragility syndrome subsequent adhesion cytoplasmic plaque protein (plakophilin) Tyrosinase mutation causes inability of melanocytes to produce Hypopigmentation melanin Hypopigmentation - usually splotchy; symmetrical involvement of Autoimmune destruction of melanocytes produces decreased body parts or absent melanocytes Exuberant scar usually from trauma Excessive collagen in the dermis Inflammation of subcutaneous adipose tissue Yellowing, hyperkeratosis of nails; possible presence of debris Tinea unguium (see Fungal infection of nail under nails Dermatophytosis) Edematous epidermis causes skin to become swollen, raised, Inflammation of skin inflamed --> erythema and itchiness severe inflammation and edema causes edema fluid to leak oozing, crusted vesicles (poison ivy) from skin surface --> oozing & crusting Lichenification Lichenification and spongiosis with crusting on surface Hypersensitive, twitchy skin - overreaction to various stimuli, causes skin to turn red--> white when scratched; same "twitchiness" also seen in lung/nasal membranes Abnormal cytoskeleton? Mutation in filaggrin causes abnl barrier fx so increased dryness; mutation also causes chronic, pruritic dermatitis that waxes & wanes; face & extensor bundling/collapsing of keratin fibers extremities of infants; flexural surfaces of older children/adults; lichenification and linear excoriations can be present (chronic); Aberrant inflammatory response? abundance of TH2 cells in xerosis, dermatographism dermal inflammatory infiltrate Hygiene hypothesis? overreaction upon antigen exposure due to "too clean" of environment Probably all of these! Abnormal circulation in skin comprises the skin barrier, causing dryness and inflammation --> itch --> LSC & SD Xerosis, erythema, red-brown discoloration from hemosiderin OLD theory - SD caused by stasis and hypoxia, but pts actually deposits and degraded extravasated RBCs, dilated superficial have high flow rate and oxygen veins; often involves medial ankle, possible lipodermatosclerosis (hard feeling from underlying fat Abnormal microcirculation - increased permeability of dermal necrosis); hypopigmentation, ulceration capillaries allows leakage of fibrinogen, which polymerizes to fibrin to form fibrin cuff around capillaries --> ultimately inflammation May or may not have underlying primary dermatitis; skin itches Lichenification of skin, very pruritic beginning chronic scatching cycle that causes the skin to lichenify Itching, redness, erythematous papules; possible spongiosis and 1. edema --> crusted vesicles; 2. Allergic - patient becomes sensitized from previous allergen exposure (no rash at first exposure); upon re-exposure to Diaper dermatitis (irritant, also caused by Candida), poison ivy ACD - due to oleoresin in Rhus group of plants); nickel ACD antigen, there is a delayed-hypersensitivity reaction neomycin ACD; formaldehyde ACD variation of dandruff, can be on scalp/face 1. irritant - not allergic, but burned/inflamed by substance (occur in anyone exposed) 2. Allergic - allergy response (poison ivy, does not occur in everybody) Once child outgrows AD, can have asthma/ allergies later; higher prev in developed countries suggest environmental factor
side effects of steroids
Histology? Melanocytes present (just not making melanin!) Histology? No melanocytes seen African American race Histology? Dermis has taken over! Histology? KOH prep or PAS stain reveals hyphae Histology? Epidermal spongiosis (intercellular edema; white) Histology? Spongiosis causing fluid-filled vesicles (subcorneal vesicles) Histology? Acanthosis of epidermis (thickening) Histology? Marked acanthosis, elongation of rete ridges, spongiosis Complications due to abnl barrier function of skin or abnl immune response? Secondary infections of AD skin with S. aureus, MRSA, HSV (tingling, stinging at lesion), molluscum --> pustulosis or folliculitis, weeping/oozing/yellow crust - have less AMPs due to acute/chronic lesions! Food allergies
Atopic Dermatitis (AD)
20% of children, 1% of adults "childhood eczema"; 2More common if parent has AD 3x more common now; more developed countries
Moisturizers for xerosis, antiinflammatory cortisone creams; if no relief to those, systemic immunosuppressants for severe cases (prednisone, cyclosporin); oral antibiotics for presence of secondary infections; acyclovir for secondary HSV infections (especially if periorbital)
Stasis Dermatitis (SD)
Often require hospitalization for tx of Can be complicated by LSC venous ulcers
Lichen Simplex Chronicus (LSC)
Can complicate other types of dermatitis Avoid irritant/allergen; wash immediately after exposure; calomine to soothe/dry out (AVOID sensitizers like topical benadryl/Caladryl); topical corticosteroid Anti- fungals controling Pityrosporum carriage Topical/oral antibiotics (reduce bacterial density and macrophage activation) Retinoic acid (downregulates TLR2 expression on monocytes) Do NOT give topical steroids!
Contact Dermatitis 1. Irritant 2. Allergic (ACD)
Inflammation of skin related to host response to normal P. ovale flora Starts w/ occlusion of follicle and formation of microcomedone, leading to hyperkeratosis of the opening that blocks eggressive sebum. Cyst forms with sebaceous material, forming comedone. Follicular unit further expands, allowing Propionibacteria acnes growth of Propionibacterium acnes and inflammation that (nl skin flora) leads to follicular wall rupture Inflammation mediated by bacteria intxn w/ TLR2 on monocytes Colonization at birth that peaks in early adult life with increased sebaceous gland activity Malassezia furfur (P. ovale, P.orbiculare; nl Unclear factors trigger overgrowth & conversion of yeast to skin yeast) pathogenic hyphal form
hyper- or hypopigmented patches with readily inducible scale; chest & back; warm/moist environment; usually asymptomatic but may be pruritic
People living in warm/ humid climates have higher bacterial carriage
Hot/humid environment AB use Immunosuppressant Hi sebum prod S. aureus, occlusion of non-dermatologic areas
Pityrosporum folliculitis Bacterial folliculitis Bacterial folliculitis
Follicular centered inflammation on chest or back
Inflammation of hair follicle due to fungal colonization/infection
People living in warm/humid climates Chronic S. aureus carrier Irritation Shaving Occlusion
Histology? Massive infiltration of neutrophils around hair follicle
Responds to anti-fungal tx
Do NOT give topical steroids!
Follicular centered pustules or erythematous papules that are slightly pruritic and/or tender
Bacterial infection of hair follicles transmitted from direct contact with infected person or autoinoculation
Clinical (pustules/papules w/ hair follicle in middle) Gram stain/Cx
Topical Abs Oral Abs (if extensive, recurrent) Self-limited Sx usually don't require tx May give Ciprofloxacin if needed Localized? Topical antibacterial cream (Mupirocin)
Hot tub folliculitis
Exposure to Pseudomonas in water that has not been sufficiently chlorinated
Bullous impetigo (S. aureus) Impetigo Impetiginized eczema (2ndary inf)
Small vesicles/pustules, erosions w/ golden honey-colored crust
Superficial bacterial infection of epidermis caused by S. aureus, GAS; highly contagious (direct contact)
S. aureus, GAS
Increased incidence in SE, day care settings
Childhood Crowded areas Heat/humidity
Clinical (honey crust) Gram stain/Cx
Widespread? Oral Abs (Dicloxacillin, cephalexin, erythromycin, etc) Drainage (hot compresses or surgical) Oral Abs (dicloxacillin, Cephalexin, Bactrim)
Furuncle (smaller) Furuncles/ Carbuncles Carbuncle (larger!)
Inflammatory, tender nodules or abscesses around follicle (or underlying tissue if carbuncle) that is purulent or necrotic; hot/red, fluctuant (compressible)
Continuum from folliculitis --> furuncle --> carbuncle that is transmitted via autoinoculation/direct contact
Chronic S. aureus carrier Folliculitis Obesity Immunodeficiency
Clinical Gram stain/Cx
Abs not effective until necrotic/purulent tissue is DRAINED!! Recurrence Bacteremia (rare)
"Spider bite phenomenon" CA-MRSA Looks like spider bite, furuncle, abscesses, pyomyositis, cellulitis Bacterial infection caused by methicillin resistant S. aureus asymptomatic --> fatal Well demarcated scaly plaque w/ hyperkeratosis, may be pruritic Fungal infection of non-viable, keratinized structures like or erythematous (jock itch), moccasin scale or toe web stratum corneum, hair, nails; transmitted person-person, maceration (tinea pedis), annular w/ central clearing (tinea contact with infected fomites, autoinoculation corporis/faciei), alopetic patch w/ possible neck LN swelling (tinea capitis) Keratinases of fungal hyphae CA-MRSA
Increased prevalence as SSTI, furunculosis; can cause infections in Pts lack typical risk factors pts typically lacking RFs for MRSA (hospital/prison/ sports) Often none Humid/occluded skin Common infection even Atopy (eczema) in healthy hosts Immunodeficiency TOPICAL STEROIDS VERY common 20% of kids have at some time Common in adults Often none HIV Organ transplantation
Culture w/ sensitivity testing
NO beta-lactams, possible adjunct therapy Use Bactrim or clindamycin
Erythromycin & methicillin resisitant
Tinea pedis (athlete's foot) T. unguium (onychomycosis) T. cruris (jock itch) T. corporis/faciei (ring worm) T. capitis (cradle cap)
Filamentous fungi (Microsporum, Trichophyton, Epidermophyton)
Histology? Fungal hyphae caused by dermatophytes in stratum corneum KOH prep Fungal Cx (takes wks) Wood's lamp (hair) Bx for histology w/ PAS stain
Topical anti-fungals (Azoles, TOPICAL STEROIDS CAN allylamines: naftifine, terbinafine) MAKE WORSE!!! Oral anti-fungals (azoles, allylamines, griseofulvin) for hair/nail infections Spontaneously resolution (SLOW) Nail disfigurement (rare) Alopecia
Verruca (warts) Verruca vulgaris Verrucus (bumpy/rough), hyperkeratotic skin colored papules; usually asymptomatic unless 2ndary infection/inflammation Infection of basal layer of skin with HPV (dsDNA virus), resulting in the slow division of cells in the spinous layer; Hyperkeratotic papules/plaques that are less exophytic, black eventually leads to hyperkeratosis and papillomatosis macules of thrombosed capillary loops ("seeds" = lay term) Transmitted from skin to skin contact, autoinoculation, Genital warts; flatter, gray/brown papules contaminated surfaces Thinlike projections common on face Pinkish warts common on hands/face HPV 2, 4
Histology? Hyperkeratosis of epidermis and granular layer, inward bending of rete ridges, papillomatosis (fingerlike projections of epithelia) Clinical Bx (rare) DNA testing to determine type of HPV present
Verruca plantaris Condylomata acuminata Filiform warts Verruca plana
Various OTC tx modalities that aren't all that effective (Salicylic acid, imiquimod, duct tape) Paring Cryosurgery Podophyllin (topical chem agent) Spontaneous resolution (can take up to 2y) Imiquimod Canthardin (good for kids) Liquid nitrogen Curettage Self-limited in immuno-competent host Oral antivirals for immunocompromised/ recurrent or severe episodes
possible some HPV types are cancer-forming
Molluscum Contagiosum N/A
Umbilicated (central), small, dome-shaped, pink papules
Superficial poxvirus infection of epidermis only transmitted via Molluscum skin to skin (considered STD in young adults) contagiosum virus
Children HIV Sexually active young adults
Clinical Crush prep Bx (rare) Histology? Henderson-Patterson bodies (eosinophilic inclusion bodies) Clinical Tzanck prep (cannot distinguish HSV from VZV) Direct fluorescent antibody (CAN distinguish HSV from VZV) Viral culture Bx (rare) Clinical Tzanck prep DFA (distinguish HSV from VZV) Viral Cx Bx (rare)
Herpes Simplex Virus (HSV)
HSV-1 (classically oral) HSV-2 (classically genital)
PAINFUL, TENDER grouped vesicles or erosions on erythematous base; prodrome (tingling); can occur on lips, finger (Whitlow), genitals
HSV infection of keratinized skin/mucus membranes transmitted skin-skin, skin-mucosa (possible STD) Latency phase, asymptomatic shedding VZV goes latent after active infection/vaccination in the ganglia until risk factors cause reactivation of varicella zoster virus
None - pretty ubiquitous virus
Potential risk for wide-spread dissemination Neonatal transmission POST-HERPETIC NEURALGIA
Varicella Zoster Virus (VZV) (Shingles)
PAINFUL, DERMATOMAL vesicles, crusted papules, erosions often in unilateral fashion
NOT contagious (represents reactivation state) but patients with varicella zoster can transmit chicken pox to those who have never had it
Varicella zoster virus
Lifetime risk of 10-20%
advancing age immunosuppression Stress!
ORAL ANTI-VIRALS ASAP!! (w/I first 48-72h)
dissemination transmission of varicella (chicken pox)
Topical creams (scabicides) PRURITIC, thread like linear burrows produced by the tunneling of the mite; can have erythematous papules; commonly seen on wrists, genitals, waistline, axilla, web spaces Eruption caused by tunneling of mite in stratum corneum that causes delayed type IV hypersensitivity response and Sarcoptes scabiei var. diffuse pruritic eruption after 4-8 weeks hominis Transmitted via skin-skin contact or contact with fomites Nursing home residents Children Hospitals Close contact areas Histology? Mites (ovals) in stratum corneum Mineral oil prep? Mites with oval gray eggs and fecal pellets treatment of fomites and close contacts can use oral anti-parasitic if severe (ivermectin) Antibiotics that cover staph and strep (dicloxacillin, some cephalosporins- Cefazolin, Cephalexin; vancomycin- if MRSA; Unasyn --> Augmentin if from bite) NOT Bactrim! Penicillin DOC
Rare (psychological burden?)
Carbuncles w/ pus present? Think S. aureus Cellulitis Diffuse erythema w/ no pus? Think GAS
Rapidly spreading areas of edema, redness, heat; possible vesicles/bullae/cutaneous hemorrhage; systemic sx (fever, tachycardia, confusion, hypotension, leukocytosis)
Acute infection arising when organisms enter the deep dermis/subcutaneous layers through skin breaches
Group A Strep Other beta-hemolytic strep S. aureus (CA-MRSA)
Previous cutaneous damage (trauma, ulceration, fissured toe webs, inflammatory dermatoses) Obesity Edema (venous insufficiency, lymphatic obstruction) More common in infants/ children/ elderly
EMPIRICAL KNOWLEDGE (cx not always positive, low sensitivity of needle aspiration cx)
Raised, sharply demarcated erythematic lesions, commonly seen on face; acute onset
Acute infection caused by GAS entering the upper dermis
Group A Strep Less common than cellulitis
Diabetic foot ulcers
Infection by S. aureus or B-hemolytic Streptococci Often polymicrobial infection with enterococci, obligate anaerobes, P. aeruginosa, and/or Enterobacteriaceae Initially presents with cellulitis, blood-filled bullae, ecchymosis, systemic toxicity, elevated CPK RED FLAGS: severe pain out of proportion w/ skin findings, large bullae, skin necrosis/ecchymosis, wooden hard feel of subq tissue, numbness of skin, systemic toxicity, rapid spread w/ AB tx Rapidly progressive, toxemic infection in previously injured muscle (blunt trauma), edema, crepitus (gas bubbles), brown bullae; abrupt pain Initial break in skin from trauma or surgery causes advancing infection to fascial and/or muscle compartments Aerobic + Anaerobic bowel flora Clostridium perfringens C. novyi C. histolyticum Early? Think GAS or Clostridium GI or female GU surgery? Bowel flora Clean procedure? Skin flora (S. aureus, Strep sp) Historically seen with war injuries but now associated w. blunt trauma GAS, S. aureus, or anaerobic streptococci Less common in children NSAIDs Diabetes Venous insufficiency Completely normal hosts Abdominal Surgeries Decubitus ulcers Perianal ulcers Bartholin abscess IVDU h/o severe penetrating trauma or crush injuries XR shows edema and gas in soft tissue
clindamycin Unasyn (ampicillin + SulbactamIV) Extensive debridement, surgery Monomicrobial - clindamycin + penicillin G Polymicrobial - Ampicillin, clindamycin, and ciprofloxacin Aggressive surgical debridement PCN + clindamycin
Possible CA-MRSA infection associated with worse outcomes
Necrotizing fasciitis (NF) Monomicrobial
Usually bacteremic 30-60% mortality
Gas gangrene (myonecrosis)
Blunt trauma causes non-viable tissue to lose blood supply, creating anaerobic environment for spore-forming, gram positive rod bacteria to infect injured muscle
Spontaneous (hematogenous) gangrene from Clostridium septicum in pts with GI malignancies or neutropenia
Superficial incisional (subq space) Surgical Site Infections (SSI) Deep incisional (fascia/muscle) Organ/space Can be early onset or take 5-14 days Adverse infection associated with hospitalized patients who have undergone recent surgery
Inherent risk with clean contaminated, contaminated, or dirty-infected operative wounds
Prophylactic superficial antisepsis Perioperative ABs Incision & Drainage
BMD T-score < -2.5, increased incidence of fractures
skeletal disorder characterized by compromised bone strength (bone density & bone quality- arch, turnover, mineralization, damage accum) predisposing a person to increased risk of fracture With age, lose trabecular volume, #, thickness, connectivity Decreased estrogen is related to high bone turnover that results in stressful micro-cracks and loss of bone density Estrogen deficiency = oxidative stress in bone marrow = increased ROS = activation of T cells = increasd TNF = formation of osteoclasts and bone marrow stromal cells via RANKL
Loss of bone trabeculae (microarchitectural deterioration) Genetic predisposition Estrogen deficiency activates immune response Increased RANKL
Age Postmenopause FH of osteoporosis Adjustable RF? Excessive alcohol sedentary lifestyle
Low dose Ca/VitD Estrogen calcitonin raloxifene (estrogen Ag in bone, Antag in breast) Bisphosphonates -Alendronate, Zoledronic acid (Reclast) Anti-RANKL Ab - Denosumab Anabolic agentForteo (teriparatide) - transient PTH = bone formation Odanacatib - Cat K inh Sclerostin Ab
Long term bisphosphonate use causes increased BMD but increased fractures, increased osteonecrosis of jaw (rare) High dose calcium linked to CV events and vascular calcification
Polyostotic Paget's disease Monostotic
Genetic predisposition (chrom 18, overlap w/ familial expansile 3 stage of localized, chaotic(mosaic) bone remodeling: misshaped legs/head, gait problems, progression over 1. osteoclastic activity osteolysis, p62 time,warm to touch; moth-eaten deteriorated bone, pitting of 2. mixed osteoclastic-osteoblastic activity, where osteoblasts try mutation- nl degrades pagetic bone; usually involves spine/ skull, most painful in to compensate with deposition of disorganized, RANKL signaling; pelvis/long bones hypervascularized lamellar bone Juvenile Paget's 3. exhaustive (burnout) stage (dense pagetic bone as mutated OPG) hearing loss, platybasia (softening at skull base--> headache hypercellularity of bone diminishes) w/ valsalva), Pagetic steal syndrome (shunt blood to ext Problem with osteclasts carotid, stroke-like sx), osteoporosis circumscripta (bone loss All results in deformity, fracture, metabolic derangement (inc #, size, nuclei, fx, around skull), leontiasis ossea (rare, enlarged facial/jaw bones), sensitivity to vitD); nl DIsorganized communication btwn osteoclasts and osteoblasts osteoblasts high output heart failure (coupled chaotic activity) possible involvement of slow viral inf Dense, brittle bone that fractures, bleeding/infections, hypersplenism, hemolytic anemia Count osteoclasts - RANKL mutation (low OC #) v. TC1RG1/ ClCN7 (nl OC #)
More common in people from British Isles, Caucasians adult disease (~60y.o.) Age 200,000 cases in U.S. (~3% prev) 5-20% w/ symptoms M>F
Elevated bone-specific alkaline phosphatase (overactive osteoblasts, >2x inc) Histology? Woven mosaic bone XR? Pagetic flame lytic lesions, cotton wool skull, sclerotic + resorbed areas, inc Calvarian thickness), picture frame vertebral bodies (thick cortex frames lesion), fissure/chalk stick fractures (straight across) Bone scan? show sclerotic dz
Most people are asymptomatic sx? NSAIDs, COX2 inh, PT, surgery for fx Advanced disease? Use osteoporosis drugs (bisphosphonates, since they too kill osteoclasts) hypercalcemia tx if know pt will be immobilized
Pagetic bone is hemorrhagic so activity needs to reduced before surgery Spinal cord/nerve root compressions Fractures Osteosarcoma!! (10% of older pts) - but no inc in non-skeletal malignancy! hypercalcemia (immobilization) gout (23% of pts w/ gout have paget's) Cranial nerve compression --> blindness, deafness Death by 10y.o. if not treated
Autosomal recessive infantile malignant (ARO) Osteopetrosis Autosomal dominant (Albers-Schonberg) (ARO)
Mutation in RANKL (rare) or ion pumps (TC1RG1, ClCN7) causes defective bone resorption and apoptosis of osteoclasts Mutation in TC1RG1 causes inability of osteoclast to secrete hydrogen ions into the bone matrix, thereby decreasing bone resorption Mutation/defect in cathepsin K, so osteoclasts can no longer function properly in bone resorption Mutation in CAII renders the cell unable to generate protons from CO2 and H2O, causing loss of osteoclast resorptive function and generalized disease
Spine sclerosis with sandwich vertebrae (rugger jersey spine), variable penetrance/ severity Disproportionate (big head, small body), pectus excavatum, lumbar lordosis, nail hypoplasia (missing nails)
Bone overgrowth due to Infancy loss of osteoclast resorptive fx Late childhood/ adolescence onset Onset in infancy, early Bone overgrowth due to childhood loss of osteoclast resorptive fx Very rare! Bone overgrowth due to loss of osteoclast resorptive fx Unregulated TGF-B causes overstimulation Variable age, severity, of osteoblasts and course excessive bone formation Autosomal recessive inheritance Dutch ancestry (Afrikaners) Autosomal recessive
Osteoclast number, anemia labs
Bone marrow transplantation
XR? Rugger jersey spine
Fractures, osteomyelitis, possible nerve compression
N/A Facial dysmorphism? Missing jaw look, large forehead, underdeveloped nose, asymmetry renal tubular acidosis, cerebral calcifications, hypotonia, weakness, mental subnl Phenotype less severe w/ age
XR? Dense orbital ridge, sclerotic skull base, hypoplasia of facial bones, dense vertebrae w/ preservation of TVP UA - check for RTA Measured in erythrocytes
Recurrent fractures in lower limbs
Carbonic Anhydrase II deficiency
Progressive Diaphyseal disease
gradual appearance of symmetric hyperostosis on periosteal and endosteal surfaces of long bones
mutation in TGF-B1, a latency protein that is a normally a chronic sequesterer and inhibitor of TGF-B in bone
Glucocorticoids for pain relief
Endosteal hyperostosis Sclerosteosis
Fibrodysplasia ossificans N/A progressive (FOP)
Disruption of Wnt signaling system causes decreased inhibition of Wnt, resulting in the inhibition of APC/GSK3 complex. Now, B-catenin is active and able to promote transcription of genes involved in osteoblast differentiation, Heavy bones! causing osteosclerosis Progressive asymmetrical enlargement of mandible (w/o Disruption of Wnt signaling system causes decreased dental malocclusion like osteopet), pain w/ point pressure on inhibition of Wnt, resulting in the inhibition of APC/GSK3 longbones complex. Now, B-catenin is active and able to promote transcription of genes involved in osteoblast differentiation, Heavy bones! causing osteosclerosis BMD T-score >0, no fractures, nl bone remodeling, flat forehead, Disruption of Wnt signaling system causes decreased elongated mandible, toras palatinus (bony protrusion of palate), inhibition of Wnt, resulting in the inhibition of APC/GSK3 benign presentation complex. Now, B-catenin is active and able to promote transcription of genes involved in osteoblast differentiation, Heavy bones! causing osteosclerosis Inflammatory swelling of soft tissues that eventually transforms into encasement of bone during first decade of life via Soft tissue swelling that progressively turns to bone esp at sites endochondral ossification of injury (avoid trauma!!); malformed great toe, progressive heterotopic ossification pattern; spares heart/ diaphragm/ Missense mutation of ACVR/ALK2 inactivates binding site for extraocular muscles inhibitor (FKBP12), causing excessive and constitutive BMP stimulation occurs rapidly over days-wks, new bone pain at site of inf, Infection of the bone via hematogenous entry, contiguous swelling spread, or inoculation via trauma TALL, heavy, Dutch ancestry, syndactyly, pain w/ point pressure on long bones
Deactivating mutation in SOST (Wnt inhibitor)
Nl OC Possible inc alk phosphatase Possible optic atrophy, facial nerve palsy, deafness
Deactivating mutation in SOST (Wnt inhibitor)
Autosomal recessive inheritance
Nl OC Possible inc alk phosphatase
Mutation in LRP5, prevents binding of DKK1 (Wnt inhibitor)
Autosomal dominant inheritance
Excessive BMP stimulation --> increased osteoblast formation
Patients usually die of R heart failure, Pulmonary HTN NO BIOPSY!!!! Require wheelchair by 3rd decade More common in kids XR? Moth eaten appearance of bone Surgical debridement, drainage, obliteration of dead space, wound coverage Cure = resolution of signs and sx for >1y Kids - use AB that covers TB can cause Pott's disease in staph/strep (empirical) spine CT guided needle bx (adults) for Cx 4-6 wks AB tx MSSA- nafcillin, oxacillin MRSA- vanco, dapto Strep- PCN G, ceftriaxone, cefazolin Enteric GNs- Cipro, ceftriaxone Serratia, Pseudomonasceftazidime, cefepime, piperacillintazobactam Anaerobes- clinda, metronidazole Surgical debridement if necrotic
Occurs over weeks/months/yrs; necrotic bone w/ loss of vascular supply, swelling
untreated acute osteomyelitis
Assess response after tx with ESR, CRP
bactermic seeding of bone, swelling, long bones (kids), vertebrae (adults), periosteal abscesses in kids Long bones - fever, chills, malaise, soft tissue swelling and pain Vertebrae- neck/back pain, localized tenderness, low/absent fever, neurological deficits (epidural abscess)
In presence of bacteremia, bacteria may get trapped in small end vessels. In kids, bacteria enter venous sinusoids of metaphysis in long bones via leaky capillary fenestrations. In adults, bacteria often seed in vertebral bodies (wellvascularized) or bugs can drain from Batson's venous plexus (from urinary tract) IV DRUG USERS? Sternoclavicular joint, SI joint, pubic bones
Kids- S. aureus, GBS (infants), CoAN staph Elderly- S. aureus, GramImmunocomp - fungi IVDU- S. aureus, P. aeruginosa, Serratia Sickle cell- S. aureus, Salmonella
MOST common in kids IVDU - novel organisms in unique Adults - elevated ESR/CRP sites XR? Takes a while to show signs, but periosteal elevation, areas of demineralization, loss of sharp bony margins, moth eaten appearance, possible soft tissue swelling CT? sensitive Bone scan? Early dz (lots FPs) MRI? GOLD Standard! detects early changes & abnl soft tissu; adjacent vertebrae involvement
increasing pain, skull/mandible/ small bones hand/ long bones/feet, mild fever, minimal drainage Contiguous Bacterial infection from localized ulceration/ trauma travel Diabetic osteomyelitis? Painless (due to peripheral neuropathy further to the bone in most DM pts) ulcer extending to bone, mild cellulitis, crepitance [If it probes to the bone, it's osteomyelitis]
Possible polymicrobial (see diabetic foot ulcer bacteria) Mixed gram+/-, anaerobes
Imaging hard to interpret bc surrounding soft tissue inf MOST common in adults Chronic skin ulcers (arterial sclerotic dz), trauma, diabetes, post-op ortho surgery, chronic edema Bone scan sometimes reveals contiguous spread from ulcer site Bone sample for culture
Revascularization Amputation/ surgical debridement Abs for 4-8wks (Avoid empiric ab tx)
Recent trauma (animal/ human bites) Immunocompromised RA/gout/sickle cell IVDU
Joint drainage (serial taps, open procedure) Systemic Abs 2-4wks
swollen, hot, monoarticular arthritis w/ passive motion; less Generally hematogeous spread of bacteria or possible uncommon - fever/chills iatrogenic spread (joint injections for RA/OA) Chronic septic arthritis Other infectious diseases causing arthritis
S. aureus Streptococci GN rods Mycobacteria (Tb) Lyme disease Fungi Rubella, mumps, parvovirus
Tap joint? Elevated WBC Gram stain & cx
Disseminated gonococcial infection (DGI)
Bactermic form: Dermatitis that coincides w/ pustules/papules that are sometimes hemorrhagic; centrifugic distribution, fever, tenosynovitis, polyarthalgia/arthritis Localized form: purulent arthritis (1,2 joints) Acute onset joint pain, effusion, erythema, warmth, fever
F>M Arthritis associated with gonococcal bacteremia Neisseria gonorrhoeae declining incidence
Sexually active young adult Timing associated with menses Pts w/ terminal complement deficiencies Joint replacement
Cultures from mucosal sites
Prosthetic joint infection Early (<3m after surgery)
Low grade sx, implant loosening, chronic joint pain Delayed (3-24m)
Acute contiguous infection from virulent pathogens seeded after S. aureus, surgery Streptococci, Gram rods, enterococci, anaerobes, fungi (rare) Chronic contiguous infection from less virulent pathogens CoNS (form biofilms seeded after surgery; well) usually biofilm-forming pathogens Hematogenous seeding from variety of sources (skin, resp, dental, UTI)
Rising incidence w/ increased joint replacement surgeries
XR? Lucency at bone/cement interface, loose cemented prosthesis Synovial fluid aspiration? Elevated WBCs w/ increased neutrophils Synovial fluid Cx may be negative if biofilm formation
One-step procedures (remove and replace prosthesis at same time) Two step procedures (debridement, removal, then replacement later) debridement and retention (stable joint w/ early inf) long term Ab (3-6m) for all
Late (>2y) Ehlers Danlos Syndrome (EDS) Classical Skin & joint hypermobility (Beighton's score >5 for joints), atrophic scarring (not well healed), easy bruising, smooth/velvety skin, hypotonia & decreased motor development
S. aureus, Streptococci, Gram rods, enterococci, anaerobes, fungi (rare) 1/5000 individuals; classical form is most common Autosomal dominant
Sonication of removed prosthesis for cx
Clinical exam for manifestations Beighton score baseline echocardiogram for kids <10 y.o. Evaluate clotting factors Tx manifesting sx Low-resistance exercise to increase muscle tone Vit. C & D, Ca supplem Avoid high impact force
Mutation in collagen type V (COL5A1, COL5A2), disrupting structural integrity of connective tissues
Hypermobile joints but do not have major/minor skin findings, soft skin w/ only minor extensibility, absence of skin/soft tissue abnl Severe generalized hypermobility, congenital bilateral hip dislocation, tissue fragility and skin hyperextensibility
Unclear but haploinsufficiency of tenascin X(TNXB) Mutation in collagen type I (COL1A1, COL1A2) causes abnormal processing of amino terminal ends
Autosomal dominant inheritance Autosomal dominant inheritance
Clinical & FH only No genetic testing Clinical genetic testing Very severe - dissection of carotid artery, arterial/digestive/ uterine fragility or rupture Clinical genetic testing Celiprolol (cardioprotective) 80% develop significant med probs by age 40 Sudden death (median age 48)
Arterial, digestive, uterine rupture/fragility, characteristic facial appearance (acrogeria, tightened skin over face, hollow Dominant-negative mutations in pro-a1(III) chain of collagen cheeks, thin upper lip and skin), extensive bruising, spontaneous type 3 pneumo/hemothorax, hypermobility of small joints, talipes equinovarus (clubfoot)
Autosomal dominant inheritance Family history Sudden death in close relative
Severe skin fragility, sagging/redundant skin, large hernias Deficiency in type I procollagen N-peptidase Generalized joint laxity, severe hypotonia and scoliosis at birth, scleral fragility, rupture of ocular globe Extremely tall (arm span longer than height), long fingers, dilated aortic root, ectopia lentis-dislocated lens, pectus carinatum OR pectus excavatum Mutation in PLOD1 causes decreased lysyl hydroxylase in dermis and loss of connective tissue cross-linking capabilities Connective tissue disorder caused by missense mutations in FBN-1 gene on q15, disrupting TGF-B-fibrillin complex and increasing amount of active TGF-B Decreased lysyl hydroxylase Abnl Fibrillin protein 3 collagen genes: COL2A1, COL11A1, COL11A2
Autosomal recessive inheritance Autosomal recessive inheritance
Clinical findings only (no genetic test!) Clinical genetic testing Clinical exam tests? Walker Murdoch wrist sign, Steinberg thumb sign Currently testing use of angiotensin II type I receptor antagonist (Losartan)
Cleft palate, bifid uvula, midfacial hypolasia (underdeveloped cheek bones, flattening of midface), high myopia causing retinal Mutations in any of detachment, early onset arthritis, MVP, later hearing loss Type 1 - mild sx, fx w/ minor trauma, no bony deformities, bluish-grey sclerae Type II - perinatal lethal form, multiple fx in utero, dark blue Group of heritable conditions characterized by bone fragility and low bone mass; usually caused by mutations that silence sclerae one allele, resulting in decreased amount of normal type I Type III- may have in utero fx or fx @ birth, thin ribs, popcorn collagen synthesized epiphyses, short stature, hearing loss common, dentinogenesis imperfecta (gray/brown teeth that break easily Mutations in COL1A1 and COL1A2; especially, substitution of and look translucent) any amino acid for glycine disrupts collagen helical molecule Type IV- mild-mod, maybe DI, sclerae nl or grey, some hearing loss
Autosomal dominant inheritance Genetic testing Multiple family members affected
Type I Osteogenesis Imperfecta Type II (OI) Type III Type IV
Point mutations with dominant-negative Prev? 6-7/100,00 effects cause structural defects in collagen
XR? Wormian bones Most autosomal dominant inheritance Skin bx? Analyze structure/quantity of type 1 collagen molecular genetic testing
Treat fx but avoid immobilization for long periods of time! Type II - perinatal lethal Use light-weight casts PT rodding Use high-risk Obs to manage pregnancy
Short stature w/ disproportionately short arms/legs, macrocephaly, frontal bossing, mid-face hypoplasia, hypotonia in infancy, delayed developmental milestones Pain in femur/tibia/vertebrae @ night, relieved by NSAIDs
Mutations in FGFR3 genes cause excessive signaling of FGFR3, resulting in impaired chondrocyte fx w/I epiphyseal growth plates
Compression of spinal cord/ upper airway obstruction increased risk of death in infancy
Dominant inheritance pattern
BENIGN >2cm? Osteoblastoma
Males age 10-25
Histology? central nidus of woven, hemorrhagic bone surrounded by reactive sclerosis CT? sclerotic bone on outside w/ pinpoint middle nidus
Remove to prevent recurrence
Chondroma / Endochondroma Osteochondroma
(Endochondroma - inside bone; Chondroma - outside bone) Incidental finding after fx Most common bone tumor, cartilaginous entity, medullary canal is contiguous all the way thru stalk, usually stop growing w/ pt
Residual bits of cartilage that were displaced during development Occurs when bits of cartilage from the physis that get incorporated into the bone begin to grow, producing a stalk in the bone Autosomal dominant disease
XR? Popcorn calcifications Histology? Benign cartilage Histology? Cartilage cap, bone marrow inside XR? Benign polypoid projections from cortical bone Increased alkaline phosphatase XR? Lysis, blastic sclerotic bone, or even mixed; ill defined border (R/O osteomyelitis), elevated periosteum (periosteal rxn) M>F Histology? Periosteal rxn Tumor resection, prosthesis MRI? Soft tissue extension CT? metastases
None - benign If cartilage cap >1cm, start to worry about development into chondrosarcoma (RARE)
Osteoblastic Fibroblastic Chrondroblastic Telangiectatic Parosteal Periosteal Central low-grade Secondary
Kids: occurs around knee Adults: axial skeleton Occur in the metaphysis, knee pain/swelling (loss of ROM),weight loss (disseminated), pathologic fx w/ nl activity
Neoadjuvant therapy (Chemo before surgery)
80% of metastases are to the lungs
Trunk/pelvis/long bones; pain, swelling, resistant to radiation/chemo (low blood supply/growth), possible dedifferentiation (abrupt transition from low--> high grade tumor) Flat or long bones of young children Translocation btwn EWS gene and FLI1 gene so ETS DNA binds at ETS DBD spot, causing loss of RNA recognitiion motif from EWS Caused by X-linked recessive mutation of dystrophin, resulting in absent (or <5%) dystrophin. W/o dystrophin, the sarcolemic membranes are leaky, there's secondary Absent dystrophin inflammation from necrosis, and cycles of degeneration & regeneration. X-linked recessive mutation resulting in decreased dystrophin Decreased dystrophin Maternal anticipation Autosomal dominant inheritance associated with trinucleotide (increases number of CTG repeats in myotonin-protein kinase gene on C19 CTG rpts) VERY VERY RARE M>F Adolescents/ young adults Most common MD, especially in children 1/3000 live births 1/30,000 live births
M=F 35-60 y.o.
XR? Popcorn calcification
Histology? "small round blue cell tumor" Imaging? Onion skin appearance Associated w/ dilated Histology? Increased CT, fibrofatty and macrophage infiltration, variable muscle fiber size and abnl cells, bluish cardiomyopathy Steroids at early age prolongs ability fibers are regenerating (inc DNA) to walk No cure! Limited life CK levels 10-100x>nl expectancy Similar histology to DMD Longer life expectancy (40-60y.o.)
Ewing sarcoma Muscular dystrophy Duchenne MD
Pseudohypertrophy (large calves), scoliosis, lumbar lordosis, protuberant abdomen, toe walking, Gower's sign, mental deficits Variable onset (5-15y.o.), similar symptoms as DMD but later onset and less severe Maternal anticipation, asymmetric distal weaknes w/ myotonia, pt can make a fist but can't open it back up easily; frontal balding, cataracts, cardiac conduction probs, endocrine dysfunction (hypogonadism, insulinR), GI hypomotility
Myotonic dystrophy type I
5-20/100,000 live births
Multisystem disorder; possible complete heart block
Central core disease
Autosomal dominant dz caused by point mutations of the ryanodine receptor gene on 19q, encoding the Ca-release hypotonia, poor feeding, high arched palate, delayed motor milestones, joint contractures, resp probs, pectus carinatum (bird channel of the sarcoplasmic reticulum of skeletal muscle; mutations of this gene also account for some cases of chest) inherited malignant hyperthermia exercise intolerance w/ premature fatigue in anaerobic ex, stiffness/weakness in exercising muscles relieved by rest; rhabdomyolysis w/ intense ex, second wind phenomenon Recurrent rhabdomyolysis in adults after prolonged exercise or fasting, proximal weakness later in life Maternal transmission, extra-muscular manifestations (in tissues/organs w/ high met rates) Furrowed brow, high-arched eyebrows
Autosomal dominant defect in ryanodine
Asymptomatic but affected mother --> drastic increase in trinucleotide rpts
Nl CK because not a lot of muscle degen/regen Histology? Central cores appear as central/ eccentric areas of muscle fibers w/o oxidative enzyme activity none
Known association w/ malignant hyperthermia- fever, muscle rigidity/necrosis, lactic acidosis (excessive Ca release)
Metabolic myopathy McArdle's disease
myophosphorylase deficiency, preventing the breakdown of Defect in glycogen glycogen to glucose (glycogen cannot be converted to G6P) breakdown Deficiency in enzyme required for transport of LCFA from cytosol to mitochondria
Histology? Abnormal deposits of glycogen Diagnosis needed to treat pts and avoid recurrent hospital admissions for renal failure
Carnitine palmitoyltransferase II deficiency
nl CK and EMG; dx requires direct measure of muscle CPT or genetic testing
Mitochondrial myopathy Progressive External Opthalmoplegia (PEO) - ptosis, opthalmoparesis MELAS - stroke <40, encephalopathy, RRF, lactic acidosis MERRF- myoclonus, epilepsy, ataxia, ragged red fibers Inflammatory myopathy
Abnormal amounts of mitochondria
Histology? Ragged red fibers representing abnl excess mitochondria
Histology? Perifascicular atrophy, inflammation of dermal-epidermal jx (interface dermatitis) Histology of Gottron's papules? Increased stratum cornum thickening, interface dermatitis Humoral immune process against vascular endothelium, resulting in the deposition of C5b-9 MAC from complement -> CD4+ T cell and B cell response --> ischemic muscle Complement mediated injury ischemic muscle injury 1/100,000 F>M Kids (more calcinosis) & adults Elevated muscle enzymes Myositis specific Abs (Anti Jo-1- worse prognosis, Anti Mi-2 -better prognosis) corticosteroids Methotrexate, azathioprine (LT) IV immunoglobulins
Heliotrope rash (periocular edema + violet color) on sunexposed areas; Gottron's papules (red, thickened plaque-like rashes on extensor surfaces), nailbed hemorrhages, violaceous erythema (shawl sign), dilated capillary loops of proximal nail folds, cutaneous calcinosis (ROCK hard)
Increased risk of malignancy in +/-4 yrs before/after dx Interstitial lung disease Diaphragm/ intercostal weakness --> resp arrest Cardiac rhythm disturbance
DM = DZ of body attacking blood vessels around muscle, SYMMETRIC WEAKNESS OF PROXIMAL MUSCLES (usually causing watershed inflammation around muscle. lower extremities first, then upper extremities)
Bx evidence? Necrosis, upregulation of MAC around photoprotection blood vessels, regeneration, varied fibers, inflammation around blood vessel (not in the muscle fibers) (CD4+ T/B cells) XR? Calcinosis MRI? Muscle inflammation
Proximal muscle weakness, no rash (more of just ruling out other myopathies…) Most common acquired myopathy >50y.o; Distal and asymmetric weakness of finger/wrist flexors, knee extensors, ankle dorsiflexors
Cell mediated immune response within the muscle (endomysial inflammation) involving T cells & macrophages ? Myopathy from following "toxins": Alcohol, Statins, Colchicine, Glucocorticoids, AZT Myopathy associated with following systemic diseases: Hypokalemia, Hypophosphatemia, Critical illness myopathy, or endocrine disorders (thyroid dz, parathyroid dz, adrenal disorders, hypopituitarism, acromegaly)
Histology? CD8+ T cell/mo infiltration in NORMAL looking muscle! Histology? Centrally-placed nuclei, red-rimmed vacuoles (fibers w/ holes in them)
Inclusion body myopathy Toxic Myopathy
Myopathies from systemic dz
Polymyalgia Rheumatica N/A (PR)
Dx critieria: Persistent proximal pain (>1m) involving (neck, shoulders, pelvic girdle- 2), >1h morning stiffness, abrupt onset of illness (<2wks), age>50, Rapid response to low dose prednisone, elevated ESR, absence of other disorders (flu, hypothyroidism)
Polygenic (environment & genetics)
Genetic component (HLA-DR)
F>M Extremely unlikely in pts <50y.o.
Activation of innate immune system leads to elevated levels of Genetic polymorphisms NE descent: TNF in adhesion molecules & 20-53/100,000 in pts TNF >50 (less in Italians)
Can be associated w/ Giant cell arteritis
Elevated ESR/CRP Thrombocytosis (hi platelets) Nl CPK Anemia of chronic dz Negative ANA, RF Clinical dx
Corticosteroids (Should be RAPID response if right dx)
Soft tissue pain disorder
Widespread and migratory pain/tenderness; waxes & wanes, No inflammation or tissue pathology! other nonspecifc MSK sx (IBS, headaches), fatigue, weight change, night sweats, weakness, SLEEP PROBLEMS, trouble Abnl neurochemistry affects pain perception; mood & sleep concentrating, TMJ, ENT sx, nondermatomal parasthesias disturbance along w/ changes in HPA axis causes decreased Physical/emotional blood flow to thalamus (pain perception center), resulting in triggers can precede or Chronic widespread pain involving ALL 4 quadrants and aggravate sx (virus, decreased pain thresholds axial skeleton; Presence of 11/18 tender points trauma, dep/anx)
Pain perception thresholds decreased (abnl neurochem)
Prev? 4% of population F>>M (10:1) Peak onset 30-55y.o. First degree relatives w/ FM (8x higher risk!) Mutations in serotonin gene
Clinical? Should not see weakness! Dramatic pain/tenderness at pressure points No anemia Nl CPK, aldolase Nl ESR/CRP Nl thyroid studies Negative ANA, RF
Pt education Anti-inflammatory/ analgesic meds (not better than placebo) AVOID NARCOTICS tricyclics (muscle relaxant, antidep) Serotonin reuptake inh Lyrica (decrease perception of pain) FITNESS TRAINING! (low impact aerobics and muscle strength)
Clinical exam? Prodrome malaise/fatigue, stiffness that improves w/ activity, non-reducable deformities (swanneck, boutonniere, trigger finger, MCP subluxation, ulnar dev, hammer toes) Elevated ESR/CRP Anemia Thrombocytosis +RF (80-85%, worse dz) Anti-CCP (90-95%SP) >2000 WBCs in joint fluid XR? periarticular osteopenia, uniform narrowing around joint, marginal erosions, C1-C2 subluxation, ulnar dev
Extra-articular manifestations? Heart - pericarditis, atherosclerosis Lung - pleural effusion, interstitial lung dz Skin - nodules, vasculitis Neuro- carpal tunnel (Bilateral), cervical myelopathy, entrapment neuropathy Heme- anemic, thrombocytosis, FELTY'S TRIAD (RA, leukopenia, splenomegaly) Bone- osteopenia Eye- inflammation Kidney - rare Risk for neuro damage w/ C1-C2 subluxation
NSAIDS DMARDS: -Immunosuppressants (MTX, leflunomide, azathioprine) - secondary agents (hydroxychloroquine, glucocorticoids) -TNFa antagonists (Etanercept, Infliximab, Adalimumab, Golimumab) -IL-1R Antagonists (Anakinra) -T cell costimulatory blockers (Abatacept) -Combo tx
increased angiogenesis to joint space, Hyperplastic synovia, hypertrophic synoviocytes, painful overgrown synovia (PANNUS) Morning stiffness (>1h), 3+ joint arthritis, hand joint arthritis, symmetric, rheumatoid nodules (extensor surfaces, pressure points), +RF, XR changes [4/7 criteria for 6+ wks to R/O inf] Fusiform swelling, SPARES THE DIP JOINT! Systemic sx (fever/malaise, poor energy, weight loss, tissue damage in other organs)
Aberrant immune response in genetically predisposed person leads to synovial inflammation and destruction of the joint Genetic & environmental factors--> innate immunity->macrophages--> T cells through TNFa and osteoclasts through RANKL; when DCs get to lymphoid organs, they activate T/B cells that release inflammatory factors/antibodies into the joint. Cytokines, Proteinases, cathepsins responsible for joint destruction. RANKL increases osteoclasts causing bone erosion. Prev? 1% of pop F>M (2.5:1) Peak onset? 35-50y.o. RA in men <45 unusual! First degree relatives w/ RA HLA-DR4 (shared epitope- HLADRB1) SMOKING!!! (2 copies of SE + smoker = 21x RA risk) periodontal dz mucosal surface toxicity
W/ age, side chains in cartilage shrink and hold less water = less resilience & more dessication = stress fx & fissures Use-related pain, loss of ROM Morning stiffness <30min Bouchards (PIP) & Heberdens (DIP) nodes Crepitus Mild effusion (but NOT warm) Mal-alignment of joints (bowlegged-varus; knock-kneed-valgus) SPARES MCP joints!! Chondrocytes try to make new collagen but there is a shift towards collagen 1, 3, 10 --> shortened proteoglycans (less H2O retention) 1. Edema of ECM w/ loss of chondrocytes & smooth cartilage causing microcracks 2. Microcracks deepen to form vertical fissures & pits 3. Fissures loosen & fragment, forming erosions & mild synovial inflammation (from MMPs). As body tries to repair, it scleroses and forms osteophytes. Focal loss of articular cartilage followed by hypertrophism of underlying bone and formation of osteophytes at joint margin Nl ESR/CRP/platelets Nl hematocrit <2000 WBC in joint fluid XR? Osteophytes (bone spurs), asymmetric joint space narrowing, NO PERIARTICULAR OSTEOPENIA!
Degenerative joint disease
Trauma Infection Crystsal dz Neuropathy
Acetaminophen NSAIDs Eventual joint replacement surgery
beaked nose) mat telangiectasias dilated capillary loops at proximal nail folds leukoderma (salt&pepper skin). Telangiectases Localized cutaneous SS morphea (erythematous plaques that are proximal.Inflammation. dactylitis (sausage digits. cough. decreased chest wall expansion. tophi >6.7mg/dL solubility of monosodium urate crystals Paget's. asymmetrical sacroilitis & spondylitis. sclerodactyly (skin tightening due to fibrotic changes --> ischemia & pitting of fingertips--> autoamputation) facial disfigurement (microstomia . retroauricular. conjunctivitis. isolated? cutaneous lupus) Chronic fatigue! Raynaud's periungal erythema Cutaneous vasculitis (palpable purpura) Seen w/I first few months of life Unclear but thought to be of 2 mechanisms: 1. hard to trace bone margins of SI joint. fever/leukocytosis. loss of flexion at back Classic . (somewhat older than lupus) XR? Bone resoprtion of digits. drugs. often on hard palate) Arthritis (reducable deformities. low dose steroids (but watch renal!) Raynauds? Smoking cessation Lungs? Heavy immunosuppression Pulmonary fibrosis (caused by fibrosing alveolitis. silica) Positive ANA.o. PT.tx ACE inh Diffuse Localized skin involvement (distal/upper extremities). follicular plugging. polymyositis. arrythmias Widespread skin involvement & rapid progression Crackles w/ inhalation Onset of skin changes w/I 1 year of Raynauds Truncal & acral skin involvement PFTs detect poor gas exchange XR? Interstitial fibrosis CT? ground glass opacities in lung SRC histology? Sheared RBCs. renal insufficiency. affected organs Autoimmune mediated diffuse fibrosis of skin & internal organs F>M Cell mediated and humoral immunity Onset age? 30-50y. & serum of affected pts. GERD (from fibrotic esophagus) Scleroderma renal crisis (SRC) malignant hypertension. Autoantibodies to phospholipids produce nuclear autoantibodies hypercoaguble state and clots (antiphospholipid syndrome thrombosis. paradoxical prolonged PTT) Rashes? Topical steroids Joint pain? NSAIDs FH (mostly sporadic tho) Environmental factors (uv light. anti-phospholipid Abs) Neurologic (seizures. Anti-Scl-70 (nucleolar pattern ANA).o. arthritis of girdle joints. 3. small joint enthesitis. positive direct Race .Indomethacin (acute pain relief) ALWAYS TAP JOINT & CULTURE FLUID! (yellow parallel crystals) XR? Nl mineralization. wall fibrosis SRC . GERD (from fibrotic esophagus) NSAIDs & glucocortocoids for pain & inflammation Chronic inflammation causes bone formation and erosion --> fusion of joints (ossification of annulus fibrosus in vertebrae) Axial arthritis (bilateral sacroilitis. Chronic inflammatory causing inflammation) F>M (9:1) systemic autoimmune Peak incidence ages 15dz characterized by anti40y. overhanging edges Colchicine (acute pain relief. arthritis mutilans (teloscoping digitsjust skin bc bone has been eroded away). psychosis) Malar rash (spares nasal labial folds!) Discoid rash (erythematous scaling. submental regions) Blood d/o (hemolytic anemia. Psoriasis certain cancers excessive alcohol intake Co-infection of joint NSAIDs.genetically susceptible person w/ HLAB27 is exposed to unkwn antigen that causes an immune response that exhibits cross-reactivity w/ self tissues..later onset Dysphagia. narrowing of lumen. smoking. females 16/1000 Equal incidence after menopause! M>F (5:1) Age onset? M 40-50. spondylitis). psoriasis. anti-RNP. systemic arthalgias/inflammation induced/triggered by procainaminde. anti-SM. low complement Prev? 1/2000 Others? Antimalarials (hydroxychloroquine) Systemic corticosteroids for serious complications Immunosuppressants for steroidresistance Accelerated atherosclerosis Neonatal lupus erythematous pathces that form blanchable rings on head/neck Lack skin findings. causes dz bc 1. psoriatic nails involvement w/ sausage digits Symmetric polyarthritis (indistinguishable from RA except RF-) Ankylosing spondylitis w/ or w/o peripheral arthritis but +psoriasis Inflammatory arthritis associated w/ psoriasis HLA-B27 (see AS path) XR? Pencil and cup formation (peripheral phalynx whittled down to pencil joint and distally has extra bone formation to where it looks like a cup). Enthesitis = primary hallmark of Spondyloarthropathies. Asymmetric. pregnancy morbidity. punched out erosions w/ sclerotic borders. leukopenia. slower pace of progression Limited (CREST) Calcinosis. spinal cord compression. prostacyclin derivatives Pulmonary hypertension (no fibrosis) . iritis. quinidine Mom w/ lupus Thrombocytopenia Anti-rho antibodies Positive ANA congenital heart block Drug-induced lupus Scleroderma (SS) Major organ involvement! proximal scleroderma (hardening of skin) extensive fibrosis. 2. thrombocytopenia) Renal d/o (proteinuria. appears like cellulitis/septic joint. peripheral joints. inflammation precedes fibrosis. dysregulated endochondral bone formation at sites of enthesopathy. leukemia. lip retraction.SLE. low dose steroids (but watch renal!) Raynaud's? Smoking cessation PAH? Oxygen. infections. erosion of entire bone in digit (telescoping). sparing knuckles. conduction abnl. certain meds. or other conditions cause difficulties excreting uric acid Hyperuricemia --> tophi (uric acid deposition that are engulfed by granulocytes) --> inflammation (NALP3 inflammasome)--> lactate production & pH drop --> formation of more crystals --> more inflammatory cells recruited --> renal damage if deposited on tubules Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Episodic monoarticular Gout Polyarticular Tophaceous gout Crystals in WBCs = active gout flare Hyperuricemia (except during flare) Painful/red/swollen joints/bursa. anti-Ro/La. skin discoloration/firmness/induration) Scleroderma + one or more features of other connective tissue disease Overlap syndromes Mixed connective tissue disease (MCTD) . Sclerodactyly.PIP swelling & inflammation). PT. acute anterior uveitis (inflamed iris). excess bone formation near where tendon would insert (enthesitis evidence) Psoriatic Arthritis . 2. nail fold involvement. calcium channel blockers.new bone formed in inappropriate location cause fusion through T-spine) Ankylosing Spondylitis M>F Age onset? 20s HLA-B27 Pneumonia. excess deposition of collagen by fibroblasts --> all lead to impaired fx of skin. look like white dots. lymphopenia. Esophageal dysmotility. symmetric) Photosensitivity (erythema on distal hands. Raynaud's (long duration). cauda equina syndrome) Loss of nl spine curvature & ability to flex Symptoms progress upwards (start in SI joint --> cervical spine) Molecular mimicry impt. podagra (1st MTP). hispanics Coombs. causing clinical expression of spondyloarthropathy (joint dz of vertebral column) High levels of TNFa in SI joints.atrophy. extraskeltal manifestations (aortic insufficiency. deficiency of salvage enzyme HGPRT) Underexcretion of uric acid? (~90%) hereditary factors. causing syndesmophyte formation Immunosuppressants only help peripheral arthritis TNF inhibitors relieve axial arthritis XR? Fuzzy.DIP joints of hands & feet Arthritis mutilans w/ sacroilitis Peripheral polyarthritis (symmetrical). polyarticular. SS. etc) or problems with purine synthesis (overproduction of PRPP synthetase. lungs.pursed mouth. subcutaneous calcinosis Widemouth diverticuli Watermelon stomach (telangiectases in stomach) pericarditis.anti-RNA pol III Anti-Scl-70 Ab Tendon friction rubs SRC? ACE inh GERD? PPIs MSK? NSAIDs. pauciarticular (<4). Anticentromere Lung impairment (dyspnea on exertion. pulmonary vasculopathy). dispigmentation. cellular casts) +ANA Immunologic d/o (anti-DNA. F postmenopause Hyperuricemia. pericarditis) Oral ulcers (PAINLESS. prophylactic w/ LT meds) Probenecid (chronic gout) Allopurinol (chronic gout) Initial tx for chronic gout can actually increase the severity/freq of acute attacks so take prophylactic colchicine simultaneously Systemic Lupus Erythematosus (SLE) Serositis (pleuritis.Disease Clinical Variants Defining Characteristics Pathogenesis Overproduction of uric acid? (~10%) High nucleic acid turnover in predisposed populations (Paget's.early onset Dysphagia. tophi (distal joints. anti-cardiolipin Abs. bamboo spine (syndesmophytes. feel like gravel) Prev? Males 5-28/1000. calcinosis Positive ANA. microangiopathic hemolytic anemia . & positive anti-RNP Anti-RNP Abs Histology? Nl epidermis but extensive collagen deposition & loss of epidermal appendage structures Anti-centromere Abs GERD? PPIs MSK? NSAIDs. pulmonary fibrosis) (General) Unclear but key features? Endothelial cell damage (vascular injury). Autoantibody-mediated inflammation (autoantibodies form immune complexes that drive complement consumption.A.A. Deregulated osteoclast activity --> bone erosion. bursa. hydralazine.
can't climb a tree" Arthritis. C. conjunctivitis.deep ulcer w/ lots of pus. Salmonella. uveitis. joint activity parallels bowel dz. Yersinia. GI infections . axial involvement (identical to AS. Sterile joint inflammation that develops after infection (throat. joint activity does not parallel bowel dz). uveitis) NSAIDs & glucocortocoids for pain & inflammation Arthritis associated with Crohn's Dz & ulcerative colitis HLA-B27 (See AS path) Immunosuppressants only help peripheral arthritis TNF inhibitors relieve axial arthritis . but can have recurrences Inflammatory bowel associated arthritis peripheral joint arthritis (pauciarticular.palms & soles. tenosynovitis.Chlamydia. Campylobacter. Circinate balanitis. pyoderma . GU. whitish pustule that develops scales. Shigella.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications "Can't see. enthesopathies). osteitis. skin (kertoderma blenorrhagicum.painless. tendonitis.dificile) (See AS path) Reiter's / Reactive arthritis M=F young adults HLA-B27 Spontaneous recovery. shallow erythematous ulcer on gland skin) & mucus membrane lesions. extra-articular features (erythema nodosumPAINFUL. mostly asymmetrical. enthesopathy. myalgia. can't pee.
vit D supplementation for immunocomp. 1&2 (thicker but limited to skin). avoid mid-day sun. protective clothing. monitor CHANGES in lesion . Importance for early detection and treatment (cure rates >90%) Staging .0 (tumor in epidermis). vit D supplementation for immunocomp. no sunbathing/ tanning bed. 4 (metastatic. daily use of sunscreen.CAPABLE OF DEVELOPING INTO SCC Protective clothing. daily use of sunscreen. no sunbathing/ tanning bed. daily use of sunscreen. self-skin exams. no sunbathing/ tanning bed. 3 (LN). systemicmedian survival of 7. screening for field disease changes .Screening / Education Protective clothing.5m) Emphasize prevention (sunscreen. vit D supplemenation) Need to talk to parents about how size of congenital nevi can affect risk for development of MM. vit D supplementation for immunocomp. grafting). surgical options (staged removals. TBSE. screening for recurrent BCC Protective clothing.
Screening / Education Oral form of Mucus Membrane Pemphigoid has better prognosis (very little scarring) Pretty good prognosis with treatment Worrisome in diabetics or pts with autoimmune dz .
bleach bathes Avoid gross hot tubs! Prevention (bleach baths.Screening / Education Prevention to avoid recurrenceAntibmicrobial washes. treating chronic carrier state w/ nasal Ab creams) Examine (& possibly treat) home/school for infected contacts! Screen for STDs in young adults Avoid skin-skin contact during active outbreaks Prevention with immunization w/ zoster in people > 50y. GAS/GBS screening for women undergoing C/S .o. treating chronic carrier state w/ nasal Ab creams) Prevention (bleach baths.
sedentary lifestyle) Prophylactic bisphosphonate treatment prior to surgery!!! .Screening / Education Adjustment of risk factors (excessive alcohol.
Screening / Education Stay active!! .
need to be aware of risk for malignant hyperthermia w/ anesthesia age/gender appropriate cancer screening .Screening / Education Diagnosis is impt in case patient needs surgery ever.
Screening / Education .
spinal extension exercises high risk for traumatic fractures .Screening / Education Avoid sun exposure. use sunscreen! Counsel on posture. stretching.
Screening / Education .
TLC nl/. FEV1/FVC nl. NO PREEXISTING ACUTE TRAUMA Pathogenesis abnl accumulation of fluid in the lung outside of the vasculature Etiologies Epidemiology Risk factors Lab/Imaging Treatment Resolution? Hydrostatic: intact alv epithelium pumps fluid out w/ Na/K ATPase. abnl anatomy. FEV1 nl. volumes shift towards RV neuromuscular dz: somewhat higher RV. sx of congestive heart failure. low IC PFTs: FVC nl/. destroyed alveoli--> decreased functional space & DLCO ability to move air out of lungs is impaired so takes longer Hydrostatic: risk CXR: Hydrostatic: factors for heart bilat interstitial dz markings @ basal lung/ perihilar area. FEV. FVC. spirogram shows no late vol changes/ rapid upstroke. alv interstitium. Complications increased hospital stay (leading to other comorbidities) and high mortality for permeability edema Thickened membranes = diffusion. reduced airflow during inspiration (-)P inside the airway sucks trachea walls in while Patm around trachea pulls airways closed) Patm > Paw during inspiration reduces airflow and causes aw collapse. concavity on exp limb of flow-vol. muscular weakness. disease/ obstruction outside of the lung Equal pressure point has variable migration depending on transmural pressure. FEV. LV heart failure (MI. asthma severe dynamic compression --> hyperinflation as a compensatory mechanism to get more air out allows increased lung recoil so lung can expel more air. DLCO Permeability: alv epithelium injured so takes longer to resolve. separation of interstitium w/ protein coat (pink hyaline membrane) PFTs: FEV1/FVC<70. trauma. gravitational gradient (more edema at base). inhalation. hi comp areas (perihilar interstitium. edema: diffuse leakage of space overflows the alveolus gradient btwn with proteinaceous fluid (can fluid (patchy. permeability: dense liver appearance. tx primary injury cause. Permeability . supportive care Obstructive lung disease Restrictive lung disease Parenchymal lung reduced lung volumes disease (interstitial lung dz). DLCO pulmonary vascular disorder Central Airway Obstruction Extra-thoracic obstruction Plateau on inspiration. bilateral interstitial fluid & be caused by pneumonia. tx underlying cause. acute lymphatic flow inf. aspiration. alveolus).patchy. RV nl. laryngeal edema.RBCs/ WBCs. nl expiration Tracheomalacia. volumes (due to air trapping). Hydrostatic edema (most common): Increased hydrostatic IV fluids pressure (due to LV heart failure) injury to capillaries = Pulm edema --> backup of (free radicals. enlarged heart. cardiac dysfxn. nl anatomy. bronchospasm seen more commonly.alv spaces filled w/ pink edema. OBESITY . Kerly's B lines (horizontal lines towards edge of XR). less shifted towards RV) less total volume but no problems with air flow PFTs: nl or >70 FEV1/FVC. hypoxia hydrostatic pulm edema: fluid accumulates in low P. FVC. no CHF Emphysema. flow-volume has VC. asymm infiltrates. nl heart histology: Hydrostatic . tracheal stenosis. ARDS) capillary leakage into interstitial interstitial hydrost permeability pulm pressure. manage fluid balance. heterogenous patchiness. PFT: Plateau in insp laryngeal limb paralysis. fluid into pulm vasculature --> chemicals) blood vessel distention by Jreceptors --> tachypnea Starlings law reasons for edema: Permeability edema (more gradient btwn severe): direct injury to capillary & capillaries (ALI. spirogram shows slow initial upstroke & late vol changes. sepsis. fluid overload.Disease Pulmonary Edema Clinical Variants Defining Characteristics tachypnea. pancreatitis. protein leakage. chronic CHF). oncotic press. nonparenchymal (chest wall disorder. renal failure. transfusion) leakiness of capillaries. accumulation). tracheal strictures from ET tube. chronic bronchitis.
limb tracheomalacia. PFT: plateau in exp tracheal tumors. reduced airflow during expiration Etiologies Ppl > Paw during expiration reduces airflow and causes aw collapse.Disease Clinical Variants Intra-thoracic obstruction Defining Characteristics Plateau on expiration Pathogenesis Equal pressure point has variable migration depending on transmural pressure. mediastinal lymph nodes . nl inspiration asthma Epidemiology Risk factors Lab/Imaging Treatment Complications Tracheal lesions. tracheal inflammation.
pirbuterol. diffuse sometimes emphysema in other phosphodiesterase variants) inhibitors (theophyline. anticholinergics like ipatropium) hoarseness = common side effect of steroids Could require oxygen. cough. problems with driving pressure accessory muscle use. tracheal stricture hyper capillary surface #4 mortality in responsiveness.o. distant mismatch. flat diaphragm. pulmonary rehabilitation. DLCO all persons >45 y. inspiratory capacity). (decreased elastic recoil) retraction of intercostal and/or airflow resistance spaces). tripod position Subglottic stenosis. cell mediators? F>M exposure to Epithelial cells. w/ chronic cough/ sputum production & exposure/ risk factor hx should be tested for airflow limitation (even if no dyspnea) spirometry = gold std CXR: retrosternal air space ( lucency). middle aged occupational CD8+ (TH1). early presentation A1AT def (protease inhibitor that most common prevents destruction of alveolar phenotype? PiZZ wall)--> loss of a1 globulin (Z allele is a single point mutation that causes severe dz) alpha1antitrypsin deficiency. mometasone) home O2 if hypoxemic (prevents cor pulmonale) Chronic bronchitis typically presented as overweight. and recruitment of D13 = release of associated w/ abnl inflammatory response proteases (presence of protease inhibitors less effective due to to noxious tobacco) = destruction of particles/gases alveolar wall hyperinflation of lungs (low diaphragm position. Severe (pursed-lip breathing.) dusts & chems/ neutrophils infections/ SES SMOKING (USA) develops in about nutrition 15% of smokers Air pollution (global) decreased elastic recoil management? Prevent dz progression. lung vol (TLC & RV. reduce mortality drugs generally less effective Short acting bronchodilators (Bagonists . edematous. (bullae = sac-like wheezing. metaproterenol. alveolar ventilation.salmeterol. release of chemotactic factors = progressive. dyspnea at rest exposure to smoke = activation SMOKING of alveolar macrophages = release of chemotactic factors = loss of elastic recruitment of neutrophils = recoil release of proteases (presence of protease inhibitors less chronic productive cough for 3 consecutive effective due to tobacco/infection) = mucus months for 2 hypersecretion consecutive years . breath/heart sounds. roflumilast) PFT: see obstructive dz responds poorly to meds anti-inflammatory inhaled steroids (fluticasone. hyperinflation CT R/Os alt dx Treatment Complications COPD Emphysema (blow a balloon up and release it? No air flows out bc loss of elastic recoil) Equal pressure point migrates independently of location/ pressure relationships Airflow limitation that is exposure to smoke = activation of alveolar macrophages = not fully reversible. kerosine. goiter.Disease Clinical Variants Fixed lesion Defining Characteristics Plateau on inspiration & expiration Pathogenesis Etiologies large tumor Epidemiology Risk factors Lab/Imaging PFT: plateau in exp & insp limbs PFT: see obstructive dz. wheezing. PiSZ smokers long acting bronchodilators (Bagonists .albuterol. and/or lung transplantation cor pulmonale A1AT deficiency panacinar emphysema DOE. CXR: radiolucency in formoterol) base of lung (vs. tetherings that support airway = barrel chest). dust. (~50y. Alveoli destruction = VQ hyper-resonance. levalbuterol. prevent/ treat exacerbations. area = diffusion. productive cough. cyanotic. world & USA lung growth. FH of A1AT def. improve ex tolerance. lung volume reduction surgery. improve health status. budesonide. dypsnea or dynamic airway acute chest illness compression = abnl (initially DOE but then enlargement of small airways starts to affect DALYs). tobacco smoke/ macrophages. relieve sx. bullous changes.o. smoke. prolonged abnormalities) expiratory time.
immediate Type I IgE retraction of intercostal mediated spaces bronchoconstriction chronic. early AM. CD4+ (TH2). FEV1/FVC. lung hyperinflation (low allergic asthma diaphragm position. IgE.Disease Asthma Clinical Variants Defining Characteristics Pathogenesis hygiene hypothesis: early exposure to infectious agents= TH1 response= suppression of TH2 activation= allergy /asthma frequency. indoor/ outdoor pollutants. infections. IL4. certain meds. FEV1. mast cells. fibrosis.(wheezing. foods/ preservatives. occupational exp. eosin. Factors contributing to severity? Environmental (animal/insect/ mold/outdoor allergens). edema. significant bronchodilator response (loss of FVC. theophylline. vagal reflex) expiratory time). prolong forced short sprints. mild persistent. hyperresponsive airflow limitation Etiologies inflammatory cell mediators? Epith cells. Xolair) methacholine + rescue meds challenge (high NPV (SABA . widespread/ varying obstruction.Singulair. distant nocturnal asthma (vagal heart/breath sounds) reflex) severe disease? Accessory resp muscles. epithelial damage) = Smooth muscle hypertrophy = reversible bronchoconstriction. thick BM. hyperresonance. infiltration of inflammatory cells. immunotherapy cold= vagal reflex = ACh = bronchoconstriction Epidemiology Risk factors Lab/Imaging PFT: exp arm has concavity. people less likely to be exposed to these infections today= TH2 cells mediate onset of asthma Airway remodeling occurs in pts w/ uncontrolled chronic asthma (older pts) morphological changes in asthma (hyperplastic mucus gland/goblet cells. severe persistent) (inhaled corticosteroids + avoid chronic LABA steroid use leukotrieneR blockers . maintenance meds moderate persistent. nl DLCO) Treatment Complications exercise-induced asthma Airflow obstruction (15-30min post exercise. FEV1/FVC <70 but other values highly variable. inflammatory airway dz w/ recurrent sz (esp @ night. peak flow meters for varying levels of home monitoring severity (intermittent.albuterol) so R/O asthma in pt w/ Short term oral atypical sx) steroids (prednisone) for CXR: nl flareups subQ allergen immunotherapy if allergic asthma .
immotile ciliary syndrome. upon expiration. iatrogenic) chest pain!! Spontaneous (Primary absence of lung disease. Kartagener syndrome (KS) Clinical Variants Acute Chronic Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging PIO2:FIO2 2. male/female infertility. rupture of trachea/ main bronchi. ribs go in & try to deflate the lung. or else death! CXR: Air collection btwn right diaphragm & liver or peritoneal cavity CXR: Abnormal lucencies w/I lung parenchyma Pneumoperitoneum Lung cavities Pulmonary nodules (<3cm). collapse of alveoli) Collapsed lung (air btwn visceral & parietal pleura). pressure -> more (-) but lung does not inflate. ribs go out & try to inflate the lung Balls of air in lung Multiple rib fractures. thin white line (Spont) Histology: 2nd spont PTX has rupture of subpleural emphysematous blebs in lung apices Repeated PTXs? Pleurodesis MRI: ruptured bullae (installment of from emphysema (2 sclerosing agent -talcso visceral & parietal spont) surfaces adhere) Small PTX in healthy Tension PTX is person? Observe. medical emergency!! supplemental O2 Causes shift of mediastinum = Large PTX or increased symptomatic person? interthoracic pressure = disrupts systemic Chest tube circulation placement. trachea shifts to opposite side (Subplural alveoli rupture into trauma. acquires soft tissue (gray-white) density.partial collapse of lung. low BP (due to low venous return). fallopian tubes.complication of underlying lung dz like COPD) Tension? Hi RR. the lung collapses CXR: increased lucency.Disease Hypoxia Primary cilia dyskinesia (PCD). some ribs trauma free-flowing. dissection of air from neck/abdomen Emphysema CXR: bilateral balls of air Bind and fixate the ribsPoor prognosis due to ineffective ventilation Lung bullae Pneumomediastinum gas in the interstices of mediastinum Tracheo-bronchial tree/ esophagus rupture from trauma/ prolonged vomiting Fistula btwn 2 structures. & no flow). and sperm flagella chronic sinusitis/ bronchiectasis. consolidation (think pneumonia) Infection. pulmonary masses (>3cm). w/o (-)Ppl. hypoxemia (VQ Traumatic (Penetrating mismatch). Secondary . Pleuritic trauma. tumors . respiratory tract. vasculitis. Ventilators CXR: air along L heart border.3-DPG Treatment Complications defective ciliary action lining the TRIAD: L-R pattern defects (situs inversus). Tension (causes heart to hyperresonant push to opposite side) percussion. emergent decompression w/ needle (esp for Tension PTX!) Flail chest Upon inspiration. causes air to move back & forth rather than pulling air from outside into the chest Destruction of alveoli in emphysema/ lung dz cause damaged areas to fill with air & bulge Non-subpleural alveolar rupture with air pouring into the mediastinum. decreased lung vol. continuous diaphragm sign Pneumopericardium Air in the pericardial space (around heart). active pleural space) Hole in the lung-. sudden onset of dypsnea (less efficient muscle fx). when the pt inspires. hydrocephaly (CSF doesn't move in brain ventricles) Autosomal recessive mutation in gene hydin failed dynein motors or central pair assembly = cilia paralysis Pneumothorax (atelectasis .inspiration > Ppl = 0 (since now in connection w/ atm. muffled heart sounds Requires immediate identification and treatment. tension pnemothorax can push heart over to opposite side. HR. focal area of absent breath sounds.
PE. foreign body Viral. Exudative (occur when pleuritic chest pain Starling's forces: Pcap (CHF. (lung cancer. dec serum onc press) . heart. local dz stimulates pleural fluid formation. organized: scarring. inc cap Decreased breath sounds vol overload). tx w/ Abx 2. blunted costophrenic angle. obstruct of lymph synd). pressure (cirrhosis. empty alveolus space CXR: Complete Opacification Hemithorax. hypersensitivity rxns Epidemiology Risk factors Lab/Imaging CXR: Complete Opacification Hemithorax.inc hydrostatic press. Lymphocytes? cancer.low protein content decreased pleural pressure (atelectasis. mycoplasma pneumoniae.cancer). consolidation Histology: thickened septa due to infiltration of inflammatory cells. loss of nl structures at lung base thoracentesis!! (dx & tx effects) Light's criteria >1 exudative Cell types: Neutrophils? inf/symp causes. trauma). requires chest tube drainage 3. meniscus sign (upside down U). cap oncotic over area of pleural perm -pneumonia. which becomes a vulnerable place due to large size & surface area. post surgical TB (global cause) Hepatic hydrothorax transudative pleural effusion ascites liver related pleural effusion due cirrhosis. Common sx? Dyspnea (increased inefficiency of negative pressure pulls fluid in. trapped lung) . RBCs: hemorrhagic (malignancy. fibrinopurulent: loculations. malignancy. low ventilation) OR R->L shunt hypoxemia infiltration of lymphocytes & monocytes expands the interstitium either spontaneously resolves or persists (if persists. nephrotic effusion (Base of lung). less resorption) 3 stages: 1. and relatively leaky borders from resp muscles. cough. hemothorax Treatment Complications Alveolitis Pleural effusion pathological accumulation of Mediastinum pushed away from affected side fluid in pleural space. leads to interstitial fibrosis) Etiologies Obstructive Atx of whole lung? Cancer. liver 1. requires surgical decortication 40% of bacterial pneumonia develop PPE Thickened visceral membrane (makes lung expansion difficult) Antiobiotics for exudative stage. lymphoma) capillary barrier disrupted so high protein content Increased permeability pleural dz. mucus plug. PNA/ Infxn. TB. exudative: inflammatory/ capillary leakage. liver to high portal pressure (from failure cirrhosis usually) RUQ diuretics Beta blocker to decrease portal pressure transplant do not attempt pleurodesis!! Parapneumonic Effusions (PPE) Exudative pleural effusion no bacteria or pus in pleural fluid Pleural effusion ipsilaterally Pneumonias associated with underlying pneumonia.fluid moves into lung Kidney. PE. NOT gap jx btwn mesothelial cells hypoxemia). infxn Transudative (occur when systemic imbalance of Starling's forces . due to inflammed visceral fluid (inc fluid prod. TB. pleural peel formation.Disease Atelectasis Clinical Variants Defining Characteristics Mediastinum pulled towards affected side on CXR Pathogenesis Collapse of alveoli or partial lung --> VQ mismatch hypoxemia (perfusion.5 million pleural failure effusions yrly malignancy. Lymphatic clearance dullness to percussion drainage . chest tube drainage for fibrinopurulent stage. decortication for organized stage complicated bloody surgical procedure .
vasoconstriction. does not smell (empyema). inotropes for Class IV prostacyclins. nl causes vasodilation. Echo.empyema will look different based on viewing position Thoracentesis: gross pus or positive gram stain. broken down by phosphodiesterase CXR: right heart enlargement EKG: signs of right heart strain (high R wave in V1 suggests increased ventricular mass) Doppler Echo: bulging of RV septum. scleroderma need supplemental O2. congenital heart dz (atrialpersistent septal defect shunts systemic pulmonary HTN of blood into pulm circ). or thromboembolic dz Proliferation. St. other disorders. endoglin).Disease Empyema Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Exudative pleural effusion Infection (collection of pus) in pleural space CXR: distinguish from Drainage neoplasm (which always appears spherical) . d/os like CTD (Scleroderma). Alk1. chronic hemolytic doesn't close) anemia ( NO = vasoconstriction) Endothelin pathway: in PAH= vasoconstriction & smooth muscle hypertrophy Nitric oxide pathway: in PAH. pleural fluid culturesfluid cytology pleural (always low positive in 60-80% possible pleural bx Malignant Pleural effusion Exudative pleural effusion hematogenous metastases to parietal pleura cancer cells erode through visceral pleura cancer cells occlude lymphatics 2nd most common cause for exudative effusion pleurodesis high recurrence rate. heritable (BMPR2. aggressive tx digoxin for CHF. represents high lipid content in pleural space trauma or CANCER! Pulmonary Arterial PAH Hypertension (PAH) (WHO Group 1) mPAP >= 25 PWP <= 15 No significant obstructive/ restrictive lung dz. remodeling idiopathic (see below). drug/ HIV(Δs vascular mediators to toxin induced favor vasoconstriction). left heart dz. remodeling). hemodynamic improvement. wort). newborns schistosomiasis (eggs from (foramen ovale organism occlude pulm artery. PDE-5 inhibitors monitor tx effects via exercise capacity. QoL . milky white pleural effusion. (amphetamines. enlarged RV Right heart catheterization: evaluation of mPAP & PCW Blood tests for underlying causes oral anticoagulants. no pus disruption of thoracic duct or LN dissection. thrombosis. usually represent an advanced malignancy Chylothorax Exudative pleural effusion turbid. regurgitant tricuspid valve. functional class. cocaine. John's portopulmonary dz ( portal vein press. endothelin antagonists. backflows to heart). Pts with HIV or diuretics.
diastolic dysfunction mPAP >= 25 PWP > 15 no meds approved for this population Pulmonary arterial hypertension from lung disease/ hypoxia (WHO Group 3) severely decreased DLCO chronic hypoxemia leads to shunting of blood away from non-ventilated areas and increased backflow to RV (L-R shunt). F>M (2:1) Risk factors Lab/Imaging histology? Intimal/ smooth muscle/ adventitia hypertrophy & formation of plexiform lesions Treatment see PAH Complications High mortality without treatment (median survival 2. palpitations loud pulmonic valve closure (P2). sleep apnea. edema.o. systemic dysfunction. chest pain. mixed restrictive/ obstructive lung dzs. JVD Pathogenesis Etiologies Epidemiology 20-30 y. problems w/ perfusion natural hx? Pre-symptomatic (RV hypertrophy to compensate for increased PVR. symptomatic (vascular remodeling causes decreased CO.cor pulmonale Significant overgrowth in Unknown? endothelial layer of pulmonary arterioles (vascular remodeling) = obstruction of blood flow (plexiform lesions) = pulmonary vascular resistance (PVR is too high!!). severe hypoxemia increased mPAP and PVR due to vasomotor constriction or pulmonary vascular remodeling see PAH Pulmonary arterial hypertension from Left heart disease (WHO Group 2) Valvular diseases. larger PE. syncope w/ exertion. peripheral edema. tricuspid regurgitation murmur on LSB. hx of previous PE 10% of pts have antiphospholipid antibody syndrome only PAH that is curable!! (pulmonary thromboDx requires VQ scan endarterectomy) (shows areas of mechanically dissect mismatched flow) clot off the artery .Disease Clinical Variants Idiopathic Pulmonary Arterial Hypertension Defining Characteristics slowly progressive DOE. ascites. idiopathic VTE.years uncommon. ILD. right ventricular heave. allows CO to keep up). right sided fourth heart sound (increased press through tricuspid valve). alveolar hypoventilation disorders. (COPD) increases workload for developmental abnl remaining vessels see PAH Chronic Thromboembolic Pulmonary HTN (CTEPH) (WHO Group 4) DOE after asymptomatic period of months . declining (loss of PAP = declining CO & cor pulmonale) Pulmonary venoocclusive disease (PVOD) (WHO Group 1') shared similarities with PAH venular proliferation on postleft-sided capillary side (left heart) leads to predominant dz narrowed lumen of small pulmonary veins --> development of pulmonary infiltrates.8 yrs) . while PAP & PVR continue to increase). chronic exposure to hi loss of pulmonary vasculature altitudes. increases vasoconstriction of pulmonary arteries COPD. subacute manifestation of pulmonary embolic disease that evolves via proximal pulmonary artery obstruction from failed clot resolution --> remodeling to increase pressure backflow to RV incidence of CTEPH happens w/I 2y of acute VTE younger age.
syncope. MD. LAM. psychogenic sepsis. <3: hypocapnia --> demand. CHF (J-receptors) Non-physiologic causes? Pain. lung: pulmonale (terminal (headaches). pregnancy NOT related to RR treat underlying disease. brown Diagnostics? paper bag Pregnancy test. Asthma. visual changes. dypsnea. impaired hypoxic drive (problems with unconscious breathing only) Neuromuscular cause? FEV1. forces. tetany. CV signs (arrythmia. dizziness). splenectomy. careful O2 supplementation. cor resp acidosis? pulmonale) DRUGS.. sleep arousal COPD. end stage renal dz Epidemiology Risk factors Lab/Imaging Treatment see PAH Complications Hepatopulmonary syndrome Secondary to liver disease Diffusion-perfusion impairment = overdistention of capillary = RBCs escape w. CO2 because closed pCO2). MG. weak muscle fx (low pressure. pulm common cause for vasoconstriction (pulm HTN. hypoxemia PCO2 causes less minute secondary to hypercapnia ventilation than expected). carpopedal muscle contraction and mucus spasm. sarcoidosis. irritants (P. intubate Central alveolar hypoventilation? Respiratory stimulants. nocturnal ventilation neuromuscular? NO stimulants. FVC. nocturnal ventilation do not give supplemental oxygen to patients with chronic hypercapnia (only drive to breathe is hypoxia!!) . rapid shallow Lung dz cause? obst/rest pattern on PFT. hypoventilation? obesity Orthopnea (loss of 2° consequences? -HCO3. diaphragmatic pacing. nl muscle fx. kussmaul system). glycogen storage diseases. breathing classic in sedation? acidosis) Hypoventilation / Hypercapnia decreased effective minute ventilation = PaCO2 > 45 (hypercapnia) Brain: congenital central hypoventilation (hirchsprung's dz).E. on secondary drive to breath muscle & PNS: ALS. hypoxic drive alone w/ chronic hypercapnia Respiratory acidosis? Correct w/ drug antagonist.Disease Pulmonary arterial hypertension w/ unclear or multifactoral causes (WHO Group 5) Clinical Variants Defining Characteristics Pathogenesis miscellaneous diseases that all cause PAH Etiologies Chronic myeloproliferative dz. MVV). hyper/ hypothyroidism. NO edema (stiffer. nl pCO2 w/ sleep-psych hypervent Physiologic causes? Hypoxia. RV (restrictive pattern). neuromuscular (hypoxia) kyphoscoliosis. chronic hypercapnia? pH w/ hypothyroid. nl muscle strength but low MVV/endurance. muscle weakness. O2 delivery = electrical increased work of abnormality --> arrythmia breathing. bronchiectasis. acidosis. dypsnea. polycythemia). sedatives/narcotics hypoventilation? No baroreceptor sensitivity (high / benzos. TLC. RBCs (polycythemia). cor cerebral vasodilation syndrome. chest pain). event) (sleep disturbance. PE. time. anxiety. nocturnal ventilation pulm? Treat underlying dz. stroke hypoventilation = acute CO2 = pH = O2 Central cause? Nl PFT. rely Ondine's curse. breathing (slow deep reassurance. more resistant) -> HEADACHES hyperventilation. inhalants). anesthesia. hypoventilation diaphragm fx). kidney compensates w/ central alveolar HCO3. pO2. somnolence). pulmonary langerhans cell histiocytosis. ABG (increases blood (pH. Lung: hypocapnia --> smooth parasthesias. Hb desaturation/ pulm fibrosis erythropoiesis (cyanosis. dypsnea & work of breathing nl/ hi pO2. tx underlying condition. HCO3-.o oxygen traveling to other side (bc capillary is too wide) = R-L shunt hypoxemia (PVR is too low!!) Liver disease (causes vasodilation & capillary overdistention) supplemental oxygen can cause R-->L shunting w/ severe pulmonary vascular dilation Hyperventilation / Hypocapnia increased effective minute Brain: hypocapnia --> ventilation = PaCO2 < 35 vasoconstriction --> (hypocapnia) hyperexcitability of neurons and poor perfusion to brain --> seizures neuro signs (seizures.
FIO2; hypoventilation; diffusion impairment; VQ mismatch; shunt (RL), altitude induced hypoxemia
Check A-A gradient
hypoventilation induced hypoxemia
PaCO2 > 45 mmHg; nl A- elevated PaCO2 means there is extra-pulmonary less amount of O2 in the causes a gradient, responds to alveolus = less O2 that will move increased FiO2 from alveoli to pulmonary capillary = hypoxemia; no abnormalities in gas exchange disease process causes amplification of VQ mismatch, where composition of alveolar gas varies in different lung regions, causing hypoxemia hi ventilation, low perfusion (PE) low ventilation, hi perfusion (pneumonia, PECHF, ALI/ARDS, atelectasis, pulmonary fibrosis, COPD) anatomic shunt (intracardiac shunts, pulmonary AV malformations, hepatopulmonary syndrome) physiologic shunt (atelectasis, pneumonia, ALI/ARDS)
usually corrects with small doses of O2 (FiO2); correct with drug antagonist (opoid antidote)
VQ mismatch hypoxemia increased A-a gradient, nl PaCO2 (unless severe hypoxemia), respond to increased FiO2
patients respond to increased FiO2
Right to Left Shunt hypoxemia
severe hypoxemia that is not readily fixed with increased FiO2, increased A-a gradient, nl PaCO2
blood moves from right side of heart to left side of heart without being oxygenated (extreme form of VQ mismatch)
Diffusion limitation hypoxemia
increased A-a gradient, exercise-induced hypoxemia, usually responds to FiO2 increases
difficulty moving the oxygen out of the alveoli and into the pulmonary capillary exercise-induced hypoxemia? Blood moves faster during exercise, so not enough time for O2 to diffuse from alveoli to capillaries; nl there are compensation mechanisms (dilate cap surface area, increase alveolar O2 content) but in these patients, compensatory mechanisms are impaired
interstitial lung disease, pulmonary fibrosis
Acute respiratory failure (ARF)
nl CXR? Possible causes = CNS event (stroke, drug OD, head injury), neuromusc dz, airway obst (asthma, COPD), PE abnl CXR? Possible causes = ALI/ARDS, aspiration, pneumonia, hydrostatic pulm edema, obst lung dz (nl/abnl CXR), PE (nl/abnl CXR), pneumothorax
at-risk dx? Direct lung injury (aspiration of GI contents, pulmonary contusion, pneumonia/ sepsis); indirect lung injury (nonpulm sepsis, abdominal trauma, multiple fx, hypertransfusion)
300<PaO2/FiO2<200 CXR: bilateral infiltrates ABG: worsening CO2 and O2 levels despite increased oxygenation
manage underlying cause provide supportive care restore oxygenation to better levels (PaO2 of 55-60, O2 sat 88-90%) intubation & low tidal volume mech ventilation if necessary
mortality ~30-40%, long recovery time
Acute lung injury (ALI) defining criteria? Acute respiratory distress syndrome (ARDS) Acute onset post "at risk" dx Bilat infiltrates on CXR PaO2/FiO2<300 (ALI) PaO2/FiO2<200 (ARDS)
Acute lung injury --> flooding of alveoli w/ edematous fluid = VQ mismatch, shunting, & capillary leakage; decreased surfactant production/function; all leads to stiff lungs from diffuse alveolar damage & pulm edema --> respiratory load = No LA HTN (no evidence worse alv ventilation = lung of CHF) compliance (low compliance means more pressure required to make a change in vol)
loss of capillary volume
chest pain, dyspnea, apprehension, syncope, cough, hemoptysis, sweats
Large clots increase the pressure of RV, which cannot compensate to acute changes in pressures --> enlargement of RV --> decreased preload & contraction of LV (can't fill anymore) --> decreased CO virchow's triad
600,000 PE, 1 same as those million silent PE; for DVT 3rd most common CV disease in US
DLCO gross: thickened pulmonary arteries (white macaroni) DLCO
anti-coagulation!! (short term - LMWH Well's criteria: >6pts = heparin, unfract high risk (78%), 2-6 heparin; long-term pts= mod risk (28%), coumadin) <2pts = low risk (3.4%); modified (>4 Thrombolytics if pts = PE likely!!) low BP (shock state) Christopher study: low modified Wells = D-dimer (nl - done; abnl - CT scan), CT scan (nl - done, positive -tx); hi modified Wells = CT scan (nl - done; positive- tx) Alternatives? VQ scan, abnl pulm angiography
increased mortality if PE+shock 65% of people die w/I 1st hr of dx Thrombolytics contraind in pts >80, major surg w/I 7d, major trauma w/I 10d, TIA/ neurosurgery in last 6m, GI bleed in last 3m, uncontrolled HTN, known bleeding disorder Thrombolytics have increased risk of intercranial hemorrhage
Deep Vein Thrombosis
swollen leg, tenderness in leg near deep veins, unilateral swelling >3cm, unilateral pitting edema
2 million cases, 1/1000 per yr; M>F, blacks more affected
Trauma, spinal cord injury, ortho surgery, Gyn surgery, critical care
Well's criteria: >3 pts = high risk (75% chance of DVT), 1-2 pts (moderate risk), <1 pt (low risk)
Prox/ pelvic DVT? Catheter-directed thrombolysis
AVOID giving anticoagulation prophylaxis to spinal surgery patients
direct injury to deep veins or occurs in deep endothelial cell activation --> veins of pelvis and activation of tissue factor (TF) -- proximal thigh > activation of extrinsic coagulation cascade --> activates VIIa --> activates thrombin --> cross-linked fibrin clot Virchow's triad: vessel wall damage, venous stasis (stagnant blood coagulates), increased blood coagulability (cancer, Factor V Leiden)
Obj confirmed DVT? Fast-acting antiImmobilization, Suspect DVT? coagulation bone fxs, age, D-dimer (R/Os (LMWH) for 5 days, prior DVT, thrombosis) - abnl? also start vitK antag cancer, varicose Ultrasound of whole (coumadin), veins, leg - abnl? Rpt 1 compression anesthesia, week later stockings severe COPD, high estrogen 3m follow up duration of antistates, HIT, regardless coagulation depends thrombophilias on rev/irrev cause
increased membrane thickness, increased VQ mismatch hypoxemia, increased diffusion limitations (fibrosis prevents O2 movement out of alveoli and into capillary) chronic inflammation = increased cytokines = induced fibroblast secretion of collagen = fibrous scarring
DLCO histology: blue-pink color as collagen deposits develop fibrosis; thick, stiff looking alveolar spaces; temporal heterogeneity (normal septum next to disease septum) gross: honeycombing (bumpy cobblestone pleura; tethering of fibrin); traction bronchiectasis (dilated bronchi)
Obesity hypoventilation syndrome
morbid obesity, sleepiness & hypoventilation during day, hypercapnia, cyanosis, hypersomnolence
increased capillary blood volume
cor pulmonale difficult to reverse
sound horrible but ventilating ok starts w/ rhinorrhea/ sore throat/ mild fever --> barking cough w/ inspiratory stridor --> resp stridor, tachypnea/cardia, nasal flaring, retractions --> inc distress--> fatigue, cyanosis, biphasic stridor --> silent airway tota obst)
inflammation of larynx, trachea Parainfluenza viruses 1-3 are most common agent (>75%) less common? RSV, influenza, adenovirus, herpesvirus (more severe illness) preceded by coryza-like illnesses/URIs before croup onset
viral extrathoracic obstruction
uncommon in kids < 6m (maternal Abs) peaks btwn 1824m most common cause of upper airway obstruction in kids
Clinical dx, can make child worse by trying to get CXR CXR: steeple sign (narrowing of subglottic region)
Spontaneous resolution w/ hydration, antipyretics, humidified air severe cases? Oral corticosteroids, nebulized epinephrine for immediate symptomatic relief (does nothing for tx though!!)
inflammation can extend into lower airways/bronchi = laryngeal tracheal bronchitis
reduced vaccination rates
can occur at any age, but most common in kids < 5 y.o.
"Beefy red" & swollen epiglottis w/ bronchoscopy
dyspnea, stridor, tripod bacterial cellulitis of superior glottis structures position abrupt onset w/ early toxicity preceding URI (sometimes), very sore throat w/ choking sensation, difficulty swallowing, drooling, respiratory distress, anxiety, high fever, muffled voice (dysphagia), toxic appearance Haemophilus influenzae type B (Hib) - but more rare now that there's vaccination B-hemolytic streps (A, B, C) Staph aureus other organisms cause more gradual onset but slower recovery
MEDICAL EMERGENCY!! High Do NOT inspect risk of death (if edema progresses airway or place IV thumb sign on lateral enough to position XR (but really would intubation by most epiglottis over the never get bc could experienced person airway) worsen obstruction) Hib manifestations swollen, enlarged IV fluids, labs, elsewhere (meningitis, epiglottis antibiotics (3rd gen otitis, pnuemonia, cephalosporin), cellulitis) airway/blood cultures, rifampin prophylaxis for close contacts, NO nebulized epinephrine peanuts, popcorn, hotwheels, any small toy CXR: hyperinflation of affected airway (air trapping) OR completely nl CXR!! Atelectasis w/ aspiration remove foreign object
Foreign Body Aspiration
sudden cough/ wheeze after eating or playing (although sometimes onset may be insidious) persistent cough or wheeze, current/persistent pneumonia, decreased breath sounds, delayed air entry
typically objects are aspirated down the right main bronchus because shorter and straighter than left bronchus intrathoracic obstruction
tachypnea (RR>50,60), chest retractions, cough, wheezing, prolonged expiratory phase, crackles, signficant resp distress, apnea in young infants, irritable, dehydration
inflammation of bronchioles, intrathoracic obstruction caused by RSV --> necrosis of airway epithelium --> influx of inflammatory cells --> release of inflammatory mediators = edema = narrowing of airways
RSV, followed by parainfluenza
usually limited to URI in respiratory droplet transmission healthy infants; in <40% it progresses to bronchiolitis
most commonly in daycare, hospital, ICU, children <2 y.o. regional differences, Most common cause of hospital premature admission for <1 infants, winter or late fall birth y.o. month, M>F, anatomic abnl, malnutrition, metabolic/ genetic diseases, SES
CXR: hyperinflation (air trapping), flat diaphragm, peribronchial thickening, collapsed lung (RUL), dense infiltrates behind heart (frank consolidation, pneumonia)
hospitalize young child if it looks like RSV bc high incidence of sleep apnea --> SIDS possible O2 supplementation fluids (hypertonic saline), hold feeds, humidified O2, infection control no routine bronchodilators, antivirals, corticosteroids, or antibiotics
Many develop recurrent wheezing that may be associated with persistent abnormalities in lung function
Childhood wheezing Transient early wheeze
early wheezing but sx resolve btwn ages 3-5
NOT FH of asthma reduced lung fx before respiratory event (prematurity, day care, prenatal maternal smoking, post natal smoking exposure) preschool age kids
lower lung fx earlier in life associated w/ viral respiratory RSV, rhinovirus that improves w/ age; tract infections generally resolves by age 6
Ig-associated wheeze (asthma)
Wheezing before age 6
atopy, increased airway hyperresponsiveness, & elevated IgE; more persistent disease w/ early exposure to allergens decreased risk w/ exposure to other children (daycare) and animal exposure
FH of asthma, allergy, elevated IgE @ age1, early sensitization to mold, obese females, maternal prenatal smoking
Multisystem disorder reproductive (congenital bilateral absence of vas deferens, decreased female fertility), sweat glands (increased salt sweat content), GI (pancreatic insuff, meconium ileus, intest obstruction, biliary obstruct, DM) sinusitis, nasal polyps, chronic bronchitis (leads to atelectasis, bronchiectasis, pneumothorax, hemoptysis, resp failure)
autosomal recessive mutation in long arm of chrom 7 creates gene product CFTR, which is an ATP dependent chloride channel and also regulates ENaC (CFTR: regulates movement of salt & H2O across membrane) Abnl CFTR = decreased Cl secretion = increased Na reabsorption = decreased airway surface liquid = dysfunctional cilia, chronic mucus infection, & airway inflammation (due to hyperresponse inflammatory response) --> bronchiectasis
>1500 CFTR muts but 50% of pts are homozygous for delta508 mutation in CFTR (deletion in phenylalanine); Class I (nonsense mutation); Class II (protein degradation by proteosome; milder); Class III &IV (defective regulation but CFTR makes it to cell surface; mildest); Class V (linsuff production of functioning protein); Class VI (accelerated protein turnover)
Most common life- 1/3200 births in shortening genetic whites dz in Caucasians 30,000 Americans, 60,000 cases globally;
Sweat test (pilocarpine iontophoresis) - nl ~40; CF ~90-100
Spirometry CFTR modulators (Ivacaftor, VX-809, PTC124) aw clearance Gentoyping (specific, (dornase alfa, not sensitive) hypertonic saline, bronchodilators, PT) Newborn screening Aerosilized abs for (measures IRT exacerbations combined w/ Anti-inflammatories genotyping; confirmed (prednisone, by sweat test) macrolidesPsuedomonas) Late stage PE findings Nutrition: caloric (respiratory failure, foods, appetite FTT, malnutrition, stimul, tx constipat, steathorrhea) pancreatic enzymes & PPIs to minimize CT: air trapping, malabsorp bronchiectasis yearly CT scans @ age 1 lung transplant CT: cysts Gross pathology: irreversible damage PFTs: restrictive pattern (low TLC0, decreased DLCO (thickened alv membrane) CXR: bilateral reticular infitrates, basilar distn, small lung vol CT: diffuse ground glass infiltrate, mixed pattern (consolidation + GG), reticular peripheral infiltrates; honeycombing (advanced fibrosis), traction bronchiectasis ABG: hypoxemia
Life expectancy ~40y.o. but improving w. earlier dx and better tx Increased tendency for infections (never really eradicated, just controlled) - Staph, H.flu, Pseudomonas Pulmonary exacerbations usually require hospitalization (better adherence w/ aw clearance therapies) prednisone leads to decreased loss of lung fx but toxic w/ chronic use
irreversible lung damage
Interstitial Lung Disease (ILD) general overview
Dry cough, DOE, insidious onset, end inspiratory crackles @ lung bases, possible digital clubbing, no wheezing
Injury results in inflammation & tissue remodeling in lung - if uncontrolled, tissue progresses to fibrosis & scarring of lung
connective tissue diseases, exposures contributing to hypersensitivity pneumonitis, drug/smoking induced, radiation, toxic inhalation unk causes? IPF, other idiopathic interstitial pneumonias (COP, NSIP, LIP, AIP), sarcoidosis, eosinophilic pneumonia, rare (LAM, PLCH, PAP)
Chronic, progressive, fibrosing, interstitial limited to lungs! Dyspnea (insidious but progressively worsening); non productive cough (difficult to control), clubbing, decreased breath sounds, bilateral crackles DDx? Other ILD, connective tissue dz (RA, scleroderma), occupational exposure, meds (MTX, bleomycin, nitrofurantoin)
"repeated cycles" of epithelial activation or injury by some unknown agent
DX = exclusion of other causes, +UIP pattern on HRCT/bx CXR: restrictive findings (smaller lung volumes), fibrotic changes CT: honeycombing, reticulation, traction bronchiectasis, subpleural & basilar changes histology: dense fibrosis + honeycombing, subpleural involv, temporal heterogeneity, fibroblastic foci
No FDA approved med tx steroids HARMFUL!! treat GERD Enroll in clinical trials Evaluate for lung transplant O2 supplementation, pulm rehab, vaccination for flu/pneumonia, tx comorbidities, maintain BMI
About 50% survival after 2 years dx; 1520% 5 yr survival
Idiopathic Interstitial Idiopathic Pulmonary Pneumonias fibrosis
Age (>50) familial pulm Older adults, M>F fibrosis 128,000 pts (US) smoking 40,000 new GERD cases/yr exp to metal 25-30/100,000 dust, wood dust, solvents
Desquamative interstitial pneumonia (DIP)
Chronic onset of dyspnea & cough; sometimes clubbing
M>F, mean age 45 y.o.
>90% of cases involve smokers!
CXR: nl in 1/5 pts smoking cessation mortality rate 20-30%; CT: diffuse/patchy mean survival 12 ground glass steroids sometimes years opacifications effective PFTs: restriction + low DLCO histology: increased alveolar macrophages, pigmented
Acute interstitial pneumonia (AIP) Respiratory bronchiolitis interstitial lung disease Cryptogenic organizing pneumonia (COP) "Bronchiolitis obliterans organizing pneumonia" BOOP
localized or diffuse fibrous plugs filling airway into alveoli sometimes present w/ fever (after which Abs don't help)
consequence of infection or inhalational injury
a/w CTD, drugs, idiopathic
CT: multiple patchy consolidations; sometimes GG Histology? Fibrous plugging of airway
responsive to steroids!! (~6m)
Lymphocytic interstitial pneumonia (LIP) Non-specific interstitial pneumonia (NSIP)
chronic onset of dyspnea varying degrees of inflammation & cough; sometimes fever & fibrosis w/I alveolar walls, temporally uniform
Females > Males; Connective younger mean age tissue diseases of onset (46-55) (more females!), HSP, other exposures
CT: UIP pattern HRCT: reticular infiltrates, peripheral & basilar distn, ++ ground glass, NO HONEYCOMBING, TEMPORALLY UNIFORM Histology? Inflammatory cells, fibrosis, uniform thickening of lung interstitium
better prognosis than UIP!! Good results with steroids
remove responsible drug!
Lung toxicity in response to Talc in illicit drugs antibiotics (nitrofurantoin), antiinflammatory agents (methotrexate, cyclophosphamide), cardiac drugs (amiodarone), chemotherapeutic agents (bleomycin, busulfan), recreational drugs non-necrotozing granulomatous dz immunologic-mediated, inflammatory reaction around small airways in response to inhaled antigen (organic dust) Microbial agents (bacteria, fungi, amoeba, atypical mycobacteria), Animal proteins (bird antigens), low & high MW chemicals Non-smokers Histology: bronchiocentric lymphoplastic infiltration, poorly formed nonnecrotizing granulomas, mutlinucleated giant cells around bronchioles, CXR: may be normal CT: sometimes nl HRCT: mid to UL Δs (chronic HP), fibrosis/ honeycomb (chronic HP), any pattern (GG, retic, nodul, consolidn) IgG- not spec/ sens BAL: CD8 predominance (diff from sarcoid)
Hypersensitivity Pneumonitis (extrinsic allergic alveolitis)
Farmer's lung Pigeon breeder's lung Humidifier lung
NO WHEEZING! NOT multisystemic (like early stage: type III mediated sarcoidosis) Acute HP (sx w/i 48h, selflate stage: type IV delayedresolving, recurring type hypersensitivity reaction episodes more severe, against antigen nonspecific sx; tachypnea, tachycardia, fine crackles), does not involve IgE subacute/ intermittent HP (gradual sx, low dose rptd exp, sx resolve w/i 24h of removal from agent, tachypnea, crackles) chronic HP (chronic exp, prod cough, DOE, weight loss, tachypnea, crackles, irreversible after removal of agent) multi-organ (hilar/ mediastinal LNs, lungs, liver, spleen) granulomatous dz of unknown etiology abnl immune response to unk antigens --> increased proliferation of CD4+ T helper cells in involved tissues = recruitment of macrophages = formation of granuloma CD4+ alveolitis
must stop exposure!! Only then will steroids be effective
may progress to chronic HP w/ end stage fibrosis & honeycombing
asymptomatic Non-infectious, nonnecrotizing granuloma Systemic disease, nonspecific & variable presentation (lungs, skin) Heerfordt's syndrome: parotid swelling, uveitis, Bell's Palsy, fever Lofgren's triad: arthritis, erythema nodosum, hilar adenopathy - good prognosis The sicker a person appears on presentation, the better the prognosis!
3x higher incidence/ severity in African Americans
histology: nodular aggregate of mo w/o necrotizing center; periphery of lymphocytes (wreath Scandavian arrangement of countries decreased risk nuclei), in HIV pts! multinucleated giant young person's cells disease (age<50) Worse CXR: prognosis? Pts lymphadenopathy in F>M >40y.o, A.A., young person; hypercalcemia, interstitial fibrosis; nephrosclerosis, determines staging (0extrapulm dz no pulm inv, 4irreversible fibrosis), nodular sarcoids PFT: any pattern but classic (nl ratio, low DLCO, restriction or mixed pattern) BAL: increased lymphocytes, >3:1 ratio of CD4:CD8
Some genetic component (HLA II on chromosome 6 short arm)
spontaneous resolution but management differs based on location of involvement glucocorticoids if worsening pulm sx, worse lung fx, changes in CXR; 612m lung transplant if stage 4
should always stain tissue bx with acid fast for bacilli to avoid missing TB (early TB looks very similar to sarcoidosis)
sometimes gram+ cocci in pairs fluoroquinolone & chains blood cx positive in 20% of patients Strep pneumo is #1 cause of meningitis in all age groups can also cause other clinical syndromes (bacteremia. cirrhosis. 3rd gen Sputum gram stain: cephalosporins. shipyards) Lab/Imaging Histology: alveolitis & development of giant cells. patchy infiltrates. dyspnea. diabetes. Chlamydia pneumoniae. defective antibodies. endocarditis) Increased rate of blactam resistance (altered PBPs) CAP . sinuses) Aspiration of nasopharyngeal carriage --> pneumonia settling in the alveoli Strep pneumo can invade the blood stream and enter joints (septic joint) or meninges (menigitis) Strep pneumo. milder (EXCEPT Legionella). elevated systemic WBC. Blacks > Whites Elderly & influenzae. sinusitis. many neutrophils. benign pleural plaques (marker of asbestos exp). stone cutting/ polishing. fabricate. would require special testing to distinguish Berylliosis Anthracosis Community acquired pneumonia (CAP) Typical pneumonia (Pneumococcal pneumonia) usually harmless except in coal miners w/ massive exposure detectable on gram stain. working w/ abrasives (pottery) histology: nodular type pattern of fibrosis. others risk increases with infants age HIV. viral . splenic dysfunction (SSD). abrupt onset of fever/chills.Disease Pneumoconsioses (occupational lung dz) Clinical Variants Asbestosis Defining Characteristics diffuse fibrosis Pathogenesis Etiologies Epidemiology Risk factors industries that mine. rusty sputum . or install asbestos (roofing. cough (productive. sometimes blood-tinged. African/ Native Americans (due more to SES) CXR: lobar consolidation. Legionella. bacterial peritonitis. bone/joint infs. insidious onset w/ URI sx Mycoplasma pneumoniae. sandblasting. pleuritic massive amounts of carbon pigment in the lung Strep pneumo enters human host via airborne droplet spread --> person can become asymptomatic carrier (children) or become locally infected (ear. dry cough. productive cough than serpentine) causes the recruitment of macrophages --> failed attempt to phagocytose --> formation of fibrogenic cytokines -> gradual development fibrosis Coal workers pneumoconiosis Silicosis CT: diffuse nodules nodular fibrosis that gradually 10-15 years of develops following the inhalation silica exposure increased susceptibility of cystalline silica in occupational settings --> intxt to TB!!! w/ epithelial cells & macrophages --> phagocytosis of silica particles --> activation / release of mediators by macrophages --> eventual death of macrophages --> fibrosis acute & chronic exposure to NON-NECROTIZING GRANULOMAS (similar beryllium in fluorescent light bulbs. brakes. H. mining & industry --> to sarcoidosis) hypersensitivity reaction nodular fibrosis mining and processing of ores. otitis media. silica particles (needle like structures) visible under polarized lens high incidence of TB (silicosis = macrophage wasting dz so can't fight off TB) slight risk for carcinoma cor pulmonale mining & industry Histology? Appears just like sarcoidosis. localized lobar infiltrate. pneumo).Atypical pneumonia general can't be seen on gram stain. and mesothelioma inhalation of asbestos body Asbestos body (amphibole more pathogenic DOE. dyspnea. interstitial fibrosis Treatment Complications amphibole body a/w mesothelioma asbestos exposure also increases risk for bronchogenic carcinoma. insulation. bronchitis. pleural effusions sometimes Macrolides (arithromycin). fever. require special media to grow in cx. doxycycline.classic for S. purulent.
MSK. non-spore adults forming. rabbits lymphocytic response due to intracellular nature of organism histology? interstitial & alveolar infiltrates of macrophages . malaise. droplet spread fever. dry cough. hyponatremia. unencapsulated bacilli Macrolide (Azithromycin) Legionella urinary immuno-deficient antigen . nl WBC count Infectious spores (EB) attach and enter host cell. multiplies in the phagosomes. azithromycin). after which the EB's are released to infect next host cell person to person droplet spread >1/4 of no seasonal pneumonias in variation school-aged kids Coxiella burnetti (Q fever) often asymptomatic focal pneumonia caused by inhalation of aerosols of birth products from sheep. closed populations (military recruits. doxycycline (adults). cats. dorms) Empiric dx due to difficult cx No tx for localized URIs (without pneumonia) cold agglutinins: antibodies to RBC I Ag B-LACTAMS do not work (no cell wall!!) = agglutination of RBCs at 4 degs C Pneumonia Antigen & NA present? Use detection kits (future) macrolides (erthromycin. young Gram negative.myalgias. focal pneumonia myalgias. myalgias. insidious onset. Mycoplasma pneumoniae 2-3 week incubation transmitted via person-to-person period. arthalgias. self-limiting flu-like illness. asymptomatic carriage. fluoroquinolones (adults) CXR: patchy infiltrates Empirical tx CBC: nl WBC cell cx not really tried PCR/NA techniques (Future) doxycycline. ciprofloxacin) Complications L. no fever really. pneumophilia = rare in healthy children.SJS. mild URI sx followed by prolonged cough. silver stains for visualization Treatment Fluoroquinolones (Levofloxacin.+ in 80-90% Alternatives? of dz age> 50 Doxycycline culture on selective NO B-LACTAMS!! media . malaise. RB multiply via binary fission.acute. "walking pneumonia" persistent cough. headache. pleural effusion Pathogenesis Enters alveolar macrophages thru coiling phagocytosis.. cattle. 21 day incubation period.slow but GS serology. malaise. endocytosed and transformed into metabolically active RBs. aerobic. Heme hemolytic anemia. goats. diarrhea. high attack rate among exposed Legionnaires' dz . fluoroquinolones NO B-lactams!! immune mediated systemic manifestations (Derm.Disease Clinical Variants Legionella Defining Characteristics Pontiac fever .. reaches critical mass. disparity btwn CXR and physical findings (few) YOUNG PEOPLE! older adults with bronchitis or (5-20 years old) pneumonia. requires fuchsin. anorexia. etc) Chlamydia pneumoniae re-infection possible. life-threatening pneumonia. boarding schools.slow.mild respiratory dz to severe. macrolides. CNSencephalitis. moxifloxacin. RBs transformed into EB to make cytoplasmic inclusion. headache. then lyses the macrophage transmitted to humans via aerosolization of contaminated water Cell mediated immunity = host defense Etiologies Epidemiology Risk factors Smokers or people with damaged mucociliary defenses (COPD) Lab/Imaging Gram stain: Gram rod that does not stain well. HI fever.
cancer. S. digital clubbing can be caused by aspiration of infective material (especially when cough reflex is depressed). foul-smelling purulent sputum. pyogenes. intranuclr inclusions w/ blurred nuclr membrane smudge cell. cytomegalic cells (large cells with intranuclr & cytoplasm inclusions) HSV? Eosins w/ halo Measles? multinucl giant cells w/ intranuclr inclusions w/ indistinct halo & cytoplasm inclusions Pneumocystis jirovecii pneumonia (PCP) focal infiltrates fungal pneumonia that invades immunocompromised hosts with CD4 T cell count <200 (presence of PCP = AIDS dx) immunocompro mised pts (AIDS. characterized by cough. antecedent bacterial pneumonia. aureus. transplant Aspiration pneumonia (severe necrotizing bronchopneumonia) Aspiration of gastric contents Polymicrobial or oral flora resulting in a necrotizing pneumonia that has chemical (irritant) and polymicrobial components debilitated pts unconscious pts repeated vomiting Histology: hemoptysis & necrosis High mortality lung abscess in those who do survive . pus filled CXR: abscess formation Histology: alveolar space filled w/ PMNs scarring --> fibrosis R/O carcinoma extension into brain. transplant. pneumonia adenovirus. POLY-MICROBIAL Immunocompro mise. CMV? Intra-alveolar hemorr. neoplasm (postobstructive pneumonia) S. steroids) Histology? Looks bubbly with widened alveolar septa due to inflammatory cells. edema. septic embolism. or measles virus CMV? Adenovirus? Immunocompro Exudates w/ necrosis mised individuals & hemorr. fever. hemorrhage Necrotizing Pneumonia (Lung Abscess) inflammation & pus that has been walled off. characteristic cysts seen w/ silver staining antimicrobial Gross: cavitation (gangrene of lung) w/ surrounding fibrosis. HSV.Disease Clinical Variants Viral pneumonias Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications difficult to detect but may diffuse alveolar damage & precede bacterial necrosis caused by CMV. Pseudomonas.
+ fluoroquinolones/ injectable Abs) Pulmonary TB: insidious onset of prolonged Latent TB (not all cough. productive cough +/weight loss/fever) HIV.2m. atypical CXR findings primary progressive dz (LL & interstitial infiltrates. & tissue destruction cavitations on CXR: resistance = higher 4 drugs -2m. narrow based budding if replicating . poorly ventilated settings malnutrition immunosuppress ed (TNF-a inhibitors. active TB inf.aw centered fibrosing lung dz Histoplasma pneumonia granulomatous pneumonia Disseminated histoplasmosisresembles miliary TB nl & immunoHistology: calcified Ohio & Mississippi River compromised pts necrosis. silicosis. pre-existing lung conditions susceptible. 7m cost DOT!!! immune reconstitution inflammatory LTBI . mortality. 3. 2 drugs 2m) Complications Lots of undetected TB cases globally so need single point of care test (GeneXpert RT-PCR $$) MDR-TB (resistance to at least INH + RIF) XDR-TB (resistance to INH. weight/ controls inf.5 million deaths/yr.morbidity. pleuritic chest organisms are eradicated pain. weight loss) non-AIDS pts rarely become infected (but if so.Disease Tuberculosis Clinical Variants Active TB Defining Characteristics Pathogenesis Etiologies Epidemiology 1. especially aggressive in AIDS pts (feverish. pyrazinamide. after which only the fungi intracellularly reside immunocompromised individuals progress w/ in macrophages production of Histoplasmoma .tx with INH for syndrome (IRIS) 9 months (or INH/RIF response in TB-HIV pts started on ARVs for 1x q 12wks) Atypical Mycobacteria M. which can be stained with mucicarmin capsules turn pink Histoplasmosis narrow based budding Inhalation of histoplasma capsulatum causes isolation of spores into the lung. fibrotic changes on CXR Lab/Imaging Acid Fast Bacillus Broth cx w/ Ab susceptibility . unencapsulated valleys organisms seen w/ silver stain inside alveolar macrophages. yeast in the heat! GEOGRAPHIC localization Cryptococcus granulomatous inflammatory response caused by Cryptococcus neoformans.GS DNA probes on smear + specimens (NAAT . RIF. 2drugs. hemoptysis. 2nd leading cause of death after HIV. especially tuberculosis with prolonged exposure. hypersensitivity.hi sen/spc) to ID species (TB rough colonies) CXR: typical UL infiltrates. 2. but immune system night sweats.localized lung granulomas lesion that becomes walled off and calcified NOT really capsulated! chronic fibrosing histoplasmosis . which is an encapsulated yeast and transmited to humans via inhalation of soil & bird droppings opportunistic infection! Gross: caseous necrosis of lung just like TB Histology: yeast (spheres) surrounded by clear space (capsule). (inf followed by active dz adenopathy) usually in HIV pts) Miliary TB = disseminated (looks like millet seeds in the lung) NECROTIZING GRANULOMAS person to person transmission Mycobacterium of airborne droplets. once have susceptibilities. not infectious appetite loss. TH1 response is mounted (due to inc IL-12). miliary nodules histology: necrotizing granulomas in center. AFB stain= "red snappers". bilat infiltrates. fever. renal failure. can cut back to 2 drugs (4 drugs . Ghon complex. ~3wks later. cavitations (caseous) Treatment RIPE = Rifampin. Ghon focus. isoniazid. ethambutol for 6-9mdrug susc TB start on 4 drugs if suspicious of TB. night sweats. 3 outcomes with exp? 1. fatigue but at risk for reactivation in future) TB + HIV: extrapulmonary dz. no inf most infectious pts? Cough + AFB smear+ MTB enters alv macrophages and replicate in phagosome (leads to asymptomatic bacteremia & multiple seeding sites). COPD/other lung dz Multi-drug therapy DIFFICULT TO ERADICATE Granulomatous fungal diseases (very similar to TB clinically. pathologically) dimorphic: mold in the cold. prednisone) recent inf w/ latent TB (<2y) substance abuse DM. chemo.variable patterns (hilar adenopathy. cavitary UL) in HIV coinfected. #1 cause of death in HIV pts most cases in Asia & Africa HIV epidemic is driving TB coinfection Risk factors HIV poor. cancer. latent inf. TH1 cells make IFN-y which stimulates macrophages to contain the MTB inf --> formation of necrotizing granulomas. avium intracelluaire complex (MAC) Hot tub lung. crowded.
night sweats. Kidney involvement saddle nose deformity ANCA associated vasculitis const sx (fever. mostly asymptomatic (80% of people in endemic areas infected) but some people can have lung lesions. mean age of 40 y. hemoptysis) M=F. weight loss). useful marker for dz activity & evaluation of systemic vasculitis. IV line. perinuclear): IgG autoantibody w/ specificity against antineutrophil granules & lysosomes in monocytes. fever. cough. mediumsmall vessel vasculitis Blood test ANCA (cytoplasmic. renal involvement.o. delay in dx. commonly seen with aspiration pneumonia or lipoid pneumonia (lipid in the lung) Histology? Lipids in alveoli cause formation of granulomas . or can persist as a chronic lesion Wegener's Granulomatosis unknown but probably represents resembles TB but must be distinguished bc diff T cell mediated hypersensitivity reaction to tx inhaled infectious or environmental agents (due to Necrotizing systemic response to immunosuppressive vasculitis agents) ELK Triad: Ear/nose/throat. chills. age. more common in Caucasians Histology (surg bx): cavitation. weight loss) Southeastern & south central US Histology? Broad based budding CXR: UL involvement Spontaneous resolution. erythema multiforme Pathogenesis inhalation of spores from Coccidiodes immitis causes delayed type hypersensitivity to the fungus Etiologies Epidemiology Southwest & Western US Risk factors Lab/Imaging Histology? Large organism containg secondary component (spherule w/ endospores) multiple budding Treatment Complications Blastomycosis Inhalation of spores from Blastomyces dermatitidis.Disease Clinical Variants Coccoidoidomycosis Defining Characteristics multiple budding various dz presentation. dyspnea. chest pain. Can give azathioprine & MTX medication to maintain remission intolerance CXR/CT to monitor response to tx Foreign Body Granulomas Diffuse pulmonary emboli entrapped foreign material (not blood clot!) in pulmonary vasculature talc from IVDU Iatrogenic (indwelling catheter. anorexia. Lung. pulm sx (cough. ENT sx (sinusitis. wheezing. skin. migratory arthalgias. birefringent (polarized light will show talc) Localized parenchymal mass tissue reaction to foreign material. necrotizing granulomas. & bone producing various dz presentations lesions broad based budding pulm sx (productive cough. silicone from breast implants) IVDU Histology? Multinucleated giant cells. Pulmonary. abdominal pain. stridor. mortality corticosteroids + cyclo-phosphamide w/I 1 year poor prognosis related to # sites involved. pleuritic pains. malaise. + in other dz!! if untreated. otitis). alveolar hemorrhage w/ capillaritis. anorexia.
takes a few days PCR (future) Treatment Oseltamivir/Tamiflu (tx. ?encephalitis . GI sx Pathogenesis person-to-person. prophylaxis) Tamiflu allergy? Zanamivir/Relenza Tamiflu resistant flu subtype? Amantadine. shedding of virus 1d before & 5d after sx begin HI fever. cough. 36. headache. airborne transmission of influenza virus from symptomatic or asymptomatic hosts Etiologies Epidemiology 5-20% of US population gets flu each yr.Disease Influenza virus (Orthomyxoviridae) Clinical Variants Defining Characteristics Incubation period (2d_.poor sensitivity Viral cx . severe myalgias. Rimantadine Complications More complications & mortality in elderly EXCEPTION: deaths from H1N1 were middle aged adults primary viral pneumonia. secondary bacterial pneumonia. Reye's Syndrome (aspirin +flu). chills.000 deaths/yr (>90% in people >65 yo) Risk factors Elderly (seasonal flu) Middle aged adults (H1N1) Lab/Imaging Rapid Antigen Detection . otitis media. abrupt onset. myopericarditis. DOE.
pneumonia. hemorrhagic cystitis. bronchitis in older children/adults incubation period of 2-8 days. from RSV coinfection w/ RSV = severe illness upper & lower respiratory tract infections 50% of inf are asymptomatic seasonal (winter/spring) pattern where it is transmitted by close contact elderly. winter PCR 10-30% of common colds SARS = virus endemic in bats that crossed into humans via intermediary (cats). pneumonia. risk of SARS (severe acute respiratory syndrome) transmission greatest around day 10 of illness. Latent infection that can hemorrhagic cystitis reactivate & cause severe inf in Adults: URI. oral form for transplant pop) inhaled form of ribavirin can cause supportive care bronchospasms in transplant pts Human metapneumovirus (paramyxoviridae) clinically indistinguishable illnesses similar to RSV. fecaloral route. transplant pts conjunctivitis (pink eye) Immunocomp: pneumonia. necrosis --> intense diarrhea inflammatory responses --> possible viremia Children: URI. otitis infected epithelial cells undergo media. increased w/ kids antigen detection. very few in adults Respiratory Syncytial Virus (RSV) (Paramyxoviridae) severe lower respiratory tract disease in infants bronchiolitis. premature birth significant resp pathogen in transplant pop Ribavirin hi secondary (aerosolized form for infection rates infants. then parainfluenza) Less common cause of pneumonia Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment No specific antiviral no vaccine supportive care Complications 20% of resp infs in young children kids. young children Molecular detection w/ PCR severe lung dz in lung transplant pts Adenovirus spread by droplet nuclei. hepatitis. who have cong PCR heart failure. bronchopneumonia. and can persist for some time in the environment Infants: pharyngitis. viral shedding for 1-2 weeks or longer droplet transmission and direct contact community outbreaks in late fall to early spring severe inf risk diagnosed via Cx. diarrhea.Disease Parainfluenzae virus (Paramyxoviridae) Clinical Variants Defining Characteristics Laryngotracheobronchitis (Croup) Bronchiolitis (RSV first. gastroenteritis. pneumonia. interstitial nephritis Cx less valuable Infection control because virus may not be shed for years after Antiviral therapy inf cidofovir for disseminated sx direct antigen assay for conjunctivitis PCR Common cold Rhinovirus (Picornaviridae) Coronavirus 30-50% of common colds circulate in spring. early fall circulate in fall. underlying pulm dz. summer. HCWs were high risk group for acquisition PCR . immunocomp.
Pressure . acidosis = sleepiness. (effective in 50% of neck circumference. STOP BANG so distends the questionnaire pharynx during (Snoring. hi pharyngeal compliance.reset of CO2 setpoint during sleep (transient period PaCO2 is below apnea threshold = min vent = PaCO2 to apnea threshold = minute ventilation Etiologies hi altitude (longer periods of sleep apnea) hypercapnia. exaggerated output to resp muscles. acidosis -> arousal from sleep -> resumption of airflow -> return to sleep -> cycle starts over Obesity (narrow airways). 95% of all sleep apnea MRI: narrowed CPAP (changes 30% noncomplicance pharynx behind tongue negative airway to CPAP pressure to positive. restless arousal from sleep sleep sleep onset -> apnea -> hypoxia.Disease Sleep apnea Clinical Variants Central Sleep Apnea Defining Characteristics cessation of airflow during sleep due to cessation of respiratory effort as result of decreased ventilatory motor output nl or slightly lower PaCO2 levels during the day. Tired. thick tongue. increased nocturnal death. arousal) in normocapneic CSA. = transient hypoxia. URIs. pulmonary hypertension. decreased upper aw muscle activity) 20 million Americans. in OSA. progesteron. excessive daytime hypercapnia. gender -male) last resort option) increased risk for OSA if 3/8 factors mandibular advancement devices (makes snoring difficult by holding tongue down) weight loss . chronic hypoventilation Epidemiology Risk factors Lab/Imaging Treatment maintain resp drive (respiratory stimulants theophylline. muscle tone SNORING that wakes up can't compensate to keep the aw open so increased snoring bed partner and OSA clinical features: left heart failure. resistance outside of thorax and right heart failure. PaCO2 becomes higher than setpoint= hyperventilate = PaCO2 becomes too low = hypoventilation (Cheyne-Stokes respirations) = Increased feedback delay (brain responding to old news and tends to overcompensate) or LOOP GAIN (small stimulus = gigantor response!!) Increased hypersensitivity/ loop gain (from oversensitive medulla. pharyngeoplasty BMI>35. complete blockage of airway despite efforts to pharynx narrows. chronic hypercapnia @ night Cheyne-Stokes respiration Pathogenesis nl . nasal trauma negative oropharyngeal press (small pharyngeal cavity. Age>50.HTN.inc onset central apnea ( apnea feedback delay) time. hypercapnia. large neck. inspiration) Observed apneas. or overefficiency of lungs in gas exchange) Obstructive Sleep Apnea Aw becomes more compliant. chronic negative pressure inside pharynx pulls airway closed = less airflow hypoventilation. increase metabolic acidosis by alkalinizing urine best for altitude induced) treat underlying conditions (CHF CPAP mask) Complications Chronic hypoventilation = impaired CO2 drive since have hi PaCO2 levels = cyclical sleep CHF (CheyneStokes. unexplained as pts start to snore and try harder to breathe out. and resistance to breathing increases with breathe sleep. pts but very painful. many undiagnosed.
Screening / Education .
Screening / Education .
Screening / Education Pursed lip breathing (creates increased pressure near mouth that changes press gradient.Ppl>Paw occurs higher in the trachea where it's noncompressible) SMOKING CESSATION!!! Reduction of risk factors. Flu vaccine Lifestyle modifications most impt tx (other treamtnes not too effective) Flu & pneumococcal vaccines. possible augmentation therapy of missing protein PiZZ ($$) SMOKING CESSATION!!! Reduction of risk factors. flu vaccine .
Screening / Education asthma control parameters? No daytime sx (<2x/wk). no exacerbations mandatory patient education and environmental control. comorbidity treatment high level therapy then step down . no limitation of DALYs/exercise. no nocturnal sx. nl/near nl lung fx. no need for reliever tx (<2x/wk).
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education Prognosis? Class I (no limitation w/ exertion). Class IV (no physical activity possible) . Class II (mild limitation but no probs at rest). Class III (marked limitation of activity).
Screening / Education .
Screening / Education .
Screening / Education .
LMWH heparin.LDUH. factor Xa inhibitors) infection control practices at home mandatory!! (must clean everything) .Screening / Education DVT prophylaxis (intermittent sequential compression device adherence issues. anticoagulation .
CHD) . w/ CLD.Screening / Education Prophylactic treatment for close contacts RSV prophylaxis (Synagis) . given to children who meet certain criteria (infants born <28 wks gestation.o. those born 29-32 wks gestation during RSV season.daycare.monthly IM injections during RSV season. full term kids < 2y. those born 3236 wks gestation & risk factors . school age siblings. CF. $$.
Screening / Education importance of nutrition & exercise breathing techniques to augment airway clearance lung transplantation patients feel better but still have persistent diseases (complicated by chronic lung rej & bronchiolitis obliterans) .
Screening / Education .
Screening / Education .
reduces carriage in kids). all adults > 65 Protein conjugate vaccine .Screening / Education 23 valent Polysaccharide vaccine . better at protecting against localized dz. 13 valent conjugate for routine infant use and adults > 50 years old . not fully functional in infants) used in older children/ adults with risk factors.T cell dependent (effective memory cell response.T cell independent (no memory produced.
Screening / Education .
Screening / Education .
cross reacts with BCG vaccine) or IGRA (does not crossreact with BCG vaccine. 10mm = immigrants.Screening / Education HIV testing to ALL pts with TB Start ARVs ASAP (w/I 2 weeks) for HIV+ pts SCREEN ALL CLOSE CONTACTS w/ TST (requires 2 tests. if exposed to TB Ags. HCWs. immunodef. IDU. 15mm = nl IGRA = IFN-y release assay (T cells. contacts w/ TB inf indi. will release IFNy if inf) . single step so better for homeless) TST cutoff: 5mm= HIV.
Screening / Education .
Screening / Education Inactivated split vaccine (trivalent) . (4x dose & greater efficacy) Vaccinate HCWs!! .new vaccine for pts > 65 y. one B strain .contraind w/ allergy to chicken eggs or Guillian Barre Live attent Nasal spray mist (better mucosal immunity) .one A H3N2.o.contraind in people w/ reactive aw dz or pregnancy vaccination for everyone >6m Fluzone Hi dose . one A H1N1.
mAB) .high risk infants/premies vaccination w/ oral live attentuatd virus for military recruits .Screening / Education RSV prophylaxis (Synagis.
Screening / Education .
if large. high altitude CXR: inc cardiac silhouette (displaced apex from LVVO) Angiogram: blood moves from PA into aorta HF. systolic murmur across pulmonic = more severe septal occluder right heart failure. IE Patent ductus arteriosus nl at birth but closes w/I 48 normally functions to move blood from hours descending aorta to placenta and closes w/I 2 weeks of birth. fixed splitting of S2 (inspiration & expiration). diastolic murmur at tricuspid (severe) Hole in wall btwn 2 atria --> volume Down syndrome overload on RV. HF. slow growth. AO override Eisenmenger congenital abnl from the incomplete closure of intrauterine cnxtn btwn pulm artery & aorta --> decreased pulmnary blood flow more severe PS = more RVOT obstruction CXR: hyperlucent lungs (lack of blood getting to the lungs) central cyanosis. diastolic rumble membranous defect (high in septum) = hole betwn RV & LV --> blood moves directly into PA --> LVVO --> LV dilation (increased preload in left heart). clubbing. O2 step up in RA oxygenation. RVH 4. polycythemia (thrombosis. exercise) pushes more blood across PFO & into LA! Right to left shunts (de-oxy blood flows into systemic circ)cyanotic! Tetralogy of Fallot cyanotic skin during crying/feeding 4 parts: 1. displaced apex (if severe). primum defects are missing the upper cushion between atria. PS (RVOT obst) 3. & cryptogenic stroke!! Patent foramen ovale normally functions to move 90% of blood from RA to LA (shunts away from lungs). if not.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Left to right Atrial septal shunts defect (oxygenated blood flows thru a defect)acyanotic! parasternal impulse (severe). O2 step up in RV muscular defect (lower part of septum. pt will have dyspnea. Eisenmengers (deoxy blood in left heart from PA --> aorta movement causes PA hypertrophy = inc PA press = unoxy blood in left heart = cyanosis) septal occluder DVTs. after birth. growth retardation. maternal alcohol intake. premature birth. PH. congenital abnl when it never seals off. CVA). holes in septum) --> blood moves directly into RV --> RVVO (parasternal lift. shunt reversal (cyanotic.secundum (loss of tissue = hole between atria). 85% of ASDs occur in the (primum defect) fossa ovalis . hypoxemia. paradoxical embolus L-->R shunt that eventually reverses to R->L (acyanotic --> cyanotic shunt w/ increased pressure) Vascular/ Valvular congenital disease Bicuspid aortic valve pulmonic stenosis late peaking systolic murmur parasternal lift big "a" wave narrowing of pulmonic valve blocks blood usually part of from leaving RV --> increased afterload on tetralogy of RV --> RVPO --> RVH fallot Noonan's syndrome . trauma/MI (muscular defect) usually closes spontaneously by age 10-12. RVVO -> RV dilation increased preload on right heart diastolic murmur across tricuspid. clamshell occluder if small. asymptomatic. systolic murmur over tricuspid area) Down syndrome. it's a continuous murmur ULSE remaining fistula between aorta (hi press) diastolic rumble (MV) and pulmonary artery (low press) --> displaced apex PAVO & LVVO (if severe). MI. Eisenmengers). O2 step up in PA rubella. pulmonary hypertension (increased amt of blood in RH and PA) Ventricular septal high pitched holosystolic defect murmur (LLSE). LARGE VSD 2. PFO stays open so blood (AND clots) can pass through to LA increased right heart pressure (valsalva. Afib.
UA). ventricular HR > 100bpm Atrial Fibrillation Paroxysmal. kidneys & retina affected. profile) increased age. diet). check weight/ waist circumference. aortic dissection. while diastolic BP quickly goes down w/ meds (causes syncope) damage to target organs MI. PTH disease). fundoscopy. HF. decreased K or decreased aorta complicance (stiffer aorta) Ca intake. retina/kidney changes Secondary (about 5% of HTN) renal (abnl BUN. lipid Americans. PE: BP in BOTH arms. incidence of MI & atherosclerosis alcohol. hereditary kidney or smooth muscle defects. environmental (stroke belt). for blood flow) different contour to apex Idiopathic (95%) pre-hypertension (120Coarct (5-7%). Hct. creatinine. pregnancy arteriolar effects on brain causes hemorrhage. stroke. and reduces coronary artery filling loss of atrial contraction = blood stagnation or stasis in left atrium/ left atrium appendage = increased risk for thrombi/emboli RA/LA dilation. Stage 2 (>160/>100) aortic valve = LVPO = LVH = increased medications. stroke/ TIA) 60 million Americans EKG: fast. cerebral infarction). acute pulm edema). FBS. renal failure. reduces LV filling. irreg fibrillatory waves in middle. grossly irregular.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Tachycardia Sinus. cerebral probs (blurry vision. obesity. LVH/ CAD/ HF/ Afib. sedentary S4 (LVH causes decreased ventricular relaxation] lifestyle LV cavity size so atrial kick needs to push more blood in). obstruct sleep apnea Malignant Hypertension DBP > 120 mm Hg presents w/ acute pulmonary edema. hyperthyroidism Systemic Arterial Primary / Hypertension Essential (idiopathic) asymptomatic systolic BP Age (vessels stiffen. Cushing's. increased peripheral resistance causes vascular inelasticity/stiffness. heart/lung/neuro resistance. stroke) patients present w/ acute CVA (SAH. [inc systolic BP = inc pulse wave velocity insulin from loss of elasticity. rapid rate (110180) increased heart rate shortens diastole. drugs. loss of elasticity = stiffened LV = less exams. endocrine (pheochromocyt oma. need more pressure PE: normal position apex. aortic dissection. atrial. 139/80-89) white coat high pressure in aorta = obstruction after Stage 1 (140-159/ 90-99) effect. cardiac probs (ACS. diabetes) hard to treat bc systolic BP is less likely to decrease. retinopathy. aortic dissection. accelerated mild HTN Hypertensive Emergency Cocaine! . lipidemia. 3-4% of pts > 70 SA node years old inhibition. sustained apical impulse BP level that increases risk for CVD and target organ damage (pressure overload makes heart work harder to maintain CO. menopauses). obesity. FH Thrombi/ emboli formation pre-hypertension? Lifestyle mods (less salt. S1 intensity variation male gender EKG (but women R/O secondary catch up after causes (UA. coarct. salt. chronic no atrial activity so immediate loss of 20-25% of cardiac output. renovascular. modify risk factors (smoking. thrombosis. K/creatinine/ African calcium. atherosclerosis. NOT Pwaves PE: pulse deficit. exercise. or ischemia Renal disease. dec diastolic BP = bruits.
age amputees (asymmetric reversal of blood flow) Endovascular repair (catheter based. creating a false lumen uncontrolled HTN (95%). high pressure/ shear force from LV tears the intima and separates it from the media.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Aortic dissection proximal dissection (proximal to left subclavian a. aspirin. Marfan's. shear stress of blood flow (viscous drag of blood PE: pulsating abdominal flow across aorta surface): low and/or mass oscillatory shear stress= disturbed blood flow = increased atherosclerosis = matrix dysregulation = accumulation/ adherence of macrophages = propagation of inflammation into media & adventitia. ASYMPTOMATIC! increased BP = increased strain. the intima is damaged and friable (cystic medial necrosis= degenerative changes in media). syphilis. tearing chest pain through the back & is maximal at onset can also present w/ stroke. thrombectomy. -increased expression of AngII receptors and VCAM-1 on abdominal aorta w/ increased disturbed flow (low or oscillatory shear stress) trauma Marfan's. exercise ACEI. male gender. sedentary. DM. & head Atherosclerosis 10 million Americans. pregnancy EKG CT w/ contrast TEE (intimal flap) CXR (wide mediastinum bc now have 2 aortic lumens --> aortic dilation) nitroprusside (lowers BP) & beta blockers (lowers shear stress) until EMERGENCY surgery 50% of patients w/ proximal AD will die w/I 48h AR. catheterdirected life expectancy reduced 10 years in patients w/ PVD increased risk for death from stroke. white middle aged men. shock distal dissection can only treat medically by lowering BP and dropping shear force (betablockers) heart is sheared at the ligamentum arteriosum necrosis of all layers of aorta from MMP severe back pain. > age 70 FH. atherosclerosis (cholesterol + angiotensin II) 6% of individuals tobacco use. HTN. control of DM/BP/ chol. hi chol. viscera. M>>>F. 5% of people > 55 claudication . pericardial effusion w/ tamponade bleeding into pericardium. open surgical (graft material) progressive aneurysm expansion despite tx Aortic transection Abdominal Aortic Aneurysms (AAA) aneurysm >5cm = increased risk of future treatments: mortality external polymer + (PERFORM doxycycline to SURGERY!!) provide mechanical risk of surgical support and inhibit repair? Damage to MMPs spinal arteries --> spinal ischemia/ paralysis Peripheral Vascular Disease large difference between blood pressures of each arm claudication (stress ischemia in legs. idiopathic. used to check intervention success CT angiography: anatomic vessel narrowing risk factor modification. bicuspid aortic valve. Turner syndrome. tamponade in patients w/ HTN. stent material). MI decreased ABI = increased risk of mortality HEMORRHAGE w/ procedures . other activation --> profound inflammatory vascular sx (erectile dysfunction. lower most commonly located below renal peripheral disease) arteries (infrarenal) most patients are -aorta is exposed to deformation/ strain. antiplatelet (aspirin.9 represents obstruction) disorders of circulatory system to extremities. coarct cocaine. ascending aorta) large difference between blood pressures of each arm (but same BP in each arm does NOT R/O AD!) cold leg. predictable pain/ tightness/ weak/ tiredness) Ankle-brachial index (abnl < 0. AMA pregnancy. clopidogrel) surgery: endarterectomy. ligation. obesity. infarct. age Duplex US: increased stenosis & velocity. MI.blood supply is limited due to have ischemia so pts have calf pain w/ exercise claudication -> rest pain --> ulceration --> gangrene --> limb loss tobacco use. intermittent response (T cell & monocyte activation) claudication. bypass.
rheumatic HD. plavix. nl apex location. chronic bicuspid valve. maybe some fatigue. transient weakness) atherosclerosis of internal carotid artery: pieces of plaque embolize and enter internal carotid artery --> brain recent MI unstable angina uncompensate d CHF severe valvular dz (aortic stenosis) duplex US:carotid artery bifurcation CT angiograph stenosis of carotid symptomatic: treat/ surgery if stroke involves <1/2 or 1/3 of hemisphere.Flint diastolic rumble. asymptomatic: operate once stroke risk > surgery risk Meds: statins. early decrescendo murmur that masks S2 (longer murmur. LaPlace's Law) = higher LV contractility syphilis) (SV). Aortic the mildly hypertrophied LV too per aneurysm. BBs 50-75% stroke --> carotid stenosis!! BP control impt for pre& postoperative status (o/w inc risk of stroke & hyperperfusion syndrome poor BBB) shunt use if incomplete circle of surgery: carotid Willis? only if revascularization + seizure or loss of patching neuro capabilities perioperative Endarterectomy higher MI rate Stenting . so compensates w/ mild hypertrophy Austin-Flint diastolic rumble -mid-diastole.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Carotid Artery Disease symptomatic? Stroke. distinguish from MS diastolic rumble bc NO OS or presystolic accentuation problem w/ AV leaflets (acuteendocarditis. high output state (head bobbing. surgery if symptomatic . pressure overload --> leg fatigue LVH apex in nl location but diff contour very little hx: decreased exercise tolerance. aortic diastolic flow =loss of isovolumic transection.femoral asynchrony. some DOE sx: chronic vasodilation (warm.pressure in LV is much higher if dilation only. displaced apical impulse (dilated LV). trauma. decrease afterload) while waiting CHRONIC AR = reduce afterload. distal to subclavian. AV prolapse) CXR: enlarged LV silhouette. Austin Flint @ apex Turner syndrome rib notching (large intercostal artery erodes rib) HTN Aortic regurgitation (AR) Acute AR: sudden large regurgitant volume on nl LV = no compensation time for noncompliant LV = hi LVEDP (LV dilation) = early closure of MV = low SV = hi HR problem w/ aortic root that Abnl regurgitation of blood from aorta to LV pulls leaflets apart (acuteoccurring during diastole (retrograde AD. neck pulsations) acute AR: shock. nl MV is wide open w/ diastole but hi LVP causes MV to close sooner. acute pulm edema PE: hyperkinetic carotid w/ bifid pulse. TIA (amaurosis fugax transient monocular blindness.higher stroke rate Coarctation radial. no cardiac silhouette & pulm edema (acute AR) EKG: enlarged LV (LVVO) ECHO: degree of AR (backwards diastolic flow) + cause usually Cath: rapid decrease in aortic pressure ACUTE AR = surgical emergency!! Use vasodilators (nitroprusside.nl carotid. enlarged aortic bump (chronic AR only). wide pulse pressure = more severe) *acute AR . diastolic murmur @ URSE. diaphoresis). Austin. compliance. somewhat higher afterload (hence chronic Marfan's. relaxation = LVVO >> LVPO) --> higher preload. & wall stress DIASTOLIC PROBLEM eccentric hypertrophy (dilation/ LVEDV + some hypertrophy) .
nl neck veins. +/. annulus (aging. nl venous system.5cm severe AS: <1. S3.0-1. systolic ejection murmur. rheumatic heart dz mild AS: >1. bicuspid valve. papillary muscles (MI.5cm mod AS: 1. LV dilation (large distance from pap muscles) 3. aortic diss (w/ bicuspid AV) NO exercise stress aortic valve test! replacement (percutaneous. nl apical impulse. endocarditis) 5. holosystolic murmur @ apex that intensifies w/ handgrip Acute MR: pulm edema.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Aortic stenosis (AS) subvalvular (HCM. heart block (conduction probs). SAM in HCM) 4. endocarditis. S3+S4. bicuspid & +/.decreased aortic sound @ URSE. decrescendo systolic murmur. supravalvular. NO afterload) = loss of isovolumic contraction CHRONIC MR: Compensatory mechanisms = eccentric hypertrophy (LV dilation + some LVH) = higher compliance (LVEDV w/o LVEDP) = early effect of higher SV and EF. Afib. surgical repair/replacement for chronic MR acute MR: nitroprusside. leaflets (MVP. abnl AV Very limited meds (tri-leaflet & calcified. mitral annular calcification. VALVULAR narrowing of aortic valve area < 3cm CO maintained @ rest. hypotension (low PP). HTN) 2.thrombi ACUTE MR: non-compensated LV so regurgitated blood goes all the way back towards lungs --> pulm edema MV apparatus parts: 1. chordae tendonae (trauma.paradoxical split SYSTOLIC PROBLEM but DIASTOLIC DYSFXN endothelial disruption (leaflet injury from atherosclerosis calcification or wear & tear) --> entry of inflamm cells & lipids --> sclerosis --> stenosis blood flow across AV impeded during systole (inc afterload)--> LVPO--> concentric LVH --> dec compliance of LV (inc LVEDP) --> LA hypertrophy & diastolic dysfxn increased age. CXR: nl cardiac surgical) silhouette EKG: LVH NO exercise!! ECHO: thickened ventricle. S4 @ apex. endocarditis. RHD. mid to late systolic murmur a/w coarct in Turner's syndrome. sudden death Mitral regurgitation (MR) asymptomatic for years until LV dysfxn Sx: fatigue + weakness (low CO). membranous AS. nl location apex. eventually LA dilates = prevention of hi PAP but decreases CO --> Afib +/. rupture. sustained PMI.0cm. hi LV press (200/2040) inc LAP -> inc afterload = inc LV dysfxn = LVVO + LVPO that backtracks into pulm system = systolic HF! Mortality >90% after sx develop aortic regurgitation. acute MR . effort syncope (fixed orifice + vasodilation). NOT @ exercise LVOT obst sx: angina. enlarged & laterally displaced apex (LVVO = LV dilation). narrow LVOT). dilated CM) CXR: acute MR (pulm edema). DOE (LV failure) PE: hypokinetic carotid. chronic MR (LV + LA enlargement) EKG: LA enlargement + LVH ECHO: MR cause + severity grade Cath: acute MR: large v wave = increased PCWP = increased LA pressure decrease afterload. parasternal lift (RV dilation) SYSTOLIC PROBLEM Retrograde systolic flow from LV to LA = hi LAP + hi LA volume = hi LV volume when blood pumped backwards returns to LV during diastole = pure LVVO (hi LVEDV. mid-diastolic rumble. EMERGENCY surgery .pulm edema PE: nl carotid (less blood but coming out faster so feels nl). palpable S4.calcifcation) cath: lower AV pressure (100/80).
arrythmias. holosystolic murmur that increases w/ inspiration @ tricuspid area. TR murmur +/. RA myxoma extremely rare! . hoarseness if LA percutaneous gets so large it balloon valvoplasty impedes recurrent or valve laryngeal n. thick-walled LA = inceased pressure = Chorea. therefore.infective endocarditis.PAH). handgrip. replacement more severe if earlier opening snap or longer diastolic rumble Mitral Valve Prolapse (MVP) Hx: usually asymptomatic. Kerly's B lines (pulm edema). symptoms from LA distensibility (small Nodules.0cm dyspnea (hi LAP = pulm venous HTN). RV hypertrophy if PAH developed Echo: thickened mitral leaflets + abnl fusion of commisures. LV filling (hi LVEDP) Carditis. possible intra-atrial thrombus diuretics for HF.5cm. tensing of chordae & stenotic leaflets w/ MV opening)/ diastolic rumble w/ presystolic accentulation @ apex Rheumatic Heart Disease obstruction to flow from LA to LV. BB for afib. (since elongated in MVP). anticoagulation for afib. Valsalva. dilation of LA = increased volume Erythema migranatum. billowing of mitral leaflets into the LA stabs). loud S1 at aortic area (prominent MV closure sound). SYSTOLIC PROLAPSE atypical chest pain (sticks. low PP (low CO). OS at tricuspid area RHD. parasternal heave (RV dilation). use beta-blockers leaflets can collect microthrombi). cavity is reduced during ejection squatting increase LV cavity = later/shorter LV needs to be large for chordae to match murmur. OS (after S2. acute pulmonary edema. fatigue (low CO). reassurance!! fibrin emboli to eye/brain (abnl If symptomatic. valve spontaneous chordae tear repair preferred over replacement Men over age 45 have increased risk for thickened leaflets & MR Tricuspid Regurgitation PE: "cv" regurgitant wave. if severe MR (uncommon). pectus excavatum familial type due 2-4% of women to Marfan's syndrome or CTD (Ehler'sDanlos) ECHO: posterior displacement of one or both mitral leaflets during systole 95% are benign so endocarditis. S3 or mid-diastolic rumble if severe acute . handgrip) has less mitral cavity = earlier/longer regurgitation murmur. carcinoid syndrome pulmonary hypertension from MS or RHF Tricuspid Stenosis PE: giant "a" wave. loud P2 +/. afib (chronic hi LAP = LA dilation). impeding (remember LA emptying (hi LAP) and causing impaired CANCER mneumonic.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Mitral stenosis (MS) mild MS area >1.S3 (if severe). diastolic rumble that increases w/ inspiration at tricuspid area. Arthritis. progressive MR. prominent pulm arteries EKG: LA enlargement w/ possible Afib. severe MS area <1. palpitations (Afib) PE: hypotensive. thromboemboli. palpitations during ventricular systole due to PE: "click + murmur" (may protrusion of enlarged/thickened valve be absent)= mid-systolic leaflets (esp the posterior leaflet) OR click (leaflets popping back) thin/elongated chordae tendonae that DYNAMIC auscultations: fail to keep leaflets in apposition when pregnancy. Rheumatic fever) DIASTOLIC PROBLEM Pathology: fused commissures CXR: LA enlargement. giant "a" wave (PAH) or big "cv" wave (TR). right heart failure. interstitial edema. carcinoid syndrome. increased LV cavity (maneuvers like standing = decrease LV squatting. parasternal heave (hi RV pressure).RHD.PR murmur (Graham-Steele . chronic . hypokinetic carotid. orthopnea/ PND.
carcinoid syndrome Pulmonary Regurgitation Left ventricular hypertrophy severe PAH. S3/S4.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Pulmonic Stenosis PE: giant "a" wave. fatigue PE: JVD. systolic murmur @ pulmonic listening area PE: hi pitched diastolic blowing murmur sustained apical impulse normal placed PMI palpable S2 (presystolic component) congenital (Tetralogy of Fallot). presentation during last month or postpartum cough. CXR multiple thyroid panel gestations. ECHO multiparity. tocolysis w/ bagonists standard heart highest mortality in failure mgmt.edema postpartum thyroiditis 1/3000-4000 pregnancies AMA. exercise (nl) Diastolic dysfunction (thick ventricle walls = decreased compliance = small cavity = decreased filling during diastole!) myocardial ischemia (decreased coronary blood flow) systolic dysfunction (late! Due to narrowed pulse pressure) Peripartum cardio-myopathy (PPCM) No pre-existing heart disease. HTN/ pre-eclampsia. dyspnea. +/. soft P2/ES that increases with inspiration. tachycardia.1st 3 months coagulation until pregnancy ends LV thrombi (1/8 risk) --> stroke . congenital increased pressure overload on LV causes HTN increased wall thickness and decreased LV AS cavity HOCM coarctation Pregnancy. anti. obesity. parasternal lift.
accumulate fluid slowly so that pericardium stretches w/o marked increase in pressure Silent or symptomatic? 1. Leukocyte exudation (neutrophils. aortic dissection. T = tumor/ trauma/ TB.low blood proteins) = abnormal rub. colchicine if chronic pericarditis Pericardial effusion Symptomatic . mononuclear cells) post-MI pericarditis: 1. Dressler syndrome (>2wks post-MI) antigens from dying myocytes = activated autoimmune reseponse = inflammation of pericardium ATRIUM (A = AIDS/ Autoimmune dz. malignancies. local vasodilation & transudation of serous fluid 2. diffuse T abnl that persist for some time ECHO: +/pericardial effusion post-MI pericarditis (tx w/ hi dose aspirin) NSAIDS. volume of fluid 2. lymphatics are unable to handle extra fluid). early onset (<1wk post-MI) . or decreased muffled heart sounds.TB/ chronic inflamm) Purulent (uncommon. rate of fluid accumulation 3. tumor. TB Fluid analysis to R/O malignancy TTE: pericardial collections (quantifies volume of fluid.accumulate lots of fluid quickly under hi press (chest trauma). uremia) Pain is worsened w/ position (lying down)/ expiration/ swallowing pericardial rub + soft heart sounds pain relieved by leaning forward inflammation has 3 outcomes: 1. compliance of pericardium idiopathic. & guides pericardiocentesis) treat underlying disorder (dialysis for uremia) Observe asymptomatic effusions pericardiocentesis for therapeutic drainage & analysis Increased capillary permeability (hypothyroidism). bacterial inf) Hemorrhagic (bloody pericardial inflamm due to TB. I = idiopathic/ inf/ infarct. R = Radiation/ rheumatic fever.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Acute Pericarditis Serous (scant cells. trauma. plasma oncotic pressure (nephrotic reduced intensity friction syndrome . U = uremia from renal failure. radiation. M = meds) EKG: diffuse ST elevation that disappear as patient recovers. asymptomatic . increased capillary hydrostatic pressure (HF. viral causes. Ewart sign (dullness to fluid in the pericardium = increased percussion over posterior pressure in a non-distensible sac --> left lung by scapula) enormous compression force on the heart (cardiac tamponade) EKG: electrical alternans (QRS pericardial window complex height procedure varies from beat to beat) . increased vascular permeability (protein spills into pericardial fluid) 3.inflamm from infarction spreads/extends into pericardium 2. early acute inflammatory pericarditis) Fibrinous (plasma proteins + thickened/ fused visceral & parietal pericardium. determines if ventricular filling is impaired.
inspiration can have effusiveconstrictive pericarditis (tamponade physiology --> effusion drainage -> constriction physiology) Arteriosclerosis Medial calcific sclerosis affects arteries of lower extremities and genitalia. particularly in the kidney calcification of the tunica media. simultaneous bx) life-threatening emergency!! (if worsens. there is no filling during diastole = zero CO = pulseless arrest) Constrictive pericarditis deep Y descent. muffled heart sounds pulsus paradoxus (decreased systolic BP of >10 w/ inspiration) pericardial fluid under acute increased pressure compresses the heart continously through cardiac cycle. pressures are equalized & elevated (LVEDP = PCWP = PAP= RVEDP = RAP) cirrhotic appearance (ankle/leg edema. acute hemorrhage (acute ascending aortic dissection. hepatomegaly). compressed. dip & plateau in early diastole. common in diabetes age > 40-50 thickening of the arteriole wall that results in some degree of ischemia . increased JVP (elevated venous pressure. discordance in RV & LV pressures w. pericardial window procedure (removal of pericardium allowing fluid to drain freely into mediastinum * absorbed by lymphatics. & collapsed RV during diastole catheterization = gold standard Pericardiocentesis. difficult to find PMI.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Cardiac tamponade CC: breathlessness (decreased CO & max increased EDPs = increased press in alveoli). bacterial inf Pathology: pericardial pericardium stripping surgery becomes immovable shell w/ fused/ thick layers from chronic inflamm CXR: calcified pericardium Catheterization: elevation & equalization of pressures. hypotension.decreased filling of ventricles). impaired filling of LV = reduced SV & CO = hypotension chronic changes from inflammation. low output state (shocklike). tachycardia. the muscular coat of the artery intermittent episodes of HTN? marker of HTN. idiopathic pericarditis (postviral). Kussmaul (inc JVP w/ inspiration). TB. deep "x". tachycardia BECK'S TRIAD: Hypotension. blunt trauma. RA. hypotension. early to mid diastole knock physiologic abnormalities during diastole. y descent in RA. limiting ventricular filling --> increased venous pressure to compensate for decreased filling --> equalization of diastolic pressures to intrapericardial pressure (IPP=LVEDP= LAP = PCWP=PAP=RVEDP=RAP) any cause of acute pericarditis can progress to tamponade (ATRIUM). decreased pulse pressure. flat "y" . radiation. does NOT produce ischemia Arteriolo-sclerosis disorders of small arterioles. rigid/ scarred pericardium prevents normal mid-late filling of cardiac chambers (early filling only!) --> filling is arrested --> increased systemic venous perssure & signs of RHF. ascites. inc CVP. LV rupture) TTE: smaller.
no sx at rest PE: during angina. older ptshi risk for CABG myocardial ischemia. less inflammatory cells. lots SMCs. cytokines are fibrogenic so increases ECM secretion (collagen) --> plaque formation fatty streaks seen in 50% of teens and >85% of people over age 20 localized flow abnl. which stimulate collagen & plaque formation. lipids are released into circulation and activate thrombosis --> ischemia. MI other complications if embolization of plaque material MI @ sites of unremarkable lesions single occlusion = diffuse disease CABG decreases risk for rpt interventions Chronic Stable Stable Angina Coronary Artery pectoris Disease chest/ jaw discomfort provoked by exercise that lasts 4-5mins.early lesions). unstable plaques) stress test: ST depression (ischemia) & area of ischemia (suggests anatomic stenosis) Resting EKG CT angiography Cardiac cath if + stress test histology: increased proliferative SMCs and fibrous tissue. less inflammation receptors that internalize LDL --> foam renal arteries often spared! cells. HTN. bubbly foam cells. inflammatory cells. episodic. not much atherosclerosis & no thrombus/plaque formation no diff btwn PCI & med w/ # MIs. CHF.expression of VCAM core. macrophages have scavenger matrix. branches) localized flow abnl --> turbulent flow in arterial system --> endothelial dysfxn--> increased ROS production. valve (BBs. reduced blood flow does not cause cells to die like in MI! --> instead. new matrix being deposited. larger fibrous cellular Monocytes --> macrophages in the tissue by M-CSF. friable cracks/ fissures) histology: clear cells in intima (fatty streaks . or paradoxically split S2. FH. low HDL. does not look vulnerable bc lipid core is far from lumen & thick fibrous cap Lifestyle modification. PCI. prior known CAD Prinzmetal angina uncommon. waist circumference (W>35. by dec O2 demand myocardial rupture (BBs. smoking. abdominal aortic aneurysm if top of plaque ruptures. sites for thrombus development (mural thrombus in aorta common in HTN. high content of inflammatory cells (lymph/monocytes) accumulation of lipid. CABG. hi risk plaques? Large extracellular lipid content. fatty streaks. reduce sx thrombus. nitrates) . S3. foam cells die. releasing cytokines and leaving cholesterol crystals. smoking. diabetes (all increase ROS and decrease NO) age male gender pathology: gross large arteries (yellow spots = foam cells. M>40). decreased NO production --> increased permeability of Stable plaque? Smaller lipid lipids & inflamm cells. statins. claudication. stable sx & predictable onset. abnl PMI (if LV dysfxn). infarct risk does NOT correlate w/ amt of occlusion!. medical therapy PCI if intolerable angina despite maximal med tx & anatomy that doesn't require CABG. MR. ischemia results from increased oxygen demand (exertion) but disappears w/ rest in a predictable fashion >75% stenosis usually but no plaque disruption or thrombus formation Unlikely to rupture: thick fibrous cap.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Atherosclerosis vulnerable. CCBs. muscular arteries fibrous cap & lipid pool (stable v. histiocyte giant cells surround cholesterol crystals. HTN. occurs at rest coronary artery vasospasm. LDL is oxidized to cholesterol & cholesteryl esters. intact endothelium AS high LDL. increased LDL. you might hear a new S4. Meds: increase life arrythmias. CABG if left main no diff btwn PCI & coronary narrowing CABG for pt (>50%) or 3 vessel survival CAD MI. smoking men). dysfunctional myocytes reduced perfusion from chronic stenosis. thin fibrous cap. & ECM (collagen) in the arterial intima (large & muscular arteries at bends. LV aspirin). dysfxn. elevated JVP (if RV dysfxn) asymptomatic often in women & diabetics.
disruption of plaque diaphoresis 2. most often at vent free wall. vent aneurysm. neutrophils) 3-10d (red border. 24h (dark mottling. not all cells affected stent thrombosis equally . coronary artery emboli. also vent septum . and aggregated coronary art 4. shock. dilated) --> lack of perfusion -> heart remodeling EKG: do not always elicit changes. variable plaque disruption causes partially occlusive thrombus that damages the subendocardium but not the areas closest to blood supply progressive heart failure ischemic myocardial damage from due to ischemic myocardial coronary artery disease (atherosclerosis) damage or previous MI --> enlarged LV (hypertrophic. 6. contractile dysfxn. coagulation cascade is activated vasospasm.epicenter cells > peripheral cells) -> microvascular injury (>1h) imbalance of O2 supply and demand NSTEMI: partial occlusion STEMI: complete occlusion 500. anemia. FN) causes: 3.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Unstable angina pectoris variable progressively worse sx & frequent plaque rupture with thrombus formation. lipidemia. myocardial rupture (highest risk 4-7 days post-MI. first medical coag necrosis contact time to loss of nuclei) balloon! 1-3d (mottling w/ yellow center. ATP --> loss of contractility --> irreversible CABG. occlusive thrombus forms emboli. NSTEMI) prognosis depends on infarct size. quality of LV fxn. fissure/cracking of plaque exposes non-atheroscl thrombogenic areas (collagen. extent. tachycardia entire thickness of disruption of variabe stenosis but unstable plaque ventricular wall affected by with disruption & consequent occlusive endothelium the MI thrombus forming on the plaque --> atheromyocardial wall damage chest pain. platelets adhere. arrythmias. coronary artery heart perfused by coronary arteries vasospasm from outside --> inside (cocaine).000 die before reaching hospital DM. eroded endothelium Ischemic Heart (General) disease (also includes angina but see above) Transmural MI atherosclerotic CAD (90%). sudden death rupture plaque) Rupture? thin fibrous cap. large lipid deposits. HTN. pap muscle dysfxn. mb & troponin I/ T ability to perfuse viable myocardium 0-12h no changes. weak rapid sclerosis pulse.1st year RV infarction infarct extension new necrosis next to the infarct region. downstream ischemia --> depletion of hypotension. (fibronogen --> fibrin via thrombin) coronary art 5. smoking.L-R shunt& papillary muscle acute MR). extent of labs: elevated CK. coronary cell injury (20-40min.000 deaths/yr in U.S. ST abnl (STEMI. non-Qwave MI elderly patients . anemia. 250. partially occlusive thrombus stenosis pain more frequent/intense w/ less starts as lumen compression w/ little lipid exertion core but grows with lipid deposit increasing persistent. becoming activated arrythmia. fewer SMCs. mural thrombus. 1. site. age (although 10% of MI in age<40) most common MI 6am-11am (catecholamine s are highest and platelets stickiest!) EKG: deep Q waves. unrelenting pain -->thin fibrous cap-->subject to rupture--> thrombus formation--> vulnerable plaque for several hours (due to contributing to MI. exacerbations myocardial hypertrophy. infarct expansion dilation of infarct region. vWF.vascular disease. late CHF Subendocardial MI most susceptible to ischemia bc farthest away ischemic cardiomyopathy variable stenosis. dyspnea. increased inflammatory cells. yellow center/ neutrophils & macrophages) 14d (red-gray/ granulation tissue) >3m (scar) 30% overall mortality. pericarditis.
xanthomas Familial Hypercholesterolemia abnl high LDL (heterozygote LDL > 200. infections Histology: fibrinoid necrosis & leukocytoclastic vasculitis (neutrophils!) . smoking low triglyceride diet nutrition referral increased LDL:HDL predicts higher risk for CV event Dyslipidemia (General) Familial Hyperhigh fasting triglyceride chylomicronemia levels and low LDL levels pediatric presentation w/ chronic abdominal pain (pancreatitis). dilated CM. metabolic causes (insulin resistance pre diabetes.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Sudden death unexpected death from severe stenosis with frequent plaque cardiac cause early after or disruption and large occlusive thrombus --> w/o onset of sx fibrotic scarred myocardium that cannot conduct electricity efficiently lethal arrhythmia. GI (bloody stools. meds/toxins. renal (hematuria) inflammatory damage to the blood vessels. isolated hypertrophy) secondary causes? Diabetes. kidney dz. progestins/ steroid drugs DIET. LDL remains exceedingly high in the bloodstream. drug side effects. AS. niacin. homozygotes LDL > 500) cutaneous manifestations (xanthelasma. RA. dermatomyositis). RBCs) & possibly ischemia if damage to infections) larger vessels skin is the most commonly affected site autoimmune dz (SLE. melena). hypertrophic CM. hypothyroidism hormones). more LDL in circulation = more LDL that is able to pass through endothelium into the intimal layer of arterial wall --> atherosclerosis autosomal dominant mutation in LDLR 1 in 500 homozygous FH patients have more severe risk & dz (little or no LDLR) no specific mutation testing but cascade genetic testing for family risk assessment impt aggressive + early increased risk for tx (combo therapy CV event even at young age of statin + cholesterol absorption inhibitor). non-blanching papules/macules). myocarditis. hypothyroidism. PH. MVP. thickened Achille's) premature vascular dz defect in LPL or its cofactor apoC-II so autosomal 1 in 1 million kids cannot break down chylomicrons (>90% of recessive TGs) mutation in LPL gene or ApoC-II gene defects in LDLR so LDL is not taken up by the liver. instead. conduction abnl. lung (hemoptysis). nonatheroscl causes (congenital abnl. secondary resulting in hemorrhage (extravasation of causes (meds. genetic errors of metabolism. liver dz. hepatomegaly. corneal arcus. LDL apheresis Vasculitis (General) can affect the skin (purpuric.
ANCA negative histology: necrotizing vasculitis of medium sized vessels . weight loss. patients < 40 y. HepB antigen. abdominal pain/ melena. NO lung involvement not well understood HepB elevated BUN or creatinine. low blood pressure. mostly histiocytes & lymphocytes granulomas. neuropathy. ulceration/ necrosis seen sometimes (vascular damage & ischemia) lower legs = primary site lower extremity vasculitis from blood & extravasated erythrocytes that infiltrated the tissue Giant cell (temporal) arteritis Large vessel vasculitis scalp pain/tenderness distributed along temporal artery. eosinophilic line high dose corticosteroids for months (reduce inflammation and prevent subsequent sequelae) Elevated ESR/CRP Takayasu arteritis Large vessel vasculitis (aorta & subclavian a) Pulseless disease. mostly histiocytes & lymphocytes granulomas (cannot be distinguished from temporal arteritis histologically) Elevated ESR unpredictable course: rapid progression + quiescent stages polyarteritis nodosa (PAN) medium vessel vasculitis systemic sx (fever. visual disturbances/blindness (if opthalmic a involved). Females 7:1 histology: NO NEUTROPHILS. HTN. destruction of internal elastic lamina & narrowing of vascular lumen..o. ocular disturbances. carotid tenderness aorta & major branches become inflamed w/ granulomatous infiltrates so arteries do not distend or carry pulse wave more common in Asia. purpuric skin lesions).o. females 3:1 histology (hi false positive rate): NO NEUTROPHILS.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Cutaneous vasculitis purpuric lesions. myalgias. polymyalgia rheumatica in upper neck/shoulders "hunched over elderly person w/ lateral headache" not well understood elderly patients (>60 y. nonblanching.).
ventricular insufficiency. Kidney involvement (hematuria. Lung (cough. CNS.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Kawasaki disease medium vessel vasculitis multisystemic sx (polymorphous skin eruption. saddle nose deformity). cervical lymphadenopathy. peripheral nerves. renal glomerulonephritis) not well understood Young adults. proteinuria) other multisystemic manifestations? Cutaneous. peri/myocarditis). pulmonary infiltrates (noncavitating). M>F history of asthma or allergic rhinitis peripheral eosinophilia. erythema of conjunctiva/oral mucosa/tongue "strawberry tongue".arrythmia. hemoptysis. edema in hands/feet. middle ear. involves dermis & subcutis (cutaneous only involves superficial layers) . coronary vasculitis --> ischemic dz/infarct. red cell cast in urine c-ANCA positive (proteinase-3) histology: vasculitis w/ necrotizing granulomatous inflammation Allergic granulomatosis (Churg-Strauss) small vessel vasculitis Multisystemic disorder (fever. males 3:2 pathology: cavitary lesion in lung UA: hematuria. coronary arteritis. ocular. oral cavity (midline destructive lesions) not well understood may be a/w strep/ staph infection pediatric presentation anti-endothelial antibodies ANCA negative IV IgG and aspirin to reduce inflammation and avoid sequelae approximately 50% of cases will have CV involvement lifelong risk for coronary artery aneurysm MI in kids!! not well understood middle aged. cardiac involvement . aneurysms) Wegener's granulomatosis small vessel vasculitis ELK: Ear/nose/throat (URI. desquamation of fingertips/toes) CV INVOLVEMENT! (myocarditis --> CHF. cavitary necrotizing lesions). elevated ESR p-ANCA positive histology: vasculitis w/ necrotizing granulomatous inflammation & abundant eosinophils.
proteinuria p-ANCA or cANCA positive Cocaineassociated vasculitis ear vasculitis COCAINE contaminant (levamisole) elevated serologies common in cocaine abuse (antihistones. drug related? Elevated ESR. anemia. abdominal pain.hemoptysis.bloody stools. myalgias) pulmonary involvement distinguishes from PAN not well understood possibly Adults infection related (strep). melena. pulmonary involvement!!! .human neutrophil elastase cross reacts w/ ANCA impt to do urine drug screen!! Histology: leukocytoclastic vasculitis. c-ANCA & p-ANCA. proteinuria histology: leukocytoclastic vasculitis of superficial skin (not specific) Microscopic polyangitis small vessel vasculitis diagnosis of exclusion (overlaps w/ PAN) Multisystemic vasculitis (cutaneous purpura. M>F related Immunoflourescenc e: IgA deposition in vessel walls ANCA negative UA: hematuria. dsDNA) . intrapulmonary hemorrhage. renal glomerulonephritis.o. renal glomerulonephritis) not well understood possibly children <10 infection or drug y. focal thrombosis .Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications HenochSchonlein purpura small vessel vasculitis Multisystemic disorder (cutaneous purpura w/ leukocytoclastic vasculitis. abdominal pain . arthalgias. renal failure UA: hematuria..
cor pulmonale. valvular dysfxn thin walled. therefore. amyloidosis hypertrophied. <3remodeling! Right sided HF: inc RA pressure (>10 mm Hg). wet"): valvular dz. filling is impaired bc ventricle doesn't relax. edema (ascites. tachycardia/pneic PE: JVD (inc cardiac filling pressures & volume). SV but inc LVEDP. pulm edema. lisinopril. venous congestion 3. dilated ventricle triad of meds (carvedilol . dilated CMP. nl EF control BP. thickened cardiac myocytes Abnormalites in LV diastolic dysfxn? can be just as symptomatic slowed/delayed/incomplete relaxation. as sHF if patients have mod-severe diastolic dysfxn increased LA pressure during early filling. severe pulmonary hypertension. use ECHO instead . increased LVEDP. concentric remodeling. stomach/ liver congestion (early satiety. enlarged. HTN. orthopnea. anorexia.no lymphatic compensation=fluid leaks into alveoli (PE. displaced PMI. elevated SVR (vasoconstriction. overall fluid retention def: inability of heart to pump blood forward to meet metabolic oxygenation demand of tissues while maintaining nl filling pressures backwards! dyspnea.use cardioversion! Systolic heart failure reduced EF (LVEF < 4050%) = impaired contractility w/ progressive dilation & eccentric remodeling Almost all pts w/ systolic dysfxn have comcomitant diastolic dysfxn (impaired relaxation) CAD. relaxation. dyspnea) chronic HF: "silent" . decreased filling of LV. early rapid filling phase is delayed and need compensation by atrial contraction (atrial kick) be careful w/ diuretics (pts have small/ stiff LVs so elevated BNP diuretics can CXR: pulm edema cause LV ECHO: R/O other underfilling --> causes for hypotension. "cold") & LVEDP (inc afterload. expanded plasma volume ("wet"). left HF Left sided HF: inc LVEDP due to intrinsic LH dz. spironolactone) decrease afterload = improved SV = less ischemia. falls!) shows LA enlargement. PM dry cough. anemia. HOCM. PND.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Heart failure (General) 3 characteristic sx: 1. clammy extemities. nl LV volume. "noisy" . n/v). pleural effusions (chronic CHF). PVEDP at rest/exercise w/ diastolic dysfxn. a/w sleep apnea. distended abdomen/ hepatomegaly.BB. shift of filling from early to late diastole. CAD 5 million Americans have CHF. rales (basilar. Paget's. syncope. inability to augment relaxation w/ exercise. acute CHF). decreased early diastolic suction/recoil. PE. & pulm congestion Ischemic cardiomyopathy (atherosclerosis! !) hi CO conditions ("warm. Beri-Beri low CO conditions ("cold. S3. 1 million hospitalizations/ yr CXR: cardiomegaly if chronic HF (cardiac remodeling) Elevated BNP (nl <100) development of kidney failure (nl creatinine = 1) most impt negative prognostic factor! Afib (atria become inflamed/scarred/ dilated) . = reduced preload = reduced remodeling increased prevalence w/ age requires clinical evidence of impaired RV relaxation or LV passive stiffness: no treatment. impaired CO (weak pump) 2. HTN. volume overload (increased sodium = inc total body water). MR (if severe dilation) acute HF: no compensatory changes from body yet so cardiac output =/= peripheral tissue metabolic demand. cold extremities (inc catecholamines= vasoconstriction = low CO). EF > 50% diastolic dysfxn (abnl distensibility. sx of lung congestion (not so much peripheral) & low CO (cold. low urine output) impaired contractility. ventricular rate & heart cath = gold rhythm std but invasive. impaired LV filling. increased RR. peripheral edema. just symptom relief presence of symptoms = worse prognosis high comorbidity burden (usually elderly patients w/ dHF) majority of dHF patients die from non-cardiac causes Diastolic heart failure impaired relaxation = elevated LVEDP. or filling of LV) + signs/symptoms of HF hypertensive CMP. dilated CMP. AV fistula. LAEDP.compensatory mech (inc colloid pressure = enhanced lymphatics so no rales! retain more salt = renal failure) = maintained CO. periph edema). wet"): hyperthyroidism. PCWP > 18). COPD. rales. impaired rate/extent of LV filling.
peripartum. angiogram pathology: buildup of scar tissue. HCM. CAD. or both. arrhythmias diuretics) (ventricular tachycardia) ICD (internal cardiac defibrillator to prevent SCD) LVAD or transplant if unresponsive to meds Arrhythmogenic Right Ventricle Cardiomyopathy (ARVC) autosomal dominant mutation in desmoplakin. plakophilin-2. noncompaction) elderly women w/ HTN. desmoglein-2 dilated and poorly fxning RV. genetic (hypertrophic. Afib Hypertensive cardiomyopathy dilated. S3 african americans Familial dilated cardiomyopathy autosomal dominant mutation in myosin heavy chain or troponin T younger age (20. HTN. infiltrative). fibro-fatty replacement of myocardium 1 per 1000-2500 clustering of cases in Veneto region of Italy genetic testing ECHO: dilated RV EKG: epsilon waves in ST segment (delayed depolarization) aneurysms of RV wall on cardiac MRI.multiple family genetic testing 30s) members affected CHF tx (BB. thick heart on ECHO increased diastolic pressure (>85 or 90) dilated LV (nl 4-5cm) causes poor systolic fxn (can barely contract) PE: displaced PMI. dilated. or filling of LV EF or systolic fxn) Acquired (CAD. chemo. DM. white and yellow fibrosis (RV muscle replaced w/ fibrotic tissue) SCD Ventricular tachycardia . leading to decreased fxn asymptomatic diastolic dysfunction increased age (ventricular filling) associated w/ restrictive (age has a CM. viral. restrictive.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Heart failure w/ normal EF (HFnEF) 60% of HF patients have nl EF Cardiomyopathies (General) any disease of the heart muscle. infiltrative CM greater impact on ventricular filling than on diastolic dysfxn = abnl diastolic distensibility. relaxation. alcohol. ACEI. CHF. valvular. arrythymogenic.
valsava. volume overload. sarcoid) prior radiation ECHO: huge. 2+ risk factors (FH. troponin T) that causes LV hypertrophy in absence of another identifiable cause LVOT obstruction SAM associatd MR (systolic anterior motion of MV) 1 in 500 adults family history of HCM/SCD Increased LV pressure (higher than aortic pressure) during systole sucks MV in Diastolic obstructing the LVOT dysfunction squatting--> standing makes murmur worse (decreased preload = less venous return = LV cavity shrinks = smaller distance btwn MV and septum = worsened obstruction). bisferiens pulse autosomal dominant sarcomeric mutation (B-myosin heavy chain. syncope (drop in BP. thin dilated atria w/ normal appearing ventricles and normal systolic function Left Ventricle Noncompaction decreased LV function. handgrip. craters sporadic (similar to RV) rather than being smooth (like normal LV) sarcomeric mutations but also other nonsarcomeric mutations implicated… increased risk for LV dilation. CCBs. ventricle. wall thickness >30mm. Increased collagen alcohol septal = increased ablation.(-) inotropy (BB.MI.intramural scarring -> Vtach) remove part of septum= widen MVseptum gap. increased LV dilation Embryological problem where the LV wall variable genetics. VT.fibrin. thromboembolic events Hypertrophic Cardiomyopathy most common of all genetic cardiac dz LV thickening (appears later in life) heterogenous hypertrophy (interventricular septum. SAM of MV.disopyramide) most common cause of SCD in athletes! (especially if surgical myectomy. stiff ventricle that can't relax during diastole) stiffness in ventricle causes chronically elevated atrial pressures (dilated atria) idiopathic infiltrative dz (amyloid. paradoxical embolus (thrombus from a DVT enters systemic circulation via PFO) hypercoagulable states. apex) Sx: dyspnea. angina. unexplained syncope.from obst of MV) that worsens w/ squatting--> standing. valsalva increases intrathoracic pressure = decreased preload = smaller LV cavity = worse obstruction bisfeirens pulse (early rapid ejection of blood from ventricle followed by MV obstruction.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Restrictive cardiomyopathy sx of CHF (dyspnea. septal base. tall QRS. possible MR (MV pulled open in systole) Pathology: calloused IVS from MV hitting HR. nonsustained VT Non-neoplastic Thrombi Cardiac masses most common masses in nonbacterial thrombotic endocarditis . recesses. myocyte disarray EKG: Brockenbrough's sign (PVC --> press gradient --> aortic press drop). myosin binding protein C. edema) very difficult to distinguish from pericardial constriction non-dilated. invert T ECHO: thick LV wall w/ nl systolic fxn. LV overcomes obst so late ejection of blood) histology:collagen. is not compacted properly so has appearance of crypts. S4 (atrial kick against stiff ventricle).induce MI arrhythmia risk in basal septum= fibrosis/shrinking) ICD: indicated if aborted SCD or sustained VT. Afib (or other rhythm disorders) Tuberculoma normally TB will affect the pericardium but there is potential for it to appear as a myocardial lesion Infective endocarditis . SAM) PE: holosystolic murmur (MR. CHF. aortic midsystolic notching (late ejection from obst) Doppler: turbulent flow (MV obstruction in LVOT). abnl BP drop. DVT composed thrombi on valves that do NOT heart! destroy the normal anatomic structure of valve post-MI thrombus. non-hypertrophied LV w/ advanced diastolic dysfxn (thin walled.
no cardiac myxomas w/ this syndrome: lentigenes. ocular hypertelorism. variable cellularity. could be syndromic association). pulmonary stenosis.deafness . endocrine d/o (Cushings.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Primary cardiac tumors (General) diagnosis often dependent anatomic site? Mostly atria (due to on anatomic location myxomas . Rhabdomyoma inc ESR. gonadal hypoplasia.different from sun induced bc occur also in axilla. mucinsecreting cells embolus (stroke. can be bilateral/ multiple (more likely to be syndromic). distal toe/finger infarct) Carney/LAMB/NAME genetic syndromes w/ myxomas autosomal dominant mutation that results in cardiac myxomas(multiples). etc). fever. retarded growth. GI infarct. EKG abnormalities. lentigenes (freckle like lesions . etc). +/calcifications microscopic: myxoid (gelatinous) matrix.most common cardiac tumor) (pericardium. usually solitary (if multiple. systemic manifestations (fever. emboli most common malignant cardiac tumor? Angiosarcoma very rare delayed dx bc mimic many dz that impair cardiac fxn Cardiac myxomas most common primary tumor found most commonly in LA possible MV dysfunction. endocardium) majority are benign (due to myxomas) clinical manifestations: most common pediatric cardiac tumor? impaired cardiac fxn. breast & testicular disorders genetic FH differentiate from other lentigenescausing syndromes: LEOPARD . melanotic schwannomas (neural tumors). ESR) cytokine associated (IL6) 10% are inherited (multiple myxomas think Carney complex/ NAME/ LAMB see below) macroscopic: pedunculated (move w/ position. blue nevi. pressure) or sessile (no movement). myocardium. cutaneous myxomas (multiple papules around eyes). malaise.
5-6m mean age around 40 y. infiltrative mass in RA . rare to see childhood sarcomas Macroscopic: angiosarcoma (violaceous/ reddish purple color . mental impairment. renal tmors) can occur spontaneously but often caused tuberous by tuberous sclerosis sclerosis macroscopic: circumscribed ventricular mass (not encapsulated). chest pain. M=F. the sarcoma is confined to the heart bc low survival (pts don’t survive long enough for metastasis) angiosarcomas have early metstasis (lungs. tamponade.blood forming tumor) microscopic: rhabdomyosarcoma has rhabdomyoblast (eccentric nuclei + eosinophilic cytoplasm) resection is not curative most of the time. occurs in atrium (commonly posterior wall). rhabdomyosarcoma malignant! vague sx (dyspnea. mean ages affected 2030s. a/w tuberous sclerosis (autosomal dom neurocutaneous syndrome w/ CNS tumors/seizures. pleomorphic undifferentiated sarcoma 3. 3m survival pleomorphic undiff sarcoma: = cell origin is unknown. clinical features depend on size of tumor. liver brain) mean survival 7m2y . angiosarcoma 2. survival 1. low survival Rhabdomyosarcoma = atrial & ventricular lesions. cutaneous lesoins. spontaneous remission often. rhabdomyomas of heart.o. white-yellow & waxy appearing Primary cardiac sarcomas 1.. early mets (usually lungs).Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications cardiac rhabdomyomas most common pediatric tumors involves the ventricles. usually in atria Angiosarcoma = most common cardiac sarcoma. mimics atrial myxoma. vertebrae. palpitations). usually multiple.
3m f/u. US (if nl .2 million/yr immobilization. anesthesia. leukemia/ lymphoma. gen local tenderness along deep veins = 1 inflamm. recurrent episodes of DVT. male gender. no further testing but 3m f/u. ovarian often asymptomatic unilateral calf swelling (large clots overwhelm lymphatics). active cancer (rx<6m) = 1 obesity) leg paralysis/ immob = 1 endothel injbedridden >3d from surgery = 1 surgery. arrhythmias. renal cell carcinoma usually involve pericardium direct extension: mediastinal tumors sx: dyspnea. MI.think cardiac squamous cell carcinoma --> endocardium metastasis Pulmonary stenosis Deep vein thrombosis LEOPARD syndrome Virchow's Triad: Venous stasis + venous stasis. pleural/ intracavitary extension to IVC or RA pericardial effusions (direct extension): hepatocellular (breast/ lung ca).treat + 3m f/u) immediated LMWH or heparin. positive Homan's sign (inflamed venous wall). melanoma. sarcomas low metastatic cancers? Prostate. IVC filter (if cannot take anticoag) chronic swelling. overlap with oral anticoagulation (coumadin). if abnl . adrenal tumors. IBD. African Americans High Wells' score? D-dimer (if nl. Hypercoagulable state varicose veins. trauma. pulmonary emboli! . hi estrogen. Intimal (endothelial) injury + other (age>40. renal cell carcinoma. pitting = 1 DVT.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Metastatic tumors clinically uncommon. pain. risk (<1pt) smoking. prior unilateral swelling (>3cm).think pericardial effusions). sepsis. calf tenderness. Lymphatic spread: epithelial tumors. hypercoag cancer. central collateral superficial veins = 1 line. primary thrombophilias highly metastatic cancers? Melanoma intermediate metastatic cancers? Breast & lung cancers. HIT. GI. to heart usually incidental finding melanoma on autopsy hematogenous spread: sarcomas. sometimes hx of lung/breast cancer pericardium + pericardial effusion or leukemia/lymphoma --> anywhere pericarditis . carcinoma. if abnl US). skin ulceration. hepatocellular. alternative dx more likely = -2 **High risk (>3pts). low major venous surgery. mod risk (1-2pts). sometimes myocardium cardiac metastasis sarcomas --> myocardium. breast --> pericardium (hence + new heart finding . Wells' Clinical Prediction Rule for DVT: severe COPD. pericarditis melanomas --> myocardium multiple melanoma mets lung. RCC. blood transfus. pancreatic. venous cords pregnancy. uterine tumors ischemic disease (tumor emboli). outflow obst.
major pulm hemorrhage. GI bleed in 3 get CT scan (if nl. angina. immob/ surgery past 4wks (1. PH w/ lung dz clubbing. PH from direct S2P. score <4 intermediate to low risk pulmonary artery obstruction. PAP Pathology (#1): SMC proliferation (endothelin) & vascular remodeling #4 is surgically treatable (pulm thromboendartectomy) #2 needs BB. Pulm venous (fixed CO so BP drops w/ HTN (Left heart vasodilation. done. atrial arrhythmias. digoxin if arrhythmias. if HTN. always elevated transpulmonary gradient mediators: increased activity of vasoconstrictors (endothelin 1).treat for PE) bleeding disorder) decreased CO and BP --> Vtach. diaphoresis/ hemoptysis (if severe!) acute RV afterload increased (dilation.contraindicated in get D-dimer (if nl . syncope. cerebral abcess. pleuritic chest pain. dysfxn) edema (RV failure) 3. ASD). hemoptysis (1). palpable PA impulse @ ULSE. NO) stiffened LV causes inc LA pressure = inc PAP (#2) sarcoidosis.5). syncope 2. supplemental O2 if hypoxic poor survival. fatigue. HR> 100bpm (1. RV lift thromboemboli @ LSE. RV dysfxn) --> increased RV volume --> decreased LV distensibility --> decreased LV preload --> dec CO hemodynamic response determined by: 1. female prominent right gender (#1) heart border (RA) ECHO: dilated large RV and flattened septum compressing LV Cath: increased RVEDP. anticoagulants to prevent clots. CCBs if vasoresponsive diuretics to prevent RHF. PH w/ chronic wave. normal PCWP (<15. TR murmur Fixed obstruction in lungs prevent flow from right to left heart = reduced CO = reduced oxygen transport = hypoxia in lungs = increased work of breathing & ischemia (angina) pulmonary arterial hypertension (primary) PAP > 25 mmHg. months. chronic thromboembolic dz 3rd most common CV illness in US.Chro nic pulmonary hypertension w/ recurrent emboli. people. general pulm hypertension has ANY wedge press). PAH (primary) dyspnea on exertion. 25% mortality if untreated Virchow's triad ECHO: RVPO (large PE) spiral CT: best! anticoagulants thrombolytics (patient in shock. apprehension. rales/crackles. hyper/ hypothyroidism. underlying cardiopulm status 3. cough. reduced activity of vasodilators (prostacyclin.CVA. If low to int wells . chronic severe hypoxia from shunting. major trauma in 10 days. sudden death . ACEI. paradoxical emboli (PFO. cor pulmonale. previous DVT/PE (1. giant "a" or "cv" 4. diuretics nitrates #1 requires heart & lung transplant.age>80. renal dz (#5) idiopathic (#1) younger CXR: enlarged RV. other dx less likely than PE (3). loud 5. known abnl . exercise. neurohormonal adaptations (make PE worse!!) Wells' clinical pred for PE: Sx of DVT (3).5). uncont PE excluded.get surgery in pats 7 acute cor pulmonale CT) days. ejection sound.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Pulmonary embolism dyspnea. Vfib pulseless activity to heart Pulmonary arterial hypertension 1.score 4+ intermediate to hi risk. tachycardia. effect on pulm Graham Steele diastolic vasculature but murmur (ULSE). arrythmias). TIA/ If int to high Wells. ischemia. paradoxical emboli. small carotid pulse. absent PMI.5). if abnl . malignancy (1) . right unclear cause sided S3 (RVH). amt of vasculature occluded 2.
Screening / Education .
non-dippers have increased risk of CVD) .Screening / Education 5 mm Hg increase in DBP or SBP = 2030% increase in CVD increased SBP = decreased survival BP monitoring at home (night BP nl dips 10-20%.
their legs can wait! . if positive.Screening / Education DHHS: screen men aged 65-75 who have ever smoked w/ 1x abdominal US. make sure the patient isn't going to have a stroke/ MI . all women age 6085 w/ CV risk factors. yearly screening recommended Society of vascular surgery: screen all men btwn age 60-85. and all men/women over age 50 w/ +FH for AAA with abdominal US if you see PVD.
Screening / Education .
Screening / Education .
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Screening / Education 50% maternal mortality w/ subsequent pregnancies if CM persists avoid combined oral contraceptives increased risk of recurrence! .
Screening / Education .
Screening / Education .
or > 2 blocks on level ground. SMOKING CESSATION. lipid mgmt (diet) . daily exercise.angina w/ strenuous ex Class II . Class III: angina w/ one flight of stairs or <2blocks Class IV: angina w/ walking around house or at rest BP control.Screening / Education functional class: Class I .angina w/ walking or stairs. weigh reduction.
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
C = symptomatic dysfxn. B = asymptomatic ventricular dysfxn.Screening / Education Stages: A = at risk (DM. HTN. but can move between functional classes . etc). D = end stage HF Can't move between stages.
Screening / Education competitive sports restriction common cause of SCD in athletes .
Screening / Education
competitive sports restriction
ALL first degree relatives need to be screened Screening of adolescents & competitive athletes q 1218m Screening of adults q 5y
Screening / Education
Screening / Education
Screening / Education
DVT prophylaxis mechanical, medical (anticoagulation!unfractionated heparin, LMWH)
Screening / Education
immunodeficient can loss of tooth supporting tissues have rapidly (gingiva, periodontal ligament, progressive forms bone, cementum) --> mobile teeth Odontogenic infection Mandibular infection --> submandibular sace involvement --> Ludwig's angina (airway compromise due to displacement of tongue) Maxillary infection --> midface (facial veins) --> cavernous sinus thrombosis Primary oral herpetic lesions (12% of infected)
dental plaque/host interaction
systemic diseases (ChediakHigashi, chronic granulomatous dz, neutropenia, DM, HIV)
65% of US adult population
mixed microflora infection within and around the teeth, usually secondary to dental caries
mid-face infection, swelling [maxillary anterior infxn] or airway compromise [mandibular infxn] bacterial endocarditis (GAS; HACEK); CNS abscess or septic embolus
HSV-1, HSV-2; dormant virus resides in trigeminal nerve sensory ganglion
Antibodies in 90% of U.S. population
Clinically & histologically indistinguishable for Varicella Zoster 3Ms: multinucleated cells, nuclear molding, chromatin margination; lots of eosinophils
Primary Herpetic Gingivostomatitis
Secondary oral herpetic lesions
1-2% of population that comes in contact multiple, painful, ulcerated vesicles on lips, gingiva, palate, with HSV will develop this entity tongue; high fever; cervical lymphadenopathy; distinguish from impetigo or eczema by PAIN vermillion border of lips; if in mouth, exclusively on attached gingiva (never on movable mucosa!), hard palate, or tongue sometimes prodrome present (tingling prior to lesion)
Self-resolving +/- acyclovir
Hospitalization for dehydration
40% of U.S. population
prophylaxis w/ acyclovir
immunocompromised have more widespread lesions
occurs on movable mucosa (labial/buccal mucosa, soft palate, floor of mouth) appear round or oval with yellow center and erythematous border
stress induced; associated with Crohn's disease
?? Not known
20-60% of population
High SES, immunocomp (more severe)
can become a functional problem if large
multiple oral, genital ulcerations +/- relatpsing iridocyclitis (eye) can have recurrent arthritis & thrombotic CVD most common URT malignancy occurs most commonly on lateral and ventral borders of tongue (NEVER the dorsal tongue), floor of mouth, soft palate and less commonly on gingiva and buccal mucosa white patch anatomic site can increase lesion risk: lateral tongue, central tongue, floor of mouth, soft palate red patch (large, red persistent lesion) hard palate, maxillary gingiva; maxillary sinus arises from enamel forming tissues; benign but locally destructive; posterior mandible parotid gland (usually benign), submandibular gland (50% benign), sublingual (malignant mostly), and minor glands (malignant mostly)
HLA types B5, B27, B12
Oral Squamous Cell Carcinoma
Ulcerative, exophytic, plaque like
tobacco!! Can also have a synergistic effect w/ alcohol; Plummer-Vinson syndrome, betel leaf (India), HPV
M>>>F; 5th-6th decade; age, tobacco use 2-4% of all U.S. malignancies
surgical + adjunct radiation/chemo
prognosis related to stage (overall 5y survival 20-60%) increased risk for 2nd primary tumor surgery often causes functional impairment 1-17% of the dysplastic lesions can transform to malignancies
Premalignant oral lesions
oral hyperkeratosis or callous but some degree of dysplasia
Erythroplakia Oral/ sinonasal melanoma Ameloblastoma
VERY uncommon VERY rare compared to cutaneous melanoma most common odontogenic neoplasm
almost always a/w in situ or invasive SCC 20% 5y survival
en bloc resection (treated as if can be fatal if affect maxilla malignancy because so destructive)
Salivary gland neoplasm
Salivary gland neoplasm
most common type of benign salivary gland neoplasm 85% occur in parotid Most common bilateral tumor commonly in parotid most common malignant salivary neoplasm (60-90% occur in parotid despite parotid glands nl having benign lesions) extremely aggressive; minor glands; invasive growth pattern Maxillary sinus most frequently affected
contain salivary and lymphoid tissue
histology: large deposits of mucin
40% 5y survival but gradedependent prognosis
Adenoid cystic carcinoma Paranasal sinus neoplasms Squamous cell carcinoma Adenocarcinoma
histology: perineural invasion
high recurrence rate
Gastroesophageal reflux (GERD)
smoking, nickel, chromium, wood working industry (soft wood) Nasal cavity & maxillary sinus smoking, nickel, chromium, wood working industry (hard wood) symptoms or tissue damage due external factors (diet, fatty foods, smoking, diet, obesity, smoking, to reflux of gastric contents into meds - b-agonists); diminished esophagus impaired esophageal mucosa esophageal clearance (defective resistance peristalsis, saliva); gastric factors sx: heartburn, regurg, chest (overproduction of acid - meds, H.pylori; pain; dysphagia, water brash bile acid; gastric emptying - DM; gastric (increased salivation); atypical distention - causes LES to relax more); sx (laryngitis, hoarseness, defective anti-reflux barrier chronic cough, asthma, dental (PROLONGED transient LES erosions, laryngeal cancer) relaxations, low resting pressures of LES scleroderma, CT d/o) --> overall causes impaired esophageal mucosa resistance complication of untreated GERD (>5 years GERD Barrett's mucosa (normal of moderate to severe symptoms; 3x/week squamous epithelium of esophagus replaced by intestinal to daily) columnar epithelium)
10% of population globally; 15-44% of Americans affected monthly
diet, obesity, CT disorders, CVD/asthma (bagonists), DM
PPI trial (hi dose x 30d) - if lifestyle mods (avoid trigger response, taper to tolerable foods, small frequent meals, dose; if no response, use quit smoking) endopscopy to r/o mucosal d/o H2 blockers, PPIs, antacids Endoscopy - negative in 50% for breakthrough sx of patients w/ GERD surgery (Nissen gold std - ambulatory pH test fundoplication) (done in pts w. refract/ atyp sx complications in 5-10% (ileus, pneumothorax, gas bloat or typ sx if neg endoscope) syndrome, diarrhea) histology: intestinal metaplasia (columnar epithelium + Goblet cells + villus pattern development) endoscope: salmon colored mucosa above Zline Barium swallow: narrowing of esophageal lumen, nodular appearance (could not R/O adenocarcinoma v. Barrett's... need endoscopy & bx) endoscope: food + concentric esophageal rings + linear furrows pathology: >15 eosinophiles per field (distinguishes from reflux esophagitis, which can also have eosinophils) endoscopy: coated white plaques w/ raw erythema below barium swallow: shaggy appearance; pan esophageal deep, penetrating ulcers histology: pseudohyphae
erosive esophagitis/ reflux esophagitis (inflamm of esophagus from stomach contents) esophageal strictures (narrowing due to inflammation) esophageal adenocarcinoma Barrett's esophagus (see below)
more common in middle to older aged Caucasian men
Barretts --> dysplasia -> esophageal adenocarcinoma
acute dysphagia and food impaction
infiltrative disorder -possible that certain foods trigger eosinophilic infiltration of esophageal body
hx of atopy (asthma, allergic rhinitis, eczema); younger men
PPIs, steroids (oral flonase), mast cell inhibitors, allergy referral
odynophagia (painful swallowing) + dysphagia
immunocomp (HIV, chemo, chronic steroid use - asthmatics)
CMV . acute illness w/ increased vomiting Esophageal varices life threatening bleeding variceal rupture produces massive hemorrhage into esoph lumen longitudinal tears at the GE junction from severe retching or vomiting cirrhosis. cough/ heartburn opening of LES inflammatory infiltration of myenteric plexus --> defective NO --> chronic excitation --> chronically closed LES Manometry: failed relaxation of LES (no drop in LES pressure) and absent peristalsis Endoscopic pneumatic dilation. ulcerative histology: glandular structures eroding through esophageal wall gross: umbilicated ulceration at surgical resection organ surface large tumors & metastases treated by Imantinib (Gleevec) metastasis (middle esophagus --> mediastinal. chronic esophagitis.viral inclusion bodies w/ surrounding halos .equipotent replicative ability. then protrude through submucosa & mucosa into lumen bleeding mutation in c-kit Small cell carcinoma Melanoma Achalasia Primary esophageal motility disorders dysphagia to liquids and solids aperistalsis of the esophagus. chronic steroid use . botox injection in LES during endoscopy (short term) Medical tx: CCBs. loss of nl maturation and polarity. portal hypertension endoscopic sclerosing or banding most patients have coexisting hiatal hernia (stomach slips into esophageal hiatus) Esophageal lacerations (MalloryWeiss tears) bleeding (hematemesis) alcoholic binge .S. chronic inflamm cells present gross: white mucosa replaced by red mucosa from stomach. Barrett's more common now due to Barrett's Caucasians GI stromal tumors (GIST) begin in the muscularis propria (interstitial cells of Cajal myenteric plexusi) of esophagus. aspiration (if TEE fistula). regurgitation.chest pain/cough/ hematemesis weight loss.owl's eye appearance esophageal neoplasm (General) Squamous cell carcinoma progressive dysphagia. stomach. paratracheal LN. gross: irregular. firm. CMV . or intestine. keratinized/ squamous pearl.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Viral esophagitis odynophagia (painful swallowing) + dysphagia Herpes. resulting in but worse w/ solids. mitotic figures. chemo. ruptured submucosal veins chronic alcoholics. oval/long appearance. upper 1/3 --> cervical LNs) hemorrhage & sepsis tracheo-esophageal fistulas Esophageal adenocarcinoma GERD.large ulcers Barium swallow: herpes: small shallow ulcers w/ nl esophagus between the ulcers. alcohol [synergistic effect] --> mutations in p53 HPV. polypoid SCC occur in upper 1/3 histology: no glands. CMV immunocomp (HIV. +/.multiple clustered ulcers. CMV: deep large penetrating ulcers >1cm in size histology: herpes multinucleated giant cells w/ chromatin pushed to periphery. non-progressive contractions and failed chest pain.asthmatics) Endoscopy: herpes . ulcerative lesion in middle 1/3 of esop. dietary carcinogens (aflatoxin) most common type worldwide 6/100. nitrates [overall less effective] Barium swallow: bird's beak. celiac LNs. lower 1/3 esop --> perigastric. weight loss.000 in U. dilated/distended esophagus full of debris endoscopy: pinhole opening of LES gross: enlarged venous channels @ GE junction. hemorrhage Barium swallow: apple core lesions Surface epithelium dysplasia from exposure to mutating agents --> in situ SCC --> invasive SCC smoking.
Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Peptic ulcer disease gastric. pylori & NSAIDs!! 5-10% lifetime prevalence H. Menetrier disease) Genetic factors (+FH. stool ulceration: incr antigen test. invasive .pylori. Chile. NSAIDs. pepsin) & defensive (protective mucus layer) factors in gastroduodenal mucosa H. intestinal metaplasia. lack of fruits/veggies. immediate endoscopy ONLY if anticoagulation weight loss. causing atrophic gastritis Hamartomatous majority of gastric polyps (80glandular hyperplasia 90%) non-neoplastic but may be regenerative 10% of chronic gastritis F>M associated with Peutz-Jegher syndrome (intestinal/gastric polyps + peri-oral pigmentation). larger size lesion = increased risk adenocarcinoma Staging: depth of invasion (Tis = in situ. concurrent steroid stop NSAIDs use. parietal cells. clarithromycin) as first line Bleeding (most common. pylori. FAP (fundic gland polyps.biopsy) risk w/ age>60. n/v. n/v 30-60m antrectomy/pyloroplasty/ postprandial. empty stomach) requires surgery!!) Penetrating ulcer (severe persistent pain. Russia M>F. dx: XR/CT shows free air under Surgery?? (vagotomy + diaphragm.. pylori (urea breath test. improves w/ antacids) inflammation --> ulcer formation. age use. a/w NSAID intake. can sometimes see H. NSAIDs!! rigidity. incr duration & dosage. middle of the ammonium to protect from acidic environ. pylori causes mostly duodenal ulcers (relieved by food) prostaglandins . pylori so use PPI (omeprazol) + 2 antibiotics (amoxicillin. T2 = muscularis propria.i gastric gland increased risk of dysplasia and adenocarcinoma w/ intestinal metaplasia Gastric polyps Autoimmune gastritis antibodies against gastric autoimmune gastritis . damage cells in the stomach (most vit B12 deficiency commonly the parietal cells). hi smoked/salty diet. 2nd line (rescue therapy): endoscopy for dx/tx but no omeprazol + bismuth + effect on mort) tetracycline + metronizadole Perforation (sudden severe epigastric pain. bleeding. pylori w.fullness. ZollingerEllison test for H. gurarding. dilated gland but not neoplastic Adenomatous Gastric adenocarcinoma (General) 10% of gastric polyps neoplastic. adenomatous gastric polyps. lesser curvature although cardia tumors are arising due to Barrett's esophagus exophytic. NSAIDs also directly sx = dyspepsia (upper damage epithelium abdomen. flat.lymphocytes parietal cells. prior hx of > 45 w/ dyspepsia PUD barium swallow: smooth/ uniform collection of barium representing ulcerations in stomach wall If due to H. direct injury by chem/alcohol ingestion chronic presence of etiologic agent --> mucosal atrophy --> intestinal metaplasia Alcohol. NSAIDs.. or ulcerative usually progress from atrophy and intestinal metaplasia (commonly in the background of chronic gastritis) environmental factors (H. H. post surgical histology: overwhelming amt of inflammatory cells. autoimmune gastritis) leading cause of cancer death globally. hematemesis. 1-3h produces urease and consequently postprandial. pylori . familial gastric cancer syndrome. usually >50 y. affects duodenal mucosa by instigating metaplasia [destroys D cells] of duodenal mucosa to gastric mucosa increased gastric acid secretion (nl in gastric ulcers. China. peritonitis If due to NSAIDs. low SES) host factors (chronic gastritis.NSAIDs that complaints. ischemia Chronic gastritis less severe symptoms than acute gastritis but persistent H. chronic alcohol abuse. stop rebound tenderness.need to eradicate H. T1 = lamina propria/submucosa. 1520% of PUD pts. unrestricted growth with malignant potential most common malignant gastric tumor (90-95%) usually in antrum/pylorus. scarring. more common in Japan. reduced bicarbonate secretion. IgG serology if patient NSAID-induced NEVER treated before. partial gastrectomy. pylori adheres to gastric mucosa and distention.inhibit gastric acid production AND maintain protective vague abd discomfort surface layer (meds . n/v disruption of mucus layer protective mechanisms (reduced mucin synthesis. HNPCCDNA mismatch repair gene mut. hematochezia.o. Barrett's esophagus. T4 = adjacent structures) .. night. nausea. pernicious anemia. short trial of PPIs/H2 blockers smoking. T3 = serosa. melena. H.E cadherin mut. smoking. histology: regenerative. pancreatitis) Gastritis Acute gastritis sudden inflammation of stomach transient mucosal inflammatory process lining due to numerous etiologies asymptomatic or variable epigastric pain. followed by edema. radiation. requires drainage proceduressurgery!!) decrease vagal stimulation to Obstruction (due to inflam. succession splash.).red or coffee grounds. pylori. autoimmune gastritis. usually decrease prostaglandins weaken asymptomatic but most common protective layer. bloating. hi nitrate/nitrite diet.o. bloating. usually self-resolving. intestinal metaplasia (Goblet cells). duodenal NSAIDs cause mostly gastric ulcers (worse with food) imbalance btwn aggressive (acid. early gastrojejunostomy to help satiety. 30% increase in duodenal ulcers). adenomatous polyps in large intestine that become adenocarcinomas) found most commonly in people 50-60y.
large hyperchromatic cells. pylori --> clonal proliferation of small B lymphocytes --> development of lymphoma arise de novo or in MALT lymphoma Gastric carcinoids symptoms depend on hormones being produced often secrete gastrin rare in stomach (more common in SI & lungs) patients can present w/ duodenal ulcers. and adenomatous polyps older patients w/ known risk factors gross: solitary lesions. irregular nuclear contour. formation of glands Diffuse type usually diagnosed at a high stage so worse prognosis (plus easily invades due to lack of adherence molecules) E-cadherin mutations (CDH1 gene) --> loss of cell adherence younger patients with no known risk factors besides perhaps genetics M=F gross: thick stomach wall. some signet/donut signs.loop (ligament of Treitz of symptoms) doesn't cross the midline) increased risk of adenocarcinoma Malrotation 1% of congenital population (incidence ranges from 1/6000 1/200) M slightly more than F majority diagnosed w/ 1 year of life but some go undetected until incidental find on GI imaging/surgery Intestinal atresia bilious emesis IMMEDIATELY following birth = hi grade obstruction Abd distention = mod grade obstruction maldevelopment (muscular. diarrhea. however. chronic atrophic gastritis.diffuse hypertrophy and hyperplasia of first part of pylorus --> narrowed channel bilious emesis @ ~1m between antrum and duodenum often misdiagnosed as GERD more common in males benign course post-surgical splitting of pyloric muscle none. hyperchomatic cells w/ irregular nuclear contours Gastric lymphomas MALT lymphoma Low grade Diffuse large B-cell lymphoma high grade chronic inflammation --> lymphoid stimulus H. usually resolves postsurgery . flatter lesions histology: lots of signet ring/ donut signs (eccentric nucleijammed to side by mucin).Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Intestinal type most common type slightly better prognosis than diffuse type a/w: intestinal metaplasia from environmental factors. radiation poor prognosis lymphocytes. typical) but dense resolves) t11:18 have worse lymphocyte infiltration prognosis histology: dense sheets of surgery. shock = intestinal necrosis) = very poor prog Older kids/adults: intermittent vomiting. chronic gastritis. or both) of GI tract likely due to chromosomal abnormality although not truly elucidated associated with 30% of Down Syndrome cases XR: double bubble = duodenal atresia surgical emergency!! Congenital hypertrophic pyloric stenosis intermitt abd pain + failure to thrive = partial obstruction/ atresia babies born nl but display non. abd pain. peritonitis. or (excessive gastrin --> Zollinger-Ellison syndrome increased gastric acid levels. exophytic but nl stomach ruggal folds histology: arise from intestinal metaplasia. enhanced ruggae (linitis plastica morph). neurological. hematochezia. cells appear to be falling apart due to loss of cadherin antibiotic therapy (get rid of H. causing diffuse hyperplasia of foveolar epithelium of body/fundus of stomach ?? Unknown VERY rare M>F. enteropathy. chemo. Histology: normal cells pylori then MALT lymphoma tumors with translocation (uniform. volvulus. pancreatitis. 30-50 y. ZE syndrome hyperplasia. diarrhea if ZE neuroendocrine tumors a/w endocrine cell MEN-1. peripheral edema hypochlorhydria (low gastric acid in stomach) most common congenital GI malformation majority are asymp Newborns: bilious emesis. peritonitis excessive secretion of TGF-a (transforming growth factor). extensive PUD) Menetrier Disease weight loss. gross: hypertrophy of gastric folds histology: foveolar hyperplasia Upper GI series: No duodenal Ladd procedure (required for ALL malrotations regardless C. good prognosis.o. late stage signs (hematemesis. tenderness/pain.
asymptomatic jaundice elevated indirect (unconjugated) bilirubin reduced UDP glucoronyl transferase activity causes impaired conjugation of bilirubin completely absent UDP glucoronyl transferase activity precipiated by fasting. unprotected sex. are usually immigrants or vertical transmission to infants born in U. n/v. activity less severe (Arias syndrome) neonatal jaundice (unconjugated hyperbilirubinemia) --> kernicterus (toxic encephalopathy) Neonatal hyperbilirubinemia blood group incompatability between mom & baby PLUS newborn's inadequate UDPglucoronyl transferase activity blue fluorescent light exposure (increases conversion of bili in skin to more polar/water soluble isomers) IM injection of tinmesoporphyrin (inhibits heme oxygenase to prevent formation of bilirubin) Viral hepatitis Hepatitis A viral prodrome (fatigue. needle stick. Asia) HBeAg = active infection middle aged (infectious state) adults (not vaccinated) will anti-HBs + no anti-HBc = have higher vaccination chance for acute infection anti-HBc + HBsAg = chronic infection boost immune response via risk of chronic infection. may be multiple sex partners. HBsAg.horizontal transmission + vertical 400 million carriers in world (75% in Asia) surface proteins: HBeAg.S. Africa. Asia). then replicating (using active viral reverse transcriptase w/ high mutation rate) in liver or extrahepatic reservoirs U. pegylated interfeon or cirrhosis. HBcAg. EtOH Prevalence ~ 5%. pts w/ abnl liver enzymes endemic countries IgM = acute infection (Africa. transmission DNA polymerase test immigrants from endemic region. abd distention.S. impactions. +/diarrhea Rectosigmoid area is most affected (constipation.suggests new/acute infection IgG persists to provide total immunity NO risk for chronic infection or cirrhosis!!! Hepatitis B small DNA virus that is transmitted primarily through blood and sexual exposure. benign . vomiting. soiling. & nucleoside/tide analogs ($$) HCC some drugs have activity against HBV and HIV risk of chronicity determined by age of infection acquisition pregnant? Tenofovir in 3rd (younger individuals w/ Hep trimester. contagious up to 15 weeks postinmates. constipation. symptoms pregnant women. give infant HBIG + B = hi risk for chronic hep B) HepB vaccine w/I 12h of birth #1 cause for cirrhosis & HCC globally anti-HBc = represents natural infection (either acutely or chronically) .horizontal transmission of body fluids (IVDU. arth/myalgias. MSM) Globally . endemic countries (Latin America. LONG incubation period.S. MSM. institutions. abnl functioning bowel by recto-anal inhibitory reflex resection of aganglionic segments lifelong implications 15% of HD babies have other associated congenital anomalies :( high complication risk postsurgery: strictures. stress. close contacts of known cases. M>F family history increased indirect bilirubin none Type 2 severe/fatal elevated indirect (unconjugated) reduced UDP glucoronyl transferase bilirubin.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Hirchsprung's disease (aganglionic bowel) arrest of neural crest cell migration --> autosomal recessive and aganglionic zone of bowel (no ganglions in dominant mutations myenteric plexus despite normal muscle layers) RET (receptor tyrosine kinase) . most infectious during incubation period (minimal infectivity once jaundice occurs) contaminated food products (fecal-oral) poor hygiene. IVDU.HCW. by immigrant moms increased ALT (liver damage) IgM .ganglion cells? HD pts have no ganglion cells and nerve hypertrophy Barium enema: determines transition area where no contraction/distention anorectal manometry: differentiates normal v. food outbreaks cases in U. M=F in long segment dz positive FH sometimes rectal biopsy . absent NOS in myenteric 5-10% have total colonic + small plexus therefore reduced nitric oxide bowel HD (hi mortality at birth) [anal sphincter cannot relax so unable to defecate] Presentation: delayed passing of meconium. overcrowding. liver failure. headache) followed by jaundice 1-2 weeks later non-enveloped RNA virus that is transmitted via fecal-oral route and then replicates in the liver. HIV pts.associated w/ MEN 15% have total colonic HD (high lacks inhibitory parasympathetic type Iia grade obstruction) innervation. stool overflow) starts @ birth (unlike funct constip) and rarely has fecal soiling (unlike funct constip again) 1/5000 M>F in short segment. constipation Gilbert syndrome Crigler Najjar Syndrome Type 1 Elevated indirect (unconjugated) bilirubin. dialysis pts. .
Reye's syndrome. pregnancy (3rd trimester). blood transfusion leading cause of liver if exposed. moderate-marked EtOH intake asymp in most cases clinical presentation: hepatomegaly.o. piercings. gender. exposures). fibrosis jaundice. greasy surface histology: intra & extrahepatic lipid accumulation. HIV meds (ARVs). etc) other: needlesticks in HCW. no necrosis. tattoos. portal HTN. +/.acute hepatitis & SJS. DM. diffuse nodularity.2 these will million U. even after cessation of drug unpredictable timeline of DILI presentation. phospholipidosis (deposition of phospholipids in hepatocytes). HIV). genetics. jaundice minocycline . liver new therapy: peg interferon + failure. statins (very few causes of DILI but do elevate LFTs in 1-3% of patients) dependent on drug. which causes fatty acids to be delivered to the liver where they accumulated (steatosis) excessive alcohol increases formation of toxic metabolites. yellow. chronic hepatitis. inflammation (if + eosinophils. tender liver. liver failure. drugs. can mimic autoimmune hepatitis >900 drugs implicated. protein deficiency. peripheral setting of reduced glutathione levels neutrophilia) increased endotoxin release from gut bacteria reaches liver via portal circulation gross: steatosis typically present (represents hx of alcohol abuse). MTX.S.S. mitochondrial toxicity (HIV meds. does NOT cause chronic infection contaminated food products (fecal-oral) CAN BE FATAL IN PREGNANT WOMEN!!! (Alcohol) hepatic steatosis occurs w. many drugs have cholestatic or hepatocellular signature toxicity (after which they cause elevated liver enzymes) metabolic: accumulation of toxic metabolites in hepatocytes. fever. hepC. 80% histology: progression of fibrosis --> cirrhosis if chronic transplant for cirrhosis of people will in U. weight. think hypersensitivity). acute Acetaminophen toxicity results because depletion of glutathione.elevated phenytoin. altered membrane permeability) also increased peripheral catabolism of fat. people which 15% of have been exposed. neutrophilic infiltrate. but lipid assembly and secretion are impaired (decreased MT transport. brown/ green pigmentation (bile stasis) histology: marked fibrosis. vertical transmission. extra hepatic manifestations [sulfonamides. steatosis. abd pain. hepatic necrosis eosinophilia. malaise. variable inflamm infiltrate. elevated hepatic enzymes . [cholestatic injury] . autoimmune (methyldopa). IVDU. amiodarone) antibiotics. fever. granulomas. infection (hepC. drugs. varices) Hepatitis D enveloped ssRNA virus known as a delta agent because only propagates in the presence of Hepatitis B!! Transmitted via blood or sex (usually exposed to HepB & HepD at same time) treat hepatitis B to get rid of hepD Hepatitis E non-eveloped ssRNA virus that is transmitted via fecal-oral route and can be detected in stool/bile/liver. after 4 million U.fibrosis benign course usually Alcohol hepatitis acute onset following binge drinking minimal --> severe symptoms (malaise. acute hypersensitivity: a/w rash. people have develop cirrhosis chronic HepC and 1% will develop HCC pegylated interferon + ribavirin HIGH likelihood of chronic infection w/ subsequent risk of cirrhosis. overwhelming liver's metabolic ability. immune diseases) factors patients w/ comorbidities like Adults obesity malnutrition pregnancy other drugs alcohol hx of DILI genetics PMH of liver dz [iver injury] elevated LFT. susceptibility) clinical presentation: weight loss. trichrome stain identifies collagen 10-20% risk of death Alcohol-related hepatic cirrhosis may be synergistic w/ other 10-15% of alcoholics diseases (hepB. elevated liver enzymes REVERSIBLE! alcohol shunts toward lipid biosynthesis (due to increased NADH and decreased FA oxidation). toxins. more damage in profile? Obese F zone 3 > 50y. steatosis (microvesicular has worse prognosis). who drinks EtOH dx of exclusion monitor LFTs in patients taking INH withdraw offending agent liver transplant (acute liver failure) N-acetylcysteine (Mucomyst) if acetaminophen toxicity steroids if autoimmune hepatitis carnitine if valproic acid toxicity Acute liver failure. INH (increased age). NASH gross: hepatomegaly. environ (diet. esophageal varices. bile stasis. liver will be hard to palpate bc synergistic pathogenesis shrunken size represents years of EtOH abuse IRREVERSIBLE!! not really understood increased HCC risk Drug-induced liver injury (DILI) dose-dependent (acetaminophen --> accumulation of NAPQI) Hy's law: >10% of patients w/ DILI + jaundice progress to death or transplantation.MTX. & HCC ribavirin + protease inhibitor decompensated cirrhosis (telaprevir/ bocepravir) (ascites. SOS (sinusoidal obstructive syndrome. amiodarone) increased collagen production --> anorexia. fibrosis around highest risk central vein). amoxicillin-clavulanate. parenteral nutrition. hyperthyroidism drugs (propylthiouracil). develop chronic (stellate cells.S. collagen bridges) hepatitis.liver is more susceptible to injury in the AST/ALT >2. amiodarone. 3. unk risk factors (sharing razors/toothbrush. also seen in Wilson's dz & cholestasis). sexual transmission IVDU. transplantation. nonsexual household contact. WNV) that is transmitted primarily through blood and infects hepatocytes + B lymphocytes. peripheral edema. +/hepatomegaly (unless cirrhotic) histology: hepatocyte swelling/necrosis. Mallory bodies (bright pink inclusions representing aggregates of cytokeratin. replicates in liver using RNA dependent RNA pol (hi mutation rate) blood transfusions before 1992. pruritis. antifungals.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Hepatitis C ssRNA virus from flavivirus family (same as dengue. NSAIDs. encephalopathy. ascites. death . ALP. and host (age. (no current marker for alcohol injury/inflammation --> pro-fibrotic autoimmune hep. mitochondria & MT dysfunction hepatic steatosis: alcohol. regenerative nodules. anti-seizure meds relatively low incidence (phenytoin). so liver is no histology: massive/zonal necrosis. HIV meds] bili. possible steatosis & fibrosis ?? Liver enzyme elevation (loss/death of hepatocytes so not really too many left to be injured) decreased liver synthetic function tests gross: decreased size. cytokines --> release of growth factors and hemochromatosis.
nl or mildly elevated transminases. jaundice minocycline . variable fibrosis depending on dz stage MUST exclude other dx elevated ALP. amiodarone. anti-mitochondrial antibody (AMA) histology: bile duct destruction w/ mononuclear cell inflammatory infiltrate increase immunosuppression 87% remission within 3y of (prednisone. patients.acute hepatitis & Acetaminophen toxicity results because depletion of glutathione. pruritis. more damage in profile? Obese F zone 3 > 50y. environ (diet. pruritis. hepatic necrosis eosinophilia. shellfish. psychosis). fatigue. inflammation (if + eosinophils. hepatomegaly. hepatomegaly.S. inflamm arthritis). hypercholesterolemia. ataxia). DM. dyslipidemia) oxidative stress increases free radical usually asymptomatic. immune-mediated) unpredictable timeline of DILI presentation. spasticity. IgM. 200. SOS (sinusoidal obstructive syndrome. and host (age. treat dyslipidemia w/ statins) Wilson's disease pediatric or young adult presentation w/ liver disease Autoimmune hepatitis hepatic (variable . (obesity.liver necrosis & acyte hepatitis Non-alcoholic Fatty Liver Disease (NAFLD) steatosis --> steatohepatitis --> cirrhosis histology: massive/zonal Lab/Imaging necrosis.o. INH (increased age). phospholipidosis (deposition of phospholipids in hepatocytes). jaundice (10%). weight. think hypersensitivity).32% risk leading to cirrhosis in 10reduction in death/ liver 20 years transplantation) Primary Sclerosing Cholangitis (PSC) fatigue. nuts) KF rings on slit-lamp eye exam increased 24h copper excretion in urine lifelong chelation liver transplant is curative genetic predisposition. anti-seizure meds relatively low incidence Etiologies Epidemiology (phenytoin). death liver transplant (acute liver failure) N-acetylcysteine (Mucomyst) if acetaminophen toxicity steroids if autoimmune hepatitis carnitine if valproic acid toxicity "two hit hypothesis" . so liver is no SJS. acute liver failure. fibrosis weight loss & metabolic control (treat DM w/ metformin. fever. mushrooms. liver failure. central obesity. exposure to unk environmental F>M. autoimmune disorder characterized by weight loss. acute hypersensitivity: a/w rash. ALP.elevated phenytoin. toxins. Complications transplantation. gender. hepatic rosettes (small gland like clusters of surviving hepatocytes within inflammatory infiltrate). even after cessation of drug Idiosyncratic (individualized. hepC are at greater risk! Adults Risk obesity factors malnutrition pregnancy other drugs alcohol hx of DILI genetics PMH of liver dz [iver injury] elevated LFT. splenomegaly. antifungals. psych (depression.insuline resistance metabolic syndrome increases fatty acid delivery to liver. average age 20-40 factor Elevated transaminases. elevated IgG. associated autoimmune disorders (thyroid. amiodarone) antibiotics. hyperthyroidism drugs (propylthiouracil). fever. opthalmologic (KayserFleischer rings. metabolic syndrome elevated ALT (AST/ALT <1) U/S: increased echogenicity from fatty infiltrate biopsy: steatosis. many drugs have toxicity (after which they cause elevated liver enzymes) metabolic: accumulation of toxic metabolites in hepatocytes. jaundice. HIV meds (ARVs). [cholestatic injury] . exposures).000 M>F avg age of dx 40 elevated ALP. formation --> lipid peroxidation --> cellular damage RUQ pain.5/100. inflammation. AND extrahepatic bile ducts hyperpigmentation. can mimic autoimmune hepatitis Hy's law: >10% of patients w/ >900 drugs implicated. fat soluble vitamin deficiency (ADEK). pruritis. neurological (rigidity. fibrosing inflammation of both intrahepatic hepatomegaly. MTX. towards own hepatocytes --> jaundice hepatocellular disorder. xanthelasma/ xanthomas.000 F>M median age of dx 50-55 ursodeoxycholic acid slowly progressive disease (synthetic bile acid . cholestatic hepatitis longer able to clear NAPQI (toxic met) cocaine . carries copper but is broken down if copper is not attached) chocolate. fibrosis around highest risk central vein). maldigestive fatty diarrhea sx: fatigue. hepatomegaly 20% prevalence in U. who drinks EtOH dx of exclusion monitor LFTs in patients taking INH withdraw offending agent Treatment Acute liver failure. scleroderma. tremors. xanthomas majority of patients have IBD (UC) 8."beating of the bile ducts" liver transplant! irreversible damage to bile ducts --> cholestasis --> cirrhosis increased risk of cholangiocarcinoma median survival 12-16 years post dx . +ANA/SMA/ liver-kidney microsomal-1 antibodies (1 of the 3 usually) histology: interface hepatitis. steatosis (microvesicular has worse prognosis). sunflower cataracts) aberrant immune response directed fatigue. amoxicillin-clavulanate.Drug-induced liver Disease injury (DILI) Clinical Variants DILI + jaundice progress to Defining Characteristics cholestatic orPathogenesis hepatocellular signature death or transplantation. & fibrosis a/w other autoimmune disorders (thyroid disease) gene defect responsible for copper autosomal recessive transport --> decreased biliary excretion of inheritance copper --> increased copper deposition throughout body --> increased oxidative stress & damage 1/30. NSAIDs. Sjogren's. extra hepatic manifestations [sulfonamides. granulomas. chronic hepatitis. hematologic(hemolytic anemia). immune diseases) factors patients w/ comorbidities like HepB. genetics. steatosis. mitochondrial toxicity (HIV meds.S. inflammation.000 people age of onset typically 1525 low serum ceruloplasmin (nl diet: eliminate copper rich foods (organ meats. combo therapy) treatment Primary Biliary Cirrhosis (PBC) autoimmune disorder characterized by progressive destruction of intrahepatic bile ducts (microscopic injury) aberrant immune response directed at own biliary epithelial cells (small bile ducts) 5/100. statins (very few causes of DILI but do elevate LFTs in 1-3% of patients) dependent on drug. mild elevations in transaminases cholangiogram: multiple bile duct strictures w/ proximal dilations (beaded appearance) .000 U. autoimmune (methyldopa).abnl liver enzymes --> cirrhosis & portal HTN). HIV meds] bili.
FTT) neurological problems. low HFE levels cause increased ferroportin and consequently absorption of Fe Cirrhosis compensated scarred liver --> distorted sinusoidal architecture --> increased resistance and disturbed blood flow --> shunting of coronary vein blood flow AWAY from liver (hi resistance) --> engorgement of chronic liver disease manifestations (muscle wasting/ gastroesophageal plexus --> variceal bleeding cachexia.antitrypsin deficiency (A1AT) most common inborn dz affecting the liver neonatal hepatitis (usually spontaneously resolves but can cause chronic response fibrosis) also a/w early onset COPD in non-smokers iron overload syndrome --> liver injury. FAA is converted to another toxin SAA newborn screening (elevated tyrosine --> repeat and check for urine SAA) NTBC (inhibits buildup of toxic substances) dietary (reduce protein intake) Lysosomal storage disease Gaucher's disease. HCC alpha 1 antitrypsin binds and promotes degradation of serum proteases. renal involvement mutation in either GLUT2 or glucose-6phosphatase --> hypoglycemia (glucose-6phosphate cannot be converted to glucose OR glucose cannot be transported out of liver for usage) uric acidosis. Hereditary hemochromatosis fatigue. arthritis/joint swelling. lactic acidosis. small liver span (percussion). Fabry's disease. failure to thrive. abnormal facial features Alpha1.splenomegaly. increased INR. and increased triglyceride levels severe liver dz in young infants (bleeding problems . hi Fe = increased HFE = decreased ferroportin = less absorption of Fe in patients w/ missense mutation. hyperbilirubinemia) Doppler U/S (ICU pts only) splenomegaly. progressive hepatomegaly. mutation in this enzyme causes A1AT clumping --> inflammatory response lack of protein in lung --> COPD mutant protein in liver --> toxicity homozygous missense mutation in C282 tyrosine OR heterozygous missense mutation in C282Y/H63D 1/250 people have mutation but not everyone asymptomatic family history enzyme replacement therapy (unless child has a deletion mutation. reversed blood flow MRI . varices . loss of Sach's disease developmental skills. splenomegaly. fibrosis. RUQ pain. seizures at age 3-4m.unable to produce clotting factors. splenomegaly. blood in portal vein is also shunted away palmar erythema. diabetes (toxicity to pancreas). HCC. increased uric acid. gene involved normally encodes HFE. thrombocytopenia radiographic signs characteristic of cirrhosis but no symptoms chronic abnl LFTs. then they would develop an immune response and require induced immune tolerance) minimize enviromental factors (smoking. Tay. elevated triglycericides liver biopsy (measure amt of glucose-6-phosphatase) nutritional management (continuous night feeding via ng tube. produced mainly in liver but functions in lung to inhibit elastase. hepatomegaly (glycogen stores build up bc cannot be broken down).helps lung fxn but not liver disease (malformed protein is still being produced…) monitor serum ferritin or transferrin saturation frequent phlebotomy to remove RBCs (and hence drop iron levels) cirrhosis. occupational lung hazards) IV augmentation therapy (antienzyme therapy) . cirrhosis. spider angiomas portal-systemic collaterals. lactic acidosis. impotence which regulates iron by modulating activity of ferroportin on enterocytes (absorb Fe) and hepatocytes/macrophages (store Fe). histology: regenerative hx of chronic liver nodules surrounded by disease extensive scarring or fibrotic tissue liver insufficiency (hypoalbuminemia.nodular liver.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Glycogen storage disease GSD-1 hypoglycemia very quickly after last meal. cirrhotic liver contour. hyperpigmentation. frequent feedings) liver transplant when dietary treatment fails or when adenomas develop Tyrosinemia type 1 defective enzyme (FAH) causes buildup of toxic metabolite FAA. from liver --> increased back pressure on gynecomastia) mesenteric venous drainage of gut --> splanchnic hemodynamic derangement palpable left liver lobe. uncooked corn starch before bed.
hypotensive abnormal dilation of pulmonary vasculature causing hypoxemia (in absence of radiographic shunt lesion) Platypnea (SOB when upright. ascites. TIPS (if refractory ascites) early antibiotics if SBP cerebral vasodilation (hepatic encephalopathy). where they increase NO production. conductance abnormalities. GI bleed. systolic & diastolic dysfunction. levels to measure treatment rifaximin. hepatopulmonary syndrome. schistosomiasis. venoocclusive disease. asterixis (hepatic encephalopathy) no biopsy needed (imaging + symptoms sufficient) ascites fluid . Budd-Chiari hepatic encephalopathy neurologic & psychiatric dysfunction in presence of decompensated cirrhosis hyperammonemic state different dz manifestations depending on setting of acute or chronic liver dz. nl 3-5 mmHg volume --> compensatory upregulation of neurohormonal systems (RAAS.detection of microbubbles in left heart after 3-6 cardiac cycles (in contrast to 1 cycle if intracardiac shunt lesion) supplemental O2 with curative liver transplantation Hepatopulmonary syndrome (HPS) .serum albumin to ascites gradient (SAAG) > 1. metabolic/ hemodynamic derangements abdominal compartment syndrome (restrictive lung physiology) spontaneous bacterial peritonitis: > 250 neutrophil count in pericentesis hypoglycemia (BAD sign) Portal hypertension variceal hemorrhage. splenomegaly splanchnic vasodilation (increased flow) + scarred/fibrotic liver (increased resistance + stellate cell mediated sinusoidal vasoconstriction) = increased portal pressure as back pressure to gut increases. pulmonary vasodilation (portopulmonary hypetension. or metronidazole response low platelet count (thrombocytopenia) Cirrhotic cardiomyopathy resembles septic hypotension (low BP = low SVR) compensatory mechanisms will be seen: tachycardia.(hi resistance) --> engorgement of gastroesophageal plexus --> variceal bleeding blood in portal vein is also shunted away from liver --> increased back pressure on mesenteric venous drainage of gut --> splanchnic hemodynamic derangement Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications decompensated Cirrhotic changes + SYMPTOMS compensated signs + jaundice. acute liver dz (development of intracranial HTN & cerebral edema --> herniation). more NO = splanchnic arterial vasodilation cirrhosis (increased resistance in sinusoidal space) Other causes? Portal/ splenic vein thrombosis.1.1 (hydrostatic process suggesting transudative ascites. if less than 1. bounding pulses. splanchnic vasodilation --> pathologic shunting of blood away from liver --> increased Hepatic pressure venous cardiac output into gradient (HVPG) = WHVP splanchnics --> decreased (wedge pressure) . ADH) --> inc intravascular volume (renal vasoconstriction or Na/H2O retention) --> hepatorenal syndrome OR ascites/ hyponatremia serum ammonia level not eliminate ammonia production reversible with treatment! sensitive but can use serial sources using lactulose. ascites. gut bacteria are translocated and enter mesenteric lymph nodes. wide pulse pressure. chronic liver dz (less injury bc upregulation of ammonia backup systems) conversion of ammonia (which is not eliminated by dysfunctional liver) to glutamine --> astrocyte swelling & altered neurotransmission Infection. paracentesis (especially if ACS). dehydration systemic manifestations. SNS. and impaired B-adrenergic receptor function dilation of basal pulmonary vasculature impedes diffusion mediated transfer of oxygen bubble study . diuretics.FHVP (free effective arterial blood hepatic pressure). peripheral vasodilation (shock). opposite of CHF patients) hemodynamic circulation due to peripheral vasodilation and sympathetic activation causes decreased arterial blood volume. hepatic hydrothorax). think neoplasm or infectious cause of ascites) chronic ascites? Minimize sodium diet.
n/v. OCPs. hypersecretion (increased chol synthesis and/or decreased bile acid secretion) of cholesterol from liver into the bile. stent placement associated with other congenital anomalies (Down syndrome. the ventral part remains in the initial pancreatitis position and wraps around second part of duodenum Pancreas Divisum most common congenital anomaly of pancreas failed fusion of dorsal and ventral pancreatic ducts 5-7% of population endoscopic or surgical sphincterectomy. hypoxemia accumulation of ascitic fluid in pleural space. forming cholesterol vesicles and eventually crystallizations cholesterol supersaturation (chol>> bile acids).000 surgical bypass of the area wrapped around the duodenum Here. pulm edema. jaundice. ventral portion of pancreas fuses with dorsal part of pancreas 1/20.o.difference btwn HPS & PPHTN Hepatic hydrothorax transudative pleural effusion resulting from ascites tracking across diaphragm into negative intrathoracic space dyspnea. fertile) no intervention if asymptomatic cholecystectomy + R/O complications ursodeoxycholic acid (secondary bile acid that reduces chol secretion into bile) acute cholecystitis gallstone ileus biliary pancreatitis (distal impaction) Acute cholangitis Choledocholithiasis Mirizzi syndrome . pancreatitis) sometimes n/v brown pigment (biliary infections) 1. age. gallbladder hypomotility (biliary sludge) gallbladder hypomotility (at risk? Pregnant. female. 40s. obesity. incomplete rotation so despite the ventral and dorsal pancreas attaching. use. empiric antibiotics Band ligation via endoscopy if esophageal varices TIPS if failed variceal banding or gastric varices respiratory faulure spontaneous bacterial empyema Variceal hemorrhage hematemesis.better or equivalent to y. duodenal atresia. DM. hematochezia significant portal hypertension causes back flow of blood to gastroesophageal plexus --> varice formation --> rupture --> potentially fatal hemorrhage endoscopy Hepatorenal Syndrome (HRS) functional renal failure in presence of decompensated cirrhosis splanchnic vasodilation--> decreased effective arterial blood volume (per the kidneys…) --> compensatory mechanisms by kidneys --> functional renal failure structurally normal kidneys terlipressin (splanchnic vasoconstrictor) Annular pancreas incomplete rotation of ventral pancreatic bud infants: n/v. FTT. hormonal treatments like ocreotide acromegaly) 1-2% of population Congenital pancreatic cysts very rare! surgical resection if symptomatic Cholelithiasis (gallstones) 10-15% of men > 60y. prostaglandin therapy if acute RV failure Liver transplantation does not immediately reverse PPHTN (so patients must continue prostaglandins) . it will occur before ductal system age 2 (abdominal distention. IBD.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Portopulmonary Hypertension (PPHTN) pulmonary hypertension in the setting of decompensated cirrhosis --> right heart failure RHF. duodenal stenosis. normally. tracheoesophageal fistula) can have strictures/ obstruction in duodenum Ectopic pancreas most pts are asymptomatic. particularly right hemithorax --> right sided pleural effusion CXR Thoracentesis diuretics TIPS = transjugular intrahepatic portosystemic shunt splanchnic vasoconstrictors (ocreotide). estrogen MRI . rapid weight loss. adults: PUD. long term parenteral nutrition.. feeding problems normally in embryologic development. child U/S . BB to decrease HR.o. peripheral edema unk?? Vascular injury/ inflammation mediated by serum factors abnormally persist in hepatic outflow ECHO (screens) + RH catheterization (confirms) Diuresis. pancreatitis) Cholesterol (80%) intense RUQ/epigastric pain that radiates to back about 1h black pigment postprandial (cirrhosis. other comorbidities FFFF (fat. U/S hyperF>M triglyceridemia. terminal ileum disease.98% sensitivity 20-40% of women > 60 bearing. accelerated nucleation. congenital heart defects. hemolysis. ascites. main pancreas duct drains into major papilla but in divisum. the ducts do recurrent pancreatitis or chronic idiopathic pancreatitis not fuse properly so majority of pancreas drains into minor papilla --> pressure buildup and pancreatitis accesory pancreas most people are asymptomatic can cause nodules or tiny polypoid lesions in other parts of GI tract most are asymptomatic but if anomalous development of pancreatic symptomatic. 2. secretion of free cholesterol into bile.
dull.inflammation + gallbladder in some due to hypomotility of gallbladder but no stone inflammation. ischemia. transient AST/ALT spike would suggest passage of stone into duodenum U/S . usually in stone forms fistula between gallbladder elderly so delayed diagnosis due and small bowel. jaundice) Reynold's pentad (charcot's + altered mental status + hypotension) impacted stone in common bile duct leads to permanent obstruction (unlike choledocholithiasis . Enterococcus. steady pain (15-60min) that slowly resolves. elevated WBC chronic obstruction of gallbladder outlet by gallstone --> bile stasis --> severe inflammation --> damage to gallbladder mucosa 1/3 of patients with gallstones cholelithiasis mostly clinical diagnosis but cholecystectomy + antibiotics U/S is accurate in up to 88%: (Gram negatives).diagnostic & therapeutic elevated WBC.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Biliary colic ACUTE cholelithiasis RUQ/epigastric pain that radiates to right shoulder/scapula. may or may not have gallbladder inflammation U/S gold standard diagnosis recurrent? Elective cholecystectomy +/intraoperative cholangiogram to clear out any stones in bile duct if needed Acute Cholecystitis positive Murphy's sign (inspiratory halt upon palpation of gallbladder). reassurance + lifestyle/dietary mods 2. and then migrates to become obstructed in to other comorbidities terminal ileum common hepatic duct obstruction by stone in the cystic duct (stone from the outside obstructs the hepatic duct) caused by increased intestinal motility --> heightened sensitivity due to abdominal pain for at least 3 altered visceral sensation through enteric stressors months. cholangitis (if bacterial infection too) mild hyperbilirubinemia. persistent ache that radiates to right scapula. most common complication of gallstones intermittent obstruction of cystic duct. right subcostal (usually ICU or intubated patients) tenderness RUQ pain . proceed with HIDA scan (would not see any radioactivity in gallbladder diagnostic of acute cholecystitis) majority of people have no complications diabetics can have gangrenous cholecystitis gallbladder empyema perforation (distention.coli. no response to above? Psych referral for pain management . elevated ALP. ALP positive blood cultures ERCP + cholecystectomy (unless high risk patients these will have ERCP + URSA to dissolve the stones) Cholangitis Charcot's triad (fever. bilirubin. pruritis. Klebsiella. Elective ERCP to remove stone EUS/MRCP (regular U/S would 3. Clostridium) Gallstone ileus Mirizzi Syndrome Irritable Bowel Syndrome (IBS) abdominal distention.mobile stones). escapes the gallbladder. pericholecystic fluid collection --> abscess) Choledocholithiasis often asymptomatic but wil have intermittent obstruction of common bile abnl labs/imaging duct (usually due to gallstones but small minority arise de novo) jaundice. with onset at least 6 months ago. anti-constipation) 3. NL physical exam (+/. increased pressure above the stone --> bacterial proliferation --> septicemia (gram negative bugs like E. PCT if ERCP unsuccessful miss bile duct stones) 4. IV antibiotics 2. worse with meals. increased severity? Agents that treat motility (antidiarrheals. Pseudomonas.identifies common bile duct stones in 50% of patients ERCP . nl labs. mild jaundice (slightly elevated bili). lasts longer than 6hours. that improves w/ and extrinsic nervous system --> dysregulation of brain-gut communication defecation and is associated w/ change in frequency or form more of a psychiatric problem of stool!! NO STRUCTURAL ABNORMALITIES involves small and large intestine NOT a/w fever or dehydration!! 1. cholecystectomy (after infection cleared and stone is CT if worried about out) complications remove stone + hi mortality/morbidity cholecystectomy Cholecystectomy + ERCP or cholangiogram to open the bile duct 1.RUQ tenderness). n/v fever. slightly elevated AST/ALT/ALP If U/S is questionable. IV fluids gallstones + gallbladder wall thickening/edema + distended lumen Elevated WBC. palpable acalculus cholecystitis . RUQ pain.
liver enzymes. n/v. possible jaundice (if stones in common bile duct). sepsis. high lipids. shock. intestinal uncoated pancreas pancreatic enzyme therapy) pseudocysts. RA. diaphoresis. SPINK1 (PST1) idiopathic others (hereditary.free diet steroids in refractory cases serum tissue transglutaminase replace deficient vitamins (tTG) or anti-endomysial antibody Endoscopy: scalloped pattern histology: flattened/ atrophied mucosal villi. crampy epigastric & periumbilical pain. infection. tachycardia self-limiting!! nl have protective mechanisms against pancreatitis (inactive enzyme produce as proenzymes . pancreatic diabetes hereditary pancreatitis? Gene mutations in alcohol PRSS1. vomiting. trauma. melena BUT minimal abdominal findings diarrhea. lipase/amylase. dermatitis that activate T cells --> inflammation & herpetaformis (IgA deposits on villi destruction skin) gluten allergy a/w autoimmune disorders (SLE. mesenteric arteries diarrhea. CT. bloating. folate. surgical resection of affected colon Acute mesenteric ischemia superior mesenteric artery embolus nonocclusive mesenteric ischemia endoscopy: huge ulcers due to loss of blood supply Abdominal Aortic Aneurysm (AAA) Celiac disease affects duodenum > ileum immune response to gliaden fraction of gluten --> tissue transglutaminase (tTG) alters gluten peptides when encountering malabsorptive fatty diarrhea. pancreatic ascites. U/S) Functional: parenchymal changes denoted by secretin/CCK test ERCP if gallstone in common systemic response: ARDS. diarrhea. +IgG4 Structural: dilated pancreatic duct or dilated side branch of pancreatic duct on imaging. pancreatic fistula. metabolic complications cholecystectomy if infected (after antibiotics) mortality in <20% cessation of alcohol if etiology early complications (DIC. control diarrhea (intestinal splenic vein thrombosis coated pancreatic enzyme therapy) Acute diverticulitis visceral dull pain that localizes and becomes severe somatoparietal pain in LLQ constipation. sphincter of Oddi. DM type I. bloating. vomiting. bile duct pleural effusion. DQ2 or DQ8 --> formation of complexes iron deficiency anemia. tender abdominal mass lightheaded. fat-soluble vitamin deficiencies gluten. + gallstones on imaging supportive care. WBC. thyroid disease) 1/100 Irish / European descent family history iron. hyperplasia of crypts . lymphocytic & plasma cell infiltration. maldigestive diarrhea (steatorrhea. myocardial depression. increased pancreatic infections.can only be activated by enterokinase in small intestine. autoimmune. pancreas divisum. iatrogenic ERCP. azotorrhea). fever more common in sigmoid and descending colon loss of vascular supply by superior/ inferior sudden onset. pain meds no damage to pancreas. +ANA. later complications after 1 wk (pseudocyst. multiple organ failure). nausea antibiotics. melena pain out of proportion to findings acute sudden onset severe midabdominal "tearing" pain pulsatile. majority of patients do NOT have any complications Chronic pancreatitis weight loss. hemorrhage) control pain (NSAIDs. permanent damage to narcotics. IV fluids. impaired chloride conductance --> thick autoimmune) secretions/ mucus --> blocks pancreatic duct autoimmune pancreatitis? Lymphocyte infiltration causes fibrosis of pancreas --> pancreatic dysfunction Autoimmune pancreatitis? Swollen pancreas on CT. CF. osteopenia.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Acute pancreatitis epigastric pain (severe. persistent) that radiates to back or left scapula n/v. acute renal antibiotics if infected/necrosis failure. trypsin inhibitors to prevent auto-digestion) insult (gallstones. calcium deposits throughout pancreas head (ERCP. 6mercaptopurine/ azathrioprine). anorexia. CF? gene mutation in CFTR causes pancreas divisum. neoplasm) abdominal pain + elevated lipase/ amylase Gallstone pancreatitis? Elevated bilirubin. abdominal pain (although some patients are relatively painless). alcohol) --> loss of protective mechanisms --> proenzyme activation --> digestion of pancreas --> acute changes --> ischemia --> release of inflammatory mediators --> systemic response (sometimes if severe) gallbladder stones that have migrated to become obstructed in the Ampulla of Vater (pancreatic duct + common bile duct) alcohol idiopathic other (drug induced dideoxyinosine/DDI. CF.
o/w HCC is solitary lesion histology: liver lobule cords become 4-5 cells thick. generally benign Females Pancreatoblastoma less predictable biologic behavior solid pesudopapillary young females tumors mostly indolent but some have aggressive growth malignant tumor of infancy/childhood YOUNG FEMALES epithelial and mesenchymal elements KIDS!!! (rare cases in adults.sudden RUQ pain women of childbearing age who have used OCPs age. eccentric nuclei. rapid increase in liver size. OCPs Bleeding risk!! (especially subcapsular adenomas) Common cause for sudden peritoneal hemorrhage in young women increased risk for HCC Non-neoplastic hepatocellular nodules often mistaken for neoplasms result from vascular malformation after local vascular injury or AVM women of reproductive age histology: focal nodular hyperplasia. increased pain cirrhosis hemochromatosis chronic HBV or HCV chronic alcoholism aflatoxin exposure hemochromatosis prognosis best if single tumor is <2cm in size and good liver function Cholangiocarcinoma markedly distended abdomen type of adenocarcinoma involving intrahepatic and extrahepatic bile ducts from ascites (obstruction of lymphatic drainage --> large fluid majority arise from extrahepatic biliary accumulation) tract. who would have worse prognosis) . no bile ducts visible gross: very bloody mass NO needle biopsy (could cause bleeding!) surgical excision after > 910cm possible that they could spontaneously rupture but very rare Hepatic adenoma most patients who have these benign neoplasm of hepatocytes present with hemorrhaged hepatic adenoma . no evidence of cirrhosis histology: multiple large vascular channels (full of blood or thrombosed) histology: no inflammatory infiltrates. appear as exophytic red/blue spongy masses that rise and push up against capsule.common hepatic duct) more common than cholangiocarcinoma arises in patients with recurrent trauma and inflammation due to chronic cholecystitis and/or cholelithiasis PSC. markedly enlarged and fatty appearing cells. lung] most common primary malignant neoplasm silent hepatomegaly (if noncirrhotics). mitotic figures. cysts of biliary tree.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Benign liver neoplasms Cavernous hemangioma most common benign liver neoplasm vascular tumor defined by the proliferation of blood vessels gross: enlarged blood vessels in the cavernous. worsened ascites. multifocal carcinoma areas only in HCC from chronic hep/ cirrhosis. & hypochromatic areas. chronic infection w/ liver fluke CIRRHOSIS PATIENTS DO NOT HAVE INCREASED RISK! usually occurs in presence of gallstones histology: formation of haphazard glandular structures gross: dilated duct lumen from obstruction Hispanics. especially at hilum (Klatskin tumors jaundice . resembles glandular structures Female Female Adenocarcinoma of gallbladder Cystic pancreatic neoplasms serous cystic neoplasms mucinous cystic neoplasms females. glycogen. Native histology: malginant lesions Americans have loss of cell polarity. LOTS of bile ducts gross: central scar (stellate shaped) gross: large nodule arising through a cirrhotic-appearing liver capsule. breast. vascular invasion (worse prognosis) elevated alpha-fetoprotein Hepatocellular carcinoma [FYI: most common malignant neoplasm of liver? Metastatic carcinomas from GI/colon.
DPC4. host: chronic pancreatitis. ponds (near reservoirs . T4 hereditary breast/ chronic pancreatitis! beyond pancreas. within epithelial cells but do not invade farther than this barrier histology: polar tubules Nitazoxanide (NTZ) TMP-SMX (trimethoprimsulfamethoxazole.watery diarrhea + hypokalemia syndrome + achlorhydria Glucagonoma . adenocarcinoma . celiac axis or SMA. malignant. found worldwide streams. steatorrhea.body & tail. BRCA2 exp. usually benign. T2 . camping stool microscopy for O&P immigrants & travelers to developing world stool microscopy & immunoantigens liver abscess aspirate = "anchovy paste" . BRCA3. within epithelial cells but do not invade farther than this barrier histology: shaped like an "I" but has 2 nuclei histology: small round oocysts seen with AFB stain.PanIN. larger. T3degree relatives (yellowish/whitish and firm to beyond pancreas but not yet touch) .body & tail. sepsis. weight loss.limited to around growing tumor pancreas. moderate perforation. Bactrim) ALB (albendazole). hypochlorhydria. familial Histology: fibrous tissue + abnl epithelial cells (resembles atypical mole syndrome.2/3 malignant. unexplained weight loss.) majority are surgically gross: area of scarring/fibrosis unresectable Staging (T1.secrete digestive enzymes poor prognosis but slightly better than ductal adenocarcinoma Pancreatic Islet Cell Neoplasms Clostridium dificile subcutaneous fat necrosis in the skin (painful) majority are functional (secrete Insulinoma . FMG (fumagillin) .inhibitory so shuts everything down. lack of fruits/veggies. pancreatic Trousseau's sign (migratory . nausea. + Kras) diabetes. muskrats) daycare centers daycare. enzymes that determine hard to control hypoglycemia. painless jaundice.1: mild dysplasia (Her-2neu. to development of trophozoites in large dysentery colon --> invasion into epithelia (unlike Giardia. increased frequency in bowel colonization --> disruption of normal flora movements by antibiotics --> toxin elaboration (particularly toxin B) --> diarrhea & colitis pseudomembranous colitis a/w fever. hereditary pancreatitis Pancreatic Acinar Cell carcinoma rare malignant tumor tumors secrete lipase/ trypsin/ amylase arise from acinar cells . Ulcerative colitis CT: pericolonic stranding & colonic wall thickening indicating infectious process Metronidazole (Flagyl) if mild. steatorrhea. fever ingestion of cysts from environment leds bloody stools (inflammatory). asymptomatic until late stage alcohol (due to chronic progression from PanIN to then present with epigastric pancreatitis) pain. dif toxins (A/B) on cases PCR probiotics decrease recurrence metronidazole or tinidazole [toxicity/ side effect = disulfuram effect = nausea and severe symptoms] Giardia lamblia (Flagellate) Entamoeba histolytica symptoms: malabsorptive diarrhea. peritoneum 4th leading cause of cancer death age (older patients elevated CA 19-9 surgery for symptom relief but <5% 5y prognosis 60-80 y. hospital setting. they have metastasized to liver. dehydration.shock.o. gram positive spore forming Antibiotic induced diarrhea! inflammatory diarrhea anaerobic bacillus characterized by tender LLQ. which is local and stays in duodenum/jejunum) Cryptosporidium parvum self-limiting watery diarrhea (can sexual & asexual stage be very mild) immunosuppresed have chronic refractory illness w/ high recurrence rate cysts in environment/water are ingested -> once in GI tract.chronic pancreatitis) Jegher's syndrome. abnl HI symptoms) insulin secretion 15-35% are silent (subclinical gastrinoma .PanIN-2: moderate dysplasia (p16) intraepithelial neoplasia thrombophlebitis) . involving ovarian cancer celiac axis and/or SMA) (BRCA2). & death oral vancomycin for severe positive C.same fibrosis as w/ hx. cramps.rust colored metronidazole for trophozoites. tachycardia majority of cases are asymptomatic 1-2 week incubation period 2% of all pancreatic tumors gross: abundant blood supply (unlike adenocarcinomas which are more white/ yellowish) histology: monotonous appearing malignancy determined by hormone secreted. Zollinger-Ellison syndrome associated w/ MEN-1 VIPoma. size of tumor. paranomycin for cysts extra-intestinal manifestations (amoebic liver/lung/ brain abscess) Apicomplexa parasites contaminated surface water or global water supplies Isospora belli Cyclospora cayetanesis mostly tropical regions contaminated fruits & veggies mostly tropical regions Microsporidia Enterocytozoan bienusi fungal organisms that produce pathology when spores are inhaled or ingested global histology: small round oocysts seen with AFB stain. (PanIN) DPC4) most common malignancy of pancreas (80-90%) distributed most commonly in pancreas head. they develop trophozoites that attach to duodenal/ jejunal mucosa --> local inflammation & villi blunting --> hypersecretion & malabsorption contaminated water supplies. & aggressiveness Antibiotic use. HNPCC. Peutz. excess acid hormone levels) production --> PUD.PanIN-3: severe dysplasia (p53. difficult to predict biologic refractory hyperglycemia/ diabetes. DM. smoking. cholithiasis toxigenic. petroleum product p53 tumor suppressor.beavers. LNs. chemotherapy.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Pancreatic ductal adenocarcinoma etiologic agent causes genetic mutations environmental: cigarete in k-ras oncogene. surgery. p15 tumor suppressor. behavior necrolytic migratory erythema Somatostinoma . elderly. bloating.limited genetics: 1st to pancreas. small. toxic megacolon. vomiting. but time of diagnosis.
rectal prolapse major contributor to global malnourishment high worm burden --> significant blood loss. more common in children.characteristic eggs Trichuriasis stool exam +/. low albumin. jaundice occur usually after travel to resource poor country. hemoptysis. macrocytic anemia swimmer's itchy. urticaria. causing colitis & rectal prolapse infects cecum & colon acquired through skin. renal failure [1wk post diarrhea. Katayama fever. transitory pulm infiltrates. wheezing. where they lay eggs ANAL ITCHING whipworm colitis (bloody stools). invasive disease. southern US poor sanitation places barefeet immunocomp at risk for hyperinfection syndrome serology biopsy would show adult worm burrowing in small bowel IVERMECTIN (binds to glutamate-gated chloride channels causing parasite paralysis & death) Other nematodes Ascariasis ingestion of eggs poor sanitation places stool exam +/.coli hemorrhagic colitis (bloody O157:H7) diarrhea) heat labile enterotoxin causes increased cAMP secretion --> secretion of chloride into lumen --> water follows chloride (hence watery diarrhea) Shiga cytotoxin damages cells/brush border/ mucosa --> bloody colitis hydration. abd pain. gaining access to alveoli & lungs--> move towards trachea where they are swallowed --> reach GI tract (small bowel) --> larvae mature and burrow in duodenum & jejunum --> lay eggs that hatch in the intestine --> autoinfection --> hyperinfection syndrome tropical. E. water. diarrhea. FMG (fumagillin) Complications Strongyloides stercoralis Encephalitozoon intestinalis (Nematodes) symptoms: itchy rash/ ground itch (initial penetration). 6-48h post-food ingestion & lasts 3-7days watery stools. and low nutrients cysticercosis --> epilepsy hyatid cysts vitamin B12 deficiency. shortlived secretory diarrhea invades & destroys colon mucosa. female nematodes migrate out of rectum to the anus. Sickle cell ANTIBIOTIC TX NOT decreased gastric acidity RECOMMENDED in lowers infectious dose uncomplicated gastroenteritis increased susceptibility (could increase organism carriage) . abdominal cramping.eosinophils Hookworm 700 million people affected. coli EHEC (SHEC. SHEEP FRESHWATER FISH FRESHWATER RAW FRESHWATER FISH WATERCRESS contaminated food & water E. Shiga toxin assay (antibiotics are contraindicated) Hemolytic uremic syndrome (HUS) = anemia.eosinophils Enterobiasis migrates from skin & lung as adult worm to asymptomatic unless high worm jejenum burden --> obstruction ingestion of eggs --> infection of colon & pinworm anus most common helminth in U. larva currens (serpentigous mobile rash).fever. dyspnea. malabsorption) hyperinfection . but 12% affected require dialysis or die from ESRD] food. antimotility meds. sepsis most common infection worldwide infection from skin penertration by larvae soil in soil --> larvae migrate to blood. chronic dz increased risk of Cholangiocarcinoma RUQ pain. eosinophilia).thrombocytopenia.self-limiting watery diarrhea (can be very mild) immunosuppresed have chronic refractory illness w/ high recurrence rate Disease Microsporidia Clinical Variants Defining Characteristics Pathogenesis fungal organisms that produce pathology when spores are inhaled or ingested Etiologies Epidemiology global Risk factors Lab/Imaging histology: polar tubules Treatment ALB (albendazole). after which the worm uses teeth to attach to lungs & small bowel mucosa tropical areas ALB (albendazole. immunocomp. subtropical areas. fever. Loeffler's syndrome (wheezing. & person-toperson transmission Salmonella Salmonella typhi Salmonella typhimurium Salmonella enteritidis typhoid fever self-limited acute enterocolitis. fluoroquinolones (CIPRO) appears colorless on sorbitol SUPPORTIVE CARE ONLY agar plate.S. MBZ daycare!!! scotch tape . n/v contaminated human sewage contaminated food with animal waste seen often during environmental crises elderly. primarily developing countries Cestodes/ flatworms Blood flukes Liver flukes Taenia solium Taenia saginata Echinococcus Diphyllobothrium latum Schistosomiasis Clonorchis sinensis Fasciola hepatica ETEC (Traveler's diarrhea) PORK BEEF DOG. MBZ (mebendazole) ALB.inhibits polymerization of tubulin & tubulin dependent glucose uptake). GI symptoms (if high worm burden: abdominal pain.
beef. n/v. metastasis.poultry. then proceed to surgery Large Bowel Obstruction (colonic) CT. weakness. hypotension) sigmiod colon & cecum are malignancy. abdominal tenderness. abscess (strangulation/ bowel ischemia).surgery narrows off (should use colonoscopy to biopsy tumor) malignant strictures . hi pitched or musical BS. intermittent abdominal pain. Vomiting. abdominal cramps B. raw milk. intussusception (bowel telescopes sounds followed by intervals of quiet. endometriosis. inflammatory causes PE: periods of increased bowel (IBD. peanuts. eggs. rectal tube. meds (narcotics) poorly localized abdominal pain.systemic Abs + obstruction occurs laparotomy air fluid levels partial SBO . watery or inflammatory quickly produced toxins (C. weight loss. cream pastries. vomiting (bilious. NG tube (decompress stomach.evidence of transition point where peritonitis .poultry. into another part of the bowel). aureus .ground beef.above recommendations unless no improvement. NG tube. drugs). norovirus) Rotavirus primary cause of acute gastroenteritis in young children in U.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications Food Poisoning immediate disease about 1-16h preformed toxins (S. Shigella. Campylobacter . to malignancy? Dilated colon minimize further distention) until tumor. radiation.fried rice. neurogenic. diverticulitis. ischemia. AMS. obstipation hypoactive bowel sounds XR/CT: presence of gas in stomach. iron def anemia. abdominal distention relatively low infectious dose so easy to spread from person to person fecal-oral. fecal impaction periumbilical/ hypogastric abd pain. aerosol-vomitus. vomiting. neoplasms. XR IV fluids. watery diarrhea --> dehydration & electrolyte abnl nonenveloped dsRNA virus fecal-oral. unpast juice. raw veggies. cereus) microbial contamination of food products (V. gallstones. diarrhea or obstipation benign colonic strictures? Thinner stool malignant colonic strictures? Hematochezia. contaminated food cruise ships supportive treatment only Small bowel obstruction post-operative intra-abdominal adhesions. cecostomy. spores) n/v. stricture most common sites for colonic secondary to diverticulitis. renal failure electrolytes. short lasting watery diarrhea acute onset. resection NPO until symptoms resolve. ETEC. dairy. in absence of obtructing lesion pancreatitis). metabolic (abnl electrolytes). abd distention. inflammatory (diverticulitis. correct electrolytes.shellfish.surgery sigmoid volvulus? Bent inner or colonic stents tube appearance + dilated sigmoid volvulus colon protoscopic/colonoscopic decompression. oliguria. crustaceans.congenital atresia/stenosis. SI. insiduous onset Elevated WBC count. abdominal distention. guarding volvulus. hernias (bowel leaves peritoneal cavity and becomes obstructed). fecal). obstipation. RT-PCR.S. sigmoid resection & coloproctostomy cecal volvulus . barium studies. EHEC. XR: dilated SB loops minimize further distention) CT: dilated SB loops + complete SBO +/. endometriosis. correct serum serum electrolytes. limit narcotics. culture rehydration Norovirus most common cause of foodborne outbreaks investigated sudden onset N/V. mayo. volvulus. tachypnea. fomites. systemic manifestions of dehydration (tachycardia. correct serum electrolytes. colon + dilated small bowel no mechanical obstruction!! . NG tube colonic obstruction secondary (decompress stomach.NO COLONOSCOPY. Salmonella . Bacillus post ingestion cereus . intussusception. perfringens. Crohn's. extrinsic volvulus tumors. possible airborne spread winter season 600-850K deaths/ year globall antigen assays. fever.cholera . Vibrio parahemolyticus mollusks.potato salad. abnl IV fluids. get patient moving out of bed! Bowel ileus failure of nl intestinal motility postoperative. after which colon Benign strictures . diarrhea.
blunted haustrations. rectum ALWAYS involves. fever 250. rectal bleeding. & colon but can affect ANY part of GI tract colonoscopy: severe maintenance of remission? (stomach. tenesmus. mortality 0-32% neostigmine (AChE inhibitor). endoscopy w/ bx endoscopy: mild (erythema. after which formation complications are more likely after recovery complicated? Peritonitis (IV antibiotics + surgical exploration). fistulization uncomplicated . elevated ESR/CRP. usually in sigmoid colon microscopic or macroscopic perforation of diverticulum (usually via erosion of wall by fecoliths or by increased intraluminal pressure) western world low fiber diet age!! 10-25% of patients w/ diverticulosis CT . PSC (more in UC. early recurrence post-surgery. impaired resolution).000 cases per year in US ages 10-30 M>F histology: erosion of mucosa. erythema nodosum (extensor surfaces). dull --> appendix distention. fistulizing/microperforating subtypes extraintestinal manifestations? FTT. inflammation & periumbilical pain later: well-localized RUQ pain @ infection McBurney's point. MAJORITY of cases LLQ pain & tenderness. increased pathogenic bacteria) > abnormal processing of antigens (deficient autophagy) affects any portion of GI tract. uveitis.inflammation w/o complications. spares rectum. abscess requires drainage surgery (laparoscopic resection) after complicated episode or 2-3 episodes of uncomplicated. biologics 40% proctitis alone. toxic megacolon. LLQ pain. endoscopic decompression. erythema nodosum (extensor surfaces). Europe & North America defective mucosal integrity (altered mucus.a/w ileocolonic dz. delayed surgery in lieu of long course antibiotics Diverticulosis Diverticulitis complicated diverticulitis perforation. skip lesions. coli.(decreased protective bacteria. immediate appendectomy if abscess formation. colonoscopy a second attack. watery diarrhea inflammatory.complicated will show 20-40% of patients will have uncomplicated? Cipro + peritonitis. stool culture to R/O infection. severe (denuded mucosa. runs independent course from IBD). small Steroids. dysbiosis secretion of IL-23 by macrophages --> induction of TH17 cells to activate IL-17 -. weight loss. 30% left sided disease. obstructing. pylori. moderate (edema. SMOKING in Crohn's disease NSAIDs genetic predisposition correct reversible causes. thickend w/ inflamm material) induction of remission? Steroids. runs independent course from IBD). PSC (more in UC. low albumin (if weight loss). 6MP/AZA. perforation. abscess. uveitis. extent. crypt abscesses (due to neutrophilic infiltration) elevated WBC count pre-op antibiotics + perforation --> peritonitis. colon extremely severe? Colectomy cancer (correlates w/ duration. inflammation in mucosa only disruption of intestinal epithelial barrier + dysregulated immune response --> secretion of IL-23 by macrophages --> induction of TH17 cells to activate IL-17 -> defective epithelial barrier function CBC: microcytic anemia. pyoderma gangrenosum. arthritis/ arthalgias extraintestinal manifestations? FTT. Listeria). episcleritis. highest prevalence in invasive E. ankylosing spondylitis persistent infection (H. immunosuppressed . sepsis CT: donut sign = thickened sx present for 24-72h appendix wall if sx longer than 5d. inflammatory cell infiltrate. n/v. non-necrotizing granulomas Ulcerative colitis only involves colon. antibiotics bowel. 5-ASA (reduce prostaglandins) Maintenance of remission? 5-ASA. severity of UC) Acute appendicitis obstruction of appendix lumen by fecolith early: non-specific. ankylosing spondylitis bloody diarrhea. preserved circular muscles). surgical decompression CBC. elevated ESR/CRP. sacroileitis. 30% pancolitis intractable disease. bleeding/ ulcerations). percutaneous cecostomy. pyoderma gangrenosum. low grade fever herniations of mucosa and submucosa through defects in muscularis. increased M=F disruption of intestinal epithelial barrier + perm. episcleritis. monoart/ asymm/ large joint peripheral arthritis. early onset. esophagus) inflammation leading to Antibiotics + 6MP/AZA ulcerations/ obstruction (inhibit purine biosyn in B & T cells) + biologics (antibodies histology: transmural inflamm against cytokines & adhesion process w/ lymphocyte molecules) infiltrates.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epidemiology Risk factors Lab/Imaging Treatment Complications acute colonic pseudo obstruction severe abdominal distention with absence of stool/gas passage critically ill patients dilation of ALL segments of colon Inflammatory bowel disease Crohn's disease RLQ pain. familial CD Caucasians Ashkenazi Jews. early surgery. perforation. continuous distribution in involved area (no skip lesions). hemorrhage. monoart/ asymm/ large joint peripheral arthritis. low induction of remission? mostly affects ileocolic albumin if weight loss area/terminal ileum. granulomas CARD15/NOD2 mutation . dysregulated immune dysregulated immune response --> response. sacroileitis. abscess metronidazole. arthritis/arthalgias. transmural inflammation.
Screening / Education certain foods or trauma can precipitate the lesion cancers a/w HPV have better prognosis though! .
Screening / Education .
Screening / Education Prognosis determined by depth of invasion Prognosis determined by depth of invasion aggressive behavior determined by size and number of mitoses .
recurrent bleeding despite endoscopic tx. recurrent bleeding during hospitalization .Screening / Education indications for surgery (PUD bleeding): massive hemorrhage leading to shock. prolonged blood loss w/ more than 6 units transfusion.
Screening / Education .
Screening / Education IgG antibody vaccination to protect against HepA vaccination [IM injection @ 0. 6 months] provides HBaAg required for all HCWs Hepatitis B immunoglobulin (HBIG) . exposed infants. 1 week post-transplant) . 1.offered to high risk patients. or liver transplant patients (before new liver in.
statins. etc) 5.Screening / Education screen all baby boomers!! 1. DO NOT RECHALLENGE (exception: tylenol) . known common patterns (INH. stop all non-essential meds 4. consider every drug/ med/ herbal 3. R/O other causes of liver disease 2. Know potential specific treatments 6.
etc) 5. Know potential specific treatments 6. stop all non-essential meds 4. DO NOT RECHALLENGE (exception: tylenol) . known common patterns (INH.1. R/O other causes of Screening / liver disease Education 2. consider every drug/ med/ herbal 3. statins.
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
assess Ht. can figure out morbidity & mortality . pO2. LDH enzymes.Screening / Education Ranson criteria for severity upon admission: initial admission. if initial and/or 48h labs meet criteria. within 48h. Ca++. & glucose. base deficit. fluid deficit. WBC. BUN.assess patients age > 55. AST.
Screening / Education .
Screening / Education .
avoid food cross contamination.Screening / Education bottled beverages. diaper hygiene at pools . hand wash after all animal contact. avoid ice & uncooked food cook ground beef.
oral vaccines for infants (Rotarix) .Screening / Education live.
Screening / Education .
thus. prominent forehead. profound cortical collecting duct. FTT. absence of functional sodium channels in hyponatremia. coarct of aorta. thus CCD cells do not metabolic acidosis.Disease Fanconi's Syndrome Clinical Variants Defining Characteristics Pathogenesis Etiologies Cystinosis (auto recessive.catecholamines.bow legged. Adrenal glands (cortex aldosterone. hypomagnesemia. Aldosterone then acts on CCD to increase Na+ reabsorption and K+ secretion [excess aldosterone effect] A. hypocalciuria. hyponatremia early age presentation similar sx to side effects of loop diuretics hyponatremia. metabolic alkalosis active despite normal volume levels and no aldosterone present. hence. wrist widening. hypercalciuria Secondary causes of hypertension (listing) Liddle syndrome autosomal dominant disorder Congenital adrenal hyperplasia 21-hydroxylase life-threatening hyperkalemia. growth hormone) severe HTN from Na retention. diet E .drugs. Cushing's syndrome D . hypokalemia. the adrenal gland has genetic defect in which it cannot respond to ATII to make aldosterone [aldosterone deficiency/ absence] elevated aldosterone levels.obstructive sleep Apnea. osteomalacia). however. H secretion volume depletion --> renin secretion --> ATII production. glucosuria. hyponatremia. cortisol. salt cravings. aldosterone is constitutively active despite volume repletion. causing volume depletion disorder and aldosterone production . hypochloridemia. hypokalemia.erythropoietin excess. most common cause in childhood) Epi Risk factors Lab/Imaging Treatment Complications Screening / Education metabolic acidosis (bicarb proximal tubule dysfunction from global wasting). 1/2 of collecting duct sodium channels have low aldosterone & renin levels. metabolic alkalosis. low serum uric acid. endocrine (thyroid. hypophosphatemia defect in all PT transporters (Ricket's . bad kidneys C. hyperkalemia reabsorb Na or secrete K despite very high levels of aldosterone [aldosterone deficiency/ absence] similar symptoms to side effects genetic defect in Na/Cl cotransporter in DCT of thiazide diuretics (same transporter that is blocked w/ thiazides) volume depletion. amino aciduria Adrenal adenoma metabolic alkalosis. medulla pheochromocytoma) B . constant CD sodium reabsorption and K. severe volume depletion autosomal recessive disorder usually diagnosed @ birth w/ NBS synthetic aldosterone infusion Pseudohypoaldosteronism Type I autosomal recessive disorder Gitelman syndrome autosomal recessive disorder check magnesium because hypomagnesemia can cause refractory hypokalemia replace K. metabolic alkalosis. adrenal gland autonomously produces refractory HTN aldosterone. hypokalemia.bruits (renal artery stenosis). Mg losses. restore intravascular volume w/ salt Bartter syndrome genetic defect in NKCC co-transporter in TAL autosomal recessive of loop of Henle. mutation that renders them constitutively hypokalemia. without signals from ATII. deficiency profound metabolic acidosis.
mildly hypervolemic (NEVER hypovolemic) 2. vasopressin tannate in oil. GI loss. nl renal. normovolemic. weight (kg) x (120cerebral edema plasma Na) overcorrection of normal saline is sodium levels can contraindicated!! cause central pontine neurolysis 3% hypertonic saline + (CPM) loop diuretic Hypernatremia water loss (insensible loss from skin. lithium (manic depressive d/o). partial X. cyclo-phosphamide IV. or renal failure osmotic diuretics like glucose. hypoxic encephalopathy. med hx. calculate serum osmolality thyroid function tests. or reset osmostat Etiologies Epi Risk factors Lab/Imaging electrolyte panel. primary (psychogenic) polydipsia.linked mutation in V2 vasopressin receptor OR autosomal recessive mutation in aquaporin P2 water channels causes failure to respond to ADH. bladder enlargement & obstruction (from attempts to retain urine). nephrotic syndrome). Sheehan's syndrome Central diabetes insipidus complete. demeclocycline (contraind in liver dz). hypothyroidism. resulting in the retention of water. cirrhosis.Disease Hyponatremia Clinical Variants Defining Characteristics seizures (neuro emergency) or can be gradual onset (intact neuro exam) Pathogenesis decreased effective circulating volume from true volume loss (GI loss) or perceived volume loss (edematous states . serum hypotonicity WITHOUT maximally dilute urine (patients have inappropriately concentrated urine) normally. rhabdomyolysis) hypertonic saline IV problem with the production (damage to idiopathic. osmotic diuresis. thiazides. carbamezipine. mannitol. hypernatremia water deprivation study (water deprivation = increased plasma osmolality but NO concurrent increase in urine osmolality) exogenous ADH helpful for complete and partial central DI [dDAVP desmopressin nasal spray. preventing water reabsorpton). analgesic nephropathy. adrenal. renal loss from DI. hypokalemia) children hydration + low sodium diet water deprivation study (water deprivation = increased plasma osmolality but NO concurrent increase in urine osmolality) not responsive to exogenous ADH (because problem with end-organ!) thiazide diuretics + low sodium diet (decreases overall urine output by keeping mild volume depletion state and increasing PCT reabsorption) . dilute urine. sarcoidosis. dilute urine. loss into cells from seizures. decreased solute intake (beer potomania). however. Vaptan (V2 receptor antagonist. urea electrolyte abnl (hypercalcemia. hyponatremia Treat sodium deficit (Na+ hyponatremia can needed = 0. aqueous vasopressin] partial central DI . cortisol deficiency. hypernatremia polyuria.can also use chlorpropamide.suggesting that ADH is active despite normal or hypertonic volume levels (would expect very dilute urine in low serum osmolality situations) CNS disorders. vaptan Syndrome of Inappropriate Anti-Diuresis (SIAD) 1.CHF. meds (chlorpropamide.water restriction (though horrible QoL).water restriction seizures (<150 mL/day). hypothalamus) or secretion of ADH (damage hypothalamus to posterior pituitary) trauma. ectopic ADH production. pulmonary disorders.6x body cause seizures. loop diuretic. or clofibrate Nephrogenic diabetes insipidus Congenital high urine output (20L/day). partial polyuria. and thyroid functions 3. loop overcorrection can diuretic (creates cause CPM isoosmotic medulla. posthypophysectomy. urine osmolality Treatment Complications Screening / Education acute . hypertonic saline. severe exercise. lungs. hypernatremia Acquired complete. carbamezepine) Imaging of head/lungs. neoplastic infiltration. normal urine osmolality. SIAD. thus water is not reabsorbed (water wasting) destruction of renal medulla (papillary necrosis) from sickle cell anemia. patients with SIAD have hyponatremia with very concentrated urine . ADH is released with hypovolemia (hi serum osmolality).$$) chronic (tumor). low serum osmolality. hi salt/ hi protein diet. urea.
myocardial ischemia. progressive renal failure elevated creatinine subepithelial dense deposits and thickened GBM 60% of pts will have persistent proteinuria (10-30% may have partial --> complete remission). but usually within a few days a/w premature birth.nephrotic penicillamine.SLE. poor motor development. s melanoma. Silver stain . Liver realizes that so much protein is being heroin. generalized edema (due to loss of oncotic pressure from loss of large blood proteins). H2O = decreased delivery of Na.Disease Edematous states Clinical Variants CHF Defining Characteristics edema Pathogenesis Na retention: Chronic CHF = decreased baroreceptor sensitivity & increased SNS/RAAS activity = increased PTC reabsorption of Na. cases from increased production accompanied by hep. primary infxn .hepB/C. infection 40% of adult lost and ramps up production of lipoproteins. penicillamine. vasoconstriction. glomerular syphilis. 40% develop progressive renal insufficiency or ESRD resistant to most treatments. thickened capillary loops. lung. severe cases require bilateral nephrectomies and subsequent lifelong dialysis death secondary to sepsis other complications hyper-coagulopathy. thickened GBM IF: granular subepithelial deposits for IgG along capillary loops ACEI + steroids (or immunosuppresants like cyclophosphamide if not response) . manifestation lymphoma.increased mesangial matrix. drugs . & ADH = Na & H2O retention = ascites = increased plasma volume and cardiac output Nephrotic syndrome (general) severe proteinuria (>3. HIV.o. syphilis. thromboembolism (loss of anticoagulant factors) Congenital Nephrotic Syndrome onset of nephrotic syndrome (massive proteinuria. melanoma) Renal bx: PAS . malaria. gold. glomerular spikes EM: subepithelial immune complex deposits. of adult Amyloidosis. stroke Membranous nephropathy vast majority are primary/ idiopathic onset ages 30-50 y. loss of proteins like Ig.5g / 24h urine). causes of schistomiasis.colon.cases) gold. RAAS. malaria. syndrome in captopril. hyperlipiduria Derangement in the glomerular capillary walls increased permeability to plasma proteins massive proteinuria and loss of albumin (so much that the liver can’t catch up) loss of albumin (oncotic pressure) causes leakiness of the vasculature edema 95% of cases in children related to systemic disease w/ primary glom renal manifestations dz (only 60% (DM. SLE. misc bee sting allergy) genetics most common in Finland Primary glomerular disease UA 24h urine protein albumin blood test. malignancies . infection. hypoalbuminemia) within the first 3 months of life.thickend GBM.osmotic ADH release = activation of V1 receptor (heart remodeling. hyperlipidemia (triggered by hypoalbuminemia). complement) thrombosis. and increased cardiac afterload) and V2 receptor (water retention in CCD. low serum albumin. drugs . lipid panel renal biopsy w/ immunofluorescence hepatorenal syndrome (cirrhosis = portal HTN = splanchnic vasodilation = stimulation of vasoconstriction in kidney = hepatorenal syndrome) renal failure infection (Staph. pneumococci. coronary constriction. skeletal deformities. increased preload) = worsening wall stress Etiologies Epi Risk factors Lab/Imaging Treatment Complications Screening / Education Cirrhosis ascites early cirrhosis results in hepatocyte damage and NO release = splanchnic arterial vasodilation and mechanical obstruction to portal flow = portal hypertension (portal press > 12mmHg) = activation of SNS (NE). Hg. systemic dz abnormal transport and decreased malignancy w/ renal catabolism leads to hyperlipidemia carcinoma. H2O retention = increased cardiac filling pressure water retention: chronic CHF = non. adults NSAIDs. 15% of cases are One of most result of systemic dz common (autoimmune . H2O to distal tubule = activation of aldosterone (failure to escape ald) = even more Na. large placenta.
+/. predominantly C3 deposition. mesangial interpositioning w/ formation of new GBM silver stain: tram-tracking none very effective few spont remissions slowly progressive but unremitting (50% develop chron renal failure in 10 y) . fever. periorbital edema. +/. poor prognosis in contrast to APSGN. +/. & hematuria 1-4 glomeruli and activation of classical pathway 10 y. but weeks after streptococcal also adults of complement infection of pharynx or skin (impetigo) also has in-situ formation of immune complexes from cross-rxn of anti-strep coca-cola colored urine antibodies w/ glomerular antigens RBC casts in urine. heroin use. thickened capillary loops. unilateral renal agenesis/ dysplasia. HTN little tendency for spontaneous remission primary /idiopathic secondary (HIVcollapsing variant of FSGS.edema. mild proteinuria. become severely oliguric. primary glomerulopathies. mild proteinuria. subendothelial immune deposits under EM. proteinuria w/ preserved kidney function Pathogenesis epithelial cell (podocyte) injury Etiologies Epi most common nephrotic syndrome in kids Risk factors Lab/Imaging Creatinine: nl (nl GFR) LM: nl glomerulus IF: none EM: diffuse foot process effacement (fusion) Treatment Complications Screening / Education steroids (90% resolution) <5% develop chronic renal failure Focal Segmental Glomerulosclerosis (FSGS) important to distinguish from minimal change dz!!! Sclerosis involving segments of some. mild-mod HTN similar to EASS serology: elevated anti-streptolysin >95% of kids recover w/ conservative tx (selfO (ASO) titers.S. SCC. oliguria. microscopic. diabetic nephropathy. oliguria). focal/ segmental scarring of glomerulus (proteinaceous collection of hyaline in the sclerotic segment @ higher power) IF: none EM: diffuse foot process effacement + focal/segmental sclerosis of glomerulus 50% have renal failure in 10y 20% rapidly progress to ESRD in 2y recurrence in 2550% of transplants Nephritic presentation (general) hematuria (gross. HTN. obesity) renal bx: scarred interstitium poor response to steroids (thyroidization). +/. RBC casts in tubules.o. but not all. and develop rapidly progressive GN Acute poststreptococcal GN (postinfectious GN) Membranoproliferative GN Type I (MPGN1) variable presentation (hematuria.cryoglobulins limiting dz) histology: diffuse (>50%) proliferation of glomeruli. C3 <1% of kids do not improve. mesangial immune deposits IF: starry sky for IgG. acute renal failure (azotemia increased BUN. pink dense obsolete & scarred glomeruli. endocapillary proliferation EM: sparsely distributed subepithelial humps. hypercellularity (PMNs). can have RBCs/ hematuria on UA (in addition to typical nephrotic syndrome sx).Disease Clinical Variants Minimal change disease Defining Characteristics normal biopsy findings EXCEPT diffuse foot process effacement insidious onset in o/w healthy kids.proteinuria. glomeruli (hence focal/segmental) Abnl creatinine (abnl renal function). HTN. characterized by diffuse proliferative GN but looks like APSGN under LM. usually secondary to acute GN very similar to expt acute serum sickness! strains of group A B. hypocomplementemia. variable endocapillary prolif IF: granular pattern of C3 deposition EM: subENDOthelial immune deposits. mesangial interpositioning and tram-tracking by silver stain kids > adults histology: diffuse proliferative GN w/ lobular appearance.decreasing hemolytic freq in U. renal transplant. reflux nephropathy. mixed nephroticnephritic) MPGN is predominantly hematuric but an be nephrotic/nephritic.RBC casts in UA). Children 6of circulating immune complexes in nausea. mesangial proliferation. one-shot antigenemia results in deposition streptococci Abrupt onset of malaise.
renal involvement.hypo-complementemia histology: endocap proliferation. inc mesangial matrix & GBM thickening Diabetic nephropathy: affects glomeruli. CVA. hyperfiltration (inc GFR). foot process effacement time course: thick GBM --> diffuse mesang sclerosis --> nodular glomerulo-sclerosis (KimmelstielWilson nodules) atherosclerosis (AAA.) anti-dsDNA . karyorrhexis. wire loops. fibrinoid necrosis (pink fibrin material). retinopathy. peripheral neuropathy.GBM dz: limited to kidneys. etc. glom and decreased intracellular antioxidant hyalinosis lesions. interstitial radical damage fibrosis. vessels. amputation. inadeq pancreas compensatory response Early events: microalbuminuria. increasing susceptibility to free microaneurysms. dec GFR. MI. renal bx: inc mesangial matrix. thus.sx + active sed UA + proteinuria. elev creat & serologies.Disease Clinical Variants Membranoproliferative GN Type II (MPGN2) Defining Characteristics looks similar to Type I under LM dense deposit disease linearized bands of C3 deposits a/w partial lipodystrophy hypocomplementemia for C3 only!! Pathogenesis abnormalities suggest activation of alternative complement pathway: decreased serum C3 but normal C1. hypercellularity. fatigue. persistent C3 degradation and hypocomplementemia Etiologies Epi Risk factors Lab/Imaging LM: diffuse proliferative GN w/ lobular appearance (just like type I) linearized bands within the GBM IF: linearized C3 dense deposits along peripheral capillary loops. Hyperglycemia disturbs the polyol pathway. weight loss. fever. C3 convertase normally stabilized by properdin & C3NeF = C3 nephritic factor (70% of patients w/ MPGN2) to keep alternative pathway active C3NeF = autoantibody that binds to C3 convertase. C4. Hyperglycemia activates PKC. IF & EM (mesang deposits . slit-like lumen.ARDs + formation of cellular crescents RPGN) similar to expt anti-GBM dz Goodpasture's dz: anti-NC1 domain Abs cross react w/ pulmonary BMs. causing rupture and pulmonary hemorrhage IF: linear IgG appearance along glomerular capillary loops histology: cellular crescents (parietal epithelial cell proliferation) Systemic diseases w/ renal manifestations Diabetes mellitus diabetic nephropathy Type I (10%) .IgG) Class IV: >50% of glomeruli have histologic activity. infection. anti-dsDNA. HTN. pseudothrombi (pink globs) Class II: LM (meangial expansion. causing the metabolism of sorbitol diffuse/nodular GS. uniform thickened cap loops . thick GBM. increased GFR year 5: GFR drops and plateaus year 15-25: steady decline in GFR (leading to massive proteinuria) Systemic lupus erythematous lupus nephritis general: unpredictable lupus flares (hematologic sx. High level of glucose causes nonenzymatic glycosylation of proteins. diminished levels of factor B and properdin (components of alternative complement pathway) C3 convertase cleaves C3 to C3bBb.8 million children and adults in the U. creating advanced glycosylation end-products that can result in tissue damage 2. glom capillary reserves. tubular atrophy. arthritis. V (membranous LN) breakdown of central and peripheral selftolerance --> autoimmunity resulting in a wide range of autoantibodies renal involvement 30-90% of SLE patients serologies: ANA. some mesangial deposits Treatment Complications Screening / Education Crescentic GN (Anti-GBM. skin rash. glomerular hyalinosis. antiSm. hyaline ateriolo-sclerosis. nephropathy leading cause of kidney failure papillary necrosis (acute pyelonephritis seen more in DM but also PN w/ obst and NSAID abuse) year 2: kidney enlarges. kidney enlargement.S. Goodpasture's dz) Anti. inducing activation of pro-angiogenic molecules like VEGF 3. subend dep Class V: granular IF of glom cap loops. accelerated atherosclerosis 25.suggests kidney involvement Class II (mesangio-proliferativebenign presentation). hyaline arteriolo-sclerosis of afferent & efferent glomerular arterioles. in-situ antibody formation to fixed antigen in rapidly progressive GN (RPGN) non-collagenous domain of Collagen type IV in GBM w/ nephritic presentation and ARF ruptured GBM from antibodies attacking antiNC1 domain causes destruction of collagen Goodpasture's: involves type IV and release of fibrin. stimulating the kidneys & lungs (pulmonaryproliferation of parietal epithelial cells and renal syndrome . stroke. cellular crescents. subepit dep w/ spike form. glomerular microaneurysms.deficiency of insulin secretion Type II (80-90%) . IV (diffuse LN. stabilizing the convertase and protecting it from enzymatic degradation. PVD). & tubointerstitium 1. hypocomp). thickened tubular BM (tubulointerstitial scarring) IF: none EM: greatly expanded mesangium.peripheral insulin resistance.
femur. acute necrotizing GN (segmental fibrinoid necrosis of glomerulus w/ +/formation of cellular crescents) Treatment Complications Screening / Education Wegener's Classic triad (acute necrotizing granulomatosis granulomas of ENT. scapula unbound light chains become filtered in the urine as BenceJones proteinuria bone pain/ fractures due to osteoclastic lesions. mucus membranes. capillaries) autoantibodies against myeloperoxidase Pauci-immune mechanism: presumed immune mech but no IF or EM evidence of immune complex deposition in organs Etiologies precipitating immune reaction (PCN. HSP nephritis (IgA nephropathy. clavicle. bx: atypical plasma cells in bone marrow (lots of neoplastic Ig and light chains in cytoplasm. microbes. tumor antigens) Epi Risk factors Lab/Imaging histology: leukocytoclastic vasculitis (fibrinoid necrosis. arthalgia. lungs hemoptysis. fibrinoid arteriolitis). anemia/ thrombocytopenia. hematuria + proteinuria) children & young adults cutaneous bx: fibrinoid necrosis of blood vessel (fibrinoid arteriolitis) + perivascular cuffing of inflamm cells IF: IgA within dermal capillaries kidney bx: mesangial prolif. transmural arteritis. muscle clinical features depend on involved organ system: hemoptysis.Russell bodies) XR: buckshot lesions of the calvarium M-protein (neoplastic Ig) + BenceJones protein (kappa chain) in serum/urine (respectively) protein electrophoresis histo: light chain cast nephropathy w/ eosiniphilic casts (light pink blobs) & ATN generally poor prognosis . mesangial dense deposits.o. heterologous proteins. cavitary lesions autoantibodies directed against proteinase-3 affecting both small and medium sized vessels M>F avg age 40. muscle pain/ weakness kidneys: leukocytoclastic vasculitis and acute necrotizing (and often crescentic) GN Pathogenesis systemic necrotizing vasculitis of small vessels (arterioles.skin. nerves. hemorrhage. acute abd pain (+/HSP nephritis bloody diarrhea). kidneys. forms cytoplasmic inclusions .Strep. pelvis. necrotizing vasculitis of small & med vessels. abd pain. IF: deposition of IgA in mesangium Plasma cell myeloma (multiple myeloma) light chain cast nephropathy multifocal destructive bone tumors composed of plasma cells --> osteoplastic breakdown manifested most often in vertebral column (lower back). peak incid in 50y. eventually occluding and damaging the renal tubules 50-60 y. brain. skull. acute necrotizing/crescentic GN) C-ANCA mimics TB -necrotizing granulomas. heart. hematuria/ proteinuria. inc infection susceptibility proliferation of a single B-cell clone that synthesizes and secretes a single homogenous immunoglobulin or its fragments (plasma cell dyscrasia) proliferation and survival of myeloma cells dependent on IL-6 (hi IL-6 levels a/w poor prognosis & chromosomal abberations) neoplastic plasma cells make excess fragments of light or heavy chains along with the complete Ig excess light chains cross glomerular filtration barrier. lungs.arthritis. causes leukocytoclastic vasculitis and activation of alternative complement pathway Purpura (HSP) .'s histology: transmural arteritis + granulomatous vasculitis Henochdeposition of polymeric IgA1 within arterioles unknown palpable cutaneous purpura Schonlein (usually on lower half of body). GI. venules.Disease Clinical Variants Microscopic polyangitis Defining Characteristics P-ANCA vasculitis palpable purpura . ribs.o. hypercalcemia.
Berger's proteinuria. dense deposits in complexes. endothelial cell swelling. attenuated GBM no effective tx 50% ultimately die from ESRD (although dz is decades in length) redistribution . Do not mix Ca IV w/ avocados. hamburger. (causes precipitation potatoes. weakness (diminished reflexes. increased intake (usually only if abnl kidneys) crush injuries EKG . but target Ag = NC1 of collagen type IV Animal model: Anti-GBM antibodies are preformed in animals.SCD). and injected into other animals.complexes GBM disease) Anti-GBM dz does occur in humans. allowing formation of MACs and subsequent direct injury (lytic pores). mesangiopathic dz disease) usually manifests as slow insidious progression towards ESRD Hyperkalemia EKG abnormalities (can be life threatening . the classical pathway mesangium. the concentration drops precipitously as Ag becomes bound to circulating Ab. stabilize cardiac membrane (esp if serious EKG changes) . strength). DKA.decreased effective volume (less urine output so less excretion of K+). GN frequency drops Etiologies Epi Risk factors Lab/Imaging biopsy: diffuse proliferative GN (>50% of glomeruli have lesions). due to rhabdomyolysis.K+ moves from inside --> outside of cells. hyperosmolar hyperglycemic state (HHS). remove K+ by giving kayexalate/sorbitol (bind K+. activating complement and causing GN EM: NO dense deposits (Immune complexes planted in each ind anionic site.give calcium (Ca gluconate by periph IV) 2. primary/ secondary hypoaldosteronism. bactrim). non-org metab acidosis. unable to aggregate) IF: linear IF for IgG along capillary loops IgA asymptomatic & persistent Nephropathy hematuria (gross or micro). short duration Pathogenesis After injection of antigen. calcium. resulting loss of glycosylation pattern --> underglycosylation --> aggregation into polymeric IgA1 --> uptake by MPS and activation of mesangial cell proliferation/expansion most common GN in developing world (Western Pacific rim) bx: proliferation of mesangial cells (>3 cells in mesangial matrix) IF: IgA deposition in mesangium EM: mesangial immune deposits. tumor lysis. of CaCO3) bananas. tomato NaHCO3 solutions paste. OJ. resp acidosis. due to hi WBCs. or hemolysis) transtubular K+ gradient (nl 6-12. meds (ACE. tubular mineralicorticoid resistance. forming immune complexes. specifically. insulin deficiency. subepithelial deposits w/ regular periodicity and spike formation (chronic antigenemia) IF: granular IgG and C3 deposits along capillary loops with relative periodicity Masugi in situ formation of immune Nephritis (Anti. lipoproteins. heavy mononuclear infiltrate. causing diarrhea) or hemodialysis Ca IV is avoid potassium contraindicated if pt in diet for 6 on digoxin!! months (artichokes. necrosis. K+ sparing diuretics. NSAIDs. more immune complexes = more GN. oliguria (low urine output).peaked T waves. etc) . activation/ recruitment of neutrophils & used as model for postmonocytes --> inflammation streptococcal GN in humans Heymann nephritis (idiopathic membranous nephropathy in humans) In situ formation of immune complexes expt model for idiopathic membranous nephropathy in humans. prolonged QRS duration. target heparan sulfate. if hyperkalemic and TTKG is hi suggests extra-renal etiology) 1. platelets. milk. cell death. target antigen = PLA2 antibodies then shed and aggregate on the receptor EBM. +/(IgAN. redistribute K+ by giving insulin (causes K+ to go back into cells) or B2 agonists 3. endothelial wall is activated. acute kidney injury. solvent drag (impt for hyperkal in DKA. and certain drugs bx: foot process effacement. condensing into subepithelial deposits and causing foot process effacement circulating Abs bind in situ target antigen = megalin (rats)= scavenger receptor on podocytes & PT brush border that mediates endocytosis of protein. stripping the GBM of its anionic charge --> formation of immune complexes within GBM. HHS) reduced excretion .Disease Clinical Variants Defining Characteristics single injection of Ag (acute antigenemia) stereotypical course self-limited. as free Ag is cleared. steak. extracted. R/O pseudohyperkalemia (hyperkalemia but no EKG changes. subepithelial humps IF: IgG mesangial deposits + starry sky pattern Treatment Complications Screening / Education Glomeruloneph Experimental ritis acute serum sickness (similar to human poststreptococcal GN) deposition of circulating plasma soluble immune complexes in the C3 complement also activated by immune glomeruli. respiratory failure from diaphragm paralysis alteration in IgA type I. flattened P waves.
B2 agonists.K Citrate if renal stone prevention diuretics. hypertension <6 pyramids (nl 10). resp impairment (if severe) pseudohypokalemia (large # abnl leukocytes) non-renal K+ loss .insulin. flat/low set ears). characteristic facial features (beak nose. profuse sweating renal K+ loss . Gitelmans.diarrhea. kidney weight < 50% of expected weight for age very rare Renal atrophy diminutive kidney less likely to be hypoplasia more likely to be caused by renal artery atherosclerosis. 3:1 M:F bilateral in utero demise or death shortly after birth due to renal or pulmonary insufficiency (Potter syndrome) associated 2ndary anomalies of Potter syndrome: absent fetal urine --> reduced amniotic fluid production (oligohydramnios).diuretics. vomiting. decreased intake . moderate dec GFR (30-59) 4. constipation.starvation palpitations. limb deformities. then measure BP. redistribution . hi BP .variable degree of renal insufficiency. kidney damage w/ nl or inc GFR (>90) 2. think about diuretics. amnion nodosum sporadic inheritance 1/4000 births. vomiting) If must give IV. especially in adults . Bartter syndrome. mineralicorticoid excess. pulmonary hypoplasia.KP if phosphorus alkalosis. 2:1 M:F Renal hypoplasia unilateral . Kidney failure (GFR<15) Chronic Kidney Disease (CKD) Renal agenesis unilateral normal function but late complications of glomerulosclerosis failure to form ureteric bud or induce differentiation of metanephrogenic blastema minority of cases due to involution of dysplastic kidneys sporadic inheritance 1/1000 births. Gitelman's syndrome.loop/ thiazide . Liddle's syndrome) if normal BP. you need to have less than 60 mmol K in 1L IV fluid given at a rate of 10 mmol/h Diabetes. DKA. severe dec GFR (15-29) 5. vol depletion Check acid-base status (acidosis renal tubular acidosis.Disease Hypokalemia Clinical Variants Defining Characteristics Pathogenesis Etiologies If HTN. skin folds under eyes. renal dysfxn for mild cases. low/nl BP . HTN CVD = leading cause of death decreased life expectancy Staging: 1. Liddle syndrome.depletion . oral management preferred over IV . fatigue.KCl if from diuretics.no problems bilateral . muscle cramps. hyper-aldosteronism. think about conditions w/ inc aldosterone secretion (renal artery stenosis. mild dec GFR (60-89) + kidney damage 3.KHCO3 if acidosis mineralicorticoid excess. vomiting Epi Risk factors Lab/Imaging EKG shows U waves after T waves TTKG > 4 suggests renal loss Treatment Complications Screening / Education weakness. Bartter syndrome. severe burns. meds) (if .
severe serum acidosis (HCO3. Lowe's. AngII moderate renal failure (GFR 20.resistance prevents the secretion of K+ inhibitors. toluene) UAG > 0 (not much NH4+) easy to correct w/ low doses of HCO3- Type 2 (PT) normal anion gap acidosis. impaired NH4+ and phosphate excretion Type 4 Childhood hereditary dz (cystinosis. hyperkalemia ammonia --> maximally acidic urine] Problems in proximal tubule prevent reabsorption of HCO3. problems with distal tubule prevents H+ secretion so unable to maximally acidify (because does not have ammonia for the H+ to attach and be excreted in urine) the urine for excretion of acid --> acidosis Hereditary (auto recessive mutation in Cl/HCO3exchanger).to correct!! UAG > 0 (not much NH4+) fix hyperkalemia . renal transplant rejection (very rare). serum bicarb 14-20. moderate renal failure (GFR 2050). thyroiditis. nephrocalcinosis. autopsy slight risk of infections. PBC. variable urine pH (diet dep). which is broken down into CO2 & H2O by CA.Disease Renal ectopia Clinical Variants Defining Characteristics kidney in abnl anatomic location (NOT T11-L1) simple . RA. SLE. impaired NH4+ and phosphate excretion urine is not maximally acidic (pH > 5. indirectly causing charge aldosterone phosphate excretion exchange during which causes H+ to enter antagonists) the cells [low aldosterone prevents K+ maximally acidic urine (pH < secretion. GSD. Wilson's. moderate renal failure (GFR 2050).3). drugs . mild acidosis (HCO3production. interstitial nephritis (rare). so H+ in urine is not bound to >15). hypoaldosteronism.usually fixes the acidosis (if not.3).amphotericin B. generally normal fxn (even used for transplantation) fused lower (95%) or upper (5%) poles. subdiaphragmatic. or aldosterone drugs (ACEI. multiple myeloma normal anion gap acidosis. surgery. autoimmune Sjogren's. normal/low carbonic anhydrase K+ inhibitors (acetozolamide. hi K+ blocks ammonium 5. interstitial nephritis (lead/lithium/ analgesic abuse. tyrosinemia. topiramate). galactosemia). impaired NH4+ and (hyperkalemia). 50). hypokalemia distal tubule nl secretes H+ for the formation of carbonic acid. amyloidosis.and the formation of ammonia from glutamine --> acidosis UAG > 0 (not much NH4+) requires high doses of HCO3. minimal HCO3.<10). thoracic crossed .pelvic. low renin. and renal pelvis tumors increased risk of Wilms tumor (isthmus) Renal tubular acidosis Type I (DT) normal anion gap acidosis. kidney stones.with or without fusion a/w other GU malformations Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications increased risk of UTI from stasis increased risk of injury Screening / Education sporadic (very rarely 1/900 familial) Horseshoe kidney incidental finding most of time.needed) . fusion during development prevents rotation so renal pelvis faces anteriorly unable to migrate out of pelvic cavity because inferior mesenteric artery blocks them sporadic 1/400-600 incidental finding during imaging.
pathologic mineralocorticoid excess. Cushing's syndrome. hereditary metabolic defects (mitochondrial myopathies) decreased L-lactate destruction liver disease. insuff Cl. low renin: primary aldosteronism. incidence increased w/ age Metabolic alkalosis spot urine to determine if chloride sensitive or chloride resistant [Ucl > 20 mEq/L implies chloride resistant met alk] hi FP rate for Ucl > 20 so check Uk (if < 30. increased glucagon --> leading to the formation of acetoacetate and B-hydroxybutyrate Decreased carb intake causes decreased insulin. respiratory comp (post Na+ deliverychronic hypercapnia). pseudo-hyperald) Maintenance: low EABV (chloride deficiency activates RAAS preventing base secretion & increasing HCO3 reabs secondary to Na+. Liddle syndrome) common. MC excess hypercapnic state. malignant HTN. if multiple mass . renal failure. severe hypokalemia chloride resistant metabolic alkalosis (hi renin: renal artery stenosis. mineralocorticoid excess. anion drag) or maintenance (prevention of bicarb excretion) chloride sensitive metabolic alkalosis from bicarb load/drag (calcium alkali syndrome) or Generation: vomiting. cancer. shivering. decreased EABV increased distal Na+ delivery in volume (vomiting. sepsis. well circumscribed lesions histology: finger like projections (fibrovascular projections) histology: angioma + myoma + lipoma < 4cm size: follow w/ CT scan or surgery if growing rapidly > 4cm size: surgical removal to prevent complications majority are asymptomatic but if large. ethanol results in increased lipolysis and free fatty acids Generation (bicarb addition or acid loss.75%. hypoglycemia. alkali consumption/ diuretics. exercise. cycle --> leads to decreased tissue increased metabolic oxygenation rate (sepsis. ETOH.Disease Clinical Variants Defining Characteristics high anion gap acidosis Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Screening / Education Lactic acidosis Type A LA increased L-lactate production from no Krebs altered redox states. replete K+ and rpt Ucl) and HTN (if no HTN. and fat <1% of renal tumors usually in adults Oncocytoma usually unilateral. thiamine def).to exchange w/ HCO3 in distal nephron). AKA >90%) Type B LA high anion gap acidosis Ketoacidosis Diabetic KA high anion gap acidosis Alcoholic KA high anion gap acidosis pancreatic beta cell destruction causes decreased insulin. decreased O2 delivery (shock.o usually M:F 2:1 pathology: well described lesion w/ brown central stellate scar histology: numerous cells w/ abundant cytoplasm (low NC ratio) and no nuclear pleomorphism . salycilate OD urine nitroprusside test detects acetone and acetoacetate serum ketone test detects Bhydroxybutyrate (DKA . hypercalcemia) syndromes (Bartters. seizures. decreased gluconeogenesis causes increased glucagon. CO toxicity). metformin. postadmin.think syndromes uniform population of pink cells loose fibrous stroma mixed w/I tumor cells 4-7% of adult renal epithelial tumors age > 50 y. might need surgical removal if compressing adjacent structures spont retroperitoneal hemorrhage (pts present w/ severe back pain) Angiomyolipoma usually one large mass. smooth muscle.suggests tuberous sclerosis!! Can present w/ pain or hematuria benign neoplasm composed of thick walled blood vessels. NG suction. nonreabsorb anions). increased depleted states (loop/ thiazide diuretics. recheck Ucl) chloride supplementation reverses the alkalosis (if chloride sensitive) Benign renal neoplasms Papillary (cortical) adenoma a/w long term hemodialysis and papillary RCC pathology: small (<5 mm diameter). but if multifocal or bilateral .
. lymph nodes. or loss of Y chromosome!! Tumors arise from proximal OR distal convoluted tubules hereditary papillary carcinoma (VERY rare) 10-20% of adults RCCs males 3:1 Urothelilal arises from renal pelvis (collecting system hematuria carcinoma urothelium) (transitional 40-50% of cases have cocell carcinoma) existing bladder urothelial tumors most common tumor of renal collecting system and ureter adults (7% of smoking primary renal cancers) phenacetin nephropathy 70% males thorotrast mean age 70 radiologic dye cyclophosph amide horseshoe kidney histology: large tumor w/ papillary structures (finger like vasculature. radical nephrectomy. dz (dialysis).o. males abdominal mass. atypical mitotic figures. and spindle cell differentiation path: hemorrhagic (sometimes necrotic) appearance poor prognosis if not staging (based detected early! on tumor size!!): T1 = good Can cause tumor prognosis. skin) Fuhrman nuclear grading system (Grade IV . benign autosomal dominant w/ close to 100% uterine fibroids. erythro/ thrombocytosis 30K new US smoking. elevated LFTs (Stauffer's syndrome). pancreatic cysts. obesity in women.sporadic . cadmium. cryotherapy (if not surgery candidate). clear cell RCC autosomal dominant mutation in VHL gene (3p25). Rising incidence usually > 50 y. Path: necrosis + hemorrhage 12K US meds deaths/ yr (diuretics).Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment hereditary? CT imaging to monitor dz progression. renal cysts. tuberous sclerosis pathology: very fatty (yellow) appearing lesion histology: clear tumor (intracytoplasmic lipids & glycogen). papillary) 1% are bilateral (majority are unilateral!) paraneoplastic syndromes hypercalcemia. hematuria.000 cases. very round nuclei. M=F 85% are renal cell carcinomas (clear cell. benign skin leiomyomata. heart. lead).prognostic combined w/ staging (see above) Papillary renal cell carcinoma associated with trisomy 7. endolymphatic sac tumors. epididymal tumors. CNS hemangioblastomas. screen family members Complications Screening / Education Malignant renal (general) neoplasms "classic triad" (<10% of patients) . fibrovascular cords). adrenals. often found incidentally w/ imaging! cases / yr HTN. brain. highly vascularized (chicken wire vasculature) high grade tumors will actually appear darker from increased nuclei.o.multiple lesions. aggressive type penetrance for SOME manifestation of 2 papillary RCC syndrome 10-16% risk RCC .S. flank pain hereditary . presence of fibrovascular cords Inherited disorders of RCC von Hippel Lindau (VHL) syndrome increased risk of clear cell RCC retinal angiomas. obesity. calcium deposits. poor surgical candidates) metastases (LUNGS. earlier onset in life. variable expression & reduced penetrance mutations promote transcription of vascular growth factors --> unusual vascular tumors 20% de novo mutations (neg FH does not R/O VHL!!) Hereditary papillary renal cell cancer Hereditary leiomyomatosis RCC increased risk of papillary type 1 RCC increased risk for papillary type 2 FH gene codes for fumerase hydratase RCC enzyme. onset 60-70 y. hereditary RCC w/o VHL. bone.bad!!) . spleen. M>F smoking. IVC. occupat exp M>F (asbestos.single lesion. contralateral kidney. acquired usually > 50 renal cystic y. 13500 deaths in U. intestine. unilateral lesions. liver. trisomy 17. anemia. nephron sparing surgery. HTN. pheochromocytomas. petroleum. bilateral lesions. infiltration of macrophages / histiocytes histology: papillary tumor arising from nephroureterectomy urothelial lining (NOT renal tubules). T4 = thrombus if enters bad prognosis renal vein.o. genetics (VHL) 65. RA Conventional (clear cell) RCC most common type of renal cancer (70%) majority are unilateral genetic mutation or deletion in 3p25 locus of von Hippel Lindau gene (VHL gene) --> tumors that arise from proximal convoluted tubules partial nephrectomy (nephron sparing surgery) radical nephrectomy cryoablation (small tumor. VHL disease (develop RCC in 50% of cases). pale cytoplasm.
removal/treatment of obstruction . epithelium. Beckwith-Wiedemann syndrome (exophthalmos.coli. older men .Disease Clinical Variants Defining Characteristics Pathogenesis autosomal dominant mutation in BHD gene (17p11.benign prostatic hyperplasia adenovirus. spontaneous pneumothorax Familial Renal Oncocytoma Lynch Syndrome Wilms' tumor (nephroblastom a) increased risk for oncocytoma increased risk for CRC & endometrial/ovarian cancer. hemihypertrophy) most common kidney tumor of childhood 1/8K-10K no gender preference histology: triphasic (blastema. causing chlamydia. GU anomalies. RCC. radiation. very multinucleated. Denys-Drash syndrome (gonadal dysgenesis male pseudohermaphroditism. a/w poor prognosis lung metastases (cough) or traumatic rupture Tuberous sclerosis autosomal dominant neurocutanous disorder a/w harmatomas. infiltration of histiocytes/PMNs broad spectrum Abs. gigantism. mental retardation. leading candida or abd pain + dysuria (pain/ to obstruction and urinary retention cryptococcus in burning during urination) immunocomp. transitional cell pathology pediatric . glomerulosclerosis.2). inflammation of urothelium leads to compression of urethra. lung (LAM) if see angiomyoplipomas on kidneys . colon cancer.esp if no access to HC (developing world) pyelonephritis!!! Acute cystitis triad: urinary frequency + lower younger women (pregnant) .think tuberous sclerosis! increased risk for RCC (clear cell or others) a/w ADPKD Bladder exstrophy exposed bladder --> increased risk of infections & ulceration developmental defect in lower abdominal wall and anterior wall of bladder from the failure of the cloacal membrane to properly glandular or squamous differentiate --> exposure of bladder to metaplasia --> adenocarcinoma body surface (opened sac) or squamous cell carcinoma bladder is on outside of patient (no skin covering bladder mesenchymal defect) infection ulceration adeno-carcinoma squamous cell carcinoma death . macroglossia. heart (rhabdomyomas). stroma). compresses distal aspect of bladder.90% < age 6 presents as large abdominal mass a/w syndromes: WAGR syndrome (Wilms' tumor. Wilms tumor). + mitotic figures nephrectomy and/or chemotherapy very aggressive. trauma older men younger women of reproductive age immunosupp histology: thickened urothelium. urinary retention and infection mycoplasma non-infectious: chemo. renal cysts. Aniridia. cutaneous angiofibromas. mental Retardation).head of fetus Infectious: E. pulmonary cysts. infantile/ childhood from mutations in TSC1 and TSC2 genes seizures. disrupting BHD protein which makes folliculin penetrance of cancer is lower than some of the other syndrome manifestations not a/w certain pathological type of RCC Etiologies Epi Risk factors Lab/Imaging Treatment Complications Screening / Education Birt-Hogg-Dube variable risk for oncocytoma fibrofolliculomas.
bladder ulcers. urethra. renal pelvis. etc. leading to degeneration and inflammation early changes . the cells become more discohesive and can end up in urine Urothelial papilloma benign uncommon lesion seen discrete papillary growth w/ central fibrovascular core lined by urothelium of in younger patients normal thickness and cytology small size (3.enlarged arylamines urothelium (dyes) Schistosoma hematobium 4th most (70% cases common are SCC) cause of Phenacetin cancer death use in males long term cyclophosph M>F amide use histology: cells at least 5x size of stromal lymphocytes. or lined by squamous epithelium instead of urothelium schistosoma infection (globally) histology: hemorrhage of bladder may require cystectomy if death secondary to bleeding will not stop! severe hemorrhage Polypoid cystitis Malakoplakia immunocomp. CMV. bacteria common incidental finding. enlarged/ hyperchromatic nuclei. pagetoid cells (malignant cells interspersed w/ benign cells) urine cytology . squamous metaplasia leads to squamous cell carcinoma Etiologies Schistosoma hematobium common in Egypt (water borne parasite. discohesion (shedding). lesions fistulous tracts benign lesions occuring most defects in phagocytic or degradative E. coli commonly in bladder but also functions of histiocytes in response to GN Proteus ureters. renal failure squamous cell carcinoma Screening / Education Hemorrhagic cystitis irritative voiding symptoms. chronic (preneoplastic atypia . histiocytes.fibrosis w/ lymphocytes. metastasis staging: pTa & pTis = noninvasive (>95% 5y survival). squamous metaplasia w/ Schisto oval cystoscopy Treatment Complications hydroureter. invasion radiation (>90%) most common urinary tract cancer smoking histology: dysplasia . bacterial infections. adenovirus benign course once injury source chronically inflamed bladder w/ grossly noted bladder removed polypoid lesions w/ edema or papillary catheterization. obstruction.transformation to abnl cystitis (SCC). hydronephrosis. urothelial carcinomas are the most common bladder cancers lesions OR noninvasive papillary lesions) --> cyclophosphamide.necrosis. mostly benign reactive phenomenon that implies infection of chronic cystitis the bladder & presence of glandular bladder exstrophy structures ureteral reimplantation neurogenic bladder bladder trigone in females becomes glycogenated. appearing nucleus) --> carcinoma (CIS flat chemical exposure.look like eyeballs!) histology: glandular (intestinal) metaplasia remove source of injury remote risk of adenocarcinoma Squamous metaplasia of bladder Nonoccurs commonly in females. radiation HSV. prominence of vessels. lodges in pelvic veins around bladder) Epi Africa & Middle East Risk factors Lab/Imaging histology: pink cytoplasm & granules represent eosinophils.not a/w SCC Keratinizing long-standing cases may be associated with squamous cell carcinoma histology: hyperkeratosis Bladder cancer (general) long standing in dwelling catheters (US) Normal urothelium --> dysplasia painless hematuria smoking. foreign body granulomas. women Cystitis cystica et glandularis histology: can see polyps + edematous area from subepithelial fluid accumulation (polypoid) histology: large histiocytes & small extracytoplasmic calculospherules (Michaelis-Gutmann bodies . gross destruction of overlying vessels in bladder --> cyclohematuria (Med emergency!!) excessive bleeding phosphamide. T1T4 based on depth of tumor invasion Urothelial carcinoma in situ (CIS) malignant noninvasive flat cancer hematuria presence of cytotologically malignant cells regardless of quantity as grade increases.can sometimes show CIS if discohesive visible on cytoscopy (but need histo to tell if malignant or benign lesion) histology: finger like projections w/ presence of umbrella cells and abundant cytoplasm (low N/C ratio) bleeding. eosinophils w/ mucosal ulceration later changes .Disease Schistosomiasi s Clinical Variants Defining Characteristics world's leading cause of hematuria and bladder cancer Pathogenesis ova are deposited in veins of muscularis propria.0 mm) . dystrophic calcification. keratinizing particularly at bladder trigone (glycogenated) benign . high N/C ratio (CIS cells have very little cytoplasm).
require alkaline pH Uric acid stones . few mitotic figures Treatment Complications Screening / Education High grade papillary urothelial carcinoma histology: scattered single cells (discohesion). sarcoidosis. infection. decreased renal function (reversibility related inversely to amount of time obstructed). uretero-vesical junction (most common). hyperuricosuria) immobilized. hyper-PTH. discohesive single cells Pathogenesis Etiologies Epi Risk factors Lab/Imaging histology: finger like projections w/ cohesive epithelial cell lining. apoptotic bodies. postobst diuresis. they can aggregate to form stones genetic predisposition. numerous mitotic figures.cystectomy or cystoprostectomy Squamous cell malignant carcinoma Adenocarcinoma malignant can sometimes arise from urachus (dome of the bladder. muscularis propria infiltration of thick muscle bundles. HTN.most common. RTA. favoring formation of uric acid stones .better prognosis. 75% of bladder tumors in Egypt. hyperoxaluria. increased vasculature look for invasion for grading purposes (lamina propria . necrosis (pink). less pain than unilateral obstruction occasionally. acute symptoms hydronephrosis renal distention increases susceptibility to trauma bilateral UPJ Nephrolithiasis calcium oxalate . seen in people w/ recurrent infxns. short bowel syndrome removal of stone. electrolyte abnl acute . ureteral orifice acute obstruction = pain. can occur @ any pH Struvite (MAP) stones . infection.produces mucin umbilicus) or other parts of bladder wall malignant glands + mucin Small cell carcinoma Renal obstruction Unilateral histology: high N/C ratio but small cells. increased fluid intake ureteral stones usually at UPJ. metabolic states (hypercalciuria. few mitotic figures malignant usually invasive overall disorderly arrangement w/ irregular clusters of cells & fused papillae. favoring formation of IBS patients at risk for calcium calcium oxalate stones oxalate AND uric acid stones IBS + uric acid stones . crossing of iliacs. excretion of phosphate and K+ impaired urine concentrating ability followed by marked diuresis & natriuresis after release chronic obstruction that occasionally causes acute symptoms abnormal muscle developmenet. increased # mitotic figures. dehydration. minimal atypia (scattered enlarged hyperchromatic nuclei). weight gain. impairing urine concentrating ability and response to ADH. Schisto infection. nuclear polymorphism. fibrovascular core w/ blood vessels.genetic abnl IBS + calcium oxalate stones . marked atypia (similar to CIS).T1. hypocitraturia.rare.disrupted bowel mucosa so unable to absorb bile salts = excess bile salts in bowel lumen = bile salts bind calcium = loss of calcium increases oxalate absorption.silent fluid overload.require acidic pH (only stones to be treated by pH adjustment) Cysteine stones . dehydration urinary stasis. hyperchromatic (Dark appearing). numerus thick walled blood vessels poor prognosis) dedifferentiation background of keratinizing squamous metaplasia long term catheterization Schistosoma hematobium bladder exstrophy smoking 5% of bladder tumors in US.RTA patients.Disease Clinical Variants Low grade papillary urothelial carcinoma Defining Characteristics malignant non-invasive usually orderly arrangement w/ minimal variation in polarity. Sudan smoking. chronic catheter placement does tumor invade muscularis propria? NO local chemotherapeutic agents. chronic obstruction = loss of kidney function may spontaneously resolve in infants urinary stasis.painful renal colic + CVA tenderness chronic . connected from ligament of gland forming . crossing vessel that kinks ureter crystals form in the urine when certain substances reach supersaturation at a particular pH and temperature if crystals are retained. decreased secretion of H+.diarrhea = dehydration = low urine volume + decreased pH. require alkaline pH Calcium phosphate stones . rapid proliferation obstruction affects distal tubules. YES .
flank pain.loss of renal parenchyma Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Screening / Education women w/ Microscopy: WBC casts FH or PMH of recurrent CT Imaging if persistent sx despite tx UTIs. bladder irritation (infection) causes strong bladder spasms overflow incontinence . very rare! obstruction Urethral cancer Squamous cell carcinoma is most common type obstructive symptoms . diabetics. gas forming uropathogens Abscess Perinephric . inpt mgmt if dizziness when standing. E. fistula or ectopic ureter childbirth developing countries FEMALES Vesicoureteral reflux bidirectional urine flow stasis --> infection. men (R/O complications) w/ GU abnl. hypotension. trauma (urethral disruption) Urinary incontinence (general) involuntary loss of urine through urethral meatus treatment dependent on type of incontinence & cause leakage of urine despite higher brain function Stress Urge Overflow Stress incontinence .occurs secondary to obstruction of inf kidney. fungal infection of kidney unable to void urine diabetes CT shows gas formation within the kidney urgent nephrectomy 70% mortality even w/ app Abs perinephric renal calculi.complete inability to hold complicated urine. prior instrumentation only urologic cancer more common in females. n/v. dehydration. when pt voids.fever. STDs (gonorrhea urethritis). chills. S. straddle urethra) obstruction injury. elderly IV antibiotic therapy obstruction (stones) Fluoroquinoles preferred over TMP-SMX [Cipro] uncomplicated? Same as cystitis but for 10-14days (depends on local resistance to TMP-SMX) Pyonephrosis infection + obstruction (secondary to stagnant pus building up in the collecting system) Emphysematou EMERGENCY . & confusion + signs of PN Chronic . WBCs on UA. urethral stricture. scarring.increased abd pressure stressing the ureter Urge incontience . valsalva bladder infection diabetes Total Total incontinence .Disease Kidney infections Clinical Variants Pyelonephritis Defining Characteristics Acute . DM. diarrhea.requires acute air filled pockets within kidney parenchyma s drainage due to infiltration of gas-forming bacteria pyelonephritis severe necrotizing infection due to anaerobic. chronic pyelonephritis congenital bladder anomaly genetics Urethral stricture (when the bladder squeezes. sneezing. increased vesicular pressure pushes urine back up to the kidney) pathologic narrowing of the urethra inflammatory.coli or Proteus Intrarenal . pelvic fx). anorexia.comp of ascending PN or hematogenous seeding of kidneys. n/v. laughing. CVA tenderness. aureus TB infection. prior GU sx Others Urinary retention problem w/ bladder not being able to squeeze (detrusor muscle) or obstruction of bladder outflow pathway neurologic issues.accompanied by sudden urge to void. trauma males (long interrupting flow of urine (stasis) and possible (catheters. urine moves back up to kidneys.bladder has reached capacity (autonomic neuropathy in diabetics) coughing. abd pain. certain drugs. prostate enlargement.
stones histology: hyperplasia of stroma (fibro. hypertrophied detrusor muscle Treatment Complications Screening / Education reduce symptoms & limit stasis of urine = progression infxn. hypo & hyperechoicity (should nl look like snow on TV) path . incontinence estrogen increases hypercoag (coronary art thrombosis) Scrotal swellings hydrocele serous fluid surrounding the testes from the acute testicular/scrotal pain.relax the bladder to prevent uregency. filling it full of fluid hydrocele occurs inside the testis so feels like a huge mass if torsioned. feeling of incomplete bladder emptying (interruption of primary stream). estrogen. (ED) leading to grow together GnRH analogues) impotence. dribbling.open the ext urethral sphincter & cancer. left gonadal vein is more at a right angle so more prone to static flow from valve dysfunction benign solid mass malignant solid mass (testicular cancer) outside the testis within the testis parenchyma usually discovered by abnl self exam involves most commonly the germ cells (seminiferous tubules) 10-15% of men. renal dysfxn. 10% of these are bilateral unilateral right varicocele concerning bc probably due to pressure on the vena cava directly from kidney tumor or retroperitoneal mass peak incidence in males aged 15-34 undescended testes genetics HIV atrophy FH? Trauma? U/S . weak stream.relaxes smooth muscle. usually osteoblastic so a/w elevated serum alkaline phosphatase BPH highest incidence of all US male cancers (outside of skin Ca) 2nd leading cause of cancer deaths in men age. poorly anti-androgen tx (scrotal cavernous nerves differentiated glands that start to orchiectomy. retrocaval LNs. diet (lycopene maybe protective) PSA screening (measurable levels increase in pathologic states) bone scan for metastatic metastasis to earlier screening lesions regional LNs in for African pelvic area.Disease Benign prostatic hypertrophy/ hyperplasia (BPH) Clinical Variants Defining Characteristics occurs most commonly in transition zone obstructive sx (prostatism)hesistancy. FH. urge incontinence (make sure you R/O cancer!!) Pathogenesis enlargement of prostate gland from upregulation of androgen-R (inc prod of DHT) = overgrowth of stromal tissue. bleeding uncontrolled BPH meds (a-adrenergic can cause infection.rare!!] prognosis but rarely see that) radiation surgery can cut histo: large prominent nucleoli. bones. untwist the spermatic cord testicular torsion (dead testis from lack of bloodflow) spermatocele / spermatocele occurs outside epididymal cyst the testis so almost feels like extra testicle varicocele blood filled. (although some can be hematogenous spread (vertebrae. urinary watching waiting retention. medial lobe hypertrophy.abnl heterogeneity. race (African Americans). perineum space. fluid came down with the nausea. blockers.central necrosis area w/ surrounding tumor removal of retroperitoneal LNs (both sides since L to R spread) .interaorto-caval LNs. lymphatic spread occurs most are very slow growing first to pelvic / obturator LNs. combo tx) surgery (TURP transurethral resection of prostate) Prostate cancer occurs most commonly in require androgens in order to progress peripheral zone (posterior part) patterns of spread: direct local extension adenocarcinoma into seminal vesicles (T3) or base of bladder (T4). frequency. prolonged micturition (urination). most occurs more commonly on left side because common cause of male the right gonadal vein actually drains into the infertility vena cava.<6 is better removal of LNs + [except liver . enlarged veins blocked cysts or ducts from the epididymis dilation of veins of spermatic cord (pampiniform plexus) more common on left side.catheterization if decrease DHT to shrink urinary retention prostate. vomiting (think testicular torsion! Occurs most testis in the tunica vaginalis in adolescents or perinatal) internal spermatic fascia and tunica vaginalis wrapped around the testis. pelvis. biologically aggressive) proximal femur) if metastasize to bone.needle biopsy for radical prostatectomy w/ then solid organs grading (Gleason score . nocturia. straining to pass urine.(less specific for BPH) urgency. anticholinergics . stone. inhibition of glandular cell apoptosis = hyperplasia glands & stroma enlarge = compression of prostatic urethra = need for higher pressure in order to open the bladder neck & pass urine = bladder muscle hypertrophy (weakened) & thickening (trabeculation) + diverticula = functional degeneration (can't store urine or empty easily) 2 main pathophys mechanisms: blockage of outflow tract (= obstruction) & bladder hypertrophy/ diverticula irritative sx due to hypersensitivity of bladder Etiologies presence of androgens (DHT testosterone converted to DHT by stromal cells via 5a reductase) Epi Risk factors age Lab/Imaging prostate exam cystoscopy for bladder diverticulum gross: nodular hyperplasia. muscular) & glands 5a-reductase inhibitors . urinary retention irritative sx . right paracaval LNs chemo removal of testis surgery can result in cutting of sympathetics --> retrograde ejaculation . Americans if elevated .
hematogenous route (secondary seeding of urinary tract from primary bacteremia. incontinence. S. enterococci. Ab prophylaxis (LAST RESORT) Symptomatic bacteriuria/ uncomplicated UTI kids: non-spec sx. downward bend. coli. often a/w ED right hook. 90% of UTIs. correct underlying structural abnl. fever. tadalafil.hi sens & spec but rarely correct underlying risk done unless requested factors urine cx . S. coli is the most frequent cause of UTIs!! Elderly . Cephalosporins. Amoxicillin. hourglass in later stages (veins that maintain erection can become repetitive trauma through intercourse in compressed) predisposed individual causes micro tear in corpus cavernosum or tunica ablicans. GN rods. pregnancy). nitrite+ (nitrate reducing bacteria) [if both LE & nitrite are neg. AMS. vomiting adults: urgency.Disease Male infertility Epididymitis Clinical Variants Defining Characteristics Pathogenesis Etiologies varicoceles most common factor Epi Risk factors Lab/Imaging Treatment Complications Screening / Education Erectile dysfunction male infertility occurs in 50% of infertile couples sudden scrotal pain & swelling acute inflammation of the epididymis that is often caused by reflux of urine through the ejaculatory duct problem w/ vascular. & couple PDE5 inhibitors (sildenafil. abd pain. disruptions in urine flow (obstruction. dysuria elderly: worsening incontinence. inability to achieve and/or maintain an erection sufficient psychogenic.Enterobacter. nitrofurantoin. foreign bodies rare (however. left hook.so need to find signs/sx of UTI . AMS mechanism: ascending route (bacteria in perineum travel up urinary tract. leading to formation of scar/ fibrosis almost always occur in uncircumcised males usually squamous cell carcinoma (bc skin cancers) spread by local extension rather than lymphatics 10% of men by age of 5060 mostly Caucasians but other races too Penile cancer Urinary tract infections (general) urinary frequency. vardenafil.usually on dorsal side acquired abnl curvature of the penis during genetic erection that interferes w/ sexual intercourse. fever. bowel flora .produce sx but hard to culture (culture neg) healthcare/Ab associated . epidermidis. or endocrine factors for sexual function any age Flouroquinolones (Cipro) sometimes send for cardio referral tx patient. predisposition but thought to be a/w causing psychological stress to the patient trauma interferes w/ intercourse. nitrofurantoin Gram stain . and burning on urination E. partner. midstream. vesicoureteral reflux).often have asympt bacteriuria. males most common as infants (suggests GU abnl) elderly (inc bactereriuria. FTT. neurologic. FTT . TB) E. saprophyticus (5-15% of cystitis in young sexually active F) Ureaplasma urealyticum. pain can happen early. Candida. cranberry juice/ supp to reduce sx. avanafil) contraind if pt is on nitrates exercise in earlier ages prevents ED Peyronie's disease curvature of penis . prostatic secretions. or TMPSMX.clean catch. comorbid conditions) genetics (P group Ag on RBCs & uroepith cells) Urine microscopy . pyuria (>5-10 WBC/mm^3). WBC casts UA . avoid flouroquinolones!! lower threshold for hospitalization D/C indwelling devices ASAP void after intercourse. frequency. Candida. Mycoplasma hominis . upward bend. intravag estradiol in postmenop women. recurrent infxn prev treated w/ Abs pregnancy? 7d w/ amoxicillin/ oral cephalosporin. urgency.elevated WBC count. Corynebacteria Adenovirus causes hemorrhagic cystitis in kids & BMT pts loss of nl bacterial flora (Abs). aureus. Enterococci.atyp present. >97% predictive value that UTI is NOT present] treat all sx patients! 1.E. early sx of recurrence after tx. sexual activity. Pseudomonas. Estrogen. Trimetoprim/ Sulfamethoxazole (Bactrim) OR fluoroquinolones (Cipro) 2. environment of bladder. coli > Proteus > Klebsiella S. Candida). 1% of cancers in Africa are penile) women @ higer risk (shorter urethra.LE+ (any inflam etiology). clinical susp for pyelonephritis.
remove ASAP 3. urgency. remove catheters if source (and no longer needed) Cystitis lower tract infection frequency. and prostate) 15% of homeless extrapulm TB disease imaging: renal/ GU mass. or stricture Urine AFB culture or biopsy may respond to TB therapy but usually requires surgery bc very extensive dz by time dx Asymptomatic bacteriuria positive urine cultures in absence significance? Presence during preg of clinical signs or symptoms increases risk of PN. insert catheters only for appropriate indications 2. suprapubic pain. Nitrofurantoin x7d sexual mandatory pelvic exam for vag d/c or lesions (Chlamydia/ gonorrhea. antiseptic solutions in drainage bags. aseptic technique 5.coli) very small proportion of prostate cases urine cx: increased WBCs and positive culture would NOT want prostate specimen (tenderness of prostate. properly train those who insert/maintain 4. antibmicrobial prophylaxis. Levofloxacin 250 daily x3d.mod to marked elevation treat based on culture results initial therapy: IV Ab (fluoroquinolones) later therapy: oral Ab Prostate abscess Vaginitis. (Type I) back pain. testis. hand hygiene GU tuberculosis elevated WBC without microbial growth (sterile pyuria) secondary seeding from hematogenous spread of TB (only 20-30% have concomitant pulm TB) to involve the lower GU tract (epididymis. dysuria w/o pyuria Prostatitis Acute bacterial very severe clinical onset prostatitis fevers. ureter. trichomonas. higher mortality rates in hospitalized patients changes in GU tract prevalence (occur w/ age) inc w/ age catheters --> asympt Candiduria catheters Only time you treat asymp bacteriuria: Kids: workup for congenital/ obstruct abnl Pregnancy: treat bc hi risk fo PN & complications Pre-op pts: treat to avoid bacteremia otherwise. have pathogens w/ Ab resistance. a/w GU treatment requires symptoms!!! abnl in kids. +/. calcifications. possible obstruction PE: VERY tender prostate Chronic bacterial prostatitis (Type II) indolent course . a/w bacteremia during procedural manipulation of GU tract.possibly due to urethral GN enteric reflux or post-GU instrumentation organisms (E. UTI sx. gross hematuria if local TMP-SMX resistance <20%: TMPSMX DS BID x3d If local resistance >20%: Cipro 250 PO BID. obstruction) minimize unneccessary tx (asymp bacteriuria) Limit Ab use unless underlying process is resolved! Avoid routinely changing catheter bags. BV) new partners or hi risk sexual practice unclear mechanism . history of HSV. routine screening for asympt bacteriuria Complications indwelling devices can become havens for biofilms. maintain unobst urine flow 7.freq and/or urgency. catheterassociated UTIs) Defining Characteristics patients who need longer course of therapy. encrusted Screening / Education 1. sometimes doxycycline or macrolides . inc risk for bacteremia) PSA . bladder. interventional procedures. perineal pain. urethritis gradual onset of milder dysuria.Disease Clinical Variants Complicated UTIs (e. bladder irrigation. chills.g. dysuria.may present as recurrent UTI Ureaplasma. Chlamydia R/O complications if unresponsive prostate massage: less inflammation treat based on culture but positive culture results semen culture if prostate massage uncomfortable fluoroquinolones. maintain closed drainage system 6. or secondary complications Pathogenesis urinary stasis and obstruction are primary mechanisms for complicated UTIs biofilm formation by uropathogens can cause chronic bacterial presence on devices (catheters) --> resistance Etiologies Epi Risk factors Lab/Imaging Treatment remove underlying mechanism (catheter.
skin nephrology consult. and acid/base balance RIFLE .rare).0mg/dL nonoliguric: urine vol >400 mL/d oliguric: urine vol 100-400 anuric: urine vol <100 inc mortality risk? Pts who need renal perfusion (give vol. loss. varices. no FH and 5 cysts bilaterally w/ consistent phenotype extral-renal: liver cystic dz (massive polycystic liver dz females. liver/ renal dz . upper/low vasoconst bleed). renal loss (diuretics. form cysts instead of tubules. HTN. early sepsis (hi CO) increased BUN/Cr ratio. HTN. CHF. abnl infarct ATN. burns). skin/resp occlusion of renal loss (insensible. JVD/S3/rub.tumor lysis. crackles.ATN.serum Cr >200-300% above baseline Stage 3 . no detectable inflamm (Type III) Defining Characteristics most frequently seen conditions (>90%) sometimes evidence of WBCs & inflamm cells in expressed prostatic secretions.5 million better prognosis than peeps PKD1 worldwide M=F more severe CT/MRI: fluid filled sacs w/ nl renal massive enlargement & disease in parenchyma on either side. stones/ prostate dz . fluid balance by for renal replacement therapy excretion of free water. DI). poor renal recovery? turgor. abnl cell matrix proteins. new edema. ATN . increased treat primary prob if dec age. less likely to see inflamm cells autosomal dominant mutation in PKD1 gene (which lies very close to TSC2 gene so patients can have tuberous sclerosis too!) + second acquired mutation =phenotype 10-15% spont PKD1 mutations phenotype: renal cysts.serum Cr >300% or 4.ethylene glycol intoxications. no polarization.Disease Clinical Variants Chronic pelvic pain. fluid filled cysts and enlarged kidneys BUT nl renal fxn (differentiates from acquired PKD) a/w tuberous sclerosis U/S criteria for dx: +FH and 3 cysts distributed bilaterally in pt <40y.GI loss (v/d.true vol depletion. advanced liver disease (nl-hi CO). proteinuria Pathogenesis Etiologies Epi Risk factors Lab/Imaging usually negative culture but some inflamm cells present after prostate massage Treatment Complications Screening / Education Asymptomatic inflamm (Type IV) Autosomal dominant polycystic kidney disease (ADPKD) culture negative. urine output. uric acid cryst.prerenal (bilateral renal a ESRD occlusion).inc serum Cr >0.CHF/MI (low CO). obstr mg/dL above baseline in kidney) Stage 2 . ARF from calcium oxalate .dec EABV. dialysis. early PE: volume status (orthostatics. or need of nitrogenous wastes.3 ureteral obstruction. mild renal involvement.anuria CT for complications comp of polycystic liver dz (ascites.ATN. AV fistula (hi CO). enlarged prostate. dosing. corticosteroids (acute Oliguric/ anuric distended bladder. multiple organ EABV). 8 cysts >60y. postrenal (bilateral Stage 1 . bladder neck obst. GN). UTI long before dec GFR! PKD2 patients have 12. intracranial aneurysms. gross hematuria. change drug system failure. IV contrast . injury. renal cortical necrosis. renal cortical ext edema/ cyanosis (anti-GBM) necrosis. overload in ingest anuric patients. uremia [AEIOU] Prerenal azotemia ARF caused by hypoperfusion of glomerulus.risk.postrenal. electrolytes. enlarged variable cyst burden men kidneys before loss of renal fxn so hard to decide when to treat hemorrhage of cysts . meds . HTN. acute pancreatitis.o. FENA <1%. no active bacterial process incidental finding related to elevated PSA large. atheroembolic renal UA & microscopy (muddy casts dialysis if acidotic. true volume decreased glomerular capillary hydrostatic depletion pressure decreased EABV severe renal true vol depletion .acute onset of pain localized to kidney ESRD Acute renal failure/ acute kidney injury (general) clinical definitions vary based on rapid inability of kidney to maintain excretion creatinine. dietary malignancies restrictions.o.. secrete fluid Hx: n/v/d/bleeding . hi rate of div & apop. urine color . liver cyst infection) HTN. diff urine vol . Una <20. proteinuria ARPKD (PKD2) appears same loss of primary cilia fxn: altered mechanosensation of Ca+2 currents altered mitotic orient & cell polarity cystic epith cells: dedifferentiated. 4 cysts in pt 40-60y..o. Uosm >500. rash. hepatic venous obst. plasmapheresis ARF. AIN. causes of anuria . liver cysts.acute GN. intrinsic (acute GN. more hospitalizations). nephrolithiasis. asymp intracranial aneurysms. portal hypertension. sequestration into arteries 3rd space (crush injuries. internal hemorrhage) dec EABV .. pain. FEurea <35% . failure.
increased hydrostatic pressure in BC U/S for obstruction . acute GN or vasculitis. chemo agents. myoglobin. rejection). neurologic d/o Epi Risk factors Lab/Imaging path: muddy brown casts .injured tubular cells = loss of polarity = apop/nec. immuno (SLE. BPH. malignancy LUT . lymphoma) UUT nephrolithiasis. nephrotoxins (Abs. increased hydrostatic pressure in BC. FEurea >50 Treatment Complications Screening / Education ATN. leuk. others).DM. releasing inflamm mediators & cytotoxins AIN . uric acid) AIN .drugs (NSAIDs. prostate Ca Neurogenic . Infxn (PN).vasoconst of blood supply.ATN. retroperitoneal fibrosis.injured tubular cells interact. Abs.AIN BUN/Cr ratio 10-15:1. infilt (sarcoid. decreased hydrostatic glomerular pressure. Una >40. backleak of urine. tubular obst.ischemic causes. heavy metals.Disease Clinical Variants Intrinsic Renal Failure Defining Characteristics Pathogenesis Etiologies ATN . blood clot. contrast dyes.stricture.prolonged ischemia or toxins leading to tubular damage (PT or TAL).immune mediated injury in the interstitium. non-oliguric Postrenal failure mechanical or functional obstruction to flow. decreased acute renovascular dz Kf. FENA >2. diuretics. calcium phosphate stones. interactive cell bio . Uosm <350. AIN. eosin infiltrate + edema between tubules . anticholinergics. ATN . hemodynamic . Hg. cell fate .
ANS ketones = acid = DKA reg excessive urination.pump or basal injection w/ bolus injection at meals) Type 2 DM metabolic syndrome: waist circum > 32"F or 38"M + any 2 factors (HTN. more sat fat.osmotic diuresis. impotence. + urine glucose (weight loss). low HDL <40M or <50F. body attempts to inc gut: slowed chronic hyperglycemia: 3Ps intracell glucose and dec gastric motility. + ketones (fruity odor. poor wound healing. blunted 2nd phase. lipolysis).8-10x w/ sx. CD8. ident twins GAD65 Ab. islet distn (4-6y. impaired FBS >100) . middle aged veggies.000 FH: 15% w/ positive antibodies (anti+FH. inc BUN:Cr ratio (catabolic state. blurred vision. inflamm/ox stress/ ER stress) = dec need for endogenous insulin and less B-cell apoptosis = dec progression of DM . fatigue. in 2012 FBS > 126 OR 2h 75g OGTT dec insulin resistance: > 200 OR random BG > 200 lifestyle mods (diet. see chronic complications below pancreas: inc glucagon. >125 mg/dL fasting) population higher risk Large urine ketones. TZDs). hyperinsulinemia islet cell dysfxn: inc glucagon. no physical activity. insulin .3% general DR 3/4 genotype Serum glucose (>200 mg/dL Caucasian (HLA) . TZDs) A1C > 6. FFA output dehydration bc body H2O is muscle: dec used to eliminate extracell glucose uptake glucose in the urine liver: inc hepatic dec intracell glucose = dec glucose output energy. polyphagia). inc Asians> glucagon post whites prandial (opp of nl) 24 million diabetics in U. ABG: low pH. excessive thirst. hi triglyc deposit = inc DAG accum = dec insulin signaling. dec insulin secretion fat: dec glucose nutrients pass into the urine uptake. highest risk for T1DM.same amt of insulin = less response) & dec insulin secretion insulin resist (aging. postprandial.5% Repair dual defect: inc insulin action (metformin. mom (3%) Whites colder climate subcutaneous insulin DKA therapy that mimics physiologic insulin (continuous insulin . hypoglycemia. inc postprand gluc MODY: mutations w/ B-cell fxn = T2DM in nl weight kids w/ -FH typical T2DM: inability of B-cells to overcome insulin resistance (dec insulin action . minority groups. dec insulin obese adipose tissue = inc oxid stress from inc NADPH oxidase polygenic muts in TCF7-L2 (dec insulin secretion) + dec insulin action (resist via inactivity + obesity) strong FH.rather than storing energy. sequest of GLUT4 inside the cell insulin secretion defects: no 1st phase.S.dec caloric intake. hyperlipidemia >150. tachypnea (metab acidosis compensation). weight. inc FBS.siblings (5% cell Ab. as unable to use to drive glucose intracell) uptake glucose. incretins . 20/100. & protein) CD4. & MOs infiltrate & accumulate in islet cells --> insulitis. insulin auto-Ab) 14y) risk). father (6%). 2. 10. inc (weight loss. weight loss progressive autoimmune destruction of B-cells --> insulin deficiency (causing the opposite of insulin .assist B-cells) B-cell rest for pre-DM (dec insulin resistance.basal & bolus. suggesting dual defects in T2DM DKA. the body tries to make glucose & breaks down glycogen. highest higher glycemic inc IHL a/w dec incidence in load (less fruits. body attempts to brain: dec increase energy by using fats = satiety. dry mouth.Disease Diabetes mellitus Clinical Variants (general) Defining Characteristics 3Ps (polyuria . insulin action. sedentary activity) compensated early by inc in beta cell fxn. overweight.these pts have bimodal age (25-50%). glucose levels. fruity odor (increased breakdown of fats to form ketones) Pathogenesis hyperglycemia & glycosuria due to inability to oxidize/utilize carbs + disturbance in insulin function + imperfect fat combustion (hi ketones) Etiologies Epi Risk factors Lab/Imaging Inc urine volume + hi SG (polyuria). prevalence is pregnancy highest in older people Diet: more trans (60+) but fat. polydypsiarehydration. unk triggering event occurs promoting autoimmune destruction of islet cells clinical manifestations when 8090% B-cells destroyed Type 1 DM 0. beta cell fxn falls = inc glucose levels (1. w/ sx metformin. ex. + severe cachexia (unable extracell glucose (osmotic inc glucose diuresis). dry skin. dec Americans> insulin syn & blacks> secret hispanics >> dec insulin. insulin secretion dec significantly w/ impaired glucose tolerance. fatigue (unable to utilize glucose). polyphagiareplenish carbs). low HCO3-. more fat) inc oxid stress (40-59) a/w inc B-cell Native apop. inc insulin secretion (B-cell enhancers. weight loss (urine carb loss). dehydration). fats. low pCO2 (metabolic acidosis w/ resp compensation) Treatment Complications Diabetic ketoacidosis. pre-prandial) insulin resist: post-receptor defects (dec phosph after insulin binds).a/w underlying insulin resistance inc risk of CVD & DM insulin action impaired but does not get much worse btwn pre-diabetes to DM.
80% of GDM. 3h > 140) UA: check for ketonuria postpartum screening: if DM . PI) Lab/Imaging universal screening 24-28 weeks: 1h 50g glucose challenge test (>140 .o. inc glucose = inc metabolism to sorbitol & fructose = inc osmolarity = inc water = osmotic cell injury inc glycation products (HbA1C) react w/ arterial wall components. massive dehydration. plasma glucose levels nausea. epinephrine urine or serum ketones ketotic or non-ketotic hypoglycemia oral glucose (tablets. eclampsia). coma low blood glucose (sx usually when <60 mg/dL. Ex during pregnancy. resp distress syndrome.90% of GDM. stillbirth. & inc arterial stiffness inc LDL promotes atherogenesis Hypoglycemia (general) most common complication clinical syndrome w/ diverse causes related to decreased ANS sx: sweating. confusion. HA. childhood obesity carbohydrate intolerance . C/S. >200 diagnosed w/ GDM & do not need 3h GTT) if failed 1h glucola. trembling. 14% FP. add insulin (does not cross placenta) OCP postpartum. behavioral mods to avoid GDM recurrence) Complications frequently resolves after delivery Maternal comps . >130 . operative delivery. cross link collagen. glucagon (if seizures or coma). assess q 1y elevated anion gap metabolic acidosis hyperglycemia (usually > 300) ketosis pseudo-hyponatremia (dilutional). birth trauma. 25%FP. preconceptual glycemic control imperative (diet. ex. NA. if still not controlled. neonatal hypoglycemia. stress. shoulder dystocia. if impaired weight loss. nutrition.5 mg --> 10 mg). seizures. trauma fetal comps macrosomia. hyperbilirubinemia. if nl . sugary sodas). the brain) fatigue.assess q 3y. activity. GH.) h/o poor obstetric outcome h/o GD ethnicity (AA. counsel for weight loss. hyperkalemia pre-renal azotemia Treatment A1: 30kcal/kg/day diet BMI>30: 30% caloric restriction nutritional counseling.maternal hyperglycemia --> fetal hyperinsulinemia --> inc -> hyperglycemia with onset during pregnancy production of fetal fat cells --> obesity --> insulin resistance --> A1: controlled w/ diet & ex impaired glucose tolerance in A2: require meds for control childhood --> DM macrosomia (excessive fat deposition on fetal shoulders & trunk due to stimulation by IGF-I & 2) insulin resistance increases as pregnancy progresses (higher the maternal glucose levels = worse fetal outcomes) Diabetic Ketoacidosis (DKA) severe insulin deficiency nth degree of diabetes sx: massive polyuria. unable to concentrate. macrovascular ischemic heart dz insulin is not needed for glucose utilization in the microvasculature. anxiety. or omission of insulin T1DM Chronic complications of DM Retinopathy microvascular Nephromicrovascular pathy Neuropathy microvascular CAD. inc B-oxidation of FFA = inc acetyl CoA which is converted to ketone bodies in the liver medical illness. hispanic. IV glucose (if compromised airway) neurological compromise or mental retardation . metformin.refer to endocrinology. life threatening electrolyte shifts and metabolic acidosis increased gluconeogenesis causes hyperglycemia increased lipolysis = release of FFA.HTN d/o (pre-eclampsia. difficulty speaking. maintain FBS < 95 & 2h postprandial <120 A2s: lifestyle mods + glyburide (low doses 2. then give 3h GTT (diagnosis requires 2 abnl blood draws: fasting > 95. 2h > 155. feelings of warmth eventually leads to neuroglycopenia (low sugar in neuroglycopenia: dizziness. brain fxn impaired < 50 mg/dL) + presence of cortisol. 1h > 180.Disease Clinical Variants Gestational diabetes Defining Characteristics Pathogenesis Etiologies Epi 7% of all pregnancies complicated by GD 1/3 of GDM patients will have DM postpartum 50% of GDM patients will develop DM within 10y of affected pregnancy Risk factors FH of DM h/o macrosomia obesity AMA (>35y.
inc NH3 levels around 40 acute tx: oral glucose (best if possible) of sugary most patients with diffuse areas of liquids or IV glucose hyperinsulinism will develop DM chronic tx: diazoxide. ATP. cortisol def (Addison's.Disease Clinical Defining Characteristics Pathogenesis Variants Ketotic hypo.000 mutation (SUR1/Kir6.000 avoid periods of reduced carb intake (problematic when sleeping) mutations in ABCC8 gene (SUR1) causes abnl of the outer subunit (50-60% of cases) or the KCNJ11 gene (kir6.2) K-ATP >> GDH > glutamate glucokinase dehydrogenas e mutation (AD) GOF GDH mutation: hyperinsulinism + hyperammonemia (which does not inc w/ protein feeds) intra-arterial calcium gluconate infusion: determine insulin levels across pancreas (splenic a.Jamaican vomiting sickness) or CPT deficiencies prevent the shuttling of fatty acids into mitochondria autosomal recessive mutations in ACADM gene that results in abnormality in B-oxidation --> non-ketotic hypoglycemia Medium Chain Acyl Dehydrogenas e Deficiency (MCADD) HyperCongenital insulinism presents at 3-24 months (peak at 15 months). valproic acid. surgery. epi def. cirrhosis) Alcohol? metab by alcohol dehydrogenase in liver.2) causes abnl in the inner subunit. during periods of fasting or sickness PHHI = persistent hyperinsulinemic hypoglycemia of infancy 1/15. dx w/i 1st weeks of life. hi calorie feeds. so insulin is despite oral or IV supplementation constitutively released K-ATP channel 1/40. B-cell of glutamate dehydrogenase = dysmaturation syndrome inc oxid of glutamate = inc aketoglutarate.Ketones in urine or serum substrate limited: unavailable glycemia carbs/ poor storage = unable to fast for a long time w/o becoming ketotic (MSUD) Hormone deficiency: panhyopopituitarism (GH. or glucokinase mutations carb load before protein (Leucine) intake if GDH mutation autosomal recessive KATP mutations are most severe (diffuse islet cell hyperplasia) while autosomal dominant K-ATP muts are more mild severe developmental disorders and mental retardation from lack of blood sugar to brain glucokinase also called nesidioblastosis. 1st step in glycogen synthesis & glycolysis) shut down = activation of insulin until BG is GDH mut . celiac axis). inability these mutations cause K-ATP to maintain glucose levels channel to be permanently closed. gastroduodenal a. areas of highest insulin levels are prob location of faulty enzymes and must be removed surgically (focal or diffuse lesions) PET scan to eval high uptake at high insulin concentrations (only avail at CHOP) pancreatectomy if AR KATP mutation of clonal loss of heterozygosity diazoxide TID if mild AD K-ATP. ocreotide (somatostatin). results in NADPH accumulation. transient to severe. SMA. systemic d/o (can't meet body's energy demands). quinine. salicylates. insulin Epi Risk factors Lab/Imaging Treatment Complications hyperinsulinism shuts down the hyperinsulinism production of ketones Fatty acid ox D/O d/o in fatty acid oxidation carnitine or prevents the generation of CPT I or II ketones (Acyl dehydrogenase deficiency deficiencies like MCADD) carnitine (akee fruit . HRT . ACTH def). GDH. & insulin glucokinase mut decreased glucose GOF muts of glucokinase threshold for insulin to (glucose sensor. inhibiting gluconeogenesis by inh malate -> OAA Non-ketotic hypoglycemia Etiologies Substratelimited Hormone deficiencies GSDs D/Os of gluconeogenesis Drugs alcohol. congenital adrenal hyperplasia) Others: drug-induced. GOF muts (activated by leucine) mutation (AD) B-cell hyperplasia. liver disorders (can't make or use glucose . glucagon def. requires NAD+.hepatitis.
large tongue. severe mental retardation. slow tertiary: hypothalamus is pulse (brachycardia). IV glucose. hunger. T4.6ug/kg body weight). no advantage Thyroid (USP) and thyroglobulin (Proloid) dried animal thyroid. palpitations. affected (tumors.goiter if dyshormogenesis newborn screen .weakness. increased prevalence w/ age 10% of elderly primary: low T3.pure T4. tremors. coarse hair. treat moms if maternal thyroid deficiency CRETINISM = mental retardation if not treated early!!! Signs?? Impaired skeletal/CNS development) risk of bleeding if removal of lingual thyroid Hashimoto's most common cause of thyroiditis hypothyroidism in FEMALES goiter. infiltrative dz) release/ synthesis cool/dry/ puffy skin. hi TSH. diet reduced metabolic state. exercise induced. T4.most common cause thyroid gland dysgenesis or agenesis iodine def = elderly most common cause globally of hypothyroidism F>M.o. extremely hi TSH (compensation to increase TH) hi TSH/TRH could possibly cause prolactinemia secondary: low T3. coarse facial absence of TPO features. DOC for replacement/ suppression. not recommended diabetes.deficiency or lingual thyroid stature. droopy (rare). ablation). subacute thyroiditis.if unsure. eyelids. sweating.congenit al errors of TH slowness. or thyroidectomy. psychiatric probs.Disease Clinical Variants Acquired Defining Characteristics Whipples triad suggests insulinoma (hypoglycemia + symptoms . +/most common causes? goiter. primary: thyroid gland is iodine def. low TSH Levothyroxine (Synthroid. progresses to hypothyroidism in 40-50% of patients 2nd most common cause of hypoT AFTER iatrogenic! low T3. thinning of lateral 1/3 Autoimmune dz. keep TSH WNL. short dyshormogenesis . or glucagon (if seizing or unconscious) Complications reactive hypoglycemia can be a precursor to T2DM exogenous delivery to someone Exogenous who doesn’t need insulin = delivery hypoglycemia insulinoma insulinoma = tumor that secretes insulin retroperitoneal tumors retroperitoneal tumors = tumors that mediate IGF-2. autoimmune destruction of the thyroid defect of T cells causes production of anti-thyroid antibodies that are cytotoxic to the thyroid gland initial thyrotoxicosis followed by hypothyroid state abrupt onset of thyrotoxicosis.confirm w/ TSH (extremely hi if no thyroid hormone present) & serum free T4 thyroid hormone (Levothyroxine) increases growth & mental development . treat shortly after birth bc brain growth 8085% complete by 3y. slow titration of Levothyroxin in elderly to avoid complications w/ coronary heart disease Congenital impaired development of CNS & skeleton. & postpartum poor school performance thyroiditis underproduction of T3&T4 reduced production of T3 & T4 Failure to thrive! thyroid gland dysgenesis or agenesis . T4. which binds reactive insulin receptors hypoglycemia reactive hypoglycemia = ingestion of simple sugars w/o fats or carbs = insulin spike that easily takes up simple sugars Hypothyroidism (general) Hashimotos thyroiditis. dry skin. +/. watch free T4 w/ sec/ tert hypothyroidism Liothyroxine (Cytomel) pure T3. Thyrola) mixture of T4/T3 in 4:1. positive thyroid antibodies (TPO) Subclinical Painful thyroid following URI or viral infection Painless thyroid NO uptake on I-123 scan transient . CNS sx.supportive care rarely progresses to & treatment of underlying overt hypothyroidism dz postpartum . pituitary tumor) (rare). pituitary iatrogenic cold intolerance. used ONLY for acute/severe hypothyroid (Myxedema coma) Liotrix (Euthroid. dec affected appetite w/ inc weight secondary: pituitary is affected lithium OD gain. weight gain. atherosclerosis. radioiodine radiation exposure. relief w/ glucose) Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment glucose tablets. protruding tongue & umbilical. of eyebrows. insufficiency (radioactive iodine tx or KIDS: same sx as adults surgery BUT poor linear growth. excess weight gain. lethargy. constipation. 1. mental (TSH deficiency. dec CO.
Clinical Variants (general)
Defining Characteristics overproduction of T3&T4 inc metabolic state, nervousness, insomnia, fatigue, irregular heart beat (afib), tachycardia, inc appetite w/ dramatic weight loss, heat intolerance, exopthalmos, +/- goiter, hyperhidrosis, alopecia, hyperdefecation, abnl LFTs, osteopenia, hi Ca, tremors, proximal myopathy, periodic paralysis, onycholysis (separation of fingernail)
Pathogenesis exaggerated T3 and T4 production causes suppressed TSH (negative feedback)
Complications osteoporosis, bone fx
85% of the Graves dz cases caused (young F) by Graves see below toxic, 5-10% of pts will have nl T4 but multinodular exaggerated T3 (T3 toxicosis) goiter (elderly) - see pituitary tumors can sometimes below cause inc T3, T4, AND TSH! TH overdose (most common cause!) thyroid tumor, subacute thyroiditis, postpartum thyroiditis, painless thyroiditis amiodarone
hi T4, T3; undetectable TSH Thioureylenes (compensation to decrease (Propylthiouracil or Methimazole/Tapazole) TH) I-123 scan: hot nodules brain MRI if pituitary tumor suspected (hi T4/T3, hi TSH) should try & get I-123 scan on all hyperthyroid patients (not all thyrotoxic patients are hyperthyroid - i.e. subacute thyroiditis)
most common cause of spontaneous hyperthyroidism under 40 years old
autoimmune disorder resulting in the production of anti-TSH receptor antibodies (thyroid stimulating immunoglobulin IgG) that bind TSH-receptor and diffuse toxic goiter, mimics natural TSH; thus, exophthalmos (protrusion thyroid produces TH of eyeball from thickening of retro-orbital tissues), thyroid "stare" (stare from the spasm of levator palpebrae muscle form inc B-adrenergic stimulation), pretibial myxedema (orange peel appearance on lower legs from mucopolysaccaride infiltration: non-pitting edema), onycholysis, Afib (most common sx in elderly) amount of TH made is autonomous functioning related to mass of nodule "single" thyroid nodule
a/w HLA-B8 & DR3, other autoimmune d/o
F>M (7:1) 2% US women
hi T4, T3; undetectable TSH, "cool down" with antithyroid drugs; 50% of pts positive TSI (thyroid will be cured w/ meds stimulated IgG), goiter alone possible T3 toxicosis (inc in med tx: propanolol T3 only) (tachycardia, inhibits Hot, diffuse nodule on I-123 conversion of T4 to T3), anti-thyroid meds scan (methimazole, PTU for pregnant women ONLY), GCs (inhibit T4-->T3) usually require radioactive iodine surgery also option
blindness and decreased ocular vision if exophthalmos not treated! Radioactive iodine --> hypothyroidism
2% of hyperthyroid cases
low iodine intake I-123: hot nodule w/ complete to partial supression of paranodular thyroid tissue Propanolol + thioureylenes + large doses of Lugol's
Thyroid storm (Thyrotoxicosis)
tachycardia, fibrillation, shock, heart failure
Thyroglossal duct cyst
sudden acute exacerbation of thyrotoxicosis secondary to severe hyperthyroidism and upregulation of metabolism/ sympathetic nervous system mass in midline of neck + remnants that occur when duct does not sufficiently close thyroid tissue present
Lateral aberrant thyroid
lateral to sternocleidomastoid
usually metastasis from papillary thyroid carcinoma
histology: variable epithelium cyst lining (nondescript cuboidal, sometimes squamous) histology: lymphoid tissue + thyroid glands
Clinical Variants (general)
Defining Characteristics enlargement of the thyroid gland
Pathogenesis in low iodine areas, TH cannot be produced so hypothalamus increases TSH secretion = increased growth of thyroid gland causes in developed countries: diffuse simple goiter, Graves, Hashimotos, subacute thyroiditis, multinodular goiter, malignancy, genetic
Etiologies endemic (iodine deficiency, goitrogens!), sporadic, familial
Risk factors endemic areas (Alps, Andes, Himalayas; iodine def = TSH = hyperplasia)
Lab/Imaging histology: large colloid lakes w/ involuted areas of variable appearance, surrounded by smaller thyroid follicles
Treatment Iodine if related to iodine def
diffuse, symmetrical enlargement Toxic (Graves disease) Non-toxic (simple)
diffuse non-toxic: diffuse hyperplasia w/o nodularity; usually related to goitrogens (Ca, Fl, veggies), may develop in multinodular diffuse toxic (Graves dz): a/w autoimmune dz
FH of Graves
euthyroid - nontoxic hyperthyroid - Graves gross: Graves - red, hyperactive appearing thyroid histology: Graves scalloping (clefts around colloid), inc # cells & hyperplasia I-123: hot nodules multinodular PE: can sometimes feel lumpy thyroid gland, but 25% of patients have nonpalpable U/S
nodular, lumpy enlargement Toxic (Plummer's dz) non-toxic (simple) toxic sx: unexplained weight loss, depression, Afib
autonomous function of nodular thyroid tissue --> hyperthyroidism (toxic)
hypothyroidism if tx w/ anti-thyroid meds prevent sx BUT DO NOT radioactive iodine (although less CURE DZ!! common than Graves patients) Radioactive iodine +/surgery (only if trouble swallowing, compression of trachea) - surgery can sometimes be better option if VERY large
benign / non- solitary or part of neoplastic multinodular goiter R/O malignancy by measuring TH & TSH - if abnl do fine needle aspiration (also done if nodule > 1cm) follicular adenomas uniform follicular pattern; no goitrous nodules (if present, think multinodular goiter), complete fibrous capsule, sharp demarcations, no vascular or transcapsular invasion!!!
occur in almost any thyroid disorder 50% - non-neoplastic colloid nodules 30% - adenomas (benign epithelial follicular neoplasms; slow growing, rarely fxnal) 10% - carcinoma 5% - benign cysts
carcinoma, benign hyperplasia
palpable nodules in 6% women, 2% men
usually euthyroid require fine needle aspiration cytology to define hyperplasia OR malignant epithelium I-123 scan: nl thyroid nod will have diffuse filling/uptake; "cold" nodules (no iodine uptake - VERY concerning for Ca) gross: if uniform tan/ gooey material w/o capsule - colloid nodule; capsule w/ complete integrity - adenoma; thick capsules - malignancy histology: uniform w/o transcapsular invasion (adenoma)
Clinical Variants Thyroid carcinoma
papillary - sporadic, PMH of neck radiation; slow growing, good prognosis follicular - more aggressive but good prognosis; common in iodine def countries medullary - arise from Ccells (parafollicular cells secrete calcitonin), neuroendocrine neoplasm (MEN IIa, MEN IIb, nonMEN) w/ amyloid deposition undifferentiated - no follicular/ papillary morph, elderly, rapid growth, local invasion, poor prognosis Malignant lymphomaelderly women, a/w Hashimotos thyroiditis
Pathogenesis normal follicular cells --> adenomas under influence of RAS oncogenes --> subset of adenomas progress into follicular carcinomas normal follicular cells --> papillary carcinomas under influence of RET mutations pre-existing follicular or papillary cancer acquires p53 mutation to become anaplastic carcinomas (hi grade!!)
Lab/Imaging histology: Papillary (fibrovascular core lined by epithelial cells; finger-like; enlarged, optically clear cells w/ intranuclear grooves; little orphan Annie's eyes Psammoma bodies); Follicular (hard to diff from adenoma; vascular &/or transcaps invasion; Hurthle cells - more agg lesions); Medullary (C- cell hyperplasia, amyloid deposition, neuroendocrine + stains - calcitonin, ectopic hormones) gross: transcapsular invasion (follicular!!); necrosis (malignant lymphoma)
Treatment thyroidectomy, radioactive iodine Thyroid replacement therapy if hypothyroidism results whole body scan post surgery serum thyroglobulin tumor marker after total thyroidectomy
Complications papillary carcinoma lymphogenic spread follicular carcinoma angio-invasion/ vascular spread to bone & lungs total thyroidectomy required exogenous hormone replacement
uncommon radiation to neck but increased incidence w/I genetic past 20 years, (medullary) F>M pre-existing young- mid thyroid disease age females (hashimotos (papillary) malignant lymphoma, Papillary (75- carcinoma) 80%), follicular (10- elderly (malignant 20%), undifferentiated lymphoma, undiff (1-5%), medullary (3- carcinoma) 5%)
Acute Chronic Hashimoto's thyroiditis
inflammation of the thyroid caused by bacteria or fungus a/w other autoimmune d/o: deficiency of suppressor T cells --> immunologic abnl (anti-microsomal autoantibody) --> thyroid destruction
very rare <1% F>M
immunocomp familial histology: lymphocytic thyroiditis, reactive follicular centers (germinal centers); destruction of thyroid follicles, Hurthle cells (abundant pink reactive cytoplasm), fibrosis gross: enlarged thyroid, bosselated (bumpy) w/ creamy surface from lymphocytes serum autoantibodies: antimicrosomal, antithyroglobulin, anti TSHR, blocking antibodies hyperthyroidism followed by hypothyroidism (if gland stops functioning) histology: granulomatous giant cells w/ lymphocyte infiltrate (no giant cells seen in Hashimotos!) I-123: no uptake (inflammation of thyroid responsible for hyperthyroidism) inc risk for thyroid carcinoma & malignant lymphoma
uncertain - possibly post-viral DeQuervain's / granulomatous thyroiditis inflammation causes hyperthyroidism from rapid small goiter AND DIFFUSE PAIN!! (unable to release of TH palpate bc of pain), fever of TRANSIENT - complete unknown origin resolution over 2-6 months hyperthyroidism state --> hypothyroidism state (sometimes)
Riedel's thyroiditis woody/ stone hard thyroid gland
long-term inflammation --> fibrosis --> destruction of thyroid gland and adjacent neck structures clinically resembles malignancy
gross: woody hard area around periphery of thyroid gland
Clinical Variants Postpartum
Defining Characteristics painless thyroiditis appearing 1-2m postdelivery, lasts 2-5m goiter increases 1-2m postpartum, fatigue/ moodiness (hard to dx!!) hyperthyroidism state --> hypothyroidism state
Epi very common!!
Complications severe depression
high recurrence hi T3/T4 (hyperthyroidism), rate! low TSH, positive antithyroid antibodies; followed often by hypothyroid phase!
Multiple endocrine neoplasm
MEN1 (Werners syndrome)
recurrent stomach ulcers, hypercalcuria w/ nephrolithiasis, headaches, bitemporal visual field loss, hypercalcemia 3Ps: pituitary adenomas (prolactinomas most common), hyperparathyroidism (4 gland hyperplasia from 2ndary hyper-parathyroidism leading to hypercalcemia), pancreatic islet cell tumors (gastrinomas --> ZE syndrome-inc gastric acid secretion & PUD from gastrinoma; insulinomas --> hypoglycemia) adrenal hyperplasia
germline mutation in menin (tumor suppressor gene) chromosome 11 other early signs of menin mutation? Facial angiofibromas & collagenomas
0.25% population all ages, no sex pref 80% manifest tumor by 5th decade first manifestation s occur earlier than in sporadic dz
dx: 2 or more of "3Ps" + relative w/ 1P 4 gland hyperplasia (sporadic dz only has single parathyroid adenoma) genetic screening if mutation known in the family
total parathyroidectomy pancreatic islet cell tumors (usually & autotransplant multiple, small, & benign) can become PPIs if gastrinoma; malignant ocreotide or pancreatectomy if hi surg failure & insulinoma recurrence necrolytic migratory erythema - if glucagonoma
medullary thyroid germline mutation in RET carcinoma or hyperplasia oncogene (tyrosine kinase of thyroid C cells + pheo- receptor) chromocytoma (adrenal medullary tumor) + parathyroid neoplasms (adenoma or hyperplasia)
path: medullary thyroid carcinoma will be immunoreactive for calcitonin
some variants of MEN2A have Hirschsprungs dz (megacolon from lower intestinal obstruction) or cutaneous lichen amyloidosis (upper back)
Pheochromocytoma + thyroid medullary carcinoma (or C- cell hyperplasia) + mucosal neuromas (neural tissue nodules in GI tract or mouth) + marfanoid habitus hypercalcemia, pathological fractures, bone pain hyperparathyroid bone disease
germline mutation in RET oncogene
Osteitis fibrosa cystica
excessive bone resorption by osteoclasts related to parathyroid overactivity --> dissecting osteitis in cancellous bone --> osteoblastic bone formation (fibrous replacement results in weakened bone and scarring)
XR: thin cortex & bone cysts path: dissecting osteitis
Clinical Variants (general)
Defining Characteristics tetany (neuromusc irritability, musc cramps, tonic-clonic seizure; elicited musc contractions w/ Chvostek & Trousseau signs), ocular abnl (cataracts, papilledema, pseudotumor cerebri), prolonged QT interval & nonspecific T wave changes, anxiety, confusion, depression, intracranial sx (basal ganglia calcification, parkinsonism), dental manifestations (dental hypoplasia, failure of eruption), macrocytic megaloblastic anemia, diarrhea
Pathogenesis hypoparathyroidism (insuff activity of parathyroid = low PTH, hypocalcemia), pseudohypoparathyroidism (active parathyroid gland but unresponsive end organs), vit D def/insufficiency, vit D dependent rickets I & II (genetic deficiency of 1-a hydroxylase prevents activation of vit D in kidney), end organ resistance to vit D; renal failure (unable to make RBCs, active vit D; can't reabsorb Ca or eliminate P = inc PTH) activating defects (GOF) in CaR of parathyroids(takes a lower calcium to induce PTH; would have nl PTH levels); PTH resistance inherited activating mutation of calcium-sensing receptor on parathyroid chief cells; results in constitutive supression of PTH release and low serum calcium levels
Etiologies low Mg+2, low albumin (binds calcium so can cause unadjusted low total calcium) meds (Lasix, calcitonin, antineoplastic agents, anticonvulsants, citrated blood products)
Lab/Imaging low total calcium, high phosphorus PTH deficiency - low Ca, low PTH PTH resistance or renal failure - low Ca, high PTH ALGORITHM: low PTH? hypoPTH (gland defect, no PTH production, prob w/ CaR); nl PTH? hypoPTH, transient hypoPTH; hi PTH? Renal failure, vitD deficiency (would mean PTH is less effective at raising calcium so parathyroids would continue to release more...)
Treatment acute - IV calcium gluconate chronic - calcium carbonate vitamin D - if PTH problem, give calcitriol; if vitD deficient, give cholecalciferol (precursor)
Familial hypercalcuric hypocalcemia
sx related to sites of calcium action/reg: ("stones, bones, groans, psychic overtones") - bone: fxs, osteoporosis, osteomalacia, osteitis fibrosa cystica -kidney: nephrolithiasis, nephrocalcinosis, polyuria - CNS: depression, seizures, obtundation, muscular contractions - EKG changes (shortened QT interval) - GI: gallstones, acute pancreatitis, peptic ulcers
parathyroid hormone related (primary or tertiary hyperparathyroidism - SEE BELOW) vitamin D related (vitD intoxication; granulomatous dz like sarcoidosis, TB) malignancies (ectopic hormone production - PTHrP; osteolytic metastases) Meds (thiazides, lithium, antacids) genetic (CaR mutations inactivating) hyperthyroidism
excess PTHrP (cancers) causes release of PTH
hi PTH? Hyperparathyroidism, familial hypocalcuric hypercalcemia
symptomatic - fluids followed by furosemide once volume is corrected; calcitonin IM/SC (acute relief), low PTH? Tumor induced bisphosphonates (PTHrP), granulomatous dz (slower relief); GCs (if myeloma, granulomatous or lymphoma, bone dz, or vitD toxicity), metastases, meds dialysis - last resort bone mineral density test for osteoporosis 24h urine calcium & creatinine clearance for kidney fxn
Hypercalcemia from malignancy
most common cause of symptomatic hypercalcemia PTH independent hypercalcemia FATIGUE, polyuria
humoral hypercalcemia of malignancy (HHM) - major cause of severe hypercalcemia, usually due to ectopic PTHrP osteolytic metastases: ectopic PTHrP from SCC, RCC, lymphomas, HTLV; vitD producing tumors (lymphomas), ectopic PTH tumors, local osteolysis (breast Ca or myeloma metastasizes to bone)
SCC - lung cancer, RCC, lymphomas. Local bone metastasis from breast Ca or myeloma
LOW PTH, hi Ca (nl feedback system, but hi calcium from hi PTHrP) often have low albumin from malnourishment/ weight loss MRI or CXR to find malignancy
Clinical Variants hypercalcemia from granuloma dz
Defining Characteristics PTH independent hypercalcemia
Granulomas make 1aTB, sarcoid, hydroxyase = increased 1alymphomas, hydroxylase activity = increased fungal infection production of vitamin D = increased calcium absorption inherited inactivating mutation of the calcium-sensing receptor on parathyroid chief cells; results in constitutive release of PTH and high serum calcium levels CaR senses low calcium when the Ca levels are actually normal --> causes hi PTH, hi calcium Hispanic origin FH low 24h urine excretion of calcium benign condition that usually doesn’t require tx
Familial hypocalcuric hypercalcemia
PTH dependent hypercalcemia
PTH dependent hypercalcemia most often asymptomatic hypercalcemia
lesions directly to the parathyroid gland cause excessive PTH release
25/100,000 cases in U.S.
hi PTH, hi Ca, hi 24h urine excretion of Ca
parathyroid adenomas = most common cause of asymp hypercalcemia; usually sporadic, solitary lesions Can also cause STONES, diagnosed incidentally; often have mutations in cyclin D1 BONES, GROANS, (promotes cell division), menin PSYCHIC OVERTONES (MEN1), RET (MEN2)
diffuse/ nodular Females 3:1 hyperplasia parathyroid carcinoma (rare)
path of parathyroid adenoma: small tumor w/ encapsulated growth pattern, lack of nl fat component of PT, uniform if do not meet surgical cells w/ round nuclei (tumor criteria, monitor blood nests w/ dense chromatin), tests every 6 months rare mitoses path of parathyroid carcinoma: much larger than adenoma; bland cytology (may have fibrosis, scarring within tumor nests, subtle infiltrative growth); local invasion & metastasis
parathyroid adenomas are treated by surgical excision IF criteria met (Ca > 11.5, reduced kidney fxn, T-score on BMD <-2.5, age <50)
brown tumors of hyperparathyroidism (reactive mass formed secondarily to microfractures and hemorrhages as a result of multinucleated giant cells and fibrous tissue influx) osteitis fibrosa cystica (see above)
chronic hypocalcemia --> hyperstimulation of the parathyroid gland --> hyperplasia of parathyroid and increased/chronic release of PTH accumulation of mutations from secondary hyperparathyroidism hyperplasia leads to the development of calciumindependent lesion
renal failure vit D deficiency
PTH > 500 REQUIRES medical intervention
parathyroidectomy if PTH cannot be controlled w/ meds
possibly associated w/ duration of dialysis; can occur in post-kidney transplant patients
Clinical Variants primary
Defining Characteristics insuff activity of parathyroid gland = low PTH and hypocalcemia
Lab/Imaging low (or nl) PTH, low calcium, hi phosphate
Treatment slow infusion of IV calcium (too fast can cause cardiac probs + burns) oral vitD (if low PTH which means that 1ahydroxylase cannot be activated to make active vitD) recheck calcium levels in 3m (if rise in Ca, suggests transient hypoPTH)
dysfunctional or hypofunctional parathyroid gland usually related to an autoimmune process, infiltrative process (hemochromatosis, Wilson's dz decreased serum PTH (deficienct PTH secretion) copper, aluminum, breast cancer metastasis, granulomatous dz), or magnesium deficiency (chronic alcholism, malnutrition, TPN, diuretics - thiazides, furosemide, familial)
history of neck surgery, thyroidectomy, cervical lymph node dissection
removal of parathyroids from surgery (thyroidectomy), TPN, thyroid ablation w/ radiation
most common cause of hypocalcemia
DiGeorge syndrome (pharyngeal pouch maldevelopment) posteriorly rotated ear, flat nasal bridge, hypertelorism (lots of space btwn eyes), small chin Velocardiofacial syndrome
absence of 3rd & 4th pharyngeal pouches, the embryological origin of parathyroids DiGeorge syndrome - defect in chromosome 22; 95% de novo mutation
agenesis/ dysgenesis of parathyroids; transient (maternal hypercalcemia shuts down baby's PTH), syndromes
digeorge 1:5500 (M=F)
if patient's calcium levels rise after 3m of meds, suggests transient hypoPTH
DiGeorge syndrome abdominal aortic arches, VSDs life threatening after birth; immune dysfxn (abnl thymus development)
candidiasis, hypoparathyroidism, Addison disease
recessive autoimmune regulator gene (AIRE) mutations cause autoimmune polyendocrine syndrome 1
increased serum PTH Type 1a = Pseudohypoparathyroidism (abnl biochem findings) + Albright's hereditary osteodystrophy (AHO) (short stature, obesity, brachymetaphalangia, calcifications, mental retadation)
end organ resistance to PTH (PTH resistance) due to production of abnl PTH molecule that does not properly interact w/ receptor (abnl alpha subunit of G protein - GNAS1 gene)
low Ca, hi phos, hi PTH, nl renal fxn, low 1,25(OH)2vitD, problems w/ other hormones that work through G proteins (TSH, LH, FSH) XR of hands: short metacarpals
Xlinked hypophosphatemic rickets . (renal failure). chondroitin sulfate. low vitD3) low vitD3 PHEX mutation low vitD3.mutation in PHEX prevents FGF-23 degradation. also nl PTH causes kidney excretion of phos). 25. refeeding syndrome) bone pain. pathologic fx increased urinary loss of phosphate (hyperparathyroidism. metaphyseal flaring. & phosphaturia? Check MRI of head/chest/pelvis for tumor (suspect oncogenic osteomalacia). rhabdo) . autoimmunity 1 billion limited worldwide sunlight exposure. phosphate enemas) decreased excretion (usually chronic kidney disease. rickets/ osteomalacia (osteoid does not mineralize --> "soft bone"). thickened wrists from hi bone turnover. T2DM. def in vitD hypophosphatemic rickets. alcohol. rickettic rosary (palpable nodules on ribs) osteomalacia in adults def = vitD < 50 mmol/L insuff = vitD < 75 mmol/L Pathogenesis normal bone development involves mixture of osteoid (nonmineralized component of collagen. vitD dependent rickets I&II. kidney dz (increased vit D deficiency = dec calcium.25(OH)2 vit D OR total 25(OH) vitD2/D3 better indicator bc longer half life low Ca. preventing PTH action) Hyperphosphatemia increased intake (TPN. hypoparathyroidism) excess bone resorption transcellular shift (tumor lysis. resistance to resistance to calcitriol vitD Hypophosphatemia respiratory & cardiac arrest decreased absorption of (lack of ATP) phosphate (vitD def. cancer. nutritional vitD deficiency. excretion of phosphate absorption = poor phos + inability mineralization of bone --> to create active rickets in kids or vitD).bone resorption > bone formation).25-OHase def receptors. low phos (bc vitD increases GI absorption of Ca + phos.Disease Vitamin D deficiency / insufficiency Clinical Variants Defining Characteristics rickets: bowed legs. 1. leukemia) hi PTH hi FGF-23 (low P. DKA. RTAs. low serum phosphate. & osteocalcin) with mineralized component (calcium phosphate) Etiologies Epi Risk factors Lab/Imaging decreased 1. weakness. enlarged epiphyses. could also suggest PHEX mutation preventing FGF-23 degradation (suspect Xlinked hypophosphatemic rickets or autosomal dominant hypophosphatemic rickets) give VitD (increases phosphate & calcium absorption. however. hi alkaline phosphatase. GI dz osteomalacia in adults (dec absorption). CVD. kyphosis. autosomal dominant hypophosphatemic rickets FGF-23 resistant to PHEX degradation) transcellular (respiratory alkalosis. rickets dx REQUIRES radiographic changes XR: cupping/ metaphyseal flaring Treatment Complications bone disease/ inc fx (osteoporosis . oncogenic osteomalacia tumors that make FGF-23.enzymes/ OHase def. inadequate dietary intake.
prolactinomas. LH.bitemporal heminopsia. 6 palsy). young pt w/ potential for cure.. TSH. liver tests. acne. M=F) (CREB. osteoporosis. o/w monitor dopamine agonists (Bromocripitine. hypersecretion of hormones MENI (menin most common mutation).loss of anterior / posterior pit fxn (DI) Nonfunctional no clinical manifestations Corticotroph Cushing's disease microadenoma that secretes (obesity. spread to osteoporosis ICA). papillary config. HTN. fxnal compromise (infertility. no response/ recurrence (16%) tolerance for med tx. neurocytic rosettes around vessels. or ribbon appearance). excess ACTH DM) 20% of pituitary adenomas 15% of pituitary adenomas . galactorrhea). pregnancy test. somatotroph adenomas macroadenomas (usually present w/ mass effect without syndromic effect) >1cm . enlarged nuclei. diplopia (CN3. in adults (40other mutations 50 y. amenorrhea/ hypogonadism.o. Cabergoline) for tx of microadenomas mass effect can interfere w/ secretion of other pituitary hormones prolactin inhibits gonadotropin release & steroid prod in end organs --> amenorrhea or secondary surgery if macroadenoma hypogonadism in w/ critical mass effect men (loss of vision. reduced facial hair in men adenomas that secrete prolactin occur in 20% of patients with MEN1 syndrome 30% of pituitary adenomas increased serum prolactin (usually > 200 ng/mL) & positive immunohistochemistry for prolactin (brown = positive) possible decrease in FSH. loss of glandular structure (sheet effect) like proliferation. excessive growth factor production) macroadenomas are histology: loss of cellular harder to manage (mass heterogeneity. amenorrhea. mass effect. corticotroph adenomas. headache order of hormone disruption: GH--> LH/FSH -> TSH --> ACTH Pathogenesis mass effect macroadenomas grow so large that impinge the optic chiasm.Disease Pituitary adenoma Clinical Variants (general) Defining Characteristics microadenomas (usually secrete hormones) . infertility. stria. if severe necrosis/ hemorrhage think apoplexy! MRI: homogenously contrast enhancing (no cystic components or calcifications) Prolactinoma galactorrhea. 4.<1cm. Gs protein. recurrence surgery . decreased libido. rapid progression. loss of Rb. which supplies the medial aspects of the globe and responsible for lateral portions of visual field (lateral field deficits) evasion of apoptosis -> unlimited replicative potential > growth signal independence -> anti-growth insensitivity -> sustained survival -> adenoma formation Etiologies Epi Risk factors Lab/Imaging Treatment Complications pituitary apoplexy pituitary adenoma infarction from expansion --> severe headache & loss of vision (MED EMERGENCY!! Interferes w/ ACTH secretion) pressure/mass effects. possible hypopituitarism depending on size of prolactinoma R/O secondary causes (kidney. med eval) MRI of pituitary for mass Treatment IF macroadenoma.
wide nasal bridge. TSH. diabetes.Disease Clinical Variants Somatotroph Defining Characteristics Gigantism (if adenoma occurs in childhood before closure of epiphyses) acromegaly (if adenoma occurs AFTER closure of epiphyses) . leading to hormone hypersecretion without presence of obvious tumor Pituitary hyperplasia Craniopharyngioma suprasellar tumor proliferative or neoplastic conversion of cysts in "intermediate lobe" --> ectopic remnants of pharangeal epithelium hemorrhagic mass in suprastellar space that impinges on CNS structures -> calcifications. squamous differentiation somatic cell more mutations in B. recurrence cystic spaces w/ oily risk substance/ cholesterol MRI: cystic components + calcifications deposits Rathke's cleft cysts located within sellar space or extends into suprasellar space single cell layer (simple) cyst hyperplasia of cystic structures of intermediate lobe of pituitary histology: lined by single layer of columnar ciliated epithelium. vasculature. analogs (ocreotide). panhypopituitarism dopamine agonists (if after radiation tx dual prolactin & GH (causes loss of GH. auditory probs.matching to references) OGTT suppression test (hyperglycemia) results in sustained elevation of GH (nl the GH level would be reduced w/ hyperglycemia) impaired glucose intolerance insidious onset . obstructive sleep meds: somatostatin apnea. locally undergo calcification). proportionally enlarged organs. thickened skin/ lips. coarse/ enlarged /spongy hands. radiation for residual dz or ACTH) suboptimal response to surgery & meds Gonadotroph Thyrotroph excess secreted by adenoma could cause precocious puberty 5% of pituitary adenomas 1% of pituitary adenomas overgrowth of cells of one type. everything else is cyst fluid Pituitary carcinoma aggressive lesions that invade soft tissue structure.check pictures of pt from years before Treatment Complications usually macroadenomas acromegaly: requiring debulking surgery . increased malignancy receptor antagonists (Pegvisomant). secretion) then FSH/LH.large feet. furrowed brow). & bony structures <5% of masses . neuropathy Pathogenesis adenoma that secretes excess GH GH over production leads to gigantism or acromegaly. GH colon cancer. most likely due to pituitary adenoma can also have mixed GH & prolactin secreting adenomas (better prognosis than GH adenoma alone) Etiologies Epi 15% of pituitary adenomas Risk factors Lab/Imaging elevated IGF-1 (even after age.common in catenin gene kids (ages 1016) 10% of all pediatric intracranial tumors difficult to resect (due to radiation can cause oily substance secretion & pan hypopituitarism keratin) (lifelong hormone replacement therapy) Histology: usually don't see epithelium in the brain but surgery + radiation proximity to 3rd this has epithelium (from ventricle/ optic nerves/ Rathke's cleft) lined w/ optic chiasm/ basal lamina that create hypothalamus keratinaceous material (wet keratin nodules that large size.1st option! cardiomyopathy. arthritis. invasive.
Oct4 markers. nephrogenic cause if hi serum ADH but NOT responsive to ADH R/O psychogenic polydipsia (hi fluid intake & polyuria). positive for PLAP. amyloidosis. low urine osm & serum osm surgical resection low.no ADH resp. c-kit.5L/d). nl expect hi serum osm to cause inc urine osm) water deprivation test . tumors. hyperosmolarity central causes: loss of posterior pituitary function --> deficiency of ADH nephrogenic causes: end organ resistance to ADH acquired central (neurosurgery. lysosome filled benign tumor cells that PAS positive hi serum osm. grade benign lesions Granular cell tumor suprasellar tumor arises from posterior pituitary gland ADH deficiency Diabetes Insipidus excessive urinary loss of solute-free water excessive thirst/ H2O intake (polydipsia).IF of glial cells) histology: large pink. similar pathologic features as testicle/ovary neoplasms MRI:homogenous & compact suprasellar mass Treatment Complications Pituicytoma suprasellar tumor that resembles glial tumors arise from posterior pituitary (pituicytes) histology: stains positive for GFAP (glial fibular acidic protein . urine osm < serum osm (DILUTE urine bc no ADH & H2O reabs. idiopathic) acquired nephrogenic (hypercalcemia. polyuria (>2. central cause of DI if low serum ADH but responsive to ADH . give ADH. positive lymphocytic infiltrate & granulomatous inflammation. hypokalemia. aquaporin mutation) . hypernatremia. prominent nucleoli. head trauma. infiltrative dz. lithium use.Disease Germinoma Clinical Variants Defining Characteristics suprasellar tumor Pathogenesis Etiologies Epi Risk factors Lab/Imaging histology: clear tumor cells w/ large nuclei.once plasma osm > 295. low urine osm. Sjogrens) Congenital nephrogenic (defective V2R.
velocity. hypotension.Disease ADH excess Clinical Variants Syndrome of Inapprop ADH (SIADH) Defining Characteristics gradual onset of dilutional hyponatremia (mild sx: headaches. pneumo. improve IGF-BP3. genetic syndromes.3. severe sx: AMS. degenerative dz. renal/ adrenal insuff. trauma) drugs. CNS d/o (mass lesions. skeletal dysplasia dads ht)/2 (estimate body proportions). anemia. other (AIDS) Epi Risk factors Lab/Imaging hyponatremia w/ inapp low plasma osm urine osm > plasma osm (would nl expect dilute urine if low plasma osm) exclude secondary causes of hyponatremia (hypovol. meningitis.5) . hypothyroidism) renal sodium excretion > 20 mmols Treatment Complications Short stature (general) analyze growth velocity. death!) Pathogenesis inappropriate (nl/hi) concentration of ADH for low plasma osmolality --> water retention & hypo-osmolality despite euvolemic status Etiologies malignancy (small cell lung para-neoplastic synd. congenital heart disease w/ hi Final ht = MPH +/. delayed bone age idiopathic genetic . osteochondrodysplasia.SLE. adequate/ excessive weight gain. bone age) malnutrition (ask re: 24h dietary intake). nl bone age (-2sd) hormone probs . increased weight: height percentile nl causes: genetic/ familial. GI/ genetics eval?? GH stimulation testing Bone age: XR of LEFT wrist HRT?? & hand (girls: 95% of ht at BA 13. coma.nl growth velocity. systemic illness (chronic renal failure. GC excess) 90% of referrals are normal most common cause for failure to grow?? GC excess (Cushings) blood or urine test: IGF-1 & WAIT . GH def. generalized edema d/o. non-pulm cancers). seizures. counseling. hormone problems (thyroid def. inflam dz .9" output or cyanosis. boys: 95% of ht at BA 14. nausea. subarach hemorrhage. free T4 & TSH caloric delivery.poor linear growth. improper measurement abnl causes: poor weight gain. mech ventilation). final height prediction (mid parental height. hormone const delay . muscle cramps. const delay of growth.most improves w/ time. delayed BA. males: (5"+ moms ht + IBD).nl growth deficiency/resistance. lethargy. females: (moms ht + dads chromosomal aneuploidy ht .5)/2 (Turners syndrome). pulm dz (TB.
somatostatin excess). target (GHreceptors. HESX1). central defects in pituitary hormones (all or optic glioma.Disease Clinical Variants hypothalamic defect Defining Characteristics GHRH deficiency Pathogenesis Etiologies hypothalamus (GHRH def. pituitary (GHRH receptors. transc factors like Pit-1. & optic nerves congenital or acquired .usually knocks GH out first Idiopathic inborn errors of pituitary development . L-DOPA) +GH released w/ direct administration of GHRH (if intact blood supply of anterior pituitary).use age of onset. IGF-1. septum pellucidum. & impairment of visual fields to assess suspect genetic cause if early onset. medical hx. founder effect . no hx of trauma/ radiation. & IGF. GH1 gene to encode GH.treat w/ GH until growth complete.craniopharyngioma.histiocytosis. & IGF-BP3 no GH released following indirect stimulation testing (hypoglycemia.suggest GH insensitivity rather than problem w/ GH Hypopituitarism (general) tumors . associated findings. intact Jak/Stat pathway. PROP1. may need as an BP3 adult also no GH released following indirect stimulation testing no GH released with direct admin of GHRH End organ defect GH receptor mutations (deletion. IGF-1. non-functional) prevents end organs from responding to GH GH receptor mutations? (Laron Syndrome) low IGF-1 levels.incomplete development of hypothalamus. a-2 agonist.physical abuse. HI basal and stimulated GH levels low levels of GHBP (extracellular domain of GH receptor that has broken off) . or GHRP Treatment Complications Pituitary defect GH deficiency low basal GH. imaging. pituitary adenoma trauma . ghrelin.septic optic dysplasia (SOD) . intact IGF-1 and IGFBP3 response systems) possible craniopharyngioma Epi Risk factors Lab/Imaging GHRH def = low basal GH. MVA partial) (usually posterior & anterior defects bc severed neural stalk) inflammation . distinct growth & hormone phenotypes. hypophysitis cranial radiation .
PROP 1 promotes development of lineage cell PROP1 mutations . ovarian cysts. severe hypothyroidism Precocious puberty (general) signs of clinical puberty (breast/ testicular development and/or pubic hair) increased sex steroids central or non-central (see below) causes of early menarche (vaginal bleeding) w/o other signs of puberty?? FOREIGN BODY. McCune Albright caloric intake (excess adipose) early maternal menarche. FEMALES evaluate girls/boys showing clinical pub before 7y(white) or 6y (black) / 9.enlarged testes bc stimulation w/ FSH/LH) GnRH agonist (lupron) advanced bone age early but finish treat underlying problem growing so end up (eliminate exposure to being smaller than agents.inhibits androgen synthesis Central gonadotropin . injury/ head trauma Early exposure to sex steroids (inc bone age w/ estrogen or testosterone) . LHX3 & LHX4 involves loss of less hormones. cerebral malformation. surgery for tumor/ expected cysts. HESX1 a/w SOD.think non-central cause if small (if central .early & extreme growth retardation. Growth velocity? Growth chart? Significant weight gain? (more chol = more androgens) Check neuro/ fundoscopic exam. Check estrogen / testosterone.5y respectively Check urinary/GI tract if bleeding. 45% males) CNS abnormality hypothalamic/ pituitary mass. check testes size . estrogenic chemicals. low birth weight. trauma. abnl rosy cheeks. check for physical signs of puberty If child has muscle development.dependent (inc FSH & LH.AR mutation involved in pituitary development multiple sibling involvement SHH .expect w/ normal parents holoprosencephaly. international adoption. inc testosterone or estradiol) idiopathic (>90% females. treat hormone abnl like CAH/ hypothyroidism) ketoconazole . inc weight gain (obesity) in childhood.Disease Clinical Variants MPHD Defining Characteristics Multiple pituitary hormone deficiency Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications consider transcription factors genetic . absence of father in household. PIT1 & PROP1 (PROP1 is spont puberty necessary for appearance of Pit1. Pit1 mutations .no precursors in anterior pituitary) pubertal stage.
independent (decreased FSH/LH.-> secretion of estradiol/ stimulatory G testosterone--> precocious au-lait skin findings. SERM (tamoxifen .blocks estrogen receptor) however. adrenal tumor (muscle development + small testes) exogenous exposure to sex steroids Tumor . café. once brain senses that bone age is appropriate. protein (Gsa) puberty hyperostosis fibrous dysplasia Excess estrogen exposure = increased growth velocity & marked advancement in skeletal maturity ovary will be hyperfunctional for some time but then involutes.ovarian cysts (Granulosa cell / androgen producing). tx is controversial as this d/o usually does not progress Van WykGrumbach Syndrome only condition w/ precocious puberty w/o bone age advancement (growth arrest)!! Primary hypothyroid + precocious non-central puberty dec T4 = inc TRH = inc TSH & Prolactin TSH shares alpha subunit w/ FSH so FSH also increases = increased estradiol in ovary . Leydig cell tumors in testicle. see below). pulsatile GnRH & LH/FSH secretion will begin.CAH. increased testosterone or estradiol) autonomous gonadal activation. hCG producing tumors in liver van Wyk-Grumbach syndrome (see below) Etiologies Epi Risk factors Lab/Imaging Treatment Complications McCuneAlbright Syndrome early non-central puberty + activating mutation in GNAS mutation in the gene that hyperthyroidism causes ovary/testicle to codes for the develop independently of TRIAD: non-central stimulation by gonadotropins .Disease Clinical Variants Non-central Defining Characteristics Pathogenesis gonadotropin . activating mutation of LH receptor gene adrenal d/o . normalizing puberty XR: smoked out appearance on XR of femur aromatase inhibitors (dec estrogen).McCune-Albright Syndrome (GNAS activating.alpha subunit of the precocious puberty.
acne.premature death add androgens when (related to CVD. gonadotropins. or aromatase inhibitors for anovulation live birth rate better w/ clomid + met or clomid alone (NOT met alone) increased risk of endometrial cancer (unopposed estrogen). horseshoe kidney. non-pitting edema (sign of lymph prob) Pelvic XR . pulm edema AFTER ductus closes). infertility Clinical clues? Pterygium colli (abnl ear). appropriate for puberty coarct). aortic dissection. hi LH/FSH ratio . no p short arm. etc sensorineural deafness. oligoanovulation. acral lymphedema (nail dysplasia. hi arched palate.maldeveloped head of femur. polycystic ovaries on U/S.Disease Turner Syndrome Clinical Variants Defining Characteristics Short stature. infertility. duplicated UT Treatment short stature . infertility.1:2500 live female births disjunction structural chrom abnl (isochromosome = 2q's .DISLOCATED HIP ECHO . strabismus (cross eyed) secondary amenorrhea. T1DM. probs w/ social intxns & visual/ spatial defects Y chrom mosaics . CVD. PCOS appearing ovaries on U/S (>12 cysts. non-pitting edema hi arched palate --> feeding/ speech problems. cystic hygroma (fluid filled mass prenatal U/S). hypogonadism.hyperinsulinemia might potentiate LH response to produce hyperandrogenemia 6-10% prevalence accounts for ~75% anovulatory infertility FH DX OF EXCLUSION: supportive data? Hyperandrogenism. hyperlipidemia. ENT. hirsutism/acne. premature ovarian failure . 2-9 mm) acanthosis nigricans Pathogenesis phenotype that occurs in patients w/ one normal X chromosome & complete/ partial absence of the other X chromosome = 45X OR 46X. progressive endocrinology. anxiety. osteoporosis. displaced from foramen . congenital hip dislocation. cervical hypoplasia. aorta coarctation (HTN. IR/DM.SHOX (pseudoautosomal region) deficiency --> skeletal abnl & short stature Etiologies Epi Risk factors Lab/Imaging amniocentesis: abnl chromosomes karyotype: One X chromosome with absent 46th chromosome PE: signs of coarct & HF (crackles.horsehoe kidney. obstetric risks.long arms. displaced apical impulse. any evidence of hyperandrogenism (clinical hirsutism.bicuspid aortic valve Renal/pelvic U/S .inc risk for gonadoblastomas --> dysgerminoma require ovary removal!! weight loss & exercise for insulin resistance & hirsutism (can also use OCPs) metformin for hyperinsulinemia & possible improved response to clomid ovarian wedge resection for hyperandrogenemia clomiphene. infertility Polycystic ovary syndrome (PCOS) androgens cause early follicular arrest & atresia --> oliganovulation. biochem findings). puffy feet). hepatomegaly. sensorineural deafness. DM. primary amenorrhea.o. insulin resistance Diagnosis REQUIRES 2 of 3 criteria: oligomenorrhea. obesity. structurally abnl X OR mosaics lymphatics drainage prob --> cystic hygroma. Madelung deformity. & cysts on ovaries androgens provoke accelerated GnRH pulsatility. cardiomegaly.GH replacement Complications paternal non. hypothyroidism. ovarian multi-disciplinary failure/ dysgenesis interactions w/ cardio. T2DM. psych. CHF. obesity. dental crowding gene dosage effect . early systolic click). depression. ring chromosome) most common recognizable cause of spont Ab median age of dx? 15 y. causing enhanced release of LH and subsequent production of more ovarian androgens insulin resistance might also be underlying mechanism for PCOS . shield chest.
programmed shedding of polymenorrhea ..o. NSAIDs. GnRH agonists (preop pts). postmenopausal. D&C (hemodynamically unstable) Ovulatory bleeding: NSAIDs (dec prostaglandin). C corpus luteum) intervals < 24d (coagulopathy menorrhagia . heparin. estrogen tx (only if hemorrhaging w/ low hematocrit).normal ). O (ovulat intervals but excessive flow absent menstrual flow during pill dysfxn).think or duration (endometrial).Disease Abnormal uterine bleeding (AUB) Clinical Variants (general) Defining Characteristics any disruption from normal cycle (24-35d x 46d. PCOS Malignancy postmenopausal bleeding endometrial cancer . tx symptomatic intrauterine pathology) Menstrual diaries Treatment Anovulatory bleeding: progesterone (oral tx. prolonged anovulation) transvaginal U/S (hi risk for cancer/ hyperplasia if endometrial stripe > 5 mm) hysteroscopy (dx.irregular I (Iatrogenic). herbals . OCPs. thrombocytopenia) TSH (hypo/hyperthyroidism a/w AUB) cervical cancer screening chlamydia (hi risk patients) screening for bleeding d/o (adolescents) endometrial bx (>40 y. thecoma) von Willebrand factor. bleeding (use short interval of intervals. Mirena IUD) . Mirena IUD. increased tissue plasminogen activator (TPA) activity. normal flow or M (Mullerian estrogen) duration anomalies) menometrorrhagia irregular intervals.gingko. motherwort) Coagulopathy 20% w/ heavy menstrual bleeding have underlying bleeding d/o CBC/platelets prothrombin time partial thromboplastin time Ovulatory dysfunction nl H/P/O axis.induces regular bleeding & prevents endomet hyperplasia (opposes estrogen). E free week of OCP . hysterectomy Complications PALM-COEIM P (polyp). making the uterus globular benign tumor from the smooth muscle of the uterus myometrium diagnosed with pathology only! most common lesion causing AUB in reproductive aged women obese. antifibrinolytics (tranexamic acid) surgery: endometrial ablation. progesterone breakthrough metrorrhagia .bleeding most likely due to atrophy . combined OCPs.cycle more regular due to intervals > 35 days (malignancy. hyperplasia PCOS Endocrinopathy Endometrial usually PCOS .cycle hyperplasia). anovulatory?? Ask ). ginseng. elderly. can be hyperplastic in menopausal women endometrial glands that grow into the myometrium (muscle) of the uterus. 30 ml blood loss) Pathogenesis structural or functional abnormality?? Etiologies Epi 2nd most common reason for OB/GYN visits most common cause of adolescent hospital admissions Risk factors perimenopause Lab/Imaging Pregnancy test!!! CBC (R/O anemia. increased local fibrinolytic activity bleeding due to unopposed estrogen endometritis. nl steroid hormones local abnl prostaglandin synthesis. ristocetin often in adolescents or patients with chronic AUB cofactor certain meds (warfarin. A (adenomyosis Ovulatory v. L (leioabout timing (ovulatory bleeding myomas) M oligomenorrhea . can cause intermenstrual spotting. excessive flow or duration Polyps intermenstrual spotting Adenomyosis painful periods Leiomyomas (fibroids) primarily benign but can convert to tumor (rare) submucosal fibroids (in uterus) have severe bleeding benign growths.must R/O endometrial cancer ovarian neoplasms often functional tumors (granulosa cell.
000). antihypertensives). & LD & away from kidneys). impaired liver function.000 . give fetal risks: IUGR. assessment for maternal sequelae. antito brain/heart/adrenals hypertensives. seizures). considered chronic HTN (diagnosed post-hoc) Gestational HTN hi BP >20 weeks gestational age BP > 140/90. diastolic > 90 predating pregnancy or identified before 20 weeks gestation if PNC began at > 20 weeks and she has HTN > 12 weeks postpartum. renal failure. and delivery cause of maternal mortality . Preeclampsia hi BP > 20 weeks AND PROTEINURIA BP > 140/90. fetal growth restriction maternal starts w/ up & down BP. bedrest for 48h before placental delivering infarct/abruption. if left untreated. low platelets improper trophoblast implantation --> immunologic response Eclampsia mild or severe preeclampsia PLUS SEIZURES!!! HELLP: liver hematomas.think MOLAR ectopic pregnancy. chronic HTN. endometritis. elevated liver enzymes. oligohydramnios antenatal (decreased amniotic corticosteroids & stabilize w/ MgSO4 (anti. trauma implantation bleeding 1-2d following missed menses (often mistaken as menses) Etiologies Epi Risk factors Lab/Imaging Treatment Complications Iatrogenic Pregnancy bleeding bleeding + PAIN .think ECTOPIC!! snowstorm pattern on U/S molar pregnancy gestational sac seen outside of the uterus ectopic pregnancy Uterus S>D.Disease Clinical Defining Characteristics Pathogenesis Variants Inflammatory bleeding without relation vulvitis. occuring after 20 weeks without proteinuria mosy common med comp of pregnancy 6-8% of all live births 17. inc TbxA2) --> primary DIC] severe pre-eclampsia sx: oliguria of 500mL in 24h. 6 h apart while on bedrest OR proteinuria of >5g/24h OR proteinuria of >3g in 2 random urines >4h apart) vasoconstriction/ vasospasm [circul vasoconstrictors + endog vasoconstrictors -> endothelial damage (dec prostacyclin. thrombocytopenia (platelets < 100. DIC If <32 weeks. hepatic failure. cervicitis. coital lacerations. cerebral/ visual disturbance.S. quant b-hCG > 100. prematurity consequences. vaginitis.6% of maternal deaths in U. DM hx of HTN in pregnancy minority groups DELIVERY!! HELLP syndrome (>24wks): hemolysis. DIC. or <20 weeks gestational age systolic > 140. death stabilization (MgSO4.fluid = dec urine output from blood flow shunt seizures). pulmonary edema or cyanosis. molar pregnancy pregnancy! 20-25% of women spot/ bleed during 1st trimester Hypertension during pregnancy Chronic HTN hi BP before pregnancy. salpingitis. perinatal death maternal risks: CNS problems (stroke. C/S. epigastric or RUQ pain. extremes of age progresses to >140/90. then proteinuria followed by 1st child signs & sx of severe preeclampsia. uteroplacental insufficiency. occuring after 20 requires weeks gestation with placenta!! proteinuria (> 300 mg/24h collection) severe: 1+ of following criteria (BP>160/110 >2x. will progress to eclampsia vascular disease. PID to menses a/w signs of infections foreign bodies (children).
HTN. endometriosis Type & Cross .Rhogam Rh. maternal hemorrhage shock. Ampullary end of Fallopian diffuse tenderness. if tissue remains (missed) D&C or medical tx heavy bleeding? D&C Ectopic pregnancy pregnancy/ implantation of Chlamydia gestational sac OUTSIDE of the replicates uterus intracell & Bleeding + pain!! lyses cells Adnexal mass + tenderness interstitial tubal pregnancy most dangerous bc least rupture?? Unstable vitals. U/S NOT helpful. tube and abdomen most bleeding (low HCT) conducive to embryonic development 1st trimester bleeding 1-2% prevalence prior ectopic.Unstable? Send directly to OR Transvaginal U/S Certain ectopic? endometrial stripe w/ no Methotrexate (1st line!). intraventricular Deliver if unstable (vag hemorrhage.ruptured ectopic Arias-Stella reaction hyperplastic endometrial cells. manage fetal hypoxia (cerebral palsy.Disease Clinical Defining Characteristics Variants Atypical pre. distensible! positive pregnancy test.monosomy X0 or trisomy 16 50% of 1st trimester bleeding Type & Cross . DIC (abruption) . surgery. gest sac in fallopian tube/ outside uterus surgery Blood in belly .uterus is empty and hCG levels drop off following day aneuploidy . stable? Expectantly fetal anemia.some tissue still present Complete . EXAM!!) multiparity. dx is smoking/ clinical (NO CERVICAL cocaine. small headache.os is wide open.Rhogam if Rh- usually no intervention is required. or C/S) blindness). Fetal prematurity IV access/ fluids/ type & (Resp distress cross syndrome. gestational sac. PID.vague RUQ or epigastric eclampsia discomfort. general sick appearance Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Spontaneous abortion 1st trimester bleeding Threatened Inevitable . stroma with decidua but no chorionic villi / placenta= pregnancy but outside of uterus gross: decidual cast partially necrotic membranous tissue expelled from vagina 10% mortality w/ rupture INFERTILITY chronic pain Placental abruption 3rd trimester bleeding AND PAIN!!! 10% have no bleeding (blood could be retained behind the placenta) increased uterine contractions separation of placenta from uterus 15% of 3rd trim bleeding 1:120 deliveries trauma. prior abruption. AMA immediate hospitalization. lots of blood missed/incomplete . incidental thrombocytopenia new swelling of legs. seizures). however. enterocolitis.
maximal tumor reduction. increased CA-125. and suspicious U/S --> SURGERY (exploratory surgery. maternal hemorrhage IV access/ fluids/ type & shock. post-menopausal bleeding. seizures). useful if hi clinical suspicion) + transvaginal U/S to assess pelvis (best in peri & postmenopausal women) palpable mass on pelvic exam If mass on PE. North American/ North European descent. pelvic pressure.(twins. abnl bleeding.TAH endometrial biopsy perform if abnl bleeding + >4mm endometrial thickness on U/S.5% of births previa. Disease Placenta previa Clinical Variants Defining Characteristics 3rd trimester bleeding PAINLESS bleeding Pathogenesis placenta covers the internal cervical os Etiologies Epi 10% of 3rd trim bleeding Risk factors Lab/Imaging Treatment Complications fetal hypoxia (cerebral palsy.S. asymptomatic mass most are spontaneous cases. change in bleeding pattern in women on HRT or perimenopausal . back pain. multiparity. nulliparity. postmenopausal bleeding. dyspepsia. prior history retained placental frags: prior C/S.fetal anemia. leucorrhea (thick smoking (gross) white discharge). cross C/S delivery if unstable or term Stable & pre-term? expectantly manage. protective factors? OCP. urinary frequency. prior U/S 0. prior D&C.prolonged labor. accreta evaluate uterine fundus bogginess? Inspect for lacerations if uterus is firm feeling evaluate the placenta & explore uterus IV access/fluids/ type & cross immediately atony? Pitocin-like oxytocin. hemorrhage prolonged use of induction agents. placental episiotomy. so events that decrease # cycles protective] estrogen sensitive neoplasm unopposed estrogenic stimulation of endometrium increased estrogen synthesis (obesity. prior NO CERVICAL EXAM!!! C/S. fragments or rapid labor coagulation disorders uterine atony: hi parity.selective endometrioid type . retained compound presentation. most common macrosomia). OCP use. AMA immediate hospitalization. more common in older women) Endometrial cancer abdominal discomfort & distention (usually advanced stage). granulosa cell tumors) decreased estrogen metabolism (hepatic dz) inapprop HRT (estrogen only) Leading cause of death for gyn malig 1/70 women FH of ovarian cancer. PMH of breast/ colon/ uterine cancer CA-125 (low specificity. tamoxifen (breast cancer pain/pressure chemoagent) . cause of post. abnl bleeding + tamoxifen use. smoking.most estrogen receptor that has common histology type and antagonistic effect on breast BUT agonist effect on CURATIVE! endometrium age > 60 obesity unopposed estrogen chronic anovulation (PCOS) tamoxifen use endometrial hyperplasia (atypical complex) surgery . eventual C/S DIC (abruption) Postpartum hemorrhage blood loss with delivery most loss after separation of placenta. weight loss. hereditary although 5-10% have hereditary breast & component ovarian cancer (BRCA1) unknown etiology protective factors? Multiparity. prostaglandins Ovarian cancer Germ cell & stromal cell (more common in younger women) epithelial (most aggressive form. control the contraction (involution) of uterus & coagulation/ thrombus formation noncontracting uterus (UTERINE ATONY) 5% of deliveries uterine atony = lack of involution or contraction down genital tract laceration genital tract lacerations caused by large baby. overdistention uterine atony . breast feeding [increased risk of ovarian cancer a/w increased ovulatory cycles. biopsies) + postoperative treatment w/ IV chemotherapy or clinical trials no screening test so patients present at later stage (Stage III) -> higher mortality primarily affecting peri/postmenopausal women most common gyn malignancy in U. operative delivery. chorioamnionitis. partum rapid labor. uterine curretage. advanced age.
IV: chemo+radiation Complications stage I . & surgery improve 5y survival malignant tumor embryonal carcinoma polyembryoma Choriocarcinoma histology: embryoid body markedly hemorrhagic produces hCG!! +pregnancy test in men! arise from trophoblasts gestational: arise from placenta & products of conception non-gestational: arise from germ cell tumor gross: marked hemorrhage gestational: methotrexate sensitive.cervix Stage II . DVT. lymph node involvement = worse prognosis surgical comps? ureteral injury. globules with alpha-feto protein AFP . treated malignant but good conservatively (R/O mixed prognosis germ cell tumor!!) Endodermal sinus (yolk sac) tumor young women gross: solid tumor w/ multiple areas of necrosis histology: Schiller Duval body (central vessel surrounded by tumor cells).Clinical Variants Cervical cancer Squamous (80-90%) adenocarcinoma (10-20%) small cell & sarcomas (worst prognosis) Disease Defining Characteristics abnl bleeding. fistulae. dysuria advanced stages Pathogenesis Etiologies HPV 16 & 18 Epi globally.hi but decrease postsurgery (unless some tumor remaining) combo of chemo. most common gyn malignancy (lower in U.analyze kidney partners.S. discharge POST-COITAL BLEEDING back/ flank pain. better histology: prognosis syncytiotrophoblasts that stain brown for hCG non-gestational: NOT responsive to monitor w/ hCG methotrexate. persistent HPV/ HIV infection Germ cell Ovarian Dys.screen for to screening) dysplasia young age at 1st Colposcopy sexual exposure (duration of Biopsy HPV) CXR . often a/w pregnancy gross: solid.dysplastic germ cells tumors of ovary germinoma (similar to testicular seminoma) usually NO hormone production unilateral germ cell tumor young women. bladder/ rectal dysfxn. radiation. bc screening) 3rd most common gyn malignancy Risk factors Lab/Imaging Treatment Stage I-II A: radical surgery/ hysterectomy + additional cervical tissue Stage IIB . high risk male partner. no necrosis histology: large nucleus & nucleoli.R/O lung metastasis multiple sexual IVP . hematuria.lower vag each stage has A (vertical progression) and B (lateral progression) larger masses. bleeding low SES (access Pap smears . lobulated/ septated tumor. function cigarette smoking. lobular appearance radiosensitive. yellow. more invasive/ vascularized.upper vag Stage III . worse prognosis .
filled w/ yellow solidified sebum (nl in skin). or both solid .malignant immature teratomas are arrested in embryonic development .Disease Ovarian Teratoma Clinical Variants (general) Defining Characteristics benign teratomas? Brain & choroid plexus (nonfunctioning) sacrococcygeal teratoma sacral growth in newborns Pathogenesis germ cell tumors that make somatic tissue Etiologies Epi Risk factors Lab/Imaging gross: .multiple glial nodules? Benign teratoma (brain) Treatment Complications torsion of cystic teratoma (acute abd pain resulting form vasculature strangulation --> teratoma hemorrhagic infarction) teratomas w/ teeth at risk for rupture Immature solid. resembles brain tissue in newborns) postmenopausal teratoma SCC Mature solid or cystic (dermoid cyst or dermoid cyst w/ malignant transformation postmenopausal women) struma ovarii: benign but functioning thyroid in a teratoma monodermal struma ovarii carcinoid (serotonin-like substances) struma ovarii: looks like thyroid tissue but also has carcinoid appearance ovarian carcinoid in a teratoma? Monotonous w/o necrosis gross: soft.hemorrhagic & necrotic histology: neuroepithelial rosettes (immature brain glial tissue.hemorrhage w/ hair.BAD!! gross: solid . menometrorrhagia (irregular. yellow. benign ovarian fibroma) . nodular tumor hysterectomy!! that is solid. some have teeth at risk for rupture . pleural effusion. cystic. excessive periods) in reproductive aged women. check intestines for metastasis Ovarian Granulosa cell tumor (GCT) initially benign but usually produces estrogens (rarely androgens) FEMINIZATION estrogen can cause AUB in post-menopausal women. etc? think teratoma infarction . early puberty in young women malignancy shown by recurrence > 15 years later a/w uterine endometrioid carcinoma (unopposed estrogen) Ovarian Theca cell tumor MOSTLY benign! Usually produces estrogens gross: solid yellow mass WITHOUT necrosis! Histology: benign spindle shaped cells (Theca cells) that stain red for fat (steroid production) gross: solid. & hemorrhagic histology: Exner bodies (small acinar arrangement w/ tumor cells surrounding gland) check opposite ovary if similar appearance.cystic teratoma . white firm mass histology: benign spindle shaped cells CXR: ipsilateral hydrothorax Ovarian fibroma usually benign but can produce Meigs syndrome (ascites.
Disease Sertoli. choriocarcinoma) Sex cord Sertolistromal tumors Leydig cell of testes tumors usually benign. no spermatogonia (no fried eggs) gross: tumors of the testis w/ cartilage.Leydig cell tumor of ovary Clinical Variants Defining Characteristics benign masculinizing tumor --> clitormegaly.95% radical inguinal cure rate orchiectomy. Leydig cells). hemorrhage if mixed w/ embryonal carcinoma Teratoma composed of tissue components resembling normal or immature organ tissue can be associated w/ embryonal carcinoma or other components (yolk sac. resembles spermatogonium 5% of contralateral testes of men who had orchiectomy for germ cell neoplasm cryptorchidism. often hormonally active (may produce androgens & estrogens) Leydig cells --> testosterone (precocious puberty) Leydig cell or Sertoli cell tumors --> gynecomastia in adults 5% of testicular neoplasms 90% are benign! . histology: enlarged nuclei prior germ cell neoplasm (contralaterally) 50% of men who develop ITGCN will develop invasive germ cell tumors w/I 5y Seminoma DO NOT BIOPSY!!! Risk spreading germ cell tumor embryonal carcinoma composed of primitive undifferentiated epithelia best prognosis . & hemorrhage respond to orchiectomy + post-surgery chemo histology: epithelial cells. followed by radiation to histology: fried egg cells like abdominal LNs spermatogonia gross: varigated appearance NOT radiosensitive. hirsutism Pathogenesis Etiologies Epi Risk factors Lab/Imaging histology large columnar cells (Sertoli cells. Leydig cells have Reinke crystals (androgen producing) CXR: check for mediastinal masses in Klinefelters pts hCG & alpha-feto protein are markers for spread of germ cell or recurrence following orchidectomy Treatment Complications Germ cell tumors of testes (general) testicular mass but may also arise in anterior mediastinum germ cell tumors that present in chromosome prepubertal males may be 12 abnl benign (mature teratomas) or low grade malignant (yolk sac tumors) adult germ cell tumors = MALIGNANT! 90% of testicular neoplasms 15-34 year old males Caucasians cryptorchidism familial clustering testicular dysgenesis (Klinefelters) radical orchidectomy + chemo/radiation MALIGNANT in adults Intratubular germ cell neoplasia (ITGCN) preinvasive form of germ cell immediate precursor tumors lesion for all types of germ cell tumors of testis found as focal lesion in 2% of cryptorchid testis & biopsies performed for infertility testing asymptomatic. sometimes pain/ discomfort most common pure type.
blood proliferative lesion gross: pale. Bowen disease -gray or erythematous plaque. +/.HPV related precursor lesion hygiene in uncircumcised (rarely progresses) men. risk of HPV 16&18 invasion 10% other HPV histology: loss of polarity.S. America Risk factors Lab/Imaging Treatment Complications uncircumcised males > precursor lesion? Carcinoma in HPV age 40 w/ poor hygiene & situ = Bowen disease = solitary chronic penile infections gray or erythematous plaque related to HPV 16 phimosis . moist papilloma from collecting duct histology: nodule that projects into the duct w/ proteinaceous secretions (pink lines). gritty bilateral nipple discharge secretions NO PAIN histology: dilation / stretch of duct w/ dried out secretions No predisposition to carcinoma! Papilloma unilateral. metastasis may occur at inguinal & iliac LNs but widespread dissemination uncommon poor genital Bowenoid papulosis .Disease Squamous cell carcinoma of penis Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi <1% of male cancers in U. weakened duct tissue Duct ectasia sagging of the breast dilation of duct due to dried out non-bloody. KERATIN PEARLS Carcinoma of scrotum Periductal mastitis topical exposure to coal tars/ soot inflammatory. disorganized growth that occupies full thickness of epithelium (rather than more abundant cytoplasm at top like nl). locally invasive lesion. genital warts mitotic figures. overlapping nuclei usually good prognosis bc bloody discharge is alarming enough to seek help . non-milky nipple discharge from 1 duct orifice. S. Africa. epithelial lining WITHOUT myoepithelial layer. bloody nipple discharge clonal lesion (no myoepithelial cells) with vascular supply ~ 60 years old histology: fibrovascular core. blood supply present (fibrovascular core).inability to Bowenoid papulosis . epithelial + myoepithelial layers present small risk of carcinoma development Papillary carcinoma unilateral.rare retract prepuce/foreskin progression to SCC SCC = slow growing. More common in Asia. benign lesion in large ducts of breast development of inflammatory cells in the periductal area of breast middle aged older women histology: inflammatory cell infiltration.
Disease Cysts (breasts) Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi VERY common! Risk factors reproductive aged women Lab/Imaging gross: dark orange structures (cysts) that are firm & tender.benign!) needle core biopsy: sharp demarcation of lesion w/ characteristic feature of enlarged duct. TDLUs do not dry out btwn pregnancies so always a baseline secretion that increases in luteal phase of cycle --> increased pressure and secretion build up --> cyst formation Fibroadenoma BENIGN solid mass that is movable within the breast tissue non-proliferative lesions arising from terminal ductule units arise in TDLUs in response to hormones --> hypertrophy of lobules (stroma. expansion and interconnection of TDLUs. cysts change monthly w/ each cycle. apocrine cells + calcifications . oval. increased number of cells WITHOUT MUTATION!! > age 40 women age 3040 histology: very cellular stroma that grows in leaflike pattern usually picked up on mammogram due to calcification formation MUST BE TOTALLY EXCISED usually does not require routine f/u . ductules. bumpy stroma from collagen response to hormones histology: pink secretions seen in TDLUs. ducts) --> fibroadenoma formation teenagers African Americans histology: sometimes large calcifications (sclerosis w/ age . narrowed spaces) but no pattern of identical mutations mammogram: calcifications in the lobule unit spaces very low probability of becoming malignant! Benign lesion w/ minimal risk of malignancy .benign findings Treatment aspiration if extremely painful Complications recurrence non-proliferative lesions arising dense firm breasts w/ from terminal ductule units palpable (sometimes tender) lumps & frequent exaggerated response of breast gross cysts stroma & epithelium to cycling of hormones during reproductive years hormones make TDLUs more edematous. ductules. however. swell during luteal phase of cycle. & stroma Phyllodes tumor Adenosis more cellular lesion in women after age 40 lumpy breasts due to cyclical hormone changes Benign sclerotic collagenous material causes FIRM breasts non-proliferative lesions arising from terminal ductule units proliferative lesions arising in TDLUs adenosis = increase in lobular units proliferative lesions arising in TDLUs proliferative lesions arising in TDLUs.no RR of malignancy development absolutely recurrent so excision required! Sclerosing adenosis Usual hyperplasia histology: proliferation of both epithelial & myoepithelial cells into the lumen (creates bridges). phenotypic mixture of cells (linear.
lobular Defining Characteristics Pathogenesis Etiologies deletions in chromosomes 16 &17 --> "Roman bridge" structure Epi Risk factors Lab/Imaging Treatment Complications increased risk for DCIS or invasive carcinoma proliferative lesions arising in non-obligate precursor TDLUs. round/ punched out spaces (Arches of Roman Bridge!). fast growth --> disintegration of nuclei. calcifications in lumen of spaces Complete excision + histology: monoclonal radiation population of low grade. DCIS cells perforating the epithelial layer AVOID corticosteroids may or may not be invasive . calcium phosphate crystals (stain purple). no myoepithelial layer! invasion present? small patches of monoclonal cells lacking myoepithelial layer outside of the main DCIS lesion mammogram: atypical pattern of calcifications (jagged + small round calcifications) Ductal Carcinoma In Situ (DCIS) Low grade deletions in chromosomes 16 &17 --> "Roman bridge" structure very hi risk for development into invasive ductal carcinoma (if not excised adequately w/ clean margins) High grade usually ER/PR negative & HER2/neu amplification mutation positive non-motile mass on breast exam NOT related to ADH HER2/neu amplification mutations in duct epithelial -> high grade DCIS histology: no punched out spaces like low grade. dilated blood vessels (hence. usual hyperplasia + clonal lesions like Roman bridges! SMALLER than DCIS.Disease Atypical hyperplasia (ADH) Clinical Variants (general) ductal. positive stain for HER2/neu overamplification mammogram: calcifications that form mold/cast in duct (linear calcifications) gross: linear pattern. consistent mutations lesion for DCIS (some capable of progressing into in certain chromosomes DCIS) begins w/ proliferation (usual hyperplasia) --> deletions in chromosome 16 & 17 --> atypical hyperplasia non-motile mass on breast exam atypical hyperplasia + persistent mutations --> low grade DCIS excision of lesion w/ histology: has some needle core biopsy cytologic features of low grade DCIS.mutated cells. necrotic material in the duct (yellow) do NOT respond well to estrogen antagonists like tamoxifen respond to chemo like Herceptin (Trastuzumab) hi risk of invasion!!! Recurrence w/I 3y if not adequately excised Paget's disease of the nipple UNILATERAL red/ scaly/ erosive nipple appear moist DCIS in the ductal system leading to the nipple histology: DCIS riding towards nipple in the duct. redness). necrotic material in lumen (pink material representing disintegrating nuclei) = comedo necrosis. scaly appearing surface.
Disease Infiltrating ductal carcinoma.difficult to detect! Gross: looks like fatty fibrous breast but can't see lesion histology: tumor cells arranged in linear fashion or concentric circles (bull's eye) responds to tamoxifen!! bilateral risk!!! (if lesion in one breast. positive HER2/neu amplification non-motile mass progression of high grade DCIS to poorly differentiated lesions like infiltrating ductal carcinoma grade 3 determined by differentiation (gland formation). mitotic figures Atypical lobular hyperplasia (ALH) Lobular carcinoma in situ (LCIS) precursor lesion to LCIS! histology: ductule spaces full of round cells non-calcifying lesion so hard to find!! progresses from ALH precursor!! ALL LACK E-CADHERIN = poorly cohesive!! deletion of gene for Ecadherin adhesion molecules mammogram: no calcifications histology: proliferation of round cells within the lobule (bag of marbles) Infiltrating lobular carcinoma diffuse spread within the progression from LCIS breast (lack of E-cadherin) no masses or calcifications (i. small round mass ER/PR negative. necrotic cells. grade 1 over time due to digestion of basement membrane and acquisition of vascular supply Etiologies Epi Risk factors Lab/Imaging Treatment Complications potential to invade lymphatic spaces! gross: firm. Clinical Variants Low grade Defining Characteristics receptors for estrogen & progesterone non-motile mass Pathogenesis low grade DCIS--> infiltrating ductal carcinoma. nuclear anaplasia.5 cm carcinoma…) low grade bc ER/PR positive and HER2/neu negative!! Induration might be felt on breast exam 10% of invasive breast carcinomas mammogram: no calcifications . and mitotic figures histology: poor gland formation. low grade nuclei. gland formation invasive into stroma High grade not estrogen/ progesterone responsive (ER/PR negative). fibrotic (lots of collagen! byproduct of vascularization).e. woman w/ consistent mammograms suddenly has a 2. immobile mass suppressed by antiw/ irregular spiculations estrogen drugs (tamoxifen) mammogram: spiculations (stars) @ periphery histology: infiltrating pattern w/ remnants of DCIS. check same spot on the other brest w/ biopsy!) Medullary carcinoma firm. HER2 negative or positive round infiltrating ductal carcinomas commonly seen in patients w/ BRCA1 or BRCA2 mutations BRCA1/2 2-3% of infiltrating ductal carcinomas histology: rounded carcinomas w/ lymphocytic infiltration! pretty good prognosis but confused for fibroadenoma often! .
alcohol. increase bone density. before age 45. ER/PR stattus. greater number of radiation to primary site + axillary nodes = lymphatics. vasular supply related to the number of uninterrupted menstrual periods (hence more estrogen exposure) pregnancy is protective in the long-run estrogen exposure (endogenous or exogenous) hi risk mutations (BRCA1. TP53) #1 cancer among U.Disease Mucinous (colloid) carcinoma Clinical Variants Defining Characteristics rounded periphery lesions that also resemble fibroadenomas (BUT fibroadenomas appear at younger age usually & would have been noticed in earlier mammograms) ER/PR positive Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications good prognosis if properly diagnosed!! women ages 55. a/w increased risk for thromboembolic events Breast cancer (general) see above for deets BRCA1/2 mutations . cramping lower abd pain (radiates to the back & legs). neurological symptoms.underlying pelvic pathology (endometriosis. lymph node status (axillary lymph nodes first!!) mortality early menarche. Asian tamoxifen & raloxifene reduces breast cancer risk by 50%. consideration worst prognosis of systemic tx presence of axillary partial mastectomy w/ or other LNs is the local radiation therapy most impt risk factor (preferred over radical for recurrence & mastectomy) mortality sentinel LN studies Dysmenorrhea (general) painful menstrual period. ovarian cysts) 50% of menstruating women 5-10% dysmen affects QoL OCPs NSAIDs for moderate pain .S. FH of papillary ovarian cancer.without pelvic pathology secondary . greatest in AA nulliparity.mammogram: round 60 years old calcifications (looks like fibroadenoma) gross: infiltrating mucinous (wet. #2 cause of cancer mortality in women increased age Caucasians (after age 45. estrogen replacement tx. AA have higher risk) > AA> NA. Hispanic. sticky appearing) w/ hemorrhage histology: islands of DCIS lesions floating in mucin (clear).2. women. however.FH breast cancer < age 50. late women menopause. & malaise A/w cyclical periods!! primary / idiopathic . HER2 status. FH localized tumor . plus GI.excision. OCP (but decreased risk affects 1/8 for endo/ovarian women Ca). triple negative (ER/PR. HER2) staged based on tumor grade. PTEN. obesity.
constipation. low back pain. adenomyosis. colicky pain (improves w/ massage. valproic acid. abuse pelvic adhesions in 25% multidisciplinary (bc 50% of women have usually multiple causes of comorbid psych pain) diseases (DEPRESSION!) include mental health provider (counseling + med tx way more effective than med tx alone!) 1. laparoscopy. fibromyalgia. antidepressants) . cervical stenosis. chronic pain meds (gabapentin. topamax. fibroids. continuously ever 6-8h to prevent reformation of PG No response to NSAIDs after 3-6 cycles? OCPs (suppress endometrial proliferation.uterine myomas GI: IBS. R/O underlying pelvic pathology Treatment prostaglandin synthetase inhibitors NSAIDs taken prior to or at onset of pain. rare n/v/d increased uterine tone + hi amplitude contractions = reduced blood flow = ischemic pain Secondary Chronic Pelvic Pain (general) underlying pathology: endometriosis. consideration of narcotics 3. PID less likely to respond to NSAIDs or OCPs multi-factorial non-cyclical pain > 6m GYN: endometriosis. paracervical block. nerve pain occurs many years after onset of menarche PE: abd & vaginal exam may reveal underlying lesion U/S of vaginal/abd. thus dec PG synthesis) others? Tinge unit. urinary calculi. radiation cystitis MSK: pelvic floor pain. pain begins 3-5d prior to period. diverticulitis Urologic: IC. uterine nerve ablation (last resort) spontaneous resolution post-delivery Complications appears within 1-2 yrs of incresaed endometrial menarche when ovulatory prostaglandin production cycles are established PGF2a + PGE2 hi in secretory Pain occurs few hrs prior endometrium due to decline of or just after onset of progesterone levels in late period. congenital uterine anomalies (bicornuate. movement). endometrial onset polyps. relieved by period non-communicating horn). lumbosacral backache (radiates to anterior thigh). PID. lasts 48-72h luteal phase suprapubic cramping. septate. drug/alcohol endometriosis in 30%. adenomyosis. IBD. chronic UTI. pelvic adhesions. hysteroscopy analgesics treatment of underlying cause 15% of reproductive age women h/o sexual or impt to do rectovaginal & physical abuse bimanual exam in these patients! PTSD Laparoscopy .Disease Clinical Variants Primary Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging PE: nl except some tenderness confirm cyclical nature of pain. NSAIDs 2.nl in 35-40%. colitis.
dec direct invasion. flow obstruction. fixed retroverted uterus. vulva. U/S Treatment presumptive tx before laparoscopy (interrupt menstrual cycle) monophasic OCP (daily hi dose progestin) / vag ring/ patch for 3m NSAIDs. active or latent disease GC infects mucus glands endocervix (NO ECTOCERVIX involvement). HPV. uretotubal T-cell reactivity & NK activit most common area? Posterior cul-de-sac protective factors? Habits that in situ decrease peripheral estrogen (congenital) celomic (exercise. Immunologic abnl cause inc vascular pelvic pain. increased exposure to menstruation (early menarche. hep A/B/C) parasites (Trichomona. HIV. laparoscopy.minor salivary glands (mouth = gonococcal oral pharyngitis). syphilis) racial minorities HIV+ PE: examination of pelvic floor muscles --> tenderness and pain in bladder. oral . not FDA approved for all receptive sites) pain meds. post-coital dilation of ovarian veins. hysterectomy Complications endometrial tissues (glands & Endometrial stroma) that occur outside the retrograde severity of pelvic pain =/= uterus menstruation. 2050% of infertile population Risk factors FH. Botox injections syphilis? Penicillin +/. consistent history hi fiber diet (avoid stool buildup) surgical lysis (dense adhesions) surery. infertility presence of circulating dissemination. conjunctivitis (bilateral small painless papule that involvement in infants. HepC. endometrium. Zoladex) surgery? Laparoscopic destruction of lesions.relieved by lying down +/. obesity Lab/Imaging PE: possible to find tender pelvic structures. chancroid) viruses (HIV. HSV. GnRH analogs (Lupron. PID (untreated DONOVAN BODIES: chlamydia) Granulosum inguinale. condyloma. pelvic bands of scar tissue form between two pelvic organs --> surgery. stillbirth. pelvic vein embolization pain worsens w/ prolonged incompetence of valves & standing. cervical GN diplococci .HSV. bilateral uterosacral ligament resection.CT or U/S diagnosis 45 w/ multiparity Pelvic floor dysfunction pelvic floor muscles myofascial pain usually involving levator ani Interstitial cystitis (80%) Sexually transmitted infections (general) syphilis: primary = chancre/ painless ulcer. Synarel. subq spread --> elephantiasis of external genitalia 19 million new bacteria cases/ yr (gonorrhea. fallopian tubes.GC cancer. trauma infertility & chronic pain Pelvic adhesions (asherman's syndrome) Pelvic venous congestion syndrome exclude other pathology. Depo-Provera. vagina. laparoscopy. inc # peritoneal macrophages. Granuloma inguinale: Klebsiella granulomatis. can cause blindness) eventually forms beefyred granulomatous ulcer that bleeds easily. septic vasculitis & arthritis. nodularity along uterosacral ligament Laparoscopy . mucopurulent d/c from malignant syphilis in os?? CT immunocompromised GC: bartholinitis --> Bartholins cyst or abscess (if pus filled) . lymphatic pathology by laparoscopy dissemination. adnexal masses. or perineum NAATs more sensitive (however.Disease Clinical Variants Endometriosis Defining Characteristics pain worsens w/ age Pathogenesis Etiologies Epi cause of chronic pelvic pain in young women 3-15% of general population. secondary = rash. premature birth. CT/GC. smoking) metaplasia. chlamydia.vulvar or upper thigh varicosities women aged 20.HIV women: asymptomatic treatment if indicated dz --> reproductive health consequences (infertility. Mullerian duct remnants infection. other veins draining pelvis dull pelvic pain/ pressure/ heaviness . trigger point injections. alopecia. syphilis). mouth lesions. autoantibodies. easily treatable HIV transmission PE: purulent d/c from os?? lues maligna GC. pubic lice) 15-24 year olds MSM (LGV.gold standard others? Elevated Ca-125. congenital urethral cultures transmission . physical therapy. Wolffian duct remnants. syphilis. nulliparity).
vulvovaginal candidiasis (2025%) Trich: pH>4.1g PO once OR doxycycline endocervical exudate. non-tender bilateral reactivation?? Hypopigmentation. wet mount: motile flagellated protozoa w/ many WBCs Candidiasis: pH<4.5.5. herpes (immunocomp.syphilis "hamburger meat lesions" irregular shaped. herpes. intermittent penile discharge painful meatus? HSV Pathogenesis gonorrhea. urinary frequency. CT (15-40%). fixed drug eruption. easily induced endocervical 100mg/ PO bid x7d bleeding NAAT for GC/CT & trichomonas or wet mount culture for trich/ BV Genital ulcers elevated edge lesion . psoriasis Granuloma mostly in Caribbean HSV . culture/ PCR serology Crohns). wet mount: Clue cells Trich: metronidazole. scalloped/ LNs . residence. bulboes appear in LN regions after resolution irregular shape lesion + of ulcers pseudobuboes (LNs) Granulosum inguinale Syphilis . NGU (non gonoccocal urethritis .PAINLESS ulcers. a/w sex). transmission thru subclinical shedding HSV2 . odor majority due to HSV or syphilis noninfectious sources? Yeast.1g PO once if NGU infection OR doxycycline 100mg/ PO bid x7d Complications Writer's syndrome Keratoderma blenorrhagica (autoimmune syndrome w/ rash after CT infection) Cervicitis frequently asymptomatic chlamydia. vulvar itching.acyclovir (pt + partner) HSV = chronic lifelong infection.1/4 young people underlying dz syphilis serology. rectal bleeding . tender & unilateral Chancroid .clinical/ epi superinfection w/ staph or co-infection (HSV + syphilis) HSV . women w/ rectal intercourse inflamed rectum w/ blood gonorrhea.HSV inflammation (causing vaginal firm.Disease Clinical Variants Urethricitis Defining Characteristics dysuria. syphilis. trichomonas. demarcated d/c). herpes & pus mucoid anal discharge. LNs . firm & volcano appearing Trich: frothy/gray smelly d/c. KOH: pseudohyphae BV: positive KOH whiff test. painless. strawberry cervix Candidiasis: cottage cheese d/c BV: fishy odor Trichomonas. swelling. irritation. BV (40-45%. wet mount: few WBCs. VERY painful lesion. painful lesion.all other agents) Epi Risk factors Lab/Imaging Gram stain: increased polys (>5 per HPF). travel hx # partners empiric treatment for most possible likely agent .Chancroid then ulcerated. bacterial vaginosis vaginitis: vaginal D/C.CT syphilis. HIV increased HIV risk w/ screening trich BV: metronidazole Genital warts Proctitis HPV HPV low risk types 6&11 MSM. chlamydia. Mycoplasma genitalium Etiologies GC (5-20%). BV chlamydia recurrent or persistent infection (30% of pts) .tender papule w/ erythema that becomes pustular LNs .a/w risk of HIV acquisition Vaginal discharge Trich (15-20%). edge. herpes. Granuloma inguinale circular. H.suff for dx in men only!) GC/CT NAAT Treatment Azithromycin . chlamydia.white plaques. erythematous edge. + painful ulcers. firm bilateral & tender hemorrhage/ erythema. chlamydia (LGV). GN intracellular diplococci (Gonorrhea . ducreyi (chancroid).retreat if non-compliant. gonorrhea. conjunctivitis? a/w think Trichomonas or CT autoinoculation resistant ureaplasma or mycoplasma PE: purulent / mucopurulent azithromycin . HSV .
mild rebound. actinomyces. weakness/ fatigue/ anorexia.saline volume expansion.Disease Clinical Variants PID Defining Characteristics lower abdominal pain AND uterine/ adnexal/ cervical motion tenderness. multiple thickened luteal cysts & abscess path: actinomyces if a/w IUD IV antibiotics first followed by draining/ removal of abscess usually requires removal of uterus and ovaries bc fibroids present! Pyosalpinx Hydrosalpinx Fallopian tube filled with pus Fallopian tube dilated with watery fluid gross: retort shaped path: villi of fallopian tube are pressed into a flat lining (short broad & thickened papillae) confirm low cortisol. myalgia/ arthalgia loss of cortisol production hyponatremia. cortisone acetate.no cortisol = vasodilation = syncope GC replacement hydrocortisone. tachycardia. fever. 1-3% w/ mucosal infection. ovaries. dysuria. shaking chills. lower abd pain. prednisone (less preferred bc long t1/2) Addisonian crisis hypotension. check ACTH levels (primary v. tenosynovitis/ dermatitis (rash). ectopic pregnancy. postural hypotension . joint pain .unk.double daily requirements . nausea. chronic pelvic pain NO USE OF IUD!!! IUD + PID = TUBAL ABSCESS FORMATION Pelvic inflammatory disease chlamydia.pustula (pus filled vesicle) Tubo-ovarian abscess sepsis symptoms (fever. hypercalcemia . sexually active women DGI monoarticular septic arthritis of large joints. diarrhea. mycobacteria (TB) disseminated gonococcal infection very uncommon (decline in etiologic strains for unk reason) complement deficiency patients younger. fallopian tubes. purulent vaginal d/c Pathogenesis Etiologies Epi Risk factors Lab/Imaging PE: severe PID can have swollen uterus/ tubes w/ extruded pus Treatment Complications tubal inflammation --> scarring & loss of function = tubal factor infertility. fever/ chills septic vasculitis . weight loss. & adjacent tissues others: mycoplasma. AMS. abd pain.dilution of Na by excess free water (nl cortisol inhibits ADH prod). hi dose MC replacement (primary hydrocortisone IV insuff only) (achieves GC & MC fludrocortisone effects) adjust for surgery/ minor stress/ fever . BV uterus. HSV. weight loss (acute = weight gain from edema & H2O retention) chronic adrenal insuff has diarrhea so H2O loss. postural hypotension. large tender adnexal mass PID + IUD vaginorectal exam: pus palpated btwn rectum & uterus gross: ovary. hypercalcemia. anaerobes. elevated WBC). secondary) ACTH stimulation test Adrenal insufficiency (general) hyponatremia. 1M women/yr infection & inflammation of gonorrhea.
IV ACTH will cause no change in cortisol secretion Treatment chronic replacement of GC & MC Complications hyperpigmentation does NOT resolve even post-tx adrenal destruction --> unable autoimmune. infiltrative: sarcoid. adrenal leukodystroph infectious . trauma. Pseudomonas. amyloid. polyglandular autoimmine sarcoid/ I&II. 85% of pts who die from TB have adrenal involv Risk factors Lab/Imaging HI ACTH (pit trying to stimulate adrenals but adrenals unresp) short cosyntropin test . coag d/o. adrenal hyperplasia. hemochromatosis. CMV.MUST wean these patients & test for HPA axis responsiveness HIV.reversal of atrophy proves secondary adr insuff gross: caseous necrosis histology: Acid fast stain for Mycobacterium tuberculosis bacilli (red fish) usually not biopsied but would see lymphocytic infiltration Chronic replacement of GC Adrenal tuberculosis adrenal insuff (see above) Autoimmune adrenal disease WaterhouseFriderichsen syndrome adrenal insuff (see above) polyendocrinopathies.influenzae. HIV. iatrogenic (most common!!) prolonged GC treatment HP axis dz (tumors of pit. infiltrative dz. hypothalamus. trauma) Secondary NORMAL POTASSIUM LEVELS!!!! + symptoms above in general category LOW ACTH (unable to produce so adrenals aren't stimulated) short cosyntropin test . vitiligo (autoimmune attack of melanocytes).Disease Clinical Defining Characteristics Variants Primary Symptoms above in gen (ADDISONS category + adrenal ) calcification (fungal/ TB cause). hereditary/ candidiasis. Staph gross: hemorrhage of adrenals histology: massive extravasation of RBCs in cortex .3% of TB patients Addisons.TB. adrenal idiopathic hemorrhage .IV ACTH will cause slight increase in cortisol secretion (suggests partial insuff) Long Cosyntropin test repeated ACTH infusion awakens the atrophic adrenals and shows cortisol secretion . hyperkalemia (loss of zona glomerulosa = loss of aldosterone = inc K+) Pathogenesis Etiologies Epi 0. adrenal hemochromato leukodystrophy/ sis. isolated autoimmune adrenalitis acute hemorrhagic necrosis /infarct of adrenal glands as a complication of DIC child presents w/ adrenal insufficiency + infection + pic of hemorrhagic adrenals a/w systemic more infection: common in children Neisseria meningitidis. iatrogenic: adrenalectomy. autoimmune: infarction. steroid synt inhibitors hypothalamic/pit dysfxn --> no ACTH produced or secreted --> no stimulation of adrenals --> insuff no ACTH = adrenal atrophy = adrenal insuff Stopping GCs suddenly will cause adrenal insuff . thrombosis myeloneuropathy. antiphosph hemorrh syndrome. y. hereditary: congenital amyloid. histo. others?? HIV.WaterhouseFriderichsen syndrome. to respond to ACTH --> insuff TB. H. hyperpigmentation (ACTH binds melanocytes).
alopecia. EXCESS deoxycortisol from 17 hydroxyprogesterone (no TESTOSTERONE/ cortisol made) ANDROGENS!! shunts pathway towards formation of sex hormones (DHT.Disease Polyglandular Autoimmune Disease (PGA) Clinical Variants Type I Defining Characteristics Pathogenesis Etiologies autosomal recessive Epi Risk factors Lab/Imaging Treatment Complications adrenal insuff (see above) antibodies form to 17a & 21hydroxylase + mucocutaneous candidiasis (thrush) + hypoparathyroid disease AIRE gene mutation Other disorders? Pernicious anemia. hirsutism. estradiol. ambiguous loss of 21-hydroxylase prevents autosomal hydroxylase genitalia. spinal loss cord Adrenal myeloneuropathy . DR3. brain. T1DM. replace aldosterone if needed (fludrocortisone) .000 Cortrosyn stimulation testing = gold standard for dx . chronic active hepatitis CHILDHOOD Type II adrenal insuff (see above) unknown gene mutation but chromosme 2q33 linkage + thyroid problems (Hashimoto's). salt.formation of recessive deficiency deoxycorticosterone from wasting hypotension progesterone (no aldosterone made) and formation of 11NO CORTISOL OR ALDOSTERONE. etc) most common of CAH!! 1:15. & gonad disorders + vitligo ADULT ONSET autosomal dominant HLA B8 (DW3).later onset variant w/ slower progression (ABCD2 gene) 10% of all adrenal insuff cases X-linked recessive mutation of ABCD1 gene (MALES only) 25-35% of "idiopathic" Addisons now known as mild ALD neuropsychiatric testing MRI for prognosis Congenital Adrenal Hyperplasia (CAH) (general) most common cause of ambiguous genitalia enzymatic defect in steroid biosynthesis --> impaired cortisol secretion --> chronic ACTH stimulation --> adrenal gland hypertrophy --> overproduction of androgens/ testosterone 21adrenal insuff. DR4 Adrenal Leukodystrophy abnl peroxisomal transporter = defective oxidation of very long chain fatty acids = progressive neurological accumulation of lipid in adrenal. malabsorption.measures 17-OH progesterone & cortisol levels pre& post stimulation surgery for females replace cortisol (hydrocortisone). gonads.
DEOXYCORTICOSTERON and act as a powerful E STILL ABLE TO BIND mineralocorticoid = HTN MR 11B. and sex steroids the lack of cortisol secretion leads to elevated ACTH. ambiguous genitalia. salt wasting hypotension NO CORTISOL.hydroxylase also used to make cortisol from 11deoxycortisol. the pathway shunts towards aldosterone production only 3B-hydroxysteroid dehydrogen ase II adrenal insuff. OR ALDOSTERONE loss of 3B-hydroxysteroid dehydrogenase results in decreased production of all 3 groups of adrenal steroids. severe hydroxylase HTN + ambiguous prevents formation of deficiency corticosterone & aldosterone = genitalia accumulation of deoxycortisone. which is able NO ALDOSTERONE & to bind aldosterone receptor CORTISOL. thus these patients will have adrenal insuff and accumulation of 11deoxycortisol pathway is shunted towards the androgens 17aadrenal insuff. so no cortisol or sex androgens are made thus. ambiguous hydroxylase genitalia. EXCESS ALDOSTERONE loss of 17a-hydroxylase affects adrenal production early in the steroid pathway. sexual deficiency infantilism. HTN NO CORTISOL OR SEX ANDROGENS. which include mineralocorticoids. HOWEVER. primary amenorrhea. ANDROGENS. which results in the bilateral adrenal hyperplasia Etiologies Epi Risk factors Lab/Imaging Treatment Complications much less common . bilateral adrenal hyperplasia.Disease Clinical Defining Characteristics Pathogenesis Variants 11B loss of 11B-hydroxylase adrenal insuff. glucocorticoids. pregnenolone or progesterone cannot be converted into their subsequent forms.
just at a new set point) plasma ACTH > 200 Imaging of other organ systems for masses pituitary disease: transsphenoidal resection + radiation post-surgery cortisol supplementation until HPA axis recovers panhypopituitarism from radiation therapy (90% patients over 10y time frame) complications of transsphenoidal resection? Transient DI (disruption of post pit). still stimulates ACTH prod from ant pituitary . endocrine tumors (adrenal cortical. (aldosterone stimulates K+ functional hirsutism. insulin resistance. ACTH stimulates melanocytes primary decreased linear growth --> hyperpigmentation. CSF leak. skin stria. tumor in ant pit hypokalemic alkalosis central obesity (thin extremities). excess Cushing dz (pituitary) v. affects collagen --> thin skin. skin thinning. weakness. cortisol adrenal tumors (kids). testicular or breast ductal carcinomas ovarian tumor or pancreatic tumor produces ACTH. carcinoma) appetite. resorption --> osteoporosis. > 200 ectopic ACTH tumor). non-pituitary causes are NOT suppressed) (exogen CRF stimulates pituitary to make ACTH . edema. pasireotide) Pituitary ACTH production gross: enlarged cortex of adrenal 20> plasma ACTH < 200 medical suppression w/ dexamethasone (presence of negative feedback still so urine free cortisol suppressed) . melanocytic schwanomas. meningitis Ectopic ACTH Carney complex Cushing syndrome hypercortisolism + lentiginosis (spotty pigmentation) + cardiac myxoma. suppression/ stimulation tests (pituitary adenomas will be suppressed w/ exogen ACTH. peripheral cortisol --> insulin resistance neoplasm (adenoma. corticotroph cell hyperplasia. increased wasting --> proximal myopathy. petrosal sinus samples (detect gradients of ACTH lelves peripherally). amenorrhea. hypothalamic corticotrophin releasing hormone tumor ACTH induces adrenocortical hyperplasia ACTH producing adenomas still under negative feedback but new setpoint.if pituitary cause) adrenal CT if ACTH < 10 for adrenal sizes/ masses Treatment adrenal disease: adrenalectomy (last resort) + radiation Complications adrenal androgen production . paraneoplastic erythematous face. impaired (not understood). cortisol inc bone striae on abd.distinguishes Cushing dz from syndrome CRH stimulation test: elevated ACTH prod (if give CRH. hypercortisolism adrenolytic drugs. wasting). hyperglycemia. iatrogenic immune suppresion. inhibitors of ACTH release (carbergoline. overstimulating the gland and shutting down pituitary production of ACTH (HPA axis no longer under negative feedback) autosomal dominant gene heterozygous inactivating rearrangement mutation of regulatory subunit of PKA --> cortisol production & Cushing syndrome autonomous cAMP pathway stimulation downstream treat underlying cancer .autonomous adrenal activity. cortisol binds aldosterone ACTH Cushing syndrome producing receptors --> HTN. dorsocervical Ca) buffalo hump Cushing disease caused by ACTH producing microadenoma (maj). neuropsych probs. GH. requiring much more cortisol to stop secretion of ACTH --> bilateral adrenal hyperplasia 70-80% of endogenous Cushings Females 5:1 50% of ACTHproducing bronchial carcinoids suppress w/ dexamethasone pituitary disease: trans(exception to the nonsphenoidal resection + pituitary causes radiation being nonsuppressible) med tx: steroid synthesis petrosal sampling inhibitors (block risk for thrombosis & 11BHSD1). GR bleeding antagonists psych illness <--> (mifepristone). cAMP virilization.elev even @ midnight etiology? measure plasma ACTH (<10 . moon facies. & acne. or thyroid adenomas/ carcinomas.activation of > hirsutism.Disease Cushing syndrome/ disease Clinical Variants (general) Defining Characteristics adrenocortical hyperfunction Pathogenesis Etiologies Epi Risk factors Lab/Imaging hi 24h urine free cortisol (excess cortisol > capacity of CBG) . cortisol stimulates adrenal appetite --> obesity osteoporosis. HTN.constitutive -> androstenedione production -. oily renal stones (small cell lung hair. protein LH/FSH release.
excess cortisol shuts off a/w Beckwithfunctional or non-functional pituitary ACTH. hi urinary potassium aldosterone-producing adrenocortical adenoma F>M adenomas in kids usually occur at age <5 gross: solitary encapsulated nodules (yellow-tan on cut section). adults: ~45yo F>M very rare compared to adenomas gross: large mass + hemorrhage + necrosis in cortical section (yellow) histology: sheets of eosinophilic to clear cells. pheochromocytoma. or kidney cancer Bilateral. >1cm if macroscopic. hypokalemia. renal dz .THINK METS! Secondary hypertension (general) resistant HTN (BP>140/90 w/ full doses of >3 meds + suddent onset + younger/older age at onset) hyperaldosteronism. MC excess. hypo/hyperthyroidism. notencapsulated. OSA) most common causes? Hyperaldosterone.loss of heterozygosity involving autosomal tumor suppressor gene leading dominant -> Cushing syndrome + to activation of cAMP signal. nonfunctional adrenal masses in older individuals . alkalosis. necrosis of larger cells plasma ACTH < 10 (ACTH independent cause for hypercortisolism) need CT scan of adrenals for masses CXR: check for lung mass adrenalectomy + radiation very poor prognosis (med survival ~2y) Adrenal metastasis adrenal mets from primary lung. hi nuclear polymorphism. mutation virilization succession of mutations cause progression from: adults: functional & nonhyperplasia --> adenoma --> functional. adrenocortical nodules (<1cm.virilization >> syndrome hyperaldosteronism (p53 mutation). endocrine causes (Cushings.Clinical Variants Adreno-cortical (general) adenoma Disease Defining Characteristics Pathogenesis Etiologies Epi very rare Risk factors Lab/Imaging plasma ACTH < 10 (ACTH independent cause for hypercortisolism) need CT scan of adrenals for masses Treatment adrenalectomy (last resort) + radiation Complications panhypopituitarism from radiation therapy (90% patients over 10y time frame) Nelson's syndrome unrepressed growth of pituitary adenoma from hi ACTH levels (complication of adrenalectomy) kids: most often functional . renal disease. atypical mitotic figures. causing adrenal Wiedemann in adults atrophy syndrome. breast.o. multiple & bilateral) histology: lipid rich cortical cells. renal artery stenosis. & hemimost common cause of hypertrophy Cushings in kids kids: ~4y. La Fraumeni Cushing +/. cannot determine if functional by visual inspection Adreno-cortical carcinoma usually functional in kids. Cushing> carcinoma hyperaldosteronism > virilization Conn syndrome HTN.
Phenoxy-benzamine.Disease Clinical Defining Characteristics Variants Pheochromo onset of HTN at young age. displacement of cortex histology: polygonal spindle cells. perspiration (drenching sweats) Pathogenesis adrenal medullary (neuroendocrine) tumor arising from chromaffin cells = production of catecholamines = stimulation of alpha & beta receptors = inc BP. high aldosterone alkalosis. or onset of HTN at young age lowest dose of longacting steroid (dexamethasone. 10% bilateral. terazosin) B-adrenergic blockers (only start AFTER ablockers. angII stimulates the adrenals to secrete aldosterone. strokes at young age. & HR = cerebrovascular & cardiovascular consequences Etiologies Epi Risk factors Lab/Imaging urinary catecholamine metabolites (vanillylmandelic acid. neurofibromatosis. retinopathy. suggests autonomous prod of ald) Treatment preoperative alpha-adrenergic blockers (lowers BP&catech surges. pallor. this MC is able to contribute to HTN .might require rpt testing bc episodic nature of tumor Clonidine suppression testdistinguishes pheo from false positive inc in catech MRI/CT nodules? last option gross: gray-tan hemorrhagic mass > 1cm. palpitations. prednisone) to control BP Deoxycortic osterone HTN deoxycorticosterone is made in the zona fasciculata in response to ACTH. nested pattern (Zellballen). anxiety (adrenergic stim). aldosterone increases sodium retention and potassium excretion aldosterone producing adrenal adenoma. nausea. cytoma episodic HTN. usually adults (50y. ileus Classic triad?? Palpitations w/ tachycardia. SturgeWeber Rule of 10s: 10% a/w syndrome. used for tachycardia) SURGERY required!! Complications 50% 5y survival in malignant tumors certain drugs can interfere w/ catecholamine assay so might need to change meds around syndromes: rare MEN2. suppressed renin w/ severe HTN. adrenal carcinomas. headache. >20 suggests autonomous prod of aldosterone) confirm hyperald w/ oral salt loading --> should shut down aldosterone (if not suppressed. or CAH thus. 10% malignant Hyperaldost adrenocortical eronism hyperfunction Conn's syndrome . polyuria/ polydypsia. hypokalemia. low renin. epleronone. hyperglycemia. in response to ACTH family h/o hemorrhagic stroke. metanephrines) . bilateral adrenal hyperplasia. kaliuresis.HTN. chest pain. hypokalemia. elevated levels of deoxycorticosterone seen in adrenomas. hypertensive forms of CAH (11B &17a hydroxlase def). hyperreninemia (orthostatic hypotension). profound ACTH DRIVES hypokalemia w/ thiazide ALDOSTERONE SYNTHESIS admin RARE: <1% of hyperald cases CT scan of abdomen bilateral adrenal vein sampling (aldo:cortisol > 4 suggests adenoma) FH hemorrhagic genetic testing for GRA stroke (uncont mutation on all pts w/ history HTN) of hyperald.o. ACE converts angI to angII.) von HippelLindau. weakness. contractility. amilioride (K+ sparing) Glucocorticoid remedial hyperaldoste ronism adrenal adenoma + HTN + translocation in which the gene autosomal hypokalemia involved in cortisol production is dominant transferred to the gene involved aymptomatic severe HTN in aldosterone production --> aldosterone being produced in child or young adult. tremor. adrenal cancers 2-15% prevalence adenoma? Surgery (curative) medical mgmt? aldactone. 10% kids. tachycardia. extensive vascular pattern. bilateral in familial cases (a/w syndromes). alkalosis. hi Renin nl converts aldosterone angiotensinogen to angiotensin I. variable nuclear pleomorphism aldosterone:renin ratio (nl<20.
surgical excision of vestibule (which is mesodermal derivative so might be reacting differently to surrounding tissues) & reconnection to other tissues tx infections Vaginismus signs? Unconcumated marriage. BV. failure to thrive.Disease Clinical Variants Liddle syndrome Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging low renin & aldosterone (RAAS system not part of the etiology of this syndrome) Treatment Complications autosomal severe HTN. nonfunctional 11BHSD2 from mutations cause AME Type 2 . low inhibiot of 11B-HSD2 renin & aldosterone. trich. psychogenic therapy. metabolites & decrease in & chewing tobacco cortisone adrenocortical excess sex hormones hyperfunction stop offending agent & BP reverts to normal Sexual pain disorders Dyspareunia recurrent or persistent involuntary genital pain associated w/ sexual intercourse vulvodynia hypersensitivity to touch. candidiasis vulvodynia = most common cause of dyspareunia estrogen creams (unless contraind) if related to atrophy address etiologies . GC.decrease or HSD2 by converting cortisol to cortisone. cortisol has equal affinity for MR Syndrome of Apparent MC Excess (AME) HTN normally prevented by 11BAME Type 1 . genital rash. with active metabolite of glycyrrhetinic acid = potent HTN. increase in cortisol found in candy. loss of lubrication & genital blood flow = tearing w/ penile penetration) vulvodynia/ vestibulodynia = inflammation of vulva or vestibule infection vulvo/ vestibulodynia = hypersensitivity to yeast. hi urinary cortisol metabolites (elevated ratio of cortisol metabs: cortisone metabs) BP control & tx of hypokalemia supression of cortisol w/ dexamethasone spirinolactone kidney transplant Licorice Virilizing syndromes mineralocorticoid excess licorice contains glycyrrhizinic HTN acid. mutation in gamma or beta subunits of amilioride sensitive dominant low aldosterone & low renal sodium epithelial channels mutation renin in distal nephron --> ENaC channels stay open longer increasing Na reabsorption & decreasing Na excretion childhood: low birth weight. muscle relaxatants . difficulty placing tampons recurrent or persistent involuntary spasm/ contraction of muscles surrounding introitus prevent penile insertion -> personal distress. which is unable to absence of 11B-HSD2 bind MR.normal cortisol levels. HPV. allergic response. childhood trauma vaginal dilators.milder phenotype w/ expression as cortisol to bind MR and young age. HPV. pain w/ penetration vulvovaginal atrophy . estrogen def inf = HSV. despite generally in urinary products and decreased aldosterone activity HTN AME type 1 . hypokalemia. severe HTN + hypokalemic alkalosis cortisol circulates at much higher levels than aldosterone. CT. difficulty w/ pelvic exam. hypokalemia. chewing gum. UTI.if not helpful. erythema. PID. short stature. milder alteration activate aldosterone response. autoimm. normal ACTH feedback regulation (problem is with cortisol breakdown!!).often results from menopause (loss of estrogen = loss of keratin & epithelial lining of vaginal wall = thinning.
swelling response of sexual excitement arousal is mediated by relaxation of arteriolar smooth muscles (NO. anxiety reduction techniques. all genital sexual contact w/ appropriate sexual partner persistent or recurrent inability to attain or maintain an adequate lubrication .DM.inhibition of gonadotropins = reduced production of estrogen & androgens + inc synthesis of steroid hormone binding globulin = reduced testosterone Dopamine = excitatory for sexual desire/arousal Serotonin = inhibitory for sexual desire/ arousal Etiologies menopause (natural or surgical) meds (OCPs. downregulated smooth muscle receptors. give in combo w/ SSRI to compensate for dec libido Complications Sexual aversion disorder Sexual arousal disorder persistent or recurrent extreme aversion to. and avoidance of. and adequacy of stimulation directed masturbation program (if lifelong d/o). relationship therapy (if situational d/o). Dysfxn? Inadequate afferent PVD. and/or efferent neural obesity transmission to sexual organs (psychogenic or organic) OR inadequate response of erectile & vaginal tissue (insufficient release of NO or VIP. testosterone/ DHEA/ local estrogen/ oxytocin . SSRIs . insufficient second messenger regulation of relaxation) Orgasmic disorder Female Orgasmic Disorder persistent or recurrent delay or absence of organsm following nl sexual excitement phase orgasmic capacity < reasonable for age. OCP side effect?? Lab/Imaging Treatment treat only if distressful! Flibanserin . education about sexual fxn & response.reduced androgen production = reduced testosterone = decreased libido a/w OCPs . poor relationship. VIP mediated) in genitals that increases blood flow into clitoris and vaginal epithelium psychogenic sexual trauma. tadalafil) to prevent the breakdown of cGMP organic . drugs possible female use for PDE-5 inhibitors (Sildenafil.Disease Sexual desire disorders Clinical Variants Hypoactive sexual desire disorder (HSDD) Defining Characteristics persistent or recurrent deficiency or absence of sexual fantasies and desire for sexual activity Pathogenesis a/w menopause . sex experience. metabolic syndrome.inhibit pleasure pathways) Epi Risk factors menopause.although not FDA approved low dose testosterone Wellbutrin (Buproprion) blocks reuptake of dopamine.
neoplasm/ inf of testis/ epididymis. or infection of testis/ epididymis. thin membrane so able to see veins & tunica vaginalis Treatment Complications Varicocele painless dilation & tortousity of veins more common on left side of scrotum (right spermatic vein drains into IVC at a narrow angle so less probs w/ drainage. a/w inguinal hernia acquired hydroceles: usually due to lymphatic obstruction from trauma. M. fibrosis & chronic obstruction of epididymis duct may result --> infertility young men gonococcal & chlamydial infections older men E.gubernaculum attached horizontally instead of at the bottom of the testis 2nd decade of life minor injury? gross: necrotic testis.Disease Paratesticular disorders Clinical Variants Hydrocele Defining Characteristics painless enlargement of scrotum that transilluminates lymphatic obstruction Pathogenesis accumulation of fluid in tunica vaginalis that surrounds testis congenital hydroceles: occur during first year of life as patent processus vaginalis fails to close. a/w parasites (filariasis) in tropical parts of world Etiologies congenital or acquired Epi most common cause of scrotal enlargement usually 1st year of life congenital more common Risk factors prior surgery.coli. trauma Lab/Imaging gross: distended testis full of fluid. neoplasms. prior surgery. allowing fluid to enter & distend tunica vaginalis. pea-sized nodules above the testis inflammation of epididymis enlarged & TENDER epididymis small cysts that arise from efferent (testis --> meatus) ductal system of testis. testis may also become infected & difficult to distinguish from epididymis. edematous spermatic cord surgery to manually untwist spermatic cord testicular infarction / necrosis if not surgically managed in time! Bilateral risk so gubernaculum is fixed on both testes . tuberculosis most common intrascrotal inflamm d/o gross: purulent exodate in the epididymis (above the testis) if gonococcal NOT a/w infertility!! BENIGN! Epididymitis untreated gonococcal epididymitis --> epididymis abscess spread to testicles infertility if chronic scarring & obstruction Testicular torsion EXTREME PAIN that may occur spontaneously during sleep or be related to minor injury urologic surgical EMERGENCY!! twisting of spermatic cord = compression of venous drainage = vascular engorgement & congestion = infarction of testis anomaly of testicular suspension . left spermatic vein --> L renal vein = long column of blood that rests atop valves) dilation of vein plexus in spermatic cord 10% of young adults PE: veins engorge w/ blood when standing a/w infertility (inc termpature in scrotum optimal spermatogenesis is more efficient at lower temps) Spermatocele cyst formation in epididymis hard. particularly epididymis often arises from direct extesion of UTIs from prostatic urethra or prostate with advanced infection.
injections of FSH/LH or hCG) insemination (sperm is placed directly onto uterus near ovulation time) IVF other (gestational carriers. 35% tubal factor. PCOS.no signs of spermatocyte differentation (resemble those of prepubertal testes). CAH). 5%cervical factor. Kallman's syndrome.Kartagener syndrome drugs: CCBs ovulatory dysfxn: anovulation (PCOS.male factor. or decreased spermatogenesis mumps 30% of postchildhood virus pubertal males w/ mumps 1/12 couples 35% . Turner syndrome sperm analysis (oligospermia.dec spermatogenesis from inh of LH/FSH. TSH. hi prolactin. Klinefelters .Disease Cryptorchidism Clinical Variants Defining Characteristics condition where one or more testis has not descended to its nl position in the scrotal sac Pathogenesis usually arrested along the inguinal canal (dangerous bc this area is injury prone). low gonadotropins.o treatment. sometimes the top of the scrotum. diminished ovarian reserve. ovarian reserve testing (Day3 FSH & estradiol. androgen excess. renal agenesis. elev FSH immotile sperm: primary ciliary dyskinisia . DES exp. androgens. immotile sperm). fibrosis of seminiferous tubules Orchitis Bacterial Syphilitic inflammation of testis Mumps orchitis extension of bacterial infection from epididymis inflammation of testis infiltration of lymphocytes causes obliteration of small blood vessels --> tubular atrophy & fibrosis enlarged & PAINFUL testis viral mumps infection --> lymphocytic infiltration --> edema & pain --> focal atrophy in 50% of involved testis Oligospermia: exogenous testosterone. OCPs. hydrosalpinges. hysterosalpingogram. endometrial bx. acromegaly. oocyte cryopreservation. eval tubal/ uterine/ peritoneal factors (hysteroscopy. lack of GnRH neuronsKallman's syndrome. antral follicle count) induce ovulation (meds = clomiphine . Klinefelters.SERM. ovulation detection (basal body temp chart. urine LH surge. mid luteal serum progesterone >3ng/mL). congenital bilateral absence of vas deferens . uterine anomaly. clomiphene challenge. FSH/LH. pituitary gland . and even less commonly the abdomen Etiologies Epi 3% of male infants at birth Risk factors Lab/Imaging Treatment Complications if not repaired within 2 years --> testicular atrophy & fibrosis --> infertility (low sperm counts) INC risk of germ cell tumors (5-10x) . laparoscopy). endometriosis Ovarian reserve: problems with hypothalamus GnRH. AMH. primary ovarian insuff.low testosterone. Cushings. Leydig cells are indistinguishable from stromal cells .no one year of unprotected prior preg intercourse w/o conception Secondary preg in the past Male infertility Supratesticular above the testis results from abnormalities in organs that regulate hormonal & metabolic aspects of spermatogenesis no gonadotropins histology: anatomic seminiferous tubules but no active spermatogenesis. endometriosis. submucosal fibroids. prolactin.this risk never returns to baseline. ovarian transplant) fertility usually preserved in unilateral infections Infertility Primary . hypothyroidism tubal/uterine dz: PID. even after orchiopexy histology: atrophy of orchiopexy cryptorchid testis after 2y w. systemic diseases that suppress spermatogenesis (those a/w fever) result in immature seminiferous tubules . TB. CF. appendectomy. letrazole (aromatase inh). donor embryo. donor gametes.lack of gonadotropins. abnl mesonephric duct diff. 10% unexplained scar tissue (Asherman's). inhibin B.CF. 15%ovulatory dysfxn. eval anovulation (preg test.
pathology) trauma (testicular or head) check other pituitary hormones and adrenals! Hypogonadism (general) testicular failure symptoms? Low testosterone in adulthood = dec libido. gonad androgen receptor defects Hypergonad increased FSH & LH. dec body hair central defects . echovirus. hi pitched voice. radiation therapy to abdomen).IM q 2w. no germ cells) Treatment Complications Posttesticular obstruction of excretory ducts. replacement . (low watch out for levels.hypothalamus or pituitary problem w/ secretion of gonadotropins testicular defects feedback loop defects . transcription factors biochemical defects . gynecomastia. soft testes but nl size. nl pituitary & hypothalamus but congenital or otropic hypo. bone age. prolactin.Disease Clinical Variants Testicular Defining Characteristics Pathogenesis disorders or lesions of testis itself varicoceles --> increased temperature = low spermatogenesis Cryptorchid testis can develop atrophy & peritubular fibrosis Klinefelters syndrome . particularly the epididymis results in no spermatozoa in the ejaculate.sex chromosomes. karyotype. doses then dose hi and inappropriately every 2weeks) semen analysis normal gonadotropins!! (if testosterone cranial imaging.atrophy of gonads --> fibrotic testis Etiologies varicocele cryptorchid testis w/ scarring Klinefelters idiopathic Epi most common cause Risk factors Lab/Imaging histology: IDIOPATHIC? Germ cell maturation arrest.suspect R/O pituitary lesions). dangerous to liver!) hypothalamus med hx (anabolic steroids?).HPG v HPA axes genetic defects .adrenal v. U/S of scrotum & adrenals. dec body hair. drugs (spironolactone . cyproterene or ketoconazole . dec strength/ muscle mass. arbovirus). germ cell aplasia (Sertoli cells only. delayed bone age. INABILITY TO FOCUS pre-pubertal = small testes. iatrogenic (chemo agents.decreased testosterone = primary testicular failure acquired gonadism primary testicular failure either congenital or acquired Primary CONGENITAL (see below) .blocks androgen receptor). dec muscle mass. low testosterone.genetic abnormality (gonadal dysgenesis. would expect to have neuro exam (visual fields skin gels/ patch (cannot hi FSH/LH . be given as pill bc pituitary/ testicular size. LH & FSH. Vanishing testes syndrome Primary ACQUIRED Infectious (mumps. Leydig cell hyperplasia. Sertoli cell only syndrome**.blocks test synthesis. despite being made properly in the testis untreated epididymitis trauma vasectomy check morning testosterone start tx around 12y.o. CAH). eunuchoidal skeletal proportions. trauma . cocksackie B virus.
LH) failure pituitary or hypothalamus Secondary CONGENITAL: gene mutations (FSH/ LH deficiencies . tumors .craniopharyngioma). transcription factor excess (DAX1) karyotype abnl or transcription factor problems -> impaired development of testis --> dysgenesis Klinefelter's Syndrome congenital hypergonadotropic hypogonadism from gonadal dysgenesis increased limb length. anorexia (malnourishment shuts down HPG axis). hemochromatosis. elevated prolactin (inhibits FSH&LH). central midline defects (cleft lip palate. SOX9). Genetic syndromes (Kallman's. transcription factor deficiency (SF-1. systemic illness. "odd" impulsive behavior 47XXY --> impaired seminiferous tubules 1:10. decreased verbal IQ. HI FSH NO seminiferous tubules or sperm! . acquired decreased testosterone = insufficient signal from central (GnRH.PROP1). SRY. Prader Willi) Secondary ACQUIRED: brain abnl (trauma. obstructive sleep apnea Gonadal dysgenesis congenital hypergonadotropic hypogonadism caused by abnormal karyotype (Klinefelters .000 prisoners Leydig cell hyperplasia congenital hypergonadotropic hypogonadism male pseudohermaphroditism 46XY but inactivating mutations of LH receptor --> female phenotype LH required for Leydig cells to produce testosterone Germ cell aplasia/ DelCastillo syndrome sertoli cells are not functioning --> impaired sperm production normal secondary sexual characteristics bc nl testosterone & LH levels autosomal recessive mutations of LH receptor Sertoli Cell Only Syndrome congenital hypergonadotropic hypogonadism Male sterility without sexual abnormality & nl secondary sex characterisitics nl testosterone & LH.Disease Clinical Variants hypogonado trophic hypogonadism Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications testicle is functioning but congenital or decreased FSH & LH.47 XXY). infectious. septo-optic dysplasia).
acute androgen therapy . calcium & vit D supplements. estradiol levels osteoporosis. urinary tract. or discontinuation of meds (if exogenous anabolic steroids) often also have low HDL so at risk for CVD Menopause natural final menstruation during oocyte atresia dimacteric phase (no menses for 1y w/ inc FSH) menstrual cycle changes: follicular phase shortens. psychological changes. decreased androgen levels: atrophy (vaginal. FSH > 50-100 hypothyroidism becomes more common endometrial bx if postmenopausal bleeding treatment only if symptoms impact QoL. due to prenatal testicular torsion or INSUL3 transcription factor defect regression of testes during 814w gestation de Morsier's syndrome --> absent septum pellucidum Etiologies Epi Risk factors Lab/Imaging low testosterone. adrenal gland abnormality. small from excessive androgen testes secretion endogenous (central precocious puberty. testosterone. acne. hx of DVT/PE. hi FSH & LH Treatment Complications Septo-optic dysplasia congenital hypogonadotrophic hypogonadism optic nerve hypoplasia. early pubertal development virilization. androgen secreting tumor) exogenous (anabolic steroids) anabolic steroids treat cause inhibit testosterone w/ GC (if adrenal cause). radiation/ chemo exp.000 M>F 5:1 Hypergonadism (general) HYPOSMIA OR ANOSMIA (loss of smell) a/w hypogonadism bc same anatomic location as olfactory bulb androgen excess. perimenopausal women estradiol & progesterone can sometimes have irregular & heavy bleeding decrease --> irregular & anovulatory cycles reduced estrogen effects? Hot flashes.Disease Vanishing Testes Syndrome Clinical Variants Defining Characteristics congenital hypergonadotropic hypogonadism Pathogenesis nl 46XY karyotype but absent testes (anorchia). use lowest effective dose of HRT. unexplained uterine bleeding. surgery (if tumor). bisphosphonates. clonidine vaginal estrogen or lubricants for atrophy & dyspaurenia osteoporosis tx: estrogen. autoimmune.risks liver dz. can also use transdermal / transvag admin of HT to reduce blood clot risk endometrial hyperplasia & cancer if continuous estrogen exposure w/o enough progesterone in perimenopausal women Mirena IUD . ovaries. migraine w/ aura or alternatives to HRT? TIA SSRIs.lowest DEXA scans for osteoporosis systemic dose of progestin contraind for HRT? Hormone sensitive cancer. surgery. exercise . med induced (Lupron) estradiol < 20 pg/mL. inhibin is lower so FSH levels rise. anger. & DHEAS leads to decreased breasts. genetics. be beneficial for dec libido uncontrolled HTN. uterus & androstenedione. skin). calcitonin. loss of cardioprotection & neuronal protection occurs around age 50 early menopause? Smoking. SERMs. potential hypopituitarism Kallman's Syndrome congenital hypogonadotrophic hypogonadism problem w/ KAL gene (codes for adhesion molecule) = loss of migration of cells required to make GnRH 1:10. uncertain but thought to confirmed CVD. hair.
calcitonin. Turners syndrome.SSRIs. familial. galactosemia. pelvic irradiation Epi premature or primary ovarian insuff occurs <40 1% of women Risk factors Lab/Imaging vaginal estrogen or Treatment lubricants for atrophy & dyspaurenia osteoporosis tx: estrogen. calcium & vit D supplements. SERMs. pelvic surgery. chemotherapy. exercise Complications . clonidine Disease Clinical Variants Premature Defining Characteristics Primary ovarian insufficiency Pathogenesis Etiologies idiopathic (maj). bisphosphonates. gonadal dysgenesis (46XY).
Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications .
diet CVD risk factors and complications screening . CV. TFTs. ex. healthy lifestyle (diet. prevent dz in those w/ autoimm 3. realistic BG targets.autoimm 2. intervene to preserve islet cells OGTT = most sens way to dx pre-diabetes or diabetes (post prand gluc rises first) gluc monitoring & self-mgmt of insulin adjustments for stress. sickness. office visits q 3-4m for evaluation of retina. lower extremities.Screening / Education daily glucose monitoring. lipids) Prevention 1. & routine screening (A1C. ex).
Screening / Education A1s are at low risk for IU demise. 2x/week PP: screen 612 wks w/ 75g 2h OGTT (DM if FBS >126. 2h > 200) pre-preg ex a/w lower GDM risk prevent w/ early INTENSIVE glucose control . do not need antepartum surveillance or early elective induction A2s: antenatal surveillance w/ US & NST at 32 weeks until delivery.
Screening / Education .
Screening / Education every patient over age 60 should have TSH checked! Increase levothyroxine dose by 30% in pregnant patients!! .
Screening / Education .
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Screening / Education recurrent parathyroid dz possible .
Screening / Education .
Screening / Education .
Screening / Education rarely malignant dopamine agonists limited during pregnancy (no progression of microadenoma during pregnancy despite estrogen stimulation) surgical debulking of macroadenomas prior to pregnancy bc can worsen .
Screening / Education .
Screening / Education .
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Screening / Education .
blood glucose/ fasting lipids. FSH/LH. anticipatory mgmt for aortic dissection. celiac screen. DEXA. renal & liver fxn. ENT/ audiology . thyroid function. psych consults.Screening / Education routine evaluation? Cardiovasc screen.
Screening / Education .
Screening / Education .
Screening / Education expectant management & reassurance .
pelvis.Screening / Education Stages: I .outside of abdomen. lymph nodes.ovaries only II . parenchymal liver lower survival w/ higher stage . ovaries III .abdomen. superficial liver IV .
Screening / Education yearly paps beginning ages 21-29. if lowrisk.o. paps every 2-3yrs after age 30 if 3 normals in a row stop paps at 70y. if no abnl in last 10 years & 3nls in a row stop paps if hysterectomy & no h/o CIN2/3 .
Screening / Education .
Screening / Education continue to monitor other testicle if prior germ cell tumor! .
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Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education yearly mammograms for women > age 40 breast exams q 3y for women 20-40. yearly age > 40 hi risk women yearly MRI of breasts .
Screening / Education .
Screening / Education female screening.yearly if sex active: syphilis. selective males . hep. HIV. syphilis.CT if at risk or less <24. gonorrhea / HIV/syphilis (at risk). GC/CT.CT (sex active <24. HepB MSM . at risk >25). cervical Ca (all sex active women w/ cervix) pregnant women .
Screening / Education screen women < 25 for chlamydia! PROTECTIVE SEX!! Gardisal quadrivalent vaccine .
Screening / Education Chlamydia = leading preventable cause of tubal factor infertility .
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
sex selection . even after orchiopexy! Pre-implantation genetic diagnosis (PGD) aneuploidy screen. HLA matching.Screening / Education check testes regularly to screen for development of neoplasms. single gene defect.
Screening / Education .
Screening / Education .
Screening / Education CVD & osteoporosis screening .
Screening / Education .
Screening / Education .
blastic phase (acute leukemia. of proliferation & differentiation via hepatomegaly if adv.5 (males) or pegylated interferon 16. Hct. low EPO. can develop myelofibrosis . platelets (basically myeloid cell line expansion) Diagnosis: Hb > 18. rubra vera platelet counts + aqua (PRV) induced pruritis splenomegaly. injury occurs at a level beyond stem cell splenomegaly mutations in tyrosine kinase --> increased proliferation but INTACT differentiation Chronic pre-malignant disorder caused by fusion protein (BCRmyelogenous ABL gene) formed via t(9. always hi WBC (leukocytosis) smear: increased lymphocytes. terminal & poor prognosis) only leukemia w/ thrombosis Essential 50% JAK2 nonfunctional platelets --> thrombomutation bleeding cytosis splenomegaly CBC: all cells lines present & in excess.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Aplastic anemia all cell lines are down!! premalignant condition w/ loss of Paroxysmal self renewal (affects the stem cell) nocturnal hemoglobinuria (PNH). Hb. PRV) pegylated interferon suppresses abnl hematopoiesis some patients transform to polycythemia vera some patients. inhibition of apoptosis. good proliferative disorder of appetite but weight loss bc hematopoietic stem cells without early satiety) arrest in maturation. suppresses abnl hematopoiesis inc WBCs. WBCs at every level of maturation Cytogenetics: t(9. Dasatinib. RBCs. activation splenomegaly. BM bx does not need to be done. Fanconi's anemia BM: hypocellular (empty marrow). thrombosis (common & unusual locations) some patients. fat vacuoles only. inc platelets. difficult to control leukocytosis). over time. asymptomatic but abnl CBC). more BCR-ABL. hi power reveals lymphs only (suggest that whole myeloid line is gone) CBC: loss of all cell lines sometimes immunosuppression helps restore cell lines allogeneic stem cell transplant infections . confirmed w/ karyotype/ FISH/ PCR eradicated Philadelphia can progress to AML chromosome (causative (blastic phase) agent). Jak2 mutation.5 (females).22) FISH: fusion protein PCR: ABL-BCR gene flow is not diagnostic. develop Nilotinib) mutations to prevent Allogeneic HSCT if resistant drug MOA) to imatinib elevated platelet count (>450K) MUST R/O iron deficiency (iron studies). early RAF-MEK-MAPK) satiety (big spleen/liver compresses stomach. prevent progression to blast phase (AML) mean survival of chronic phase = 4-6y targeted therapy against resistance to Imatinib by BCR-ABL via tyrosine kinase inhibitors (Imatinib/ cancer cells (pump drug out of cell. accelerated phase (symptomatic. thrombosis inappropriate absolute JAK2 mutation polycythemia (EPO independent colony growth) from mutation in JAK2/STAT pathway --> upregulated transcription of lineage specific myeloid genes for WBCs. splenomegaly. over time.unable to generate new lymphocytes Myeloproliferative syndromes (MPS) (general) expansion in peripheral blood premalignant condition w/ = high counts of affected growth advantage and loss of myeloid line apoptosis. due to 3 phases of presentation: single molecular abnormality chronic phase (maj of patients. other MPDs (CML. produce Gleevec. can develop myelofibrosis Poly-cythemia elevated WBC.22) leukemia typically presents w/ [Philadelphia chromosome] (CML) whole dz is driven by mutation in splenomegaly + BCR-ABL (probs w/ adhesion so leukocytosis (nl plt & Hb) abnl myeloid cells leave marrow.
3 cell lines affected) refractory anemia w/ anemia. bleeding. HSCT poor cytogenics or normal cytogenics but poor mutational risk profile . 8 or complex. hypogranular). if poor prognosis while on consolidation therapy. exam: pallor. induction therapy (anthracycline. (stuck in progenitor cell phase) dyspnea. petechiaes. HLA-DR+ FISH: t(15:17) prog&tx response . rubber). LDH > 700. roaring in ears (Hb<6). splenomegaly. WBC # at presentation. multilineage infections dysplasia refractory anemia w/ excess blasts 5q syndrome premalignant condition where an radiation. marrow excess blasts demethylation drugs like azacitidine frequently progresses to AML (30% of cases) Prognosis depends on proportion of blasts in bone marrow. cytarabine) 2. CD117. altered cytokines --> decreased hematopoiesis & delivery of mature blood cells to periphery --> leukemic transformation apoptosis is shifted to bone marrow = inappropriate cell death before delivery to peripheral blood prior chemo/ more common in radiation treatment elderly Smear: abnormal segmentation Stem cell transplant of WBCs (Pelger-Huet immune suppression for the nucleus. splenomegaly. radiation. good ecchymosis.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Primary anemia. low WBCs if cells stuck in marrow. sideroblasts) thrombocytopenia (1. not helpful for clone reduction Myelo-dysplastic Refractory subacute presentation syndromes anemia (w/ or ("feeling bad") w/ anemia +/(MDS) w/o ringed neutropenia.17). skin nodules Primary: exposure to chemicals (benzene shoes. CD33. & arrested bone pain (wakes patient at differentiation --> impaired night). hematologic dz (CML.21) lymphadenopathy. consolidation therapy 4. >3% primary granules flow cytometry: express CD13. low (immature blasts). hereditary (Fanconi's.useful for reducing spleen size and improving symptoms.cytogenic & molecular markers. Down's) Secondary: chemotherapy. cigarettes insult (damage to bone marrow) affects differentiation and maturation of myeloid line --> clonal hematopoiesis --> cytoplasmic & nuclear asynchrony -> immune dysregulation. anemia sx . 7. perirectal abscess. infection). low RBCs & platelets smear: Auer rods. myelofibrosis elevated or decreased WBC & platelets portal hypertension fibroblasts prompted to make extra JAK2 mutation fibrous tissue --> filling of bone marrow w/ fibrotic tissue --> hematopoiesis then occurs at other sites (extramedullary hematopoiesis) tear drop RBCs (dacrocytes). DOE. immature granulocytes. hypolobated megakaryocytes small proportion of patients that have immune dysregulation & hypocellular BM bx: ringed sideroblasts. vision. clonal.000 bimodal age distribution (15-59) CBC: possible hi WBC if driven by blasts. blasts (all cells look alike). 2. chloroma (skin infiltration by cytogenic abnormalities leukemia) common . Observe patients.poor prognosis = chrom 5.do not survive beyond 2 years & require transplant! Worse survival out of the leukemias hyperleukocytosis --> CNS injury & pulm leukostasis . nucleated RBCs "dry tap" on marrow aspiration (scarring of marrow) hypercellular marrow + fibrous tissue JAK2 inhibitors . bruising). poor initial reponse to tx genetic profiling for intermediate risk patients eradicate AML & restore hematopoiesis 1. = t(15. low or nl WBC if arrested development. t(8. low platelets & RBCs. spont bleeding). platelets (bleeding. gingival hyperplasia (monocytic leukemia). age. cytogenetic features. subtype. MDS) 1/150.fatigue. & number of cytopenias Acute myelogenous leukemia (AML) completely immunodeficient (pancytopenia) mutation in early progenitor myeloid cell causes complete replacement of bone marrow with no normal lineages being made. establish risk stratification 3. low cells no longer have nl function WBC (feveres. check therapy response. intermediate = nl karyotype. hyperviscosity production of nl blood cells (mental status change. hi WBCs if cells are in blood BM bx: hypercellular. proliferative.
000). malaise. ARDS).mixed leukemia.represent BM response) LN bx: well differentiated lymphocytes. CNS sx topo-isomerase chloromas. M>F slightly increased lymphoid proliferation -.mucosal.favorable (TEL-AML). poor prognosis a/w CD38+.22)). CD5+ (T cells but occurs briefly in B cell development). leukemic II inhibiters meningitis. with subsequent delayed exposure to pathogens at time of to pathogens in incidence) dz leukopenia (infxn. > extremely robust response others . lymphocytosis only. t(9. location of dz (hi risk if CNS positive).initial present (age hi risk if <1 or >10. disease med survival 7y Rai 3 = anemia. fever).infancy systemic involvement (fever. unfavorable (MLL . 4w tx assessment . nucleated.8/100. cytogenetics . "late" splenomegaly. high birth extramedullary involvement rate.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Acute lymphocytic leukemia (ALL) malignant d/o of lymphoid progenitor cells that completely replace the marrow --> pancytopenia higher SES. microspherocytes . Treatment includes fludarabine or chlorambucil lymphadenopathy. anterior mediastinal mass (T cell disease . med survival 4y Rai 4 = thrombocytopenia. hyperleukocytosis (cause sludging --> stroke. hyperdiploid. pain. Evan's syndrome mutation in B cells post antigen exposure in the lymph node --> clonal B cells arrested in the B-cell differentiation pathway.000 per yr MBL (monoclonal B cell Caucasian> lymphocytosis AA>Asian ) patients > age 60 most common overall leukemia & most common cause of general lymphadenopathy in adult > 60 flow cytometry: cell population CD19+ (B cells).o. high risk Rai 0 = low risk. WBC hi risk if >50. these cells resemble mature lymphocytes neoplastic B cells do not differentiate into functioning plasma cells = hypogammaglobulinemia 3/100. calcium and uric acid can block kidneys oncologic emergencies: tumor lysis syndrome (renal failure).hallmark of ALL CNS prophylaxis tumor lysis syndrome rapid cell death and turnover causes phosphorus and potassium to be released. med survival 7y in older patients Rai 2 = intermed risk. diffuse primary & secondary follicles FISH: poor prognosis a/w 17p &11q deletion SPEP: hypogammaglobulinemia important to observe asymptomatic patients!! Richter's transformation (1% per year) .5-2. coag screen prognostic factors . lumbar puncture (CNS?) LFTs.4% of MBL becomes CLL .block airway and compress SVC). sepsis Chronic lymphocytic leukemia (CLL) lymphadenopathy + elevated WBC/ ALC infections . lymphadenopathy + HSCT for poor prognosis spleno/hepatomegaly. weight loss. immunophenotype .bilateral. ionizing (lymphadenopathy. 4. CD20 clonal population PCR: TEL-AML rearrangement LDH: elevated (marker of cell turnover) tumor lysis labs CXR. med molecular studies survival 14y Rai 1 = intermed risk.2-3y.T cell or biphenotypic higher risk. thrombocytopenia environmental . ITP.normocytic anemia w/ low retic count.5y) . smudge cells (fragile cells that have burst). lymphocyte count doubles staging: <1y. leukopenia. bruising). infections. thrombocytopenia. hepatoradiation. late 2. radiation exposure. possible leukocytosis (malignant cells) Peripheral smear: blasts in periph blood (20% of pts do not have blasts in periphery at time of dx) BM morphology: hypercellular w/ monotonous cells resembling lymphocytes BM flow cytometry: blasts > 25% = confirmed dx. RBC abnormalities (polychromatic. ZAP70. of (hemorrhage . CD23. skin or testicular masses) stem cell gives rise to slightly more genetic mature lymphoid progenitor cell sensitivity to B that proliferates out of control cell hypersensitization (FH of autoimmune genetic & environmental dz) combination of etiologies most common childhood malignancy CBC .trisomy decreased activity).evolve into large cell lymphoma treatment indicated if: Rai 3.slow early responders or induction failure need intensification use of maintenance tx (administer low dose drugs 1. bone/ joint common inf. intermediate between pre-B cells and mature B cells. infant. med survival 4y Monoclonal Bcell Lymphocytosis precursor to CLL 6-15% of age relatives of (increased CLL patients CLL clones) detectable clonal CLL cells at less than 5000 1. edema.000 common S/S: anemia (dec energy. CBC: extremely elevated ALC/ WBC (>5000 circulating cells w/ CLL phenotype) smear: high number of mature lymphocytes.decreased polyclonal immunoglobulins autoimmune disorders AIHA. in the peripheral blood. Down's syndrome. FH CHF). lack of pathogen exposure as an lack of exposure (peak autoimmune petechiae. B symptoms. 21.2-1. renal failure.
+/. B symptoms (unexplained fever. SLE (other autoimmune dz) malignancies arising from cells of lymphatic system (lymph nodes. renal insuff. reddened patches of skin should always order HIV test if suspect lymphoma!! . absent CRAB! 1/3 of MGUS patients progres to myeloma obligated to observe and follow these patients!! Evan's syndrome Lymphomas (general) painless swelling of LNs. lenalidomide. recurrent infections w/ encapsulated organisms (H.plasma cells Skeletal survey: compression fractures. osteopenia. hi globulin Smear: Rouleaux formation of RBCs. cytogenetics for high risk mutations Monoclonal Gammopathy of Undetermined Significance (MGUS) precursor to myeloma!!! Fight infections fine bc normal polyclonal Ig's not decreased. or organ damage (CRAB). osteopenia. hi total protein but nl albumin. lytic lesions SPEP: IgG kappa paraprotein present at high levels (monoclonal gammopathy) BM bx: plasma cells in bone marrow (>10%) DX REQUIRES: presence of serum/ urine M protein. observation <3g monoclonal protein. thrombocytopenia Chemistries: hypercalcemia. anemia. unexplained weight loss > 10% of body weight). lytic bone lesions) autologous transplant Thalidomide. no lytic lesions. renal dysfunction. bortezomib most impt for remission rates & improved outcomes incurable! Staged by Beta-2 microglobulin (total body burden of plasma cells) & albumin. hypercalcemia. thymus.3/100. decreased normal immunoglobulins --> recurrent infections 2. alcohol induced pruritis.000 AA> Caucasians median age 66y. anemia.influenzae. clonal bone marrow plasma cells. hypercalcemia 4. bone pain. drenching night sweats. monoclonal immunoglobulins + hyperviscosity of blood (decreased blood flow) + hypercalcemia + amyloid (light chains converted to amyloid) --> renal failure MGUS 4. CBC: low WBC.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Plasma Cell Myeloma fatigue. MALT). organ/ tissue impairment (CRAB = increased plasma calcium. bone destruction from the release of IL-1 (osteoclast activating factor) --> lytic lesions. can move to the bone marrow majority are B cell origin. constant fatigue. pathologic fractures. < 10% plasma cells in marrow autoimmune hemolytic anemia + ITP a/w ALPS. very few are T cell origin <10% plasma cells in marrow. thrombocytopenia 3. spleen. hypercalcemia. Strep pneumo) plasma cell dyscrasia (B cell malignancies) common because germinal centers have such high error rates! malignant plasma cells --> 1. marrow infiltration --> anemia.o.
very aggressive plasmablastic indolent . painful lymph node when drinking alcohol contiguous LN involvement suggests spread via lymphatic system Reed Sternberg cell . chemo + autologous HSCT w/ treatment. cure rate >50% 3% follicular lymphomas transform to aggressive forms NonHodgkin's lymphoma adults .mature places heavy chain next to cMyc oncogene.B cell tx of infectious agent neoplasm w/ translocation 8. environment al exposure (chemicals fertilizer. rare hepatosplenomegaly. pylori a/w anti-apoptotic) MALToma . rituximab If relapse. immune suppression. autoimmune dz (Sjogrens. human herpes virus 8. Stage 2 = 2 LN Stage 2. Stage 4 = diffuse/ dissem involv of extralymphatic organ Indolent .75% no treatment . incurable aggressive .releases cytokines that cause severe inflammation.both respond to Burkitt lymphoma . performance status 2-4.mos w/o tx. light chain restricted. Stage 2 = 2 LN regions on same side of diaphragm. motile. supraclavicular.90%.Ann Arbor staging: extended field radiation Stage 1 = single LN region. very aggressive / high grade .dec apoptosis.~90%. HIV/AIDS. immune deficiencies anemia of chronic inflammation. 4% of new malignancie s. immune dysreg. observation after chemo. infectious (HTLV1.usually present as lymphomas. combo chemo outpt. EBV. Stage 4 = Stage 4 disease diffuse/ disseminated combination chemo cocktail involvement of extralymphatic organ (ABVD) If relapse occurs >1 year.diffuse large B cell lymphoma (AGGRESSIVE). combo chemo inpt. Stage 4. adults at age > 30 fastest growing malignancy !! age (50-60 y. neutropenia < source (Pseudomonas) 7days.firm. pesticides. H. chemotherap y. elevated LDH. but if abnl lymphocytes automatically stage IV disease CHOPR = Cyclophosphamide. Stage 2. profound anemia) secondary malignancies.survival mos yrs w/o tx.18 (moves diffuse large B involve the BM Ig heavy chain next to Bcl-2 = cell lymphomas marked overexpression of Bcl2 = hepC a/w splenic marginal zone lymphoma. use rituximab determine prognosis via IPI = (improves lifespan) inc risk is age > 60. RA.dec apoptosis. endemic (Africa) T cell lymphoma --> disfiguring skin lesions --> forms a/w jaw swelling & EBV. radiation. elevated LDH LN bx: Reed Sternberg cell (transformed post-germinal B cell w/ EBV transcripts present) Staging: PET scan + CT. lymphoblastic spreads hematologically so random lymphadenopathy indolent / low grade . if relapse occurs <1 year. H.survival wks . 5y survival: Stage 1.o. Burkitt's lymphoma monomorphic cell population w/ vacuoles + c-myc rearrangement BM bx: not std of care.14 mycosis fungoidies . Celiac). CAD Ann Arbor staging: Stage 1 = single LN region. prednisone. ALL/NHL in GN bacteremia from enteric remission. Hashimotos. hepC. slightly inc mitosis. follicular lymphoma . rubbery.3 disease regions on same side of combination chemo + diaphragm. VERY inc mitosis see risk factors Fever neutropenia Low risk HIV a/w increased Burkitt's lymphomas.nodular/ follicular pattern. Stage 3 85%.death!! (mass effect. rising incidence Burkitt lymphoma peaks in kids age 11. no localization most common type of lymphoma.burkitt's lymphoma (VERY AGGRESSIVE). >50) later exposure to EBV. iatrogenic immunosupp . Stage 3 = radiation to residual areas LNs on both sides of diaphragm. extranodal manifestations (rare except in HIV+ or advanced stage). lower cervical). AIHA).18).50% can be cured if respond to salvage + transplant recommend observing indolent NHL like follicular lymphoma if asymptomatic. HSCT .pylori) LN bx: Diffuse large B cell large abnl lymphocytes that replace nl LN architecture. HIV.dec apoptosis.Disease Clinical Variants Hodgkin's lymphoma Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications asymmetric lymphadenopathy (90% of cases . fever. follicular lymphoma (INDOLENT) kids . bone marrow biopsy Localized disease (Stage 1) . >50% cure rate very aggressive survival days to weeks. retreat as new HL patient. EBV stage) negative) Solid tumors. hydroxy doxirubicin. solvents). Stage 3 = LNs on both sides of diaphragm. extranodal involvement. higher SES autoimmune cytopenias (ITP. cytogenetics show t(14. B symptoms (1/3 of cases). once symptomatic. oncovin (Vincristine). diffuse large B cell. elevated ESR. Ann Arbor stage 34 Ceftazadime (3rd gen cephalosporin) . expected neutropenia < 10days. diffuse lymphadenopathy & follicular lymphomas usually aggressive have translocation 14. aggressive / intermediate grade . deranged immune system bimodal age distribution (15-34. Sezary syndrome (end non-endemic (a/w HIV.).
CMV. Strep) abdominal symptoms present? GN bacteremia (Pseudomonas). respiratory distress maintain platelet count > 2050K (dilutional effect w/ transfusion) exchange transfusion (plasmapheresis. port pocket infection GN enterics. nutrition IV fluids + urate oxidase + hyperkalemia. obstruction. AML. significant at >300K. varicella. IV calcium gluconade/ hyperphosphatemia. seizures hyperuricemia & hyperphosphatemia -> renal failure hyperkalemia --> arrhythmias (sine wave. GP bacteremia (Staph. double exchange) . and potassium DNA gets further metabolized to uric acid via xanthine oxidase Calcium and phosphorus can complex & precipitate --> kidney stones & renal failure inability to excrete potassium --> cardiac manifestations monitor coags pain mgmt. hypocalcemia. Strep). hyperuricemia chloride if seizure/ heart failure + amphogel + treatments for hyperkalemia hypocalcemia --> muscle spasm. vancomycin. pneumatosis/ perforation abdominal pain in the setting of neutropenia = emergency!! electrolyte imbalance + renal failure bacterial overgrowth syndrome in the intestine (usually cecum) --> increased risk of sepsis and GI manifestations CT: thickened bowel wall from fluid/ air/ bacteria within the lumen BSA management of constipation/ diarrhea Tumor lysis syndrome Normally. pulmonary leukostasis (similar to ARDS) ALL: 9-13% patients. Anaerobes other sources? HSV. urate neurological changes oxidase (stroke.Fever neutropenia Disease Clinical Variants High risk Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications ALL/NHL in induction. the administration of chemotherapy causes the release of DNA. Torsaud's) Hyperleukocytosis WBC > 100K AML: 5-22% patients. high dose cytarabine. syndrome . GI. thrombosis). +/tobramycin unstable: meropenum. GI bleed. Staph/ Strep. amikacin (double coverage against pseudo) Typhlitis RLQ pain. however.hydration. potassium load is excreted by the kidneys. hypotension. clinically significant at > 200K -> CNS injury (cerebral hemorrhage. phosphorus. localized (central line. CNS bleed). complications related to tumor lysis syndrome treatment for tumor lysis tumor lysis syndrome. or Anaerobes unstable? Tachycardia. rectum) require very aggressive antibiotic treatment!! GN bacteremia (Pseudomonas). HSV). yeasts/ molds GN bacteremia: ceftazadime GP bacteremia: vancomycin abdominal symptoms: meropenum (anaerobes. evidence of sepsis (chills). GP bacteremia (Staph. vancomycin. Pseudo). heart failure. respiratory distress perirectal abscess. mouth sores (mucositis). dysphagia (fungal.
+/anti-platelet antibodies produced bleeding manifestations persistent by B cells adhere to platelets & (3m-1y) target them for destruction. sensory changes. vitB12/ folate def. prevention of cerebral perfusion (presents w/ edema of upper extremities. TPO receptor agonists . secondary: HIT. TTP) . infection induced. platelets nl or increased in size consider drug induced.bone marrow exam Thrombocytopenia dec platelet prod by marrow: primary: marrow failure (SAA). block release of platelets most kids spontaneously remit. MDS.obstruction of venous return to the heart -> compression. scurvy. IVIG. previously healthy.consider hemolytic anemias (DIC. hep). done only if suspect other abnl Check HIV & Hep serologies! Check for other autoimmune d/o: Anti-phospholipid antibodies. nonhemostatic dz like Cushing's. usually antibodies also inhibit chronic (>1y. mostly isolated thrombocytopenia. infxns.000 per year avg age 2050 CBC: platelets < 100K Smear: dec # platelets. mucosal bleeding. posttransfusion purpura platelet sequestration (spleen) dilutional thrombocytopenia (blood transfusions) pseudo-thrombocytopenia (clumping of platelets) Immune thrombo. congenital thrombocytopenia . Anti-D if pt is Rh+ 2. HUS. purpura (platelet d/o.nl RBC morphology. chemo. alcohol. collagen-vascular.Newly heterogeneous autoimmune primary immune-mediated cytopenia (ITP) diagnosed destruction of platelets in d/o characterized by: (<3m. secondary: meds. accessory muscle usage .clumped platelets . orthopnea. drug. abnl laminar flow. head. hoarseness. follows infection megakaryocyte maturation/ mostly adults) proliferation. vasculitis. TSH. rituximab. liver dz (dec TPO) accelerated destruct of platelets: non-immune: DIC. can encroach on spinal column. rad. viral infxn (HIV. neonatal alloimmune thrombocytopenia. decreased strength. acute respiratory changes . dysphagia. large platelets BM bx: increased megakaryocytes. glycoprotein antiplatelet Abs. age) chloromas = masses of WBCs in leukemia patients. steroids. just enough to stop bleeding) maintain platelet count > 30K for stable hemostasis 1. lymphoprolif dz. rectal tone petechiae (platelet dysfxn or severely low platelet counts).PE) CXR!! sedation is contraindicated!! Spinal cord compression back pain. immune suppression. most adults have chronic or persistent ITP 1. MPDs.induced platelet consump.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Mediastinal mass tripod position. thrombosis.54/100. causing paralysis 3-5% of newly diagnosed oncology patients platelets <150K Normal WBC & Hb? Check peripheral smear . wheezing) SVC syndrome . ANA prevent/ stop bleeding if present increase platelet count (but not to nl levels.suggests airway compression (presents w/ cough. ITP. immune: primary: ITP. coag d/o. lymphoproliferative d/o. peripheral blood kids) no underlying cause.redraw in sodium citrate or heparin Abnl Hb & WBC? . increased reflexes. TTP. chemo.fragmented RBCs . AMS changes. marrow infiltration. splenectomy. CTDs.
skin necrosis.low score (<3 pts) a/w up to 1. heparin + PF4 attaches to IgG to form immune complex immune complex attacks the platelet --> immune mediated platelet destruction & removal of platelets by splenic macrophages at same time. HbH inclusions CBC: mild anemia + significant microcytosis = alpha thal minor. & activation of clotting cascade --> thrombosis & significant risk of VTE pre-test clinical scoring system: 4Ts (thrombocytopenia: platelets fall >50% reaching nadir >20K. low normal MCV but hematologically normal = alpha thal carrier . timing: clear onset btwn days 5-10. thrombosis: new thrombosis confirmed. TB) Hyperplastic responses (chronic hemolysis) blood & fluid resuscitation results in fall in platelet count generally. loss of at least 1-2 blood volumes occurs before significant decrease in platelet count becomes apparent after HbF decreased production of globin chains during hemoglobin transitions to HbA synthesis Deletion of 1 or 2 alpha genes rarely problematic bc gene (usually in African Americans as duplication an evolved protection against malaria) HbH disease . splenomegaly) infiltrative diseases (MPD. other causes: none apparent) . acute reaction.6% +HIT assay.severe anemia + splenomegaly loss of all alpha genes = no HbF = Hb Barts = hydrops fetalis (fatal in utero) loss of 3 of 4 alpha genes = HbH disease loss of 2 of 4 alpha genes = alpha thalassemia minor loss of 1 of 4 alpha genes = alpha carrier state thrombocytopenia Dilutional thrombocytopenia replete 1 unit of platelets per every 5-6 units of blood Thalassemias (general) Alpha Hb Electrophoresis: HbH Iron studies: normal ferritin Smear: target cells. there is platelet activation. leading to platelet destruction splenomegaly hepatic cirrhosis w/ portal HTN (low TPO.Life & limb threatening coagulation therapy!! condition Treat thromboembolic event continue anti-coagulation after d/c from hospital thrombosis risk remains Drug induced thrombocytopenia Platelet sequestration drugs induce antibodies or caused by direct antibody formation to drug OR drug+ lupus-like syndrome protein on platelet can form hapten. Guacher's dz) Inflammatory dz (Sarcoid. & high (6-8 pts) a/w 21-100% HIT+ assay requires IMMEDIATE thrombotic events!! discontinuation of heparin & use of alternative anti. release of platelet granules. intermediate (4-5 pts) a/w 8-28%.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Heparin-induced thrombocytopenia (HIT) heparin attaches to platelet factor 4 (which is released from platelets). platelet aggregation. microcytic.
dec serum ferritin Iron deficiency anemia weakness. unknown Smear: microcytic hypochromic RBCs Iron studies: low serum iron. dec % sat. excessive menstruation). & DM (from iron deposition on other organs) Hypoproliferative anemias (general) decreased absolute retic count (<75. jaundice. dyspnea loss of iron > absorption of iron PE findings: pallor.colon Ca. high RDW (very different cell populations) -----------Beta thal minor: anemia w/ elevated RBC count.Disease Clinical Variants Beta Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications B+ has mutation that disrupts translation B0 has mutation that stops translation B0 = beta thalassemia major = severe transfusion dependent anemia. fatigue. frame shift. abnl globin synthesis. liver. more microcytic than anemic. inc TIBC. inc requirements (pregnancy. pathologic bone fractures & deformities Beta thal major: blood transfusion Hb Electrophoresis: small amt or absent HbA. nl RDW. abnl assembly of porphyrin ring inc blood loss (GI . hypochromic. spleen sequestration. GI dz. splicing) --> abnl translation --> decreased production of beta globin chain (B+) or no production of beta globin chain (B0) excess alpha chains --> insoluble & precipitates producing inclusion bodies in RBCs --> membrane damage. growth retardation.require iron chelating agents cardiac dz. pica sx of underlying disease process . normocytic. endocrine failure B+ = beta thalassemia minor = asymptomatic + splenomegaly multiple mutations (promotor mutations.000) or corrected reticulocyte % (<2%) Microcytic. lactation). hepatosplenomegaly. or macrocytic (see below) decreased production of hemoglobin/ RBCs Microcytic anemias (general) corrected retic % < 2% MCV <80 anemia resulting from problematic hemoglobin synthesis inadequate iron supply (deficiency or not free for utilization). predominant HbF Smear: microcytosis. angular stomatitis. iron malabsorp). koilonychia (spoon nails). increased HbA2 & HbF on electrophoresis hemochromatosis (iron overload following blood transfusions) . & profound anemia marrow amps up to make more RBCs and expands --> frontal bossing. bone changes. iron overload --> cardiac. infections. dec iron intake (diet. glossitis.
hormones secreted cause plasma expansion.Disease Clinical Variants Anemia of chronic disease (ACD) Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications underlying problem for >6 weeks activated monocytes & macrophages --> decreased RBC survival & blunted response to EPO --> EPO deficiency inflammation induces hepcidin release from liver --> inhibition of ferroportin on macrophage surface --> iron is locked in RES (metabolically unavailable) so cannot re-enter circulation to make new RBCs chronic infections (TB. resulting in less EPO production. neoplasms. nutritional deficiency w/ dialysis Metabolic . RA. hospitalize d patients! Iron studies: low serum iron. thus less RBC & Hb production. lead CBC: high RDW poisoning Iron studies: high iron. dilutional . low % saturation. high ferritin BM bx: increased RES iron storage Thalassemia (SEE ABOVE SEPARATE CATEGORY) autosomally inherited deficiency in rate of synthesis of nl globin chains Sideroblastic require smear for diagnosis anemia defect in heme synthesis --> accumulation of iron in mitochondria most endemic high RBC & low Hb or low common malaria areas MCH monogeneti c d/o worldwide inherited defects Smear: dimorphic picture (normal RBCs+ hypochromic secondary microcytic cells) defects .preBM bx: ringed sideroblasts leukemia. high ferritin Normocytic anemias (general) corrected retic % < 2% MCV 80-94 anemia resulting from inadequate stem cells that become RBCs or decreased demand for RBCs Pregnancy pregnancy = pseudoanemia. (rings around nucleus & iron in drugs (INH). EPO deficiency. mitochondria) alcohol. shortened RBC survival. abscess. nl TIBC. chronic inflammation (arthritis. causing renal failure measured hemoglobin to be slightly low renal failure = lower limit of creatinine clearance indicates severe kidney disease. low transferrin. syphilis). gout) 2nd most common cause of anemia.
RBC precursors. hypercellular homogenous blasts = leukemia Anemia of chronic disease (ACD) initially presents as normocytic anemia (as disease progresses.Disease Clinical Variants Endocrine Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications androgen deficiency testosterone stimulates EPO release from kidney. when androgen deficient. tear dropped RBCs = infiltration BM bx: fibrosis = myelofibrosis. membrane (target cells) obstructive jaundice. tumors. most likely due to abnormal DNA synthesis retics are not recognized by CBC as different RBCs so can cause increased MCV. must correct retic count with anemia!!! large RBCs from increased red cell liver disease. scar tissue aplastic anemia leukemia Marrow failure stem cells can't differentiate so they accumulate in primitive forms CBC: normocytic anemia + alterations of other cell lines Blood smear: early WBC. Howell-Jolly bodies (inclusions in RBCs) suggest splenectomy high reticulocyte count Target cells Severe hypothyroidism . fat cells / hypocellular = SAA. post splenectomy mild increase in MCV due to increased lipid in membrane (usually normocytic though!!) bull's eye appearance on smear. no testosterone to stimulate EPO Hypothyroidism = reduced thyroid hormone causes reduced metabolic rate & decreased need for O2 (thus Hb) adrenal failure = corticosteroid deficiency causes anemia androgen deficiency hypothyroidism adrenal failure Marrow replacement damage to bone marrow --> fibrosis infections. it becomes microcytic anemia) Macrocytic anemias (general) corrected retic % < 2% MCV >94 anemia resulting from problematic RBC division.
methionine is used to make folic acid def: SAME myelin (no B12 = demyelination & hematologic & symptoms as neuropathy) B12D EXCEPT no neurological involvement!!! Folic acid def etiologies . NL methylmalonate increased retic count isolated elevation of non-conj/ indirect bilirubin increased LDH decreased haptoglobins hemosiderinuria . myelodysplastic syndromes. immature chromatin (more euchromatin than dark heterochromatin). pernicious anemia. high LDH. proprioception. increased marrow is mounting a normal urobilinogenin in urine. removing normal RBCs from circulation = shortened RBC survival = increased retic count vitB12 deficiency. folate deficiency. conversion is blocked &THF is lateral corticospinal tract trapped as N-methyl THF. Crohns). fish tapeworm FH of autoimmune dz (B12d) CBC: large RDW B12 injections / oral supplementation Smear: macro-ovalocytes. the spleen will defect resulting in nonimmune mediated hemolysis collect the RBCs and destroy them in states of splenomegaly (infxn. malignancy). bone in the vessels --> hi plasma marrow. nl serum folate. small bowel dz). glossitis (beefy red synthesis tongue). probs homocysteine to methionine via w/ posterior columns methyl group from THF. imp absorption (liver dz. inc TIBC B12D: low serum B12. elderly). small bowel dz Celiacs. increased delivery of iron from RBC breakdown Immune mediated hemolysis products antibody and/or complement fixation to RBCs results in intravascular hemolytic phagocytosis by macrophages in anemia . inc homocysteine. hereditary defects in DNA synthesis B12D = vegans.o B12. hemoglobinuria (rare) decreased measured RBC survival . inc indirect bilirubin. insuff substrate stomatitis (cracking at corners (thymidine) to support DNA of mouth). liver dz. nl serum B12. if acquired extrinsic RBC RBCs are abnormal. a probs . hi urine Hb. or liver Hb.intravascular hemoglobinemia.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Megaloblastic corrected retic % < 2% anemias MCV >94 Acquired hemolytic anemias (general) Splenomegaly problem with DNA synthesis folate def: THF (derived from folic acid) converts dUMP to dTMP. def interconversion (drugs like MTX) represents destruction corrected retic >2% or (hemolysis) or loss of RBCs in 75.inadeq dietary intake (chronic alcohol. vibration. absorption probs (low pancreatic enzymes. large platelets Other tests: inc LDH. high response to the anemia iron % sat. B12 def: jaundice. inc homocysteine. hypersegmented neutrophils. and iron-stained renal tubule cells spleen normally filters blood. angular w.spasticity. dementia) metabolically useless substrate. the spleen will filter the blood too effectively. autoantibodies to parietal cells/ IF/ thyroid if autoimmune Folate def: low serum folate.000 circulation (bleeding . inc requirements (pregnancy).GI or GU extravascular hemolytic tract) anemia .destruction of RBCs in RES--> increased increased retic count means indirect bilirubin. w. neurologic irreversible probs B12 def: B12 converts (peripheral neuropathy.RBCs burst apart splenic fenestrations. chemotherapy. inc methylmalonate.o folic acid.
TTP. hemangiomas. warm or cold antibody AIHA occurs mainly in spleen infections Cold antibody . low phosphate). IgG+Complement.IgG or Idiopathic. RA. nonimmune mediated Physical & chemical agents (burns. when transfused w/ these RBCs. acanthocytes (abnl lipid deposition w/ severe liver dz.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Fragmentatio acquired extrinsic RBC RBCs encounter an abnormal n hemolytic surface in circulation (heart valve. marrow/ other RES sites idiopathic. paroxysmal cold hemoglobinurea (actually IgG mediated cold antibody AIHA) acquired extrinsic RBC defect resulting in immune mediated hemolysis Smear: microspherocytes + increased reticulocytes.breakdown of RBCs or membrane lipids Lipid abnormalities & hypophosphatemia . SLE. Cold antibody? hemolysis occurs in liver/ bone Infections. & death Autoimmune hemolytic anemia Antibodies developed to self RBCs Warm antibody? Warm antibody . HUS.IgM antibodies so complement activation only. severe AS. defect resulting in nonanemia immune mediated hemolysis fibrin deposits) --> shearing apart of the RBCs also a/w thrombocytopenia valvular/ vascular prosthesis. bacterial infections) . malignant hypertension. infectious agents (malaria) Alloimmune hemolytic anemia acquired extrinsic RBC defect resulting in immune mediated hemolysis transfusion acute transfusion reaction major blood group incompatibility -. pulm HTN systemic illness Smear: schistocytes Other acquired extrinsic RBC abnormalities defect resulting in noncausing immune mediated hemolysis acquired. Cold antibody (Complement only) Warm antibody responsive to steroids & splenectomy Cold antibody unresponsive to steroids & splenectomy .abnormal lipid deposition (liver dz) or dehydration from abnl fxn of Na/K ATPase (hypophosphatemia) Infectious agents . lymphoprolif d/o. renal failure. DIC. the Hb goes up but then immediately falls (hemolysis) delayed transfusion reaction Hb increases but then begins to fall 7-10d later (hemolysis). eclampsia.malaria. cold antibody AIHA has prominent agglutination or clumping of RBCs Coomb's test: Warm antibody (IgG or IgG+complement). babesiosis Smear: marble appearing RBCs (physical or chemical agents). hemolysis lymphoprolif d/o. autoimmune dz. pt made new antibodies that attacked the transfused RBCs acute transfusion rxn activation of coagulation system. vasculitis.reactions > preformed antibodies to RBCs.
aldomet for HTN Inherited hemolytic anemias (general) corrected retic >2% or 75. elliptocytosis.hemolysis at higher concentrations (membrane is already very leaky) abnl cytoskeleton proteins deficiencies in proteins that bind to spectrin (which is the foundation of the protein matrix) Smear: microspherocytes. which stops RBC production for 7-10d (usually childhood presentation) disorder in RBC membrane autosomal shaped causing "marble shaped" dominant. splenectomy helps with elevated retic count (looks just symptoms but morphological changes persist like AIHA so need Coomb's test to R/O) Hereditary elliptocytosis hemolytic anemia (mild to moderate) high phenotypic variability within families severe hemolytic anemia abnormal RBC shape with heat abnl spectrin interactions with other matrix proteins autosomal dominant Smear: elliptical RBCs (if >20% = diagnosis) Hereditary pyropoikilocytosis major deletions in portions of spectrin molecule = abnormal fragments of RBCs autosomal recessive Smear: fragments of RBCs.Antibody Hapten against a drug that is bound to penicllin type? RBC --> IgG positive Coomb's Penicillins. RBCs sometimes AR osmotic fragility .Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Drug induced acquired extrinsic RBC hemolytic defect resulting in immune anemia mediated hemolysis Hapten-Penicillin type . personal or FH of premature gallstones/ anemias/ splenectomy/ or specific dz. worse w/ heat . Autoimmune-Aldomet type (very quinidine. recurrent "hepatitis". cephalosporins.000 neonatal jaundice. chronic or recurrent symptoms that have not been adequately addressed intrinsic defect in RBC leads to hemolysis gallstones? Increased Hb breakdown = inc indirect bili = inc bile salts = inc pigmented gallstones --> cholecystectomy problem w/ membrane? Hereditary spherocytosis. ceftriaxone Innocent Bystander type (most common!) . pyropoikilocytosis problem w/ hemoglobin? sickle cell anemia problem w/ enzymes? G6PD deficiency Hereditary spherocytosis hemolytic anemia (mild to severe) aplastic crisis w/ infection (ParvoB19).antibody against the Innocent drug forms an immune complex that adheres to RBC surface --> bystander complement positive Coomb's type? Sulfonamides. phenothiazines rare now since don't really use these meds) autoantibody to Rh Autoimmine components of RBC --> IgG Aldomet type positive Coomb's L-DOPA.
pneumo. substitutions. or increased temperature. hemolysis w/ infxns or DKA 7-8% of African Americans. Duffy response) --> intravascular and/or minor antigens extravascular hemolysis ARF. sepsis. sickle nephropathy #1 cause of death? Acute Chest Syndrome G6PD deficiency can present w/ drug-induced hemolytic anemia (antimalarials. anemia severely immunocompromise d.a. there is inadeq defective NADPH so Hb and proteins become oxidized and precipitate enzyme fxn. liver.Disease Clinical Variants Sickle cell disease Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications hemolytic anemia increased severity of infections (s. neonates Transfusion reactions Acute hemolytic transfusion rxn intravascular hemolysis. healthcare $) Hb electrophoresis: HbS only (Sickle cell disease).nonopiods (absolute dose ceiling). stroke. neonatal jaundice. gut skin sloughing often due to ABO incompatability.fever inc sickling. Kidd. increased MCHC. IgM STOP transfusion!! Flush w/ IVF Check CBC to monitor platelets & Hb. mild jaundice. staining of Heinz body inclusions Transfusion associated GvHD nearly uniformly fatal involves marrow. sudden onset pain in extremities & back) Sickle cell carriers asymptomatic except when exposed to severe hypoxia or dehydration Hb SC dz . chills. n/v Delayed hemolytic transfusion rxn 3-10d after transfusion of blood that appeared compatible often asymptomatic w/ fever.occlusion of large vessels sickle nephropathy .sickled RBCs disrupt vasa recta & glomeruli Leg ulcers. complement mediated. back pain. renal failure antibody not detected preantibodies to transfusion (Anamnestic antibody Rh. polymerization makes RBCs rigid & unable to circulate well -> mechanical destruction in circulation. nephropathy) severe pain episodes (bone degeneration from sickling --> arthritic pain & loss of function.increases production of HbF to interfere w/ sickle cell polymerization & reduce frequency of sickle events pain mgmt . 10-15% of Mediterrane an heritage Smear: bitocytes. HbS + HbA (sickle cell trait). opiods (no abs dose ceiling) stroke. hypotension. check renal fxn labs and coagulation studies DIC. inc meningtiis Stroke . or in RBC --> inclusions of Hb that combos bind RBC membrane (Heinz bodies) occurs if immunocompromised patients receive blood that is not irradiated!! 8-10% of African Americans pain is the most severe complicatio n (disability. Mediterranean favism.milder sickle anemia. reducing capacity (requires NADPH & NADH) a. mild probs in childhood so might present later in life mutation in 6th position of beta globin chain where valine is substituted for glutamic acid = Sickle cells polymerize during states of deoxygenation. meningitis) tissue infarction w/ organ failure (leg ulcers. plugging of small vessels --> ischemia & pain severe infxns . skin.pneumo (which can cause sepsis in these pts!). DIC . acidosis. deletions. inc S. or insertions resulting in G6PD instability. In G6PD def. sickle pain Mature RBCs depend on anaerobic glycosis for ATP generation. HbS + HbC (Hb SC disease) hydroxyurea . sulfonamides). congenital nonspherocytic hemolytic anemia. most likely due to clerical error (misidentification of patient) Sx: fevers.
One degree Celsius rise in temperature to the febrile range cannot be distinguished from fever in acute hemolytic rxn so transfusion must be stopped!!
occurs from cytokine release from WBCs in the unit being transfused, antibodies to donor WBCs, or bacterial contamination
rash and/or itching ONLY reaction where blood can be restarted & work up is not mandatory
unit becomes contaminated w/ Platelets bacteria (much more likely to occur usually Staph in platelet units which are stored at room temp) RBCs - usually Yersinia enterocolitica, Citrobacter recipient is previously sensitized to soluble allergens in donor unit
3% of transfusions (second most common reaction) consider IgA deficiency!
Benadryl, then start transfusion again
hypotension, chills, fever, dyspnea, n/v, diarrhea, urticaria
antihistamine, epinephrine, steroids, supportive care
Transfusion respiratory insuff, fevers, antibody mediated situation often FFP related acute chills, hypotension due to HLA antibodies present in transfusions lung injury the transfused product (TRALI) mimics ARDS but resolves w/I 48h Tranfusion fluid overload --> breathing associated problems circulatory overload (TACO) Iron overload liver/ cardiac/ endocrine problems occurs in patients w/ pre-existing cardiopulmonary compromise, perhaps a/w hypertension
#1 leading cause of death from transfusion
CXR: bilateral chest infiltrates does not improve w/ diuretics
improves w/ diuretics (UNLIKE TRALI!)
each unit of RBCs contains 200mg of iron; patients who are chronically transfused (sickle cell) have higher risk of iron overload transmission of Aspergillus mold from environmental source CT of head to check for dissemination to brain CT: characterisitc halo description of nodular infiltrate
chelation therapy (Exjade)
most popular fungal infxn in HSCT pts Colonization - non-disease state; Aspergilloma = mold fills lung cavity & releases spores; a/w colonization in CF patients Invasive disease pulmonary, sinusitis, tracheobronchitis, cutaneous, disseminated
mold w/ high mortality rate Rhinocerebral nasocongestion, pain behind eye, proptosis, AMS Pulmonary - dyspnea, fever, non-productive cough, pleuritic chest pain
spores are inhaled and deposit on mucosa, then germinate and invade tissue; angioinvasion --> tissue necrosis
low incidence (1.7/100K)
neutropenia, immunocomp (HSCT, organ transplant, cancer, autoimmune dz), poorly controlled DM
MRI shows opacification of sinuses, brain edema & invasion CXR shows dense infiltrates; CT does NOT have halo infiltrates like Aspergillus Cx: grows very quickly, branching hyphae
most common fungal infection in hospitalized patients variety of presentations - UTI, pneumonia, mucocutaneous (thrush, esophagitis, diaper rash), tissue, bloodstream
bloodstream infxn risk factors? Neutropenia, indwelling devices, hemodialysis, DM, AIDS, abd surgery, critical illness, neonate, age>65, TPN, broad spectrum Abs
if affects lung via hematogenous do not treat asymptomatic spread, can see lung abscesses UTI (unless prior to GU surgery, immunocomp, or white plaques on soft palate, neonates) esophagus symptomatic UTI hepatosplenic candidiasis amphotericin B or microabscesses in liver & fluconazole spleen seen on MRI (heme-onc pts only) dx? Blood/ mucus/ bx culture,
Qualitative (general) platelet disorders
platelets present in adequate acquired causes - meds, MPS, numbers but do not function systemic illnesses, renal dysfxn, properly cardiopulmonary bypass Congenital causes - granule disorders, absent/ dysfunctional adhesion receptors
DDAVP - synthetic derivative of ADH/vasopressin so causes release of VWF from endothelium (increases stickiness of plasma) anti-fibrinolytic agents block plasmin and prevent lysis of fibrin within clots
aspirin, NSAIDs bruising, bleeding
Aspirin = irreversible COX1 inhibitor; platelets do not synthesize new COX1 (anucleated) so reversal of aspirin effect depends on platelet half life (3-5d); after new platelets are made, function returns NSAIDs = reversible COX1 inhibitors; reversal of NSAID effect depends on half life of the drug
Clopidogrel (Plavix) Uremia (renal dysfxn)
irreversible inhibitor of ADP receptor, blocks platelet activation accumulated metabolites impair fxn of circulating platelets dialysis corrects platelet dysfxn
normal platelet count w/ mucocutaneous bleeding
absence or dysfunction of integrin aIIbB3, preventing platelet aggregation
mutation within the binding site of aIIbB3 or talin deficiency (talin nl exposes binding site)
PFA - no aggregation but will agglutinate w/ ristocetin
BernardSoulier syndrome Absence of platelet granules
thrombocytopenia w/ giant platelets
absence or dysfunction of platelet adhesive receptor (GP1b), preventing platelet adhesion dense granule def - patients will also have varying degrees of albinism alpha granule def - gray platelet syndrome
PFA - aggregation but no agglutination w/ ristocetin
PFA - loss of 2nd wave (no aggregation because deficiency of granules or dysfunctional granule release)
von Willebrand disease (VWD)
Dysfunctional granule release (general) VWF activity less than 30% certain conditions can also change autosomal the amount of circulating vWF; ie dominant = increased bleeding risk sympathetic response has increased vWF in preparation for injury hi vWF - stress, exercise, pregnancy, age, acute & chronic inflamm, DM, OCP use, malignancy, hyperthyroidism low vWF - hypothyroidism, blood type O significant bleeding history, decreased synthesis & plasma FH of inc bleeding or VWD, secretion of VWF; can also occur as a result of inc clearance low levels of VWF activity low factor 8 activity leading to hemarthrosis high circulating VWF but defective function
low agglutination with ristocetin
plasma derived factor 8 products w/ high concentrations of VWF DDAVP
Type 1 (7580%)
Type 3 (13%) Type 2 normal VWF levels but (qualititative; decreased VWF activity 15-20%) from: 1. decreased multimers circulating 2. decreased binding to factor GP1b 3. abnl binding to factor 8 4. dysfxnal hi affinity interaction w/ GP1b
Hemophilia A = factor 8 deficiency Hemophilia B = factor 9 deficiency Bleeding into joints/ muscles, prolonged bleeds from lacerations or dental procedures, excessive bruising / hematomas, bleeding w/ surgery or trauma, intracranial hemorrhage, kidney / GU tract bleeding
defect in platelet surface thrombin generation (factors 9 & 8 are required to provide platelet surface for activation by factor 10)
X-linked 20-30% = spontaneous mutations
A = 1/10K male births B = 1/30K male births
replace missing clotting factor - recombinant release of stored factor 8 w/ DDAVP
60% of patients are severe - spontaneous bleeds 15% are moderate trauma/ surgery bleeds, occasional joint bleeds 25% are mild - major trauma/ surgery bleeds, rare joint bleeds 25% of hemophilia A pts will develop spontaneous antibodies to factor 8 other complications? chronic hemarthrosis w/ pain/ joint destruction, HCV, HIV risk
severe bleeding in pt w/ no auto-antibodies bind native factor known bleeding problems 8 in persons without congenital hemophilia bruising, mucosal bleeding, muscle bleeding
a/w autoimmune 1.4/1million conditions, pregnancy, mortality 6malignancy 20% (highest in elderly)
prolonged PTT, elevated mixing study (suggests inhibitor to intrinsic pathway factor)
control bleeding eradicate inhibitor w/ steroids, IVIG, rituximab
looks like DVT…
antibodies that inhibit phospholipid dependent coagulation; neutralized by presence of excess phospholipids
symptoms + factor 8 >10% that "titers up" with dilution titered up PTT post mixing!!!
Vitamin K deficiency
muscle bleeding, deep bleeds
blocks conversion of vit K dependent factors (2, 7, 9, 10, protein C, protein S) to activated forms --> bleeding
infancy, malabsorption, hyperemesis gravidarum, fasting, alcoholism, drugs (warfarin, Abs, salicylates)
intercerebral, GI, prolonged PT, prolonged PTT, asymptomatic? Oral or IM vitK umbilical, or ENT post mixing study corrects bleeding PTT active bleed? Emergency! Requires FFP then correct vitK
liver makes all coagulation factors (except VWF), anticoagulants (protein C & S), and TPO (stimulates platelet production) liver failure = deficiency of majority of coagulation cascade, splenomegaly, thrombocytopenia, bleeding
Factor 12 deficiency
Hageman factor NOT a/w bleeding
increased fibrinogen? Acute prevents stable formation of crossphase reactant, inflammation, linked fibrin clot OR overproduction of fibrin clots pregnancy decreased fibrinogen? DIC, liver dz, ascites, alcohol
deficiency? Abnl PT & PTT, prolonged thrombin time, abnl fibrinogen assay
Hemolytic Uremic Syndrome (HUS)
#1 cause of acute renal failure formation of clots in the glomerulus in kids acquired (90%) - infection (prodrome of bloody diarrhea --> classic triad - intravascular release of large vWF multimers = hemolytic anemia increased thrombosis) genetic (atypical HUS) - mutations (schistocytes), in complement pathway (factor H thrombocytopenia, renal normally suppresses C3b failure convertase; however, without factor H, convertase able to activate complement all the time --> thrombosis)
Smear: schistocytes from fragmentation
acquired? Supportive tx only Atypical? Poor prognosis w/ renal failure; cannot be transplanted (intrinsic dz)
clots generated in small vessels, turbulent flow shears RBCs, platelets consumed by thrombosis & shearing --> excessive thrombin generation & loss of compartmentalization (diffuse endothelial injury, loss of endothelium = loss of inhibition) Thrombotic Thrombocytopenic Purpura (TTP) pentad: hemolytic anemia (schistocytes), thrombocytopenia, renal insufficiency, neurologic changes, fever absent ADAMTS13 = large multimers of VWF formed that activate platelets = widespread thrombosis (primary hemostasis) Acquired - Ab formed to ADAMTS13 congenital - def ADAMTS13 sepsis, malignancy, trauma/ head injury/ burns, obstetric causes (eclampsia, retained fetus, abruptio placenta) others? AA, toxins, transfusion, immunologic elevated clotting times & decreased platelet count ELEVATED D-DIMER FFP transfusions but watch for volume cryoprecipitate to keep fibrinogen elevated platelet transfusions (keep platelets > 50K) ??heparin plasma exchange & vWF inhibitors
Disseminated Intravascular Coagulation (DIC)
bleeding + subclinical or clinical thrombosis sepsis patients!
uncontrolled activation of primary & secondary hemostasis, activation of fibrinolysis, consumption of factors & inhibitors, and evidence of end organ damage Cytokines, TF, LPS, hemolysis, acidosis, turbulence all contribute to factor activation, endothelial damage, & platelet activation
abnl formation of blood clot inside venous system (fibrin mediated) embolism - detached intravascular solid mass that is carried by blood to site distant from its origin Virchow's triad - endothelial injury (atherosclerosis, TTP, HIT, trauma) + abnormal blood flow (stasis from immobilization, stenosis) + hypercoagulability (thrombophilias)
age, comorbid Wells score conditions (OCP use, lower extremity U/S, CT of chest HRT, to R/O PE hospitalizati on, cancer, surgery) immobilizati on, burns, HIT, DIC, pregnancy persistent risk factors? Inherited thrombophilia, acquired thrombophilia s, obesity, CHF, nephrotic syndrome,
heparin (LMWH or UFH) UFH cleared by macrophages so no effect on kidney or liver + short half life; LMWH is fast acting and more predictable but renally cleared bridge with warfarin (at least 5 days overlap) before d/c heparin
anticoagulation continued if high risk of recurrence (i.e. no reason for VTE at time of diagnosis unprovoked VTE, type of underlying syndrome, gender - men, elevated D-dimer 1m after d/c warfarin) post-thrombotic syndrome (see below)
Superficial vein thrombosis (SVT)
generally benign & self limiting becomes more serious if extends into deep vein tender, palpable cord w/ surrounding erythema & heat
thrombosis in superficial vein
low dose heparin for at least 4 weeks
Deep vein thrombosis (DVT)
occlusion of deep veins in leg --> lack of venous return of blood --> congestion & pain
major risk of embolization to lungs (PE) and post thrombotic syndrome (PTS) 20-50% of pts w/ symptomatic proximal vein DVT common femoral or iliac vein DVT hi BMI prior ipsilateral venous thrombosis female older age regular use of compression stockings! (must be replaced every 6 months, worn daily for 2y after DVT)
Postthrombotic syndrome (PTS)
develops within 1-2 y of acute DVT; a/w poor QoL possible ulcer formation, lower extremity swelling, pain, itching, heaviness, edema, venous ectasia, hyperpigmentation, pain w calf compression worse sx w/ activity; better w/ rest
damage to venous valves (mechanical damage from clot & inflammation provoked by acute thrombosis)
variable presentation but overall risk of thrombosis increased 15-20x
AT normally inactivates thrombin & factor X to shut down coagulation cascade; deficiency leads to increased thrombosis
1% of pts with VTE 1/250-1/500 prevalence
anti-thrombin activity assay low activity & low numbers of AT (type 1) or normal numbers but low activity (type 2) exclude acquired causes - liver disease, nephrotic syndrome
Protein C deficiency
variable presentation but overall risk of thrombosis increased 15-20x
Protein C (along with Protein S) normally inhibit factors 5&8 of coagulation cascade
2-9% of patients w/ VTE
make sure patient has d/c warfarin for 2 weeks prior to testing Protein C prolonged PTT in protein C deficient plasma Prolonged PTT w/ protein S deficient plasma make sure patient has d/c warfarin and not on hormonal therapy or pregnancy APC sensitivity ratio = PTT in presence of protein C/ PTT in absence of protein C PCR based assay for specific mutation lupus anti-coagulant test (requires 2 tests since insensitive): prolonged clotting time that does not correct w/ mixing + clotting time that shortens w/ addition of phospholipid
Protein S deficiency
cofactor to activated protein C, enhances anticoagulant effect of protein C deficiency a/w increased thronbosis risk
3% of pts w/ VTE
Factor V Leiden
Heterozygotes - VTE risk increased by 5-7x Homozygotes - VTE risk increasd by 50x
mutation in factor 5 gene --> resistance to factor 5 inactivation by protein C
Antiphospholipid syndrome (APS)
synergism w/ OCPs enhanced platelet activation & thrombosis (1+ episodes confirmed by imaging/ path) subsequent aggregation OR pregnancy morbidity (recurrent pregnancy loss) enhanced TF expression thru monocyte activation PLUS inhibition of protein C/S anticoagulant pathway high anti-B2 glycoprotein/high aCL activation of complement antibodies/ high Lupus anticoagulant
Screening / Education .
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Screening / Education .
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Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education newborn screening = early diagnosis & prompt tx of infxns & comps informed reproductive decisions for sickle traits PCN prophylaxis birth to age 5 can be prevented if blood is irradiated for at risk patients!! .
transfuse from IgA def donors if pt is IgA def declining incidence due to use of male only FFP . premedicate.Screening / Education avoid transfusion of plasma containing products. wash products prior to future transfusion.
Screening / Education .
Screening / Education .
Screening / Education give VitK to all newborns as prophylaxis against hemorrhagic disease of newborn .
Screening / Education .
Screening / Education Compression stockings IVC filters if contraind for anticoagulation .
Screening / Education .
left gaze deviation/ preference. right hemiparesis (weakness). inc metastatic tumors ICP in cerebral cortex --> uncal herniates through the herniation thru tentorium tentorium cerebelli cerebelli --> inc pressure impaired pupillary light midbrain & CN3 --> impaired pupillary light reflex reflex (ipsilateral dilated pupil). 3) to other side of skull (primary Brain to skull insult)--> brain bruising on both sides --> swelling & subdural hematoma (secondary insult) --> Increased ICP Falx cerebri Foramen magnum brain herniates from left to right side brain undergoes tonsillar/ cerebellar herniation Brain herniation Tentorium cerebelli (uncal herniation) Hydrocephalus Left (dominant) hemisphere lesion inc ICP in foramen magnum (near cerebellum & medulla) --> herniation of cerebellum --> pressure against medulla --> compromise of basic homeostasis mechanisms --> respiratory arrest tentorium cerebelli separates primary or Uncus (bump protruding from medial temporal lobe) occipital lobe from cerebellum. uncal herniation normalize inc ICP by elevating head. intubating & hyperventilate. forming a bulge between regions of dural attachment to bone --> increased intracranial pressure tearing of the middle meningeal artery (high pressure rapid bleed that separates dura from skull) epidural space = potential space btwn dura & skull. falls. severe vasogenic edema. ring enhancing masses. do NOT use if herniation due to ischemic stroke!) decompressive surgery surgical placement of shunt to divert CSF from brain . aphasia CT: no CSF space. inflammation of underlying tissue. left decerebrate posturing. right hemisensory loss (numbness). fills w/ blood or fluid w/ trauma blow to skull (baseball) CT: best for acute bleeds MRI: best for subacute bleeds. 2) Skull to windshield.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Subdural hematoma tearing of the bridging veins (low coup contra coup injuries pressure venous bleed that from MVA. 3) blockage of CSF of CSF --> increased flow ventricular volume. & decreased brain tissue right visual field deficit (hemianopsia). Cheynes-Stokes respirations. 2) not enough increased pressure & volume reabsorption of CSF by arachnoid granulations. giving mannitol & dexamethasone (reduces edema. intracranial hemorrhage Coup contra coup injury sudden onset. dec consciousness causes? 1) overproduction of CSF gradually inc ICP by choroid plexi. Neurosurgical consult 3 points of impact: 1) Car to brain hits skull then bounces back tree. shows blood spread out across the surface of the brain Epidural hematoma PE: lucid interval (delayed neurological signs) CT: best for acute bleeds MRI: best for subacute bleeds Subarachnoid hemorrhage. "worse headache of life" CT: blood in ventricles or other brain areas ABCs. blood is often crescent increases w/ time) shaken baby shape over brain surface -syndrome > increased intracranial subdural space = deep to dura pressure (nowhere for extra mater btwn dura & arachnoid layers of meninges volume to escape) usually in shaken brains blood accumulates rapidly.
contralateral loss of fine touch. ipsilateral ataxia. dysphagia). right gaze deviation/ preference ptosis. possible development of horizontal diplopia tumor impinges on pontomedullary junction. emotional triggers?? Complication of AIDS. nucleus ambiguus (dysarthria. tumors. lyme dz. vibration). interruption in this pathway causes Horner's syndrome lesion affecting the corticospinal tract (CL weakness). unable to close eyes. left hemiparesis.7. impaired taste (dysguesia). +/spinothalamic tract (CL light hoarseness. ipsilateral tongue weakness Bell's palsy recent onset of unilateral facial weakness (weak forehead. miosis (pupil constriction) oculosympathetic pathway projects from hypothalamus to lateral tegmentum (MB. where CN 6. damage to corticospinal tract (CL hemiparesis).8 all exit . weak lower face. nucleus (IL facial sensation loss). unable to wrinkle forehead on same side as lesion. peripheral facial weakness. syndrome inferior cerebellar peduncle (IL ataxia). Horner touch & temp loss of body).Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Right (nondominant) hemisphere lesion Medial midbrain syndrome left visual field deficit. dysarthria. pons. hiccups. dysphagia. DM most common mononeuropathy Medial medullary syndrome contralateral weakness. diplopia. hyperacusis on right Cerebellar pontine angle tumor unilateral hearing loss. lateral medulla lesion causes contralateral body sensory problems with spinal trigeminal loss.Horner syndrome) Lateral medullary syndrome infarct to the vertebral artery or posterior inferior cerebellar artery Horner's syndrome ptosis. HSV. anisocoria (uneven pupils). and descending autonomic tracts (sympathetic . contralateral hemiparesis. dorsal column-medial lemniscus (CL loss of fine touch. and damage to corticobulbar tract (CL facial weakness) ipsilateral facial sensory loss. ipsilateral flattened nasolabial fold). left hemineglect. late stage syringomyelia) infarct of vertebral artery or anterior spinal artery (posterior circulation) reactivation of viral inflammation of facial nerve by stress. sarcoidosis. and hypoglossal nucleus (IL tongue weakness) LMN lesion of facial nerve or nucleus --> peripheral ipsilateral facial paralysis with inability to close eye on involved side lesion above T1 (Pancoast tumor. contralateral UMN facial weakness CN3 palsy. BrownSequard syndrome. anhidrosis & flushing of affected side of face. medulla) to the intermediolateral cell column of the spinal cord. left hemisensory loss.
stroke. loss of driving privileges. rare GTC. resolves by teenage years no underlying pathology. chronicity. extensor plantar responses loss of CN6. medication responsive Benign Epilepsy with Centrotemporal spikes (BECTS) simple partial seizures or secondary GTC seizures onset age: 4-10 y. anxiety. medication responsive generalized > focal Childhood Absence Epilepsy absence seizures ("spacing idiopathic generalized epilepsy syndrome. olfactory/ gustatory hallucinations. behavioral arrest.o. social stigma. head trauma. repetitive movements. & posterior column tracts BUT preserves ascending RAS (so pt remains conscious) intact cerebral cortex that is unable to interact w/ external world Epilepsy (general) syndromes depend on age of onset. spinothalamic tracts. require lobectomy unemployment. infarction pt is awake & alert but quadriplegic and unable to knocks out both corticospinal speak. myoclonic seizures in AM normal development EEG: 3Hz spike wave good prognosis. wandering. MRI findings. recreational drug use. encephalitis. bilateral quadraplegia. predisposing factors. infrequent nocturnal seizures normal development idiopathic localization related epilepsy syndrome EEG: centro-temporal spikes good prognosis remission by teenage years . clusters/cycles. confusion 2+ unprovoked seizures. EEG déjà vu. inability to abduct both eyes. + bilateral corticospinal involvement. severity body experience.o. normal development considered genetic usually med responsive but co-morbidities: some can be refractory and depression. frequent daily seizures normal development myoclonic (muscle twitching).o. FH. develop delay. focal brain lesions FH of epilepsy Idiopathic (primary) relatively self-limited. genetic seizures can be triggered by EtOH or lack of sleep most FH common idioathic generalized epilepsy EEG: 4-5Hz spike wave lifelong valproic acid or lamotrigine exacerbated by AEDs like carbamazepine & phenytoin requires lifelong treatment. 7. alcoholism. memory loss (Verbal > visuospatial) Juvenile Myoclonic Epilepsy idiopathic generalized epilepsy syndrome. disconnection / out of findings. relationships post-op complications: visual deficits.Disease Clinical Variants Locked in syndrome Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Basilar pontine infarction bilateral facial weakness. or breathe tracts. GTC seizures onset age: 13-20 y. amnesia. genetic out") onset age: 3-8 y. as well as UMN deficits basilar artery supplies vasculature to majority of pons. generalized or focal 1-2% of population PMH of complex febrile seizures as a kid. unresponsiveness. swallow.
epigastric rising sensation small focal seizure (abnl electrical discharges) .cognitive dysfunction seizures occur most often during sleep! (most common in stage2 sleep so early in night) Seizure clusters (up to 20/night). +/recall. night terrors.hallucinations. asleep & awake Simple partial no loss of consciousness (auras) variable S&S (motor.o. often 85%) refractory to meds LennoxGastaut Syndrome symptomatic (structural or metabolic) generalized epilepsy syndrome EEG: 1-2Hz slow spike wave poor prognosis. déjà vu. tonic) onset age: 1-6 y. structural (abnl MRI) or unknown (nl MRI) EEG: temporal spikes MRI: mesial temporal sclerosis (scarred hippocampus) often refractory to meds. very difficult to control Nocturnal Frontal Lobe Epilepsy (NFLE) mean age of onset 14y (mostly kids) 70% men Carbamazepine or other AED Safe environment Focal seizures (general) symptoms vary depending on location of seizure activity (i.déjà vu. olfactory/ gustatory hallucinations.visual disturbances.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Symptomatic frequent seizures. occassional daytime events in 1/3 pts. very frequent seizures a/w mental retardation & abnormal MRI Temporal Lobe Epilepsy simple partial or complex partial seizures age of onset: ANY +/. temporal . occipital . complex partial seizures) MRI of brain with and without gadolinium EEG. atonic. difficult to structural or metabolic neurologic abnormalities control focal > generalized any type of seizures can occur (GTC. a/w frontal lobe lesions Can mimic non-REM sleep disorders (confusional arousals. stereotyped behaviors. autonomic. but poor prognosis for surgery can be curative (80. psychic). if temporal lobe source . motor cortex disruptive motor coordination) aura of any kind indicates focal onset of seizure more common in adults (acquire risk factors. sensory.e.remission. sleep walking) symptomatic localization related epilepsy syndrome.
cyanosis & ictal cry (respirations inhibited) lateral tongue bite common. bladder/bowel incontinence. shoulders. S&S can vary depending on area of seizure activity (aphasa if left temporal lobe. surgical resection Secondarily generalized tonic-clonic Generalized seizures (general) evolves from focal seizure to bilateral. & upper extremities consciousness preserved. subtle movements/ automaticisms (eye blinks. old stroke. Alzheimer's) require brain MRI to look for causative agent EEG: focal spikes over epileptogenic focus AEDs or if refractory to multiple meds. precipitated by waking may progress to generalized tonic-clonic seizure Clonic Tonic . posttrauma. lasts 1-2m automatisms (involuntary non-purposeful behaviors: lip smacking. convulsive seizure Todd's paralysis (transient. postictal confusion Tonic-clonic Absence brief loss of awareness. AVM. post-ictal hemiparesis CL to seizure focus) more common in kids most common type of seizure abnl electrical activity starts deep in the brain then simultaneously spreads to all areas of cortex loss of consciousness. no aura no postictal period ALWAYS start in childhood & resolve before adulthood 2nd most common seizure kids EEG: 3Hz generalized spike & waves AEDs: ethosuximide & valproic acid often misdiagnosed as ADHD Myoclonic brief shocklke muscle contractions in head. often occur at night if frontal lobe) amnesia post-ictal confusion or weakness convulsive seizure focal seizure focal brain lesion (tumor. repetitive arm movements. abscess. mesial temporal sclerosis. HIV dementia. tonic (fall with muscular rigidity) followed by clonic (rhythmic jerking. eye blinking).Disease Clinical Variants Complex partial Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications loss of consciousness. fast jerks then slower jerks). lasts 1-2m. head nod). lasts 5-20s staring spells.
TTP. avoid sympathomimetic agents (Claritin D) & estrogen conversion disorders EEG: normal brain activity throughout Ischemic lack of blood flow due to clots occluding artery (deprives brain of O2 & glucose needed for energy production) Large vessel causes: atherosclerosis. sickle cell. can be subtle (head drop). cryptogenic) THROMBOEMBOLISM = MOST COMMON CAUSE! Cardioembol.Disease Clinical Variants Atonic Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications loss of consciousness. hypercoag. arm. arterial diss/ vasculitis. aspirin after 24h no improvement w/ IV tPA? clot retrieval devices. HTN. avoid meds that inc bleeding. very irregular movements last up to 45 minutes (normally seizures last 1-2m at most) Stroke (general) apopletic (sudden onset) 5SUDDENS (weakness/ numbness on one side. EKG (r/o cardioembolic source & afib).S. small vessel/ lacune. hypotension . afib. time) 4th leading cause of death leading cause of long-term disability blacks are at higher mortality risk than other races.A. difficulty walking/ dizziness/ loss of balance. loss of vision in one or both eyes. young pts need sickle cell & hypercoag workups) clinical pic cannot reliably differentiate types of strokes! Prevention: HTN (ARBs. BP < 180/105. chem panel (hypoglycemia?). atheroscl. clonic jerkings do not slow down like characteristic GTC seizure. "drop attacks" so injuries common Psychogenic seizures no tonic phase.). severe headache) Act F. other. elev homocysteine). cardiomyopathy (stasis of blood). smoking (nicotine patch. difficulty speaking or understanding speech. CAD. PT & PTT (blood clotting d/o?). myeloprolif d/o.cannot see acute ischemic change) IV t-PA if sx onset w/I 3h window (DO NOT give tPA if subacute ischemia or hemorrhage!!) do NOT treat high BP in acute ischemic stroke (unless above tPA criteria of 185/110) post-tPA mgmt? ICU. aspirin etiologic eval (DWI MRI. DM. BMI Stat labs: CBC (severe anemia. (face. cardio-embolic. vasculitis. intra-arterial tPA to site of clot. sudden onset & lasts few seconds (but very frequent in number!!) kids a/w developmental delay very difficult to treat (poor prognosis) often a/w falls. inflammation. cardiac myxomas Other causes: coagulopathies (Protein C. EtOH. cardiac biomarkers (acute stroke pts at risk for MI). neuro checks for ICH. TTE. DM (HbA1c<7%). hyperlipidemia (statin). bupropion). aerobic ex (>20m.A.T. smoking. ACE-i). M>F. DIC. embolic Cardioembolic source: CHF. noncontrast CT scan of brain (nl CT proves ischemic stroke . race (A. small vessel dz. afib. 3x/wk). diet hi in fruits/ veggies. arteritis Small vessel/ lacunar: lipohyalinosis. aortic dissection TOAST criteria 85% of strokes (atherosclerotic. AT3 def. speech. thrombocytosis). limit alcohol. stroke at earlier age in blacks age. carotid duplex. geographic region (Stroke belt) CHF (poor heart fxn). S def.
n/v. n/v. misosis. vasospasms aphasia (loss of fluency. repetition). dizziness. left face & arm weakness > leg weakness aphasia? Apathetic.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Hemorrhagic In addition to SUDDENS. left homonymous hemianopsia (loss of R optic radiations). uncont HTN.denial of weakness. idiopathic. the amount of perforators affected correlates w/ symptoms MRI: hyperintensity in brainstem . R homonymous hemianopsia (loss of L optic radiations). comprehension. right leg weakness >> right arm weakness apathetic. nystagmus. PICA) produces lesions in brainstem PICA supplies the inferior portion of the cerebellum & lateral portion of medulla MRI: hyperintensity in inferior cerebellar territory Left ACA stroke Right ACA stroke Vertebral crossed signs (ipsilateral artery / PICA face numbness + stroke contralateral arm & leg numbness). into the aneurysms. trauma hydrocephalus. reading/ writing. crossed signs. can bleeding into the brain tissues also have vomiting & (intracerebral hemorrhage) --> headache more than mass effect ischemic aneurysms. R face & arm weakness > leg weakness CT scan - Stroke syndromes Left MCA stroke Right MCA stroke contralateral neglect (left hemineglect. strokes the brain tissue --> raised ICP. ipsilateral ataxia Basilar artery stroke (locked in syndrome) see above for basilar pontine infarction Quadriplegia or hemiplegia. left leg weakness >> left arm weakness posterior circulation stroke (vertebral artery. left gaze deviation (loss of L FEF). hemorrhagic conversion of infarct. vertigo. diplopia. 5% of SAH than ischemic subarachnoid space but not within AVM. Horner's syndrome (ptosis. visual/ auditory/ sensory neglect). ipsilateral ataxia basilar artery infarct produces lesions in the perforators that feed the brainstem. tumors. limb. right gaze deviation. naming. arteriovenous malformations. vertigo. amyloid angiopathy 10% of strokes more fatalities than ischemic strokes Subarachnoid hemorrhage Headache more prominent in bleeding around the brain. anhidrosis).
posture. meds. drugs) MS. playing musical instruments increase in resistance to passive movements stiffness but not major disability "lead-pipe" "cog-wheeling" Parkinsonism Akinesia/ bradykinesia slowness / fatigue or arrest in ongoing movements interferes w/ all activities and very disabling Parkinsonism . intention) tremors occurs while body part is maintaining posture against gravity occurs during goal-directed movements Parkinsons. clumsy hand dysarthria (weak hand + slurred speech) small (<1. valproic acid. stress. deep infarcts in territory of the deep penetrating arteries pure motor hemiparesis affects internal capsule & corticospinal tracts long standing HTN --> lipohyalinosis --> ischemia CT: small round hypodensity (darker) in deep white matter or subcortex from infarct of penetrating arteries Tremor (general) involuntary rhythmic oscillating movements alternating or synchronous contraction of reciprocally innervated antagonist muscles Rest tremors occur during rest Postural tremors Kinetic (action. occurs at rest. & action) Task specific occur during specific tasks tremors like writing. pure sensory stroke (if affects thalamus). physiologic (caffeine. MS) Parkinsonism most common movement disorder essential tremor. or sensorimotor stroke (if between internal capsule & thalamus) ataxic hemiparesis. stroke).Disease Clinical Variants Lacunar syndromes Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications pure motor hemiparesis (if affects internal capsule). neuroleptics. drugs (lithium. rubral (stroke. stroke check meds!! Rigidity Mixed tremor combination of above tremors. Essential tremor. rugral tremor (slow.5 cm diameter).
PT . may be stereotyped or repetitive. excessive blinking Tic repetitive. rapid.indicated in DYT1 generalized dystonia. OCD. tx refractory dystonias. eye exam for KF-rings) and given tx trial of Levodopa (check to see if Levodopa-responsive!) Anticholinergic drugs . drugs .early onset.indicated for focal dystonias specific dystonias? Writer's focal dystonias . spontaneous movements that are irregularly timed. slow onset of effect Botulinum toxin . use of "tricks".muscle becomes silent --> jerky flaps. & stereotyped movements can be suppressed temporarily by the pt Myoclonus rapid. or drugs Alzheimer's disease. arrhythmic & repetitive involuntary movements generalized.action dependent Wilson's (related to overuse of muscle) disease Doparesponsive dystonia Chorea excessive. cervical dystonia. involuntary. brief. DYT1 generalized dystonia (AD w/ low penetrance) excessive use.well tolerated in kids but difficult to use in adults muscle relaxants. likelihood of dz Primary is 0 if no sx onset by age 26 dystonias focal dystonia . metabolic d/o. focal. multifocal lasts milliseconds in duration negative myoclonus (asterixis) . generalized dystonia usually begins in legs contractions stop during sleep co-contraction of muscle agonists & antagonists generalized genetic origin (DYT1). shock-like. usually action induced & worsen w/ stress/ fatigue can be a/w tremor (jerky) blepharospasm (invol closing of eyes).Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Dystonia involuntary sustained muscle contractions that produce twisting/ squeezing movements & abnl postures.adults cramp. result of liver/renal disease. prion disease. nonrepetitive. & randomly distributed involves multiple body parts Huntington's chorea tardive dyskinesia (iatrogenic Levodopa in PD pts) Tourette's syndrome. purposeless.less useful? Pallidal DBS . focal adults dystonias DYT1 . kids kids generalize dystonias Ashkenazi jews (DYT1) genetic testing not very helpful bc low penetrance any pt w/ dystonia needs to be tested for Wilson's disease (24h urine copper.
anxiety . MPTP. dementia other organs (cardiac denervation. tremor dementia anticholinergics. depression. post instability. PSP (abnl eye movements). Wilson's dz. resting tremor. low volume). mitoch damage. difficulty getting up from chair. 2. micrographia early signs? trouble maintaining plan of action. treat sx (mild . early autonomic patterns = disrupted cortical failure. sleep d/o. inflamm. toxins (MPTP). internal segment of globus pallidus. drugs (neuroleptics). amantadine. smoking. gait d/o (festination/ shuffling. gaze palsy. oropharyngeal muscle dysfxn) genetic? young onset. bradykinesia/ akinesia (masked face. Lewy body formation Histology: Lewy bodies in SNc (composed of alpha synuclein & found in Lewy neutrites) 1. freezing. . autonomic dysfxn. toxin exposure (herbicides. wood preservs). hypophonic speech (fast. sleep probs. protect neurons late stage? Orthostatic (exercise). depression anti-depr.15y to develop Low dopa ultimately affects NOT seen in PD: cerebellar transmission (inc basal ganglia output @ putamen = abnl firing signs. aspiration. orthostatic hypotension. strokeinduced (rapid. neurodegen d/o high risk of falls! Dyskinesia/ dystonia from Levodopa tx PD bradykinesia + one of cardinal features (rigidity. rigidity inhibition of cortex (cogwheeling). LDOPA/carbidopa) too many side effects or ineffective? Surgery/ DBS directed at thalamus. heavy metals. difficulty turning). head trauma possible protective factors? Caffeine. rapid progression sporadic? susceptibility loci sporadic M >= F (>80%).no arm swing. or STN treatment of non-motor sx: depression.Disease Clinical Variants (Parkinsonis m) Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Parkinson's disease inc output from basal ganglia = tremor at rest. hyposmia PD. freezing. antiinflamm drugs Path: SN & red nucleus look pale. postural instability) loss of cells in SNc = fast loss of dopamine (oxid damage. genetic (<20%) 5-24/ 10^5 incidence genetic suscept (inc w/ aging + environm pop) factors old age. striatum anatomy. protein aggregation) = change in striatum anatomy (loss of asymmetric mode of onset. severe sx . flexed posture. etc. NO voice tremor Other S&S: sialorrhea (drooling). medium spiny neurons) unilateral tremor possible that PD ascends: BS to SN to cortex slow progression . stepwise prog). dystonia. drug induced (symmetric). no arm swing). early processing).hypotension.dopamine agonists.benzos.
tumor. impaired smooth pursuit . genetic testing (depending on phenotype) symptomatic tx of ataxia PT. fixed dystonia (does not improve w/ tricks) Cerebellar syndromes Ataxia Inferior olive sends information directly to the Purkinje cells. & caffeine. depression disease modifying tx lithium for SCA1. vitE. abnl regulation of movement speed/ force/ distance (movement delay. diminished w/ alcohol location: upper extremities > head > voice > leg/ chin often asymmetric 1-6% of population (most common movement d/o) bimodal age of onset (peaks in early adult & later adulthood) M=F FH beta blockers (propanolol) more rapid progression in younger patients & those without head primidone (precursor of tremor (head tremor GABA receptor binding =better prognosis) barbituates) .a/w inc genetic repeats MRI of head.jerky acquired (primary) = idiopathic saccades.cognitive effects (fuzzy memory) Progressive supranuclear palsy shock/astonished look on face. "drunken stumbling" intact Doll's eye maneuver suggests intact brainstem Parkinsonism disorder that presents with cardinal features + eye movement abnormalities (gaze palsy) fall very early in dz course! Wilson's disease facial dystonia w/ retraction of mouth. dysdiadochokinesia) inherited (AD. ?riluzole reduces deep cerebellar nuclei hyperexcitability symptomatic tx of assoc sx swallowing. stroke. inborn errors) . Mitochondrial. antitissue transglutaminase. vitE def. spasticity. Keyser-Fleischer rings in eyes (sunflower cataracts). dizziness.hyperexcitable evoked nystagmus. B12. which normally inhibit the deep cerebellar nuclei (output system of cerebellum). the Purkinje cells become disinhibited. dyssynergia. in ataxia. suppress vestibulo-ocular autoimmune (paraneoplastic reflex by fixation) degen. X-linked. Surgery . pain.present 5x risk increased if first degree throughout ENTIRE relative w/ ET movement exaggerated by fatigue. therefore the deep cerebellar nucli are abnl eye movements (gaze. antithyroglobulin. unable to move eyes vertically. gluten ataxia). (secondary) = hypothyroidism. anti-GAD. AR. toxic loss of coordination.but some contraind in DM & interventions do not last depression very long side effects of primidone . dantrolene for SCA2. HDAC inh & antioxidants for FRDA .Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Essential tremor Action/ kinetic tremor (goes unknown away with rest) . MS. hyperreflexia. TSH. ?ceruloplasmin. ?chantix. MSA. slow optokinetic nystagmus (occurs when following an object w/ eyes). anti-gliadin.try first in elderly patients! side effects of BB bradycardia. square wave jerks during fixation & saccadic intrusions during pursuit. stress. inability to late onset cerebellar degen. dysmetria + dysrhythmia. anti-GAD65.
spinocerebellar tracts. lithium.Disease Clinical Variants Toxic syndromes Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications chronic alcohol history? Midline cerebellar atrophy. dystonia.medulla death within 5-10y . others (nystagmus. blindness. permanent cerebellar damage oxcarbazepine). dystonia neuropathy. speech spared Alcohol can cause midline atrophy EtOH. incontinence) cardiomyopathy. areflexia (loss of reflexes). inc repeats = inc clinical severity Spinal cord pathology: loss of dorsal colums. orthotics) anti-oxidants? HDAC inhibitors? Anti-GAD ataxia stiff person syndrome. downward nystagmus. nodding midline problem in the cerebellum ataxia tremor. glucose intolerance/ DM.sx vary w/ spectrum of anti-GAD antibody burden autoimmune process where antibodies are made against GAD65 --> CNS disease and pancreas diseases like DM MSA Multiple Systems Atrophy = Parkisonism + cerebellar ataxia + autonomic dysfunction Axial/ midline wide stance & gait. of cerebellum AEDs (phenytoin.pons inferior peduncle . loss of vibration/ position sense. dysarthria. motor neuron disease. dysarthria. corticospinal tract Peripheral nerves: damage to dorsal root ganglion CNS: affects brainstem & cerebellar nuclei heart: fibrotic cardiomyopathy (hypertrophic) sx onset in late childhood/ adolescence most Indocommon European inherited races ataxia (1/3050K) supportive (balance. periocular or perioral fasics. weakness legs>arms.extensor plantar responses. parkinsonism Neuro: ataxia. nystagmus syndrome Appendicular dismetria. or autoimmune encephalitis . random alternating problem with cerebellar inputs & ataxia movements. hearing loss.midbrain middle peduncle . Acute lithium toxicity can lead to carbamazepine. mild ophthalmoplegia. adult onset epilepsy. scoliosis. pes cavus Friedreich's ataxia (FRDA) autosomal recessive ataxia with strong founder effect (IndoEuropean races) mutation in frataxin (trinucleotide repeat GAA). amiodarone autosomal dominant disease w/ large degree of phenotypic variability & hi genetic anticipation MachadoJoseph Disease (MJD) = SCA3 ataxia. discoordination outputs (peduncles) syndrome w/ limb motor dexterity superior peduncle . legs & trunk >> arms. cerebellar ataxia.
manage sx avg lifespan 65y men more likely to develop chronic progressive form of disease a/w other autoimmune dz like thyroiditis & psoriasis With every 1 clinical event. dystonia. interrupting the flow of electrical impulses in the CNS negative sx (weak/numb) . & oxid damage. Nystagmus) bladder/ bowel probs (constipation. geography (inc risk if far from equator). bradykinesia Autosomal dominant mutation in the huntingtin gene. psychotx early in dz impulsivity: remove temptations (guns. 8500-10K new cases per yr Th1 cells secrete IFN-y & Th17 cells secrete IL-17 & Il-23. genetic testing if FH unknown NONE . degenerative neuropsychiatric d/o Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Huntington's disease 90% adult onset. dystonia.due to loss of conduction (low # Na channels) --> nodal widening & disbursed electrical current = dec safety factor & instability of demyelinated axons gen predisposition + abnl immune system (EBV. impaired executive fxn emotional disturbances: depression. keys). incontinence). primary progressive (10%). mood stabilizing meds clinical trials Juvenile onset Multiple Sclerosis (MS) Relapsingremitting (80%). hemiparesis. tetrabenazine if chorea affects ADLs Attention deficits: one task @ a time. speech & swallowing therapy. seizures.reduces the # of circulating & activated T sx exaceberated by temperature cells by dec MMP generation & fever Natalizumab . impulsivity. Hungarians Glatiramer acetate (GA)mimics myelin so it is attacked instead of actual myelin on axons OR beta-IFN . anxiety. attention deficits. smoker) --> abnl attack on CNS leading cause of nontraumatic disability in young adults 70% women.behavioral probs Charcot's triad (SIN: Scanning speech. fatigue. hemisensory loss. on average. chorea. EBV+. HLA-DRB 1 gene MRI of brain: white plaques in CNS CSF analysis: Inc IgG & oligoclonal bands from B cells (suggests BBB breach) Evoked potentials: slowed (loss of myelin) histology: loss of myelin. leading to unstable expansion of CAG repeats (nl < 26) in the polyQ area Htt role unknown? Protein folds incorrectly --> aggregation --> dysreg transcription & abnl RNA prod. hypocellular Vitamin D supplements (lowers dz severity). pain.progressive & fatal discuss end of life issues manage symptoms & social support Movement d/o: PT. vision changes (optic neuritis = sudden loss of vision). impaired visual spatial abilities. FH. intranuclear inclusions w/ mutant Htt aggregates pathology: severe atrophy of caudate nucleus (but also atrophy of other brain regions) MRI: inc CSF (due to atrophy) FH & typical movement disorders. low vitD.SAM inhibitors (blocks a4 integrin. dec inflamm & NO. psychosis. OCD. urgency. there are 5-10 new lesions More attacks = more brain damage = more brain atrophy inflammatory dz --> neurodegenerative dz age of genetically onset: 15-50 protected? Eskimos. alcohol. avoid meal distractions disorganization: routine. cognitive difficulties. smoking. protein is cleaved & forms polyglutamine fragments (toxic!) AD inheritance 5-10/100K w/ hi penetrance huntingtin gene mutation FH histology: substantial loss of medium spiny neurons in basal ganglia striatum. OT. hemiparetic gait (circumduction. & glial ensheathment. remyelination myelin. step by step instructions decision-making: simple choices. to do lists. preventing T cell migration across BBB) Fingolimod – blocks T cells from leaving LN IV steroids for relapses . impaired memory. rigidity. semi-flexed arm) dx: mult lesions in time & space 10% of Huntington's is juvenile onset autoimmune inflammation & demyelination of axons. personality/ beh change movement d/o: eye movement abnl. progressive relapsing bradykinesia prominent & early (chorea less prominent).& axonal transection hyperexcitable response to demyelination females.Disease Clinical Variants slowly progressive. school failure. muscle rigidity/ stiffness. irritability. mitoc dysfxn. Lhermitte's) . tremor. myoclonic jerks. duration of 15-30+y dx requires FH or genetic confirmation + typical choreic movements cognitive decline: slow thinking & distractibility. no open ended ? depression: antidepressants. B cells make Abs -(but shorter internodes than nl) >demyelination positive sx (tingling. Intention tremor/ Incontinence/ Intranuclear ophthalmoplegia. recruiting remission occurs (sx microglial cells improvement) when: inc Na+ that display channels. vitD def. ataxia. depression. secondary progressive. Native Americans.
CSF). neuro exam. disregard for personal appearance. exercise. statins. delusions. neurofibrillary tangles. red wine CT: mesial temporal atrophy PIB: increased amyloid burden CSF: measure biomarkers like beta-amyloid & tau protein (predicts MCI conversion to AD) pathology: brain atrophy. personality change characterized by acquired memory impairment + performance impairment in functional domains (language. antidepressants.with age. brain tumors. executive fxn. subdural hematoma. difficulty performing tasks/ finding words.o. blood tests (B12. executive skills) AD. misplacing objects in weird places. rivastigmine). repeating ?. Lewy body dementia. depression. atypical antipsychotics . poorly tolerated dopaminergics) distinguished from PD bc dementia begins at around same time as dementia sx thought to be an intermediate syndrome between AD & PD decreased cortical ACh & striatal dopamine formation of amyloid plaques.Disease Clinical Variants (general) Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Dementia acquired. language. presenilin-1. syphilis. vascular infarcts… increased incidence w/ baby booming population 50% of people >85 have dementia history. presenilin 2. low B12. HTN. & Lewy bodies cortical Lewy bodies & Lewy neurites widespread in DLB (correlate w/ dementia severity). rapid progression compared to PD. neuroleptic sensitivity. HIV. NSAIDs. loss of initiative. PD. hypercholesteremia . visuospatial skills. HIV). depression. autonomic dysfxn. or ApoE4) most common type of dementia F>M age. asynuclein = major component of Lewy bodies at risk genes? APOE4. anxiety). imaging. FTD. organ failure. neurosyphilis. depression. pseudodementi a. identification skills. word recall (immediate & delayed). severe impairment of multiple areas of higher brain functions (>2 deficits in memory. naming test (line drawings) executive fxn (connect the dots. emotions. persistent. presenilin sx genes. tau release -> AD clinical amyloid clearance mechanisms slow down. praxis. low B12/ folate protective? Education. TB. memantine Neuroprotective? VitE Lewy Body dementia dementia + Parkinsonism (bradykinesia/ rigidity) + psych sx (hallucinations. head trauma. amyloid aggregates symptoms forming oligomers --> BetaFAD: APOE4 amyloid deposits in neuritic plaques --> neurotoxicity & AD gene. APP mutations tau protein accumulates in neurofibrillary tangles. CJD. hi homocysteine . neurofibrillay tangles. Med diet. thyroid.). galanthamine. fluctuating cognitive state (attention/ arousal). mutation in alphasynuclein 10-20% of dementia M>F age of onset? 5080 FH cannot be distinguished neuropathologically from Parkinson's dementia d/c anticholinergics. TBI. neuropsy testing Montreal cognitive assessment or MMSE logical memory (read a paragraph then talk about what was read). visuospatial skills. disorientation in familiar locations. clinical features (genetics. hydrocephalus. autosomal dominant w/ 100% penetrance (mutations in APP. Down syndrome. clock drawing) visuospatial (intersecting pentagons) very vulnerable to delirium Alzheimer's disease memory loss dramatic loss & degeneration of amyloid accumulation -> neurons containing ACh neuron injury--> 90% of AD is sporadic. which correlate w/ sx & degree of dementia 10% of AD has familial form: early onset (<65y. MS. senile amyloid plaques symptomatic? AChE inhibitors (donepezil. personality) cog complaints: altered consciousness. lower doses of dopaminergics AChE inhibitors. inappropriate clothing. other features (REM behavior d/o.
thought. aroused by vigorous & repeated stimuli (require these stimuli to respond) . head trauma. colon. hypo/hyperglycemia). or appropriately shift attention . sedatives. hypoxia. impaired attention (waxes & hyponatremia). aroused w/ stimulation to answer questions but lapses back without verbal/ tactile stimuli Stuporous deeply depressed consciousness. mood. autonomic encephalitis). endings suicidal/ homicidal. acute vascul insult. anticholinergics). aggregated tau protein). non-fluent variant. +/. toxins. early apathy. reliability) MMSE or MoCA. ICH).FTD + ALS or PSP Progressive falls early in disease course. affect. CNS path. cooperation. deficiency of vitamins. heavy metals) brain mets (melanoma. opioids. direct. vascular instability (hypertensive encephalopathy. insight. CT scan (r/o head trauma). immunoreactivity to TDP-43 or FUS MRI: frontotemporal atrophy (bvFTD). electrolytes (hypo/hypercalcemia. early ritualistic Tau can also become behavior. level of consciousness. MI. endocrinopathy.appearance. hyperorality/ diet hyperphosphorylated --> changes. endocrine (hypo/hyperthyroidism. COPD. pneumonia. epileptic seizure I WATCH DEATH (infection. exec deficits w/ microtubule dysfunction sparing of memory & visuospatial fxns FUS unclear Primary progressive aphasia (PPA) . arousal. supranuclear abnl eye movements palsy inability to sustain. CBC.Disease Clinical Variants Frontotemporal dementia Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications syndromic dx TDP-43 (normally a nuclear transcriptional regulator) undergoes translocation to form Behavioral variant FTD (bvFTD) . renal failure.semantic dementia. prostate. PE. easily aroused to wakefulness Obtunded moderately depressed consciousness. speech. organ system dysfxn wanes) (CHF. breast. SAH. intermittently fluent w/ word finding pauses autosomal dominant mutations in MAPT and progranulin TDP a/w ALS Tau a/w PSP histology: Frontotemporal lobar degeneration w/ lesions displaying Pick bodies (intracellular. UTI). subtle left atrophy (PPA) Delirium FTD plus . knowledge. nutritional (thiamine). renal transitional cell) strongly associated with morbidity & mortality dementia patients see patient serially over time to evaluate fixed/fluctuating sx Psych mental status exam (ABC STAMP LICKER .3 of following: early hyperphosphorylated disinhibition. cognition. behavior. large variability in the level of pancreatitis. trauma. cytoplasmic inclusions in FTD early loss of sympathy/ empathy.visual hallucinations. perception. SDH. infectious (meningitis. UDS.due to CNS process or another organ system affecting CNS drugs/ toxins (EtOH intox/wd. withdrawal. CMP Consciousness Awake & alert fully aware of self & environment Lethargic mildly depressed consciousness.
lack of consciousness) impaired RAS in the brainstem or diencephalon OR damage to BOTH cerebral hemispheres from structural or metabolic/toxic injury BS: trauma. to a degree incompatible w/ consciousness hypoxic ischemic encephalopathy (most common cause of PVS) pathology: diffuse laminar necrosis of cerebral cortex w/ extensive hippocampal involvement >3m of PVS. & motor response to pain (lower score = more comatose) Brain oriented ICU . hypercarbia. tumors. ischemia. non purposeful limb movements actions have no cognitive content brainstem functions without cortical function glucose in cerebral cortex is greatly reduced.damage to upper midbrain decerebrate posturing (extensor) . liver failure.Stokes resp . hi/low Na+. sepsis. purposeful behaviors like following commands) emergence: functional interactive communication and/or functional use of two different objects hypoxic ischemic encephalopathy. functional recovery is rare Minimally conscious state (MCS) severely altered consciousness w/ minimal but definite behavioral evidence of self or environment reproducible evidence of awareness (speech. drugs) MRI to r/o reversible causes Glasgow coma scale assessed for eye opening. TBI. oculovestibular). metabolic d/o. verbal output. brainstem stroke/ hemorr Both hemispheres: bilateral subdural hematomas. end up in vegetative state. hi/low gluc.midbrain lesion apneusis .Disease Clinical Variants Comatose Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications cannot be aroused to consciousness despite stimuli used decorticate posturing (flexor).liver failure or toxic insult to brain Central neurogenic hyperventilation . meningitis Neuro exam!! Respiratory patterns. smile/cry. large/ lots brain tumors. inc ICP.damange to lower midbrain/ upper pons Cheynes. patients either die. or recover (various degrees) Persistent vegetative state (PVS) wakefulness without awareness intact sleep/wake cycles. degen dz metab/toxic: hypoxia. neurodegen dz.balance cerebral metabolic supply with cerebral metabolic demand and minimize cpds that worsen neuro damage within a few months.medulla lesion total absence of awareness of self & environment (lack of sleep/wake cycles. hypo-thyroidism. & motor responses (posturing) EEG can suggest various causes (liver failure.lower pons lesion ataxic breathing . drugs. eye movements (Oculocephalic testing. stroke. congenital or developmental d/o can be permanent or transitional state . seizure. eat food placed in mouth. pupillary light responses (loss suggests struct damage). fixates visually on objects or orients head to auditory stimuli.yes/no responses.ischemic stroke to pons cluster breathing .
control DM. ESR/CRP Diabetic peripheral neuropathy burning pain. NCS. +/autonomic involvement (postural hypotension. isotope angiography) if pt cannot reliably undergo clinical testing components apnea test should be done last (risk of pneumothorax. polymeds/ toxins. combordities) pain mgmt (Neurontin. connective tissue (SLE. facial sensation & motor responses. pharyngeal/ tracheal reflexes) medical record documentation: etiology & irreversibility of condition. heavy alcohol intake. HLA DR3/4 7x increase for diabetic foot ulcers on soles of feet! Charcot's joints (severe diabetic neuropathy + osteopenia --> calcification of vascular smooth muscle & degen of bones --> changes in navicular bone of foot -> dysmorphic feet (requires joint fixation/ surgery to repair) Myelinopathy (general) inflammatory cells attack myelin -. rpt neuro exam. absence of respiration w/ hi CO2>60 mmHg) pCO2. think about vasculitis) Metabolic. absent motor response to apnea test (no respirations at pain. mild weakness. foot care! age. TSH. HbA1C. sternal rub. mechanical sensation) 30% prevalence among diabetics poor glycemic exclude other causes (meds. B12. justification & results of confirmatory tests. ocular movements. smoking. absent pupillary response. absent ankle jerks chronic (if acute. & hypotension) confirmatory tests have hi rates of false negatives so done if clinical exam cannot be performed properly! Axonal polyneuropathy (general) usually affects both sensory AND motor fibers symmetric & distal: Stocking-glove distribution (Legs>arms). neuropathy nutritional (B12 def). absent brainstem reflexes. toxin exposure. advanced Lyrica).acquired: acute > segmental demyelination in both GBS. absent cough response to bronchial suctioning REPEAT CLINICAL EXAM! Brain stem reflexes (pupillary light. Sjogren's) HbA1C or 2h GTT. round/ oval pupils. neuropathic control. serum protein electrophoresis (multiple myeloma). EEG. dyslipidemia.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Brain death documented loss of irreversible loss of all brain & consciousness (coma) + no brain stem function brain stem reflexes + apnea NO motor/facial responses to pain (nail bed pressure. time confirmatory tests (cerebral angiography. transcranial of death (time last test is completed) doppler u/s. as well as sensory large fibers (vibration. bowel/bladder probs) involves small C fibers (pain). arrhythmias. autonomic testing longer duration of DM. hypertrophic nerves motor> sensory symptoms NCS: conduction block (20% drop in amplitude btwn proximal & distal sites) . arrhythmias. majority of endocrine (DM). reduced pin prick & temp sensation absent ankle jerks symmetric distal pain/ burning. absent corneal reflex. chronic CIDP moderate -severe weakness sensory & motor fibers --> eventual total demyelination w/ normal muscle bulk Inherited: CMT areflexia. HTN. no doll's eye or caloric testing movements (eyes stay fixed in skull). nasal tickle).
exacerbated by menstrual period/ pregnancy blocks of neuromuscular transmission due to AUTOANTIBODIES binding to AChR on postsynaptic membrane --> 1) decrease in number of available receptors. recent surgery or renal transplantation may be a/w Hodgkin's dz.Campylobacter jejuni. EBV.9/100K all age groups no familial or NCS: absent F-waves & occupation conduction block triggers CSF: elevated protein w/ nl identified amount of cells (however. plasma exchange NO CORTICOSTEROIDS! Admission to ICU if autonimic dysfxn majority of pts recover.61. hypotension) PRECEDING ILLNESS (often GI . 10% have persistent severe weakness mechanical ventilation a/w 15-30% mortality Myasthenia gravis (MG) fluctuating weakness of VOLUNTARY muscles --> diplopia. difficulty swallowing/ breathing weakness may fluctuate in intensity throughout the day nl pupillary responses insidious onset. ptosis. motor neuronopathies) PAINLESS weakness & atrophy progressive course! cramps. myasthenic crisis --> thymectomy (symptomatic respiratory weakness benefit or remission) considered in all pts <60 Motor neuron (general) diseases (anterior horn cell dz.decreased muscle response to repetitive stimulation increased strength following administration of AChE inhibitor Anti-cholinesterase drugs can be a/w thymic provide symptomatic benefit tumor. thyrotoxicosis. HTN. HIV? immune mediated process (T cells)--> inflammation & demyelination of peripheral nerves & motor fibers of ventral roots most common cause of acute generalized paralysis 0. HSV. influenza. SLE steroids if poor response to AChE inhibitors aspiration pneumonia. CMV. mycoplasma). can involve CN7 (facial paralysis) & autonomic dysfxn (cardiac irregularities. fasciculations NO sensory loss. 15% have NO residual deficits. 2) less surface area due to architectural change of postsynaptic membrane --> less ability to depolarize the membrane --> chronic muscle weakness AChR antibodies lead to destruction of the AChR by activating complement fixation OR inducing endocytosis of receptors (similar to botulinum toxin) occurs at all HLA-DR3 ages women Elevated level of serum AChR antibodies (sensitivity 80-90%) CT scan of chest to R/O thymoma NCS . CSF will be nl during first 48h so does not necessarily exclude GBS) MRI if suspect spinal cord involvement IV Ig. RA. immunization.Disease Clinical Variants GuillainBarre Syndrome (GBS) Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications ACUTE ascending weakness. 50-65% are restored 2/3 normal fxn. SLE. NO ptosis or eye movement probs . absent reflexes.
echovirus.S. age 618m. can't sit independently SMA2 .adult onset. AMS. West Nile virus new cases eradicated in U. w/I 2w supportive treatment . minority of pts get meningo-encephalitis (fever.4. Coxsackie virus. abd breathing.pleocytosis (inc WBCs) w/ lymphocytic predominance. motor neuronopathies) Disease Clinical Variants Poliomyelitis Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications 1-2d nonspecific viral prodrome (many pts get better). back pain. severity of SMA depends on #SMN2 copies available (more SMN2 = less severe dz) 4-10/100K SMA1 = most common motor neuron dz Kennedy's disease mutation of androgen receptor gene on X chromosome mostly males median age 44 . > survival than SMA1.wheelchair dependency ANDROGEN INSENSITIVITY . prox weakness.Juvenile form/ Kugelberg-Welander. tongue fascics.6) & autonomic dysfxn post-polio syndrome slowly progressive weakness. tongue & limb fascics SMA4 . prox weakness X-linked bulbospinal muscular atrophy adult onset. Japanese encephalitis virus. rabies virus. spares CN 3. orthopedic deformities.gynecomastia. but cases of post-polio syndrome CSF: neg in early stages. limbs & trunk. first 6m of life--> hypotonic (floppy) infants w/ prox weakness & areflexia. occurs ~35y after initial illness. testicular atrophy. nl life expectancy. nuchal rigidity. tongue fascics/ areflexia/ prox weak/ hand tremor SMA3 . lower extremity weakness very disabling . infertility increased incidence of DM progressive hereditary diseases of anterior horn cells & select motor cranial nerve nuclei SMN (survival motor neuron) 1 on chrom 5 is deleted.intermed form.paralysis 310d later)--> paralytic poliomyelitis . +/. sits independently but can't walk.cell dz.IgM antibodies or RNA in CSF Spinal Muscular Atrophy (SMA) SMA1 .myalgias & cramps --> rapidly progressive paralysis (asymmetric. rare. elevted serum antibodies WNV . elevated CSF protein Stool/ throat viral cultures. areflexia. enterovirus. impotence.Infantile/ WerdnigHoffmann. bulbar & proximal weakness. LMN signs: muscle weakness & atrophy. fascics. onset >18m. ventilatory failure. hyporeflexia neurotropic enterovirus w/ predisposition for ventral horn in spinal cord & motor cranial nerve nuclei --> LMN destruction fecal oral route poliovirus.
depression & anxiety progressive disorder of voluntary motor system . life events. hyperreflexia. sleep paralysis. prescriptions/ herbals/ OTCs). LMN .Disease Clinical Variants Amyotrophic Lateral Sclerosis (ALS) Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications LMN signs: weakness. hallucinations upon falling asleep or awakening.6 & Onuf's nucleus)!! non-motor sx: involuntary. UMN death of Betz cells (cortical spinal tract). muscle cramps. get out of bed if cannot sleep.progressive & fatal variable dz course . relaxation/ breathing exercises. TCAs. frequent nighttime arousal.e.upper & lower motor neuron dysfxn cause unknown? 90-95% sporadic. must monitor LFTs during tx Nuedexta helps bulbar sx no cure . sx? Inability to lay flat. good sleep hygiene. Babinski's sign no cognitive deficit! ASYMMETRIC weakness.4. CSF sample lacking SSRIs. benzos for depression/ anxiety PT/OT/Speech therapy bipap for breathing nutrition Sleep apnea 10% prevalence by age 3540 AGE. exercise. inability to stay awake during the day & sustain wakefulness fragmented sleep (unable to maintain sleep) sleepiness. consistent sleep/wake schedule. tongue. local spread. sudden intrusion of muscle atonia. & thyroid hormone) .death of anterior horn cells Riluzole . avoid alcohol/ caffeine/ nicotine Multiple Sleep Latency Test (MSLT) – measures the amount before bed of time it takes to fall asleep. unprovoked laughing & crying. daytime light exposure & physical activity Narcolepsy 1/2000 people Polysomnogram: short nocturnal REM latency. atrophy (first dorsal interosseous muscle. precipitating factors (young adults) (acute stressors .if initial rapid presentation then rapid progression 50% die w/I 3-4y 20% live 5+y 10% live 10+y FTD in 5-20% MOST COMMON CAUSE OF DEATH? Respiratory dysfxn (restrictive pattern. Hoffman sign. restrict time in bed to night. EDS treatment: Modafenil latency period < 8 minutes suggests narcolepsy cataplexy tx: Sodium oxybate(date rape drug). cataplexy (can be triggered by emiotions. anxiety/ depression/ stress/ worry about difficulty falling asleep sleep). signs of disruptive nocturnal sleep. ALS is in the middle of these two) U. obesity C-PAP lifestyle modifications Insomnia (general) difficulty maintaining sleep 3Ps: predisposition to insomnia (decreased homeostatic drive or (older adults) pressure for sleep. jaw jerk. most specific finding!) loss of hypocretin cells in the hypothalamus --> loss of major excitatory influence to areas necessary for wakefulness AND loss of inhibition to PPT so early REM sleep & cataplexy --> poorly consolidated states of thalamocortical arousal (wakesleep instability) normal sleep homeostatic mechanisms but more fragmented episodes of sleep w/ REM sleep occurring right at the onset of sleep molecular mimicry & certain infections? most prevalent sleep sx F>M behavior based tx: improved sleep hygiene. 5-10% AD 1/100K avg age = mid 50s M:F 3:2 Pathology: degeneration & death of motor neurons.S. periodic leg movements Behavioral strategies: short/scheduled naps. counterproductive efforts to solve sleep issues) sudden onset of sleep (sleep attacks). insulin. ghrelin. EDS. NO sensory/ autonomic/ eye movement abnormalities (spares CN 3. perpetuating factors (poor sleep hygiene. prev = 30K El Escorial criteria (should not spasticity managed by be used to preclude clinical dx) baclofen SSRIs.illness. progressive muscular atrophy is LMN and primary lateral sclerosis is UMN.prolongs survival (2-3m). hyporeflexia. SNRIs hypocretin HLA testing: HLA DQB 10602 obesity (hypocretin system also related to leptin. fascics UMN signs: spasticity. exertional dyspnea) Cardiovascular disease (HTN) and stroke risk!! Increased rates of mortality Thought to be a continuum that eventually converge to have ALS (i. paraspinal).
older patients (alpha synucleinopathies . or abnl REM sleep behavior by PSG AND REM sleep without atonia AND not better explained by another d/o Occurs during 2nd half of sleep (REM sleep). LBD). iron def 12 million anemia. psych screening (hi # affected pts have anxiety/dep). onset/worsening of symptoms at rest or inactivity. relief with movement. panic disorder) increased rate of CVD (autonomic arousals occur w/ PLMs) Rapid Eye (general) Movement Sleep Behavior Disorder (RBD) "acting out" dreams. population pregnancy. vivid lack of atonia & presumed lack dreams w/ good recall.Pontine lesions (ischemia. violent of suppression of movement themes & behaviors common during REM sleep (injury to self or bed partner) Dx? At least one of sleep related injury. neuro exam (USUALLY NL!).PD. ambulatory actigraphy for PLMs higher rates of mood disorders (depression. inflammation). limbic cortex (limbic encephalitis) Chronic form most common RBD associated with neurological disease .Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Restless leg syndrome (RLS) urge to move legs. Barbituates/ benzodiazepines structural lesions . uremia) Dopaminergics oral or IV iron repletion polysomnogram NOT indicated! when iron def confirmed Check for medication aggravators (benadryl). (unless antidep related) Physical measures to ensure safety: remove dangerous nearby objects. uncomfortable leg sensations. anemia 10% of U. sensory dysfunction ascends to the brain in the spinothalamic tract Brain deficits in IRON --> RLS (unable to retain or mobilize iron from periphery to brain) Multiple SNPs in 2 of 4 genes are related in a dose dependent fashion to # PLMs (not severity) most often familial (AD) pregnancy.S. diabetes. a/w neurodegen dz or narcolepsy mostly men > 50y.young patients (hypocretin def --> narcolepsy).Alcohol (chronic EtOH --> downregulation of GABA -> delirium tremors that look like RBD). idiopathic Idiopathic RBD a/w future neurodegenerative dz . nightly. tumor.o. MSA.descent severe RLS R/O secondary causes (iron deficiency. careful FH. soothing alarm Change anti-depressants to wellbutrin Pharm tx: Clonazepam. anxiety. speech & dream recall? behavior changes depending on dream content. serum iron/ ferritin/ B12/ TSH. FH. disruptive behavior by hx. Americans Northern have European moderate. worsening at night disorder of the emotional motor system throught he ventromedial medulla. iron & B12 deficiencies. hemorrhage. bedrails. Melatonin RBD is dangerous!!! Acute onset Iatrogenic (anti-depressants) Withdrawal . demyelination. women.
ataxia. tinnitus. substance P. Gabapentin. symptom free between attacks can last 1h-5d FH if symptoms persist.Disease Clinical Variants Confusional arousals Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Non-REM arousal disorders overlapping spectrum (confusional arousals most basic. basilar migraine.not present in 1st or 2nd degree relative Aura w/ 2 of following affects brainstem. basilar artery vertigo. no recall incomplete arousal from slowwave sleep (N3) resulting in dissociation between behavioral state (wake) and EEG (sleep) disorders of childhood if occur in adulthood. hemisensory deficits (neurological deficits reversible >5m but <60m) inciting event in visual cortex --> lack of blood flow at that point --? Neurologic change --> positive or negative visual phenomena Hemiplegic migraine Basilar migraine Cyclical vomiting migraine migraine symptoms w/ fully Familial . dysphasia. and/or neurokinin A) --> activation of trigeminal vasculature system in brain (trigeminal nucleus caudalis) --> dilation of blood vessels (throbbing & pain) 28 million Americans 18% women.Triptans (avoid if vascular comorbidities. opiates Vitamin prophylaxis VitB2 (reduces pain. avoid triggers (chocolate. visual sx simultaneously in temporal & nasal fields of both eyes.visual. polysomnogram.inc stroke/ MI risk) regular lifestyle/ sleep. hemiplegic variants. aggravation/worsen w/ physical activity). SNRIs) IV DHE if continuous headache (need EKG before using . nausea/vomiting OR photo/phonophobia cannot attribute to another d/o Classic migraine common migraine + "AURA" . or pregnant). etc) Common migraine At least 5 attacks with: attacks lasting 4-72h. dec consciousness. diplopia. exercise. Anti-HTN (propanolol. NSAIDs. Mg2+. Antidepressants (TCAs. imaging if headache persists/worsens Migraine Abortive therapy (take as soon as symptoms start!) . feverfew Prophylaxis based on comorbidities w/ headaches: AED (Topamax. mod/severe pain. NO motor weakness vomiting at least 4x/h for 1h. Triptan/ NSAID combo. SSRIs. edema). stress mgmt. sleep walking adds Sleep terrors motor activity. imaging at ER! . pulsating quality. Tramadol. 6% men peak age: 25-55 y <10% able to fxn during HA Consider Echo to R/O PFO. CCB). 2+ characteristics (unilateral location. valproic acid). bilateral paresthesias). or location of reversible sx (dysarthria. consider occult cause of arousal (OSA) safe environment avoid triggers (sleep deprivation) Clonazepam (reduces behaviors) Migraine (general) trigger (somehow involves vascular serotonin.genetic w/ basilar sx reversible motor weakness (ataxia) often present & aphasia Sporadic . Antihistamines (pregnant women). infrequent (1-3x/m). & sleep terrors add fear & Somnautonomic activation w/o ambulism memory of event) (sleep walking) Occurs during 1st half of sleep (N3 stage). hypacusia.
radiofrequency thermocoagulation Trigeminal Autonomic Cephalgias Cluster headache severe unilateral orbital/supraorbital/ temporal pain lasting 15m180m (EXTREME INTENSITY EXCRUCIATING UNILAT HA) associated with one of the following signs on the painful side: conjunctival injection. eyelid edema freq attacks: 1 every other day to 8x/d Chronic Paroxysmal hemicrania At least 50 attacks of severe unilateral orbital/ supraorbital/ temporal pain lasting 2-45m 5x/d. lacrimation. ptosis . unilateral throbbing HA may occur nl neuro exam & EEG frontal headache accompanied by pain in regions of face/ ears/ teeth resolves within 7d after remission or tx of rhinosinusitis Sinus headache headache attributed to rhinosinusitis Evidence (clinical . sensory trigeminal interruption. neck exercises.Disease Clinical Variants Benign Paroxysmal Vertigo of Childhood Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications multiple episodes of severe vertigo. nasal congestion. therapeutic touch/ self massage/ stretching regular lifestyle/ sleep. stress mgmt Sumatriptan injection or nasal spray (>90% effective). consider prednisone Oxygen therapy DHE . Goody's powder. lasts 30m-7d. ptosis. Lithium carbonate Surgery: central parasympathetic interruption. IV Prophylaxis: Verapamil. forehead/facial sweating. miosis. Melatonin. hyposmia. mild or mod intensity.IM. occurring wihtout warning & resolving spontaneously after minutes to hours a/w nystagmus or vomiting. imaging) of acute or chronic rhinosinusitis 90% of sinus headache patients have MIGRAINE!! Medication overuse headache also called rebound or drug-induced headache chronic overuse of medications HA >15d/m + regular overuse of drugs used for prevents prophylaxis from being effective in headaches acute HA >3m + HA developed/worsened during med overuse + HA resolves within 2m after d/c meds episodic HA that occurs >15d/month. exercise. nasal congestion. no predilection for night attacks a/w lacrimation. rhinorrhea.purulence. bilateral. NO n/v. conjunctival injection. Topiramate. fever. nasal obstruction. rhinorrhea. indomethacin. pressing/tightening (nonpulsating). subq. tylenol reduce offending agents consider IV abortive therapy if difficult for pt to endure pain Tension headache non-pharm prophylaxis: spinal manipulation. no photo/phonophobia Ibuprofen.
dendritis ulcers w/ fluorescein stain seasonal itching of eyes. bilateral Lids stuck in the AM hyperpurulent?? N. gonorrhea usually resolves w/I 4-5d or sooner if use warm compresses topical antibiotic If N. Pseudomonas. topical antihistamines fluorescein dye or Rose bengal stain shows DENDRITIC ulcers Acyclovir.Disease Clinical Variants Hemicrania continua Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications non-remitting. N. allergens. "foreign body" sensation in eye. starts monocular.pink eye HSV . topical decongestants or artificial adenovirus tears.flu. gonorrhea as causative agent REQUIRES systemic antibiotics & lavage ADENOVIRUS: Eye exam: conjunctival follicles (lymphoid aggregates). toxins.sore throat. Strep pneumo. white mucus of eyes swollen lids. ice pick HA Indomethacin Conjunctivitis (general) affects both palpebral & epibulbar conjunctiva!! Bacterial purulent.S. nose) herpetic lesions following dermatome (trigeminal distribution) . steroids HSV keratitis HSV destroys corneal epithelium and periodically bifurcates --> dendritic corneal ulcers --> recruitment of antibodies --> scarring of corneal --> blindness & recurrence even in corneal grafts Herpes Zoster Ophthalmicus Acyclovir Blepharitis chronic inflammation of lid a/w seborrheic dermatitis leading margins --> swollen or closed to hyperkeratosis of basilar Meibomian glands epithelium leading to problems w/ Meibomian glands foreign body sensation. hay fever sx #1 cause of inflamm blindness in U. itching crusts on lashes . Honey-crusted lesions on erythematous base (looks like impetigo) near mucocutaneous junction (eye. aureus.Staph blepharitis . cool compresses. URI +/. burning. fever pre-auricular lymphadenopathy . refer if severe pain or decreased vision Viral watery exudates. watery discharge.ophthalmic + nasociliary lesions feel "pain behind the eye" Adenovirus pink eye HSV Allergic IgE mediated ocular surface disease affecting mucus membranes (eyes & nose) OTC lubricants & decongestants. H. remitting pain 24/7 w/ +/. lips. pain but NO blurry vision.Cool compresses. viruses. exacerbations w/ coexisting migraines or cluster HA. gonorrhea microbes. tear deficiency S.autonomic sx.
proptosis. periorbital swelling.aureus NOT infectious .lipogranuloma Dacrycystitis purulent material through the infection of lacrimal sac region. septic emboli denuded epithelium from abrasion -> irregular fibers/ scarring in stroma --> vision loss topical antibiotic Corneal abrasion evident w/ Fluorescein dye Orbital fracture associated with blunt trauma to the eye edema & ecchymosis of eyelids & periorbital region (raccoon eye).Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Stye Chalazion acute infection of the eyelid. small. proptosis fever. tender & painful. of the eye infections Hyphema bleeding of iris or ciliary body vessels usually due to blunt ocular trauma --> blockage of aqueous outflow w/ RBCs --> increased IOP tear of iris or sphincter muscle Hypopyon corneal abrasions (contact lenses). granulomatous hospitalization usually spread from infection in the periorbital redness & swelling often secondary to ethmoid air cells or maxillary sinusitis. punctum Dacryoadenitis Orbital cellulitis prominent eye lids inflammation of lacrimal gland previous facial trauma obstructing the nasolacrimal passage infxn. warm granulomatous inflammation involving the Meibomian gland of eyelid usually self-limiting S. inflamm. get better on own Scleritis red eye but able to see sclera vessels deep. RA. ophthalmoplegia (impaired eye movements) Subconjunctival hemorrhage hemorrhage/ blood in the conjunctiva. blood thinners if associated w/ trauma emergency! Otherwise. throbbing pain worse w/ touch bleeding INSIDE the eye = OPHTHALMIC EMERGENCY! (increased IOP) White blood cells layering out INSIDE the eye = OPHTHALMIC EMERGENCY! inflammatory condition in the front Wegener's. vertical diplopia . previous surgeries. impaired/painful sinuses EOM. PAINLESS SELF-LIMITING inadvertent rubbing or Valsalva maneuvers -->small vessel hemorrhage in the substantia propria of conjunctiva trauma.
engorged retinal veins with hemorrhage Open angle: bilateral. spinal cord tumor. night blindness. central scotoma MS F>M ages 15-45 (younger population) fundo exam: normal or swollen corticosteroids disc (nl if retrobulbar optic neuritis). abnl light reflex. venous thrombosis Papilledema painless. permanent visual loss ischemia to optic nerve head DM. scotomas and loss of periperal vision --> tunnel vision & blindness. idiopathic. get brain MRI 2. white matter lesions & plaques if MS fundo exam: swollen disc Anterior Ischemic Optic Neuropathy PAINLESS.meningitis. elderly penlight test: shadow produced on nasal side (bc iris is domed up blocking the light across the iris). hydrocephalus. EKG. PAIN on eye movement. giant M=F cell arteritis older population (age>50) intracranial ANY age mass lesions.A. carotid (carotid U/S or CTA. hi cholesterol) ESR/CRP normal (giant cell less no acute treatment likely) secondary prevention of workup for source of emboli cerebral & ocular infarcts antiplatelets. 3m later. nl + hi pressure idiopathic intracranial hypertension. painless loss of vision. swelling of optic disc. pressure trauma.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Optic neuritis inflammation of the optic nerve blurry vision or loss of vision. tumors. RAPD "curtain coming down" transient embolization of plaque material from ipsilateral carotid artery or ophthalmic artery suspect giant cell arteritis if elderly person c/o sudden pallor of optic disc. HTN. exam shows increased cup:disc ratio Angle closure: severe pain a/w photophobia & blurry vision.. optic pallor MRI: acute inflammation of optic nerve. angle closure glaucoma: carotid occlusive narrowing of anterior chamber dz) angle aqueous continually being made by ciliary body + insufficient filtration out of the trabecular meshwork --> increased IOP & axonal death (infero/superotemporal axons affected first) --> enlarged optic cup FH (6x risk) A. nl MRI? 3. CT scan to r/o acute bleed. venous thrombosis. "cherry vision loss + temporal headaches red" macula Central retinal vein occlusion sudden. red eye with cloudy cornea. mgmt of cardiac echo) vascular risk factors Central retinal artery occlusion sudden. uveitis. cause depends on if open angle or neovascul angle closure: prolif (retinal open angle glaucoma: vein occlusion. endarterectomy. PAINLESS loss of vision in ONE eye. do not dilate this patient's pupil!! Pilocarpine systemic carbonic anhydrase inhibitor to lower pressure enough for surgery iridotomy or ididectomy blindness!!!!! . HTN. if nl. nl + nl pressure no raised ICP Vascular risk factors (smoking. decreased rate of aqueous outflow diabetic into the canal of Schlemm retinopathy. painless. get LP. Hispanics. mass. if abnl . abnl MRI? Hydrocephalus. meningeal processes. BILATERAL usually spares central vision until late peripheral vision lost early disc edema from raised ICP fundo exam: bilateral swelling of optic nerve heads Workup of bilateral disc edema + headache: 1. fixed/non-reactive pupil late stages will have loss of central vision too hypercoagulable state DM & Chronic HTN Glaucoma progressive optic neuropathy that meds 1/50 adults is usually a/w increased intraocular (steroids).
light eyes.DM glare with bright lights. progressive loss of deposits (drusen) fine vision (inability to see centrally. miotic inflammation of uveal tract (iris. Caucasians. UV light exposure. white eye reflex malignant melanoma adults "near sightedness" = unable to see far Enucleation Myopia focal point falls short of the retina so the focus of light is now in the vitreous cavity --> blurry vision all uncontrolled diabetics have blurry vision bc glucose enters the lens --> osmotic change in the lens --> myopia concave lens . moving the focal point back to the retina Hyperopia "far sightedness" = unable to see close Astigmatism eye is smaller than normal so rays of light strike the retina BEFORE they come into focus abnormalities in cornea and/or lens causes the eye to lose it spherical shape convex lens . females.S. heart dz. steroid use) Malignant tumors of the eye Retinoblastoma . adhesions btwn iris & ciliary body. infection. smoking. ulcerative colitis. blind spots & distorted vision most common cause of blindness in AIDS cotton wool exudates + retinal hemorrhages #1 cause of worldwide blindness opacity of the lens Cataracts congenital (rubella) adult (agerelated) epithelial cells of lens capsule constantly divide --> thickening/ hardening of lens over time --> cataract formation advanced age.pulls the focal point forward back onto retina glasses or toric contact lens . ankylosing spondylitis FH. DM. AGE check CXR for hilar adenopathy if suspect sarcoid! Macular degeneration vitamin therapy to prevent progression from dry--> wet?? (at least eat healthy!!) CMV retinitis dry type: thinning of retina & formation of yellowish white slow. red eye + photophobia most common cause of permanent vision loss in ELDERLY degeneration of maculr retinal pigment epithelium sarcoidosis.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Uveitis pain + blurry vision. HTN.surgery in U. pupil. hemorrhages if wet hemorrhage --> death of retinal cells. unable white cortical to drive at night . poor nutrition.causes parallel light rays to diverge.think cataracts posterior subcapsular (DM) posterior subcapsular cataract (DM. unable to see faces) wet type: extension of dry type Drusens (yellow deposits) if where neovascularization of choroid vessels --> subretinal dry.) subcapsular white cortical cataracts .kids. choroid) --> WBCs in the aqueous humor anterior lens capsule. corticosteroid use cataract extraction procedures (most common smudges on retroillumination .
0 w/ uncont DM uncontrolled HTN. which normally occurs when you look at something close normal accommodation occurs when the ciliary muscle constricts. pregnancy. the lens proteins become stiffer ages 40-50 reading glasses Rubiosis iridis Blood vessels seen in the iris Neovascularization of the lens/ iris occuring when the retina undergoes ischemia --> increased increased IOP VEGF --> increased blood vessels in abnormal areas of the eye neovascular glaucoma. central retinal vein occlusion Ectropion red eye + abnl conjunctiva epithelium red eye + eye infection usually eye lid turns outward exposing the tear film and causing red eye eye lid turns inward disrupting the corneal epithelial cells and tear film causing red eye & infection (usually from eyelashes scratching cornea) hi glucose levels -> inc aldose reductase --> inc sugar alcohol by products --> loss of pericytes in endothelium of retina --> outpouching of blood vessels & bleeding/edema of retina Extropion Diabetic retinopathy (general) requires abnl glucose for 10-12y #1 cause of new adult cases of blindness 1. DM (proliferative diabetic retinopathy). capillary drop out macular edema (If exudates accumulate in central retina) Proliferative increased microthrombus formation --> retinal ischemia --> neovascularization of iris & release of VEGF--> neovascularization into vitreous retina cavity --> hemorrhage of these weak vessels --> retinal pre-retinal or vitreous detachment hemorrhage profound vision loss .Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications Presbyopia "wise old owl has presbyopia" loss of ability to accommodate. anemia longer duration of DM tight glycemic control + control of HTN + laser therapy Nonproliferative lipid exudates + microaneurysms macular edema --> dec visual acuity lack of retinal capillary endothelial integrity --> microaneurysms + fluid/ protein/ lipid exudates trypsin digest microaneurysms. edema 3. making the lens fatter & moving the focal point to the FRONT of the retina (instant myopia) (accomodation --> pupil constriction as object moves closer to eyes) with age. renal dz. neovascularization 4. weak blood vessel walls 2. bleeding >70% of pts HbA1c > 7.
etc) Retinal detachment Temporal (giant cell) arteritis temporal artery bx to confirm Corticosteroids for 2y can save the other eye! dx . diplopia. macular stars. cotton wool spots (if infarct in nerve fiber layer). jaw claudication. monocular visual vessels loss in ELDERLY SUSPECT THIS DX W/ ANY systemic symptoms (weight NEURO-OPHTHALMOGIC loss. choroidal ischemia. FLASHING lights/ falling stars/ FLOATERS followed by shadow in periphery vasculitis affecting medium-sized temporal headache + transient. headache. scalp COMPLAINT IN ELDERLY tenderness. hard exudates (infarct in deeper retinal layers). cerebral ischemia. ocular ischemia) age >50 (usually 70s.80s) abnl ESR/ CRP (suggests systemic process) start IV steroids STAT if suspect this dx follow pt for corticosteroid side effects (BMD. fatigue. central retinal artery occlusion.Disease Clinical Variants Defining Characteristics Pathogenesis Etiologies Epi Risk factors Lab/Imaging Treatment Complications HTN retinopathy av nicking. PATIENT!!!! hi ESR/CRP) 25% pts have ischemic complications involving eye & orbit (ischemic optic neuropathy. hemorrhages are not present unless GRADE 4 HTN retinopathy painless.
Screening / Education .
Screening / Education .
swimming. bathing in tubs.Screening / Education any diagnosed seizure? No driving or operating heavy machinery. sleep deprivation urge AED compliance f/u MRI . ladders until seizure free avoid alcohol.
Screening / Education .
Screening / Education .
carotid endaterectomy if stenosis lifestyle mods >> meds . smoking. Afib. hypercoag). LVH) 2ndary prevention? Antiplatelet tx (aspirin if atheroscl. CVD. anticoag tx (coumadin if cardioemb.Screening / Education Framingham stroke risk score (age. DM. small vessel dz). untx SBP or tx SBP.
Screening / Education .
Screening / Education .
Screening / Education .
Screening / Education PD progresses within 15-20y timeframe .
Screening / Education .
Screening / Education .
70% are unable to work . 50% are unable to walk.Screening / Education genetic testing not done in unaffected children at risk! w/I 15y of dx: 80% of pts have functional impairment.
Screening / Education .
Screening / Education .
Screening / Education patient autonomy .
Screening / Education must talk to family members about what to expect as brain dead testing is done (spontaneous movements after brain death) give family the option to withdraw care! Organ donation .
Screening / Education .
Screening / Education inactivated polio vaccine! progression & life expectancy ~ age of onset .
Screening / Education nutritional & caregiver education end of life decisions hospice .
Screening / Education .
Screening / Education Concerned about use of OCP. stroke/ HTN/ OSA risk in migraine patients .
Screening / Education .
Screening / Education VERY CONTAGIOUS!!! Avoid social contacts! .
Screening / Education .
Screening / Education comprehensive eye exam for everyone after age 40 early eye exams if FH .
eat healthy.Screening / Education smoking cessation wear sunglasses. control vascular dz prevention involves controlling comorbidities . get eye exams.
yearly afterwards .Screening / Education T1DM: dilated eye exam q 3-5y within dx & yearly afterwards T2DM: dilated eye exam @ time of dx.
Screening / Education .
gonorrhea - Intracellular diplococci associated with neutrophils Oxidase+ grows w/ CO2 .Bacteria Classification Gram +/- Morphology Characteristics Streptococcus pyogenes GAS + Catalase neg Facultative anaerobe hyaluronic capsule Cocci in pair/chains (mucoid appearance) strongly B-hemolytic Bacitracin susceptible Staphylococcus aureus + Cocci in grape-like clusters Catalase + Coagulase + (good test to distinguish S. aureus from other Staph) Facultative anaerobe Beta-hemolytic Mannitol + Yellow colonies (CoPS) N.
lipases (abscess formation). PVL (toxin that kills leukocytes by forming SSTIs pores in their Cellulitis membranes). leukocidin (lysis of phagocytes). Pyomyositis clumping Meningitis factor/techoic acid/ Food poisoning proteins A&B TSS (adherence). >90 Impetigo types) Strep TSS Glomerulonephritis SPEs (superantigens SSTIs that superstimulate T Cellulitis cells --> inflam Erysipelas cytokines) NF CA-MRSA: SCCmec type IV cassette w/ methicillin resistance. PFGE NF type USA 300 SSI Endocarditis General: Catalase + Pericarditis (anti-phagocytic).Por1A . Rheumatic fever superantigen. MANY toxins! Resistant to human serum .Virulence factors Diseases Strep throat M surface protein (anti(pharyngitis) phagocytic.
canimorsus Aeromonas hydrophilia Erysipelothrix rhusiopathiae Mycobacterium marinum Psuedomonas aeruginosa Gas gangrene Vibrio vulnificus Streptococci S P A C E K Nosocomial Infections Serratia Pseudomonas Acinetobacter Citrobacter Enterobacter Klebsiella .3 skin Duration of immunosuppressants Skin cancers Intensity of immunosuppressants HPV Hx of skin cancer CD4 lymphopenia Skin break Human bite (mouth pathogens) Cat bite/puncture Dog bite/puncture Fresh water Salt water/fish Aquarium Spa/ hot tub Trauma Cirrhosis & salt water Edema Pathogen Eikenella corrodens Pasteruela multocida C.Population Disease Risk factors Transplant patients Age UV exposure Type 1.
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