THE

USMLE STEP 1
BIBLE

The Ultimate USMLE Step 1 Preparation Guide

Dr. Paul Ciurysek, M.D.

USMLE Step 1 BIBLE

TheUSMLEStep1BIBLE
Copyright2010Dr.PaulCiurysek,M.D.Allrightreserved.Nopartofthisbook
maybeusedorreproducedinanymannerwhatsoeverwithoutwrittenpermission
exceptinthecaseofreprintinthecontextofreviewandpersonaleducation.

FOREWORD

TheUSMLEStep1BIBLEwaswrittenforonlyonereason:Tohelpyouunderstand
medicineaswellaspossibleandelevateyourStep1scoreashighaspossible.
TheStep1BIBLEwascreatedwiththeideathathighyieldtopicsareextremely
important,butsimplylookingatthesuperficialinformationrelatingtothemisnot
themosteffectivewaytoprepareforthisinformationrichtest.Ifwecouldgather
alloftheveryhighyieldtopicscoveredbytheUSMLEStep1exam,andthendelve
deeperandexamineeverythingthereistoknowaboutthem,thenwearegoingto
beadequatelypreparedtotacklethisexam.Notonlywillthisprepareyoufora
passingscore,butitwillhelptoelevateyourknowledgeandunderstandingbeyond
anyotherpreparationsourceavailabletoyou,whichwillultimatelyhelpgiveyou
thechanceofscoringverywellontheStep1exam.
ThebestwaytousetheUSMLEStep1BIBLEistocombineitwithaqualityquestion
bankgearedtotheStep1exam.Theinformationwithinthisguide,whenusedin
conjunctionwithaquestionbank,willadequatelyprepareyouforultimatesuccess.
BestofluckontheStep1exam,
Dr.PaulCiurysek,M.D

CONTENTS

CHAPTER1GROSSANATOMY
CHAPTER2EMBRYOLOGY
CHAPTER3HISTOLOGY
CHAPTER4NEUROANATOMY
CHAPTER5PHYSIOLOGY
CHAPTER6BIOCHEMISTRY
CHAPTER7ETHICS
CHAPTER8BIOSTATISTICS
CHAPTER9PSYCHIATRY
CHAPTER10IMMUNOLOGY
CHAPTER11MICROBIOLOGY
CHAPTER12PHARMACOLOGY
CHAPTER13PATHOLOGY

CHAPTER1

GROSSANATOMY

GrossAnatomyisaveryhighyieldtopicontheUSMLE
exam.Thequestionsyouwillencounterwillrequire
recognitionandunderstandingofstructures,andtheability
tounderstandandidentifytheirclinicalsignificance.

THEBRACHIALPLEXUS


UPPERLIMBNERVEINJURIES
Thecommonupperlimbnerveinjurieshaveclassicpresentationsandareusually
reversible.Themostcommoninjuriesinclude:
NerveInjured
MEDIAN

RADIAL

ULNAR

AXILLARY

CommonCauses
Injurytothe
supracondyleof
thehumerus.

MotorDeficit
Lossof:
Forearm
Pronation
WristFlexion
FingerFlexion
Thumbmovement
Longtermthenar
atrophyis
possible
Injurytothe
Lossoftriceps
shaftofthe
reflex,
humerus
brachioradialis
reflex,and
extensorcarpi
radialislongus
(causingthe
classicwristdrop)
Injurytothe
Causesimpaired
medial
flexionand
epicondyleofthe adductionofthe
humerus
wrist,aswellas
impaired
adductionofthe
ulnartwofingers
andthethumb
Injurytothe
Resultsinalossof
surgicalneckof
completedeltoid
thethehumerus movement
and/oranterior
shoulder
dislocation

MUSCULOCUTANEOUS Compression
betweenbiceps
aponeurosisand
brachialisfascia

SensoryDeficit
Lossofsensation
inthethumb,
lateralaspectof
thepalm,andthe
first2.5fingers
(index,middle,
andhalfofring
finger)
Lossofsensation
totheposterior
antebrachial
cutaneousand
theposterior
brachial
cutaneous

Lossofsensation
tothemedial
aspectofthe
palm,aswellas
lossofsensation
tothepinkyand
medialofthe
ringfinger
Lossofsensation
overthedeltoid
muscle,aswell
astheskin
coveringthe
inferioraspectof
thedeltoid
Lossoffunctionof Lossofsensation
coracobrachialis, intheradial
biceps,and
aspectofthe
brachialismuscles forearm


WRISTDROP
AlsoknownasradialnervepalsyandSaturdaynight
palsy.TheradialnerveinnervatestheBrachioradialis,
Extensorsofthewrist/fingers,Supinator,andtheTriceps.
Compressionand/orinjurytotheradialnervecausesthe
classicwristdrop,duetotheinabilitytoextendthewrist.

Mnemonicfor
muscles
innervatedby
theradial
nerve:
BEST
Brachioradialis
Extensorsof
wrist/fingers
Supinator
Triceps

CLAWHAND(UlnarNerve)
Compressionoftheulnarnerveattheelbowwillcausenumbnessofthesmallfinger
andthemedialaspectoftheringfinger.Withtime,weaknessofthehandwill
producetheclawhand,wherethesmallfingerandtheringfingercontractand
formaclaw.Thisislatesequelaeofulnarnerveinjury,andisasignofaseverely
injuredulnarnerve.


ERBDUCHENNEPALSY
Aparalysisofthearmduetoinjuryofthesuperiortrunkofthebrachialplexus(C5
andC6roots).Thisoccursmostcommonlywithshoulderdystociaduring
childbirth,butisalsoseenfromdirectblowstotheshoulder.Themostcommonly
affectednervesaretheaxillarynerve,themusculocutaneousnerve,andthe
suprascapularnerve.Thiscausesalossofsensationinthearmandatrophyofthe
deltoid,thebiceps,andthebrachialismuscles,resultinginacharacteristichanging
ofthearmtothesidewithmedialrotation.
Theclassicfindings:

Abductorparalysis(hanginglimbtotheside)
Paralysisoflateralrotators(medialrotation)
Lossofbicepsaction(forearmpronation)

Thepresenceofabriskreflexinthearmoftenmeansthereisagoodprognosis.

THORACICOUTLETSYNDROME
Acompressionofthesubclavianarteryandtheinferiortrunkofthebrachialplexus
resultsinthoracicoutletsyndrome.CompressionoccursatC8andT1,leadingto:

Thenarandhypothenaratrophy
Interosseusmuscleatrophy
Sensorydeficitofthemedialforearmandhand
Lossofradialpulseuponheadmovementtotheaffectedside

INTRINSICMUSCLESOFTHEHAND


THEROTATORCUFF
Therotatorcuffisagroupofmusclesthatstabilizethe
shoulder.Therearefourmusclesintherotatorcuff,they
are:

Supraspinatus
Infraspinatus
TeresMinor
Subscapularis

SITS
Supraspinatus
Infraspinatus
TeresMinor
Subscapularis

Injurytotherotatorcuffismostcommonlyexperiencedas
paininthelateralaspectofthedeltoid,andisoftenaccompaniedbythepainon
abductionofthearm.


THERECURRENTLARYNGEALNERVE
Therecurrentlaryngealnerveisanimportant
structureoftheneck.ItisabranchoftheVagus
Nerve,andsuppliesallintrinsicmusclesofthe
larynxexceptthecricothyroid.

Damagetorecurrent
laryngealnerve=
Hoarseness

Therightrecurrentlaryngealnervewrapsaroundtherightsubclavianartery,while
theleftrecurrentlaryngealnervewrapsaroundthearchoftheaortaandthe
ligamentumarteriosum.


CARDIACVASCULATURE


THELUNGS
Therightlungcontains3lobes,whiletheleftlobecontainsonly2lobes.Theleft
lungcontains,insteadofamiddlelobe,spacethatisoccupiedbytheheart(cardiac
notch).

Themostcommonsiteofforeignbodyaspirationistherightlung,becausetheangle
oftherightmainstembronchusislessacutethantheleftmainstembronchus.

Trachea Bronchi Bronchioles TerminalBronchioles Alveoli


LYMPHATICDRAINAGE
Lymphaticdrainageisquitesimple;therightlymphaticductdrainstherightsideof
theheadandtherightarm,whilethethoracicduct(leftside)drainstherestofthe
body.


THECELIACTRUNK
Theceliacarteryisthefirstmajorbranch
offoftheabdominalaorta,followedbythe
superiorandinferiormesentericarteries.
Theceliacarterysuppliestheliver,
stomach,spleen,superiorhalfofthe
duodenum,theabdominalesophagus,and
thepancreas(allstructuresofthe
foregut).

BLOODSUPPLYTOGI
CeliacStomachtoduodenum,liver,GB,
pancreas.
SMADuodenumto2/3oftransversecolon.
IMADistal1/3oftransversecolontoupper
rectum.

Thesuperiormesentericarterysuppliesstructuresarisingfromthemidgut,while
theinferiormesentericarterysuppliesstructuresarisingfromthehindgut.


DIAPHRAGMSTRUCTURE
ThediaphragmisinnervatedbyC3,C4,andC5(PhrenicNerve).Duetothis
innervation,painand/orpressuretothediaphragmcancausereferredpaintothe
shoulder.Thereareafewextremelyimportantstructuresthatperforatethe
diaphragmatthelevelofT8,T10,andT12.Theyinclude:
AtT8InferiorVenaCava
AtT10Esophagus,Vagaltrunks(2)

POPULARMNEMONIC
I810EGGSAT12

AtT12Aorta,AzygousVein,Thoracic
Duct

IVC8(T8)

EsophaGus&vaGuSat10(T10)

Aorta/Azygous&Thoracicduct
at12(T12)


STRUCTUREOFTHEBILIARYTREE
Bileissecretedbytheliverandstoredinsidethegallbladder,thensecretedintothe
duodenumasneeded.Manyabdominalpathologiesoccurasaresultofstasis
and/orobstructionofthebiliarytree.


STRUCTURESOFTHERETROPERITONEUM
Itisimportanttobeabletodecipherbetweenperitonealandretroperitoneal
structures,aslocationcanhelpyoumakeadiagnosisbasedonpresenting
symptoms.Retroperitonealstructurescanoftenreferpaintotheback,thus
knowledgeofthisanatomyisessential.


THEINGUINALCANAL
Theinguinalcanalisanobliquestructurethatholdsthespermaticcordand
ilioinguinalnerveinmales,andtheroundligamentoftheuterusandilioinguinal
nerveinfemales.Thecanalisformedbytheaponeurosesofthreeflatabdominal
muscles.
BoundariesoftheInguinalCanal:
1. SuperficialInguinalRingtriangulardefectintheexternaloblique
aponeurosis
2. DeepInguinalRinginthetransversalisfascia
3. AnteriorWallinternalobliquemuscle(laterally)andexternaloblique
aponeurosis(medially)
4. Rooffalxinguinalis(archinginferiorfibersofinternalobliquemuscle)
5. Flooringuinalligamentandlacunarligament(medially)
6. PosteriorWalltransversalisfascia(weakfascia)laterallyandconjoint
tendon(medially)

HASSELBECHSTRIANGLE
Isaninguinaltrianglethroughwhichdirectinguinalherniasprotrudethroughthe
abdominalwall.

HERNIAS
DirectInguinalHerniasThistypeofherniabulges
throughtheabdominalwall,throughHasselbechs
triangle,medialtotheinferiorepigastricvesselsandonly
throughthesuperficialinguinalring.
MDMedialtoinferiorepigastricartery=DirectHernia

Herniasarea
protrusionof
gastrointestinal
contents
throughareasof
weaknessinthe
abdominalwall.

IndirectInguinalHerniasThistypeofherniatravels
throughthedeepandsuperficialinguinalringsandintothescrotum.Protrusion
throughthedeepinguinalringislateraltotheinferiorepigastricvessels.This
occursduetofailureoftheclosureoftheprocessusvaginalis.
DiaphragmaticHerniasThistypeofherniaoccurswhenabdominalcontents
enterintothethorax.Themostcommontypeofdiaphragmaticherniaisthehiatal
hernia,whichiscommonandassociatedwithGERD.NewbornsmayhaveGI
contentsinthethoraxasaresultofadefectinthepleuroperitonealmembrane.


FEMORALHERNIA
Afemoralherniaoccurswhenthereisaweaknessinthefemoralcanal/triangle,and
occursdirectlybelowtheinguinalligament.Thistypeofherniaisuncommon,
accountingfor<5%ofallhernias.Itismostcommonlyseeninfemalesduetotheir
widerpelvicstructure.
ReducibleFemoralHerniaIsthemostcommonform,theherniacanbepushed
backintotheabdomen.
IrreducibleFemoralHerniaOccurswhentheherniaisnotreducible,and
becomesstuckinthefemoralcanal.
IncarceratedHerniaOccurswhentheherniabecomestrappedinthehernial
sack.Thisisconsideredtobeasurgicalemergencyandrequiresimmediate
treatment.
StrangulatedHerniaOccurswhenbloodsupplytoanincarceratedherniaiscut
off.Thiscancausetissuedeathandthedevelopmentofgangrene.

PORTALSYSTEMICANASTOMOSES
Theseareanastomosesthatoccurbetweenveinsoftheportalandsystemic
circulation.Thesesitesareimportantbecauseseveralconditionsmayoccurasa
resultofchangesinpressurewithineachsystem.
Themostcommonconditionsinclude:Hemorrhoids,EsophagealVarices,andCaput
Medusae.
CONDITION
Hemorrhoids
EsophagealVarices
CaputMedusae

SYSTEMICCIRCULATION PORTALCIRCULATION
MiddleRectalandInferior SuperiorRectalVeins
RectalVeins
AzygousVeins
LeftGastricVein
SuperficialEpigastricVein ParaumbilicalVeins

LIGAMENTSOFTHEUTERUS

DRAINAGEOFTHETESTCILES/OVARIES
Theleftovary/testedrainsfromtheleftgonadalvein,totheleftrenalvein,andinto
theinferiorvenacava.
LeftGonadalVein LeftRenalVein IVC

In25%ofmen,thissystemisnotcompletelycompetent,andresultsina
varicoceleoftheleftteste

Therightovary/testdrainsdirectlyfromthegonadalveinintotheIVC.Thisrarely
resultsinavaricoceleinmenduetotheangleofdrainage.

THEPECTINATELINE
Thepectinatelineismostcommonlyusefulwhenapatienthashemorrhoids.
Hemorrhoidsthatareabovethepectinatelinedonotcausepainduetovisceral
innervation.Hemorrhoidsthatarebelowthepectinatelinehavesomatic
innervation,andarethereforepainful.
Thepectinatelineisformedwherethehindgutandtheectodermmeet.
Arterialsupplyabovethepectinatelineisfromthesuperiorrectalartery.Venous
drainageisfromthesuperiorrectalveintotheinferiormesentericvein,andinto
theportalsystem.
Arterialsupplybelowthepectinatelineisfromtheinferiorrectalartery.Venous
drainageisfromtheinferiorrectalveintotheinternalpudendalvein,thenintothe
internaliliacveinandintotheIVC.


ANATOMYOFTHEKIDNEY


ANATOMYOFTHEGLOMERULUS


ANATOMYOFTHECORTEXANDMEDULLA


ANATOMYOFTHEKNEE

KNEELIGAMENTANATOMYANDINJURIES
MenisciThecommonpresentationofameniscalinjuryiskneepainandswelling,
aswellaslockingofthejoint,especiallywhenbearingweightonthejointandfully
straighteningtheleg.Themeniscicanbetornwhendoinglowimpactactivities
suchaswalking,andcanbetornwhendoinghighimpactactivitiessuchasweight
liftingandplayingsports.Commoncausesofinjuryareimpacttothekneeanda
twistingmotionofthekneewhenitisfirmlyplanted.
MedialCollateralLigamentAlsoknownasthetibialcollateralligament.Attached
proximallytothemedialcondyleofthefemurbelowtheadductortubercleand
medialsurfaceofitsbody.Theposteriorfibersareshortandinclinebackwards
upondescent,andareinsertedintothetibiaabovethesemimembranousmuscle

groove.Itinsertsintothemedialsurfaceofthetibialbodyabout2.5cmbelowthe
levelofthecondyle.Injuriesarecommoninskiingandinfootballwhenvalgus
stressisapplied(thisisabductionstressakastresstothelateralaspectofthe
knee).
LateralCollateralLigamentAlsoknownasthefibularcollateralligament,is
narrowandlessbroadthatthemedialcollateralligament.TheLCLtravelsobliquely
fromthelateralepicondyleofthefemurtotheheadofthefibula.Theanatomyof
theLCLgivesitmoreflexibilitythantheMCL,andthusitislesscommonlyinjured.
AnteriorCruciateLigamentTheACLgetsthetermanteriorbecauseitattaches
totheanterioraspectofthetibia,withanoriginfromdeepwithinthenotchofthe
distalfemur.Injurytotheanteriorcruciateligamentisthemostcommonknee
injury,andisespeciallyseeninathletes.Lateralrotationalmovessuchasthosein
soccer,basketball,andskiingarecommoncausesofACLstrainsand/ortears.
TestingforACLinjuryisdonewiththeanteriordrawertest,wheretheflexed
kneeisdrawnforwardinanattempttoidentifyanincreasedamountofanterior
tibialtranslationascomparedtotheoppositejoint.TheLachmantestisanother
diagnostictestthatissimilarinnature,butwiththepatientskneein2030degree
flexioninsteadofthe90degreeflexionusedintheanteriordrawertest.
PosteriorCruciateLigamentTheposteriorcruciateligamentgetsitsname
becauseitattachestotheposterioraspectofthetibia.Itconnectstheposterior
intercondylarareaofthetibiatothemedialcondyleofthefemur.InjurytothePCL
causeslesspainanddisabilitythanthosetotheACL,andoftengoesundiagnosed.
ThecommoncauseofPCLinjuryisthedashboardinjury,wheresomething
forcefullystrikesthetibiaanddrivesitposteriorly.Acommonmechanismofinjury
duringsportingeventsisafallonahyperflexedkneewiththefootpointed
downwards.Patientsoftencomplainofapopduringtheinjury.ThePCLinjuryis
diagnosedinitiallywiththeposteriordrawertest,wherethetibiaispushed
backwardsandadecreasedresistanceisexperienced.
TheUnhappyTriadThisisacommonkneeinjuryseeninfootball,whereaplayer
ishitonthelateralaspectoftheknee,causingdamagetotheACL,MCL,andMedial
Meniscus.


THESCIATICNERVE

CHAPTER2

EMBRYOLOGY

Mostoftheinformationfromtheembryologysectionis
highyield.Memorizationoftheembryologicderivativesis
important,asitislikelytoshowupontheexam,asisthe
majorityoftheinformationfromthischapter.

SPERMATOGENESIS
Spermatogenesisistheprocessbywhichthespermatogoniadevelopintothe
maturesperm(spermatozoa).Thisoccursinthetestesandepididymisinastepby
stepfashion,takingapproximately65days.Thestartingpointforspermatogenesis
istheseminiferoustubulesofthetestes,wherethestemcellsthatareadjacentto
theinnertubulewalldivideinacentripetaldirection(movingtowardsthelumen).
Maturationofspermoccursintheepididymis,whereitacquiresitsmotility.
Throughoutspermatogenesis,thesertolicellsplayanimportantroleinthe
following:

Maintainingtheenvironmentnecessaryformaturation/developmentviathe
bloodtestisbarrier
Secretessupportingfluidsandsubstancestoinitiatemeiosis
Secreteandrogenbindingproteins,whichcreatetheenvironmentfora
higherleveloffertility
Secreteinhibininordertostimulatethepituitaryglandtofurther
spermatogenesis
SecretesantimullerianhormonetopreventtheformationofMullerianDucts
Providesprotectiontothespermatidsfromautoimmuneattack


THEANATOMYOFSPERM


FROMFERTILIZATIONTOIMPLANTATION
Uponfertilization,therearemanyrapidchangesthatoccurtotheegg,including
migrationthroughthefallopiantube,implantation,celldivision,growthand
development,etc.Thefollowingtableandillustrationdemonstratethemost
importantpointsfromfertilizationtoimplantation.
TIME
InitiatingEvent
Week1
Week2
Week3
Week38

Week4
Week10

EVENT
Fertilizationofeggbysperm
Implantationofblastocyst
Formationofbilaminardisk
Formationofprimitivestreak,
notochord,andneuraltube.
Gastrulation
Neuraltubeformation.
Formationoforgans.
Mostlikelytimetobeharmedby
teratogenicagents.
Limbbudsbegintoform.
Heartbeginstobeat.
Genitalsaredifferentiated.

HISTOGENESIS
Istheformationofthedifferenttissuesofthebodyfromundifferentiatedcells.
Thesearetheectoderm,mesoderm,andendoderm.
EctodermTheectodermisthemoresuperficialtissue,theyinclude:

SurfaceEctoderm:Epidermis,Liningoftheepithelium,Lensoftheeye,and
theadenohypophysis.
Neuroectoderm:CNSNeurons,Neurohypophysis,Oligodendrocytes,
Astrocytes,andthePinealGland
NeuralCrest:AutonomicNervousSystem,DorsalRootGanglia,Melanocytes,
ChromaffinCellsofAdrenalMedulla,EnterochromaffinCells,PiaMater,
CeliacGanglion,SchwannCells,ParafollicularCellsofThyroid,Laryngeal
Cartilage

EndodermTheendodermisformedbycellsmigratingalongthearchenteron,
formingtheinnerlayerofthegastrula,thusdevelopingintotheendoderm.The
cellsoftheendodermbeingassquamouscells,butfinallychangeintocolumnar
cells.Thetissuesoftheendoderminclude:

Theentiregastrointestinaltractexceptpartofthemouth,pharynx,andthe
terminalrectum(formedbyectodermalinvolution)
Thetrachea,bronchi,andalveoli
Liningofthefolliclesofthethyroid,thymus,andparathyroidglands

MesodermThemesodermisthemiddlegermallayer,givingrisetomanydifferent
tissues.Somemesodermaltissuescontaintheabilitytodifferentiateintoadiverse
rangeoftissues,suchasthebonemarrow.Thetissuesofthemesoderminclude:

Theadrenalcortex
Thespleen
Duraofconnectivetissues
Muscletissues
Bone
Structuresoftheheart
Thelymphaticsystem
Theurinarysystem(kidneysincluded)
Serousliningsofperitonealbodycavities
Blood

THEUMBILICALCORD
TheumbilicalcordisuniqueinthatitcontainsTWO
arteriesandONEvein.Theumbilicalveinis
responsibleforsupplyingthefetuswithoxygenated
blood,whilethearteriesareresponsibleforcarrying
deoxygenatedbloodfromthefetus.

UMBILICALVESSELS
VEIN=Oxygenated
ARTERY=Deoxygenated

EMBRYOLOGYOFTHEHEART
Theembryonicstructuresoftheheartcorrespondwiththematurestructuresofthe
heart,theyare:
TruncusArteriosusAscendingaortaandpulmonarytrunk
BulbusCordisSmoothpartsofleftandrightventricle
PrimitiveVentricleTrabeculatedpartsoftheleftandrightventricle
PrimitiveAtriaTrabeculatedleftandrightatrium
LeftHornofSinusVenosusCoronarysinus
RightHornofSVSmoothpartofrightatrium
RightcommoncardinalveinandrightanteriorcardinalveinSVC

FETALCIRCULATION
Oxygenatedbloodiscarriedfromtheplacentatothefetusviatheumbilicalvein.
Approximatelyhalfofthisbloodentersthefetalductusvenosusandiscarriedto
theinferiorvenacava,withtheotherhalfenteringtheliver.Asthebloodentersthe
rightatriumoftheheart,mostofitflowsthroughtheforamenovaleandintothe
leftatrium(bypassingthepulmonarycirculation).Thebloodthenmovesintothe
leftventricleandispumpedthroughtheaortatothebody.Someoftheblood
travelingthroughthebodyenterstheinternaliliacarteriesandtotheumbilical
arteries,reenteringtheplacentaanddisposingofcarbondioxideandotherwaste
products(whichtraveltothematernalcirculation).Notethatthereisaconnection
betweentheaortaandthepulmonaryarterycalledtheductusarteriosus,which
shuntsmostbloodawayfromthelungsbecausetheyarenotuseduntilthefetusis
born.
Uponbirthoftheinfant,thefirstbreathcausesadecreaseintheresistanceofthe
pulmonaryvasculature,increasingthepressureintheleftatriumrelativetothe
pressureoftherightatrium.Thisleadstotheclosureoftheforamenovale(now
thefossaovalis).Thereisalsoaclosureoftheductusarteriosusbecausethe
increasedconcentrationofoxygencausestheprostaglandinlevelstodecrease.This
closurepreventsthebloodfrombypassingthepulmonarycirculation,allowingthe
lungstofunctionproperly.

TERATOGENICAGENTSOFPREGNANCY
Congenitalanomaliesoccurinapproximately3%ofalllivebirths,withmaternal
exposuretoteratogenicagentsbeingresponsiblefor4%6%ofthosecases
(approximately1/400liveborninfants).
Timingisanimportantfactorinateratogensilleffectonthefetus,withthemost
susceptibletimebeingbetweenthe3rdand8thweeksofpregnancy,whichisthe
mostactivetimeoforganogenesis.
TERATOGENICAGENT
AndrogenicHormones

Warfarinandothercoumadinderived
anticoagulants

Antithyroidmedications(PTU,
Methimazole,Iodide)
Diphenylhydantoin
ValproateandCarbamazepine
Lithium
Diethylstilbestrol
Isotrenitoin
Alcohol
Tobacco

Cocaine
Thalidomide
ACEinhibitors

EFFECTONFETUS
Clitoralenlargement,labioscrotalfusion
whengivenbefore13weeksgestation.
*OCPsnotshowntoproduceanomalies
whenusedin1sttrimesterofpregnancy.
Multipleanomalies,mostcommonly:
Developmentaldelay,hydrocephalus,
agenesisofcorpuscollosum,
meningoencephalocele,midfacial
hypoplasia.
Variousocular,skeletal,andotherbirth
defects.
Occasionallyproducestransientfetal
hypothyroidismandgoiter.
Abnormalfacies,microcephaly,growth
deficiency,mentalretardation,
hypoplasticnails,hypoplasticphalanges.
Neuraltubedefects
Ebsteinsanomaly
Structuraldefectsofthefemalegenital
tract,vaginaladenosis.
Microphthalmia,hydrocephalus,
microtia,cleftpalate,blindness,
deafness,heartdisease,thymicagenesis.
Fetalalcoholsyndrome
Spontaneousabortion,increasedriskof
placentalabruptionorprevia,preterm
delivery,andprematureruptureof
membranes.
Placentalabruption
Limbdefects
Renaldamage


FETALERYTHROPOIESIS
Theformationofredbloodcellsiscarriedoutbyfourdifferentstructures
throughoutfetaldevelopment.
Fromapproximately38weeks,itiscarriedoutbytheYOLKSAC
Fromapproximately630weeks,itiscarriedoutbytheLIVERandSPLEEN
Fromapproximately28weeksandbeyond,itiscarriedoutbytheBONEMARROW

BRANCHIALARCHINNERVATIONANDDERIVATIVES
Arch1derivativesaresuppliedbyCNV2andV3
Arch2derivativessuppliedbyCNVII
Arch3derivativessuppliedbyCNIX
Arch4and6derivativesaresuppliedbyCNX
ARCH1
Meckels
cartilage:
Mandible
Malleus
Incus
Sphenomandibular
ligament
Musclesof
mastication:
Masseter
Lateral/Medial
pterygoid
Mylohyoid
Anteriorbellyof
digastric
Tensortympani
Tensorvelipalatini
Nerve:CNV3

ARCH2
ReitersCartilage:
Stapes
Styloidprocess
Lesserhornof
hyoid
Stylohyoid
ligament
Muscles:
Stapedius
Stylohyoid
Posteriorbellyof
digastric
Nerve:CNVII

ARCH3
Cartilage:
Greaterhornof
hyoid
Muscles:
Stylopharyngeus
Nerve:CNIX

ARCH4&6
Cartilage:
Thyroid
Cricoid
Arytenoids
Corniculate
Cuneiform
Musclesof4th
arch:
Mostofthe
pharyngeal
constrictors
Cricothyroid
Levatorveli
palatini
Musclesof6th
arch:
Allintrinsic
musclesoflarynx
exceptcricothyroid
Nerve:4tharchis
CNX,6tharchisCN
X

BRANCHIALCLEFTDERIVATIVES
1stbranchialcleftExternalauditorymeatus
2nd4thcleftsFormationoftemporarycervicalsinuseswhenthe2ndarch
mesenchymeisobliterated

BRANCHIALPOUCHDERIVATIVES
1stpouchmiddleearcavity,Eustachiantube,mastoidaircells
2ndpouchepithelialliningofthepalatinetonsil
3rdpouch(dorsalwings)inferiorparathyroids
3rdpouch(ventralwings)thymus
4thpouchsuperiorparathyroids

TWINPREGNANCIES
Therearetwotypesoftwinpregnancies,MonozygoticandDizygotictwins.The
DizygotictwinsareakaFraternalTwins,andhave2placentas,2amnioticsacs,
and2chorions.Monozygotictwinsareidenticaltwins,andcontain1placenta,1
chorion,and2amnioticsacs.
MONOZYGOTICTWINS:

1placenta
1chorion
2amnioticsacs

DIZYGOTICTWINS:

2placentas
2chorions
2amnioticsacs


EMBRYOLOGYOFTHEEAR
Thebones,muscles,andotherstructuresoftheearallhaveembryologicderivates.
Thesestructuresandtheirderivativesare:
EarStructure
TympanicMembrane
EustachianTube
ExternalAuditoryMeatus
Incus
Malleus
Stapes
TensorTympani(V3)
Stapedius(VII)

EmbryologicDerivative
1stpharyngealmembrane
1stpharyngealmembrane
1stcleft
1starch
1starch
2ndarch
1starch
2ndarch

EMBRYOLOGYOFTHETONGUE


EMBRYOLOGYOFTHETHYMUS
Thethymusisderivedfromtheepitheliumofthe3rd

branchialpouches.Thethymusfunctionsinproductionof
Tlymphocytes,whichareessentialpartsoftheadaptive
immunesystem.Thecortexofthethymusisdensewith
immatureTcells,whilethemedullacontainsthematureT
cells.

Cortex=Dense,
immatureTcells.
Medulla=Pale,
matureTcells.

EMBRYOLOGYOFTHETHYROIDGLAND
Thethyroidglandisderivedfromtheflooroftheprimitivepharynx,andupon
developmentitdescendsintotheneck.Thethyroidconnectstothetongueviathe
thyroglossalduct(disappearsinnormaldevelopment).Duetotheanatomyand
relationshipofthethyroidtothetongue,ectopicthyroidtissueismostcommonly
foundinthetongue.

EMBRYOLOGYOFTHEPANCREAS
Asawhole,thepancreasisderivedfromtheforegut.
VentralPancreaticBudPancreatichead,Uncinateprocess,andmainpancreatic
duct.
DorsalPancreaticBudBodyofpancreas,tailofpancreas,Isthmus,Accessory
pancreaticduct.

DEVELOPMENTOFGENITALDUCTS
MESONEPHRICDUCT(Wolffian)
Testiclessecretemullerianinhibiting
substanceinordertosuppressthe
developmentofparamesonephricducts.

Developsinto:Epididymis,Ejaculatory
duct,SeminalVesicles,DuctusDeferens

PARAMESONEPHRICDUCT
(Mullerian)
LackofsecretionofMullerianinhibiting
substancecausesgrowthof
Paramesonephricducts.

Developsinto:FallopianTube,Uterus,
Upperpartofvagina

HOMOLOGUESOFTHEDEVELOPINGGENITALTRACT
By68weeks,afetushashistologicallydistinguishablegonads.By7weeks,the
fetushasagenitaltubercle,urogenitalgrooveandsinus,andlabiosacralfolds.Ina
female,withoutexcessandrogensthesewillbecometheclitoris,urethra,vagina,and
labia.Themalefetusbecomesdistinctbetween812weeks,andtheandrogenswill
enlargethephallusandcausetheurogenitalgrooveandsinustofuseinthemidline.


EMBRYOLOGYOFTHEDIAPHRAGM
Duringinitialdevelopment,thediaphragmisinnervatedbynervesC3,C4,andC5.
Asthediaphragmdescends,itmaintainsthisinnervation.
Thediaphragmisderivedfromthefollowingembryologicstructures:

SeptumTransversum
PleuroperitonealFolds
BodyWall
DorsalMesentaryoftheEsophagus

FORMATIONOFBONE
Therearetwomaintypesofbonedevelopment,thosebeingintramembranous
boneandendochondralbone.Intramembranousboneisformedspontaneously
withoutthepresenceorneedofanypreexistingcartilage.Ontheotherhand,
endochondralbone(longbones)requiresthepresenceofcartilaginousmoldsin
ordertoformitsbonystructure.Thecartilaginousmoldossifiesandproducesthe
endochondralbone.

CONGENITALABNORMALITIESOFTHEPENIS
Hypospadiasisthemorecommoncongenitalpenileabnormality,anditcanbe
associatedwithUTIsinchildren.

CHAPTER3

HISTOLOGY

Histologyisnottraditionallyaveryhighyieldcomponentof
theStep1exam,butitisimportanttoknowwhichtypeof
epitheliummakesupallofthestructuresofthebody,as
wellasallpathologiesthatarelinkedtohistological
changes.

HowarebloodcellproductsmadeBLOODCELL
DIFFERENTIATION/PRODUCTION:

WHITEBLOODCELLSakaLeukocytes
Thewhitebloodcellisresponsiblefordefenseagainstinfections.Theyaremadeup
oftheGranulocytes(Eosinophils,Basophils,Neutrophils),andtheMononuclearcells
(Lymphocytes,Monocytes).


REDBLOODCELLSakaErythrocytes
Thebloodcellresponsibleforoxygentransport.Ithasmanyimportantfunctions,is
withoutnucleus,isbiconcave,andhasalargesurfacevolumethatenableseasygas
exchange.

NEUTROPHILSInvolvedintheacuteinflammatoryresponse,andmakeup
approximately4070%ofWBCs.Theyengulfviaphagocytosis,aremultilobed,and
containlysosomes.Lookforhypersegmentedneutrophilswhenapatienthasa
vitaminB12and/orfolatedeficiency.

EOSINOPHILSTheseareprotectiveagainsthelminthandprotozoalinfections.
Theyarehighlyphagocyticagainstantigenantibodycomplexes.Theyproduce
histamineandarylsulfatase.Eosinophilsmakeup1%6%ofallWBCs,arebilobed,
andarepackedwithlargeeosinophilicgranules.


BASOPHILSBasophilscompriselessthan1%ofallWBCs,andarethekey
componentsofallergicreactions.Basophilscontainhistamineandheparin,aswell
asothervasoactiveamines.

MONOCYTESContainsakidneyshapednucleus,comprisesapproximately2%
10%ofWBCS.

LYMPHOCYTESAresmall,round,andstaindensely.Tlymphocytesproducea
cellularimmuneresponse,whileBlymphocytesproduceantibodies.


NEUROHISTOLOGY
DENDRITICCELLSAntigenpresentingcells,seeninsometissueswhocomein
contactwiththeskin(Langerhanscells),innerliningofthenose,lungs,stomach,
andintestines.

MICROGLIAThesearethephagocytesoftheCNS,theyarethemainformof
defenseintheCNS.

OLIGODENDROGLIAThesecellsacttomyelinatetheaxonsoftheCNS.Theseare
thepredominantglialcellinthewhitematter.

SCHWANNCELLSSchwanncellsmyelinatetheaxons,theyalsopromoteaxonal
regeneration.

PERIPHERALNERVESTRUCTUREConsistsoftheEpineurium,Perineurium,and
Endoneurium.Theepineuriumisdenseandsurroundstheentirenerve,the
perineuriumiswhatallowsforpermeability,andtheendoneuriumiswithinthe
nerveandsurroundseverysinglenervefiber.


HISTOLOGYOFTHESKIN

MEISSNERSCORPUSCLESAreencapsulatedsensoryreceptorsinthedermisof
thepalms,soles,andfingers.Theyareinvolvedinlight,discriminatorytouchof
hairlessskin.
MERKELSCORPUSCLESThesearetactilediscs,whichmediatelightcrudetouch.
PACINIANCORPUSCLESThesearelargeencapsulatedsensoryreceptorsofthe
deeperlayersoftheskinatligaments,jointcapsules,mesentery,andserous
membranes.Theyareinvolvedindetectingpressure,vibration,roughtouch,and
tension.

EPITHELIALCELLJUNCTIONS


THEGLOMERULARBASEMENTMEMBRANE
Theglomerularbasementmembraneisformedbythefusionofendotheliumand
podocytebasementmembranes.Itservestofilterplasma


THEGOLGIAPPARATUS
Thegolgiapparatusservesthepurposeofprocessingandpackagingproteinsand
lipidsbeforetheyaresecretedtotherestofthebody.
Thegolgiapparatusismadeofstackofmembraneboundstructuresofcisternae,
whichcarrygolgienzymestohelpormodifytheproteinsthattravelthroughthem.

Themainfunctionsofthegolgiapparatusinclude:

Distributionofproteinsandlipidsfromtheendoplasmicreticulumtothe
plasmamembrane,lysosomes,andthroughsecretoryvesicles
AdditionofanOoligosaccharidetoSerineandThreonine
AdditionofNoligosaccharidetoAsparagine
Proteoglycanassembly
Sulfationofsugarsinproteoglycans

ROUGHENDOPLASMICRETICULUM(RER)
TheRoughEndoplasmicReticulumisresponsibleformanyfunctions,including:

Nlinkedglycosylation
Additionoflysosomalenzymeswithmannose6phosphatemarker
Integrationofmembraneproteins

Insideofneurons,thereistheNisslbody,whichistheRERoftheneuron.
SMOOTHENDOPLASMICRETICULUM(SER)
TheSmoothEndoplasmicReticulumiswheresteroidsaresynthesizedandwhere
drugdetoxificationtakesplace.


ALVEOLARCAPILLARYBARRIER
Thisbarrierispresentinthegasexchangeregionofthelungs,andservestoprevent
theformationofairbubblesintheblood,andfrombloodenteringintothealveoli.
Thisbarrierisextremelythinandverystrong(thankstotypeIVcollagen),allowing
forsufficientdiffusionofoxygen.
Thealveolarcapillarybarrierisformedbytype1pneumocytesofthealveolarwall,
theendothelialcellsofthecapillaries,andthebasementmembranesbetweenthe
twocells.Thisbarrieriseasilypermeabletomanygases,especially02,CO2,andCO.

PNEUMOCYTES
Therearetwotypesofpneumocytes,andtheycontributetothemaintenanceofthe
alveoli.Theyextendintothebronchioles,whilegobletcellsextendonlytothe
terminalbronchioles.
Therearetwotypesofpneumocytes:Type1andType2
Type1Pneumocytesareresponsibleforgasexchangeinthealveoli,andcover
>95%ofthealveolarsurface
Type2Pneumocytesareresponsibleforsecretingsurfactant,whichhelpsto
decreasethealveolarsurfacetension.Thetype2pneumocyteisalsoaprecursorto
type1pneumocytes.

THEDIGESTIVETRACT
Thehistology/anatomyofthedigestivetractiscomplex,consistingofsupportive
structures,muscularstructures,andglandularstructures.TheGItractisalsoan
importantpartoftheimmunesystem.
TheupperGItractconsistsoftheesophagus,stomach,andduodenum.
ThelowerGItractincludesmostofthesmallintestine,thelargeintestine,andthe
anus.
Histologically,theGItractcanbedividedintothemucosa,submucosa,muscularis
externa,andtheadventitia.
MUCOSATheinnermostlayeroftheGItract,surroundsthelumen.Itisimportant
intheprocessofdigestion,asitisresponsibleforabsorptionandsecretion.The
mucosacanfurtherbesubdividedintoepithelium,laminapropria,andmuscularis
mucosa.
SUBMUCOSAThesubmucosaisadenselayerofconnectivetissuethatactsas
supporttotheGItract.ItholdstheMeissnersplexus,whichisanentericnervous
plexusthatsitsontheinnersurfaceofthemuscularismucosa.Thesubmucosaalso
containsbloodvessles,lymphatics,andnervesthatbranchintothemucosaandthe
muscularisexterna.
MUSCULARISEXTERNAThisstructureconsistsofaninnerandouterlayerof
muscletissue.Theinnercircularlayercontractstosqueezethecontents,whilethe
outerlongitudinallayercontractstoshortenthetract.Thesetwocontractions
togetherhelpwithperistalsis,thuspropellingthefoodalongthetract.
ADVENTITIATheadventitiaisonemorecomponentinGItractsupport.

TherearetwoentericplexusesthathelpcoordinateallofthefunctionsoftheGI
tract.
TheMyentericPlexusCoordinationofmotilityalongtheentiregutwall.This
plexusislocatedbetweenthelongitudinalandcircularsmoothmuscleoftheGI
tract,andisalsoknownasAuerbachsplexus.
TheSubmucosalPlexusThisplexusregulatessecretions,bloodflow,and
absorption.Locatedbetweenthemucosaandtheinnerlayerofsmoothmuscle,itis
alsoknownasMeissnersplexus.
*Bothplexusescontainparasympatheticterminaleffectorneurons.

BRUNNERSGLANDS
BrunnersglandsaretheonlyglandsintheGIsubmucosa.Theyareresponsiblefor
secretingalkalinemucus,andmayhypertrophyinthecaseofaduodenalulcer.

PEYERSPATCHES
Peyerspatchesareaggregationsoflymphoidtissuethatarefoundintheileum.
Theyareovallyshapedlymphoidfolliclesinthelaminaproprialayerofthemucosa,
extendingintothesubmucosaoftheileum.
Thesepatchesareunencapsulated,coveredbyasinglelayerofcuboidalenterocytes
withspecializedMcellsinterspersed.TheseMcellsareresponsiblefortakingup
antigens.
StimulatedBcellstravelfromthePeyerspatches,goingthroughthelymphand
bloodtothelaminapropriaoftheintestine,wheretheydifferentiateintoIgA
secretingplasmacells.TheIgAisprotective,travelingacrosstheepitheliumtothe
guttodealwiththeintraluminalantigen.


LYMPHNODES
Lymphnodesaresecondarylymphoidorgansthatfunctionasnonspecificfiltration
bymacrophages,antibodyproduction,andstorageorBandTcells.Thelymphnode
containsmanyafferents,andatleastoneormoreefferent.
StructureoftheLymphNode:
CortexTheoutercortexconsistsmainlyofBcellsthatarearrangedinfollicles,
whichcandevelopagerminalcenterwhenincontactwithanantigen.Theinner
cortexismainlyTcells.
MedullaTherearethemedullarycordsandthemedullarysinuses.Thecordsare
mainlyplasmacells,lymphocytes,andBcells.Thesinusestakeintheflowoflymph
fromthecorticalsinuses,andcontainmacrophagesandreticularcells.
FollicleThefollicleiswhereBcellsarelocalizedandwheretheyproliferate.
Primaryfolliclesaredense/dormant,wherethesecondaryfollicleshaveapale
centralgerminalcenter,andtheyareactive.
Lymphnodecirculation:
Thelymphcirculatestothelymphnodethroughtheafferentlymphaticvessel,
drainingintothesubcapsularsinus.Thissubcapsularsinusthendrainsinto
trabecularsinuses,andfinallyintothemedullarysinuses.
Subcapsularsinus trabecularsinus medullarysinuses

ADRENALCORTEX&MEDULLA
Thereare3layerstotheadrenalcortex,theyare:
1. ZonaGlomerulosasecretesAldosterone(Glucocorticoids)
2. ZonaFasciculatasecretesCortisol(StressHormones)
3. ZonaReticularissecretesAndrogens(SexHormones)
Theadrenalmedullacontainschromaffincellsthatsecretethecatecholamines
EpinephrineandNorepinephrine.

Themostcommontumoroftheadrenalmedullainadultsisa
pheocromocytoma,whilethemostcommontumorinchildrenisa
neuroblastoma.

THELIVER

CentralVeinReceivesthebloodmixedinthesinusoidsoftheliverandreturnsit
tocirculationviathehepaticvein.
PortalVeinDrainsbloodfromtheGItractandthespleenintotheliver.Usually
formedbytheSMV,splenicveins,IMA,gastricvein,andcysticvein.Thisisoneof
themainportalvenoussystemsofthebody.
HepaticArteryRunsalongsidetheportalveinandthecommonbileducttoform
theportaltriad.
BileCanaliculusIsathintubethatcollectsbilethatissecretedbythe
hepatocytes.Thesecanaliculimergetoformthebileducts,whichthenbecomethe
commonhepaticduct.


THESPLEEN


CILIA
Ciliaisstructuredinawaythatallowsformaximummobility.Insideeachciliathere
isa9+2axoneme,ascanbeseenintheimagebelow.Each9+2axonemeactsasa
scaffoldforproteincomplexesandprovidesbindingsitesformotorproteins.
Especiallyimportantisdynein,whichisamotorproteinthatconvertsthechemical
energyofATPintothemechanicalenergyofmovement.Adefectindyneincausesa
conditionknownasKartagenersSyndrome,whichresultsinimmotilecilia.
Therearealso9+0cilia,whicharenonmotile.

THEINNEREAR

THEBONYLABYRINTH:
ConsistsoftheCOCHLEA(hearing),theVESTIBULE(responsibleforsensinglinear
acceleration),andtheSEMICIRCULARCANALS(responsibleforangular
acceleration).Thislabyrinthisfilledwithafluidcalledperilymph,whichisa
sodiumrichfluid,similartotheextracellularfluid.
THEMEMBRANOUSLABYRINTH:
ConsistsoftheCOCHLEARDUCT,UTRICLE,SACCULE,andtheSEMICIRCULAR
CANALS.Thislabyrinthisfilledwithendolymphthatisrichinpotassium,similarto
thefluidinsidethecells.Therearehaircellsthatactasthemodeofsensation
withinboththevesticularapparatusandthecochlearapparatusoftheinnerear.
LOWFREQUENCYsoundsareheardattheapexofthecochlea
HIGHFREQUENCYsoundsareheardatthebaseofthecochlea.

CHAPTER4

NEUROANATOMY

NeuroanatomyisahighyieldsectionoftheUSMLEexam.
Focusonbasicneuroanatomy(bloodsupply,nervesupply),
aswelltheassociatedneuropathologyand
neurophysiology.

REFLEXES
Therearemanyreflexesbelongingtoboththeadultandtheinfant,andasetthatare
seenonlyininfants.
Thereflexarcisanimportantconcepttounderstandasitrelatestotheclinically
importantreflexes.

DERMATOMES
Dermatomesareareasoftheskinthataremostlysuppliedbyasinglespinalnerve.
Eachofthesenervesrelaysensationsfromeachparticulardermatometothebrain.
8CranialNerves12ThoracicNerves5LumbarNerves5SacralNerves
Understandingandbeingabletolocatedermatomesisimportantneurologicallyas
itallowsustodeterminethesiteofdamagetothespine.Themostcommonlyseen
infectionisaherpeszosterinfection,whichisaninfectionthatliesdormantinthe
dorsalrootganglionandmanifestsitselfalongadermatome,wrappingaroundthe
bodyalongthespecificdermatomalarea.
NERVEROOT
C2
C3
C4
C6
C7
C8
T4
T5
T6/T7
T10
T12
L1
L4
S2,S3

AREAOFDISTRIBUTION
Posteriorhalfoftheskullcap
Areathatcorrelateswithahigh
turtleneckshirt
Areacorrelatingtoalowcollarshirt
Thumb(radialnerve)
2ndand3rddigit(medialnerve)
4th,5thdigits(ulnarnerve)
Nipples
InframammaryFold
XiphoidProcess
Umbilicus
Pubicboneregion
InguinalLigament
Kneecaps
Genitalia


CRANIALNERVES
Cranial
Nerve
1

Name

Function

NerveType

Foramen

Olfactory

Smell

Sensory

2
3

Optic
Oculomotor

Sensory
Motor

4
5

Trochlear
Trigeminal

Sight
Eyemovement
PupilConstr
Accomodation
Eyelidopening
EyeMovement
FacialSensation
Mastication

6
7

Abducens
Facial

Cribiform
Plate
OpticCanal
Superior
Orbital
Fissure
(SOF)
SOF
V1:SOF
V2:
Foramen
Rotundum
V3:
Foramen
Ovale
SOF
Internal
auditory
canal

Motor
Motor,
Sensory

EyeMovement
FacialMovement
Anterior2/3taste
Lacrimation
Salivation
Vestibulocochlear
Hearing
Balance

Motor
Motor,
Sensory

Glossopharyngeal

Motor,
Sensory

10

Vagus

Motor,
Sensory

Jugular
foramen

11

Accessory

Posterior1/3
taste
Swallowing
Salivation
Carotidbodyand
sinusmonitoring
Taste
Swallowing
PalateElev
Talking
Thoracoabdominal
Viscera
Headturning
Shouldershrug

Internal
auditory
canal
Jugular
foramen

Motor

Jugular
foramen

12

Hypoglossal

TongueMovement

Motor

Hypoglossal
canal

Sensory


MnemonicfortheCranialnerves:
OnOldOlympusToweringTopsAFriendlyVikingGrewVinesAndHops

DEVIATIONSTOWARDSANDAWAYFROMCNLESIONS
CN5motorlesionJawwilldeviatetowardssideoflesion
CN10lesionUlnadeviatesawayfromsideoflesion
CN11lesionWeaknessinturningheadtotheoppositesideoflesion
CN12lesionTonguewilldeviatetowardssideoflesion(lickthewound)

BRAINSTEMCRANIALNERVENUCLEI

THETRACTSOFTHESPINALCORD
Memorizationofthefunctionsofdifferentareasofthespinalcordisessentialto
beingabletoidentifywhereaparticularspinalcordlesionmaybelocated.

Pyrimidal:
LateralCorticospinalControlsmovementofipsilaterallimbs
AnteriorCorticospinalConductionofvoluntarymotorimpulsesfromprecentral
gyrustothemotorcenterofthecord

Extrapyrimidal:
RubrospinalMainrouteformediationofvoluntarymovement(largemusclesand
finemotorcontrol)
ReticulospinalCoordinatesautomaticmovementoflocomotionandposture,
influencesmuscletone,mediatesautonomicfunctions,andmodulatespainimpulses
VestibulospinalLateral:Ipsilateraldescenttoparavertebralandproximallimb
extension.Medial:Bilateraldescent,controlseyemovement,neckposition,gaze

DorsalColumnMedialLemniscusSystem:
GracileFaciculusFinetouch,vibration,proprioceptiontolowerbody
CuneateFasciculusFinetouch,vibration,andproprioceptiontoupperbody

SpinocerebellarTract:
PosteriorSpinocerebellarTractLimbandjointposition
AnteriorSpinocerebellarTractLimbandjointposition

AnterolateralSystem:
LateralSpinothalamicTractPainandtemperature
AnteriorSpinothalamicTractSoftnocioception

SpinoOlivaryTract:Proprioceptionfrommusclesandtendonsaswellas
cutaneousimpulsestotheolivarynucleus

BROWNSEQUARDSYNDROME
BrownSequardsyndromeoccurswhenthereisahemisectionofthespinalcord.It
presentswiththefollowing:

Ipsilaterallossofmotorfunctionandthepresenceofspasticity(pyramidal)
Ipsilaterallossoftactile,vibration,andproprioceptionsenses(dorsal
column)
Contralaterallossofpainandtemperature(spinothalamic)
Ipsilaterallossofallsensationatthelevelofinjury


UMN&LMNLESIONS
SIGN
Weakness
Atrophy
Reflexes
Tone
Fasciculations
Babinski

UMNLESION
Present
Absent
Increased
Increased
Absent
Present

LMNLESION
Present
Present
Decreased
Decreased
Present
Absent

MUSCLESOFTHEEYE


ANATOMYOFTHEEYEANDRETINA


THEPUPILLARYLIGHTREFLEX
Themechanismbywhichthepupilsreacttolightisquitestraightforward.
Step1Lightisdetectedandtheretinalganglioncellsconveythisinformation
throughphotoreceptorstotheopticnerve.Theopticnerveisconnectedtothe
pretectalnucleus,andsendsthefirstsignalherenotifyingitofincominglight.
Step2Fromthepretectalnucleus,amessageissenttotheEdingerWestphal
nucleus
Step3Theocculomotornerve(fromtheEdingerWestphalnucleus),thensendsa
messagetotheconstrictormusclesoftheiris.Theirismusclescontractbilaterally
(consensualreflex).


CONJUGATEGAZE
Conjugategazeisaprocesswherebybothoftheeyeslookinthesamedirection
simultaneously.TheprocessbeginswiththefiringofCN6,whichthencontractsthe
lateralrectusmuscletolookintoonedirection,whichsimultaneouslycontracting
thecontralateralnucleusofCN3(viathemediallongitudinalfasciculus).TheCN3
thencontractsthemedialrectusandtheconjugategazeisintact.
Withmanydiseasessuchasmultiplesclerosis,thereisalesionintheMLF,which
willinhibitthetransmissionofthesignaltothecontralateralCN3.Whenthis
occurs,thesecondeyedoesnotlooktothesamedirection,andthepatientthenhas
agazepalsy,alsoknownasinternuclearophthalmoplegia.


VISUALFIELDDEFECITS
Deficitstothevisualfieldcanoccurfromeitherdiseasesorfromdisordersofthe
eye,opticnerve,andbrain.
Thefourmostcommontypesofvisualfielddefectsare:
1. Altitudinalfielddeficits,whichisalossofvisionaboveorbelowthe
horizontal
2. Bitemporalhemianopsia,whichisalossofvisionatouraspectsofthevisual
field
3. Homonymoushemianopsia,whichisalossofvisiononthesamesideinboth
eyes
4. Centralscotoma,whichisalossofcentralvision

THECIRCLEOFWILLIS
TheCircleofWillisisacircleofarteriesthatsuppliesthebrainwithblood.The
designoftheCircleofWillisissuchthatshouldoneareabecomestenosedor
blockedcompletely,bloodflowfromotherbloodvesselscanoftenpreserve
perfusionwellenoughtoavoidischemicevents.
Thecircleiscomprisedofthefollowingarteries:

Anteriorcerebralarteries
Anteriorcommunicatingartery(connectsbothanteriorcerebralarteries)
Internalcarotidarteries(arisefromcommoncarotidarteries)
Posteriorcerebralarteries(arisefrombasilarartery)
Posteriorcommunicatingarteries(fromabranchofinternalcarotids)


BLOODSUPPLYTOTHEBRAIN
AnteriorCerebralArterysuppliesthemedialsurfaceofthebrain,andthelegfoot
areaofthemotorandsensorycortices.
MiddleCerebralArterysuppliesthelateralaspectofthebrain,thetrunkarm
faceareaofthemotorandsensorycortices,aswellasBrocasandWernickes
speechareas.
AnteriorCommunicatingArteryconnectstheanteriorcerebralarteries,andis
themostcommonsiteofCircleofWillisaneurysm.
PosteriorCommunicatingArteryconnectsthreecerebralarteriesoneachside,is
anothercommonsiteofaneurysm,andcancausecranialnerve3palsies.

HERNIATIONSOFTHEBRAIN
Certainsignsandsymptomsshouldalertyoutothepossibilityofbrainherniations.
Differentsignscanhelpyounarrowdownthespecificarea/lesionthatmaybe
present.
Therearetwomajorclassesofherniationthesupratentorialandinfratentorial
herniations.Thestructurethatdifferentiatesthesetwocategoriesisthetentorial
notch(thoseabove=supratentorial,thosebelow=infratentorial).
SupratentorialHerniationsUncal,Central,Cingulate,Transcalvarial
InfratentorialHerniationsUpward(cerebellar),Tonsillar(downwardcerebellar)

THELUMBARPUNCTURE
Thelumbarpunctureisadiagnostictoolusedtocollectandanalyzethe
cerebrospinalfluid.
IndicationsCSFanalysiswhenmeningitis,feverofunknownorigin,andsignsof
meningealirritationarepresent.Hydrocephalus,benignintracranialhypertension,
andsubarachnoidhemorrhagescanallbediagnosedandsupportedwithanLP.The
LPisalsousefulwhenintrathecal(injectionintothespinalcord)routeof
administrationisnecessary,suchaswithspinalanesthesiaorchemotherapy.
ContraindicationsThemostimportantcontraindicationtoalumbarpunctureis
thepresenceofincreasedintracranialpressure.Otherimportantcontraindications
arecoagulopathies,respiratorydifficulties,deterioratingconsciousness,andwhen
thereishypertensionplusbradycardia.

HowistheLPperformed?

UPPERMOTORNEURONS
Uppermotorneuronsaremotorneuronsthatoriginateinthemotorregionofthe
cortexorbrainstem.Theycarryinformationdownspecificareasonthespinalcord,
atwhichpointtheysendsignalstothelowermotorneurons(viaglutaminergic
receptors).Themaineffectorneuronsarewithinlayer5oftheprimarymotor
cortex,andthesearesomeofthelargestcellsinthebrain.

Uppermotorneuronstracts:
TheUMNstravelviaseveraldifferenttract,including:

Corticospinal
Corticobulbar
Tectospinal
Rubrospinal
Vestibulospinal
Reticulospinal

UMNLesions:
ThereareasetofcommonsymptomsthatoccurwithanUMNlesions,including:

Spasticity
Decreasedmuscletone
PositiveBabinskiSign
Pyramidalweakness
Hyperreflexia
IncreasedDTRs


LOWERMOTORNEURONS
Lowermotorneuronsarethemotorneuronsthatconnectthebrainstemandthe
spinalcordtothemusclefibers(ietheiraxonendsintheeffectormuscle).
TheLMNsareclassifiedbasedonthemusclefibertypesthattheyeachinnervate,
thesearethealphamotorneuronsandthegammamotorneurons.
AlphamotorneuronsArethemostnumeroustypeofneuronsofmusclefiber,are
involvedinmusclecontraction,andinnervateextrafusalmusclefibers.
GammamotorneuronsArecomponentsofthemusclespindles,involvedin
proprioception,andinnervatetheintrafusalmusclefibers.

LMNlesions:
ThereareasetofcommonsymptomswithLMNlesions,including:

Decreasedmuscletone
Muscularweakness
Hyporeflexia
Fasciculations
Atrophyofskeletalmuscle
Paralysis

IMPORTANTCLINICALCONDITIONSINVOLVINGUMN&LMNLESIONS
AmyotrophicLateralSclerosisBothUMNandLMNsigns.Isaslowlydeveloping
diseasethatisultimatelyfatal.Patientexperiencesweaknessandwastingofthe
bulbarmuscles(speech,swallowing,chewing),aswellasthearms,legs,andtorso.
Muscleweaknessandwastingdevelopsproportionallyonbothsides.Sensationand
mentationremainintact.
ProgressiveBulbarPalsyLMN
PseudobulbarPalsyUMN
PrimaryLateralSclerosis(PLS)UMN,males>females
ProgressiveMuscularAtrophyslowdegenerationofLMNs
SpinalMuscularAtrophy(SMA)LMN,degenerationofanteriorhorncells
PoliomyelitisLMNdestruction


BELLSPALSY
Bellspalsyisaunilateralparalysisoffacialmusclesduetoadysfunctionofthe
facialnerve(CN7).Therearemanypossiblecauses,suchasviral,Lymedisease,
stroke,inflammation,etc.Thisconditionisalmostalwaysselflimiting.

Signs&Symptoms:

Ipsilateralfacialparalysis
Inabilitytoblinkeyeonaffectedside

*Important*
Itishighlyimportanttolookfortheabilitytowrinkletheforehead,astheabilityto
dosousuallyindicatesthatthereisanuppermotorneuronlesion.ThisUMNlesion
resultsinaconditionknownascentralfacialpalsy,wherebytheproblemisa
paralysisofthecontralaterallowerpartoftheface.

FUNCTIONSOFTHECEREBRALCORTEX


BRAINLESIONS
LESIONAREA

RESULTOFLESION

BrocasArea Patienthasexpressiveaphasia(cantspeak),
hasgoodunderstandingofspeech
Wernickes Patienthasinabilitytocomprehendspeech,can
Area
speakwell
FrontalLobe Personalitychanges,defectsinjudgement(ie
Frontalreleasesigns)
Arcuate
Patienthasgoodlanguagecomprehensionwith
Fasciculus poorabilitytospeakinrepetition
Amygdala KluverBucySyndromepatientbecomes
hypersexual,hyperoral,andhasdisinhibited
behavior
Right
Patienthasspatialneglect,thusdonot
Parietal
recognizethecontralateralsideofthelesion
Lobe
Mammillary Confabulations,anterogradeamnesia
Bodies
Basal
Restingtremor
Ganglia
Cerebellar Truncalataxiaanddysarthria
Vermis
Cerebellar Intentiontremor,ataxiaoflimbs
Hemisphere


THETHALAMUS
Thethalamusisamidlinestructureofthediencephalon,situatedbetweenthe
cerebralcortexandthemidbrain.Itrelaysinformationbetweentheareasofthe
subcortextothecerebralcortex,regulatesconsciousness,regulatessleep,and
regulatesalertness.Itgetsitsbloodsupplyfrommanybranchesoftheposterior
cerebralartery(paramedian,inferolateral,posteriorchoroidal).
Therearethreepartstothethalamus,theyarebulbshapedmassesthatare
approximately5.7cminlength,andarelocatedalongsidethe3rdventricleata30
degreeangle.


THEHYPOTHALAMUS
Thehypothalamusisastructurewithinthebrainwithmanykeyimportant
functions.Theeasiestwaytorememberthefunctionsofthehypothalamusiswith
themnemonicTANHATS.
TThirst(Waterbalance,asregulatedbythirst)
AAdenohypophysis(Thisstructureiscontrolledviareleasingfactors)
NNeurohypophysis(Releaseshormonessynthesizedinthehypothalamicnuclei)

HHungerandSatiety(Controlledbytheventromedialnucleus)
AAutonomicregulation(Parasympatheticactivityviaanteriorhypothalamus,
circadianrhythmviasuprachiasmaticnucleus)
TTemperature(Posteriorhypothalamusconservesheatwhencold,Anterior
hypothalamuscoordinatescoolingwhenhot)
SSexualRegulation(Theseptatenucleuscontrolssexualemotionsandurges)

THEPOSTERIORPITUITARY
Theposteriorpituitaryconsistsofaxonsthatextendfromthesupraopticand
paraventricularnucleiofthehypothalamus.Theneurohypophysissecretestwo
veryimportanthormones:OxytocinandVasopressin.
VasopressinStimulateswaterretention,thusraisingbloodpressurebyarterial
contraction.
OxytocinStimulatescontractionoftheuterusandlactation


BASALGANGLIA
Thebasalgangliaareagroupofnucleisituatedatthebaseoftheforebrainandare
connectedwiththecerebralcortexandthalamus.Thebasalgangliaareimportant
inmanyfunctions,namelymotorcontrolandlearning.Themaincomponentsofthe
basalgangliaaretheStriatum,Pallidum,SubstantiaNigra,andtheSubthalamic
Nucleus.
StriatumThelargestpartofthebasalganglia,itconsistsoftwoparts(Caudate
nucleusandPutamen).ThemajorityofthecellsareGABAergic(>96%),and
cholinergicneurons(~2%).
PallidumConsistsofalargeGlobusPallidus(Internal(GPi)andexternal(GPe)
segmentsandasmallventralextensioncalledtheVentralPallidum).Thesetwo
segmentsaremainlyGABAergicneuronsthatactasinhibitoryneurotransmitters.
SubstantiaNigraLocatedinthemidbrain(mesencephalon),itplaysalargerole
inreward,addiction,andmovement.Thesubstantianigracontainslargelevelsof
melaninwithindopaminergicneurons,thesestructuresaredarkandthusstandout
fromtherestofthesurroundingstructures.Therearetwopartstothesubstantia
nigra(parscompactaandparsreticulata).Theparscompactaactsasaninputtothe
basalgangliacircuit,supplyingthestriatumwithdopamine.Theparsreticulata
servesasanoutput,whichconveyssignalsfromthebasalgangliatonumerousother
structures.
SubthalamicNucleusLocatedventraltothethalamus,medialtotheinternal
capsule,anddorsaltothesubstantianigra.Thesubthalamicnucleusreceives
signalsfromtheglobuspallidus,whichareGABAergicinnature,whileitreceives
glutaminergicinputsfromthecerebralcortex.Thesignalsexitingthesubthalamic
nucleusareglutaminergic,whichareexcitatory.Thesesignalstraveltomany
differentstructuresincludingthesubstantianigra,lateralpallidum,andmedial
pallidum.

CELLSTHATSUPPORTANDNOURISHTHECNS&PNS
SUPPORTIVECELL
Oligodendroglia
SchwannCells
Astrocytes
Microglia
EpendymalCells

ROLEINCNS/PNSSUPPORT
Producesmyelincentrally
Producesmyelinperipherally
Providephysicalsupport,potassium
metabolism,andphysicalrepair
Isthephagocyticcellofthenervous
system
Responsiblefortheinnerliningofthe
ventricles

THEBLOODBRAINBARRIER
ThebloodbrainbarrierisasystemdesignedtokeepthebloodandCSFfrom
mixing.Thebarrierisformedbytightjunctionsbetweenendothelialcellsinthe
CNSvessels,thustheyrestrictthepassageofsolutes.Thisbarrierismuchmore
restrictingthananywhereelseinthebody.
ThebloodbrainbarrierisformedbytheArachnoid,Intracerebralcapillary
endothelium,andChoroidPlexusendothelium.
Substancesthatcanpassthebloodbrainbarrierare:

LDopa
Lipidsolublesubstances
Glucose
AminoAcids

THEVENTRICULARSYSTEM


THEDURALVENOUSSINUSES
Thesearethevenouschannelsfoundinbetweenthelayersofdurainthebrain.
Theirbloodsupplycomesfromtheinternalandexternalveinsofthebrain.
Ultimately,alloftheduralvenoussinuseswillemptyintotheinternaljugularvein.
Injuriestotheheadcancausebleedingintothebrain(hemorrhages,clots,
hematomas).

CHAPTER5

PHYSIOLOGY

PhysiologyfitsintomanyaspectsoftheUSMLEexam.Itisa
highlyconceptualtopic,andfullunderstandingofthese
conceptsisessentialtosuccessontheStep1exam.

RENALPHYSIOLOGY

THEHORMONESACTINGONTHEKIDNEY
1.
2.
3.
4.
5.
6.

Aldosterone
Angiotensin2
AtrialNatriureticFactor(ANF)
Renin
ParathyroidHormone
Vasopressin(ADH)

ALDOSTERONEsecretedinresponsetoadecreaseinbloodvolumeandthe
subsequentproductionofangiotensin2.Causesanincreaseinsodium
reabsorption,increaseinpotassiumsecretion,andincreaseinhydrogensecretion.
ANGIOTENSIN2causesefferentarterioleconstriction,whichcausesanincrease
ofGFRandsubsequentlyincreasessodiumandbicarbonatereabsorption.
ATRIALNATRIURETICFACTORsecretedwhenthereisanincreaseinatrial
pressure,whichcausesanincreaseinGFRandthusincreasedsodiumexcretion.
RENINsecretedinresponsetodecreasedbloodvolume/flow,subsequentlygets
convertedtoAT1andthenAT2,whichcausesaldosteronesecretioneventuallyto
increasebloodvolume.
PARATHYROIDHORMONEactsonproximalconvolutedtubule,secretedin
responsetoalowplasmalevelofcalcium,causingcalciumreabsorptioninthedistal
convolutedtubule.
VASOPRESSIN/ADHissecretedwhentheplasmaosmolarityishighandvolume
islow.Causeswaterreabsorptioninthecollectingducts.

THEJUXTAGLOMERULARAPPARATUS
TheJGAisastructureinthekidneythatisresponsibleforregulatingbloodflowand
GFR.Itislocatedstrategicallyinalocationthatallowsittomaximallyregulate
thesefunctions(locatedbetweenthevascularpoleoftherenalcorpuscleandthe
distalconvolutedtubule).
ThreecomponentsoftheJGA:1.MaculaDensa2.Juxtaglomerularcells
3.Extraglomerularmesangialcells

JuxtaglomerularCellsaremodifiedsmoothmusclecellsthatsecretereninin
responsetodecreasedrenalbloodflow.
MaculaDensaispartoftheDCT,isasensorforsodium.

**ThebigmessageoftheJGA**itregulatesGFRviathereninangiotensin
aldosteronesystem.


IMPORTANTEQUATIONSINRENALPHYSIOLOGY
GlomerularFiltrationRate(GFR)
GFRdescribestheflowrateoffilteredfluidthroughthekidney.Creatinine
clearancerate(CCR)isthevolumeofbloodplasmathatisclearedofcreatinineper
unittimeandisaveryusefulmeasurefortheapproximateglomerularfiltration
rate.
GFRisbestcalculatedbymeasuringachemicalthathasasteadylevelintheblood
(ieneitherabsorbednorsecretedbythekidneys).Agreattoolforthisisinulin,
whichfitsthesecriteria.
TheequationforcalculatingGFRisasfollows:

RenalClearance
Calculatingclearanceisquitesimple,howeveryoumustunderstandasimple
conceptrelatingtorenalclearanceinordertodecipherwhetherthereisanet
secretion,netreabsorption,orneither.
TheequationforRenalClearance:

IfRenalClearance=GFR,thereisnosecretionorreabsorption
IfRenalClearance>GFR,thereisanettubularsecretionofwhicheversubstance
wearelookingat.
IfRenalClearance<GFR,thereisanettubularreabsorptionofwhichever
substancewearelookingat.

FreeWaterClearance

FiltrationFraction
Thefiltrationfractionrepresentstheproportionoffluidthatreachesthekidney
whichpassestotherenaltubules.Ahealthynumberisaround20%.Shouldthere
becaseswherebyGFRisdecreased(asinrenalarterystenosis),filtrationfraction
shouldproportionallyincreasetomaintainthenormalfunctionofthekidney.

FiltrationFraction=GFR/RPF

IfGFRandRPFincreaseordecreasesimultaneously,thereisnochangeinFF
IfGFRincreasesandRPFdecreases,thereisanincreaseinFF

EffectiveRenalPlasmaFlow(ERPF)
Thiscalculationisusedtocalculaterenalplasmaflowandthustoestimaterenal
function.
WeusethePAHclearance,whichistheclearanceofParaAminohippurate
Clearance.Itisfreelyfilteredandnotabsorbedinthenephron.
CalculatingERPF:

ERPH=UPAHXV/PPAH=CPAH

GlucoseClearance
Importantindiabetes,itshouldsimplybeknownthatglucosuriaoccurswhen
plasmaglucosereaches200mg/dL,becausethePCTcannotreabsorboncethese
levelsarereached.

THERENINANGIOTENSINALDOSTERONESYSTEM
Ahormonalsystemthatregulatesthebalanceofbloodpressureandfluids.
StepsoftheRAAS:
1. Lowbloodvolumeisdetectedbythemaculadensa,causingtheJGcellsto
releaserenin.
2. Reninthencleavesangiotensinogen,convertingittoangiotensin1.
3. Angiotensin1isthenconvertedtoangiotensin2bytheACEenzyme
(angiotensinconvertingenzyme),whichisfoundinthelungs.
4. Angiotensin2bindstoreceptorsintheintraglomerularmesangialcells,
stimulatingthereleaseofaldosteronefromthezonaglomerulosaofthe
adrenalcortex.
5. Aldosteronethenstimulatesthereabsorptionofsodiumandwaterinthe
PCTandcollectingductsofthekidney

PHYSIOLOGYATEACHPORTIONOFTHENEPHRON
THEPROXIMALCONVOLUTEDTUBULE
Whatoccurs:

Completeglucosereabsorption
Completeaminoacidabsorption
Nearcompletereabsorptionofsodium,water,andbicarb(HCO3)
Secretionofammonia

THICKASCENDINGLOOPOFHENLE
Whatoccurs:

Sodiumreabsorption(active)
Potassiumreabsorption(active)
Chloridereabsorption(active)
Magnesiumreabsorption(passive)
Calciumreabsorption(passive)

DISTALCONVOLUTEDTUBULE
Whatoccurs:

Activereabsorptionofsodium
Activereabsorptionofchloride
Calciumreabsorptionoccurshere(ifstimulatedbyparathyroidhormone)

COLLECTINGTUBULES
Whatoccurs:

Sodiumgetsreabsorbed(inexchangeforH+andK+),whenaldosteroneis
present
WatergetsreabsorbedinthepresenceofADH

GASTROINTESTINALPHYSIOLOGY

THEREGULATIONOFGASTRICACIDSECRETION
ThekeyplayerinregulatinggastricacidsecretionistheH+/K+ATPase,whichisa
magnesiumdependentpump.Thefollowingarethebasicstepsofgastricacid
productionandsecretion:
1. H+isgeneratedwithintheparietalcellfromthedissociationofwater.
HydroxylionsrapidlycombinewithCO2viacarbonicanhydrase.
2. HCO3istransportedoutsidethecellinexchangeofchloride(maintains
intracellularpHoftheparietalcell).
3. ClandK+aretransportedintothelumen,whichisnecessaryforsecretionof
acid.
4. H+pumpedoutofthecellandintothelumeninexchangeforK+througha
protonpump.
5. H+accumulationgeneratesanosmoticgradientthatcausesoutward
diffusionofwater,leadingtogastricacidproduction(HCl,KCl),andasmall
amountofNaCl

HORMONESOFTHEGI
GASTRIN:

SecretedfromtheGcellsintheantrumofthestomach
CausestimulationofH+secretion
Increasedwhenthereisstomachdistention,vagalstimulation,andthe
presenceofaminoacidsinthestomach
Decreasedwhenthereisastomachacid<1.5
OverstimulationcanleadtoPUD,gastritis,ZollingerEllisonsyndrome

CHOLECYSTOKININ:

SecretedfromtheIcellsoftheduodenumandjejunum
Causesanincreaseinpancreaticsecretion
Stimulatesgallbladdercontraction
Inhibitstheemptyingofgastriccontents
InhibitedbysecretinandastomachpH<1.5
Stimulatedbythepresenceoffatsandproteinsinthestomach

SECRETIN:

SecretedfromtheScellsoftheduodenum
Causesanincreaseinpancreaticbicarbonatesecretion
Inhibitsthesecretionofgastricacids
Stimulatedbythepresenceofacidsandfattyacidsinthelumenofthe
duodenum

SOMATOSTATIN:

SecretedfromtheDcellsinthepancreaticisletcells
Causesinhibitionofgastricacidandpepsinogensecretion
Causesinhibitionoffluidsecretedfromthepancreasandsmallintestine
Inhibitsgallbladdercontraction
Inhibitsthereleaseofinsulinandglucagon
Secretionisstimulatedbyincreasedacidandinhibitedbyvagalstimulation

GASTRICINHIBITORYPEPTIDE:

SecretedbytheKcellsintheduodenumandjejunum
Decreasestheamountofgastricacidthatissecreted
Increasesinsulinrelease

SECRETORYPRODUCTSOFTHEGI
INTRINSICFACTOR:

Secretedbytheparietalcells
BindsvitaminB12
Autoimmunedestructionleadstoperniciousanemia

PEPSIN:

Secretedbythechiefcells
Aidsinproteindigestion
Increasedthroughvagalstimulation

GASTRICACID:

Secretedbytheparietalcells
Decreasesstomachacid(ieLowpH)
Stimulatedbyhistamineandacetylcholine
Inhibitedbyprostaglandins,somatostains,andGIP

BICARBONATE:

Secretedbythemucosalcellsoftheduodenumandstomach
Preventsautodigestionbyacidneutralization
Stimulatedbysecretin

ENZYMESSECRETEDBYTHEPANCREAS
LipaseAidsinfatdigestion,elevatedinpancreatitis
AmylaseHelpsinstarchdigestion,alsoelevatedinpancreatitis
ProteasesAresecretedasproenzymes,helpwithproteindigestion

ENDOCRINEPHYSIOLOGY

SPERMPRODUCTION
Spermproductionreliesonafewveryimportanthormonesinordertostimulate
production,andsubsequentlytoproducetheproperamount.
Theimportanthormonesofspermatogenesisare:
LeutenizingHormone(LH)responsibleforstimulatingtestosteronerelease
fromtheleydigcells.
FollicleStimulatingHormone(FSH)responsibleforstimulatingtheSertoli
cells,whichthenreleaseInhibinandAndrogenbindingproteins(ABP)
Fromthesetwohormones,wegetthefollowing:
Testosteroneresponsibleforthedifferentiationintomalegenitalia,maintaining
gametogenesis(thesearethetwothingsweneedmostforthistopic)
Androgenbindingproteinresponsibleforkeepingthetestosteronelevelshigh
insidetheseminiferoustubules
Inhibinthisisresponsibleforprovidingnegativefeedbacktothepituitary,
inhibitingthereleaseoftoomuchFSH.

Thefollowingillustrationputsalloftheaboveinformationintoplay,
significantlysimplifyingyourunderstandingofthewholeprocess

ANDROGENICHORMONES
Theandrogenichormonesinclude:

Testosterone
Dihydrotestosterone(DHT)
Androstenedione
Potencies:DHT>Testosterone>Androstenedione

Functionsofeachhormones:
DHTSynthesizedbytheenzyme5reductase

Formationofsecondarysexualcharacteristicinmen

TestosteronePromotesproteinsynthesisandgrowthofalltissueswith
androgenreceptors.

Musclegrowth/mass
Bonedensity
Bonematuration
Maturationofsexorgans(penisandscrotuminfetus)
Hairgrowth(facialhair,axillaryhair)
Developmentofsecondarysexcharacteristics
Developmentofprostateandseminalvesicles
Libido

Androstenedioneaprecursorofbothmaleandfemalesexhormones

PROGESTERONE
Thehormoneinvolvedinthefemalemenstrualcycle,pregnancy,and
embryogenesis.
Itcomesfromthetestes,corpusluteum,placenta,andtheadrenalcortex.
ThemainfunctionsofProgesteroneare:

Relaxationofthesmoothmuscleoftheuterus
Pregnancymaintenance
Spiralarterydevelopment

Endomedrialglandsecretionstimulation
Cervicalmucusproduction(thickensbenefitofOCPuse)
Increaseinbodytemperature
InhibitsthegonadotropinsFSHandLH

THEMENSTRUALCYCLE
Thebestwaytolearnthemenstrualcycleisvisually,keepingthefollowinghigh
yieldinformationinmind:

LHsurgecausesovulation
Progesteroneisthehormoneofpregnancy,maintainingendometriumfor
implantationsupport
Thefolliculargrowthisfastestinthe2ndweekoftheproliferativephase
Normalcycleis28days
Ovulationwilltypically(withanormalcycle)occur14daysaftertheonsetof
menses.

MENOPAUSE
Menopauseisindicativeofthecessationofovarianfunction,resultinginthe
cessationofovulationandmenstruation.
Thefollowingarethehormonalchangesthatoccurwithmenopause:

Estrogendecreases
Gonodotropinreleasinghormoneincreases
LHincreases
FSHincreasessignificantly

Thefollowingarethemostcommonsymptomsassociatedwithmenopause:

Hotflashes
Vaginalatrophy
Osteoporosis
Coronaryarterydisease(estrogenissaidtobeaprotectivefactoragainst
this)

HUMANCHORIONICGONODOTROPIN(hCG)
hCGissecretedfromtheplacentalsyncytiotrophoblast,andisresponsibleforthe
followingfunctions:

Isthe#1indicatorofpregnancy
Helpstomaintainthecorpusluteumduringthe1sttrimesterofpregnancy
Helpsindiagnosingreproductivepathologiessuchaschoriocarcinomaand
hydatiformmoles(discussedinpathologysection)

REGULATIONOFPROLACTIN
Prolactinisahormonesecretedfromtheanteriorpituitaryandisresponsiblefor
someimportantfunctions,aswellitisresponsibleforcertainpathologies
(prolactinoma,infertility).
ImportantfunctionsLactation,orgasm,oligodendrocyteprecursorcell
proliferation.
InhibitedbyDopamine

THEHYPOTHALAMUSANDPITUITARY


THETHYROIDHORMONE
Thyroidhormoneisanextremelyimportantandversatilehormone,controllinga
widerangeoffunctionsandimportantforpropergrowth.
Functionsofthyroidhormone:

CNSmaturation
Bonegrowth
adrenergiceffects
IncreasesBMR(viaincreasingtheNa+/K+pump)
Lipolysis(increases)
Gluconeogenesis(increases)
Glycogenolysis(increases)

Productionofthyroidhormone:
1.
2.
3.
4.
5.
6.

Follicularcellssynthesizeenzymesandthyroglobulinforcolloid.
IodineiscotransportedintothecellwithNa+andtransportedintocolloid.
EnzymesaddiodinetothyroglobulintomakeT3andT4.
Thyroglobulinistakenbackintothecell.
IntracellularenzymesseparateT3andT4fromtheprotein
FreeT3andT4enterthecirculation

*T3providesnegativefeedbacktotheanteriorpituitary.

PARATHYROIDHORMONE(PTH)
PTHcomesfromthechiefcellsoftheparathyroidglands.Inresponsetolowserum
calcium,PTHisreleasedandperformsthefollowing:

IncreasesboneresorptionwhichincreasesCa2+andPO4
Increasesthereabsorptionofcalciumfromthekidneys(distalconvoluted
tubules)
Decreasesthereabsorptionofphosphatefromthekidneys
Stimulatestheenzyme1hydroxylaseinthekidney,whichincreases1,25
(OH)2vitaminD(iecholecalciferol)

CALCITONIN
CalcitoninworksoppositeofPTHbyrecognizinganincreaseinserumCa2+and
thusdecreasingtheboneresorptionofcalcium.Calcitoninissecretedfromthe
parafollicular(ccells)ofthethyroidgland.

LINKINGPATHOLOGYTOCa2+,PO4,andALKALINEPHOSPHATASE
Thefollowinglistofconditionsaltertheselevelsinthefollowingways
Disesase

CalciumLevel

VitaminDIntox
Increases
Osteoporosis
Nochange
Hyperparathyroidism
Increases
Pagetsbonedisease Normalincreased
RenalInsufficiency
Decreased

PhosphateLevel
Increases
Nochange
Decreases
Normal
Increased

AlkPhosph
Level
Increases
Nochange
Increases
Largeincrease
Nochange

CARDIACPHYSIOLOGY

NOTE:Cardiacphysiologyisuniqueinthatalmosteverythingisconceptualin
nature,whichmeansthattherearemanygraphs/charts,etc.Bycompletely
understandingtheconceptbehindallofthisinformation,youwillnothaveto
memorizeanything,ratheryouwillbeabletoapplyittoanyquestiontheUSMLE
examthrowsyourway.

THECARDIACCYCLE
Thecardiaccyclereferssimplytothestepsthatareundertakenbytheheartasit
goesfromfilling,topumpingthebloodsystematically,tofillingonceagain.
Thephasesofthecardiaccycle:
1. IsovolumetricContraction
Thisisthepointbetweentheclosureofthemitralvalveandtheopeningofthe
aorticvalve.Theheartiscontractedbutvalvesareclosed.
2. SystolicEjection
Theheartsqueezesandbloodisejectedthroughtheaorticvalve.Thisphasecanbe
consideredthephasebetweenthetimetheaorticvalveopensandcloses.
3. IsovolumetricRelaxation
Thisistheperiodoftimebetweentheclosureoftheaorticvalveandtheopeningof
themitralvalve.
4. Rapidfillingphase
Aftertheopeningofthemitralvalve,bloodpoolsrapidlyintotheleftventricle.
5. Slowfillingphase
Atthispoint,bloodflowsintotheLVslowlyasthemitralvalveisabouttoclose.

Importantheartsoundsthatoccurduringthecardiaccycle:
S1thisisthe1stheartsoundandrepresentstheclosingofthetricuspidandmitral
valves
S2thisisthe2ndheartsoundandrepresentstheclosingofthepulmonaryand
aorticvalves
S3thisisthe3rdheartsoundandrepresentstheendoftherapidventricularfilling
(canbeassociatedwithcongestiveheartfailure)
S4thisisaheartsoundheardonlyifthereisastiffventricle(isassociatedwith
ventricularhypertrophy)

Thefollowinggraphrepresentsthephasesofthecardiaccycle:

WIGGERSDIAGRAM:
Thisdiagramisusedincardiacphysiologytoillustratetherelationshipsbetween
severaldifferenteventsthatareoccurringsimultaneously.FortheUSMLEexam,it
isimportanttorecognizetherelationshipsonthegraphaswellastorecognize
wherethemajoreventsarelocatedgraphically.


ACTIONPOTENTIALOFTHEPACEMAKER

THESANODE:
ThecellsoftheAVnodedepolarizespontaneously,resultinginapproximately100
contractionsperminute.Thisratedoesnotcreateaventricularrateof100because
thesympatheticandparasympatheticfibershavetheabilitytocontrolhowmuch
getsthrough.
THEAVNODE:
Thisnodedischargesapproximately4060bpm.Therearebranchesthatcomefrom
theAVnode(Purkinjefibers),thatalsoproducespontaneousactionpotentialsata
rateofapproximately3040bpm(keepconductionifthenodesarenotworking
efficiently).

THEPHASESOFTHEACTIONPOTENTIAL:
Phase4SlowDiastolicDepolarization
WithaNa+conductanceincrease,themembranepotentialspontaneously
depolarizes,accountingfortheautomaticityoftheSAandAVnodes.Inthechart
below,theslopeofphase4intheSAnodeisthedeterminingfactorinheartrate.
Thiscanbeincreasedwithcatecholamines(NE,Epi)anddecreasedwith
acetylcholine.

Phase0Upstroke
Causedbyaslowinfluxofcalciumbecausetherearenofastsodiumchannels.This
resultsinaslowconductionvelocitythathelpstoprolongtransmissionfromthe
atriatotheventricles.
Phase3Repolarization
Arapidinactivationofthecalciumchannelsandadecreaseinpotassium
permeabilityslowlyrepolarizesthecell(iethereisalossofpositiveions).


VENTRICULARACTIONPOTENTIAL
Theventricularactionpotentialisbestexplainedthroughtheuseofvisualaids.
Eachphaseoftheactionpotentialiscausedbyaninfluxoreffluxofcertainions,
thusknowingwhichionsworkwhereisvitaltounderstandingtheeventsand
gettingasmanypointsaspossibleontheUSMLE.

Phase0VoltageGatedNa+channelsareopen,resultinginarapidupstroke.
Phase1Na+channelsareinactivatedandvoltagegatedK+channelsbeginto
open.Thisresultsintheinitialrepolarization.
Phase2AplateauphasewhereavoltagegatedCa2+channelresultsinbalancing
offoftheK+efflux.ThistriggersCa2+releasefromtheSRandthusmyocyte
contraction.
Phase3AmassiveeffluxofK+duetoopeningofslowvoltagegatedK+channels
andclosureofvoltagegatedCa2+channelsleadstorapidrepolarization.
Phase4AhighK+permeabilityresultsinreturntorestingpotential.

CARDIACOUTPUT
CardiacoutputisameasureofthestrokevolumeXtheheartrate.Acutely,cardiac
outputwillincreaseduetostrokevolumeincreases,whereaschronicallycardiac
outputisaresultofanincreaseinheartrate.
CARDIACOUTPUT=STROKEVOLUMEXHEARTRATE

VARIABLESOFCARDIACOUTPUT:
Contractilityincreaseswiththefollowing(asdoesstrokevolume):

Increaseinintracellularcalcium
Increaseincatecholamines
Decreasedextracellularsodium
Useofdigitalis

Contractilitydecreaseswiththefollowing(asdoesstrokevolume):

HeartFailure
Hypoxia
Blockadeofthe1receptor
Acidosis

AFEWIMPORTANTEQUATIONSINCARDIACPHYSIOLOGY

PRELOADANDAFTERLOAD
PreloadPreloadisthestretchingpressureintheventriclesoftheheartafter
fillingiscompleted.Preloadisincreasedwhenthereisanincreaseinbloodvolume,
sympatheticstimulation,andevenexercise.
Therefore,PRELOAD=ENDDIASTOLICVOLUME

AfterloadAfterloadisthetermthatmeasuresthetensionproducedinthe
ventricleinorderforcontractiontooccur.
Therefore,AFTERLOAD=DIASTOLICARTERIALPRESSURE

Venousdilatorswilldecreasethepreload,thisincludesmostcommonly
nitroglycerine.
Vasodilatorswilldecreasetheafterload,thisincludesmostcommonlydrugslike
hydralazine.

THEFRANKSTARLINGLAW
Thislawstatesthatwithagreatervolumeofbloodenteringtheheartduring
diastole,thegreatervolumeofbloodisejectedduringsystole.Thislawexplains
thatsynchronizationofcardiacoutputandvenousreturnoccurswithoutneeding
externalfactorstocomeintoplay.

THEEKG

PwaveRepresentsatrialdepolarization
PRsegmentRepresentstheconductiondelaythroughtheAVnode
QRScomplexRepresentsventriculardepolarization
QTintervalRepresentsmechanicalcontractionoftheventricles
TwaveRepresentstheventricularrepolarizations
STsegmentIsanisoelectricpointwheretheventriclesaredepolarized

ABNORMALITIESOFTHEEKG
ATRIALFLUTTER:Asupraventriculartachycardiathatpresentswithaseriesof
rapidbacktobackdepolarizations.Thismayoccurinthosewithheartdiseases
(CHF,CAD,etc),butcanalsooccurinaperfectlynormalheart.Theclassic
presentationisthesawtoothpattern,whichoccursasaresultofidenticalbackto
backdepolarizations.

ATRIALFIBRILLATION:Isaverycommoncardiacarrhythmiawherebythereisa
quiveringofthechamberinsteadofacoordinatedcontraction.Theclassicfindings
areachaoticanderraticbaselinewiththeabsenceofPwavesinbetweenregularly
spacedQRScomplexes.

ATRIOVENTRICULARBLOCKS
1STDEGREEBLOCK:AnasymptomaticconditionwithaPRintervalprolongation
>200msec.

2NDDEGREEMOBITZTYPE1(Wenckebach):Isaconditionthatisoften
asymptomatic,butifsymptomaticwillrequireapacemaker.Thepresentationisa
progressivelengtheningofthePRintervaluntilaPwaveisnotfollowedbyaQRS
complex.

2NDDEGREEMOBITZTYPE2:Presentswithacutelydroppedbeatsthatarenot
preceededbyachangeinthePRlength.Themostcommonpresentationis2P
wavesper1QRScomplex.

3RDDEGREE(COMPLETE)HEARTBLOCK:Thereisindependentbeatingoftheatria
andtheventricles.

VENTRICULARTACHYCARDIA:Atachycardiaresultinginaheartbeat>100bpm.
Thismaybenonpathologic,butmayalsoleadtoventricularfibrillation.

VENTRICULARFIBRILLATION:Thisisaconditionwherethereisaerraticrhythm
andnoidentifiablewavesonEKG.Thisarrhythmiaisfatalwithoutprompt
defibrillation.

PHYSIOLOGYOFTHECARDIACMYOCYTE
1. AdepolarizationtravelsdowntheTtubule,stimulatingthereleaseof
calciumfromtheSR(goesthroughthedihydropyridinereceptorand
Ryanodinereceptor).
2. CalciumisreleasedandbindstotroponinC,whichleadstothe
conformationalchange(movingtropomyosinoutofthemyosinbinding
grooveonactinfilament)
3. PowerStrokemyosinhydrolyzestheboundATPandisdisplacedonthe
actinfilament
4. Contractionoccurs


COMPARINGSMOOTHMUSCLECONTRACTIONANDSKELETALMUSCLE
CONTRACTION
SmoothMuscleContraction:

SkeletalMuscleContraction:
1.
2.
3.
4.

ATPbindstothemyosinhead,releasingtheactinfilament
Crossbridgecyclingandshorteningoccur
CalciumbindstroponinCandaconformationalchangeoccur
Tropomyosinmovesallowingactin/myosincycling


BARORECEPTORSANDCHEMORECEPTORS
BaroreceptorsRespondtopressure
ChemoreceptorsRespondtochemicalchanges

LocationofBaroreceptors:
Theaorticarchrespondstobloodpressure,andtransmitsasignaltothe
medulla(viathevagusnerve).
Thecarotidsinusthebaroreceptorheretransmitsitssignaltothemedullavia
theglossopharyngealnerve.

Locationofchemoreceptors:
CentralchemoreceptorsrespondtopHandPC02changesoftheinterstitialfluid
inthebrain(thesearenotinfluencedbyP02)
PeripheralchemoreceptorsrespondtoaP02<60mmHg,respondtoincreased
PC02,andrespondtoadecreaseinpH(ieincreaseinH+)

HOWISHYPOTENSIONREVERSEDBYTHEBARORECEPTORS?
1.
2.
3.
4.

Arterialpressureisdecreased,resultingin
Decreasedstretch,whichleadsto
Decreasedafferentbaroreceptorfiring,thiscauses.
Increasesinefferentsympatheticactivityanddecreasedefferent
parasympatheticstimulation,leadingto
5. Vasoconstriction,which
6. Increasesheartrate,contractility,andbloodpressure
HOWDOESCAROTIDMASSAGEWORK?
1. Massagingthecarotidarterygivesthesenseofincreasedpressure,which
2. Increasesthestretchdetectedfromthebaroreceptor,thisinturn
3. Decreasestheheartrate


EXCHANGEOFCAPILLARYFLUIDS
Forcesinsideandoutsideofthecapillariesarewhatcanmovefluidsbackandforth.
Therearedifferentmethodsbywhichfluidismoved,itcaneitherbepushedoutof
thecapillary(capillarypressure),oritcanbemovedviaosmoticpressure,whereit
ispulled.
TheforcesarecalledStarlingforces,andtheyarethefollowing:
1. CapillaryPressure(Cp)thispressureusuallycausesamovementoffluid
outofthecapillary
2. InterstitialPressure(Pi)thisispressurethepushesonthecapillariesand
movesfluidintothecapillary.
3. Plasmacolloidosmoticpressure(c)usuallymovesfluidintothecapillary
4. Interstitialfluidcolloidosmoticpressure(i)usuallymovesfluidoutofthe
capillary.
Determiningwhetherfluidwillmoveintooroutofthecapillaryisbasedonthenet
filtrationpressure.Byhavingallofthevaluesofthepressuresabove,wecan
determinethisfigure:
NetFiltrationPressure=(PcPi)(ci)

LINKINGTHEABOVETOEDEMATOUSSTATES:
Edemaiscausedbyexcessfluidsoutsideofthecapillaries,thusstatesinwhichthis
isfavorablewilllikelyleadtoedema.Thefollowingwilllikelyleadtoedematous
states:
1.
2.
3.
4.

Increasedinterstitialfluidcolloidosmoticpressure
Increasedcapillarypressure
Increasedcapillarypermeability
Decreasedquantitiesofplasmaproteins

RESPIRATORYPHYSIOLOGY

THEOXYGENHEMOGLOBINDISSOCIATIONCURVE

Ashifttotheright=decreasedaffinityofhemoglobinforoxygen
Ashifttotheleft=increasedaffinityofhemoglobinforoxygen


PULMONARYRESPONSESTOHIGHALTITUDE
WheninhigheraltitudestheP02decreasessignificantly,thusthebodymustadapt
andfindwaystomaintainoxygenationtothetissuesofthebody.Thefollowingare
themajorresponsesthathelpusmaintainadequateoxygenation:

Ventilationincreases
Erythropoietinincreases(fromkidneys)
Increasesin2,3Diphosphoglycerate(helpsmake02releaseeasier)
RespiratoryalkalosisstimulatesHCO3excretionfromthekidneys
Chronichighaltitudecancauseachronicallyhigherrateofventilation

PERFUSIONLIMITEDvsDIFFUSIONLIMITEDCIRCULATION
Perfusionlimitedmeansthatgasequilibratesearlyalongthecapillaryslength,
thustheonlywaytoincreasediffusionistoincreasebloodflow.
Diffusionlimitedmeansthatgasdoesntequilibratebythetimeitreachesthe
endofthecapillary.
Perfusionlimitedisseeninhealthypeople,whereasdiffusionlimitedoccursin
thosewithemphysema,fibrosis,orwhenexercising.

LUNGVOLUME
ThereisalistofimportantdefinitionsyoushouldknowfortheUSMLEexam,as
thereisalmostalwaysatleast1questiondealingwiththis.Thequestionmaycome
intheformofadefinition,butitwillmostlikelycomeintheformofachartwhere
youwillhavetocalculate.

Calculatinglungvolumes:
TotalLungCapacity=RV+IRV+TV+ERV
VitalCapacity=TV+IRV+ERV
FunctionalReserveCapacity=ERV+RV
InspiratoryCapacity=IRV+TV

VENTILATION/PERFUSION(V/Q)MISMATCH
Whenthereisnormalgasexchange(iehealthyindividual),theV/Qisapproximately
1,meaninganidealventilationtoperfusionratio.Ifthereisamismatch,this
indicatesthatthereisashuntandsomedegreeofdeadspaceinthesamelung.
AV/Qof0isindicativeofashunt(ieairwayobstruction)
AV/Qofisindicativeofanobstructionofbloodflow(iephysiologicaldeadspace).

Ventilationandperfusionaregreateratthebaseofthelungthanintheapex
V/Qattheapexofthelungishigher,meaningwastedventilation
V/Qatthebaseofthelungislower,meaningwastedperfusion

LUNGPRODUCTS
Thereareafewveryimportantproductsmadeinsidethelungs,theyinclude:
1.
2.
3.
4.
5.

AngiotensinConvertingEnzyme
Surfactant(type2pneumocytes)
Prostaglandins
Histamine
Kallikrein


CARBONDIOXIDETRANSPORT
Therearethreemethodsbywhichcarbondioxidearecarriedfromthetissuesofthe
bodybacktothelungs,theyinclude:
1. Intheformofbicarbonate(thisisthemajority)~90%
2. Asdissolvedcarbondioxide~5%
3. Boundtohemoglobinascarbaminohemoglobin~5%

CHAPTER6

BIOCHEMISTRY

Thissectionisveryhighyield,andincludesmanysub
categories.Themetabolicpathwaysareveryimportant;
payingspecialattentiontoregulatorystepsiscrucial.
Whilethedetailsofbiochemistryarenothighyield,thebig
pictureasawholeisveryhighyieldmaterial.

GENETICS
TheHardyWeinberglawofgeneticsstatesthatboththealleleandthegenotype
frequenciesofapopulationremainconstantfromgenerationtogeneration,unless
thereisaspecificdisturbance(s)introducedintothepopulation.
ThelawofHardyWeinbergassumes:
1.
2.
3.
4.

Nomutationsoccur
Thereisnoselectionforanyofthespecificgenotypes
Matingisrandom
Thereisnomigrationintooroutofthepopulation

Thefrequencyofdifferentallelesinapopulationcanbedetermineswiththe
Punnettsquare,whichcanbelinkedmathematicallytotheHardyWeinberg
equationforequilibrium.


HIGHYIELDGENETICTERMINOLOGY
Geneisthesectionofachromosomethatcarriesinformationforspecifictraits
Allelesarealternateformsofagene
Phenotypethephysicalappearanceofanorganisms,usuallydeterminedbythe
dominantgene.
Genotypethegeneticmakeupofanorganism.
Dominantisthegeneortrainthatappearsorexpressesitself,representedwitha
capitalletter(ieAa).
Recessiveisthegene/traitthatgetshiddeninthepresenceofadominantgene,
representedwithalowercaseletter(ieAa)
VariableExpressionisthevarianceisphenotypefromoneindividualtoanother.
IncompletePenetrancethisoccurswhennotallindividualswhocarrymutant
genotypeactuallyshowthemutantphenotype.
Anticipationoccurswhentheseverityofadiseasegetsworseatyoungerand
youngerages,classicexampleisHuntingtonsdisease.
Pleiotropyoccurswhenonegenehasmorethanoneeffectonanindividuals
phenotype.
Imprintingisadifferenceinphenotypethatdependssolelyonwhetherthe
mutationisofmaternalorpaternalorigin.
Mosaicismthecellsofthebodyhavedifferentgeneticmakeups.
LossofHeterozygositythismeansthatacomplementaryallelemustbeeither
deletedormutatedbeforetheotherallelecanshowexpressitivity.Thisdoesnot
applytooncogenes.

MODESOFINHERITANCE


LABORATORYTECHNIQUESUSEDINBIOCHEMISTRY
ThePolymeraseChainReaction(PCR)
ThistechniqueisusedwhenalargenumberofDNAcopiesareneeded.Thestepsto
creatingmultiplecopiesofDNAfragmentsthroughthePCRareasfollows:
1. DNAisheatedanddenatured,thiscausestheseparationofthestrands.
2. ThedenaturedDNAiscooled,andDNAprimersareaddedtothemix,these
adheretoeachindividualstrandofDNAatthelocationthatwillbeamplified.
3. DNApolymerasethenreplicatesthedesiredDNAstrands.
4. ThisprocessisrepeateduntilthedesirednumberofDNAisachieved.

ELISA(EnzymeLinkedImmunoabsorbentAssay)
Thistechniqueisusedasameansofdetectingthepresenceofanantibodyoran
antigeninasample.Theantibodyorantigenthatisaddedislinkedtoanenzyme,
thenatestsolutionisaddedtoseeifanintensecolorilluminates,indicatingthat
thereisapositiveresult.

ThistestismostcommonlyusedwhenlookingforHIV.
SensitivityandspecificityfortheELISAareextremelyhigh,bothapproaching
100%,howevertheyarenotperfect,andfalseresultsdooccur.

SOUTHERNBLOTTECHNIQUE
ThistechniqueisusedtodetectspecificsequencesofDNA.Thetechniquecombines
thetransferofelectrophoresisseparatedDNAfragmentsandmembranefiltration,
andthenfragmentsaredetectedbyprobehybridization.

WESTERNBLOTTECHNIQUE
Thisisatechniqueusedtodetectspecificproteins,separatingnativeordenatured
proteinsbythelengthofthepolypeptide.Theseproteinsarethentransferredtoa
membranewheretheyareprobedusingantibodiesspecifictothetargetprotein.

NORTHERNBLOTTECHNIQUE
IsatechniqueusedtostudygeneexpressionbyRNAdetectioninasample.This
techniqueallowsforthedetectionofcellularcontrolbydeterminationofgene
expressionlevelsduringdifferentiationandmorphogenesis.


DNA,RNA,ANDPROTEINS

Adeninebindstothyminewithtwohydrogenbonds,whereasguaninebindsto
cytosinewiththreehydrogenbonds,makingitastrongerbondandmoreresistant
toincreasedtemperatures.
InRNA,uracilispresentinsteadofthymine.


THEBASICSTRUCTUREOFTHENUCLEOTIDES
PyrimidinesAreheterocyclicorganiccompoundsconsistingoftwonitrogen
atomsatpositions1and3ofasixmemberedring.Thenucleotidesbelongingtothe
pyrimidinegroupare:Cytosine,Uracil,andThymine.

PurinesAreheterocyclicaromaticorganiccompoundsconsistingofapyrimidine
ringboundtoanimidazolering.Thenucleotidesbelongingtothepurinegroupare:
AdenineandGuanine.

CHROMATIN
ChromatinisthestructurethatismadeupofDNAandproteins,whichthenmakes
upthechromosome.Itisfoundwithinthenucleiofeukaryoticcellsonly.Thereare
twotypesofchromatin,thereisheterochromatin,whichiscondensedand
transcriptionallyinactive,andthereiseuchromatin,whichislooserand
transcriptionallyactive.
ThemainfunctionofchromatinistopackagelargeamountsofDNAintosmaller
areas,allowingmoretofitintocellsandthusprovideformoregeneticmaterial
overall.


DNAREPLICATION
Inprokaryotes,thereisasingleoriginofreplication,whereasineukaryotesthere
aremultipleoriginsofreplication.
Someimportantfacts:

DNApolymerase3proofreadsinthe35direction,synthesizinginthe
53direction.
PrimaseproducesanRNAprimer,onwhichDNApolymerase3initiates
replication.
DNApolymerase3elongatesthechainthroughtheadditionof
deoxynucleotidestothe3end.
DNApolymerase1degradesRNAprimeronceitisnolongerneeded.
Okazakifragmentshelpelongatethechainonthelaggingstrand.
DNAligasesealsonthelaggingstrand.
DNAgyraseunwindsthestrandbeforereplicationcanbegin.
DNAtopoisomeraserelievessupercoilsbynickingthestrand.

DNADAMAGE
ThetwotypesofDNAdamageareEndogenousandExogenous.
TypesofEndogenousdamage:
1.OxidationreactiveoxygenspeciescausesinterruptionstotheDNAstrand.
2.Alkylationalkylationofbasesbyformationofcompoundssuchas7
methylguanine.
3.Hydrolysisbasehydrolysiscausesdeamination,depurination,and
depyrimidination.
4.Bulkyadductformation
5.Basemismatches
TypesofExogenousdamage:
1.UVBdamagecausescrosslinkingbetweencytosineandthyminebases,
creatingpyrimidinedimers.
2.UVAdamagecreatesmostfreeradicals,causedindirectDNAdamage.
3.IonizingradiationcausingradioactivedecayandbreaksinDNAstrands.
4.Thermaldisruptioncausesdepurinationandsinglestrandbreaks
5.Industrialchemicaldamagecompoundssuchasvinylchlorideandhydrogen
peroxide,smoke,soot,andtarcancauseseveredamagetoDNA.Itcausesoxidation,
alkylation,andcrosslinkingofDNA.

DNAREPAIR
Singlestranddamage:
Damagetoasinglestrandisrepairedviaoneofthreemechanisms.
BaseExcisionRepairThistypeofrepairhelpstofixdamagetoasinglebase,
whichisremovedbyaDNAglycosylase.ThemissingbaseisthenrecognizedbyAP
endonucleaseandresynthesisoccursviaDNApolymerase,withDNAligasesealing
thenewstrand.

NucleotideExcisionRepairThismechanismrecognizesbulkyhelixdistorting
damageandisfixedwithtranscriptioncoupledrepairwhichemitsNERenzymes
thatareactivelybeingtranscribed.
MismatchRepairThisrepairmechanismcorrectserrorsofDNAreplicationand
recombinationthatresultedfrommispairednucleotides.

DoubleStrandDamage:
Threemechanismsexisttorepairdoublestrandeddamage,theyare:
1. Nonhomologousendjoining(NHEJ)
2. Microhomologymediatedendjoining(MMEJ)
3. Homologousrecombination

NonHomologousEndJoiningThisformofrepairismediatedbyaspecialized
formofDNAligase(DNAligaseIV),whichworksbyformingacomplexwitha
cofactor(XRCC4)andthendirectlyjoiningthetwonondamagedends.
MicrohomologyMediatedEndJoiningThistypeofrepairmechanismworksby
usinga525basepairhomologoussequencetoalignbrokenstrandsbeforejoining
them.ItusesaKuproteinandDNAPKindependentrepairmechanismandthen
repairoccursduringtheSphaseofthecellcycle.
HomologousRecombinationThistypeofrepairrequiresthepresenceofan
identicalsequencethatisusedasatemplateforrepairofthebreak.

DEFECTSTOTHEDNAREPAIRMECHANISM
Whentherepairmechanismsfail,thereisanexpressionofimproperDNA,andthis
canresultinconditionsthataresevereand/orlethal.Threeconditionsthatresult
fromfailedDNArepairare:
XerodermaPigmentosumThisconditionoccurswhenthereisadefectinoneof
thesevengenesrequiredforDNArepair.Thoseafflictedwiththisdiseaseare
extremelysensitivetosunlightandhaveasignificantlyhighriskforskincancer.
Thispatientwillonlylivetobemiddleagedatbest.
TrichothiodystrophyThisconditioniscausedbydefectsthatresultinreduced
RNAtranscriptionofproteins.Symptomsinclude:photosensitivity,brittlehairand
nails,scalyskin,protrudingears,physicalandmentalretardation,andareceding
chin.*Theproblemultimatelyliesinthefactthatthehairlackssulfurcontaining
proteins.

CockayneSyndromeThisconditionresultsfromaninabilitytorepairDNA
damagethatisdetectedduringtranscription.Thepatientsuffersfromsensitivityto
sunlight,haveshortstature,andageprematurely.


FROMDNATOPROTEIN
TheprocessofobtainingusableproteinsinvolvescreatingRNAfromDNA,then
proteinsfromthatRNA.
DNARNA(transcription)
RNAPROTEIN(translation)
Thebasicoverviewofthewholeprocessisasfollows:


TYPESOFRNA
TranscriptionistheprocessbywhichRNAismadefromeachstrandofDNA.
Thereare3typesofRNA:rRNA,mRNA,andtRNA
rRNAIsmadeviaRNApolymeraseI,andisthemostabundanttypeofRNA.
RibosomalRNAcombineswithproteininthecytoplasmtoformaribosome,which
servesasthesiteandcarriesallofthenecessaryenzymesrequiredforprotein
synthesis.
mRNAIsmadeviaRNApolymeraseII,andisthelargesttypeofRNA.Messenger
RNAistheRNAthatiscreatedfromagenesegmentofDNA.ThemRNAthen
carriesthecodeitreceivesfromDNAintothecytoplasmwhereproteinsynthesis
willoccur
tRNAIsmadeviaRNApolyeraseIII,andisthesmallesttypeofRNA.Transfer
RNAisthetypeofRNAthatreadsthecodefromthemRNAandcarriestheamino
acidtobeincorporatedintothedevelopingproteins.Therearemorethan20
differenttRNAs,meaningthereisoneforeachaminoacid.tRNAcontains
approximately75nucleotides,threeoftheseareanticodons.
*ProkaryoteshaveonlyoneRNApolymerasethatmakesalloftheRNAsubtypes.


TRANSCRIPTION
TranscriptionistheprocesswherebyDNAisusedasatemplatetoproducemRNA.
DNAmustbeintheformofeuchromatininorderforthisprocesstooccur,andit
occursinthenucleusofthecellbecauseDNAwouldotherwisebeexposedto
dangerousenzymesinthecytoplasmthatwouldcauseitsdegradation.
Thereisnoproofreadingfunction,RNApolymeraseIIwillopenaDNAsequenceat
thepromotersite,whichisaTATAbox(ATrichsequencethatisupstream).mRNA
issynthesizedinthe53direction.


PROCESSINGOFmRNA
Aftertranscription,whilethemRNAisstillinthenucleus,therearethreeimportant
stepstakentoensurestabilizationofthenewlysynthesizedmaterial.
1. Additionofa5cap
Theadditionofthecapisdonethroughthefollowing:

Phosphorylaseremovesthegammaphosphatefromthe5endofthe
transcribedpremRNA.
GuanylyltransferasecatalyzesthecondensationofGTPwiththe5endofthe
premRNA.
Theterminalguanosinenucleotideismethylatedbyguanine7methyl
transferase,usingSadenosylmethionine(SAM)asacofactor.

2. Additionofa3polyAtail(polyadenylation)
Theadditionofapproximately200adenineunitstothe3endofthemRNAhelpto
provideprotection,aswithoutthispolyAtailthemRNAwouldbequicklydegraded.

Acleavagefactorrecognizesandbindstothespecificpolyadenylation
sequence(AAUAAA).
EndonucleasescleavetheRNA
PolyApolymerasecatalysestheadditionofapproximately200adenine
nucleotidestothe3endofthecleavedmRNA.
Anadditionprotein(cleavagestimulationfactor),helpsstabilizethe
complex.
Onceassembled,mRNAiscleaved1035nucleotidesdownstreamofthe
AAUAAAsequencebytheendonucleaseandapproximately20adenine
nucleotidesareaddedbythepolyApolymerase.
ThepolyAtailsarethenboundbypolyAbindingproteins,whichhelpto
shifttheprocessivemodeofsynthesisandthisresultsintheadditionofupto
250nucleotides.

3. Splicing
SplicingisamodificationofmRNAwherebyintronsaresplicedoutandexonsare
joinedtogether.ThisstepisrequiredbeforeRNAcanmoveoutofthenucleusand
gothroughtranscription.

StepstomRNAsplicing:
1.
2.
3.
4.
5.

Theprimarytranscriptcontainsbothintronsandexons
Spliceosomesmediatethesplicing
The1stsplicesiteisatthe5endofanintron
The2ndsplicesiteisatthe3endofthatsameintron
Intron,oncesplicedatbothsites,isremovedandtheexonsarecombined,
formingamaturemRNAstrandthatispreparedfortranslation


STRUCTUREOFtRNA
TransferRNA(tRNA)isanRNAmolecule(thesmallest)whosepurposeisto
transferanactiveaminoacidtothepolypeptidechainduringtranslation.Thereisa
3terminalsite,atwhichtheaminoacidattachescovalentlythroughanaminoacyl
tRNAsynthetase.Theotherimportantstructureisatthebase,andisknownasthe
anticodon,whichcarriesa3nucleotidecodethatpairstothecorrespondingthree
basecodonregionofthemRNA.

AminoacylationTheaminoacidbecomeslinkedtothetRNAviaAminoacyltRNA
synthetase,usingATPtoattachtheaminoacid.Theaminoacidisboundtothe3
endcovalently.ThisleavesthetRNAmoleculeinachargedstate.
tRNAWobbleistheconceptthatonlythefirst2nucleotidepositionsofthemRNA
codonmustmatchinorderfortheprocesstoproceedcorrectly,thethirdposition
doesnothavetobetheexactcorrectnucleotidesinceitsdifferencecanstillcodefor
thesameaminoacid.


TRANSLATION
TranslationistheprocessbywhichmRNAisusedtocreateproteins.
Therearethreestepstotranslation,theyare:
1. Initiation
2. Elongation
3. Termination

Initiation:
Initiationbeginswhenthesmallribosomalsubunitattachestothe5capofmRNA
andmovestothetranslationinitiationsite.

Elongation:

tRNAhasacomplementaryanticodontomRNAstartcodon(AUG),where
methionineisthecorrespondingaminoacid.
ThelargeribosomalsubunitjoinstoformthePandAsites(1sttRNAisinthe
Psite,2ndenterstheAsiteandcomplementsthe2ndmRNAcodon).
MethioninethentransferstotheAAintheAsite,the1sttRNAexits,the
ribosomemovesalongmRNAandthenexttRNAenters.
ThegrowingpeptideiscontinuallytransferredtotheAsitetRNA

Termination:

Astopcodon(UAG)iseventuallyencountered,atwhichpointarelease
factorenterstheAsite,andtranslationisterminated.
Theribosomedissociatedandthenewlyformedproteinisreleased.


METABOLISM

HighYielddisordersofmetabolism:
Glycogenstoragediseases:
Type1vonGierkedisease(HepatorenalGlycogenosis)

Causedbyglucose6phosphatasedeficiency.

Patientmayexperience:

Hypoglycemia
Chronichunger
Delayedpubertyand/orunderdevelopment
Hepatomegaly
Fatigue

Type2Pompesdisease

Causedbyalysosomal1,4glucosidasedeficiency.

Patientmayexperience:

Muscleweakness,especiallyintheheart
MostcommonlyseeninnewbornchildrenORthoseintheir30sand40s
Fatigueasaresultofweakeningoftheheartandliver
Curvatureofthespineisaprogressivesymptoms
Difficultybreathing,suchaslaboredbreathing,andinfectionsofthe
respiratorytract
Dizzinessandsyncope

Type3Corisdisease

Causedbyadeficiencyofthedebranchingenzyme1,6glucosidase

Patientmayexperience:

SymptomssimilartovonGierkesdisease,butmilder
Youngchildrentypicallyhavemassivehepatomegalythatdiminisheswith
increasingage

Type4Andersendisease

ThemainclinicalfeaturesofAndersondiseaseareinsufficiencyoftheliver
andabnormalitiesoftheheartandnervoussystem
Thisdiseaseisrareandwillleadtoearlydeath

Type5McArdlesdisease

Causedbyadeficiencyofskeletalmuscleglycogenphosphorylase

Patientexperiences:

Increasedglycogenfoundwithinthemuscle
Painfulcrampsandmyoglobinuriawhenactivityisincreased

Type6Hersdisease

Causedbyahepaticphosphorylasedeficiency
Patientmayhavetheinabilitytomaintainbloodglucoselevelsduring
periodsoffasting.
Urineandserumketonesareelevatedproportionallytotheleveloffasting
Mildtomoderatehyperlipidemiamaybepresent
Prominenthepatomegalyandgrowthretardationarecommonfindingsof
Hersdisease

Type7Taruidisease

Causedbyadeficiencyofphosphofructokinase(PFK)inglycolysis
Patientwillexperienceincreasedmuscleglycogenthatcannotbebroken
down
Cramping
Higherlevelsofmyoglobinintheurinewhenthereisincreasedphysical
activity


PHENYLKETONURIA(PKU)
PKUisanautosomalrecessivediseasecharacterizedbyadeficiencyof
phenylalaninehydroxylase,whichinhibitstheformationoftyrosinefromits
precursorphenylalanine.Becauseofthisenzymedeficiency,twothingsoccur:
1. TheaminoacidTyrosinebecomesanessentialaminoacid.
2. Phenylalaninebuildsupcausingamyriadofseveresymptoms
Theincreaseinphenylalanineleadstoanincreaseinphenylketones
(phenylpyruvate,phenylacetate,andphenyllactate)intheurine.
SignsandSymptoms:

Patientsarenormalatbirth,butscreeningisnowessential
Failureofearlymilestonedevelopment
Characteristicmustyormousybodyodor
Microcephalyandmentalretardation
Hyperactivity
Hypopigmentationandeczema

ALBINISM
Aconditionwherethereisacompletelackofpigmentthroughoutthebody.Thisis
anautosomalrecessivecondition,wherethepatientcannotproducemelaninfrom
tyrosine(tyrosinasedeficiency)orfromadefectinthetyrosinetransporters.There
isanincreaseintheriskofskincancerduetothelackofprotectivemelanininthe
skin.

MAPLESYRUPURINEDISEASE
Maplesyrupurinediseaseischaracterizedbythesweetsmellofthepatientsurine
(iemaplesyrup).Thecauseisadefectintheabilitytobreakdownthebranched
chainaminoacidsLeucine,Isoleucine,andValine.Thereasonforthisisadeficiency
oftheenzymeketoaciddehydrogenase.Thepatientwillsufferfromsevere
mentalretardation,CNSdefects,andfinallydeath.


ALKAPTONURIA
Anotherconditioninvolvingtyrosine,alkaptonuriaresultsfromadeficiencyof
homogentisate1,2dioxygenaseinthepathwayoftyrosinedegradation.
Homogentisicacid(alkapton)thusaccumulatesinthebloodandisexcretedinthe
urineinlargeamounts,leadingtoblackeningoftheurineuponstanding.Excessive
amountsofhomogentisicacidcausedamagethecartilage,leadingtosevere
arthralgias.

HOMOCYSTEINURIA
AlsoreferredtoasCystathioninebetasynthasedeficiency(CBSdeficiency),itisan
autosomalrecessivedisorder.
Inthecaseofdeficiency,patientwillhaveexcessivehomocysteineintheurine.In
thiscase,cysteinewillbeessentialandshouldbeincreasedinthediet,while
simultaneouslydecreasingtheamountofmethionineinthediet.
Signsandsymptomsinclude:

Mentalretardation
Seizure
Musculoskeletalabnormalities(tallbuild,longlimbs,pectusexcavatum,pes
cavus,andgenuvalgum)
Abnormalitiesoftheeyes(glaucoma,subluxationoflens)
Vascularconditions(earlythromboses)

CYSTINURIA
Cystinuriaisaconditionwherebythereisadefectinthetransportoftubularamino
acidsforthefollowingaminoacids:Cystine,Ornithine,Lysine,andArginine.This
resultsinanexcessofcystineintheurine,whichcanpredisposethepatientto
kidneystones.Managementistoalkalinizetheurinewithacetazolamide.


RESPIRATORYBURST
Thisreactionisimportantindegradingbacteriathatarephagocytized.The
respiratoryburstreducesoxygen(viaNADPH)toproduceafreeradical,then
producingH202,whichisfurthercombinedwithChloridetoproduceHOCl,which
ultimatelydestroystheengulfedbacteria.

THEANATOMYOFADENOSINETRIPHOSPHATE(ATP)

GLYCOGENOLYSIS
Glycogenolysisistheprocesswherebyglycogenpolymerisconvertedtoglucose,
whichcanthengothroughglycolysis.Glycogenolysisoccursintheliverandmuscle,
andisstimulatedbyepinephrineand/orglucagoninresponsetolowbloodglucose
levels.


GLYCOLYSIS
Glycolysisistheprocesswherebyglucoseisconvertedtopyruvate.Glycolysis
consistsoftenreactionswithFOURirreversiblesteps/enzymes.
ThePrepatoryPhaseConsistsofthefirstfivesteps,alsoknownastheinvestment
phase.Thisphaseconsumesenergythatisusedtoconvertglucoseintotwo3C
sugarphosphates(G3P).Inthisphase,thenetATPis(2).
ThePayOffPhaseConsistsoffivestepsthatproduceanetgainof2ATPand2
NADHmolecules(perglucosemoleculethatgoesthroughthepathway).Pyruvateis
alsotheendproductoftheglycolyticpathway.

ThetotalATPgeneratedfromanaerobicglycolysisis2ATPs.Whencomparedto
ATPproducedwiththemalateshuttleandglucose3phosphateshuttle,which
create38ATPsand36ATPsrespectively.

REGULATIONOFGLYCOLYSIS
ThereareFOURstepsinglycolyisisthatareconsideredtobeirreversible,thusonce
theyhaveoccurred,glycolysismustprogressintheforwarddirection.Thefour
regulatoryenzymesare:
1.
2.
3.
4.

Hexokinase
Phosphofructokinase
Pyruvatekinase
Pyruvatedehydrogenase

Hexokinase:

Hexokinaseisresponsibleforthefirststepofglycolysisinthemusclesand
brain.
Itisinhibitedbythepresenceofglucose6phosphate,whichistheproduct
ofitsactivity.
Thisstepisimportantbecauseitpreventstheconsumptionoftoomuch
cellularATPintheformationofglucose6phosphatewhenglucoseisnot
limiting.
Hexokinasehasalowaffinitytoglucose,thusitpermitsglycolysisinitiation
evenifbloodglucoselevelsarelow.

Phosphofructokinase:

PFKistheratelimitingstepofglycolysis,thusitisthemostimportant
controlpointthroughoutthewholeprocess.
Regulationisbybothalloestericeffectorsandbycovalentmodifications(ie
phosphorylation).
ItisstimulatedbythepresenceofAMPandfructose2,6bisphosphate.
EvenifATPishigh,thepresenceofAMPcanovercomeitsinhibitoryeffects
duetotheabilitytoallostericallyactivatePFK.
ItisinhibitedbythepresenceofATPandcitrate

PyruvateKinase:

SimilartoPFK,isregulatedbyallostericeffectorsandbyphosphorylation.
PKisactivatedbyfructose1,6bisphosphateandinhibitedbyATPand
alanine.

PYRUVATEDEHYDROGENASECOMPLEX
Thepyruvatedehydrogenasecomplexregulatestheentryofglycolyticproducts
intothecitricacidcycle.Thiscomplexconsistsofthreeenzymesthattransform
pyruvate(fromglycolysis)intoacetylCoA,throughtheprocessofpyruvate
decarboxylation.

DEFICIENCYOFPYRUVATEDEHYDROGENASE
Adeficiencyofpyruvatedehydrogenaseisaconditionthatismostcommonly
seeninalcoholics,duetothedeficiencyofthiaminethatisaninevitableresultof
thisdisease.ThelackofpyruvateDHresultsinanaccumulationofpyruvate,
whichresultsinlacticacidosis.Therewillbeneurologicfindingsthatcanbe
managedbygivingthepatientaminoacidsthatarepurelyketogenic,suchas
LeucineandLysine.


METABOLISMOFPYRUVATE
Understandinghowpyruvateismetabolizedwillaidinunderstandingwhy
certainadverseeffectsoccurwhenthereisamalfunctioningpyruvateDH
and/orotherproblemswiththepathway.Inyeast,pyruvateisconvertedto
ethanolinanaerobicconditions,ineukaryotesitisconvertedtolactate.In
optimalconditions(ie.Aerobic),pyruvateisconvertedtoAcetylCoA.


THECITRICACIDCYCLE(TCA)
Thecitricacidcycleisanessentialmetabolicprocessthatisessentialforcompleting
theoxidativedegradationofmonosaccharides,fattyacids,andaminoacids.

Serves2mainpurpose:
1. ToincreasethecellsATPproducingpotentialbygeneratingreduced
electroncarrierssuchasNADHandreducedubiquinone.(QH2).
2. Toprovidethecellwithprecursorsthatcanbeusedtobuildavarietyof
molecules,dependingonthecellsneeds.

Underaerobicconditions,thefollowingquantitiesofATParegenerated:
Glycolysis=2ATP(net),2NADH(equaling6ATP)
PyruvateACoA=2NADH=6ATP
CitricAcidCycle=2GTP(2ATP),6NADH(~18ATP),2QH2(4ATP)

THEELECTRONTRANSPORTCHAIN
TheETCcouplereactionsbetweenelectrondonorsandelectronacceptors(ie.
BetweenNADHandoxygen),tothetransferofhydrogenionsacrossamembrane.
ThesehydrogenionsareusedtoproduceATPtobeusedasenergyastheymove
backacrossthemembranes.
Theconversionofoxygentowater,NADHtoNAD+,andsuccinatetofumarateis
whatwillultimatelydrivethetransferofhydrogenions.
Therearefourcomplexesthatareembeddedintheinnermembrane,whichare
electricallyconnectedbylipidsolubleelectroncarriersandwatersolubleelectron
carriers.Threeofthesecomplexesserveasprotonpumps.
Complex1Isaprotonpump.IsNADHdehydrogenase,whichremovestwo
electronsfromNADHandtransfersthemtoubiquinone(Q).Onceubiquinoneis
reducedtoQH2,itcanfreelydiffusewithinthemembrane,translocatingfour
hydrogenionsacrossthemembrane,producingaprotongradient.

prematureelectronleakageoccursinComplex1,whichisamainsiteof
superoxideproduction.

Complex2IsSuccinatedehydrogenase,inthiscomplexthereistheadditional
deliveryofelectronsintothequinonepoolwhichoriginatefromsuccinateandare
transferredtoubiquinone.Complex2consistsoffourproteinsubunits.
Complex3Isaprotonpump.IstheCytochromebc1complex,wheretwo
electronsareremovedfromQH2andtransferredtocytochromec.Twoother
electronsarepassedacrosstheproteinreducingubiquinonetoquinol,andfour
protonsarereleasedfromtwoubiquinolmolecules.Thispumpbuildsthegradient
byanabsorption/releaseofprotons.Superoxideisformedthroughelectron
leakageinthiscomplex.
Complex4Isaprotonpump.IsCytochromeCoxidase,wherefourelectronsare
removedfromfourmoleculesofcytochromec,andthustransferredtooxygen,thus
producingtwowatermolecules.Fourmoreprotonsaretransferredacrossthe
membrane,furthercontributingtothegradient.
Complex5ATPSynthase.Onceasufficientprotongradienthasbeenmadeby
complexesI,III,andIV,anFoF1ATPsynthasecomplexusesthisgradienttomake
ATPviaoxidativephosphorylation.Theprotonsinfluxbackintothemitochondrial
matrix,releasingfreeenergywhichisusedtodrivetheATPsynthesis.Coupling
withoxidativephosphorylationisimportantinproducingATP,astheyprovidein
somecircumstancestheabilityforprotonstoflowbackintothemitochondrial
matrix(occursinbrownadiposetissue),andhelpsinthermogenesis.


GLUCONEOGENESIS
Thisistheprocessbywhichnewglucoseisformedfromcarbonskeletonssuchas
pyruvate,lactate,glycerol,alanine,andglutamate.Themajorsiteof
gluconeogenesisistheliver.Theprocessofcreatingglucosefrompyruvateisquite
costlycomparedtotheamountofenergycreatedbyonemoleculeofglucose.
Activatedwhenthebodyisinastateofhungerand/orstarvation.Ketonebodies
arealsoproducedfromacetylCoA.
Thebasicprocessofgluconeogenesisisasfollows:


INSULIN
Insulinisahormoneproducedbythecellsofthe
pancreas,itsprimeroleistodriveglucosefromthe
bloodintothecellsofthemuscles,brain,redblood
cells,intestines,liver,cornea,andkidney.
Specificeffectsofinsulin:

Anaboliceffects(synthesisoffats,proteins,
andglycogen)
Retentionofsodiumbythekidneys
Inhibitionofthereleaseofglucagonfromthe
cellsofthepancreas

Cpeptideisamarker
ofinsulinsecretion.
Whenapatienthas
extremehypoglycemia,
differentiatebetween
insulinomaand
exogenous
administrationby
lookingforthe
presenceorabsenceof
Cpeptide.


GLUCAGONANDINSULININREGULATINGHOMEOSTASIS
Theregulationofbloodglucoseisdelicatelybalancedbytwoimportanthormones,
insulinandglucagon.Insulinissecretedbythecellsofthepancreasinresponse
toanelevatedbloodglucoselevel.Ontheotherside,glucagonissecretedbythe
cellsofthepancreasinresponsetolowlevelsofbloodglucose.Glucagoncausesthe
livertoreleaseglycogenwhichisbrokendownintoglucose,andusedtoincrease
theamountofglucoserunningthroughtheblood.


THESYNTHESISOFCHOLESTEROL
Cholesterolisimportantinthebodyforvariousreasons,namely:

Playsaroleinmembranestructureandfluidity
Helpswithhormoneproduction
HelpswithvitaminDmetabolism
PlaysaroleintheCNS

Thehighestyieldinformationrelatingtocholesterolisknowingitsratelimiting
enzyme,whichis:HydroxyMethylGlutarylCoaReductase(HMGCoAreductase).
Thepharmacologicalbasisofloweringcholesterol(statindrugs),isdesignedaround
theinhibitionofthisenzyme.
Themostimportantstepsincholesterolsynthesisare:

FATTYACIDSYNTHESIS
Someimportantpointsmustbeunderstoodregardingfattyacidsynthesis,these
beingthebasicsofFAsynthesis.
TheratelimitingenzymeisAcetylCoACarboxylase,whichdoesthefollowing:
AcetylCoAMalonylCoA

Thisstepispositivelyeffectedbycitrate,andnegativelyeffectedby
palmitoylCoA.
Biotinisarequiredcofactortothisreaction.
Synthesisoffattyacidsmovesinthedirectionofmethylcarboxylend,
thusC15andC16areproducedfirst,C2andC1areproducedlast.


APOLIPOPROTEINSandLIPOPROTEINS
Apolipoproteins:
Apolipoproteinsareproteinsthatbindtolipidsandhelptransportthemthroughout
thebody.Onceboundtolipids,thestructureisknownasalipoprotein.Other
functionsofapolipoproteinsincludeactingascoenzymesandasligandsbetween
thelipoproteinsandthetissuestheysupply.Theyaresynthesizedintheintestines
andtheirrateregulationisdeterminedbythecontentoffatavailablethrougha
personsdietaryintake.
Therearesixclassesofapolipoproteins:
Aincludesthesubgroups:AI,AII,AIV,AV)
Bincludesthesubgroups:B48,B100
Cincludesthesubgroups:CI,CII,CIII,CIV
ClassesD,E,andHhavenoimportantsubgroups.

Lipoproteins:
Becausefattyacidsalonehavetroublebeingtransportedthroughaqueous
compartmentsinsidethecells,amechanismmustbeinplacetoallowthemtogetto
wheretheyneedtobe,thusentersthelipoproteins.
Thebasicstructureofthelipoproteinisbelow:

Lipoproteinsaredifferentbasedontheratioofprotein:lipids,aswellasthe
particularapoproteinsandlipidsthattheycontain.Thus,lipidscanbeclassified
basedontheirdensitites:
HDL(highdensitylipoprotein):Hasthehighestprotein:lipidratioofall
lipoproteins,isalsothelipoproteinwiththehighestoveralldensity.Responsiblefor
transportationofcholesterolfromtheperipheraltissuesbacktotheliver.
IDL(intermediatedensityprotein):IDLisformedwhenVLDLgetsdegraded.
Transportsanddeliversbothtriglyceridesandcholesteroltotheliver,wherethey
getdegradedtolowdensitylipoproteins.
LDL(lowdensitylipoproteins):Arealowdensitylipoproteinwhichcontainthe
highestdensityofcholesterylesters.LDLisengulfedbytargetcells,andisavery
dangerouslipoproteinthatcanleadtohardeningofthearteriesandsubsequently
vascularpathologies.
VLDL(verylowdensitylipoproteins):Containthesecondhighestdensityof
triacylglycerols.Itsroleistodelivertriglyceridesfromthelivertotheperipheral
tissues.
CHYLOMICRONS:Arethelargestofallthelipoproteins,buthavethelowestdensity
duetoahighratiooflipidstoproteins.Alsocontainthehighestcontentof
triacylglycerolsbydensity.Hasadualroleasitsuppliestheperipheraltissueswith
triglyceridesandsuppliescholesteroltotheliver.

THESTRUCTUREOFHEME


HEMESYNTHESIS

DISORDERSOFHEMESYNTHESIS
PorphobilinogenDeaminaseAcuteIntermittentPorphyria
Acuteintermittentporphyriaiscausedbyadeficiencyintheenzyme
porpobilinogendeaminase,thuspreventingtheconversionofporphobilinogento
hydroxymethylbilane.Thisleadstoanaccumulationofporphobilinogeninthe
cytosol,whichcausesamyriadofsymptoms.
Symptomsofacuteintermittentporphyria:

Muscleweakness
Abdominalpain
Constipation
Nausea/vomiting
Hypertension
Diaphoresis
Tachycardia

Treatmentofacuteintermittentporphyria:

Mayrequirehospitalizationforseveresymptoms
Avoidanceofprecipitatingdrugs
Avoidanceofalcohol
Properdiet

UroporphyrinogenDecarboxylasePorphyriaCutaneaTarda
Thisisthemostcommontypeofporphyria,resultingfromlowlevelsof
uroporphyrinogendecarboxylase.
SignsandSymptomsofPorphyriaCutaneaTarda:

Blisteringoftheskininareasexposedtosun
Photosensitivities
Hyperpigmentationandhypertrichosis
Chronicliverdisease(fibrosis,cirrhosis,inflammation)

TreatmentofPorphyriaCutaneaTarda:
Sinceitisachroniccondition,amultidimensionalapproachisrequiredtocontrol
thegroupofpossiblesymptoms.

Avoidanceofexcessexposuretosunlight,iron,andalcohol


DISORDERSOFPURINEANDPYRIMIDINEMETABOLISM
Purinesareakeycomponentofcellularenergy(ATP,NAD),signaling(GTP,cAMP,
cGMP),andinconjunctionwithpyrimidines,theproductionofDNAandRNA.
Whenthereareproblemswithsalvage,synthesis,catabolism,andmetabolismof
purinesandpyrimidines,certaindisorderspresentthemselves.

DISORDERSOFPURINESALVAGE:
LeschNyhansyndrome,
AdeninePhosphoribosyltransferasedeficiency

LeschNyhanSyndrome:Anxlinkedrecessivedisorder,isduetotheabsenceof
theenzymehypoxanthineguaninephosphoribosyltransferase(HPRT),whichis
responsibleforconvertinghypoxanthinetoinosinemonophosphateandguanineto
guanosinemonophosphate.Thisresultsintheproductionofexcessuricacid.
Symptoms:Mentalretardation,selfmutilation,aggression,hyperuricemia,gout,and
choreoathetosis.
AdeninePhosphoribosyltransferasedeficiency:ArareATdisorderresultingin
theinabilitytosalvageadenineforpurinesynthesis.Thisresultsinanaccumulation
ofadenine,whichisoxidizedto2,8dihydroxyadenine,whichprecipitatesinthe
urinarytract,andcausesproblemidenticaltothoseofuricacidnephropathy(ie.
Renalcolic,infections,andrenalfailure).Thismustbemanagedwithahighfluid
intakeandpurinerestriction.

DISORDERSOFPURINENUCLEOTIDESYNTHESIS:
Adenylsuccinasedeficiency:IsanARdisorderthatcausessignificantmental
disabilities,seizures,andautisticbehaviors.Thereareincreasedlevelsof
succinylaminoimidazolecarboxamideribosideandsuccinyladenosineintheurine
andCSF.

DISORDERSOFPURINECATABOLISM:
Adenosinedeaminasedeficiency,
Myoadenylatedeaminasedeficiency
AdenosineDeaminaseDeficiency:Thisdeficiencycausesseverecombined
immunodeficiencydisease.TheincreaseddATPresultsininhibitionof
ribonucleotidereductaseandunderproductionofotherdeoxyribonucleotides.This
causesthecompromiseofDNAreplication.PatientwillhavelowRBCsandWBC
enzymeactivity.Stemcelltransplantandenzymereplacementisessentialto
therapy.
PurineNucleosidePhosphorylasedeficiency:ArareARdisorderwithsevereT
celldysfunctionandthepresenceofneurologicalsymptoms.Patientwilldevelop
lymphopenia,thymicdeficiency,recurrentinfection,andhypouricemia.Thesewill
causedevelopmentaldelays,spasticity,andataxia(ie.CNSdisorders)
XanthineOxidasedeficiency:Preventstheproductionofuricacidfromxanthine
andhypoxanthine.Thebuildupofxanthinecanprecipitateintheurine,causing
stones,urinarycolic,andUTIs.Patientsshouldbemanagedbymaintainingahigh
fluidintakeandtakingallopurinol.

DISORDERSOFPYRIMIDINEMETABOLISM:
UridineMonophosphateSynthasedeficiency(Hereditaryoroticaciduria):This
deficiencypreventsorotatephosphoribosyltransferaseandorotidine5
monophosphatedecarboxylasereactions.Theaccumulationoforoticacidcauses
megaloblasticanemia,oroticcrystalluria,nephropathy,cardiacmalformations,
strabismus,andrecurringinfections.Treatmentinvolvesuridinesupplementation.


LACTOSEINTOLERANCE
LactoseMetabolism:
Lactoseismetabolizedbytheenzymelactase,whichwhendeficientcausesGI
disturbancessuchasbloating,diarrhea,etc.Thereasonforthisisthatlactoseisa
disaccharides,whichcannotbeabsorbedthroughthewallofthesmallintestine.
Whenitremainsundigested,itpassesthroughtheGIsystemandcauseslarge
amountofgas,cramps,bloating,etc.Theprocessbywhichlactoseisconvertedto
gaseousproducts(fermentation)willultimatelyraisetheosmoticpressureofthe
colon.


FRUCTOSEMETABOLISMANDDISORDERS
EssentialFructosuriaAdefectoffructokinase,isabenignconditionwherethe
onlysymptomsishighlevelsoffructoseinbloodandurine.
FructoseIntoleranceIsahereditarydeficiencyonaldolaseB.Thereisaresulting
inhibitionofbothglycogenolysisandgluconeogenesisbecausefructose1
phosphateaccumulationdecreasestheamountofavailablephosphate.


GALACTOSEMETABOLISMANDDISORDERS
Therearetwoproblemsthatresultfromtheabsence/deficiencyofenzymes
involvedingalactosemetabolism.
GalaktokinaseDeficiency:Adeficiencyoftheenzymegalaktokinase,preventing
theconversionofgalactosegalactose1phosphate.Causesgalactosemiaand
galactosuria.
Galactosemia:Causedbyauridyltransferasedeficiency.Cancausesymptomssuch
ascataracts,mentalretardation,hepatosplenomegaly,allduetotheaccumulationof
toxicsubstancesthatresultfromthedeficiency.

ETHANOLANDHYPOGLYCEMIA
Whenethanolismetabolized,thereisanincreasedratioofNADH:NAD+,which
causesashuntingofpyruvatetolactateandoxaloacetatetomalate.Thiscausesan
inhibitionofgluconeogenesisandthuscauseshypoglycemia.Becausethereisa
shuntawayfromgluconeogenesisandtowardsfattyacidsynthesis,theliver
developsfattychangesaswell.


THEUREACYCLE
Theureacycleisresponsibleforthedegradationofaminoacidsintoaminogroups.
Thiscycleproducesapproximately90%ofalltheureafoundintheurine.The
locationoftheureacycleisthecytosoloftheliver,withtheincorporationofthe
carbamoylphosphatebeingintegratedinsidethemitochondria.


THECORICYCLE(LACTATETRANSPORT)
Isametabolicpathwaybywhichlactatethatisproducedthroughanaerobic
glycolysisistransportedfromthemuscletotheliverandreconvertedtoglucose.
ThiscycleproducesanetATPof2


THEPENTOSEPHOSPHATEPATHWAY
AlsoknownastheHMPshunt,thispathwayisnecessarytotheproductionofribose
5phosphatefromglucose6phosphateforthesynthesisofnucleotides,the
productionofNADPHfromNADP+forthesynthesisoffattyacidsandsteroids,and
forthemaintenanceofreducedglutathione.Theratelimitingenzymeforthis
pathwayisglucose6phosphatedehydrogenase.

THISPATHWAYIS
NECESSARYTO
PRODUCE
REDUCED
GLUTATHIONE,
WHICHISUSEDTO
DETOXIFYFREE
RADICALS.A
DEFICIENCYWILL
LEADTO
HEMOLYTIC
ANEMIADUETO
LACKOFDEFENCE.


IMPORTANTDERIVATIVESOFAMINOACIDS


AMINOACIDS:ESSENTIALvs.NONESSENTIAL
Aminoacidsarebiochemicalmoleculescontaininganaminegroup,acarboxylicacid
group,andasidechainthatvariesbetweeneachaminoacid.Theycontainnitrogen,
carbon,oxygen,andhydrogen.
BasicStructure:

VITAMINS

Breakdownofvitamincategories:
FatSolubleVitamins:

VitaminD
VitaminE
VitaminK
VitaminA

WaterSolubleVitamins:

VitaminC
VitaminsB1,B2,B3,Biotin,PantothenicAcid
Pyridoxine
FolicAcid
Cobalamin

FATSOLUBLEVITAMINS:
TYPE
VitaminD

FUNCTION
Increasesintestinal
absorptionof
calciumand
phosphate

VitaminE

Actsasan
antioxidant

VitaminK

Involvedinthe
processofblood
clotting
Isnecessaryfor
healthyretinas

VitaminA

DEFICIENCIES
Childrenget
Rickets,adultsget
osteomalacia.
Bothcandevelop
hypocalcemic
tetany
RBCbecomefragile
andareatriskof
hemolysis
Hemorrhagesin
neonates

EXCESSES
Hypercalcemiaand
allassociated
symptomsof
hypercalcemia

Dryskin,night
vision
disturbances,
immunedeficiency

Alopecia,
arthralgia,
headache,skin
conditions

WATERSOLUBLEVITAMINS:
TYPE
VitaminC

VitaminB1(thiamine)

VitaminB2(riboflavin)
VitaminB3(niacin)
VitaminB5
(pantothenate)
VitaminB6(pyridoxine)

Biotin
FolicAcid

Cobalamin

ROLEINHEALTH
Importantincollagen
synthesis(hydroxylation),
Helpswithiron
absorption
Oxidativedecarboxylation
ofalphaketoacids,co
factorfortransketolasein
theHMPshunt
Isacofactorinoxidation
andreductionreactions

DEFICIENCY
Scurvybruising,
bleedinggums,anemia,
poorwoundhealing
BeriberiandKorsakoffs
syndrome,mostcommon
inalcoholics

Chelosis,angular
stomatosis,corneal
vascularization
Usedinredoxreactionsas Pellagra(4ds)diarrhea,
constituentofNAD+and
dementia,dermatitis,
NADP+
death
Involvedinfattyacid
Adrenalinsufficiency,
synthaseandacofactor
dermatitis,enteritis,
foracyltransfers
alopecia
Isacofactorin
Causedisoniazid
transamination,
deficiency(nervous
decarboxylation,and
systemdisturbances)
transsulfuration
Acofactorin
Dermatitisandenteritis,
carboxylationreactions
canbecausedbyeating
raweggs
Coenzymeincarbon
Macrocyticanemia,neural
transferinmethylation
tubedefectsindeveloping
reactions,involvedin
fetus
synthesisofnitrobasesin
DNAandRNA
Isacofactorin
Megaloblasticanemiawith
homocysteinemethylation neurologicalsymptoms,
andmethylmalonylCoA
glossitis
activity

CHAPTER7

ETHICS

Thistopicisimportantasthereareusuallyahandfulof
ethicsquestionsontheexam.Understandingdefinitions
andbeingabletoapplythemtotrickysituationsisessential
forpickingupahandfulofeasypointsontheexam.

BENEFICENCE
Thistermdescribestheresponsibilityofthephysiciantoalwaysactinthebest
interestofthepatient.Beneficencemaynotalwaysbeinplace,asapatientsright
tomaketheirowndecisionsmaynotalwaysbeintheirverybestinterest.Inthis
situation,thephysicianhasadutytohonorthedesiresofthepatientwithrespectto
hisorherowncare.

NONMALEFICENCE
ThistermmeansthephysicianshallDoNoHarm,andisalwayspriority#1when
itcomestomedicalethicsandpracticeprinciples.

AUTONOMY
Autonomyreferstothepatientsrighttomaketheirowndecisionsafterbeing
properlyeducatedandinformed.Whetheraphysicianbelievesthesedecisionsto
berightorwrong,theyhaveadutytorespectandhonorthepatientsautonomy.

APATIENTSABILITYTOMAKEDECISIONS
Apatientsabilitytomaketheirowndecisionsisbasedonafewprinciplesthatmust
beinplace:

Patientmustbepsychologicallystable(ienotskewedbymentalillness)
Patientmustbetheonewhotellsyoutheirdesires,notthefamily
Patientdoesnotswitchbackandforthbetweentheirwishes(shows
instabilityofthepatientsmentation)
Patientreceivescompleteinformationofadvantagesanddisadvantagesof
treatmentoptions
Patientmakestheirchoice,whichisnotinfluencedbyfamily,friends,etc

INFORMEDCONSENT
Informedconsentiswhenapatientgivesthephysiciantheconsenttoproceedwith
medicalmanagement.Itmustbebasedonproperlyinformingthepatient,whereby
theyunderstandtherisks,benefits,andalternativeoptions.Decisionsmustbe
basedoncompleteautonomy,notofpersuasion.


WHENISINFORMEDCONSENTNOTREQUIRED?
Itisfullylegaltoproceedwithmedicalinterventionwithoutapatientsconsent
whenanyofthefollowingarepresent:

Interventionwillbelifesaving,suchasintheER
Patientisnotinamentalstatetomakeadecision(psychosis,intoxication)
Thepatientwaivestheirrighttoinformedconsent
Thereisatherapeuticadvantagetonotgettinginformedconsent

PATIENTSRIGHTTOCONFIDENTIALITY
Apatienthastherighttocompleteconfidentiality,wherebydisclosingapatients
informationisillegalunlesstheygiveyoudirectpermissiontodoso.

WHENISCONFIDENTIALITYBREACHABLE?
Therearecertainsituationsinwhichitisthephysiciansresponsibilitytobreach
confidentialityforthesafetyofsocietyand/orforthegreaterbenefitofthepatient.
Theseinstancesinclude:

Thereisthepotentialforharmtoothers(Tarasoffdecision)
Thepatienthasahighriskofselfharming
Thereisthepresenceofareportableinfectiousdisease
Patientiseithersuicidalorhomicidal
Thereisabusetoachildoranelder

THEADVANCEDDIRECTIVE
Therearenumerouswaysbywhichapatientcangivetheiradvanceddirective.
LivingWillsthepatientinformsthephysicianwhethertheywanttobetreatedor
notshouldtheneedarisewheretheycannotcommunicatethistothephysician
OralAdvancedwhilelesslikelytostandupincourt,thisisanoralrequestgiven
bythepatienttothephysicianinthepastrequestingtheirdesiresformedical
intervention


DURABLEPOWEROFATTORNEY
ThedurablePowerofAttorneyisapersondesignatedbythepatienttomaketheir
medicaldecisionsintheeventthattheyareunabletodosoforthemselves.

NEGLIGENCE/MALPRACTICE
Therearefourcriteriathatmustbemetinorderforamalpracticesuittobe
warranted,theyare:
DutyThisimpliesthatthereisaphysicianpatientrelationshipthatis
established.
DerelictionWhenthephysicianfailstocomplywiththestandardsofcareforthe
patient
DirectCauseWhereapatientincursinjury/damagethatresultedfromthe
physiciansbreachofduty,wheretherearenoothercircumstancesthatmayhave
causedtheinjury
DamagesTheinjuriessufferedbytheclient
**Itshouldbenotedthattheabsolutemostcommonreasonforamedicallawsuitis
alackofcommunicationorpoorcommunicationbetweenthephysicianandpatient.
Establishingastrongphysicianpatientrelationshipisthebestwaytopreventa
lawsuit.

CHAPTER8

BIOSTATISTICS

Applicationofthebiostatisticalequationsaswellasfully
understandingthetypesofstudiesandtypesofbiasis
essentialmustknowinformation.Whileitistemptingto
foregostudyingbiostatistics,itiseasytograbplentyofeasy
pointsbysimplyspendingafewhoursonthistopic.


TYPESOFSTUDIES
CaseControl/ExperimentalThistestisthegoldstandardofepidemiological
testing,wheretwoequalgroupsarecomparedwhereonegrouphasachanged
variable
ProspectiveThisisalsoknownasaCohort,Observational,andIncidencestudy.A
sampleistakenanddividedintotwogroupsbasedonthepresenceorabsenceofa
riskfactor.Thegroupsarethenfollowedovertimetoseewhatshoulddevelop.
Thesetestsareverytimeconsumingandexpensive,thuslessused.
RetrospectiveThisstudychoosesapopulationofsamplesbasedoneitherthe
presenceorabsenceofacertainriskfactor.Thesampleischosenafteradisease
hasoccurred,notbeforeithasoccurred.Thistestischeaperandmuchfasterto
performthantheothers.
CaseSeriesThissimplydescribeswhattheclinicalpresentationlookslikein
peoplewhohaveacertaindisease.
CrossSectional/PrevalenceThisstudytakesasampleofpopulationatonepoint
intime,andlooksattheprevalenceofdiseaseandtheprevalenceofriskfactors.
Thistestisoptimalforcomparingtwodifferentcultures,lookingforassociations
betweenlifestylechoicesandprevalenceofdiseases.

EPIDEMICvs.PANDEMIC
Anepidemicisseenwhenthereisanobservedincidenceofaparticulardiseasethat
greatlyexceedstheexpectedincidence,whereasapandemicisanepidemicthatis
seenoverawidegeographicalarea.

TESTMETHODS
TwoSampleTtestThistestisusedtocomparethemeansoftwogroupsof
subjects.
ANOVAThistestistheanalysisofvariance,andisusedtocomparethreeor
morevariables.
ChiSquaredThistestcomparestheproportionsofacategorizedoutcome(2x2
table).Withalargedifferencebetweentheobservedandexpectedvalues,thereis
assumedtobeanassociationbetweentheexposureandtheoutcome.
MetaAnalysisThistestisdonebypoolingdatafromseveralstudies,whichgives
thetestabigstatisticalpower.

TYPESOFBIAS
SelectionBiasThistypeofbiasresultsfromthemannerbywhichpeopleare
selectedand/orfromselectivelossesfromfollowupstudies.
ObserverandMeasurementBiasThisbiasresultsfromthedistortionof
measurementofassociationbymisclassificationoftheexposed/unexposedand/or
diseased/nondiseasedstudysubjects.
RecallBiasBiasduetoinaccuraciesinrecallofpastexposurebypeopleinthe
study.
HawthorneEffectThisbiasoccurswhenapatientdeliberatelychangestheir
behaviorbecausetheyknowtheyarebeingstudied.
ConfoundingThisbiasoccursasaresultoftheadditionofextraneousfactors.For
exampleifastudyislookingforcirrhosis,theyfindanassociationbetweensmoking
andcirrhosis,andfindtheretobeastrongassociation.Thensubsequently,the
studyshowsthatsomesmokersarealsoheavydrinkerswhilesomearenot.Inthis
instance,alcoholistheconfoundingfactor.Aneffectivewayofcontrolling
confoundingisMatching.
LeadTimeBiasThisbiashastodowiththetimeframebywhichdiagnosesand
treatmentsareexamined.
AdmissionRateBiasThisbiastypeisduetothedifferencesinhospitaladmission
rates,whichdistortstheriskratio.
UnacceptabilityBiasThistypeofbiasoccurswhentheparticipantspurposely
givedesirableresponses,whichthenleadtotheunderestimationofriskfactors.

SENSITIVY,SPECIFICITY,PPV,NPV,OR,RR,andATTRIBUTABLERISK
Thefollowingtablewillbethebasisforallcalculationsrelatingtotheabovetopics:

Sensitivity=a/a+c
Sensitivitydeterminesthe#oftruepositivesdividedbyallthosewhotrulyhavethe
disease.Screeningtestswithhighsensitivityarebest.

Specificity=d/d+b
Specificitydeterminesthe#oftruenegativedividedbyallthosewhotrulydonothave
thedisease.Confirmatorytestswithhighspecificityarebest.

PositivePredictiveValue=a/a+b
ThePPVtestisusedtodeterminetheprobabilityofhavinganactualconditionwhen
thereisapositivetestresult.Relatedtoprevalenceinadirectmanner,thuswithan
increasedprevalencethereisanincreaseinthePPV.

NegativePredictiveValue=d/d+c
TheNPVisusedtodeterminetheprobabilityofnothavingaconditionwhenthetest
resultisnegative.

OddsRatio=(a/b)/(c/d)
TheORdeterminestheincidenceofdiseaseinpeopleintheexposedgroupsdivided
bythoseinanunexposedgroup.
OR>1=Statesthatthefactorbeingstudiedisariskfactorfortheoutcome
OR<1=Statesthatthefactorbeingstudiedisaprotectivefactorinrespecttothe
outcome
OR=1,Statesthatnosignificantdifferenceinoutcomeineitherexposedor
unexposedgroup

RelativeRisk=[a/(a+b)/d/(c+d)]
Relativeriskcomparesthediseaseriskinpeopleexposedtoacertainfactorwith
diseaseriskinpeoplewhohavenotbeenexposed

AttributableRisk=[a/(a+b)d/(c+d)]
Theattributableriskisthenumberofcasesthatcanbeattributedtooneriskfactor

INCIDENCEvs.PREVALENCE
Incidenceisthenumberofnewcasesofadiseaseoveraunittime,whereas
prevalenceisthetotalnumberofcasesofadisease(bothnewandold)atacertain
pointintime.Anydiseasetreatedwiththesolepurposeofprolonginglife(ie
terminalcancers),theincidencestaysthesamebutprevalencewillincrease.
Shorttermdiseases:Incidence>Prevalence
Longtermdiseases:Prevalence>Incidence

VALIDITYvs.RELIABILITY
Validityissimplyatestsabilitytomeasurewhatitclaimstomeasure,whereasthe
reliabilityofatestdeterminesitsabilitytoconsistentresultsonrepeatedattempts.

STANDARDDEVIATION
Standarddeviationisatermthatmeasuresthevariabilityofresults.

1StandardDeviation68%ofresultsfallwithin1SD
2StandardDeviations95%ofresultsfallwithin2SD
3StandardDeviations99.7%ofresultsfallwithin3SD

MEAN,MEDIAN,MODE
MeanTheaveragevalue
MedianThemiddlevalue
ModeThemostcommonvalue

NormalBellCurve:Mean=Median=Mode

Positivelyskewedgraphindicatesthat:Mean>Median>Mode

Negativelyskewedgraphindicatesthat:Mean<Median<Mode

CUTOFFPOINTSFORSENSITIVITYANDSPECIFICITY

Shouldthecutoffpointforadiseasebemovedfromfalsepositivetofalsenegative,
thereisanincreaseinthenumberofpositiveresults.Thiswillincreasethe
sensitivityoftheresults.Thiswillalsoincreasethetruepositiveandfalsepositive
numbers,whiledecreasingthenumberoffalsenegativesanddecreasingthepositive
predictivevalue.
Shouldthecutoffpointberaisedfrombeingfalsenegativetofalsepositive,there
willbeanincreaseinspecificity,increasingthenumberoftruenegativesandfalse
positives.

CONFIDENCEINTERVALANDpVALUE
Thesevaluesstrengthentheresultsofastudy.Forstatisticalsignificance,theCI
mustntcontainthenullvalue(RR=1),andthecloserthetwonumbersare
together,themoreconfidentyoucanbethattheresultsarestatisticallysignificant.
Asfarasthesignificanceofthepvaluegoes,astatisticallysignificantresulthasap
valueof<0.05(thismeansthereis<5%chancethattheresultsobtainedweredue
tochancealone).

CORRELATIONCOEFFICIENT
Twonumbersthatarebetween1and+1,itmeasurestowhatdegreethevariables
arerelated.

Anumberofzero(0)meansthereisnocorrelationbetweenvariables.
Anumberof+1meansthereisaperfectcorrelation(bothvariablesincrease
ordecreaseproportionally)
Anumberof1meansthereisaperfectnegativecorrelation(variablesmove
inoppositedirectionsproportionally)

ATTRIBUTABLERISKPERCENT(ARP)
TheARPmeasurestheimpactoftheparticularriskfactorbeingstudiedona
particularpopulation.Itrepresentsexcessriskthatcanbeexplainedbyexposureto
aparticularriskfactor.
CalculatetheARP:ARP=[(RR1)/RR]

STATISTICALHYPOTHESES
Thestatisticalhypothesesareusedtodeterminewhetherornotthereisan
associationbetweenriskfactorsanddiseaseinapopulation.Theyarethenull
hypothesisandthealternativehypothesis.
NullHypothesis(Ho)Thishypothesisisthehypothesisofnodifference,meaning
thereisnotanassociationbetweenthediseaseandtheriskfactor.
AlternativeHypothesis(H1)Thishypothesisisthehypothesisofsome
difference,meaningthereisanassociationbetweenthediseaseandtheriskfactor.

POWER
Thepowerofastatisticaltestistheprobabilitythatatestwillrejectafalsenull
hypothesis,meaningitwillnotmakeaType2error.Withincreasedsamplesize
thereisincreasedpowerandthereisadecreasedchancesofseeingatype2error.

ERRORS
Type1Error( )Atype1errormistakenlyacceptstheexperimentalhypothesis
andrejectsthenullhypothesis.Thiserrormeansthatsomethingstatisticallyisseen
thatinfactisnotthere.
Type2Error( )Thistypeoferroroccurswhenyoufailtorejectthenull
hypothesiswhenitisinfactfalse.Thiserrormeansyouessentiallysomethingthat
isstatisticallypresentwasinfactmissed.

CHAPTER9

PSYCHIATRY/PSYCHOLOGY

Thequestionsaskedonthistopiccanrangefroma
straightforwardsimplequestiontoaquestionthatexpects
youtocombinemanyaspectsofmedicineinmakingthebest
choice.Thehighestyieldinformationincludespsychiatric
pharmacologyaswellasallofthepersonalitydisorders.

SUBSTANCEDEPENDENCEANDABUSE
Thereisabigdifferencebetweensubstancedependenceandsubstanceabuse.
Substancedependenceisapatternofsubstanceusethatinvolvesatleast3outof7
criteria,theyare:

Therearedecreasedsocial,occupational,orrecreationalactivitiesbecauseof
thesubstanceuse
Patienthasdevelopedtolerancetosubstance
Patientexperienceswithdrawalsymptomswhenrefrainingfromuse
Thereisachronicdesiretocutbackorstopuse
Patientwillspendexcesstimeandenergyintryingtoattaintheirsubstance
Thesubstanceistakeninamountsmuchlargerthanintended
Continuationofusedespitetheknowledgeofitsharmfuleffects

Whenanythreeofthepreviouspointsarepresent,thepatientisdiagnosedwith
substancedependence.
Substanceabuseisapatternofsubstanceusethatcausessignificantsocial
impairmentand/ordistress.Thediagnosisofsubstanceabuseismadewhenthere
areanyofthefollowing:

Excessandrecurrentusethatcausesfailuretofulfillmajorobligationssuch
asgoingtowork,takingcareofkids,etc
Chronicandrecurrentuseofsubstanceinsituationsthatarehazardous
Recurrentproblemswiththelawduetothedrugabuse
Persistentusedespitetheknowledgeofitsdangerouseffects

THEMOSTCOMMONTYPESOFSUBSTANCEABUSE
Therearemanydifferenttypesofdrugs,andtheyallhavedifferentkindsof
signs/symptomsanddifferentdegreesofwithdrawalseverity.Thedrugsand
substancesmostcommonlyusedandabusedinclude:

Alcohol
Amphetamines
BarbituratesandBenzodiazepines
Caffeine
Cocaine
LSD
Marijuana
Nicotine
Opioids(heroin,oxycodone,morphine,etc)

Thefollowingisalistofthemostcommondrugs,theirprimarysigns/symptoms,
andthecommonfindingsofwithdrawal
SUBSTANCE

SIGNSOFINTOXICATION

ALCOHOL

Disinhibition,slurred
speech
Psychomotoragitation,
mydriasis
Sedation,respiratory
depression
Sedation,respiratory
depression(notassevere
asbarbiturates)
Psychomotoragitation,
miosis,paranoya,MI
Visualandauditory
hallucinations
Euphoria,increased
hunger,delayedresponse
time
CNSdepression,miosis,
seizure
Psychomotoragitation,
nystagmus,belligerence

AMPHETAMINES
BARBITURATES
BENZODIAZEPINES
COCAINE
LYTHERGICACID
DIETHYLAMIDE(LSD)
MARIJUANA
OPIOIDS
PHENCYCLIDINE

WITHDRAWAL
SYMPTOMS
Tremor,tachycardia,
seizure,DTs
Depression,lethargy,
excessivesleep
Anxiety,cardiovascular
collapse
Anxiety,seizure,tremor
Fatigue,depression,
excessivesleep
Nowithdrawalsymptoms
Nowithdrawalsymptoms
Nausea,vomiting,GI
disturbances,piloerection
Depression,memoryloss

THEDANGERSOFALCOHOLWITHDRAWAL
Alcoholwithdrawalisapotentiallylifethreateningevent,andrequiresmedical
supervisionandhospitalization.Managementofalcoholwithdrawalinvolves
benzodiazepinesthataretaperedgraduallyoverafewdaysasthesymptoms
resolveandthepatientstabilizes.
Thestagesofalcoholwithdrawalare:
AcuteWithdrawalSyndromeOccursfrom2448hrafterthepatientslastdrink,
symptomsinclude:Tremors,diaphoresis,seizures,hyperreflexia.
AlcoholicHallucinationsOccursfrom2472hrafterpatientslastdrink,
symptomsinclude:Hallucinations(bothauditoryandvisual).
DeleriumTremensOccurs27daysafterpatientslastdrink,symptomsinclude:
Hallucinations,illusions,diaphoresis,tachycardia,hyperthermia.Thisstageof
alcoholwithdrawalcarriesthepossibilityofbeingfatal.

MANAGEMENTOFOPIOIDINTOXICATION
Manydrugsfallunderthecategoryofopioids.Drugssuchasmorphine,heroin,
oxycodone,andmanyothers.Symptomsareverysimilarinthattheycause
sedation,constipation,etc.
Managementofintoxication/overdoseisasfollows:
Naloxone/NaltrexoneThisisamedicationgivenintheERwhenpatientis
suspectedofopioidintoxication,itactsbycompetitivelyinhibitingtheopioid
receptors.
MethadoneAcontroversialdrug,methadoneisusedtomanagepatientswhoare
undergoingheroindetoxificationbecauseitislonglastingandisgoodforlongterm
management.

MAJORDEPRESSIVEDISORDER
Majordepressivedisorderisaseriousconditioncharacterizedbyseveralspecific
signsandsymptoms.Ingeneral,thebesttreatmentforanepisodeofmajor
depressionisanSSRIantidepressantmedication.Ifapatientisexperiencingtheir
firstboutofdepression,itisadvisedtokeepthemontheirmedicationforatleast6
months.Ifitistheirsecondormoreboutofdepression,theyshouldbekepton
theirantidepressantonanongoingbasis.Diagnosisrequiresthatthereare
symptomfreeperiodsofatleasttwomonthsinbetweeneachepisode.
ThediagnosisofdepressionismadewhenanyofthefollowingFIVEarepresentfor
atleastTWOweeks:

SleepDisturbances(patientmaysleeptoolittleortoomuch)
LossofInterest(interestlostinthingsthattheypreviouslyenjoyed)
FeelingofGuilt(theseguiltyfeelingsareusuallyunwarranted)
Energy(lossofenergy,whichresultsinalossofdrivetodootherthingsthey
previouslyenjoyed)
LossofConcentration
AppetiteChanges(mostofthetimethepatienthasaLOSSofappetite,but
theymayalsogetanincreaseinappetite)
PsychomotorRetardation(resultsinslowedmentation,relatedtolossof
concentration)
SuicidalIdeation(alwaysinquireaboutsuicide,itisnotgoingtoincrease
thepatientsriskofcommittingsuicide)

Thepopularmnemonicforfactorsofdepressionis:SIGECAPS.Females>Males

*FordepressionthatisnthelpedwithSSRIorotherantidepressants,ECT
shouldbetried.ECTisalsothemanagementofchoiceformajordepressionina
pregnantpatient.
SUICIDE
Suicideisabigconcernindepressedpatients,andanypatientwhoseemstohavea
depressedmoodshouldbeaskedaboutsuicide.Itisimportanttoaskiftheyhave
thoughtaboutit,iftheyhavethoughtofhowtheywoulddoit,andiftheyhavea
plan.Itishighlyimportanttoinquireaboutthis,asaskingWILLNOTincreasethe
riskofthemkillingthemselves.
Womenattemptsuicidemoreoftenthanmen,howevermenaremorelikelyto
succeed.Thereasonforthisisbecausewomenoftenuselessviolentmeasuressuch
aspills,whilementakemoreviolentmeasuressuchasgunsandhanging.
Riskfactorsforsuicide:

Priorattempts
Presenceofplan/lethalityofplan(gunvs.pills,etc)
Currentmedicalillness
Alcoholordrugdependence
Currentlytakingthreeormoreprescriptiondrugs
Lackofasocialcircle(fewfriends,nofamily,nospouse)

DYSTHYMIA
Dysthymiaisachronicmooddisorderthatissimilartodepression,howeveritisan
ongoing,lessseveretypeofdepression.Ithasfewersymptomsthanmajor
depression,butismuchlongerlasting.Atleast75%ofthosewithdysthymiahavea
comorbidpsychiatricdisordersuchasanxiety,alcoholism,etc.

DELERIUMvs.DEMENTIA
Thesearetwotermsoftenconfusedinmedicine,andespeciallyontheUSMLE
exams.
Deleriumisastateofdecreasedattentionspan,hallucinationsandillusions,and
cognitivedysfunctions.Thekeytomakingthediagnosisofdeliriumisthatlevelsof
functionalitygoinandout(waxingandwaning),andhasanacuteonset.Onthe
otherhand,dementiaisadiseasewithmultiplecognitivedefectsthatdevelop
slowlyovertime.Thekeytodiagnosingdementiaisthatthepatientisfully
consciousbuthascognitivedefects.


BIPOLARDISORDER
Bipolardisorderisamooddisorderwhereapatientexperiencesbothmaniaand
depression.Therearetwotypesofbipolardisorder(types1and2),wheretype1is
maniaandtype2ishypomania.Regardlessoftype,inordertomakeadiagnosisof
amanicepisodethepatientmusthavecertainsymptomspresentforatleast1
WEEK.
Thecriteriaforamanicepisodeare:

Easydistractibility
Insomnia(thepatientcangofordayswithoutsleeping)
Grandiosity(thepatienthasanunusuallyexaggeratedsenseofselfesteem)
FlightofIdeas
Increasedactivity(patientwilldonumerousactivitiesinoneday)
Pressuredspeech(fast,nonsensical,etc)
Thoughtlessness(patientwilldothingswithoutfullythinkingaboutwhat
theyaredoingfirst)

Atleast3ofthesemustbepresenttomakeadiagnosisofamanicepisode.
Maniacausesseveresocialimpairmentandoccupationaldysfunction.Hypomaniais
similartoamanicepisodeexceptthereisnoimpairmenttothepatientinanyof
theirdaytodayfunctioning.
ThedrugofchoiceforBipolardisordermanagementisLITHIUM.

PERSONALITYDISORDERS
Thesearepervasive,fixed,andinappropriatepatternsofrelatingtoothers,causing
socialandoccupationalimpairment.Patientswithpersonalitydisordersdonot
seekhelpfortheirdisorderbecausetheyarenotawarethattheyarethecauseof
theirownproblems.
Therearethreecategoriesofpersonalitydisorders:ClusterA,ClusterB,ClusterC
ClusterAdisorders:Paranoid,Schizoid,Schizotypal
ClusterBdisorders:Histrionic,Narcissistic,Antisocial,Borderline
ClusterCdisorders:Avoidant,ObsessiveCompulsive,Dependent,Passive
Aggressive

CLUSTERAPERSONALITYDISORDERS
ParanoidThispatientdoesnottrustothers,issuspiciousofeverything,and
believesalloftheirproblemsarecausedbyothers.
SchizoidThispatientwillhavealonghistoryofvoluntarilyavoidingsocial
situations.Thereisnopsychosisassociatedwiththeschizoidpersonalitydisorder.
SchizotypalThispatienthasanodd/peculiarappearance,hasmagicalthoughts
andanoddpatternofbehavior.Thereisnopscyhosiswiththeschizotypal
personalitydisorder.

CLUSTERBPERSONALITYDISORDERS
HistrionicThispatientisanextrovert,issexuallyprovocative,andveryemotional.
NarcissisticThispatienthasasenseofentitlementandlacksempathyforothers.
AntisocialThispatientrefusestoaccepttherulesofsociety,showsnoconcernfor
theirownactions,andshowsnoremorseforbadbehavior.Thisdisorderis
associatedwithconductdisorderinchildhood.
BorderlineThispatienthaserraticbehavior,impulsiveness,andminipsychotic
episodes.Lookforselfmutilationandothermooddisorders.

CLUSTERCPERSONALITYDISORDERS
AvoidantThispatientissensitivetorejectionandtimid,thussociallywithdrawn.
Theyalsofeelinferiortoothersfornoapparentreason.
ObsessiveCompulsiveThispatientisaperfectionist,orderly,stubborn,and
indecisive.Thisisnotthesameasobsessivecompulsivedisorder(OCD).
DependentThispatientallowsandwantsotherstomakedecisionsforthem,
relatedtoalackofselfconfidence.
PassiveAggressiveThispatienthasoutwardcompliancewithinnerdefiance.


ANXIETYDISORDERS
Anxietydisordersarecharacterizedbysubjectiveandphysicalmanifestationsof
fear.Thesymptomsaresimilar:Tremor,Palpitations,Diaphoresis,Dizziness,GI
disturbances,Urinarysymptoms.

Thecommonanxietydisordersare:

PanicDisorder
Phobias
ObsessiveCompulsiveDisorder(OCD)
GeneralizedAnxietyDisorder
PosttraumaticStressDisorder(PTSD)

PanicDisorderPanicattacksthatoccurapproximatelytwiceperweek,last
approximately30minutes,andpresentwithsymptomssimilartoanMI.Patients
oftenhaveafearofanotherattackinbetweeneachepisode.Managementofpanic
disorderisSSRIs,withpossiblebenzodiazepinesforacutetreatment.
PhobiasSpecificphobiasanirrationalfearofspecificobjects,suchasspiders,
snakes,etc.Asocialphobiaisanexaggeratedfearofsocialorenvironmental
situations(themostcommonsocialphobiaispublicspeaking).Managementis
desensitization,canusebetablockersforshorttermcontrolofautonomic
symptoms.
ObsessiveCompulsiveDisorder(OCD)Patientexperiencesrecurringintrusive
feelings,thoughts,andimageswhichcauseanxietythatisrelievedinpartby
performingrepetitiveactions(compulsions).Patientsrealizethattheiractionsare
irrationalanddesiretobehelped.SSRIsaremainstayofmanagement.
GeneralizedAnxietyDisorderPatientexperiencespersistentsymptomsof
anxietyforatleast6months.Thesymptomsareunrelatedtoanyspecificpersonor
situation.Seeninwomen>men.
PostTraumaticStressDisorderIsaconditionthataffectssomeonewhohasbeen
throughacatastrophicevent(classicallyawarveteran).Thepatientexperiences
hyperarousal(anxiety,sleeplessness,intrusivememories)andwithdrawal
(flattenedaffect,numbing,survivorsguilt).Thesesymptomsmustbepresentfor
atleast1monthforadiagnosisofPTSD,ifsymptomsarelessthan1month,the
diagnosisisAcuteStressDisorder(ASD).

SCHIZOPHRENIA
Schizophreniaischaracterizedbyperiodsofpsychoticfeaturesanddisturbing
behaviorthatlastsaminimumof6months.
Typesofschizophreniainclude:

Paranoid
Disorganized
Catatonic
Undifferentiated
Residual

Patientsexperience:

Hallucinations(auditory,visual)
Uncertainty
Bluntedaffect
Looseassociations

Positivesymptoms(thingsthatareadded)include:

Hallucinations
Delusions
Behavioralchanges
Looseassociations

Negativesymptoms(thingsthatareremovedfromtheperson)include:

Affect
Motivation
Appropriatethoughtpatterns
Sociallywithdrawn


SOMATOFORM,FACTITIOUS,ANDMALINGERINGDISORDERS

SomatoformDisorders
Somatoformdisordersarecharacterizedbyphysicalsymptomswithoutanyorganic
cause.Thosewiththisconditionarenotmalingering,arenotdelusional,andtruly
believetheyhaveaphysicalproblem.
SomatoformDisordersinclude:

Somatizationdisorder
Conversiondisorder
Hypochondriasis
BodyDysmorphicdisorder
Paindisorder
UndifferentiatedSomatoformdisorder

SomatizationDisorderPatientwithhistoryofmultiplesomaticcomplaintsover
severalyears,theymustinclude:4painsymptoms,2GIsymptoms,1sexual
symptom,and1pseudoneurologicsymptom.
ConversionDisorderPatientexperiencesanabrupt,dramaticlossofmotoror
sensoryfunction.Mostcommonlythepatientexperiencesparalysis,seizures,
paresthesias,anesthesias,andvisualproblems.
HypochondriasisThesepatientshaveanexaggeratedconcernthattheyhave
illnessesdespitebeingtoldrepeatedlythatthereisnocauseforconcern.Must
occurforatleasta6monthperiodforthisdiagnosis.
BodyDysmorphicDisorderThepatienthasanexcessiveandpossiblyobsessive
focusonaminororpossiblyimaginedphysicaldefect.
PainDisorderPainthatisnotexplainedbyanyphysicalproblem,oftencoexists
withanothermedicalproblem.Iflasting<6months,itisanacutepaindisorder,if
lasting>6monthsitisachronicpaindisorder.
UndifferentiatedSomatoformDisorderThisisthediagnosiswhenthepersistent
physicalsymptomsdontmeetcriteriaforanyoftheotherdisorders.Themost
commonproblemsfallingunderthisumbrellaare:Fatigue,GI/GUsymptoms,
appetitechanges.

FactitiousDisorders
Apatientwithfactitiousdisorderconsciouslycreatestheirsymptomsinorderto
assumetheroleofthesickpatientsotheycangetmedicalattention(themotivation
howeverisunconscious).Therearetwocategoriesoffactitiousdisorder,theyare:
MunchausensSyndromeandMunchausensSyndromebyProxy.
MunchausensSyndromePatientwillhaveachronichistoryofmultiplehospital
admissions,aswellasahistoryofwillingnesstoreceiveinvasiveprocedures,even
whennotwarranted.
MunchausensbyProxyThisiswhenachildisillbecauseoftheparent.

MalingeringDisorders
Patientswithmalingeringdisorderconsciouslysimulateorexaggerateaphysicalor
mentalillnessforanobviousgain(Money,Care,Avoidanceofwork).Thispatient
willavoidtreatment,asopposedtothosewithfactitiousdisorder.Oncethepatient
receivesthegaintheyareseeking,thesymptomswillresolve.

SLEEP
Understandingwavepatternsandactivitiesduringeachstageofsleepareimportant
aspectsofunderstandingthesleepcycle.
AwakewitheyesopenBetawaves,serotoninstimulatestherapenucleitoinduce
sleep
AwakewitheyesclosedAlphawaves
Stage1Thisisthestageoflightsleep.Thisstageisshort,lastingapproximately
5%ofallsleeptime,Thetawavesarepredominant.
Stage2Thisisdeepersleep,lastingapproximately45%ofallsleeptime.
PredominantlyseesleepspindlesandKcomplexes.
Stage3Thisisthedeepestsleep,butisnonREM.Lastsapproximately25%ofall
sleeptime,andischaracterizedbyDeltawaves.*Thisisthestageatwhichchildren
willexperienceenuresisandbedwetting.
Stage4ThisisREMsleep.Thepatientwillbedreamingandloseallmuscletone.
TherearepredominantlyBetawavesduringtheREMsleepcycle.


AMNESIA
Amnesiacanoccurformanyreasons,includinganesthesia,druguse,oldage,head
injuries,alcoholism,etc.Thetwoformsofamnesiaare:Anterogradeand
Retrograde.
AnterogradeThispersonwillbeunabletorememberanythingafteroccurring
aftertheincidentthatcausedtheiramnesia,thereforetheycannotformanynew
memories.
RetrogradeThispersonwillbeunabletorememberthingsthatoccurredbefore
thecausativefactoroftheiramnesia.

SLEEPAPNEA
Sleepapneaisaseriousconditionwhereapersonhasperiodsofcessationof
breathingwhileasleep.Thismaylastfromafewsecondstominutes,andmayoccur
upto30timesperhour.ThetwotypesofsleepapneaareCentraland
Obstructive.
Centralsleepapneathistypeofapneaoccursduetoalackofrespiratorydrive
fromtheCNS.
Obstructivesleepapneathistypeofapneaisusuallycausedbyexcessiveweight,
whichcausesobstructionandphysicalblockageofbreathing.Managementis
weightlossandCPAPmachine.Ifthesefailsurgerymayberequired.
Inobstructivesleepapnea,apatientwilloftencomplainofexcessivedaytime
sleepiness,andthespousewillcomplainofveryloudsnoring.

NARCOLEPSY
Aconditionwheresomeonefallsasleepsuddenlywithoutwarning,andmay
experiencecataplexy(suddencollapsewhiletheyarestillawake).Theyfallinto
REMsleepuponfallingasleep.Managethesepatientsfirstwithscheduleddaytime
naps,andifthatdoesntworkuseastimulantsuchasmethylphenidate.


EATINGDISORDERS
Thetwocommoneatingdisordersareanorexianervosaandbulimianervosa.
AnorexiaNervosaThisisadangerousdiseasewherepatientsdietexcessivelyin
anattempttoloseweightandstayskinny.Theyhaveadistortiontotheirbody
image,whichisadrivingforcebehindtheexcessivedieting.Commonadverse
effectsthatoccurinclude:Amenorrhea,Electrolytedisturbances,andseverecases
canresultincardiacetiologies.Managementisweightgainandifpatientsweight
istoolow,hospitalizationmayberequired.ABMIoflessthan19isworrisomeof
anorexia.
BulimiaNervosaThesepatientshaveanormalbodyweight,withthemain
problembeingovereating(bingeing)andthenpurging(laxatives,vomiting,etc).
Commonfindingsincludeenlargedparotidglands,enamelerosion,bruisedfingers
(fromstickingtheminthemouth),esophagealvaricescausedbythepressureof
vomiting.

STRUCTURALTHEORYOFTHEMIND
ThisisaconceptdevelopedbyFreud,anditdescribesthethreetheoriesthat
encompassthehumanmind.Thesethreetheoriesarethe:Id,Superego,andEgo.
Thesestructureshavedifferentfunctions,theyare:
IdTheIdisresponsibleforsexualurges,aggression,andotherprimalurges.
SuperegoThesuperegoencompassesthepartofyourmindthattellsyouto
controlyourprimalurges,itactsasyourconscience.
EgoTheegoisthetheorythathelpstheminddealwiththeconflictbetweenthe
wantsoftheId,andtheconscienceofthesuperego.

TYPESOFCONDITIONING
ThetwotypesofconditioningwemustknowfortheUSMLEareClassical
ConditioningandOperantConditioning.
ClassicConditioningThisisatypeofconditioningthatelicitsaresponsebecause
thestimulusispairedwiththeunconditionedstimulus.Theclassicexampleis
Pavlovsdog,wholearnedtolinkthesoundofabellwithatreat,thuseachtimethe
bellrangthedogwouldsalivateasaresultofthisconditioning.

OperantConditioningThisisatypeofconditioningthatoccursbecausetherewas
arewardgivenforperformingacertainact.Thetwotypesofoperantconditioning
arePositiveReinforcementandNegativeReinforcement.
PositiveReinforcementArewardproducesanaction
NegativeReinforcementRemovinganegativestimuluswillelicitaction

DEVELOPMENTALMILESTONESININFANTS
Age
Newborn
2months
4months
6months

GrossMotor
FineMotor
Mororeflex,
graspreflex
Holdsheadup Swipesat
objects
Rollsfrontto Grasps
back
Objects
Rollsfrom
Transfers
backtofront, objects
sitsupright

9months

Crawls,pulls
toastand

12months

Standson
own

15months
18months
24months

36months

Pincergrasp,
eatswith
fingers
Mature
pincergrasp

Language

Social/Cognition

Coos

Socialsmile

Orientsto
voice
Babbles

Laughs

Nonspecific
words

Specific
words
mama
Walks
Usesacup
Speaks46
words
Throwsaball, Usesspoon
Names
walksupthe forsolidfoods common
stairs
objects
Starts
Usesspoon
Speaks2
running,can forsemi
word
goupand
solids
sentence
downstairs
Canridea
Caneatneatly Speaks3
tricycle
withutensils word
sentence

Develops
stranger
anxiety,sleeps
allnight
Wavesgoodbye,
respondstoname
Recognizes
picturesina
book/magazine
Throwstemper
tantrum
Beginstoilet
training
Canfollowa2
stepcommand
Knowsfirstand
lastnames

PUBERTALCHANGES
MALES
Testicularenlargement11.5yrs
Genitalsincreaseinsize
PubicHairGrowthBegins
PeakGrowthSpurt13.5yrs

FEMALES
Breastbuds10.5yrs
PubicHairGrowthBegins
LinearGrowthSpurt12yrs
Menarche12.5yrs

REFLEXESPRESENTATBIRTH
REFLEX
MOROREFLEX

STARTS

ENDS

CHARACTERISTICS

Birth

~2months

WALKING
REFLEX

Birth

~6weeks

ROOTINGREFLEX

Birth

~4months

TONICNECK
REFLEX

1month

4months

PALMARGRASP
REFLEX

Birth

~6months

GALANTREFLEX

Birth

~6months

BABKINREFLEX

Birth

~1year

Suddenshiftin
positionscausesthe
legsandheadtoextend
whilethearmsjerkup
andoutwiththepalms
upandthethumbs
flexed.Thenthearms
arebroughttogether
andhandsareclenched
intofists
Whenthesoleis
touched,thelegswill
moveinawalking
motion,thoughthe
babycannotwalk
Infantturnsthehead
towardthesidewhere
thecheekgetsstroked
Whenchildsheadis
turnedtooneside,the
armofthesameside
willstraightenandthe
oppositearmwillflex
Anythinginthehandor
strokingthehandofthe
babywillcauseathe
fingerstobendandthe
handtograspatthe
object
Strokingskinonsideof
backcausesbodyto
swingtothatside
Morecommonin
prematureinfants,
pressuretopalmscause
varyingresponses.


THESTAGESOFDEALINGWITHDEATH
ThereareFIVEstagesofdealingwithdeath,theycanberememberedwiththe
mnemonicDABDA.

Denial,Anger,Bargaining,Depression,Acceptance

CHANGESSEENINTHEELDERLY
Thereareafewchangesthatoccurwithadvancedagethatareseenalmost
uniformlyacrossthegeriatricpopulation,theyinclude:

Changeinsleeppatterns,namelylessneedforsleep,decreasedREMsleep,
morefrequentawakeningthroughoutthenight.
Sexualchangessuchaslongerrefractoryperiod,delayedejaculation,slower
onsetoferection(inmen).Femalesfrequentlyexperiencethinningand
drynessofthevagina.
Medicalconditionssuchasdegenerativediseasesarequitecommon

CHAPTER10

IMMUNOLOGY

Asubcategoryofmicrobiology,immunologyisveryhigh
yield.Thereareimportantconceptsyoumustknow,andall
oftheimmunologicdisordersarefairgameontheStep1
exam.

IMMUNOLOGY

PASSIVEvs.ACTIVEIMMUNITY
PassiveImmunityThisformofimmunityoccurswhenthereisatransferof
activehumoralimmunityintheformofpreformedanitbodiesfromonehostto
another.Thisformofimmunizationisusedwhenthereisariskofinfectionandnot
enoughtimeforthebodytodevelopanampleimmuneresponse.Thisprovidesfast
butshortlivedprotection.
Examples:MaternalIgspassedtobaby,patientgivenrabiesvaccinewhenbittenby
abat.
ActiveImmunityThisformofimmunitydevelopsthroughitsownproductionof
antibodiesinresponsetoexposuretoanantigen,pathogen,orvaccine.Thisgives
theorganismslowonsetbutlongtermprotection.

THECOMLEMENTPATHWAY
Designedtoprotectagainstgramnegativebacteria,isactivatedbyimmunoglobulin
GorMintheclassicpathway,andactivatedbysurfacemicrobesinthealternate
pathway.

FUNCTIONOFTHECOMPLEMENTFACTORS:
C1,C2,C3,C4Neutralizationofviralparticles
C3bOpsonization
C3a,C5aAnaphylaxis
C5aNeutrophilChemotaxis
C5bC9MACcytolysis

DEFICIENCIESOFTHECOMPLEMENTPATHWAY:
C1EsteraseInhibitordeficiencygetoveractivecomplementpathwayandthis
leadstohereditaryangioedema
C3deficiencyrespiratorytractinfections+recurrentpyogenicinfections
C6C8deficiencycausesNeisseriabacteremia
DecayAcceleratingFactordeficiencycausesparoxysmalnocturnaldyspnea

THEMAJORHISTOCOMPATIBILITYCOMPLEX(MHC)
TheMHCisgenomicregionfoundinvertebratesthatencodesMHCmolecules,and
thesemoleculesplayaveryimportantroleinimmunefunction.Therearetwotypes
ofMHC(ieMHC1andMHC2).
TheMHCIContains1polypeptide+a2microglobulin,andcontains3genes
(geneA,B,andC).

TheMHCIIContains2polypeptides,andanalphaandabetachain.Has3genes
(DP,DQ,andDR).ThisMHCIIisthemaincomponentinorganrejection.

ANTIBODYFUNCTIONS

FUNCTIONOFTHEANTIBODY
Thevariableparts(VH,VL)willrecognizedifferentantigens,whiletheconstant
parts(C)willfixthecomplement.
FcFragmentThisfragmentisconstant,hasacarbohydratesidechain,is
complementbinding(IgGandIgMonly),andhasacarboxyterminal.
Antibodyaidsin:
1. Complementactivationviathemembraneattackcomplex
2. Opsonization(ieaidsinphagocytosis)
3. Neutralization(bypreventingtheadherenceofbacteria)

SUBTYPESOFIMMUNOGLOBULINS
UsethemnemonicGAMEDtorememberandkeepalloftheimmunoglobulin
informationorganized.
ImmunoglobulinG(IgG):

Isthemostabundantofalltheimmunoglobulins
Isthemainantibodyresponsibleforthesecondaryantibodyresponse
OnlyIgthatcancrosstheplacenta
Fixescomplement,opsonizesbacteria,andneutralizestoxins

ImmunoglobulinA(IgA):

Foundinbodilysecretions
Preventsbacterialattachmenttomucousmembranes

ImmunoglobulinM(IgM):

Responsiblefortheprimaryantibodyresponse
IstheantigenreceptoronBcellsurfaces

ImmunoglobulinE(IgE):

HasthelowestconcentrationofallIgs
Responsibleforprotectionagainstworms
Responsibleformastcellandbasophilgranulereleaseintype1
hypersensitivities

ImmunoglobulinD(IgD):

FoundonBcellsurfaces

ANTIBODYPRODUCTION


TCELLACTIVATION
ThefollowingstepsarerequiredforhelperTcellactivation:
1. Theantigenpresentingcellengulfstheviralparticle
2. TheviralparticleisthenpresentedonthesurfaceoftheMHCIIandisthen
recognizedbytheTcellreceptoronthesurfaceofthehelperTcell
3. AcostimulatorysignalismadewhentheB7ontheAPCandtheCD28on
thehelperTcellbind.
4. Thecombinationof#2and#3causethesecretionofIL2andIFN

AfterthehelperTcellisactivated,thenextstepistheactivationofthecytotoxicT
cell,thesestepsare:
1. IL2fromthehelperTcellconnectswiththecytotoxicTcell,thusactivating
ittodestroytheinfectedcell.
2. ProteinspresentedontheMHCI(ieviralrecognition)attractsthecytotoxic
Tcell,getsrecognized,andiskilled
Thefollowingdemonstratesthesestepsvisually


DIFFERENTIATION/PRODUCTIONOFTANDBCELLS

CELLMEDIATEDIMMUNITY(T
CELLS)
TCELLS
Allergies
GraftRejection
Antibodyresponse
DefenseagainstFungi,
Mycobacterium,TB,andvirus
infectedcells.

ANTIBODYMEDIATEDIMMUNITY

BCELLS

Allergies

Autoimmunity

DefenseagainstBacteria,Toxins,
andViruses


CYTOKINEFUNCTION
Thereisagreatmnemonicthatcanhelpyourememberthefirstfivecytokines,itis:
HotTbonestEAk
IL1Hot=FEVER
IL2stimulationofTcells
IL3stimulationofBONEmarrow
IL4IgEproductionstimulation
IL5IgAproductionstimulation

Nowtherestofthecytokinesareresponsibleforthefollowing:
IL8PMNchemotacticfactor
TNFIncreasesIL2receptorsynthesisbyhelperTcells,increasesBcell
proliferation,andattractsandstimulatesPMNs.Thisissecretedbymacrophages.
TNFThisissecretedbyactivatedTlymphocytes,andperformsthesame
functionsastheTNF
InterferonStimulatesmacrophages,secretedbyhelperTcells

INTERFERONS
Interferonsplayanessentialroleinpreventingtheproliferationandproductionofa
virusbyactingincertainwaystopreventitfrominfectingothercells.
Thethreemajorfunctionsoftheinterferonsare:
1. Activationofnaturalkiller(NK)cellswhichactbydirectlykillingvirus
infectedcells.
2. andinterferonactbyinhibitionofviralproteinsynthesis
3. InterferonworksbyincreasingtheexpressionoftheMHCIandMHCIIas
wellasantigenpresentationinallcells
BigpictureMOAofinterferons:
InterferonsstimulatetheproductionofaproteinthatdegradesviralmRNA.
Whenthisoccurs,theviruscannotinfectacellsincethepropergeneticmaterialsfor
thisfunctionareabsent.

TRANSPLANTREJECTION
GraftvsHostRejection:
OccurswhenthegraftedTcellsproliferateandrejectthehostcellsthatcontain
foreignproteins.Asthisoccurs,severeorgandysfunctionensues,causingdamage
totheliver,skin,mucosa,andgastrointestinaltract.Thisconditionalsoaffectsthe
bonemarrowandthelungs.
HyperacuteRejection:
Occursalmostimmediatelyaftertransplant,wherebypreformedantidonor
antibodiescausearesponse.
AcuteRejection:
ThisisacellmediatedreactionthatoccursviacytotoxicTlymphocytesthatreact
againstforeignMHCs,occurringweeksposttransplant.
ChronicRejection:
Occurringmonthsyearsposttransplant,iscausedbyantibodymediatedvascular
damage.


TYPESOFHYPERSENSITIVITYREACTIONS

TYPE1HYPERSENSITIVITY:Anaphylactic/Atopic
Averyrapidreactionthatoccursinresponsetoantigen
exposure.Antigenstriggerthereleaseofhistamineby
bindingtobasophilsandmastcells.

REMEMBERINGTHE
HYPERSENSITIVITIES:
Mnemonic:ACID
AAnaphylaxis

ExamplesHives,asthma,anaphylaxis

CCytotoxic
IImmuneComplex

TYPE2HYPERSENSITIVITY:Cytotoxic

DDelayed

IsacytotoxicreactionwherebyIgMand/orIgGbindto
cellsleadingtolysisbycomplementactivationorphagocytosis.
ExamplesAutoimmunehemolyticanemia,Goodpasturesdisease,rheumatic
fever,Rhdisease,Gravesdisease.

TYPE3HYPERSENSITIVITY:AntigenAntibodyMediated
Theformationofantigenantibodycomplexesleadstocomplementactivation,
attractingPMNsandultimatelyleadingtothereleaseoflysosomalenzymes.
ExamplesGlomerulonephritis,Lupus,RheumatoidArthritis

TYPE4HYPERSENSITIVITY:CellMediated
Isadelayedresponse,wherebyTcellsbecomesensitizedandencounterantigens,
thusreleasingcytokines.
ExamplesContactDermatitis,TransplantRejections,TBSkinTest


DISEASECAUSEDBYIMMUNEDEFICIENCIES

BCELLDEFICIENCIES

TCELLDEFICIENCIES

BRUTONS
AGAMMAGLOBULINEMIA

THYMICAPLASIA
(DiGeorge)

SELECTIVE
IMMUNOGLOBULIN
DEFICIENCY

CHRONIC
MUCOCUTANEOUS
CANDIDIASIS

BANDTCELL
DEFICIENCIES

SCID

WISKOTT
ALDRICH

PHAGOCYTICDEFICIENCIES

CHRONICGRANULOMATOUS
DISEASE

CHEDIAKHIGASHI

JOBSSYNDROME

LEUKOCYTEADHESION
DEFICIENCY

HYPERIgMSYNDROME

IL12RECEPTORDEFICIENCY

ATAXIA
TELANGIECTASIA

BCELLDEFICIENCIES

BRUTONSAGAMMAGLOBULINEMIA:
Anxlinkedrecessivedefectintyrosinekinasegene.resultsin:

AllIgclassesaredecreased
Getrecurrentbacterialinfections(after6monthsofage)
Onlyinboys

SELECTIVEIMMUNOGLOBULINDEFICIENCY:
AdeficiencyofaspecificIgclassresultingindefectIisotypeswitching,resultsin:

Sinusinfection
Lunginfections
MostcommonlythedeficientIgisIgA

TCELLDEFICIENCIES:

THYMICAPLASIA:
Thereisafailureofthedevelopmentinthethymusandparathyroids,duetofailure
ofdevelopmentofthe3rdand4thpharyngealpouch,resultsin:

Tetany
Viralandfungalinfections(recurrent)
Heartdefects

CHRONICMUCOCUTANEOUSCANDIDIASIS:
ATcelldysfunctionagainstCandida,resultsin:

Candidalinfectionsoftheskinandmucousmembranes

BANDTCELLDEFICIENCIES
SEVERECOMBINEDIMMUNODEFICIENCY(SCID):
Thisconditionleadstoadefectindifferentiationoftheearlystemcells,resultsin:

Recurrentinfections(viral,bacterial,fungal,andprotozoal)

WISKOTTALDRICHSYNDROME:
IsanxlinkeddefectintheabilitytomountanIgMresponsetothecapsular
polysaccharidesofbacteria,resultsin:

LowIgMlevels
HighIgAlevels
NormalIgElevels
Classictriadofsymptoms:Infections,Eczema,andThrombocytopenic
Purpura.

PHAGOCYTICDEFICIENCIES
CHRONICGRANULOMATOUSDISEASE:
AlackofNADPHleadstoadefectinneutrophilphagocytosis,resultsin:

Succeptibilitytoopportuniticbacterialinfections
Diagnosisbasedonnegativenitrobluetetrazoliumdyereductiontest
(CLASSICUSMLEQUESTION)

CHEDIAKHIGASHIDISEASE:
Adefectinmicrotubularfunctionandlysosomalemptyingofthephagocyticcells,
resultsin:

Recurrentpyogenicinfectionsduetostaphandstrep

JOBSSYNDROME:
Tcellsfailtoproduceinterferon,thusPMNsfailtorespond,resultsin:

Eczema,staphabscesses,andelevatedIgE


LEUKOCYTEADHESIONDEFICIENCYSYNDROME:
ThereisadefectintheLFA1adhesionproteinsonthephagocytes,resultsinsevere
earlylifepyogenicinfections.

HYPERIgMSYNDROME:
ThereisadefectintheCD40ligandontheCD4Thcells,leadingtoseverepyogenic
infectionsearlyinlife,resultsin:

HighIgMlevels
ExtremelylowlevelsofIgG,IgA,andIgE

IL12RECEPTORDEFICIENCY:
AdefectintheIL12receptorleadstodisseminatedmycobacterialinfections.

CHAPTER11

MICROBIOLOGY

Historically,bacteriologyoccupiesthemajorityofthe
microbiologyquestionsontheStep1exam.Afterbacteria,
virologyisveryimportant,bothconceptuallyandindetail.
PayveryspecialattentiontoHIVandallthatitentails,as
thisisoneofthehighestyieldingtopicsontheexam.When
itcomestoparasitesandhelminths,yourstrategyshouldbe
memorizationofmodesoftransmission,signsand
symptoms,andtreatments.

BACTERIOLOGY

THEGRAMPOSITIVEBREAKDOWN

GRAMPOSITIVECELLWALLSTRUCTURE

PEPTIDOGLYCANProvidessupportandprotectsagainstosmoticpressures.
CAPSULEProtectstheorganismfromphagocytosis.
FLAGELLUMHelpspropeltheorganism.
PILUSUsedforadheringtoacellssurfaceandformsanattachmentbetweentwo
backteriaforsex.
PLASMIDSContaingenesforenzymes,toxins,andforthedevelopmentof
antiboticresistance.
GLYCOCALYXHelpsmediateadherencetosurfaces.

THEGRAMNEGATIVEBREAKDOWN

GRAMNEGATIVECELLWALLSTRUCTURE

**Uniquetothegramvebacteria,theendotoxincontainslipopolysaccharide
thatinducesTNFandIL1.


HIGHYIELDGRAMSTAINRESULTS
GRAMSTAINRESULTS
Redcolored
Bluecolored
Gram+cocciinchains
Gram+cocciinclusters
Gram+cocciinpairs(akadiplococci)
GramRods(akacoccobacilli)
GramDiplococci
GramRodswithmucoidcapsule
SporeformingGram+Rods
Presenceofpseudohyphae
AcidFastStain
SilverStaining
IndiaInk(positive)
Gram+withpresenceofsulfur
granules
Spirochetes

ORGANISM
Gramve
Gram+ve
Streptococci
Staphylococcus
StreptococcusPneumonia
HemophilusSpecies
NeisseriaSpecies
KlebsiellaSpecies
BacillusspeciesandClostridium
Species
CandidaSpecies
MycobacteriumandNocardiaSpecies
PneumocystisCarinii
CryptococcusNeoformans
ActinomycesSpecies
Treponema,Leptospira,andBorrelia
Species

THECAUSESOFFOODPOISONING
Custard,potatosalad,mayonnaiseS.Aureus(fastonset,fastalleviation)
ReheatedriceBacillusCereus
ReheatedmeatClostridiumPerfringens
SeafoodVibrioParahemolyticus
ImproperlycannedfoodsClostridiumBotulinum(watchforbulgingcantops)
UndercookedmeatE.Coli0157:H7
RaweggsSalmonella
PoultrySalmonella


EXOTOXINS
Exotoxinscausedamagetothehostbydestroyingcellsordisruptingtheircellular
metabolism.Theymayeitherbesecretedorreleasedduringcelllysis.Mostoften
theycanbedestroyedbyheat.
Exotoxinsareseeninbothgram+veandgramveorganisms.

GRAMNEGATIVEBUGSWITHEXOTOXINS
BordetellaPertussisstimulatesACbyADPribosylation.
E.Coliisheatlabile,stimulatesACbyADPribosylationofGprotein,causes
waterydiarrhea.
VibrioCholerastimulatesACbyADPribosylationofGprotein,increasingthe
amountofchlorideandwaterinthegut,causinghighvolumericewaterdiarrhea.

GRAMPOSITIVEBUGSWITHEXOTOXINS
StaphAureusAsuperantigenthatbindsMHCIIproteinandTcellreceptor,
inducesIL1andIL2synthesisintoxicshocksyndrome.Canalsocausefood
poisoning.
StrepPyogenesErythrogenictoxin(superantigen)causesrashandscarletfever,
whilestreptolysinO(hemolysin)causesrheumaticfever.
CornybacteriumDiphtheriaCausesinactivationofEF2byADPribosylation,
causingpharyngitisandapseudomembraneinthethroat.
ClostridiumBotulinumBlocksAChrelease,causessevereanticholinergic
symptomsandCNSparalysis.
ClostridiumTetaniBlocksglycine,leadstolockjaw.
ClostridiumPerfringensLecithinase(toxin),causesgasgangrene.


ENDOTOXINS
Endotoxinsarelipopolysaccharidesthatarefoundinthecellwallsofgramnegative
bacteria.Endotoxinscauseawiderangeofproblemsthroughtheactivationof
macrophagesandthecomplementpathway.
Macrophageactivationleadsto:

Hypotensionthroughnitricoxide
FeverthroughIL1activation
Hemorrhagictissuenecrosisthroughtumornecrosisfactor

Thecomplementpathwayleadsto:

HypotensionandedemathroughC3aactivation
CausesPMNchemotaxisthroughC5aactivation

**DICcanbecausedwhentheendotoxinsactivatestheHagemanfactor.

TYPESOFSTAINS
Thereareafewdifferentstainsthatareusedinordertoisolatecertainbacteria,
theyinclude:
SilverStainPneumocysticCariniiPneumonia,Fungi
CongoRedStainAmyloid
GiemsaStainChlamydia,Borrelia,Plasmodium
PASWhipplesdisease
ZiehlNeelsenAcidfastbacterias
IndiaInkCryptococcusNeoformans


CONJUGATION,TRANSDUCTION,TRANSFORMATION
PROCEDURE

PROCESS

CELLTYPES

Conjugation

TransferofDNA
frombacteriato
bacteria
Transferfrom
virustoanother
cell
PurifiedDNAis
takenupbyacell

Prokaryotes

Transduction
Transformation

TYPEOFDNA
TRANSFERRED
Chromosomalor
plasmid

Prokaryotes

Alltypes

Bothprokaryotes
andeukaryotes

Alltypes

SPECIFICREQUIREMENTS
Somebugsrequirecertainenvironmentsinordertosurvive,theyfallunderthe
following:
OBLIGATEAEROBES/ANAEROBES,ANDINTRACELLULAR

ObligateAerobes:require02tocreateATP.Includes:

Nocardia
PseudomonasAeruginosa
MycobacteriumTB
Bacillus

ObligateAnaerobes:aresusceptibletooxidativedamageduetotheirlackofSOD
andcatalase.Includes:

Actinomyces
Clostridium
Bacteroides

Intracellular:thesebugsmustremaininsidethecellinordertosurvive,include:
ObligatesRickettsiaandChlamydia
FacultativeSalmonella,Brucella,Mycobacterium,Listeria,Francisella,Legionella,
Yersinia

IMPORTANTINFOABOUTSTAPHAUREUS
Staphaureusisaverycommonorganismbothintheboardexamsandinclinical
practice.Staphaureuscausestheirdestructionbasedonthefollowingtwo
methods:
1. ToxinMediatedIncludestoxicshocksyndrome,scaldedskinsyndrome,
andrapidonsetfoodpoisoning.
2. InflammatoryIncludesinfectionsoftheskin,abscesses,andpneumonias.

ToxicShockSyndromeAsuperantigenbindstoMHCIIandTcellreceptors,
whichcausespolyclonalTcellactivation.
Foodpoisoningfromstaphaureusiscausedbytheingestionofapreformedtoxin.
**StaphAureuscontainsavirulencefactors(knownasProteinA),thatbindstothe
FcportionofIgG.Thisinhibitscomplementfixationandinhibitsphagocytosis.

ENCAPSULATEDBACTERIA
Somebacteriahaveapolysaccharidecapsulethatactsasanantiphagocyticfactor.
Thismakesthemlesssusceptibletobeingengulfedbyphagocytes.Thesebugsare:

StrepPneumonia
H.Influenza
N.Meningitidis
KlebsiellaPneumonia

THEEXOTOXINSOFCLOSTRIDIASPECIES
C.Difficileproducesacytotoxin(exotoxin)thatkillserythrocytes,andthus
causesapseudomembranouscolitis.**Oftenoccurssecondarytoantibioticuse.
C.Tetaniproducesanexotoxinthatresultsintetanus.
C.Perfringensproducesantoxinthatcausesmyonecrosis,gasgangrene,or
hemolysis.
C.Botulinumapreformed,heatlabiletoxinisproducedthatinhibitstherelease
ofACh,whichcausesbotulism.

IMPORTANTINFOABOUTSTREPPYOGENES
StrepPyogenesisagroupAhemolyticstrepthatcancausethefollowingdiseases:
1. ImmunologicAcuteglomerulonephritisandRheumaticfever
2. PyogenicPharyngitis,Cellulitis,andImpetigo
3. ToxigenicToxicshocksyndromeandScarlettfever

DIPHTHERIA
Diphtheriacancausepseudomembranouspharyngitisthroughanexotoxin.Their
exotoxinworksbyinhibitingproteinsynthesisviaADPribosylationofEF2.

BUGSCAUSINGBLOODYDIARRHEA

E.Coli0157:H7
Entamoebahistolytica
Campylobacterjejuni
Salmonella
Shigella
Yersiniaenterocolitica

BUGSCAUSINGWATERYDIARRHEA

EnterotoxigenicE.Coli
Vibrio(ricewaterstools,highlyvoluminous)
Rotavirus
Giardia(foulsmelling)
Cryptosporidium

IMPORTANTFACTSABOUTH.PYLORI

H.Pyloriisthecauseofmostduodenalulcers(upto90%)
Isagramverodthatcreatesanalkalineenvironment
CanincreasetheriskofPUDandgastriccarcinomas

Treatment:Tripletherapy:Omeprazole,clarithromycin,amoxicillin.

PSEUDOMONASAERUGINOSA
Pseudomonasaeruginosaproducesbothanexotoxinandanendotoxin.Itsmost
popularcharacteristicisthatitproducesafruitysmellingbluegreenpigment(due
topyocyanin).
P.Aeruginosacausesthefollowing:
Pneumoniaincysticfibrosispatient
OtitisExterna(swimmersear)
Folliculitis(knownashottubfolliculitis)
Sepsis(blacklesionsoftheskin)

BUGSTHATACTONTHEGPROTEIN
TwobugsthatproducetheireffectsbyactingontheGsandGiproteinsareVibrio
CholeraandBordetellaPertussis.
VibrioCholeracausesaricewaterdiarrheabypermanentlyactivatingtheGs
protein.
BordetellaPertussiscauseswhoopingcoughbypermanentlydisablingtheGi
protein.
**Commontobothbugsistheactivationofadenylylcyclase(AC)throughADP
ribosylation.

CAUSESOFVAGINOSIS
Trichomonas,Gardnerella,andCandida
Trichomonascausedbyananaerobic,motileprotozoan.ShiftsvaginalpHto56,
anddispelsagreenishyellowfrothyvaginaldischarge.
Gardnerellaagramvariablerodthatcausesagreenvaginaldischargethathasa
fishysmell,andhasthepathognomoniccluecells.pHiselevated.
Candidaisafungalinfectionthatpresentswithacottagecheeselikedischarge
thatisstickyandwillsticktothewallsofthevagina.

BUGSRELATEDTOANIMALS(ZOONOTICS)
Manyseriousdiseasesarecausedbybitesfromanimals,ticks,etc.Themost
importantdiseasesfromanimalsinclude:
1. LymeDiseasecausedbyBorreliaBurgdorferi,whichistransmitted
throughtheIxodestickbite,whichisatickthatlivesondeerandmice.
Classicpresentationisthebullseyetargetlesion.

2. CellulitiscausedbyPasteurellaMulticoda,whichoccursthroughdogorcat
bites.
3. TularemiacausedbyFrancisellaTularensis,fromatickbite,seenin
rabbitsanddeer.ThisconditionisalsoknownasthePahvantValley
Plague,Rabbitfever,Deerflyfever,andOharasfever.

4. BrucellosiscausedbyBrucellaspecies,andcontaminationoccursthrough
infecteddairyproductsandcontactwithanimals.

5. TheplaguecausedbyYersiniapestis,transmittedthroughafleabitefound
onrodentsandwilddogs.

TUBERCULOSIS
Tuberculosisisaninfectionwithmycobacteriumtuberculosis,thataffectsthe
respiratorytractmostcommonly,howeveritcanhaveextrapulmonary
manifestationsaswell,namelyinthe:

GI
Kidneys
Lymphnodes
VertebralBodies(Pottsdisease)
Centralnervoussystem

SymptomsofTBinfection:
Usually,symptomsareverynonspecific,presentingas:

Fatigueandweightloss
Nightsweats
Cachexia


Ifthesymptomsbecomemorepulmonary,expecttofind:

Dyspnea
Hemoptysis
Chestpain(pleuriticinnature)
Productivecough

1infectionAprimaryTBinfectionreferstotheinfectiousprocessbywhichthe
bodyisabletocontaintheinfectionandpreventitsdissemination.Thisresultsin
theGhoncomplex,whichisacalcifiedfocusofinfectionusuallyinthelower
segmentsofthelung.
2infectionAlsoknownasreactivatedTB,thistypeofinfectioncanoccurto
thosewhoareinastateofweakenedorsuppressedimmunity.

Whentuberculosisissuspected?

A+vePPDtestwarrantsachestxraylookingfortheTBcavitarylesion
Acidfaststainlookingforthemycobacterium

Management/Treatment?
ActiveTBA4drugregimen(RIPERifampin,Isoniazid,Pyrazinamide,and
Ethambutol).BewareofadverseneurologicaleffectsofIsoniazid,supplementwith
vitaminB6pyridoxine.
LatentTBWithlatentTB,youwillbeginthepatientona4drugregimenlasting
upto9months.IftheypresentatafuturedatewithlatentTB,theywillnotneedto
betreatedagain.**LatentTB=1time4drugcourselastingseveralmonths.


RICKETTSIALINFECTIONSANDVECTORS
RickettsialinfectionsarethoseinfectionsthatareresponsibleforcausingRocky
MountainSpottedFever,Typhus,andQfever.
Rickettsialinfectionsusuallyleadtoasimilarpresentation,whichis:

Fever
Headache
Rash

ROCKYMOUNTAINSPOTTEDFEVER
CausedbyRickettsiaRickettsii,whichcausesarashthatstartsonthepalmsand
solesandmovesinward.Treatwithtetracycline.
TwoformsofTyphusare:
ENDEMICTYPHUScausedbyRickettsiaTyphi,whichisaflea.Treatwith
tetracycline.
EPIDEMICTYPHUScausedbyRickettsiaProwazekii,abodylouse.Treatwith
tetracycline.
Andfinally,
QFEVERcausedbyCoxiellaBurnetti,whichcausedinfectionviaaerosolized
particles.Treatwithtetracycline.

SPIROCHETES
Spirochetesarespiralshapedbacterialelementscontainingaxialfilaments.The
mostcommonlytestedspirocheterelatedinfectionissyphilis(treponema).The
othertwotypesofspirochetesareBorreliaandLeptospira,whicharestainablewith
lightmicroscopy,whereastreponemaisvisualizedonlywithdarkfieldmicroscopy.
Withthatsaid,therearethreeformsofSyphilis:
1 syphilisPatientwillgetapainlesschancre,treatwithIMpenG
2 syphilisPatienthasdisseminateddisease+constitutionalsymptoms,includes
amaculopapularrashonthepalmsandsoles.TreatwithIMpenG
3 syphilisPatienthasneurologicalproblems(neurosyphilis,ArgyllRobertson
pupil),aorticdisorders(aortitis),andgummas.TreatwithIVpenicillin.

TESTINGFORSYPHILIS
VDRLandFTAABS:
VDRLthistestisusedfornonspecificantibodydetection,howeverduetoitshigh
rateoffalsepositivesisnottheprimarytestusedforsyphilisdetection.Thistest
willbepositivewhenthereareafewotherdiseasespresent,including:SLE,RA,RF,
andafewotherviralinfectionslikemononucleosis.
FTAABSisatestspecificforthetreponemabacteria,andhasthebest
combinationofbenefitsinfindingsyphilis,includinghighspecificity,veryearly
positivity,andremainspositivethelongest.

VIROLOGY

DNAANDRNAVIRALGENOMES
AllDNAvirusesaredoublestrandedandlinear,withtheexceptionofparvovirus(is
singlestranded),andhepadnavirus/papovavirus(circular).AllRNAvirusesare
singlestranded,exceptthereovirus(doublestranded).
DNAisdouble,RNAissingle.

HOWDOVIRUSESREPRODUCE
Recombinationistheexchangeofgeneticmaterialbetween2chromosomesby
crossoverofcertainregionsthathaveimportantbasesequencehomology.
Reassortmentistheexchangeofviralsegments(fromsegmentedviral
genomes).Thisoccursathighfrequencyandisresponsibleforworldwideillnesses
(pandemics).
Complementationoccurswhenonefunctionalvirushelpsanothernon
functionalvirusbecomefunctional.
PhenotypicMixingoccurswhenacertainvirushasthesurfacecoatingfrom
anothervirusprotein,whichwillthendeterminetheinfectivityofthisvirus
particle.

VIRALPLOIDY
Retrovirusescontain2identicalsinglestrandedRNAmolecules,makingthem
diploid,whileallothervirusescontainasinglecopyofbothDNAandRNA,making
themhaploid.
DNAVirusesallreplicateinthenucleus,exceptforthepoxvirus.
RNAVirusesallreplicateinthecytoplasm,exceptforretrovirusesandthe
influenzavirus.


THEIMPORTANTCHARACTERISTICSOFVIRALDNA
ThefollowingareimportantcharacteristicsthatfitforalmostalloftheDNAviruses:
NuclearreplicationallDNAvirusesreplicateinthenucleusexceptforthe
Poxvirus,whichhasitsownDNAdependentRNApolymerase.
ArelinearallDNAvirusesarelinear,exceptforthePapovavirusandthe
Hepadnavirus.Papovavirusiscircular/supercoiled,andtheHepadnavirusis
circular/incomplete.
Aredoublestranded(dsDNA)allDNAvirusesaredoublestrandedexceptfor
theParvovirus,whichissinglestranded(ssDNA).
AreicosahedralinshapeallDNAvirusesareicosahedralexceptforthe
Poxvirus,whichiscompleteincapsidshape.

GENETICSHIFTvs.GENETICDRIFT
GeneticShiftIstheprocessbywhichthereisareassortmentofdifferentviral
strains,whichcombinetoformnewforms/subtypesthatcontainamixtureofthe
surfaceantigensofthestrainsinvolved.Geneticshiftisveryimportantbecauseit
createsnewviralpathogens,andisresponsiblefortheemergenceofnewviruses.
GeneticDriftIsaprocessofnaturalmutationsoveraperiodoftime.Thisleads
tolossofimmunityandtheinabilityofvaccinestocureillnesses.


THEDNAVIRUSES
ThelistofDNAviruses:
1.
2.
3.
4.
5.
6.

Hepadnavirus
Herpesvirus
Adenovirus
Parvovirus
Papovavirus
Poxvirus

Rememberthislistwiththemnemonic:HHAPPPy

THECHARACTERISTICSOFEACHDNAVIRUS
1.HepadnavirusdsDNApartialcircular,enveloped.
DiseasesHepatitisBvirus

2.HerpesvirusdsDNAlinear,enveloped.
DiseasesHumanHerpesVirus6&8,HerpesSimplex1&2,VaricellaZoster,
EbsteinBarrVirus,andCytomegalovirus
HHV6Reseola
HHV8Kaposissarcoma
HSV1Thoughttobeoralulcers,butnowcanbefrombothoralandgenitalulcers
HSV2Thoughttobegenitalulcers,butnowcanbefrombothoralandgenital
ulcers
VZVResponsibleforchickenpox(notseenanymoreduetovaccination),shingles
EBVCausesmononucleosisandBurkittslymphoma
CMVCongenitalinfections

3.AdenovirusdsDNAlinear,hasnoenvelope.
DiseasesConjunctivitis,Pneumonias,Pharyngitis

4.ParvovirusssDNAlinear(isthesmallestDNA),hasnoenvelope
DiseasesParvoB19(slappedcheeksyndrome)

5.PapovavirusdsDNAcircular,hasnoenvelope
DiseasesHumanPapillomavirus,ProgressiveMultifocalLeukoencephalopathy

6.PoxvirusdsDNAlinear(isthelargestofallDNAviruses),hasanenvelope
DiseasesCowpox,Smallpox,MolluscumContagiosum

THECHARACTERISTICSOFEACHRNAVIRUS
1. Picornavirus(+)ssRNA,linear,icosahedral,noenvelope.
Responsiblefor:

HepatitisA
Coxsackievirus
Poliovirus
Echovirus
Rhinovirus

2. Calicivirus(+)ssRNA,linear,icosahedral,noenvelope.
Responsiblefor:

Norwalkvirus(gastroenteritis)
HepatitisE

3. ReovirusdsRNA,linearsegmented,doubleicosahedral,noenvelope.
Responsiblefor:

Reovirus(Coloradotickfever)
Rotavirus(MCCofdiarrheainchildren)

4. Flavivirus(+)ssRNA,linear,icosahedral,enveloped.
Responsiblefor:

Denguefever
Yellowfever
HepatitisC
St.Louisencephalitis
WestNilevirus

5. Togavirus(+)ssRNA,linear,icosahedral,enveloped.
Responsiblefor:

Rubella
Eastern/Westernequineencephalitis

6. Retrovirus(+)ssRNA,linear,icosahedral,enveloped.
Responsiblefor:

HIV/AIDS
HairyTcellleukemia

7. Orthomyxovirus()ssRNA,linear/segmented,helical,enveloped.
Responsiblefor:

Influenza

8. Paramyxovirus()ssRNA,linear/nonsegmented,helical,enveloped.
Responsiblefor:

Measles
Mumps
RespiratorySyncitialVirus(RSV)
Parainfluenza

9. Rhabdovirus()ssRNA,linear,helical,enveloped.
Responsiblefor:

Rabies

10. Filovirus()ssRNA,linear,helical,enveloped.
Responsiblefor:

Hemorrhagicfevers(Ebolavirus)

11. Coronavirus(+)ssRNA,linear,helical,enveloped.
Responsiblefor:

Coronavirus

12. Arenavirus()ssRNA,circular,helical,enveloped.
Responsiblefor:

Meningitis
Lymphocyticchoriomeningitis

13. Bunyavirus()ssRNA,circular,helical,enveloped.
Responsiblefor:

Sandflyfever
Riftvalleyfever
CrimeanCongohemorrhagicfever
Hantavirus
CaliforniaEncephalitis

14. Deltavirus()ssRNA,circular,helical,enveloped.
Responsiblefor:HepatitisD


LIVEATTENUATEDvs.KILLEDVACCINES
LiveAttenuatedVaccinesthesetypesofvaccinesinducebothhumoralandcell
mediatedimmunity.
KilledVaccinesthesetypesofvaccinesinducehumoralimmunityonly.

ExamplesofLiveAttenuatedVaccines:

Measles
Mumps
Rubella
Smallpox
Polio(Sabin)
VZV
YellowFever

**Rememberthereisdangeringivingaliveattenuatedvaccinetosomeonewhois
immunocompromised.

ExamplesofKilledVaccines:

Rabies
Influenza
Polio(Salk)
HepatitisA


SUPERHIGHYIELDMICROBIOLOGYINFORMATION

HERPRESVIRUSES
Therearequiteafewdifferentformsofherpesviruses,theyareallhighyield
USMLEinformation.Themostcommonherpesvirusesandtheircommonfindings
include:
HSV1thisisknowntoberesponsiblefortheorallesionsofherpes,howeverdue
todifferentsexualpractices,itmaybeseeninthegenitalregionaswell.HSV1is
alsoacauseofkeratoconjunctivitisandtemporallobeencephalitis(HSVisthemost
commoncauseofadultonsetalteredmentalstatus).
HSV1istransmittedviarespiratorysecretionsand/orsaliva.ForHSVdiagnosis,
usetheTzancktest(smeartheopenvesicle,lookingformultinucleatedgiantcells).

HSV2HSV2ismostcommonlyseenasherpesofthegenitals(herpeslabialis),as
wellasneonatalherpes.
HSV2istransmittedviaperinataltransmissionaswellasthroughsexualcontact.

EBVcausesBurkittslymphomaandinfectiousmononucleosis(causessevere
fatigue,sorethroat,usuallyinteenagers).Transmittedthroughsalivaand
respiratorysecretions.

CMVCausescongenitalinfectionsaswellassometypesofpneumonia.
Transmittedcongenitally,throughsexualcontact,throughsaliva,andthrough
transfusion.
HHVHumanHerpesVirus,isthecauseofKaposissarcomainAIDSpatients.
Transmissionissexually.


MONONUCLEOSIS
MononucleosisisalwaysencounteredontheUSMLEexams,thusbesuretoknowas
muchaspossibleaboutthiscondition.
Presentation:

Youngadult(1620yr)
Fever
Hepatosplenomegaly
Pharyngitis
Lymphadenopathy

Cause:

EbsteinBarrVirus(EBV)
kissingdisease,becauseitiseasilytransmittedthroughsaliva
ThereareabnormalcirculatingcytotoxicTcells

Diagnosis:
ThebestdiagnostictestistheMonospottest,whichdetectsheterophilantibodies
throughsheepRBCagglutination.
Whattotellthepatient:

ThemostimportantthingforpatientsafetyistoAVOIDCONTACTSPORTS,
becausethespleenisenlargedandifitexperiencesblunttrauma,itmay
ruptureandcausesevereadverseeffectssuchashypotension,shock,and
sepsis.


HIV/AIDS
Aretrovirus,theHIVdiseaseusesthereversetranscriptaseenzymetoreplicate.
HIVinfectioncanbetransmittedthroughsexualcontact/fluids,blood,andbreast
milk.ThehelperTcells(CD4+Tcells),macrophages,anddendriticcellsare
affected.
DIAGNOSINGHIV:
DiagnosisofHIVismadewiththeELISAtestbecauseofitshighsensitivity.Whena
testispositive,aWesternBlotisperformed,whichisveryspecific.
Afterconfirmation,aviralloadcanbedonetomeasurethequantityofthevirusin
theblood,whichallowsyoutomeasuretheeffectofmedicaltreatment.
**FalsenegativeswiththeELISAtestandtheWesternBlotarecommoninthefirst
fewmonthsofHIVinfection.

IMMUNITYTOHIV:
CertainmutationsinourgenescangiveusimmunitytoHIV,cangiveuspartial
immunitytoHIV,andcanevencauseustodeterioraterapidlyfromanHIVinfection.
Themutationsresponsibleforthisinclude:
MutationcausingimmunityCCR5mutation(homozygous)
MutationcausingpartialimmunityCCR5mutation(heterozygous)
Mutationcausingrapidprogression/deteriorationCXCR1mutation

AIDSOPPORTUNISTICINFECTIONS:
Themostcommonlyencounteredopportunisticinfectionare:
FUNGALCandida(thrush),CryptococcalMeningitis(Cryptococcus),Pneumocystis
Pneumonia(PCP,whenCD4<200),Histoplasmosis.
VIRALPML(causedbyJCvirus),HSV,VZV,CMV
BACTERIALTB,MycobacteriumAviumIntracellularcomplex(MAC)
PROTOZOACryptosporidium,Toxoplasmosis

TREATMENT:
Treatmentinvolvestheuseofantiretroviralmedications,giventosymptomatic
patientsregardlessoftheirCD4countsand/ortoasymptomaticpatientswithCD4
counts<500.
Tripledrugregimens(2nucleosidereversetranscriptaseinhibitorsandeither:1
nonnucleosidereversetranscriptaseinhibitorOR1proteaseinhibitor)areused,
theseareknownasHAART,whichtargetandpreventHIVreplicationatthree
differentpointsalongthevirusreplicationprocess.

OTHERMANIFESTATIONSOFHIVINFECTION:
Pulmonary:Communityacquiredpneumonia,PCP,TB,CMV,MAC,Histoplasmosis.
CNS:Toxoplasmosis,AIDSdementia,CryptococcalMeningitis,Lymphoma,HSV,
Neurosyphilis,PML
GI:Diarrhea,Orallesions(thrush,ulcerations,oralhairyleukoplakia),Candida
esophagitis,Proctitis
Dermatological:HSV,Shingles,MolluscumContagiosum,Kaposissarcoma


HEPATITIS
Isinflammationoftheliver,characterizedbythepresenceofinflammationofthe
tissueoftheliver.Thereisawiderangeofroutesofinfection,thereisawiderange
ofsymptomsandprognosis,whichcanrangefromselflimiteddiseasestocirrhosis
anddeath.
ThereareFIVEcommonformsofhepatitis,theyare:
HepatitisA,B,C,D,andE

HepatitisA(HAV)Isusuallyasymptomatic,istransmittedviafecaloralroute.
Usuallyaveryshortincubationperiod(~3weeks).IsaRNApicornavirus.
HepatitisB(HBV)Oftenpresentswithmildsymptomssuchas:lossofappetite
N/V,myalgias,fever,andjaundice.HepBisusuallyselflimited,butcanprogress
andcausecirrhosis,hepaticfailure,anddeath.Transmissionisusuallysexual,
throughsharingdirtyneedles(parenteral),andfromthemothertofetus(vertical
transmission).IsaDNAhepadnavirus.
HepatitisC(HCV)HepatitisCusuallycarriesthesamesymptomsasdoes
hepatitisB,andistransmittedthroughbloodproducts(sex,dirtyneedles).
HepatitisCisoftenachronicillnessthatleadstocarcinomaand/orcirrhosis.
PeopleinfectedwillusuallybecomecarriersofhepC.IsanRNAflavivirus.
HepatitisD(HDV)Alone,hepatitisDcannotinfect,andrequiresacoinfection
withhepatitisBinordertoinfect(requiresHBsAgasitsenvelope).Isadeltavirus.
HepatitisE(HEV)Hasafecaloraltransmissionroute,andhasthetendencyto
causewaterborneepidemics.VerysimilarsymptomaticallytohepatitisA.HEVcan
causesignificantillnessandevendeathinpregnantwomen.IsanRNAcalicivirus.
**HepBandCchronic,causecirrhosis,andhepatocellularcarcinoma.
**HepAandEaffecttheGItract.


HEPATITISSEROLOGY
ThehepatitisserologyisveryhighyieldfortheStep1,memorizeallofthis
information.
HBsAgIstheantigenfoundonthesurfaceofHBV,whenitispresent,thereisa
carrierstate.
HBsAbIstheantibodytoHBsAg,itspresenceindicatesimmunitytoHepB
HBcAgIstheantigenassociatedwiththeHBVcore
HBcAbIstheantibodytoHBcAg,andwhenpresentindicatesthewindow
periodofinfection.WhenthereisanIgMHBcAb,therehasbeenarecentinfection.
HBeAgThisisanindicatorofhepBtransmittability,andisthe2nddeterminantof
thehepatitisBcore.
HBeAbIsthehepatitisEantigen,indicatinglowtransmittabilityofthedisease.

THEHEPATITISVIRALPARTICLE


AGRAPHICALLOOKATAHEPATITISINFECTION

PNEUMONIACOMMONCAUSESPERAGEGROUP
Upto18yrold#1RSV#2Mycoplasma#3Chlamydia#4Strep
1840yrold#1Strep
**Atypical/walkingpneumoniaMycoplasma
4065yrold#1Strep#2H.Influenza
>60yrold#1Strep#2Viraletiologies

PNEUMONIASPECIALSITUATIONS
InanalcoholicStrepPneumoniaistheMCC,howeverKlebsiellaismorelikelyin
analcoholic(becarefulwiththisquestion,becauseyoumaybeaskedwhatthemost
commoncauseofpneumoniaisinanalcoholic,whichisstillStreptococcus)
HospitalacquiredStaph
InanimmunocompromisedpersonStaphismostcommoncause,butwatch
foranHIVpatientwhocangetPCPpneumoniawhenCD4countislow.
AspirationAnaerobicoralflora
NeonatalUptothefirst6weeksoflifeGroupBstrepandE.Coli

COMMONORGANISMSINURINARYTRACTINFECTIONS
ThemostcommoncauseofurinarytractinfectionsisE.Coli.Themostcommon
symptomsarepainfulurination,frequency,urgency,andsuprapubicpain.Thiscan
ascendandbecomeasevereinfectionsuchaspyelonephritis.
Mostcommoninwomenbecausetheyhaveashortdistancefromtheoutsideofthe
urethratothebladder.TreatmentinvolvesusingTMPSMP(Bactrim)

MENINGITIS
Isalifethreateninginfectionofthemeninges.Patient
presentsmostcommonlywithnuchalrigidity,high
fever,andalteredmentalstatus.Themostcommon
causesperagegrouparethefollowing:
Innewbornsupto6monthsE.Coli
Inchildren6months6yrsStrepPneumonia
Inpeople6yr60yrsNeisseriaMeningitidis
Inpeople>60yrStrepPneumonia

TestHint:
TheUSMLEwill
giveyoua
scenariowhere
someoneisin
closecontactwith
others
(dormitory,army,
etc),thisisalmost
alwaysleading
youtomeningitis.


ALISTOFTHEMOSTCOMMONLYTESTEDSTDS
Gonorrheapresentswithurethritis,cervicitis,epididymitis(men).Cancause
pelvicinflammatorydisease(commoncauseofinfertility).CausedbyN.Gonorrhea,
treatwithceftriaxone.
Chlamydiapresentssimilarlytogonorrhea.Whenthisisfound,thereisusually
acoinfectionwithgonorrhea.CausedbyChlamydiaTrachomatis.
HerpesPAINFULulcerofthepenis,vulva,andcervix
SyphilisPAINLESSchancre(seenin1form),systemicfindingsin2form,and
neurologicalfindingsinthe3form.
LymphogranulomaVenereumPAINLESSulceratthebeginning,withinfection
spreadingalongtheinguinalpathway.CausedbyChlamydiaTrachomatistypesL1
L3.
VaginitisVaginalitching,pain,anddischarge.Maybeduetogardnerella,
trichomonas,orcandida.
ChancroidPAINFULgenitalulcers,causedbyHaemophilusDucreyi
CondylomaAcuminataCausesgenitalwartsthatcanbeonthelabia,inthe
vagina,andonthecervix.CausedbyHPVtypes6and11.

PELVICINFLAMMATORYDISEASE
Isascarringofthefallopiantubes,andisaverycommoncauseofinfertilityin
women.Thereisoftensymptomssuchascervicalmotiontenderness,vaginal
discharge,andeventuboovarianabscess.
MostcommoncauseisChlamydiaandGonorrhea.


THETORCHINFECTIONS
TORCHisthemnemonicusedtorecallthemostcommonlyencountered
congenitalinfections,theyare:
TToxoplasmosis
Ostandsforother,whichisSyphilis
RRubella
CCMV
HHSVandHIV

OSTEOMYELITIS
Osteomyelitisisaninfectionofthebone,whichcanbecausedbyanumberof
differentorganisms,theyinclude:
StaphylococcusAureusIsthemostcommoncauseoverall
SalmonellaCausesosteomyelitisinsicklecellpatients
GonorrheaCancauseosteomyelitisinsexuallyactivepeople(isalesscommon
cause)
PseudomonasAeruginosaCommoncauseinintravenousdrugusers
StaphEpidermidisCommoncauseofosteomyelitisinthosewithprosthetic
devices.

PARASITOLOGY

StudyingtheparasitologysectionfortheUSMLEexamissimpleand
straightforward,simplymemorizeallorganismsandtheirpresentations,theirmode
oftransmission,howthediagnosisismade,andfinallythebesttreatmentforeach.
PARASITE
Plasmodium
(Vivax,Ovale,
Malariae,
Falciparum)

DISEASE/SYMPTOMS

MODEOF
DIAGNOSING TREATMENT
TRANSMISSION
Anopheles
Bloodsmear
Chloroquine,
mosquito
Sulfadoxine,

Pyrimethamine,
quinine,
Mefloquine
Cystsfoundin Cystsinstool Metronidazole
H20
+Iodoquinol

MALARIA,causesa
cyclicfever+
headache,
splenomegaly,and
anemia
Entamoeba
Dystentery,bloody
Histolytics
diarrhea,liver
abscess,andright
upperquadrantpain
GiardiaLamblia
Foulsmelling
CystsinH20
Cystsinstool Metronidazole
diarrhea,flatulence,
andbloating
Cryptosporidium Severediarrheafound Cystsfoundin Cystsseenon Notreatment
inAIDSpatients,mild
H20
acidfast
diarrheainhealthy
stain
patients
Toxoplasma
Birthdefectsand
Cystsfoundin Serologyand Pyrimethamine
brainabscesses(HIV catfecesand/or
biopsy
and
patients)
meat
sulfadiazine
Trichomonas
Foulsmelling
Sexual
Trophozoites Metronidazole
discharge,greenin
seenonwet
colorfromthevagina
mount
Naegleria
Causesadeadly
Caughtby
Spinalfluid
Notreatment
meningoencephalitis
swimmingin
shows
freshwater
amoeba
lakes
Trypanosoma
CausesChagasheart Transmittedvia
Seenon
Nifurtimox
Cruzi
disease
thereduviidbug bloodsmear
Trypanosoma
CausesAfrican
Transmitted
Seenon
Suraminor
Gambiense
sleepingsickness
throughthe
bloodsmear
Melarsoprol
Tsetsefly
Babesia
Causesbabesiosis,
Transmitted
Maltese
Quinineand
whichisadisease
throughthe
crossseen
Clindamycin
similartomalaria
Ixodestick
onblood
smear
Leishmania
Causesvisceral
Transmittedvia
Smear
Sodium

Donovani

Leishmaniasis

thesandfly

showing
macrocytes
thatcontain
amastigotes

stibogluconate

HELMINTHS(Worms)

Justaswithparasites,memorizingallofthedifferenthelminthesaswellastheir
presentation,transmission,andtreatmentishighyieldaswellaseasypointsonthe
USMLEexam.
HELMINTH

TAPEWORMS

Echinococcus

TRANSMISSION

Fromeggswithin
dogfeces

TaeniaSolium

Undercookedpork

FLUKES

Schistosoma

Snails

Paragonimus
Westermani

Fromundercooked
crabmeat

Clonorchis
Sinensis

ROUNDWORMS

LoaLoa

Fromundercooked
fish

Fromdeerfly

Ancylostoma
Duodenale
(hookworm)
Ascaris
Lumbricoides

Larvalpenetration
ofskin
Eggsinfeces

PRESENTATION

Cystsinlivercause
anaphylaxisif
antigensare
releasedfromthe
cyst
Masslesioninthe
braincausedby
larvae

Spleenandliver
areaffected,get
granuloma,
fibrosis,and
inflammation
Bacterialinfection
andthus
inflammationof
thelungs
Biliarytract
inflammation

Inflammationand
swellingofskin,
canseethisworm
intheconjunctiva
Anemiaiscaused
byintestinal
infection
Intestinalinfection

TREATMENT

Albendazole

Albendazole

Prizaquintel

Prizaquintel

Prizaquintel

Diethylcarbamazine

Mebendazoleand
pyrantelpamoate
Mebendazoleand
pyrantelpamoate

(Giant
roundworm)
Enterobius
Vermicularis
(Pinworm)
Trichinella
Spiralis

Infectedfood(with
eggs)
Undercookedpork

Strongyloides
Stercoralis
Dracunculus
Medinensis

Larvafromsoilget
inthroughtheskin
Infectedwater

ToxocaraCanis

Contaminatedfood

Wuchereria
Bancrofti

Fromthefemale
mosquito

Onchocerca
Volvulus

Femaleblackflies

Intestinal
Mebendazoleand
infection,alsoget
pyrantelpamoate
analitching
Causesperiorbital
Thiabendazole
edemaandmuscle
inflammation
Causesan
Ivermectinand
intestinalinfection
thiabendazole
Inflammationand
Niridazole
ulcerationofthe
skin
Causesgranulomas Diethylcarbamazine
intheretina,may
leadtoblindness
Blockslymph
Diethylcarbamazine
drainageleadingto
elephantitis
Causesriver
Ivermectin
blindness

MYCOLOGY

Mycology(fungi)playaveryimportantroleinmedicalpathology,asthereareafew
veryimportantconditionsthatareseenonaveryregularbasisclinically.
EverythinginthissectionisSUPERHIGHYIELD,thusbesuretoknowthissection
cold.

CANDIDAALBICANS
Candidaalbicansisseenwidelyinmanydifferentclinical
situations.Itcancauseawidevarietyofconditions,andcan
beseenbothsuperficially(ontheskin),andsystemically
(anywhereelse).
CharacteristicsofCandida:

Diploidfungus
Buddingyeastwithpseudohyphaearound20C
Buddingyeastwithgermtubeformationaround37C

TESTTIP:
Youwillbegiven
imagesoffungi
ontheUSMLE
exam.Besureto
understandtheir
anatomyandhow
theylook
microscopically.

CommonproblemscausedbyCandida:

Vaginitis(yeastinfection)
Oralthrush
Esophagitis
Endocarditis(IVdruguse)

TreatingCandida:

Forsuperficialinfections(includingoralthrush),Nystatinisthetreatmentof
choice.
Forsystemicinfections,amphotericinBiscommonlyused.


COMMONCUTANEOUSFUNGALINFECTIONS
TineaPedisAthletesFoot,presentswithitching,flaking,andscalingofthe
affectedareas,causedbyTrychophyton.Treatwithatopicalazole.
TineaCapitisRingwormofthehair,causedbyTrichophytonandMIcrosporum.
Invasionofthehairshaftleadstohairlossthatoccursinpatches.Treatwithatopic
azole.
TineaCrurisJockItch,isafungalinfectionofthegroinregion.
TineaCorporisRingworm,isaskininfectionofthearmsandlegsmost
commonly,howeveritcanoccuranywhere.Theclassicappearanceisacircular
rashthatclearscentrallywithelevatededges.
TineaVersicolorIsarashofthetrunkandproximalextremities,causedby
MalasseziaFurfur.Classicpresentationishypopigmentationoftheskinwithsharp
bordersandfinescaling.Seenmostcommonlyinhotandhumidclimates/weather.
Topicalmiconazoleandseleniumsulfideareeffectivetreatments.
TineaNigraAffectsthekeratinizedlayeroftheskin,producingbrownpigments.
IscausedbyHortaeaWerneckii,istreatedwithtopicalantifungals.

ENDEMICSYSTEMICMYCOSES
HISTOPLASMOSIS:

IsendemictotheMississippiandOhiorivervalleys.
Acutephasepresentswithnonspecificrespiratorysymptoms
Chronicconditionmayresembletuberculosis,thatifleftuntreatedcanlead
todeath

BLASTOMYCOSIS:

EndemictostateseastoftheMississippiriverandtoCentralAmerica

Hasmanywaysofpotentiallypresenting:

Mildflulikeillness
Pneumonialikeillness
ChronicillnessthatmimicsTBorlungcancer
Aggressivediseasethatcausessignificantrespiratorydistress
Maycauseskinlesionsandbonepain
Isalargeyeastwithbroadbasedbudding

COCCIDIOIDOMYCOSIS:akaValleyFever

IsendemictotheSouthwesternpartsoftheUSA
Isfoundinthesoil
Commonlyitisamilddisease(flulike)
Canbesevereandleadtoseverecomplicationssuchaspneumonia,lung
nodules,andsystemicfindingsthroughoutthebody
AlsoknownasValleyFever

PARACOCCIDIOIDOMYCOSIS:

IsendemictoRuralLatinAmerica
Involvesthemucousmembranes,LNs,bones,andlungs
Maybeasymptomaticinsome
Juvenileformsareoftenmoresevereandholdaworseprognosis
Painfullesionsofthelipsandoralmucosa
Pulmonaryinvolvementusuallybeginsaslobarpneumoniathatfailsto
resolve

OPPORTUNISTICFUNGALINFECTIONS
CandidaAlbicansVaginitisindiabeticsandthoseusingantibiotics,thrushin
thosewithimmunocompromisedconditions.

PseudohyphaeandBuddingYeast

Mucor/Rhizopuscausesmucormycosis,affectspatientswithleukemiaandaffects
thosewithdiabetes/DKA.

Nonseptatehyphae,withwideangledbranching.

CryptococcusNeoformansCausescryptococcalmeningitis.Isaveryheavily
encapsulatedyeastthatisfoundinsoilandinpigeondroppings.

Heavilyencapsulatedyeast(~510umindiameter)

AspergillusFumigatusCausesafungusballcavityinthelungs.

Branchingseptatehyphaeat45

SPOROTHRIXSCHENCKII
ThistopicisaddedbecauseithascomeupoverandoveronallUSMLEexams.This
isadimorphicfungusthatlivesonvegetation.Thespreadisthroughbeingpricked
withathorn,thusthenameRoseGardenersdiseaseisgiven.Itcauseslocal
ulcerationsinadditiontonodulesthatfollowthelymphaticdrainage.

CHAPTER12

PHARMACOLOGY

PharmacologyisaveryhighyieldtopicontheUSMLEStep1
exam.Focusshouldbemadeonthefollowing:Mechanisms
ofAction,clinicaluse/applications,sideeffects.
Pharmacokinetics,pharmacodynamics,andtheautonomic
nervoussystemarealsoveryhighyieldinformation.

THEEC50
TheEC50istheconcentrationofagonistthatprovidesaresponsehalfwaybetween
thebaselineandthemaximumresponse.TheEC50isthemostcommonstatistic
usedtomeasurethepotencyofanagonist(ithoweverisnotusedtodirectly
measureaffinity).

COMPETITIVE&IRRIVERSIBLEANTAGONISTS
Antagonistsaredrugsthatwillpartiallyorcompletelyblockaresponse.
Competitiveantagonistsbindreversiblytothesamereceptorastheagonist,while
theirreversibleantagonistbindsirreversibly.Thepresenceofanantagonistwill
increasetheEC50byafactorknownasthedoseratio.
Below,thegraphwilldemonstratehowconcentrationXgivesacertainresponsein
theabsenceofanantagonist,butconcentrationX1isneededinordertoachieve
thesameresponsewhenthereisapresenceofacompetitiveantagonist,thedose
thenequalsX1/X.Usingdifferentconcentrationofantagonistwillproducea
differentdoseratio.

Inthepresenceofanirreversibleantagonistontheotherhand,theirreversibly
boundantagonistresultsindepressionofthemaximalresponseoftheagonistdose
responsecurveandarightshiftalsooccurswherethereisareceptorreserve
similartononcompetitiveantagonists.

FULLAGONISTvs.PARTIALAGONIST
Incomparingafullvs.partialagonist,theyactonthesamereceptorshoweverthe
partialagonisthasalowermaximalefficacy,thusevenwithincreaseddosages,it
cannotreachthesameefficacyasthatofthefullagonist.


DRUGELIMINATION
Therearetwotypesofdrugelimination:ZeroOrderand1stOrder
DrugClearance=Rateofelimination/PlasmaDrugConcentration
1stOrderEliminationIn1storderelimination,therateofdrugeliminationis
proportionaltotheplasmaconcentration(Cp)ofdrug.Thuswithmoredrug
concentrationthereismoredrugelimination,ifthereislessdrugconcentration
thereislessdrugelimination.Mostdrugsareeliminatedby1storderelimination.

ZeroOrderEliminationInZeroorderelimination,thefractionofdrug
eliminationremainsconstant,nomatterhowhighthedrugconcentration.There
arelessdrugseliminatedwithzeroorderelimination,twoexamplesarealcoholand
aspirin.

IMPORTANTEQUATIONSINPHARMACOLOGY

PHASE1vs.PHASE2DRUGMETABOLISM
Phase1metabolismProduceswatersolublemetabolitesthroughreduction,
oxidation,andhydrolysisofthedrugmolecules.Thesemetabolitesareslightly
polar.UsestheCYP450metabolism.
Phase2metabolismProducesinactivemetabolitesthatareverypolar,occurs
throughacetylation,glucuronidation,andsulfation.

THEAUTONOMICNERVOUSSYSTEM
Theautonomicnervoussystemregulatesmanybodilyprocesses(HR,BP,digestion,
respiration,bloodpH,etc)automaticallyonasubconsciouslevel.Theflowofthis
systemisasfollows:
CNS Preganglionicfibers Ganglion Postganglionicfibers Endorgan

Theautonomicnervoussystemconsistsofthesympatheticandparasympathetic
systems.
SYMPATHETICNERVOUSSYSTEM

Thenervescomefromthe
thoracicandlumbarregions.
Preganglionicnervesareshort
andsynapseinthepairedganglia
adjacenttothespinalcord.
Achreleasedfrompreganglionic
neurons.
NEisreleasedfromthe
postganglionicneuron.
Increasescardiacoutput,
increasespulmonaryventilation,
increasesmuscularbloodflow,
increasesbloodglucose,
decreasesdigestion,increases
filtrationthroughkidneys.

Majorreceptorsarethealphaand
betareceptors.

PARASYMPATHETICNERVOUS
SYSTEM

Thenervescomefromthe
cranialandsacralregionsof
theCNS.
Involvedcranialnervesare
CN3,7,9,10.
Longpreganglionicnerves,
shortpostganglionicnerves.
Achisreleasedfromboth
thepreandpostganglionic
neurons.
Increasesdigestion,helps
withurinationand
defecation.

MajorreceptorsaretheNicotinic
andMuscarinicreceptors.

ADRENERGICANDCHOLINERGICRECEPTORS
AdrenergicReceptors

CholinergicReceptors

Stimulatedmostcommonlyby
EpinephrineandNorepinephrine.

StimulatedbyAcetylcholine.
Nicotinicreceptorsarefoundinthe
autonomicganglion.

1Causesconstrictionofsmooth
muscleofarteriolesandGI/GU.

Muscarinicreceptorsarefoundon
allorganswithparasympathetic
nerves.

2Smoothmuscleconstriction
andneurotransmitterinhibition
1Causescontractionofthe
heartmuscle.
2Causessmoothmuscle
relaxationoflungsandbladder.

THESYMPATHETICANDPARASYMPATHETICFIBERS


THE1RECEPTOR
AGONISTS

ANTAGONISTS

Norepinephrine
Phenylephrine
Methoxamine
Xylometazoline

Prazosin
Terazosin
Doxazosin
Alfuzosin
Phenoxybenzamine
Phentolamine

AGONIST
POTENCY
NE>EPI

MECHANISMOF
ACTION
Gq:Phospholipase
Cactivated,IP3
andCalcium.

AGONIST
POTENCY
EPI>NE

MECHANISMOF
ACTION
Gi:ACinactivated,
cAMP

AGONIST
POTENCY
Isoprenaline>EPI
=NE

MECHANISMOF
ACTION
Gs:ACactivated,
cAMP

AGONIST
POTENCY
Isoprenaline>EPI
>>NE

MECHANISMOF
ACTION
Gs:ACactivated,
cAMP

THE2RECEPTOR
AGONISTS

ANTAGONISTS

Clonidine
Brimonidine

Phentolamine
Yohimbine
Atipamezole

THE1RECEPTOR
AGONISTS

ANTAGONISTS

Dobutamine

Metoprolol
Atenolol

THE2RECEPTOR

AGONISTS

ANTAGONISTS

Albuterol
Isoprenaline
Metaproterenol
Salmetrol
Terbutaline

Propranolol


CHOLINERGICDRUGS
Cholinergicdrugsstimulatetheactionofacetylcholine,whichplaysalargerolein
therestanddigestportionofautonomicfunctioning.Thesedrugshelpusdigest
andpropelfoodthroughtheGI,helpwithurination,secretionofsalivaryfluids,and
manymorefunctions.

CHOLINOMIMETICS
DirectAgonists
AGENT
Carbachol/Pilocarpine

CLINICALUSE
Glaucomarelief

Bethanecol

Urinaryretention

MECHANISMOFACTION
Activatestheciliary
musclesoftheeye
Activatesthesmooth
muscleoftheboweland
bladder

IndirectAgonists(ieAnticholinesterases)
AGENT
Neostigmine

Pyridostigmine
Edrophonium
Physostigmine
Echothiophate

CLINICALUSE
ReversalofpostopNM
junctionblockade,ileus,
urinaryretention,
myastheniagravis
Myastheniagravis
Isveryshortactingand
usedinthediagnosisof
myastheniagravis
Usefulforglaucomaand
reversesanatropine
overdose
Glaucoma

MECHANISMOFACTION
Increasesendogenous
releaseofacetylcholine
Increasesendogenous
releaseofacetylcholine
Increasesendogenous
releaseofacetylcholine
Increasesendogenous
releaseofacetylcholine
Increasesendogenous
releaseofacetylcholine


ANTICHOLINERGICS
AGENT
Atropine
Benztropine
Scopolamine
Ipratropium

CLINICALUSE
Producesmydriasisand
cycloplegiaforeyeexams
UsedinParkinsons
disease
Preventsand/ortreats
motionsickness
MainstayofCOPD
management

MECHANISMOFACTION
Competitiveantagonistat
cholinergicreceptor
Muscarinicreceptor
blocker
Muscarinicreceptor
blocker
Muscarinicreceptor
blocker

CHOLINESTERASEINHIBITORPOISONING
Cholinergicintoxicationismostcommonlyseenwithpoisoningfroma
cholinesteraseinhibitor.Thisisclassicallyseeninfarmersoranyoneworkingwith
organophosphates,andinsnakevenoms.Thesignsandsymptomsofcholinesterase
inhibitorpoisoningcanberememberedwiththemnemonicSLUDD
Therewillbeexcessive:
SSalivation
LLacrimation
UUrination
DDigestion
DDefecation

CYTOCHROMEP450METABOLISM
INDUCERS

INHIBITORS

Quinidine

Isoniazid

Barbiturates

Sulfonamides

Phenytoin

Cimetidine

Rifampin

Ketakonazole

Griseofulvin

Erythromycin

Carbamazepine

GrapefruitJuice
St.JohnsWart


HIGHYIELDSYMPATHOMIMETICFACTS
DopamineIncreasesBPinpatientswithshockbymaintainingrenalbloodflow.
Dobutamine(1)Stimulatestheheartwithoutcausingexcesstachycardia.
Isoproterenol(1,2)UsedforrefractoryAVblockandbradycardia.
Clonidine(2)Primaryuseissystemichypertension,suppressesSNSoutflow
fromtheCNS.StimulatesPNSoutflow,thusslowsHRanddecreasessympathetic
drive.Adverseeffectsaresedation,drymouth.
Albuterol(2)Primarytreatmentofasthma.
Terbutaline((2)Usedforbronchospasm,asthma.
AmphetaminesReleaseNE,crossthebloodbrainbarrier,increaseBPwitha
reflexdecreaseinHR.Toxicity:Dizziness,tremor,talkative,tense,irritable,
insomnia,fever,confusion,increasedlibido,paranoia,panic,suicidaltendencies.

HIGHYIELDSYMPATHOLYTICFACTS
PrazosinUsedforBPH,hasa1stdosephenomenonwherepatientgets
pronouncedadverseeffectswiththeirfirstdose(mostcommonlygetorthostatic
hypotensionadropinsystolicBPofatleast20mmHg,ordropindiastolicBPofat
least10mmHg).
PhentolamineCausesgreaterincreaseinHRthanprazosin(reflex),andisused
fordiagnosingpheocromocytoma.
Labetalol&blockade,usefulinhypertensiveemergencies,oneoftwodrugs
usedinpregnantpatientswithhypertension.
Propranololistheprototypicalblocker,hasgreaterlipophilicitythanothers,
usefulforhypertension,angina,acuteMI,stagefreight,andpheocromocytomas.
Preventsexerciseinducedtachycardiaandoxygendemand.
TimololUsefulformigraines,usedinopenangleglaucomatodecreaseaqueous
humorformation.
PindololHasthegreatestISA(preventsexcessbradycardia).
Majoreffectsof blockersonthecardiacsystemDecreasecontractility,
decreaseHR,decreaseBP,increaseexercisetolerance.
MajoreffectontheeyeDecreaseformationofaqueoushumor.

MajormetaboliceffectsDontuseindiabeticsasitblockssymptomsof
hypoglycemia(ieinhibitstremor,diaphoresis,tachycardia,andinhibits
glycogenolysis).Blocksymptomsofhyperthyroidism.

ANTIHYPERTENSIVEPHARMACOLOGY
ThereareSIXcategoriesofantihypertensivemedications:
1.
2.
3.
4.
5.
6.

Diuretics
Sympatholytics(blockers)
AceInhibitors
AngiotensinReceptorBlockers
Vasodilators
CalciumChannelBlockers

DIURETICS
Inadditiontolearningallofthediureticsusedforhypertension,itisveryimportant
tounderstandwhereandhowtheyworkinthekidney.Belowisalistofthe
commonlyuseddiuretics,theirmechanismofaction,theirclinicaluses,andtheir
toxicities.Followingthatisanimageofthekidneyanditsphysiologyasitrelatedto
diuretics.

ACETAZOLAMIDE:Isacarbonicanhydraseinhibitor,whichcausesdiuresisof
NaHCO3andreducesthetotalbodyHCO3stores.Itssiteofactionistheproximal
convolutedtubule.
USESAltitudesickness,glaucoma,alkalinizationoftheurine,metabolicalkalosis.
TOXICITIESNH3toxicity,hyperchloremicmetabolicacidosis,neuropathy.

MANNITOL:Anosmoticdiureticthatactsbyincreasingthetubularfluid
osmolarity,whichthencauseswatertomoveintothetubules,increasingthe
amountofurine.
USESTodecreaseintracranialpressure,todecreaseintraocularpressure,drug
overdose.
TOXICITIESDehydration,pulmonaryedema.

LOOPDIURETICS:LoopdiureticsinhibittheNa/K/2Clcotransportsystemofthe
thickascendinglimboftheloopofHenle.
USESForstatesofexcessiveedema,suchasCHF,cirrhosis,pulmonaryedema,
nephriticsyndrome.Alsousedtodecreasetotalbodycalciumlevels.
TOXICITIESThefamousmnemonicOHDANGcanbeusedtorememberthe
toxicitiesofloopdiuretics.
OtotoxicityHypokalemiaDehydrationAllergyNephritisGout

THIAZIDES:ThiazidediureticsworkbyinhibitingtheNaClreabsorptioninthe
earlydistaltubule,whichdecreasesthedilutingcapacityofthenephron.
USESIsafirstlinedrugforhypertension.Alsousedforcasesofidiopathic
hypercalciuria,CHF,andnephrogenicdiabetesinsipidus.
TOXICITIESUsethemnemonichyperGLUCtorememberthemostcommon
toxicitiesofthiazidediuretics.
Hyper:Glycemia,Lipidemia,Uricemia,Calcemia

K+SPARING:ThemostcommonlyuseddrugisSpironolactone,actsasa
competitivealdosteronereceptorantagonistinthecorticalcollectingtubule.
USESCHF,potassiumdepletion,andhyperaldosteronism(K+andaldosterone
moveintheoppositedirectioninthetubule).
TOXICITIESHyperkalemia,gynecomastia,antiandrogeneffects.

ACEINHIBITORS:Captopril,Enalapril,andLisinopril.Actbyinhibitingtheenzyme
angiotensinconvertingenzyme,whichreducesthelevelsofangiotensin2(from
Renin)andpreventstheinactivationofbradykinin.
USESHypertension,CHF,andrenaldiseasecausedbydiabetes.
TOXICITYThemnemonicCAPTOPRILcanhelprememberalloftheACEI
toxicities.
Cough,Angioedema,Proteinuria,TasteChange,hypOtension,Pregnancyissues,
Rash,Increasedrenin,LowerAngiotensin2.

CALCIUMCHANNELBLOCKERS:BlockthevoltagedependentLtypechannelin
cardiacandsmoothmuscle,thusreducingmusclecontractility.
DihydropyridinesAmlodipine,Nicardapine,Nifedipine
NondihydropiridinesVerapamil,Diltiazem
USESHypertension,angina,arrhythmias
TOXICITYFlushing,dizziness,peripheraledema,andcardiacdepression.

NITROGLYCERINE:Causesvasodilationviareleaseofnitricoxideinthesmooth
muscle,thisincreasescAMPlevelsandthussmoothmusclerelaxation.Itcauses
muchmoredilationofveinsthanarteries.
USESAngina,pulmonaryedema.
TOXICITYTachycardia,hypotension,andheadache.Bealertforsomethingcalled
MondayDisease,wherebysomeoneexposedtonitroglycerinethroughoutthe
workweekdevelopstolerance,thenlosestoleranceovertheweekend,resultingin
tachycardia,headache,anddizziness.

SYMPATHOLYTICS:blockers,2agonists,blockers

blockersIncreasebloodvesseldilation(Prazosin,Terazosin,Doxazosin)
2agonistsClonidine(DecreasesPVR,thusdecreaseBP),Methyldopa(Decreases
PVRandBPinpregnantpatients)
blockersSelectives(Metoprolol,Atenolol,Betaxolol),NonSelectives(Pindolol,
Acetabulol,Labetolol)

SITESOFDIURETICACTION

ANTIANGINALS
Anginapresentswithseverechestpain,duringactivity(stable)andwithoutactivity
(unstable).Prinzmetalsanginaoccursviaspasmofcoronaryartery,andismost
commoninyoungerfemaleswhosmoke.
GoaloftherapyReducemyocardialoxygenconsumptionbydecreasingeither:
EndDiastolicVolume,bloodpressure,heartrate,contractility,andejectiontime.
Nitratesandblockerscanalterthecomponentsthataffectmyocardial02
consumptioninthefollowingways:

BloodPressure
Enddiastolic
volume
Contractility
Heartrate
Ejectiontime
Myocardial02
consumptions

NITRATES(alter
preload)
Decrease
Decrease

BLOCKERS
(alterafterload)
Decrease
Increase

Increase
Increase
Decrease
Decrease

Decrease
Decrease
Increase
Decrease

NITRATES+
blockers
Decrease
Smalleffect
Smalleffect
Decrease
Smalleffect
Largedecrease

LOCATIONOFCARDIACDRUGACTIVITY


ANTIARRHYTHMICDRUGS
CLASS1AThisclassofantiarrhythmicdrugshasaffinityfortheopenstateofNa+
channelswithslowrecoveryrate.
DrugsQuinidine,Amiodarone,Procainamide,Disopyramide
ToxicitiesQuinidinecausescinchonism(acombinationofheadache,tinnitus,
torsadesdespointes).ProcainamidecancauseareversibleSLElikesyndrome.

CLASS1BDecreasesAPduration,affectsischemicordepolarizedPurkinjeand
ventriculartissue.ExcellentwhenusedforpostMIventriculararrhythmiasand
digitalisinducedarrhythmias.
DrugsLidocaine
ToxicitiesLidocainecancauseCNSstimulationordepressionaswellascardiac
depression

CLASS1CSlowsconductionthroughtheheart,especiallyinthePurkinjefibers.
Goodforsupraventriculararrhythmiasandlifethreateningventriculararrhythmias.
Isalastresortmedication.
DrugsFlecainide,Encainide,Propafenone
ToxicitiesIscontraindicatedinpostMIpatientsbecauseitisaproarrhythmic

CLASS2( blockers)DecreasecAMP,decreaseCa2+,decreasephase4slope,
increasePRinterval.
DrugsMetoprolol,Esmolol,Atenolol,Propranolol
ToxicitiesImpotence,Asthmaexacerbations,CNSeffects,cardiovasculareffects
(bradycardia,AVblock,CHF),hypoglycemia.

CLASS3(K+channelblockers)IncreaseAPduration,increaseERP,increaseQT
interval.AmiodaroneblockstheK+rectifierchannelthatrepolarizestheheart
duringphase3.
DrugsSotolol,Amiodarone
ToxicitiesSotolol(TorsadesdesPointes),Amiodarone(prolongsAPduration,
elongatesQRS,pulmonary/liver/thyroidtoxicities,thuscheckPFT,LFT,TFTs)

CLASS4(Ca2+channelblockers)DecreaseconductionvelocityinAVnodes,
increasesERP,increasesPRinterval,preventsnodalarrhythmias.
DrugsVerapamil,Diltiazem
ToxicitiesConstipation,Flushing,Edema

OTHERAdenosine
CauseshyperpolarizationbyblockingtheCa2+influxandpreventingK+outward
flow.
IsthedrugofchoicefordiagnosingandabolishingAVnodalarrhythmias(isa
substituteusedbetweencardioversions,hasahalflifeof10s.


CHFDRUGS

StagesofCHF:
Class1(Asymptomatic)Nolimitsonactivity,onlyaffectspatientwithnormal
exercise.
Class2(Symptomswithmoderateexercise)Slightlylimitsordinaryactivity
(fatigue,palpitations)
Class3(Symptomswithmildexercise)Nosymptomsatrest,butoccurwithless
thanordinaryactivities.
Class4(Symptomaticatrest)Severephysicallimitations,symptomsatrest
(whensitting)

SymptomsofCHF:

Tachycardia
Weakness
Fatigue
Orthopnea
Peripheraledema
Pulmonarycongestion
Hyperreninemiaandhyperaldosterone
Ventricularhypertrophyandremodeling
Increasedfillingpressure/increasedenddiastolicvolume

DrugsusedforCHF:
IONOTROPESThesedrugsincreasestrengthofcontraction,thusincreasestroke
volume.
DIURETICSMovefluidsoutofthebodythusdecreasingcongestion.
VASODILATORSDecreasevenouspressure,congestion,andedema.
CHRONOTROPESIncreasethespeedofheartcontractions.
ACEINHIBITORSDecreasemortalityinheartfailurepatients,decreases
ventricularremodeling.

IONOTROPES
CardiacGlycoside

BetaAgonists

DIGOXIN

BlockstheNa/Kpump,thus
increasingtheintracellularCa2+.

Isapositiveionotropebecauseof
theincreasedCa2+.

Increasedvagaltone,decreased
QTinterval.

STsegmentdepression(hockey
stickconfiguration).

Twaveinversion.

AdverseEffects:
Nausea/Vomiting/Diarrhea
Effectispotentiatedby
hypokalemia
Quinidinewilldisplace
digoxinfrombindingsites

AntidoteisDigoxinImmuneFab
ormoderateincreaseinK+

Contraindicatedusewhen
patientisusingaK+sparing
diuretic

DOBUTAMINE
(Beta1agonist)

Stimulatesheartin
CHFandin
cardiogenicshock.

DOPAMINE

ForacuteCHFand
shock,increasesBP
andmaintainsrenal
bloodflow.

Phosphodiesterase
Inhibitors
MALRINONE,
INAMRINONE

Increasescontractility
andrelaxessmooth
muscle.

AdverseEffects:
Longtermuse
maycause
thrombocytopen
iaand
ventricular
arrhythmias.


LIPIDLOWERINGAGENTS
ThegoalsoflipidloweringagentsistoeitherdecreaseLDL,increaseHDL,orlower
triglycerides.Someofthedrugsaremorespecifictoanindividualchange,while
someprovidealittlebitofeverything.
AGENTS

Triglycerides LDLeffects

Statins(HMG
CoAreductase
inhibitors)

Milddecrease

Significant
decrease

Bileacidbinding
resins
(Cholestyramine)
Cholesterol
absorption
blockers
(Ezetimibe)
Niacin

Verysmall
increase

Moderate
decrease

Noeffect

Moderate
decrease

Milddecrease

Moderate
decrease

Fibratedrugs
(Gemfibrozil)

Significant
decrease

HDLeffects

Adverse
Effects
Mildincrease Muscle
breakdown
(check
myoglobin
levels,
increased
LFTs)
Noeffect
GIsymptoms,
terrible
tasting.
Noeffect
Increased
LFTs
Noeffect

Flushing(can
treatby
giving
aspirin)
Milddecrease Mildincrease Muscle
breakdown,
increased
LFTs.


ANTIHISTAMINES
1stgenerationantihistamines:

CompetitivelyblocktheH1receptor.
Arelipophilicandthuscrossthebloodbrainbarrier,causingsedation.
Haveincreasedanticholinergiceffectsthatlast46hrs.
DiphenhydramineandPromethazineblocktheNa+channel,thushave
anestheticactivity.

2ndgenerationantihistamines:

Lesssedating
Lessanticholinergiceffects
Longerlasting
Lesslipophilic
UsesCYP450metabolism

Cetrizine(Zyrtec)inhibitsmastcellrelease
Fexofenadine(Allegra)
Loratidine(Claritin)


WHEREDOASTHMADRUGSWORK?


ASTHMA
ThetwomaincategoriesaretheControllersandtheMainAttackRelief
medications.
CONTROLLERS
CORTICOSTEROIDS
MASTCELLSTABILIZERS
LONGACTINGBETA
AGONISTS
LEUKOTRIENERECEPTOR
ANTAGONISTS

MAINATTACKRELIEF
ALBUTEROL
IPATRAPIUM
THEOPHYLLINE
METAPROTERENOL
LEVALBUTEROL

Albuterol

Rapidinhalant
Shortacting2agonistusedforimmediaterelief.

Ipratropium

Amuscarinicantagonist
MostcommonlyusedforCOPD
Lesseffectivethanthe2agonist
Antimuscariniceffects
Causesslowerbronchodilationthatislonglasting

Theophylline

Inhibitsphosphodiesterase
Decreaseseosinophils/lymphocytes,andmonocytes
Loweredhalflifeinchildrenandinsmokers
Narrowtherapeuticindex
Commonlycausesheadaches,dizziness,hypotension,bradycardia

Corticosteroids
InhaledBeclomethasone,Triamclinolone,Budesonide,Fluticasone
OralPrednisone,Prednisolone

InhibitphopholipaseA2
Arethecornerstoneofasthmamanagement
DecreasesarachidonicacidthroughphospholipaseA2,inhibitingtheCOX2
pathway.
Oralcorticosteroidscancauseoralthrush
Longtermusecancauseosteoporosis,hypertension,diabetes,suppression
ofthepituitaryadrenalaxis,obesity,thinningoftheskin,andmuscle
weakness.

MastCellStabilizers

CromolynandNedocromil
Preventmastcelldegranulation
Usedasprophylaxis
Aresafertouseinkids

LongActingBetaAgonists

Salmetrolistheprototype
Preventsnocturnalasthmaticeffects

LeukotrieneReceptorAntagonists

MonteleukastandZafirlukast
Antagonizesleukotrienesthuspreventinganincreaseinbronchialtone

TreatingStatusAsthmaticus
Thecornerstoneofmanagementisepinephrineorprednisone.


PARKINSONSDISEASE
Parkinsonsdiseaseresultsfromthedegenerationofdopamine(DA)neuronsinthe
substantianigra.Symptomsarerestingtremor,rigidity,andbradykinesia.

Dopaminecannotcrossthebloodbrainbarrier,thusitisconvertedtolevedopain
ordertogetacrosstheBBB.Therearecertaindrugsthatcanbeusedinorderto
preventtheconversionoflevedopatootherthingsthatcannotcross.

DrugsthatincreaseDopaminelevels:
LEVEDOPA

CARBIDOPA

AMANTADINE

Whenusedaloneit
usuallycausesnausea
andvomiting

Inhibitsperipheral
conversionofLDto
DA

Longtermusecauses
involuntarymovement

Wontcrossthe
BBB

Anantiviralthat
increasesDA
releasefrom
nigrostriatum.

Avoidinpsychotic
patients

CancauseGIand
cardiacproblems

DecreasesDA
reuptake.
Cancause
Levido
Reticularis
(Redblueskin).

SELEGELINE
AnMAOBinhibitor
thatblocksthe
conversionofDAto
DOPAC.

TOLCAPONE

ACOMTinhibitorthatblocks
theconversionofLDto3OMT.

IncreasesLDbioavailability.

Causesanon/offeffectdueto
itscompetitionwithLDfor
entryintoBBB.

DopamineReceptorAgonists:
BromocriptineAnergotalkaloid,aD2agonistandD1antagonist.
PergolideD1andD2antagonist,cancauseneurologicalsymptoms.
RopinoroleThedrugofchoiceforrestlesslegsyndrome.

ALCOHOLS

Effectsofabuse:

CNSsedation
Decreasedviscosityofcellmembranes

WernickeKorsakoff:

Causedbyathiaminedeficiency
Ataxia/Nystagmus/Confabulations

METHANOL
Alsoknownasmethylalcoholorwoodalcohol.

Usedincommercialsolvents
Causesvisualdisturbances(Snowstormpattern)
TreatmentwithIVfomepizoleorIVethanol

ETHYLENEGLYCOL

Antifreeze,hasasweetsmell.
CausesCNSexcitationfollowedbyCNSdepression,followedbymetabolic
acidosis,thencausestheblockadeofrenaltubulesbyoxalatecrystals
TreatwithIVfomepizole(inhibitsalcoholdehydrogenase)
Characterizedbyoxalatecrystalsintheurine,metabolicacidosis,andan
absenceofvisualdisturbances

DISULFIRAMIsaprescriptionmedicationtakenbyalcoholicsthatinhibitsthe
alcoholdehydrogenaseenzymes.Thiscausesanaccumulationofacetaldehyde,
whichmakesthepatientverysick.

ANTISEIZUREDRUGS
Na+channel
inhibitors:

GABA
Enhancers:

Carbamazepine

Clonazepam

Phenytoin

Gabapentin

Valproate

Diazepate

Lamotrigine

Chlorazepate

Phenobarbitol

Vigabatrin

MixedAction:
Topiramate
Felbamate

1stlinetreatmentofabsenceseizures:

Ethosuxamide(children)
Valproate
TheseblocktheTtypeCa2+channels

1stlinetreatmentofPartial/GeneralTonicClonicseizures:

Carbamazepine
Phenytoin
Valproate

1stlinetreatmentofStatusEpilepticus:

IVDiazepam

ADVERSEEFFECTSOFANTISEIZUREMEDICATIONS:
Carbamazepinesedation
Phenytoingingivalhyperplasia/hirsutism/facialcoarsening/fetalhydantoin
syndrome
LamotrigineStevenJohnsonsyndrome


SKELETALMUSCLERELAXANTS


SKELETALMUSCLESPASMOLYTICS

NSAIDS,ACETAMINOPHEN,COX2INHIBITORS
NSAIDS
IncludeIbuprofen,Naproxen,Indomethacin
MOA:ReversibleinhibitionofbothCOX1andCOX2,whichthenblocksthesynthesis
ofprostaglandins.
USES:Usedasanantiinflammatory,antipyretic,andanalgesic.Indomethacinis
usedininfantstocloseapatentductusarteriosus.
ADVERSEEFFECTS:Ulcers,renaltoxicity,aplasticanemia.

ACETAMINOPHEN
AlsoknownasTylenol
MOA:CausesreversibleinhibitionoftheCOXpathway.
USES:Isusedforitsanalgesicandantipyreticproperties,butlackstheanti
inflammatorypropertiesseeninNSAIDS.
ADVERSEEFFECTS:Anoverdoseisdeadly,becauseofhepaticnecrosisduetotoxic
metaboliteswhichdepleteglutathioneintheliver,causingtheformationoftoxic
NAPQIintheliver.

COX2INHIBITORS
IncludeCelecoxib,Rofecoxib
MOA:SelectiveinhibitionofCOX2
USES:Excellentforinflammationandpain,buthelpstomaintaingastricmucosa
becauseitdoesntusetheCOX1.Mainclinicalusesarearthritis(osteoandRA).
ADVERSEEFFECTS:Renaltoxicity,sameasotherNSAIDSwithlessriskofgastric
ulcerations

ANESTHETICS
MAC(MinimumAlveolarConcentration)isaconceptusedinanesthesiologyto
comparethepotencyofanestheticagents.AnestheticswithahigherMACarecause
fasterinductionbuthavemuchlowerpotency,whilethosewithlowerMACvalue
areslowertoinduceanesthesiabuthaveahigherpotency.
Example:
MACofnitrousoxideis104,thusitactsfastandhasweakerpotency(hasincreased
bloodandlipidsolubility).
MACofhalothaneis0.75,thusisactsslowerbuthasastrongerpotency(has
decreasedbloodandlipidsolubility).

TheIdealAnesthetic:

Immediateonsetofaction
Hasreversibleproperties
Lastsforanappropriatedurationoftime
Hasawidetherapeuticrange
Causesnotissuedamageorirritation

Howtheywork:

PreventionofNa+influxacrossnervemembranes
Significantanesthesiapreventsfiringthresholdfrombeingobtained
Noactionpotential=Noimpulse=Conductionblockade

LOCALANESTHETICS
BlockageofNa+channels,inactivationisbyhydrolysis.

GENERALANESTHETICS

OPIOIDS
Receptorresponsibleforsupraspinalandspinalanesthesia,respiratory
depression,physicaldependence.
Receptorresponsibleforspinalanesthesiaanddysphoria.

SEDATIVE/HYPNOTICS
Sedativesdecreaseanxiety
Hypnoticsinduces/maintainssleep

Benzodiazepines(endwithpam)

Diazepam
Lorazepam
Midazolam
Triazolam

MOA:BindGABAchannels,increasingthefrequencyofchannelopening.
SPECIALUSES:
AlcoholwithdrawalChlordiazepoxide
PanicdisorderAlpralozam
MusclespasmsLorazepam
StatusepilepticusDiazepam
ForbenzodiazepineoverdoseFlumazenil

Barbiturates(endwithal)

Phenobarbital
Pentobarbital
Secobarbital
Thiopental

MOA:BindtononGABA,nonBenzosites,increasesthedurationofchannel
opening.
Patternofbarbituratedistribution:1stBrain2ndViscera3rdLeantissue4th
fat
USES:Anticonvulsant,preoperativesedation,comainduction

ANTIDEPRESSANTS
TricyclicAntidepressants:Blockthereuptakeof5HTandNE
DRUG
Amitryptiline

CHEMICALAFFECTED
5HT

Clomipramine
Desipramine
Nortryptaline
Imipramine

5HT
NE
NE
NE=5HT

IMPORTANTFACTS
Highlysedative,cancause
orthostatichypotension.
IstheTCADOCforOCD.
Lowsedation.
Leastsedative.
Moderatesedation,
orthostatichypotension.

2ndGenerationAntiDepressants:
DRUG
Amoxapine

CHEMICALAFFECTED
DA

Bupropion

DA,NE,5HT

Maprotiline
Trazadone

NE
5HT

IMPORTANTFACTS
Alsousedforpsychosis,
cancausetardive
dyskinesia.
Cancauseweightlossand
isalsousedforsmoking
cessation.

Cancausepriapism,CNS
depression,and
orthostatichypotension.

SSRIs:Arethesafestgroupofantidepressants.
DRUG
Fluoxetine(Prozac)

USES
Depression,panic
disorder,anorexia.

Fluvoxamine(Luvox)
Paroxetine(Paxil)

OCD,Panicdisorder.
Depression,panic
disorder.

Sertraline(Zoloft)

Depression,panic
disorder.

ADVERSEEFFECTS
HighinhibitionofCYP450,
canalterbloodglucose,
cancauseSIADH.

Highestbioavailability,
highestsedationofSSRIs,
weightgain.
VerylittleCYP450effect,
preferredintheelderly
becauseitdoesntaffect
metabolism.

MAOIs:UsewithextremecautionastheMAOIscancauseseriousreactionswith
certainfoodsand/ordrugs.Cheese,wine,etc,cancausecrisis.
MAOAI5HTandNE
MAOBIDA
1stGenerationMAOIs:

PhenelzineandTranylcypromide
Providenonselectiveinhibition
Affects5HT>NE
Itseffectisduetodownregulationofpresynapticregulation,thusincreasing
5HTneurons

2ndGenerationMAOIs:

Meclobemide
MAOAI

3rdGenerationMAOIs:

Selegeline
MAOBIforParkinsonsdisease

AdverseEffectsofMAOIs:

Sleepdisturbances
Weightgain
Orthostatichypotension

MAOIIntoxication:

Agitation
Delerium
Neuromuscularexcitation
Lossofconsciousness
Seizure
Shock
Hyperthermia

MoodStabilizers:
LithiumIstheDOCformoodstabilizationinbipolardisease.

Calmsmania
Cancausehypothyroidism

AdverseEffects:

Drowsiness
WeightGain
Lowsafetymargin
Theearliestsignofanoverdoseisnauseaandvomiting

ANTIPSYCHOTICS
MOAD2receptorantagonistsusedtodecreasethelevelsofdopamine(DA)
USEAlleviationofpsychosisandsymptomsofpsychosis.

ANTIMICROBIALS

Drugscontraindicatedinrenal
impairment:
Sulfonamides
Tetracyclines
Nitrofurantoin
Itraconazole
Cidofovir
Ribavirin
NalidixicAcid

Drugsthatrequireadjunctsin
patientswithhepatic
insufficiency:

Clindamycin

Chloramphenicol

Erythromycin

Metronidazole

Indinavir

Ramantadine

Variconazole
Caspofungin

Antivirals:
AcyclovirUsedforherpes,cancauseGIdisturbances,phlebitis,rash,and
headache.
GanciclovirIsfirstlineforCMV,cancausemyelosuppressionandCNStoxicities.
FoscarnetFirstlineforCMVretinitis,CMVcolitis,CMVesophagitis,andacyclovir
resistantHIV/VZV.Maycausenephrotoxicity,penileulcerations,andCNStoxicities.

BacterialResistance:
1. TransferableResistance(transferofplasmids)
2. Transformation(uptakeofDNA)
3. BacterialConjugation

HIGHYIELDANTIMICROBIALINFORMATION
Penicillin:

Usedagainstgram+vecocci,rods,gramvecocci,andspirochetes
(treponema)
BindstoPCNbindingproteins
Blocksthecrosslinkingofcellwalls(viatranspeptidaseblockage)

Aminoglycosides:

Includestreptomycin,gentamycin,tobramycin,neomycin,amikacin,
spectinomycin.
CausesmisreadingofmRNAviatheinhibitionofformationoftheinitiation
complex
Usedforseveregramverodinfections
Cancausenephrotoxicityandototoxicity
Showsaconcentrationdependentkillrate(CDKR)andapostantibiotic
effect(PAE).

Chloramphenicol:

Isbacteriostatic,inhibitingthe50sribosomalsubunitspeptidyltransferase
Usedforneisseriameningitides,streppneumonia,andhaemophilus
influenza
Cancausegreybabysyndromeandaplasticanemia.

Macrolides:

Includeerythromycinandclarithromycin
Workbyblockingtranslocation
Usedforupperrespiratoryinfections,Chlamydia,neisseria
CancauseGIsymptoms,rashes,eosinophilia,andcholestatichepatitis

Tetracycline:

Doxycyclineandminocycline
Worksbybindingtothe30Ssubunitandpreventingattachmentof
aminoacyltRNA.
Shouldavoidcertainfoodswhichlimititsabsorption,suchasmilkproducts
andproductshighinFe2+

Sulfonamides:

Includesulfamethoxazole,sulfadiazine,andothersulfas
Worksbyinhibitingtheenzymedihydrofolatereductase
UsedforUTIs,andbothgram+/organisms

Fluoroquinolones:

Includeciprofloxacin,norfloxacin,ofloxacin,moxifloxacin,gatifloxacin
InhibitsDNAgyrase
UsedforgramverodsintheGUandGItracts
CommonlycausesGIdisturbances,headache,rashes,dizziness

Cephalosporins:

Arebetalactamsthatworkbyinhibitingcellwallsynthesis
1stgeneration:Proteus,E.Coli,andKlebsiella
2ndgeneration:Haemophilus,Enterobacter,Neisseria,Proteus,E.Coli,
Klebsiella,andSerratia
3rdgeneration:Seriousgramveinfectionsthatareresistanttootherbeta
lactamdrugs.Usedformeningitis.
4thgeneration:Pseudomonasandgram+veorganisms
Commonlycausehypersensitivityreactions,withcrosshypersensitivitywith
penicillin
Cancauseadisulfiramlikereactionwhencombinedwithalcohol

Vancomycin:

BindstotheDalaDalaportionofcellwalls,thusinhibitingcellwall
mucopeptideformation
Usedinseriousgram+infections,suchasMRSA
Cancausenephrotoxicity,ototoxicity,thrombophlebitis,andredman
syndrome,wherethebodygetsflushed.

Metronidazole:

Worksbyformingtoxicmetabolitesinsidethecell
Usedforgiardia,entamoeba,andtrichomonas
Hasadisulfiramlikereactionwhencombinedwithalcohol

RIPE(TBdrugs):

Rifampin
Isoniazid
Pyrazinamide
Ethambutol
CancausehemolysisinG6PDdeficientpatients
CancauseanSLElikesyndrome
VitaminB6(pyridoxine)deficiencyfrompyrazinamide

AmphotericinB:

Worksbyformingporesinthecellmembrane
Usedforsystemicmycoses
Cancausefeversandchills,arrhythmias,hypotension,andnephrotoxicity

AntiviralActivity

CHEMOTHERAPEUTICS
DrugsclassificationsarebasedontheirMOAs:
Folateantagonists(Methotrexate)
Purineantagonists(6mercaptopurine)
Pyrimidineantagonists(5fluorouracil)
Ribonucleicreductaseinhibitors(Hydroxyurea)

DrugResistance:
InnatePrimaryresistancedevelopsduetoexposure.
AcquiredCausedbygenomicmutationsthatmaybetoasingledrugortomultiple
drugs.

MOAoftumorcellresistance:

Decreaseddrugaccumulation
Alteredaffinityoftargetenzymes
Lossofdrugactivatingenzymes
Increasedfunctionoftumorcellrepairmechanisms

Highyieldchemotherapeutictoxicities:
Commonchemotherapydrugtoxicitiesmyelosuppression,nausea/vomiting,
leucopenia.
NeurotoxicityVincristine,Paclitaxel
PulmonaryToxicityBleomycin,Busulfan
RenalToxicityCisplatin
HemorrhagicCystitisCyclophosphamide
CardiacToxicityDoxorubicin

Drugspecifictoxicities:
Carmustineproducesleukocytesuppression
Cisplatin,Carmustinemostemeticantineoplastics
5HT3antagonistspreventemesis
Metochlopromideusefulinpreventingchemotherapyrelatednauseaand
vomiting.

DIABETESPHARMACOLOGY
INSULINTYPE
Ultrashort
Acting(Lispro)
ShortActing
(Regular)
Intermediate
Acting(Lente)
LongActing
(Ultralente)

ONSETOF
ACTION
5minutes

PEAKOF
DRUG
1hr

DURATION
OFACTION
3hr

TYPICALUSE

30minutes

34hr

68hr

30minutes

12hr

24hr

Morningand
night
qid

2hr

12hr

24hr

qid

Beforemeals

Thereisariskofhypoglycemiccrisisifproperregulationofinsulinnotused

Sulfonylureas:
Glyburide,Tolbutamide
MOA:Causesdepolarizationofbetacellsofthepancreas,thusincreasingthe
releaseofinsulin.

GASTROINTESTINALPHARMACOLOGY
H2antagonists:Cimetidine,Ranitidine.

Lowersacidsecretion
Notusedas1stlinedrugforGERD,PUD,etc.

ProtonPumpInhibitors:Omeprazole

IsdiagnosticandtherapeuticdrugofchoiceforGERDandPUD
AlsousedincasesofZollingerEllisonsyndrome

MucosalProtectants:Sucralfate

Worksbyadheringtoproteinaceouslesionsonthesurface
IsaseffectiveasanH2receptorantagonistwouldbein48weeks

Prostaglandins:Misoprostal

CanbegivenwhenpatientisusinghighdoseNSAIDtherapy
BlockscAMP
Alsocausedabortioninpregnantwomen
Cancausewaterydiarrhea

Antiemetics:5HT3receptorantagonists

Ondasetron

Prokinetics:Alosetron

CanbeusedfortreatmentofIBS,butislastlineafterconservativetherapies
fail

IrritableBowelDisease:

1stlinetreatmentofulcerativecolitisisSulfasalazine
1stlinetreatmentofCrohnsdiseaseisBudesonide

CALCIUMANDBONEHOMEOSTASIS
PTHforboneresorption,andisstimulatedwhenserumcalciumdecreases.
CalcitoninperformsalloppositeactionofPTH(parathyroidhormone).
1,25dihydroxyvitaminD3producedinthekidney
Osteoporosis1stlinepharmacologicaltreatmentisalendronate(bisphosphonate)
PagetsDiseaseTreatmentinvolvesbisphosphonatemedicationsuchas
alendronate.

THYROIDPHARMACOLOGY
Levothyroxine(T4)isthedrugofchoiceforalltypesofhypothyroidism.
Liothyronine(T3)morepotentthanlevothyroxine,hasashorterhalflife,isnot
usedasatherapeuticagentinthyroidproblems.
MethimazoleandPropylthiouraciltwodrugsusedforhyperthyroidism.

Propylthiouracil(PTU)InhibitstheperipheralconversionofT4T3
GravesDiseaseMethimazoleorPTUisusedtoinduceremissionortocontrol
symptomspriortosurgeryorradioiodineablation.
IodideSaltsinhibitthereleaseofthyroidhormonefromthethyroidgland.
PotassiumIodidesolutionisusedtocontrolthesymptomsofacute
thyrotoxicosis,decreasesthevascularityandsizeofthethyroid,andinhibitsthyroid
hormonereleasefollowingRAItreatment.
RAI(I131)isusedinthetreatmentofGravesdisease,worksbyemitting
chemicalsthatkilltissueofthethyroid.

PHARMACOLOGYOFPITUITARYANDHYPOTHALAMUS
Cosyntropinisasyntheticcorticosyntropinanalog,isusedtodiagnoseadrenal
insufficiency.
OctreotideisasyntheticsomatostatinthatinhibitsGHsecretion,isusedtotreat
acromegaly.
Menotropinsinducesovulationininfertilewomen.
GonadorelinisaGnRHthatisadministeredinapulsatileform,thisinduces
ovulationinwomenwithamenorrheaduetohypothalamicdysfunction.
Leuprolideusedinkidswithprecociouspuberty,itactsbysuppressing
gonadotropinsecretionfromthepituitary.
Bromocriptineisgiventothosewithprolactinomas,usedtoshrinkthenmassso
thesymptomswillcease.IsaDAantagonist.
Oxytocinusedtoinduceand/oraugmentlaborinwomenwhohavetroublewith
delivery,alsostimulatesmilkletdowninnursingwomen.
Desmopressinisasyntheticanalogofvasopressin,treatmentfordiabetes
insipidus.


NSAIDS
Acetaminophenantipyretic,analgesia,reversibleCOXinhibition.Lacksanti
inflammatoryproperties.OverdoseistreatedwithNAcetylcysteine.
AspirinHasanalgesicandantiinflammatoryproperties,inhibitstheCOX2
pathways.CausesGIirritationbyinhibitingprostaglandins,whichareprotectiveto
GImucosa.
IndomethacinisanonselectiveCOX1inhibitor,inhibitorofphospholipaseAand
C.UsedtocloseaPDA,alsousedingoutandformanagementofankylosing
spondylitis.
Ibuprofenprovidesanalgesiawithoutantipyreticproperties,haslessGIirritation
thandoesaspirin.

ANTICOAGULATION

REPRODUCTIVEPHARMACOLOGY
Thereareafewverycommonmedicationsusedtoinduceovulationandthus
increasethechancesofpregnancy.
CLOMIPHENE:Theagentofchoiceforovulationinduction,itactsbyincreasing
GnRHsecretionfromthehypothalamus,whichthenincreasesthelevelsofFSH,
increasingthefertility.Thisallhappensviatheblockingoftheestrogenreceptors,
thustrickingthebodyintobelievingthatthelevelsofestrogenaremuchlowerthan
theyactuallyare.
HUMANMENOPAUSALGONADOTROPIN(Menotropin):Isextractedfromthe
urineofmenopausalwomen.ItishighinLHandFSH,whichincreasesfertility.

CHAPTER13

PATHOLOGY

Duetosheervolume,thepathologysectionoftheStep1
examisbyfarthemostchallenging.TheUSMLEexamis
movingmoreandmoretowardsbeingaclinicalexam,thus
itisextremelyimportanttorecognizethesigns,symptoms,
commonpresentations,uncommonpresentations,and
pathophysiologyofpathologicalconditions.
Specialattentionshouldbepaidtodiseaseentitiesthatare
morecommonintheUnitedStates,asopposedtothosethat
aremoreprevalentinotherareasoftheworld.

GASTROINTESTINAL

CONDITIONSOFTHEESOPHAGUS:

Barrettsesophagus
Achalasia
Esophagealcancer

BARRETTSESOPHAGUS
Barrettsesophagusisaconditionwherebyachronicexposuretoacidiccontents
fromthestomachcausemetaplasiaoftheepitheliumatthesquamocolumnar
junctionintheesophagus.Themetasplasiachangesfromsquamousepithelium
(nonkeratinized)tocolumnarepithelium.Thereasonforthisisthatsquamous
epitheliumisnotveryprotectiveagainstacidiccontents,whilethecolumnar
epitheliumisdesignedspecificallyforthispurpose.


ACHALASIA
Achalasiaisaconditionwherebytheloweresophagealsphincterfailstorelax.This
isanesophagealmotilitydisorderthatinvolvesthesmoothmusclelayerofthe
esophagusandtheloweresophagealsphincter.Characterizedbyanincomplete
relaxationoftheloweresophagealsphincter,increasedloweresophagealsphincter
tone,andalackofperistalsisintheesophagus.
Characteristics:

Dysphagia
Regurgitation
Chestpain

Thereareafewreasonswhythismayhappen,theyinclude:

Chagasdisease
Lossofmyentericplexus
Esophagealcarcinoma

Thebestdiagnostictoolforthisconditionisabariumswallow.


ESOPHAGEALCANCER
Thetwotypesofesophagealcancerare:AdenocarcinomaandSquamousCell
carcinoma.
AdenocarcinomathistypeofcancerisoftensecondarytoBarrettsesophagus.
SquamousCellCarcinomathistypeofcancerisoftencausedbyexposureto
alcoholandcigarettesmoke(onachronicbasis).
ThepopularmnemonicABCDEFisexcellentforrememberingthecommoncauses
ofesophagealcancer.
AAlcohol
BBarrettsesophagus
CCigarettesmoke
DDiverticula(especiallyZenkers)
EEsophagealWebs
FFamilyhistoryofesophagealcancer

GASTRITIS
Gastritisiscausedbyaninflammationofthestomachlining.Themostcommon
causeofgastritisisprolongeduseofNSAIDs(ieAspirin),whichblocksthesynthesis
ofprostaglandins,thusdecreasingtheprotectionofthestomachlining.Other
commoncausesarealcoholconsumptionandH.Pylori.
Symptomsinclude:

Painintheepigastricregion(mostcommonpresentation)
Weightloss
Lossofappetite

AcuteGastritisalsoknownaserosivegastritis,thisformofgastritisiscaused
mostcommonlybydamagestothestomachsmucosaldefensesystem.NSAIDsand
alcoholaremostcommoncausesofacutegastritis.
ChronicGastritisthisistheresultofanH.Pyloriinfection.
Typesofchronicgastritis:
TypeAOccursinthefundusofthestomach,isofautoimmunenature.

TypeBOccursintheantrumofthestomach,iscausedbyanH.Pyloriinfection.

PEPTICULCERDISEASE
TherearetwotypesofPUD,oneisgastricandoneisduodenal.
ThegastricPUD:

Patientusuallyhasanassociatedweightlossasthereisincreasedpainwith
eating.
ThecauseofagastricPUDisdecreasesinmucosalprotection,thuscaused
commonlybyNSAIDs.

TheduodenalPUD:

Patientwillusuallyhaveweightgainandthepainwilldecreasewitheating.
ThisisalmostalwayslinkedtoanH.Pyloriinfection.
Themaincauseisanincreaseingastricacidsecretioninconjunctionwith
decreasedmucosalprotection.
TherewillbehypertrophyofBrunnersglands(submucosalglandsofthe
duodenumwhoproduceamucusrichalkalinesecretion).

INFLAMMATORYBOWELDISEASE
ThetwotypesofIBDareCrohnsdiseaseandUlcerativeColitis

CROHNSDISEASE
ILEUMINVOLVEMENT
Commonlyinvolvesileum
COLONICINVOLVEMENT Colonicinvolvementoften
RECTALINVOLVEMENT
BILEDUCT
INVOLVEMENT
DISEASEDISTRIBUTION
ENDOSCOPICVIEW

Rarely
None
Patchy,skiplesions
Ulcersarelinear,
serpiginous
Transmural,deep
Often
Highriskinsmokers

ULCERATIVECOLITIS
Rarelyinvolvesileum
Colonicinvolvement
always
Almostalways
Sometimes
Continuousinflammation
Ulcerationiscontinuous

INFLAMMATIONDEPTH
Shallowandmucosal
FISTULAFORMATION
Rarely
ASSOCIATIONWITH
Lowriskinsmokers
SMOKING
SURGICAL
Returnsfollowingsurgical
Curedoftenbysurgical
INTERVENTION
intervention
removal
AUTOIMMUNECAUSES?
Seenasautoimmune
Notseenasautoimmune
RISKOFCANCERIN
Lowcomparedtocolitis Cancerriskhigherthanin
ASSOCIATION
Crohns
BIOPSYREVEALS
Granulomatous
Nongranulomatous

IRRITABLEBOWELSYNDROME(IBS)
Isadiagnosisofexclusion.IBSpresentsmostcommonlyinayoungfemaleinher
twenties,whopresentswithabdominalpain/bloating,alteredbowelhabitsinthe
absenceofanyorganiccause.Symptomsarerelievedafterabowelmovement.
ManagementofIBSisincreasedfluidintake+increaseddietaryfiberintake(ie.
Fibersupplementation).Ifthisdoesnotwork,certainmedicationscanbeexplored,
butthisisusuallyacurativeapproach.


SYNDROMESOFMALABSORPTION
ThecommonlytestedsyndromesofmalabsorptionareCeliacSprue,TropicalSprue,
andWhipplesdisease.Symptomsoftheseconditionsare:Weightloss,cramping,
diarrhea,steatorrhea,indigestion,andfatigue.
CeliacSprueCausedbyautoantibodies(antigliadin,antiendomysial,antitissue
transglutaminase)againstgluten,whichcausesvillousbluntingandinfiltrationof
lymphocytes.Treatmentistoconsumeaglutenfreediet.
TropicalSprueThisisaninfectiousconditioncommonlyfoundintropicalregions,
andismarketbyabnormalflatteningofthevilliinthesmallintestine.
WhipplesDiseaseThisisrarerthantheothertwomalabsorptionsyndrome.Itis
causedbyaninfectionwiththebacteriumTropherymaWhipplei,andcancause
malabsorptioninconjunctionwithmanysystemicproblems(cardiac,respiratory,
neurological,rheumatologic,andvisual).

HEPATITIS
Hepatitisisageneraltermtodescribetheinflammationoftheliver.Therearemany
possiblecausesofhepatitis,suchasalcohol,drugs,viral,anddiseaserelated.
CausesofViralHepatitis:
Fivemaintypesofviralhepatitisare:HepA,B,C,D,andE.Hepatitiscanalsobe
causedbyEpsteinBarrvirus,cytomegalovirus,andherpessimplexvirus.
Transmissionofviralhepatitis:
HepatitisA&Efecaloraltransmission,higherindevelopingcountries
HepatitisBtransmissionisparenteralorsexual
HepatitisDrequirescoinfectionwithhepatitisB(requirestheouterenvelopeof
theHbsAg)
HepatiticCtransmittedparenterallyandisthusmorecommoninIVdrugusers
*OnlyhepatitisB,C,andDcanprogresstochronichepatitis.


CIRRHOSIS
Cirrhosisisaconsequenceofchronicliverdisease,wherebythenormalarchitecture
oftheliverisreplacedbyfibrosisorscarring.Nodulesthatarelessthan3mmare
micronodularandareduetometaboliccausessuchasalcoholism.Nodules
greaterthan3mmareusuallycausedbysevereinjurythathasleadtodeathofliver
cells.Alongwithcirrhosiscomesavarietyofadverseeffects,ontopoftheadverse
effectsfromcirrhosisthereareadverseeffectscausedbytheportalhypertension
thatoccurs.
CIRRHOTICEFFECTS
Gynecomastia
SpiderNevi
Jaundice
Asterixis
BleedingDyscriasies
Anemia
Edema
Icterus

PORTALHTNEFFECTS
EsophagealVarices
Hemorrhoids
AtrophyofTestes
Splenomegaly
CaputMedusae
PUD
Ascites


PANCREATITIS
Pancreatitisisaninflammationofthepancreasthatcausesverycharacteristicsetof
symptoms.Thepatientwillalmostalwayspresentwithsevereepigastricpainthat
radiatestotheback.Thetwomostcommoncausesofpancreatitisarealcoholand
gallstones,butthereareotherpossiblecauses,suchas:

Trauma
Steroids
Mumps
Hyperlipidemia
Autoimmuneconditions
Stingfromascorpion

Inpancreatitis,lipaseandamylasewillalwaysbeelevated(lipaseismorespecific).

PANCREATICADENOCARINOMA
Pancreaticcancerisagravediagnosisandoftencausesdeathwithin6monthsof
diagnosis.Itisoftenasymptomaticandthereforehighlymetastasizedbythetimeof
diagnosis.Themostcommonsiteofthecancerisintheheadofthepancreas,which
iswhytheonlypresentingsymptomsisoftenpainlessjaundiceandsignificant
weightloss.
Othercommonlypresentingsymptomsofpancreaticcancerinclude:

Abdominalpain
Migratorythrombophlebitis
Palpablegallbladder(Courvoisierssign)andobstructivejaundice

Possiblecausesofpancreaticcancer:

Increasedage
Malesex
Cigarettesmoking
Obesity
Diabetesmellitus
Chronicpancreatitis
H.pyloriinfection
Familyhistory

**Alcoholhasnotbeenproventocausepancreaticcancer,howeveralcohol
consumptioncanleadtochronicpancreatitiswhichmayleadtopancreatic
cancer.Thereforethepossibilitycannotberuledout.


APPENDICITIS
Appendicitisisarelativelycommonconditionandisthemostcommonindication
foremergencyabdominalsurgeryinchildren.
Presentationisdiffuseabdominalpainintheperiumbilicalregion,followedby
localizationofpaintoMcBurneyspoint.Patientwillalsohavenausea,vomiting,
andoveralllookill.
**Acomplicationofappendicitisisperforation,whichcanleadtosepsis.


INTUSSUSCEPTION
Thisisaconditionofthebowelwherebyonesegmentinvaginatesortelescopes
intoanothersegmentofbowel.Theintussusceptionalwaysmovesintoadistal
segment.Earlysymptomsincludenausea,vomiting,andpullingofthelegsintothe
chest(forpainrelief).Themostcommonassociationwiththisconditioniscurrant
jellystools,whichisamixtureofbloodandmucus.Aswell,thereisapalpable
sausageshapedmassfeltintheabdomen.
Treatmentinvolvesusinganenema,whichoftenfixestheproblem.


VOLVULUS
Avolvulusisatwistingofthebowelarounditsmesentery,whichcanleadto
obstruction.Thisisanemergencyandrequiresanemergentlaparotomytorelieve
thetwisting/obstructionandpreventischemiaofthebowel.


DIVERTICULARDISORDERS
Adiverticulumisanypouchthatleadsoffofthedigestivetract.Atruediverticula
includesthemucosa,themuscularis,andtheserosa.Manydiverticulaarefalse
sincetheydonotincludeallofthelayersofthetract.
Themostcommontypesofdiverticula:

Zenkersdiverticulum
Meckelsdiverticulum
Diverticulosis
Diverticulitis

ZENKERSDIVERTICULUM
AZenkersdiverticulumisanoutpouchingfoundinthepharynx,abovethe
cricopharyngealmuscle.Itpresentscommonwithapatientwhohasterriblebreath
(duetofoodaccumulationinthediverticula).Thisoccurs1/3distancefrom
oropharynxtoloweresophagus.Diagnosisismadewithabariumswallow.

MECKELSDIVERTICULUM
Thisisacongenitaldiverticulumthatislocatedinthedistalileum.Itpresents
commonlywithpainlessbloodinthestoolofanewborn.Itisaremnantofthe
omphalomesentericduct,andisthemostfrequentlyencounteredmalformationof
theGItractofthenewborn.Diagnosiscanbemadewithatechnetium99scan,
whichdetectsthelocationofbleedingalongtheGItract.

DIVERTICULOSIS
Diverticulosisisaconditionwheretherearemanydiverticulainthecolon.With
increasingagethereisanincreasedriskofhavingdiverticulosis.Diverticulosisis
themostcommoncauseofrectalbleedinginsomeoneover50yrofage.Increased
luminalpressureandcolonicwallweaknesscausestheactualoutpouchingofthe
serosa,wherealowfiberdietisthemostcommoncauseofthiscondition.

DIVERTICULITIS
Thisissimplyaninflammationofthediverticula.ItpresentswithsevereLLQpain
andposestheriskofperforation,peritonitis,andstenosisofthebowellumen.


HIRSCHPRUNGSDISEASE
Acongenitalmegacoloncausedbyalackofmigrationoftheneuralcrestcellstothe
lowersegmentofthecolon(knownasthetransitionzone),(Auerbachsand
Meissnersplexusareabsentonbiopsy).Aninfantwillpresentwithchronic
constipation,butthiscanalsopresentatanypointinlife.Thereisaportionofthe
colonthatisdilatedproximaltotheaganglionicsegment.

BUDDCHIARISYNDROME
BuddChiarisyndromecausesobstructionoftheinferiorvenacava.Asaresultof
thisobstruction,hepaticveinsbecomecongested(centrilobar)andthiscancause
necrosis.Thiswilleventuallyleadtocongestionoftheliverand
ultimately/eventuallyleadtofailureoftheliver.Thisconditionisespecially
commoninpregnancy,inthosewithhepatocellularcarcinoma,andinthosewith
polycythemiavera.


HEMOCHROMATOSIS
Thisisaverycommonconditionthatiscausedbyadefectinironmetabolism,
whichleadstoanironoverloadinvitalorgans,joints,andtissues.Earlydiagnosis
canhelppreventadverseeffectsoftheironoverload.
Hemochromatosispresentswithaclasstriadof:
1. Micronodularcirrhosis
2. Pancreaticfibrosis
3. Skinpigmentation
Thisconditionisclassicallyknownasbronzediabetesduetothefactthatittintsthe
skinbronzeandalsoaffectsthepancreas.Totalbodyironlevelsmayreach
upwardsof50g,andthismustbemanagedwithrepeatedphlebotomy.This
conditioncanleadtocongestiveheartfailureandcanincreasetheriskof
hepatocellularcarcinoma.
LABS:Inthosewithhemochromatosis,labswillshowIronandFerritin,witha
totalironbindingcapacity.

WILSONSDISEASE
Isanautosomalrecessivedisorderwherethereisafailureofcoppersabilityto
entercirculationintheformofceruloplasmin.Thisleadstocopperaccumulationin
certaintissues(liver,brain,cornea),andistreatedwithpenicillamine(chelationof
copper).
ThemostcommonsignsandsymptomsofWilsonsdiseaseare:

Corneadeposits(KayserFleischerrings),verycommoninWilsonsdisease
Asterixis
Parkinsonlikesymptomsduetoaccumulationinbasalganglia
Carcinoma
Dementia


HEPATOCELLULARCARCINOMAHCC)
Hepatocellularcarcinomaisaverycommoncauseofmetastasis,andspreadsby
hematogenousroute.MostcasesofhepatocellularcarcinomaareduetohepatitisB
and/orC,aswellascirrhosis.OthercausesofHCCincludeWilsonsdisease,
hemochromatosis,alcoholiccirrhosis,and1antitrypsindeficiency.
Theoutcomeisusuallypoor,however12outof10casesaretreatablewithsurgical
removalofcancers.

HYPERBILIRUBINEMIAS(HEREDITARY)
Therearethreecommonlytestesandencounteredhereditaryhyperbilirubinemias,
theyare:
1. Gilbertssyndrome
2. CriglerNajjarsyndrome
3. DubinJohnsonsyndrome

GilbertsSyndrome:
GilbertssyndromeisabenignconditionwherethereisamilddecreaseintheUDP
glucuronyltransferaseenzymes.Thisleadstoanelevationofunconjugated
bilirubin.
CriglerNajjarSyndrome:
This is a severe condition that leads to death early in life. There is a complete
absence of UDPglucuronyl transferase, which leads to significant increases in
unconjugatedbilirubinandcausesittodepositinthebrain(kernicterus),aswellas
jaundice.ThereisalesssevereversionofCriglerNajjarcalledtype2,anditcan
bemanagedwithPhenobarbital.
DubinJohnsonSyndrome:
This syndrome occurs as a result of a defect in the livers ability to excrete
conjugatedbilirubin.Itisbenignbutthereisachangeincolorofthelivertoblack.
AdifferentformofthissyndromeisRotorssyndrome,whichisevenmilderand
causesnochangeinthecoloroftheliver.


GALLSTONES
Gallstones are formed as a result of increased cholesterol or bilirubin. They can
occur anywhere in the biliary tree (including inside the gallbladder and in the
commonbileduct).Whenastonebecomeslodgedinsidethecommonbileduct,this
is known as choledocholithiasis. Pain can result when the gallbladder contracts
againstthestoneanditdoesnotgetpropelledforward.
Fourriskfactorsare:FOURFs:FEMALE,FERTILE,FAT,FORTY
Threetypesofstones:
1. Cholesterolareradiolucentwithsomebeingopaquefromcalcification.
2. Mixedthisisthemostcommontype,andisradiolucent.
3. Pigment stones this is seen in patients who have chronic red blood cell
hemolysis,alcoholiccirrhosis,biliaryinfection.Thisisradiopaque.


BILIARYCIRRHOSIS
Therearetwotypesofbiliarycirrhosis:PrimaryandSecondary
PrimaryBiliaryCirrhosis:

Isanautoimmunedisordercausedbyantimitochondrialantibodies
Causesaseverecaseofobstructivejaundicewithalloftheadverseeffects
associatedwithseverejaundice(pruritis,hypercholesterolemia)

SecondaryBiliaryCirrhosis:

Thisbiliarycirrhosisisduetoobstructionoutsideoftheliver(extrahepatic)
Causesabuildupofpressurewithintheductsoftheliver,andweget
bacterialinfections,ascendingcholangitis,bilestasis.

PRIMARYSCLEROSINGCHOLANGITIS
Anotherautoimmunediseaseoftheliver,wherethereisaslowlyprogressing
destructionofthebilecanaliculi.Destructionleadstocholestasisandtherefore
damage,inflammation,andfibrosisofthebileducts.Theclassicpresentationofthe
bileductsisthebeading,wherebythereisalternatingdilationandstrictureofthe
ductasseenonendoscopicretrogradecholangiopancreatography(ERCP).

CONGENITALPATHOLOGY

Thereareagroupofcommoncongenitalpathologiesthatarehighyieldforthe
USMLEStep1exam,theyinclude:

Defectsoftheheart
Spinabifida
Hypospadias
Cleftlip
Pyloricstenosis
Anencephaly

CONGENITALHEARTDEFECTS
Themostcommoncongenitalheartdefectsinclude:

Ventricularseptaldefects
Atrialseptaldefects
Patentductusarteriosus
Tetralogyoffallot
Truncusarteriosus
Transpositionofthegreatvessels
Coarctationoftheaorta

DEFECTSCAUSINGARIGHTTOLEFTSHUNT
Thesedefectscausedefectsthatforcebloodfromtherightsideofthehearttothe
leftsideoftheheartduetopressure,resultinginearlycyanosisbecausesystemic
bloodislackingoxygen.Thebabiesareoftenblueincolorbecausetheydonot
receiveadequateoxygen.
ThethreecommoncongenitalmalformationscausingaRLshuntare:
1. Tetralogyoffallot
2. Transpositionofthegreatvessels
3. Truncusarteriosus

TETRALOGYOFFALLOT:
Thisconditionresultsinagroupofproblems,thatultimatelyleadtoearlycyanosis
duetoshuntingofbloodfromtherighttotheleftthroughtheventricularseptal
defect.Thisiscausedbyananteriosuperiordisplacementoftheinfundibular
septum.
The4pathologiesoftetralogyofFallotare:
1.
2.
3.
4.

Pulmonarystenosis
Rightventricularhypertrophy
Overridingaorta
Ventricularseptaldefect(providesareaforshunting)

TRANSPOSITIONOFTHEGREATVESSELS:
Thisconditionresultsintheaortaconnectedfromtherightventriclewhilethe
pulmonarytrunkleavesfromtheleftventricle.Thisresultsinaseparationofthe
systemicandpulmonarycirculations.Sincethereisnooxygenatedbloodbeing
pumpedsystemically,thisconditionisincompatiblewithlife(unlessthereisthe
presenceofashunt).Transpositionofthegreatvesselswarrantsimmediate
surgicalcorrectionforsurvival.Theconditioniscausedbyfailureofthe
aorticopulmonaryseptumtospiral.

TRUNCUSARTERIOSUS:
Truncusarteriosusoccurswhenthereisanincompleteorfailedseptationofthe
embryonictruncusarteriosus.Thisresultsinasinglearterialtrunkthatarisesfrom
twonormallyformedventricles.Thepulmonaryarteriescanarisefromthe
commontrunkinamyriadofpatterns,thusgivingthisconditionseveraldifferent
subtypes.

DEFECTSCAUSINGALEFTTORIGHTSHUNT
TherearethreeconditionsthatcauseaLRshunt,theyinclude:
1. Ventricularseptaldefects
2. Atrialseptaldefects
3. Patentductusarteriosus

VENTRICULARSEPTALDEFECT
Thisisthemostcommonofallcardiaccongenitalanomalies.Thisdefectdoesnot
resultiscyanosisbecausetheLRshuntdoesntputnonoxygenatedbloodback
intothesystemiccirculation.Thiscanbedetectedbyhearingapansystolicmurmur
onauscultation.Thereisusuallynodetectionatbirth,butwithinafewweeksitwill
bedetectable.

ATRIALSEPTALDEFECT
Thisisaconditionwherethereisacommunicationbetweenboththerightandleft
atriaoftheheart.TheASDisthemostcommoncongenitalheartdefectseenin
adults.

PATENTDUCTUSARTERIOSUS
Theductusarteriosusisavascularconnectionbetweenthepulmonaryarteryand
theaorticarchinthedevelopingfetus.Uponanewbornsfirstbreath,theprocessof
PDclosureshouldoccur,howeveritsometimesdoesnot.Ifclosurefailstooccur,
theneonatewillexperiencepersistentrespiratoryproblems.ThePDAcanbeclosed
bygivingindomethacin,andcanbekeptopenedwithprostaglandinE.

COARCTATIONOFTHEAORTA
Thisisanarrowingoftheaortathatcanoccurintwodifferentplaces.The
preductalformoccursproximaltotheductusarteriosus,thepostductalform
occursdistaltotheductusarteriosus.Thepostductalformisassociatedwithrib
notching,upperextremityhypertension,andweakpulsesinthelowerextremities.
Coarctationoftheaortaisseeninmalesmuchmorethaninfemales.


NEURALTUBEDEFECTS
Neuraltubedefectsoccurmostcommonlywhenthereisalackofadequatefolicacid
intakeduringpregnancy.Upontesting,thereisoftenanelevationinfetoprotein
intheamnioticfluid.
Therearethreepresentationsofneuraltubedefects,theyinclude:
1. Spinabifidaoccultawhichresultswhenthereisanincompleteclosureof
thespinalcanal.Thereisnoactualherniationofanyspinaltissue.Thisoften
presentswithatuftofhairontheskinabovetheproblem.
2. Meningoceleresultswhenthespinalmeningesherniatedthroughthe
openinginthevertebra.
3. Meningomyeloceleresultswhenboththemeningesandthespinalcord
herniatedthroughthebonydefectofthevertebra.


TRISOMYDISORDERS
Thethreemostcommonlyencounteredautosomaltrisomydisordersare:
1. Pataussyndrome
2. Edwardssyndrome
3. Downssyndrome

PatausSyndrome:

Causedbytrisomy13
Cleftlipandpalate
Severementalretardation
Microphthalmia
Microcephaly
Deathusuallywithin1styearofbirth

EdwardsSyndrome:

Causedbytrisomy18
Rockerbottomfeet
Lowsetears
Clenchedhands
Prominentocciput
Deathusuallywithin1styearofbirth

DownsSyndrome:

Themostcommonchromosomaldisorder
Themostcommoncauseofcongenitalmentalretardation
Causedbytrisomy21
Prominentepicanthalfolds
Simiancrease
IncreasedriskofALL
Congenitalheartdisease(ASDmostcommonly)
Causedmostcommonlybymeioticnondisjunctionofhomologous
chromosomes


SEXCHROMOSOMEDISORDERS
1. XYYSyndrome
2. Turnerssyndrome
3. Klinefelterssyndrome

XYYSyndrome:
Patientsarephenotypicallynormalbutareunusuallytall,havesevereacne,andare
pronetoantisocialbehaviors.

TurnersSyndrome(XO):
Patientsarefemale,haveshortstature,webbednecks,widelyspacednipples,
ovariandysgenesis,andexperienceprimaryamenorrhea.Thispatientisalsoprone
tohavingcoarctationoftheaorta.

KlinefeltersSyndrome(XXY):
Malepatientswhoaretall,havelong/thinextremities,femalebodyhairpatterns,
testicularatrophy,andgynecomastia.

FRAGILEXSYNDROME
FragileXsyndromeisanxlinkeddisorder,andisthe2ndmostcommoncauseof
mentalretardation.Isatripletrepeatdisorderthatcanshowanticipation.Patients
havelargetesticles,longfaceswithlargejaw,andlargeears.


HERMAPHRODITISM
TrueHermaphroditepatientiseither46xxor47xxy,havingbothtestesand
ovariespresent,withambiguousgenitalia.Thisisararesyndrome.
PseudohermaphroditismFemaleandMaletypes:
Femaleovariesarepresentbuttheexternalgenitaliaarevirilizedorambiguous.
Causedbyexcessiveexposuretoandrogensduringgestation.
Maletestesarepresentbuttheexternalgenitaliaarefemaleorambiguous.The
mostcommonformistheandrogeninsensitivitysyndrome.

ANDROGENINSENSITIVITYSYNDROME
Thispatientisgeneticallymale,howevertheyhaveandrogenreceptorsthatare
insensitivetotheeffectsofandrogens,makingthemappearfemale.Thereare
normalappearingexternalgenitaliabutthevaginalcanalisnotdeveloped(blind
vagina).Therearenouterinetubesoruterus.Becausethereisnosecretionofmale
hormonesbythetestes(whicharepresentinthelabiabutoftenremoved),thereis
nonegativefeedbackandthustestosterone,estrogen,andLHwillremainelevated.

MUSCULARDYSTROPHY
Thetwotypesofmusculardystrophyare:DuchennesandBeckersmuscular
dystrophy.
DuchennesThisisthemoresevereformofmusculardystrophy,wherebya
deletionofthedystrophingenecausesanaccelerationofmusclebreakdown.
Patientwillexperienceweaknessesofthepelvicgirdleandoverallprogressive
weakness.Commonlyfoundispseudohypertrophyofthecalf(fattyreplacementof
themuscle).PatientscommonlyusetheGowersmaneuver,wheretheyusetheir
armstoclimbupthelegsandachieveastandingposture,whichischaracteristicof
musculardystrophy.
BeckersThisisalesssevereversionofmusculardystrophywherebythereisa
mutationofthedystrophingene,ratherthanacompletedeletion.
Diagnosingmusculardystrophyisdonebyfindingelevatedcreatinekinaselevels
andmusclebiopsyshowingthesegenemanipulations.


5REDUCTASEDEFICIENCY
ThisenzymeisresponsibleforconvertingtestosteronetoDHT.Whenthiscondition
occursindevelopingfetus,theywillhaveambiguousgenitaliauntilpubertywhen
levelsoftestosteroneincrease,causingamasculinizationofthegenitalia.

22q11SYNDROMES
CATCH22isthecommonmnemonicusedtorememberthisseriesofsyndromes
thatcommonlyoccurtogether.
Ccleftpalate
Aabnormalfacies
Tthymicaplasia
Ccardiacdefects
Hhypocalcemia
22Microdeletionatthe22ndchromosomeatloci11


COMMONAD,AR,ANDXLINKEDDISORDERS
Themostcommonautosomaldominantdisordersinclude:

Neurofibromatosis1and2
Huntingtonsdisease
Familialhypercholesterolemia
Polycystickidneydisease
Hereditaryspherocytosis
Marfansyndrome

Themostcommonautosomalrecessivedisordersinclude:

Sicklecellanemia
Cysticfibrosis
TaySachsdisease
Phenylketonuria
Albinism
Thalassemias
Mucopolysaccharidoses
Galactosemia
Glycogenstoragediseases

Themostcommonxlinkeddominantdisorders:

VitaminDresistantrickets
Rettssyndrome

Themostcommonxlinkedrecessivedisorders:

Duchennesmusculardystrophy
HemophiliaAandB
Glucose6phosphatedeficiency
Brutonsagammaglobulinemia
WiskottAldrichsyndrome

MICROCYTICANEMIAS
IRONDEFICIENCYANEMIA

Isthemostcommoncauseofanemiathroughouttheworld

Causedby:

Chronicbloodloss(menstruationisacommoncause)
Inamaleadult,GIbloodlossisthelikelycause(nomenstruation)

Dietarydeficiencyisapossiblecausein:

Infantsandtoddlers:especiallyifdietispredominantlybreastmilk
Adolescents:rapidgrowthratesincreasetheneedforiron,thusadeficiency
develops
Pregnancy:pregnancyisastateofincreasedironrequirement

Commonsigns/symptoms:

Fatigueandweaknessarethemostcommonsymptoms
Decreasedserumferritin+increasedTIBS(totalironbindingcapacity)

Treatment:
Oralferroussulfate

THALASSEMIAS
Thalassemiasareinheriteddisordersthatarecausedbyalackofproductionof
eithertheorglobinchainsofhemoglobin.Severityofthalassemiaisdependent
onwhichglobinchainisaffectedandhowmanyofthegenelociare
deleted/mutated.Asarule,ifanirondeficiencyanemiaistreatedunsuccessfully,a
hemoglobinelectrophoresisshouldbeperformedlookingforathalassemia.

Thalassemias:
ThalassemiaMajor:akahomozygouschainthalassemiaandCooleysanemia.

Causesseveremicrocyticanemia
Bonemarrowspaceexpansionleadingtobonemalformations
Growthretardationandfailuretothrive
PredominantlyinMediterraneanpopulation
Treatmentinvolvesbloodtransfusion,andwithouttreatmentdeathwithin
thefirstfewyearsoflifeisunavoidable.

**Thisformofthalassemiacanleadtocongestiveheartfailure.Aseverecasecan
requireachelatortoeliminateexcessiron.

Diagnosing thalassemiamajor:

HemoglobinelectrophoresiswillshowanelevationofHbF
Peripheralbloodsmearwillshowamicrocytichypochromicanemia

ThalassemiaMinor:akaheterozygouschainthalassemia

Thesepatientsareusuallyasymptomatic
Mildmicrocyticanemiaisusuallytheonlyfinding
Diagnosingisalsowithhemoglobinelectrophoresis
Sincethisconditionisasymptomatic,notreatmentisnecessary

Thalassemias:
SilentCarriers:Thisformiscausedbyamutationordeletionofonlyonelocus.

Patientsareasymptomatic
Notreatmentisnecessary

thallasemiaminor:Thisformofthalassemiaiscausedbymutationordeletionof
twoloci.
Patienthasmildmicrocytichypochromicanemia,butnotreatmentisnecessary
HbHdisease:Thisformiscausedbyamutationordeletionofthreeloci

Patientwillhavehemolyticanemiaplussignificantmicrocytichypochromic
anemia
Treatmentinvolveslifelongtransfusions
Iftransfusionsfailtoimprovesymptoms,asplenectomyishelpful

HydropsFetalis:Thisisamutationordeletionofallfourloci.

Thisconditionisnotcompatiblewithlife,anddeathoccursatbirthorvery
shortlythereafter.

SIDEROBLASTICANEMIA
Thisisaconditionthatiscausedwhenthebodycannotproperlyincorporateiron
intohemoglobin.Asaresult,ringedsideroblastsarecreatedandcanbeseenon
peripheralsmear.Thiscanbeeitherhereditaryoracquired.Ifacquired,causes
suchasalcohol,isoniazid,chloramphenicol,leadexposure,collagenvascular
disease,andmyelodysplasticsyndromesshouldbeexplored.
Findings:

TherewillbeaNORMALtotalironbindingcapacity+increasedserumiron
andserumferritin.

Treatment:Removalofoffendingagentifthisisthecause.

NORMOCYTICANEMIAS

ANEMIAOFCHRONICDISEASE
Anemiaofchronicdiseaseoccursinthesettingofachronicillnesssuchas:Cancer,
inflammatorydiseases(SLE,RA),tuberculosis,etc.

Usuallynormocytic/normochromic,howeverattimesmaybemicrocyticand
hypochromic.
Managementofthisconditioninvolvestreatment/managementofthe
underlyingcondition.

MACROCYTICANEMIAS

VITAMINB12DEFICIENCY
ThemostcommoncauseofvitaminB12deficiencyisimpairedabsorption

Perniciousanemiaisalackofintrinsicfactor,andisthemostcommoncause
ofdeficiencyinthewesternworld.
SincestoresofB12canlastfor3yearsintheliver,thereisusuallynotan
dietaryinsufficiency.
Competitionfromorganisms(diphyllobothriumlatumthefishtapeworm)
cancauseB12deficiency

Signs/Symptoms:

AnemiawithMCV>100+hypersegmentedneutrophilsonperipheralsmear

Neurologicalmanifestationssuchaslossofvibration/positionsense,ataxia,
andUMNsigns(+veBabinski,spasticity,increasedDTRs)
Glossitis
Increasedserumlevelsofmethylmalonicacidandhomocysteine(B12isaco
factorinconversionofthesetwomoleculesintosuccinylCoAand
methionine,respectively)

Treatment:IntramuscularadministrationofvitaminB12onetimepermonth.

FOLICACIDDEFICIENCY
SymptomssimilartovitaminB12deficiencywithoutanyneurologicalsignsor
symptoms.

Dietarydeficiencyisthemostcommoncause,asstoresrunoutin3months.
Commonlythepatienteatstheteaandtoastdiet
Thebestsourcesforfolatearegreenleafyvegetables
Othercommoncausesasidefromdietaryinsufficiencyare:alcoholism,
pregnancy,folateantagonists,hemolysis,hemodialysis.

Treatment:Dailyfolicacidsupplementation

HEMOLYTICANEMIA

Isadestructionofredbloodcellsbeforetheirprogrammedtimeofdeath.

Therewillbeanincreasedreticulocytecountasthebonemarrowresponds
totheincreasedneedforRBCs
Ananemiawillresultwhenthebonemarrowcannotkeepupwiththenew
demandforRBCs.

Therearefourkindsofhemolyticanemia,theyare:
1. Intrinsicthesearefactorsthatarehereditaryinnature,including:Sickle
celldisease,thalassemias,hemoglobinCdisease
2. Extrinsicthereareacquiredfactorscausinghemolysis,including:Immune
regulatedhemolysis,mechanicalhemolysis(prostheticheartvalves),toxic
insults(drugs,poisons,etc).
3. MembranedefectsdefectsofthemembranecanresultinRBChemolysis,
theyinclude:Hereditaryspherocytosis,PNH
4. DefectsoftheenzymesG6PDdeficiency,pyruvatekinasedeficiency

Ifthehemolysisoccurswithinthecirculation,intravascularhemolysisoccurs.
Ifthehemolysisoccurswithinthereticuloendothelialsystem,extravascular
hemolysisoccurs.

Mainfeaturesofhemolyticanemia:

Jaundice
Fatigue/pallor
Darkurine(causedbyhemoglobin)
Hepatosplenomegaly

Diagnosing:

Hemoglobinandhematocritlevels
Peripheralsmeartodifferentiatebetweendifferenttypesofhemolysis
HeinzbodiesG6PDdeficiency
Schistocytesintravascularhemolysis
SickledRBCsicklecellanemia
Spherocytes/helmetcellsextravascularhemolysis

SICKLECELLDISEASE
IscausedbyahemoglobinS(HbS)mutation.Thereisasingleaminoacid
replacementinthechain.

Valinereplacesglutamicacid
Alowoxygenstatecausedsicklingoftheredbloodcells
Sicklecelltraitisaheterozygote
Sicklecelltraitpatientsareusuallymalariaresistant

AdverseEffects:

AplasticcrisiscausedbyParvovirusB19infection
Increasedriskofinfectionbyencapsulatedbacteria(H.Infl,S.Pneumo,
Neisseria)Givepatientpneumococcalvaccine,Hibvaccine,meningococcal
vaccine.
Vasoocclusivecrisiscausingseverepain(duetomicrocirculation
obstructionbysickledredbloodcells)
Splenicsequestrationcrisis

Whatisasplenicsequestrationcrisis?
Thisisapotentiallyfatalcomplicationofthesicklecelldisease.Bloodpoolsintothe
spleen,resultinginsplenomegalyandthesubsequentdevelopmentofhypovolemic
shock.Thisconditionoftenwarrantsasplenectomy.

HbCdefect

Milderdisease(HbCorHbSC)

Treatment:HydroxyureatoincreaseHbFlevels(preventsthesicklingprocess),
bonemarrowtransplant,prophylacticpenicillinforchildrenfrom4monthsofage
to6yearsofage.

THECOOMBSTEST
ThedirectCoombstestisusedtodetectantibodiesboundtothesurfaceoftheRBC.
Thisisthetestusedtodetectimmunemediatedhemolyticanemia.TheCoombs
testisbasedontheideathattheadditionofantihumanantibodieswillbindto
humanantibodiesthatareboundtotheRBCmembrane.Theseantibodiesaremost
commonlyIgGandIgM.Iftheseantibodiesagglutinate,theRBCswillclumpand
thisisapositivetestresult.Iftheydonotagglutinateandclump,wehaveanegative
testresult.


HEREDITARYSPHEROCYTOSIS
ThisisanADdisorderwherethereisadefectinthegenethatcodesforspectrin,
resultinginadecreasedcontentofspectrin.Thiscausesalossofthemembrane
surfaceareawithnodecreaseinvolume.Thesetwocausetheshapetoshiftfrom
circulartospherical.

TheosmoticfragilitytestisawaytotesttheRBCsabilitytowithstand
hypotonicsaline.Thesphericalshapewilltoleratethesolutionlessthanthe
regularRBCshape,thuscausingittorupturefaster.
Peripheralsmearwouldshowspherocytes
Coombstestisnegative

GLUCOSE6PHOSPHATEDEHYDROGENASEDEFICIENCY
Thisisanxlinkedrecessivedisorderthatisusuallyprecipitatedbyinfections,fava
beans,primaquine,dimercaptol,sulfonamides,andnitrofurantoin.

Patientgetsepisodesofhemolyticanemiathatisoftenprecipitatedbyan
aggravatingfactor
Patientwillgetjaundiceandhavedarkurine
Peripheralsmearwillshowbitecells(causedbymacrophages)andHeinz
bodies(hemoglobinprecipitationinsideRBCs)
DiagnosebymeasuringG6PDlevels.

Treatment:Avoidprecipitatingfactors,transfuseasnecessary

AUTOIMMUNEHEMOLYTICANEMIA
AutoantibodiesagainsttheRBCmembranecausedestructionofRBCs.Thereare
twopossiblecausesforthis,IgGantibodiesorIgMantibodies
IgGcauseswarmautoimmunehemolyticanemia.Thismeansthatbindingof
IgGtotheRBCmembraneoccursoptimallyat37C. Thiscausesextravascular
hemolysiswheretheprimarysiteofsequestrationisthespleen.
IgMcausescoldautoimmunehemolyticanemia.BindingofIgMtotheRBC
membraneoccursoptimallyat0C to 5C. Thiscausesintravascularhemolysisand
complementactivation,wheretheprimarysiteofsequestrationistheliver.
Diagnosing:

DirectCoombstest:If+ve=warm,ifve=cold

Treatment:Ifmild,notreatmentisnecessary.Ifwarmandmoderate,give
glucocorticoids(dosplenectomyifnoGCresponse).

PAROXYSMALNOCTURNALHEMOGLOBINURIA(PHN)
Isaconditionwherebythereischronicintravascularhemolysis.

Normochromicnormocyticanemia
Pancytopenia(affectshematopoieticstemcells)
Thrombosisofvenoussystemmayoccur
Maycausemoresevereconditionssuchasaplasticanemias,myelodysplasia,
andacuteleukemias
PatientcanexperiencemusculoskeletalandGIpains

Treatment:PrednisoneorBMtransplantifnoresponsetotreatment.

PLATELETDISORDERS

THROMBOCYTOPENIA
Thisiswhentheplateletcountfallsbelow150,000
Causes:

Decreasedproductiondueto:BMinjury,suppression,invasions
Increaseddestructiondueto:DIC,TTP,infection,drugs,ITP,HIV
Sequestration
Pregnancy:usuallynotamajorconcern
Dilutionaleffectsfromtransfusion
DeterminationofcausecanbemadewithCBC,peripheralsmear,andbone
marrowbiopsy.

Signs/Symptoms:

Petechialbleeding(pinpointbleeding)
Mucosalbleeding(ieepistaxis,menorrhagia,hemoptysis)
Excessivebleedsafterinjuryand/orsurgicalprocedures

THROMBOTICTHROMBOCYTOPENICPURPURA(TTP)
Aconditionwherebythereisexcessiveplateletconsumption,leadingtoan
emergencysituationthatcanleadtodeathratherquickly(fewmonths).
Signs/Symptoms:

Alteredmentalstatus
Hemolyticanemia
Thrombocytopenia

Treatment:Plasmapharesisisrequiredtomaintainlife,corticosteroidsand
splenectomymayalsoberequired.

IDIOPATHICTHROMBOCYTOPENICPURPUA(ITP)
Isanautoimmuneformationofantibodiesagainstplatelets.IgGantibodiesadhere
toanddestroytheplateletswhicharethenremovedbysplenicmacrophages.
AcutelyIsaselflimitedconditionseeninchildren,wheretheconditionisalmost
alwayspreceededbyaviralinfection.
ChronicallyIsaspontaneousformofITPseenmostcommonlyinmiddleaged
females.Isselflimited.

GLANZMANNSTHROMBASTHENIA
ThisisanARdisorderwherethereisadeficiencyinplateletaggregationduetoa
deficiencyofglycoproteinGPIIbIIIa.Theonlyalteredtestisincreasedbleeding
time.

BERNARDSOULIERSYNDROME
IsanARdisorderofplateletadhesionduetoadeficiencyofglycoproteinGPIbIX.
Theplateletcountwillbelowwithabnormallylargeplateletsonperipheralsmear.

DISORDERSOFCOAGULATION

1.
2.
3.
4.
5.
6.
7.

vonWillebrandsDisease(vWD)
HemophiliaA
HemophiliaB
DisseminatedIntravascularCoagulation(DIC)
VitaminKdeficiency
Coagulopathyofliverdisease
Inheritedhypercoagulablestates

VONWILLEBRANDSDISEASE
IsanADdisorderthatiscausedbyadeficiencyordefectofthevWF(factor8
relatedantigen).vWFisrequiredforthefirststepofplateletaggregationinclot
formation.
*vWFisthemostcommoninheritedbleedingdisorder,affectingupto3%of
thepopulation.
Signs/Symptoms:

Cutaneousbleeding
Mucosalbleeding
MenorrhagiaseeninmorethanhalfoffemaleswithvWD
Manypatientswontshowanythingsignorsymptomsuntiltheyundergoa
surgicalprocedureandhaveexcessivebleeding
Bleedingtimewillbeprolonged,plateletcountisnormal

PTTmaybeprolonged,vWFisdecreased,factor8activityisdecreased
RistocetinlevelsshouldbecheckedindiagnosingvWD

Treatment:DesmopressintoinduceendothelialcellstosecretevonWillebrand
factor(noteffectiveintype3vWD).Factor8concentratesisrecommendedfortype
3vWD.PatientshouldavoidNSAIDs.

HEMOPHILIAA
Isanxlinkedrecessivedisorderthataffectsmalepatients,andiscausedbya
deficiencyordefectoffactor8.
Signs/Symptoms:

Bleedingintojoints(hemarthroses)
Intramuscularbleeds
Intracranialbleeds(thereforeheadtraumamustbetakenveryseriouslyin
thesepatients)

Diagnosing:

Lowfactor8levels+normalvWF
PTTisprolonged

Treatment:Replaceclottingfactors,desmopressinmaybehelpfulinsomepatients.

HEMOPHILIAB
Isanxlinkedrecessivedisordercausedbyadeficiencyoffactor9,andismuchless
commonthanhemophiliaA.Managementinvolvesreplacingmissingfactors.

DISSEMINATEDINTRAVASCULARCOAGULATION(DIC)
DICisadisordercharacterizedbyanabnormalactivationofthecoagulation
sequence,whichleadstowidespreadformationofmicrothrombithroughoutthe
microcirculation.Thisleadstotheconsumptionofclottingfactors,platelets,and
fibrin.Thereisalsoanactivationoffibrinolyticmechanisms,thusleadingto
hemorrhages.BLEEDS+THROMBOSIS
Commoncauses:

Themostcommoncauseisinfection(GramvesepsisisMCC)
Pregnancycomplications
Trauma

Malignancy
Shock

Signs/Symptoms:

Oozingfromproceduresites
Ecchymoses
Petechia
Purpura
ThrombosesseenmoreofteninchroniccasesofDIC

Treatment:Correctunderlyingconditionsandapplysupportivemeasures.

VITAMINKDEFICIENCY
TherearemanyclottingfactorsthatrequirevitaminKasacofactorinsynthesis,
including:ProteinC&S,andfactors2,7,9,10.VitaminKdeficiencyisseeninvery
illpatientswhoarebeingfedthroughatube,aswellasthosewhoareusingoral
warfarinasananticoagulant.
Signs/Symptoms:

Significanthemorrhages
PTprolongation(isthefirstfinding),thenPTTprolongation.

Treatment:VitaminKreplacement.

Ifpatienthasaseverebleed,freshfrozenplasmashouldbegivenasit
containsalloftheclottingfactors.

COAGULOPATHYOFLIVERDISEASE
Sincetheliversynthesizesallclottingfactors,anydiseaseofthelivercancause
coagulopathies(abnormalbleeding,prolongationofPT/PTT).
Treatment:FreshfrozenplasmaifPT/PTTarealteredorthereissignificant
bleeding.


INHERITEDHYPERCOAGULOPATHIES

Antithrombin3deficiency(increasedthrombosis)
Antiphospholipidantibodysyndrome(arterialorvenousthrombosis)
ProteinCdeficiency(unregulatedfibrinsynthesis)
ProteinSdeficiency(leadstoadeficiencyofproteinCactivity)
FactorVleiden(unregulatedprothrombinactivationincreased
thromboembolicevents)
Prothrombingenemutation

PLASMACELLDISORDERS

1. MultipleMyeloma
2. WaldenstromsMacroglobulinemia
3. MonoclonalGammopathyofUndeterminedSignificant(MGUS)

MULTIPLEMYELOMA
IsacancerofthebonemarrowthatproduceslargeamountsofIgGorIgA.Thisis
themostcommontumorarisinginadults
Itcauses:

Bonelesions
Hypercalcemia
Anemia
Infections

Signs/Symptoms:

Skeletalmanifestations(bonepain,fractures,vertebralcollapse)
Normocyticnormochromicanemia(duetoBMinfiltrationandrenalfailure)
Renalfailure
Infections(secondarytodeprivationofnormalIgsaffectshumoral
immunity,andistheMCCofdeath)
Amyloidosis

CharacteristicFindings:

BenceJonesproteinsinurine(areIglightchains)
Mspike(isamonoclonalIgspikeseenonserumelectrophoresis)

Rouleauformation(peripheralsmearshowingRBCsstackedlikepoker
chips)

WALDENSTROMSMACROGLOBULINEMIA
Isaconditionthatcauseshyperviscosityofthebloodduetomalignantproliferation
ofplasmacytoidlymphocytes(IgM).Shouldbemanagedwithchemotherapyand
plasmapharesis

MONOCLONALGAMMOPATHYOFUNDETERMINEDSIGNIFICANCE
Isaconditionthatisusuallyasymptomaticandseenintheelderlypopulation.


LYMPHOMAS

HODGKINSvs.NONHODGKINS
HODGKINS
ReedSternbergcellspresent.

OnlysinglegroupofLNsaffected.

Lowgradefever,weightloss,night
sweats.

AssociatedwithEpsteinBarrVirus.

Prognosisdependentonamountof
lymphocytesandReedSternbergcells
(bestwhenincreasedlymphocytesand
decreasedReedSternbergcells).

NONHODGKINS
Isassociatedwithstatesof
immunosuppression.

ManyLNsinvolvedwithextranodal
involvement.

Bcellsareofthemajority.

Veryfewconstitutionalsymptoms
Occursfrom2040yrofage.

CARDIACPATHOLOGY

ISCHEMICHEARTDISEASE
1. StableAngina
2. UnstableAngina
3. VariantAngina(Prinzmetals)

STABLEANGINA
Fixedatheroscleroticlesionsnarrowthecoronaryarteries,leadingtoanimbalance
betweenbloodsupplyand02demand.Thisleadstoinadequateperfusion,and
oxygendemandexceedsbloodsupply.Atherosclerosisleadstonarrowing>75%.
Signs/Symptoms:

Substernalchestpainlastinglessthan15minutes
Painisdescribedassqueezing,heaviness,pressure
Alwaysbroughtonbyphysicalexertion
Paingoesawaywithrestand/ornitroglycerine

UNSTABLEANGINA
Inunstableangina,thecauseofchestpainisduetoareducedrestingcoronary
bloodflow.Themaindifferencebetweenunstablevs.stableanginaisthatthepain
ofunstableanginaoccursatrest.

PRINZMETALSANGINA
Prinzmetalsanginaiscausedbyatransientcoronaryvasospasmthatis
accompaniedbyafixedatheroscleroticlesion.Thesymptomsoccuratrest.
Signs/Symptoms:

Chestpainatrest
Mostcommoninyoungerfemaleswhosmokecigarettes
TherewillbeatransientSTsegmentelevationonEKGduringtheepisodesof
chestpain


ARTERIOSCLEROSIS&ATHEROSCLEROSIS
ARTERIOSCLEROSISArteriosclerosisisaconsequenceofhypertension,whereby
thereishyalinethickeningofthesmallarteries.

ATHEROSCLEROSIS
Isplaqueformationwithintheintimaofthearteries,occurringintheelasticand
large/mediumsizedmusculararteries.Themostcommoncausesof
atherosclerosisare:HTN,smoking,hyperlipidemia,DM,dietaryfactors,family
history.
Progression:FattyStreak ProliferativePlaque ComplexAtheroma
AdverseEffects:

Ischemia
Infarction
Peripheralvasculardisease
Thrombus
Emboli

Locations:
Mostcommonlyintheabdominalaorta,coronaryarteries,poplitealarteries,and
carotidarteries.

HYPERTENSION
EssentialHTN:Noidentifiablecause,andappliesto>95%ofcasesofHTN
SecondaryHTN:Renalcauses(stenosis),endocrinecauses(hyperaldosteronism,
hyperthyroidism,Cushings,pheocromocytoma),medication(OCPs).**OCPsare
MCCinyoungwomen
EffectsofHTNontheheart:

IncreasedsystemicvascularresistanceleadingtoeventualCHF(CHFisthe
mostcommonendresultofHTN)
Atherosclerosis
CAD
Leftventricularhypertrophy
Stroke
Renalfailure

Retinalchangesanddamage
Riskofhemorrhages
Riskofkidneyatherosclerosis

HTN
Classification
Normal

SystolicReading

DiastolicReading

Management

<120

<80

Prehypertension

120139

8089

Stage1HTN

140159

9099

Stage2HTN

160

100

Notreatment
necessary
Lifestyle
modificationsonly
Lifestylemods+1
antiHTN
medication
Lifestylemods+2
antiHTNmeds

MYOCARDIALINFARCTION
Myocardialinfarctionsoccurasaresultoftheocclusionofavesselintheheart,
interruptingthesupplytotheheart,resultingininfarction.OccursintheLAD>RCA
>CIRCUMFLEX
ThebestinitialtestforasuspectedMIistheEKG.

CardiacEnzymes:
CKMBbestinitialcardiacenzyme(optimalfordetectingasecondinfarctwhilein
thehospital)
Troponinrisesafter4hrsthenstayselevatedfor710days

PathologicalchangesafteranMI:
Day1Darkmottling
Day24Hyperemia(vesseldilation)
Day510Hyperemicborderwithcentralyellowbrownsoftening
FewweeksOccludedarteryisrecanalizedandascarispresent(graywhite
coloring).

Complicationsofamyocardialinfarction:
1. Leftventricularfailure
2. Pulmonaryedema
3. Cardiacarrhythmia(mostcommoncauseofdeathbeforereachingthe
hospital)
4. Cardiogenicshock
5. Ruptureofventricularfreewall,papillarymuscles,and/orinterventricular
septum(occurs410dayspostMI)
6. Muralthrombuscausingthromboembolism
7. Pericarditis(35dayspostMI)

CARDIACTUMORS
Inadults,themostcommontumoristheMyxoma.Thisoccursmostofthetimein
theleftatrium.Theycauseaballvalveobstructionthatobstructstheleftatrium.
Inchildren,themostcommontumoristheRhabdomyomaandisassociatedwith
tuberoussclerosis.

CONGESTIVEHEARTFAILURE
Aconditionwherebytheheartspumpingabilitycannotmeetthebodyscirculatory
demandsundernormalconditions.


THEFRANKSTARLINGRELATIONSHIP
Saysthatinnormalfunctioninghearts,anincreaseinpreloadshouldresultin
greatercontractility.Basedonthisprinciple,withexertionaheartinCHFproduces
lesscontractilityandthisiswhensymptomsoccur.

Signs/Symptoms:
LEFTSIDEDHF

Dyspnea(secondarytopulmonarycongestion)
Orthopnea(difficultysleepingintherecumbentposition)
Paroxysmalnocturnaldyspnea(patientawakesshortlyafterfallingasleep
duetoSOB)
PMIisdisplacedtotheleftduetocardiomegaly
S3(ventriculargallop)
S4(atrialsystoleintoanoncompliantleftventricle)
Rales/crackles(anindicationofpulmonaryedema)
Dullnessonpercussion

RIGHTSIDEDHF

Peripheraledema(pitting)
Jugularvenousdistention

Ascites
Hepatomegaly
Rightventricularheave

VALVULARHEARTDISEASE(MURMURS)
1.
2.
3.
4.
5.
6.
7.
8.

MitralRegurgitation
AorticStenosis
VentricularSeptalDefect
MitralProlapse
AorticRegurgitation
MitralStenosis
PatentDuctusArteriosus
Hypertrophicobstructivecardiomyopathy(HOCM)

Allvalvularheartdiseasespresentwithshortnessofbreathinitially.Inyoung
people,themostcommonlyencounteredvalvedisordersare:Mitralprolapse,mitral
stenosis,orbicuspidaorticvalves.
MurmurIntensity:
I/VIOnlyheardwithspecificmaneuvers(ieValsalva)
II/VIandIII/VIThisiswherethemajorityofmurmurslie.
IV/VIPalpablethrillispresent
V/VIMurmurcanbeheardwiththestethoscopepartiallyoffthechest
VI/VIMurmurcanbeheardwithoutastethoscope

MITRALREGURGITATIONAholosystolicblowingmurmurthatisbestheardat
theapexoftheheart.
AORTICSTENOSISThecrescendodecrescendosystolicejectionmurmur
followinganejectionclick.
VSDAholosystolicmurmur
MITRALPROLAPSEAlatesystolicmurmurwithamidsystolicclick
AORTICREGURGITATIONHighpitchedblowingdiastolicmurmur
MITRALSTENOSISAlaterumblingdiastolicmurmurfollowinganopeningsnap

PDAAmachinelikemurmur
HYPERTROPHICOBSTRUCTIVECARDIOMYOPATHYAnautosomaldominanttrait
thatcanresultinsuddendeathinyoungathletes.ThewallsoftheLVand
interventricularseptumhypertrophy,creatingabananashapeintheventricle.

CARDIACARRHYTHMIAS
Tachyarrhythmias:

AtrialFibrillation
AtrialFlutter
MultifocalAtrialTachycardia
ParoxysmalSupraventricularTachycardia
WolffParkinsonWhiteSyndrome
VentricularTachycardia
VentricularFibrillation

Bradyarrhythmias:

SinusBradycardia
SickSinusSyndrome
AVBlocks(1st,2nd,and3rddegreeblocks)

ATRIALFIBRILLATION
Anirregular,rapidventricularrateiscausedbymultiplefociintheatriathatfire
erratically.Theatrialrateisashighas400bpm.
Patientwillexperience:

Palpitations
Dizziness
Exertionaldyspnea
Irregularlyirregularpulse

Goalsoftreatmentare:
1. Ventricularratecontrol
2. Restorationofnormalsinusrhythm
3. Giveanticoagulation(ifneeded)

ATRIALFLUTTER
Onefociintheatriumfiresautomatically,causinganatrialrateof250350bpm,
withonly1outof3ofthesecontractionsmakingittotheventricle.TheEKGwill
showwiththeclassicsawtoothpattern.

MULTIFOCALATRIALTACHYCARDIA
ThisisaconditionthatoccursmostcommonlyinthosewithCOPD.Therewillbeat
leastthreedifferentPwavemorphologieswithvariablePRandRRintervals.
Candiagnosewithvagalmaneuversand/oradenosineadministrationtoshowthe
anAVblockwithoutdisruptingtheatrialtachycardia.

PAROXYSMALSUPRAVENTRICULARTACHYCARDIA
IsduetoareentrantcircuitwithintheAVnode.TherewillbenarrowQRS
complexeswithnodiscernablePwavesonEKG.Thisconditionmaybecausedby
thefollowing:

Digoxintoxicity
Ischemicheartdisease
Atrialflutter
Presenceofaccessorypathways
Excessiveconsumptionofalcoholorcaffeine

WOLFFPARKINSONWHITESYNDROME
Thereisanaccessorypathwayfromtheatriatotheventriclesthatcausepremature
ventricularexcitationsduetoalackofdelayintheAVnode.
Therearetwomechanismsbywhichthisconditioncancauseaparoxysmal
tachycardia:
1. SupraventricularTachycardiasAllimpulsesgetthroughtotheventricle
inthiscondition,whereasinnormalcircumstancesonlyoneAtrialimpulse
getsthrough.
2. OrthodromicReciprocationTachycardiacreatesareentryloopthat
causesmultipledepolarizationsoftheatria.

VENTRICULARTACHYCARDIA
Thisconditionisdefinedasarapidandrepetitivefiringofthreeormorepremature
ventricularcontractionsinarow,atarateof100250bpm.Isresponsiblefroupto
75%ofcardiacarrest.
Themostcommoncausesofventriculartachycardiaare:

Cardiomyopathies
Hypotension
CAD
ProlongedQTsyndrome
Drugtoxicities

Signs/Symptoms:

Palpitations
Dyspnea
Angina
Syncope
WidenedanderraticQRScomplexonEKG

**Arapid,polymorphicformofventriculartachycardiacanleadtoacondition
knownasTorsadesdesPointes.

VENTRICULARFIBRILLATION
Occurswhentherearemultiplefociwithintheventriclesthatfirerapidly,which
leadstoachaoticquiveringoftheventricles.MostcasesofVFiboccurasaresultof
ventriculartachycardia.Thisconditionisfatalwhenuntreated.
**AssociationofVFibwithanMIcreatesafavorablelongtermprognosis,whereas
noassociationbetweenthetwogivesahighrateofrecurrence.
Signs/Symptoms:

Lackofpulse,heartsounds,andBP
Patientlosesconsciousnessandwilldiewithoutintervention

**ImmediatedefibrillationandCPRshouldbeperformedtopreventsuddendeath.
Therearenomedicationsthatcanconvertthisconditiontonormalrhythm.
**Notethatallnarrowcomplextachycardiaswilloriginatefromabovethe
ventricle,whereaswidecomplextachycardiasoriginatewithintheventricles.

Bradyarrhythmias:

SINUSBRADYCARDIA
Isasinusrateof<60bpm,andbecomesdangerouswhentheratedropsbelow45
bpm.Commoncausesofsinusbradycardiaare:Ischemia,IncreasedVagalTone,
Antiarrhythmics
**Patientsareusuallysymptomaticandmaypresentwithonlyfatigue
**Atropinewillblockvagalstimulationandthuselevatethesinusrate.

SICKSINUSSYNDROME
Thisisadysfunctionofthesinusnodethatcausespersistentspontaneousboutsof
sinusbradycardia.Patientwillexperiencedizziness,confusion,fatigue,andCHF.

AVBLOCKS
1stdegreeAbenignconditionwherethePRintervalisprolongedto>0.20seconds
2nddegreeThereareMobitztype1andMobitztype2
MobitzType1progressiveprolongationofPRintervaluntilthereisanabsentP
wave.Doesnotrequiretreatment.
MobitzType2thereisamissingPwavewithoutanychangesintheprecedingPR
interval,causingthedroppingofaQRScomplexallofasudden.Mayprogressand
becomeacompleteheartblock.Requirespacemakerimplant.
3rddegree(Completeheartblock)thereisanabsenceofatrialimpulsestothe
ventricle,thusthereisnorelationshipbetweenPwavesandQRScomplexes.
Requirespacemaker.


CARDIOMYOPATHIES

HYPERTROPHICCARDIOMYOPATHY
Asymmetriccardiomyopathythatinvolvestheinterventricularseptumresultsin
diastolicdysfunction.Thewallsoftheleftventriclebecomethickened.Abanana
shapeoccursintheLV,canresultinsuddendeathinyoungathletes.
DILATEDCARDIOMYOPATHY
Dilationoftheheartthatismostcommonlycausedby:Alcohol,Adriamycin,
Radiation,Chagasdisease,CoxsackieBvirus.Thisconditionresultinsystolic
dysfunction.
RESTRICTIVECARDIOMYOPATHY
Myocardialinfiltrationresultsinimpaireddiastolicfillingoftheventricularduetoa
decreaseinventricularcompliance.Commoncausesare:Amyloidosis,Sarcoidosis,
Hemochromatosis,Scleroderma.

PERICARDIALDISORDERS
1.
2.
3.
4.

AcutePericarditis
ConstrictivePericarditis
PericardialEffusion
CardiacTamponade

ACUTEPERICARDITIS
Isanacuteconditionthatresultsinchestpain,diffuseSTelevationsandPR
depressiononEKG,apericardialfrictionrub,andpossiblepericardialeffusion.
Maybecausedbyanyofthefollowing:

Mostcasesoccurafteraviralillness(mostcommonlyanURI)
Infectious(Coxsackievirus,hepatitis,HIV,TB,toxoplasmosis,orfungal
infections)
Collagenvasculardisease
Postsurgery
Amyloidosis
Lupus
PostMI(knownasDresslerssyndrome)

**Recoveryoccurswithin13weeksandrequiresonlyNSAIDsformanagement.
Complicationsmayinclude:

Effusion
Tamponadeoccursin10%20%ofpatients

CONSTRICTIVEPERICARDITIS
Occurssecondarytofibrousscarringofthepericardium,leadingtorigidityand
thickeningofthepericardium.Thereareafewpossiblecauses,including:

Connectivetissuedisorders
Chronicpericardialeffusion
Radiationtherapy
Uremia
Priorheartsurgeries

Signs/Symptoms:

Symptomsofhepaticcongestion(edema,ascites)
Pulmonarycongestion
JVD
Pericardialknock

PERICARDIALEFFUSION
Occurswhenpericardialspacebecomesoccupiedwithfluid.Occurswhenthereis
ascitesandpleuraleffusionpresent.OftenoccurswhenthepatienthasCHF,
nephroticconditions,and/orcirrhosis.
Signs/Symptoms:

Pericardialfrictionrub
Muffledheartsounds
Pointofmaximalimpulse(PMI)issoftened

CARDIACTAMPONADE
Isapericardialeffusionthatimpairsdiastolicfillingoftheheart.Pressureofall
chambers,thepulmonaryartery,andpericardiumareequalinpressure,thus
ventricularfillingisimpaired.
Commoncauses:

FreewallruptureafteranMI
Medicalerrorscausingpuncturetoheart
Penetratinginjuries

Signs/Symptoms:

Hypotension
JVD
Muffledheartsounds

**KnownasBecksTriad

Narrowedpulsepressure
Pulsusparadoxus(exaggerateddecreaseinarterialpressureduring
inspiration>10mmHg)
Muffledheartsounds
Cardiogenicshock

RHEUMATICHEARTDISEASE
Rheumaticfever/heartdiseaseisaconditionthatoccursasaconsequenceof
pharyngitisfromagroupAstrepinfection.Themitralvalveisthemostcommon
valveaffected.Theprogressiontoaheartdiseaseisanimmunemediatedprocess,
notaresultofthebacterialinfection.
DiagnosingismadewiththeJONEScriteria,andrequirethepresenceoftwomajor
criteriaORonemajorandoneminorcriteria:
MAJORCRITERIA
MigratoryPolyarthritis
ErythemaMarginatum
Chorea
CardiacInvolvement
SubcutaneousNodules

MINORCRITERIA
Fever
ESRelevation
Polyarthralgias
PRintervalprolongation
PriorhistoryofRFinfection
Evidenceofpreceedingstrep
infection


ENDOCARDITIS
Isaninfectionoftheendocardiumthatcanbeclassifiedaseitheracuteorsubacute.
Mostoften,themitralvalveisinvolved,whereasaninfectionofthetricuspidvalveis
usuallyduetoIVdrugabuse.
AcuteEndocarditisCausedbyStaphAureusandcreateslargevegetationsona
previouslyhealthy/normalvalve.
SubacuteEndocarditisCausedbyViridiansgroupStrepandcreatessmall
vegetationsonanabnormal/diseasedvalve.**Occurswithdentalprocedures
Thesymptomsofbacterialendocarditiccanberememberedwiththemnemonic
FROMJANE.
FFever
RRothsspots(retinalhemorrhages)
OOslersnodes(painful,raisedredlesionsonhandsandfeet)
MMurmur
JJanewaylesions(nontenderlesionsonpalmsandsoles)
AAnemia
NNailbedhemorrhage
EEmboli

**LibmanSacksEndocarditisisaformofendocarditisseeninpatientswith
Lupus,wheretherearevegetationsfoundonbothsidesofthevalve,leadingto
stenosis.


EMBOLI
Emboliarethingsthattravelthroughthecirculationangetlodgedinthepulmonary
vasculature,leadingtoapulmonaryembolus(PE).
Themostcommonlyencounteredtypesofemboliare:Fat(duetolongbonebreaks
andliposuction),Air(canoccurasaresultofinjectionofairintothecirculatory
system),Thrombus(breaksoffromadeepveinthrombosus),AmnioticFluid
(frompregnancycomplications).
**NOTE:Thrombicausingapulmonaryembolismwillpresentwithchestpainand
shortnessofbreathinthepatient.
DVT
Adeepveinthrombosis(DVT)istheprecursortoanemboli,andiscausedby
patientswhohavethefollowing:
1. Stasis(theydontmoveenoughclassicallytheytookalongflight)
2. Hypercoagulability(duetodiseasestatesorfamilial)
3. EndothelialDamage

SKINCANCER
Thethreetypesofskincancerinclude:Squamouscell,basalcellcarcinoma,and
melanoma.
SquamousCellCarcinoma:
Isaverycommonformofskincancer,andisassociatedwithexcessexposureto
sunlight.Ismostcommonlyseenonthehandsandface,actinickeratosisisa
precursortoSCC.Islocallyinvasivebutrarelywillitmetastasize.

BasalCellCarcinoma:
Presentsaspearlypapules,andismostcommonlyseeninsunexposedareasof
thebody.

Melanoma:
Melanomaposesthegreatestriskofmetastasis.Thosewithfairskinareathighest
risk.Thereisadirectcorrelationbetweenthedepthofthelesionandthedegreeof
metastasis.

BRAINCANCERS
Childhoodbraincancers:
1.
2.
3.
4.
5.

Astrocytoma
Medulloblastoma
Ependymoma
Hemangioma
Craniopharyngioma

AstrocytomaThistypeofbraincancerisusuallyfoundintheposteriorfossa,and
itcomeswithagoodprognosis.
MedulloblastomaThiscancausehydrocephalusasitoftenpressesonthefourth
ventricle.ThecellsarrangeinaRosetteand/orPseudorosettepattern.Itisa
highlymalignantcerebellartumor.
EpendymomaUsuallyfoundinthefourthventricle,itderivesfromependymal
cellsandcanalsocausehydrocephalusduetoitslocation.
HemangioblastomaCanleadtopolycythemiabecauseitproduceserythropoietin.
Itisusuallycerebellar,butcanbeassociatedwitharetinalangioma(whichgivesit
anassociationtoVonHippelLindausyndrome)
CraniopharyngiomaIsasupratentorialtumorthatisbenignandoftenconfused
withapituitaryadenoma.IsderivedfromtheremnantsofRathkespouch.

Adulthoodbraincancers:
PituitaryadenomaMostcommonlyasprolactinsecretingform,themost
commonpresentationisbitemporalhemianopsia.
GlioblastomaMultiformeIsthemostcommonprimarybraintumor,hasaterrible
prognosis.Thisisfoundinthehemispheresandoftencrossesthecorpuscallosum
(givingitthetermbutterflyglioma).
MeningiomaComesfromarachnoidcells,makingitexternaltothebrain.Isthe
2ndmostcommonbraintumorinadults.
OligodendrogliomaIsaslowgrowingandraretumor,seenusuallyinthefrontal
lobeofthebrain.
SchwannomaIsthe3rdmostcommonadultbraintumor,originatingfrom
Schwanncells.Whenlocatednearthe8thcranialnervecancauseanacoustic
schwannoma.

TUMORSOFTHEBONE
BENINGTUMORSOFBONE

MALIGNANTTUMORSOFBONE

Enchondroma

Osteosarcoma

Isacartilaginoustumorfoundin
theintramedullarybone,most
oftenindistalextremities.

Themostcommonmalignantbone
tumor,occurringin1020yrolds.
Ismostcommonlyseeninthe
metaphysisoflongbones.

EwingsSarcoma

Osteochondroma
Inmen<25yrofage,isthemost
commonbenigntumorofbone.
Originationisfromthelong
metaphysealbone.

GiantCellTumor

Occursfrom2040yrofage.
Usuallyfoundindistal
femur/proximaltibia.Hasthe
classicdoublebubblesignon
xray.

Inmales<15yrofage,hasthe
11;22translocation.Islikelyto
metastasizeearly,andhasthe
characteristiconionskinningon
xray.Seenindiaphysisoflong
bones,ribs,pelvis,andscapula.

Chondrosarcoma

Amalignanttumorofcartilaginous
bone,seeninmales>30yrofage.
Notseeninthelongbones.

WHICHTUMORSMETASTASIZETOTHEBRAIN,BONE,ANDLIVER
TOBRAIN

TOBONE

TOLIVER

Lung

Breast

Colon

Skin

Lung

Stomach

Kidney

Thyroid

Pancreas

GItract

Tested

Breast

Kidney

Lung

Prostate

TUMORMARKERS
Thefollowinglistarethecommonmarkersthatareusedtoeithermakeadiagnosis
ofacertaincancer,ortomonitortheeffectivenessoftherapy.
TUMORMARKER
CarcinoembryonicAntigen(CEA)
ProstaticSpecificAntigen(PSA)
CA125
AlkalinePhosphatase
hCG
fetoprotein
Tartrateresitantacidphosphatase

WHATISWATCHES
Colorectalandpancreaticcancers
Usedforscreeningofprostaticcancer
Detectsovariancancerandmalignant
epithelialtumors.
Bonemetastasis,bileductobstruction,
Pagetsbonedisease
Hydatiformmoles,GTDs,and
choriocarcinomas
Nonseminomatousgermcelltumorsof
thetesticles
Hairycellleukemia


TUMORSUPPRESSORS
Tumorsuppressorsworkbysuppressingthegrowthofcertaintumors,whenthere
isalossoffunction,bothallelesofthegenehavebeenchanged(iemutation,
deletion,etc)
TUMORSUPPRESSOR
Rb
BRCA1and2
p53
APC
NF1andNF2
WT1

TUMORITSUPPRESSES
Retinoblastoma
Breastcancer,ovariancancer
Helpsscreen/followalmostallcancers
Colorectalcancer
Neurofibromatosis1and2
Wilmstumor

ONCOGENES
ONCOGENE
Ret
cmyc
Lmyc
Nmyc
Bcl2
ErbB2
Ras

ASSOCIATEDTUMOR
MENsyndromestype2and3
Burkittslymphoma
Lungtumors
Neuroblastoma
Follicularlymphomas
Breast,ovary,gastric
Colon

RESPIRATORY

CANCEROFTHELUNG
CENTRALLYARISING

SmallCellCarcinomalinkedto
smoking,canproduceACTHandADH,
maybelinkedtoLambertEaton
syndrome

SquamousCellCarcinomalinkedto
smokingandtheproductionofectopic
PTrP.

PERIPHERALLYARISING

Adenocarcinomaisthemostcommon
peripherallyarisingcancerofthelung.

LargeCellCarcinomaisan
undifferentiatedcarcinomaofthelung.

BronchioalveolarCarcinomathisis
thelungcancerthatisnotthoughttobe
relatedtosmoking

Lungcancercancauseawidearrayofsymptoms(asidefromcough,hemoptysis,
wheezing,bronchialobstruction).Themostcommonsymptomsthatcanarisefrom
lungcancerare:

Pancoaststumor(acarcinomathatoriginatesintheapexofthelungand
cancompressthecervicalsympatheticplexus,resultinginHorners
syndrome)
Superiorvenacavasyndrome
Hornerssyndrome(Ptosis,Anhydrosis,Miosis)
Paraneoplasticdisorders(PTrP,ADH,ACTH)
Recurrentlaryngealnervesymptoms(hoarseness)

OBSTRUCTIVEANDRESTRICTIVELUNGDISEASE
OBSTRUCTIVEthisconditioncausesanobstructionofairlowthatresultsinair
trappinginthelungs.Therewillalwaysbeanincreasedintotallungvolumewitha
FEV1/FVCof<80%.
Thecategoriesofobstructivelungdisordersare:
1. ChronicBronchitis:Thisconditionischaracterizedbythepresenceofa
productivecoughforatleast3consecutivemonthsfor2ormoreyears.
Thereisahypertrophyofthemucussecretingglandsofthebronchioles,
givingaReidindexof>50%.Patientwillhavewheezing,crackles,and
cyanosisonphysicalexam.*Thispatientisabluebloaterbecausethey
becomecyanotic.

2. Emphysema:Thisconditionresultsinadestructionofalveolarrecoil
resultingintheenlargementofairspacesduetosmokingand/oran1
antitrypsindeficiency(causesincreaseinelastaseactivity).Patientwillhave
dyspnea,tachycardia,decreasedbreathsounds.
3. Asthma:Thisresultsinconstrictionofthebronchiolesdueto
hyperresponsiveness.Thisconditionisreversible.Triggeredoftenby
activity,butalsotriggeredbyillnessand/orallergens.Findingsinclude
cough,wheezing,hypoxemia,anddyspnea.
4. Bronchiectasis:Aconditionthatresultsindilatedairways,recurrent
infections,hemoptysis,andpurulentsputum.Causedbyachronic
necrotizinginfectionofthebronchi.Thisconditionisrelatedtocystic
fibrosis,Kartagenerssyndrome,andbronchialobstruction.

RESTRICTIVERestrictivelungdiseasepreventtheexpansionofthelungs,
resultinginloweredlungvolumesandaFEV1/FVC>80%.
Thecategoriesofrestrictivelungdiseasesare:
1. Extrapulmonary:Thismeansconditionsthataffectthebreathingmechanics
andthesupportofthelungs.Conditionsthatweakenthemusclessuchas
myastheniagravis,andconditionsthatalterthesupportivestructureofthe
lungssuchasscoliosisandankylosingspondylitis.
2. Interstitial:Anythingthatalterstheinterstitiumcancausearestrictivelung
disease.Examples:ARDS,pneumoconioses,sarcoidosis,Goodpastures
syndrome,Wegenersgranulomatosis.


PNEUMONIA
Pneumoniapresentsinmanydifferentways,suchas:lobar,interstitial,andas
bronchopneumonia.
LobarPneumonia:Consolidationofinfectiontooneareaofthelobe,oftenthe
lowerlobe.ThemostcommoncauseisStrepPneumonia.Patientdevelops
symptomsacutely(shakingchills,fever,chestpain).
Bronchopneumonia:Thereispatchyinfiltrationinmorethanonelung.TheMCC
isStaphAureus.
AtypicalPneumonia:Alsoknownasinterstitialpneumonia,presentswithdiffuse
patchyinfiltrationlocalizedtointerstitialareasatthealveolarwalls.Presentationis
atypicalinthatthepatientislesssickandslowertodevelopsymptomsthanwith
lobarpneumonia.

THECHESTEXAM
Afewtermsmustbeunderstoodinordertobeabletodifferentiatebetweenthe
differentpathologiesoftherespiratorysystem.
FremitusIsavibrationthatisfeltwhenthepatientspeaks.Itiselevatedwhena
patienthaspneumonia,decreasedineffusionandobstruction,andcompletely
absentinpneumothorax.Vibrationisfeltasaresultoffluidaccumulation.
ResonanceThesamesoundasmadebyadrum.Whenthereisnothinginthelung
cavity,suchaswithapneumothorax,thereishyperresonance.Whenthereisfluid
accumulation,suchaswhenthereisapneumoniaoreffusion,thereisdecreased
resonance(ieDullness).Thinkofadrumwithandwithoutwaterinsidetovisualize
whatisinsidethelung.
BreathSoundsThiscanbefiguredoutwithcommonsense.Whenthereisan
obstruction,therewillbenobreathsound.Whenthereisapneumothorax,there
willbedecreasedbreathsounds.
TrachealDeviationPaycloseattentiontothetracheaduringthepulmonary
examination.Adeviationcanindicateapneumothorax.Apneumothoraxwillpush
thetracheaawayfromtheaffectedside,whileabronchialobstructionwillpullthe
tracheatowardsthesideofthelesion.


GOODPASTURESSYNDROME
Aconditionthataffectsboththelungsandthekidneys.Leadstohemoptysisasthe
primarylungfinding,withhematuria/anemia/andcrescenticglomerulonephritisas
thekidneyfindings.Seenmostcommonlyinmalesfrom2040yrofage.
Causedbyantiglomerularbasementmembraneantibodies,whichproducelinear
stainingonimmunofluorescence.

NEUROLOGY

DEGENERATIVEDISEASES
ALZHEIMERSDISEASE

Isaverycommoncauseofdeath
Prevalenceincreaseswithage
Familyhistoryisabigcontributingfactortothepossibledevelopment.
Diffusecerebralatrophyoccurssecondarytoneuronalloss
Neurofibrillarytanglesareclassicallyfound

Signs/Symptoms:

Developsslowlyovertime
Deathusuallyoccurswithin510yearsfromonset
Theadvancedstageswillrequirethepatienttohavedependenceonothers

Stages:
Earlymildforgetfulness,patientwillhavedifficultieslearningnewinformation
Intermediateprogressiveimpairmentinmemory
Latepatientwillrequireassistanceintheiractivitiesofdailyliving
Advancedpatientwillexperiencecompletedebilitationanddependscompletely
onothers

PICKSDISEASE

Frontalandtemporallobedysfunctioncausedbydegeneration
Accumulationoftauproteins
Pickbodiesarecharacteristic
Memoryimpairment+impulsivebehavior+behavioralchanges

MOTORNEURONDEGENERATIVEDISORDERS

AMYOTROPHICLATERALSCLEROSIS
ALSisalsoknownasLouGehrigsdisease,whichisafatalneurodegenerative
diseaseofboththeupperandlowermotorneurons.
POLIOMYELITIS
Polioisavirusthataffectstheanteriorhorncellsandmotorneuronsofthespinal
cordandbrainstem

CausesLMNsymptoms

FeaturesofPolio:

Asymmetricmuscleweakness(mostcommonlythelegs)
Muscleatrophy
AbsentofDTRs
Flaccidity

*Sensationisintact*

WERDNIGHOFFMANDISEASE
Ageneticconditionthatpresentsininfancyand/orearlychildhood.

Progressiveskeletalmuscleatrophyduetoanteriorhorncelldegeneration
Oftenpresentswithfloppybabyatbirth(congenitalhypotonia)
Lackofsuckingability
Tonguefasciculations
Deathoccursatayoungageduetorespiratorymusclefailure


BASALGANGLIADEGENERATION

PARKINSONSDISEASE

Lossofdopaminergicneuronsfromthesubstantianigra
Usuallypresentsinmidlatelife(ie>50yr)
Diagnosisiscompletelyclinicalandbasedonsymptoms

Signs/Symptoms:

Restingtremor(pillrolling)
Cogwheelrigidity
Bradykinesia
Difficultyininitiatingmovement
Masklikefacies
BrainbiopsywillshowLewybodies
certainmedicationscancauseParkinsonism:Reserpine,Metoclopramide,
Haloperidol,Perphenazine,MPTP

HUNTINGTONSCHOREA

Isageneticcondition(AD)wherethereisatrophyofthecaudatenucleus
Diseaseonsetisbetween3050yrwithasteadyworseningofsymptomsand
deathwithin15yearsofonset.

Signs/Symptoms:

Progressivedementia
Choreaofthelimbs,face,head/neck,andtrunk
Behaviordisturbancessuchas:Depression,aggression,psychosis,changesin
personality.
Depressionoccursandsuicideissomewhatcommonbecausepatientsare
awareoftheirdeterioration
Thereisnotreatment,onlysymptomaticmanagement.


SPINOCEREBELLARDISEASES

FRIEDREICHSATAXIA

Isanautosomalrecessiveconditionthatbeginsbyyoungadulthood.

Impaired:Proprioception,vibratorysense,ataxia,andnystagmus

DIFFERENTTYPESOFINTRACRANIALHEMORRHAGE

1.
2.
3.
4.

EpiduralHematoma
SubduralHematoma
SubarachnoidHemorrhage
ParenchymalHematoma

EPIDURALHEMATOMA

Bloodaccumulatesabovethedura
Ruptureofmiddlemeningealarteries
Patientusuallyexperiencesalucidinterval
Lensshapedbleed
Usuallycausedbyafractureofthetemporalbone

SUBDURALHEMATOMA

Symptomsoccurgradually
Tearingofthebridgingveins
Seenineldersandalcoholicsexperiencingblunttrauma
Crescentshaped

SUBARACHNOIDHEMORRHAGE

Aneurysmruptureand/orAVMrupture
Classicpresentationisworstheadacheofpatientslife
LPwillshowxanthochromia

BERRYANEURYSM
Aneurysmsarefocalweaknessesinthevasculaturethatresultinoutpouchings.The
Berryaneurysmisseenatthebifurcationoftheanteriorcommunicatingartery.

Ruptureleadstohemorrhagicstroke
Createstheworstheadacheofmylife
AssociatedwithEhlersdanlos,Marfans,andAPKD
Isasurgicalemergency


DISEASESOFDEMYELINATION

ThemostcommondemyelinatingdiseasesareMultipleSclerosisandProgressive
MultifocalLeukoencephalopathy,GuillainBarresyndrome,Metachromatic
Leukodystrophy,andPostInfectiousEncephalomyelitis.

MULTIPLESCLEROSIS

Multifocalzonesofdemyelinationscatteredthroughoutthewhitematter
Commonlyinvolvesthepyramidalandcerebellarpathways,medial
longitudinalfasciculus,opticnerve,andtheposteriorcolumns
Presentswithtransientsensorydeficits,fatigue,weakness,andspasticity
Visualdisturbances(monocularvisionloss,ipsilateralmedialrectuspalsyon
lateralgaze)
Usuallypresentsinthe20sand30sinarelapsingfashion
DiagnosingismademostlywithMRI
Management/treatmentiswithcorticosteroids

ClassicTriad:ScanningSpeech,IntentionTremor,Nystagmus

PROGRESSIVEMULTIFOCALLEUKOENCEPHALOPATHY

Isthereactivationofalatentviralinfection
Seeninapproximately4%ofAIDSpatients
AssociatedwithJCVirus

GUILLAINBARRESYNDROME

Isanascendinginflammationanddemyelinationoftheperipheralnerves
andmotorfibersofventralroots
Presentsinanascendingfashion
Causessymmetricalmuscleweaknessthatstartsinthelowerextremities
Presentsmostcommonlyfollowinganupperrespiratoryinfection
Themostcommoncauseofdeathisduetoparalysisofrespiratorymuscles
(thusmonitoringrespiratoryfunctionisessentialtosafetyofthepatient)

METACHROMATICLEUKODYSTROPHY

Alysosomalstoragediseasethataffectsthegrowthanddevelopmentof
myelin
DuetodeficiencyoftheenzymearylsulfataseA,whichcausesaccumulation
ofsulfatidesinthetissuesandthusdestroysmyelinsheath
AffectsbothCNSandPNS
Childrenwiththelateinfantileformmayhavedifficultyinwalkingafterthe
firstyearoflife
Musclewasting,weakness,musclerigidity,developmentaldelays,and
progressivelossofvision,odynophagia,paralysis,anddementiaareall
possiblecomplications
Juvenileform(310yrs)getmentaldeteriorationandcandevelopdementia
Adultform(>16yr)presentsasapsychiatricdisorderorprogressive
dementia
Nocureforthiscondition

POSTINFECTIOUSENCEPHALOMYELITIS

Animmunemediateddiseaseofthebrain
Occursfollowingaviralinfectionmostcommonly
Issimilartomultiplesclerosisinthatitinvolvesautoimmunedemyelination
Symptomsbegin13weekspostinfection
Fever,headache,drowsiness,seizure,andcoma


SEIZURES

SIMPLEPARTIAL

Affectsasmallregionofthebrain(temporallobeand/orhippocampi)
Patientremainsawake,seizureisverysuddenandbrief
Patientmayexperiencefeelingsoffear,nausea,unusualfeelings/sensations,
alteredsenseofhearing,smell,taste,vision,andtactileperception.
Senseofspatialdisorientationisoftenseen
Patientmayexperiencetheinabilitytospeak
Theseizureisusuallyrememberedindetail

COMPLEXPARTIAL

Limitedtoonecerebralhemisphereandcausingimpairmentofawareness
Oftenprecededbyanaura

ABSENCESEIZURE

Alsoknownaspetitmalseizure
Patientwillstareblanklyforafewseconds
Postseizure,thepatientwillreturntowhicheveractivitytheyweredoing
priortotheonsetoftheseizure

**ClassicUSMLEquestion,treatmentiswithEthosuxamide

TONICCLONICSEIZURE

Grandmalseizure,itaffectstheentirebrain
Isthemostwellknowntypeofseizurethatoccurswithepilepsy
Associatedwithanaura

TonicPhasePatientlosesconsciousness,tensionofskeletalmusclesoccurs.Lasts
onlyafewseconds.
ClonicPhaseRapidcontraction/relaxationofmuscles,eyesrolltothebackofthe
head,tongueisoftenbittenduetojawcontractions.Incontinencemayoccuratthis
phase.

Patientwillbeconfusedandwillhavenomemoryoftheseizure
InitialmanagementiswithabenzodiazepinegivenIV

MYOCLONIC

Isabriefandinvoluntarytwitchingofthemuscles
Presentswithabnormalmovementsonbothsidesofthebodyatthesame
time
Occurscommonlywhilepatientisfallingasleep
Isnotanactualdisorder,ratherisasignofotherpotentialnervoussystem
disorders

APHASIA

Aphasiasareacquiredlanguagedisorderswherebythereisanimpairmentofeither
difficultyproducingorcomprehendingspokenorwrittenlanguage.Thetwotypes
clinicallyencounteredareExpressiveAphasia(Brocas),andReceptiveAphasia
(Wernickes).
ExpressiveAphasiaPatienthascompleteintactcomprehensionwiththeinability
tospeakinanunderstandingfashion.Thesiteofpathologyistheinferiorfrontal
gyrus.Expressive=Inferiorfrontalgyrus.E=I(twovowels)
ReceptiveAphasiaPatienthascompleteintactabilitytospeakunderstandable
withtheinabilitytocomprehendlanguage.Thesiteofpathologyisthesuperior
temporalgyrus.Receptive=SuperiorTemporalgyrus.RST


CENTRALSLEEPAPNEA

Duringcentralsleepapnea,thebrainsrespiratorycontrolcentersareimbalanced
duringsleep.Theneurologicalfeedbackmechanismdoesnotrespondtolevelsof
CO2andthuscannotreacttodrivetherespiratoryrate.Followingthispathology,
breathingratewillincreaseandexcessCO2willbeexpelledfromthebody.

BELLSPALSY

Isaconditionofhemifacialweakness/paralysisofthemusclethatareinnervatedby
CN7,duetoinflammationofthenerve.

Patientwillexperienceanacuteonsetofunilateralfacialweaknessand
paralysis,affectingbothupperandlowerface.
Idiopathic,Lymedisease,AIDS,sarcoidosis,anddiabetesareallpossible
causes

ComparingtoUMNandLMNlesions:
UMNlesionwillaffectthelowerhalfofthecontralateralface
LMNlesionwillaffecttheupperandlowerfaceontheipsilateralsides

HORNERSSYNDROME

Hornerssyndromeisaclinicalsyndromecausedbydamagetothesympathetic
nervoussystem.Onmostoccasions,Hornerssyndromeisabenigncondition,butit
canoccurasaresultofmoreseriousconditionssuchasPancoasttumoror
thyrocervicalvenousdilatation.Theseconditionscausecompressionofthethoracic
sympatheticchain,whichleadstothesymptomsofHornerssyndrome:
Ptosisdroopingoftheeyelid
Anhydrosistheabsenceofsweating
Miosisconstrictionofthepupil

NEUROTRANSMITTERSAFFECTEDINDISEASE

Manyneurotransmittersareaffectedduringdifferentdiseases,theyinclude:
DOPAMINEIncreasedinSchizophrenia,decreasedinParkinsonsdisease
NOREPINEPHRINEIncreasedinanxiety,decreasedindepression
ACETYLCHOLINEIncreasedinorganophosphatepoisoning,decreasedin
AlzheimersandHuntingtonsdisease
GABADecreasedinHuntingtons,decreasedinanxiety
SERETONIN(5HT)Decreasedinbothanxietyanddepression

TABESDORSALIS

Tabesdorsalisisaconditionwherebythereisdegenerationofthedorsalcolumns
anddorsalrootsofthespinalcord.Thisoccursasaresultoftertiarysyphilis.
Patientwillexperienceallsymptomsassociatedwithdorsalcolumnmalfunction
(lackofproprioception,ataxiaduringlocomotion).Patientwilldevelopmalformed
joints(Charcotsjoints)duetolackofpainreceptors,shootingpains,absenceof
deeptendonreflexes,andArgyllRobertsonpupilthatresultsfromreactionto
accommodationbutnottolight.


SYRINGOMYELIA

Thereisacavitythatformswithinthespinalcordthatmayexpandandelongateas
timepasses,thusdestroyingthespinalcord.Thiscausesdamagetothe
spinothalamictract,whichthenresultsinabilaterallossofpainandtemperature
sensationintheupperextremitiesinacapelikedistribution.Associatedwithan
ArnoldChiarimalformation.

RENALPATHOLOGY

PATHOLOGYOFTHEGLOMERULUS

NEPHRITICSYNDROMES

NEPHROTICSYNDROMES

Presentwith:Hematuria,
Hypertension,Oliguria,Azotemia

Presentwith:MassiveProteinuria,
Hyperlipidemia,Hypoalbuminemia,
andPeripheral/PeriorbitalEdema.

ACUTEPOSTSTREP
GLOMERULONEPHRITIS

MEMBRANOUS
GLOMERULONEPHRITIS

RAPIDLYPROGRESSIVE
GLOMERULONEPHRITIS

MINIMALCHANGEDISEASE

GOODPASTURESSYNDROME

FOCALSEGMENTALGLOMERULAR
SCLEROSIS

MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS
BERGERSDISEASE(IgA
NEPHROPATHY)

DIABETICNEPHROPATHY
SYSTEMICLUPUSERYTHEMATOUS

ALPORTSSYNDROME

NEPHRITICSYNDROMES
ACUTEPOSTSTREPGLOMERULONEPHRITIS

Themostcommoncauseofnephriticsyndrome
OccursafteragroupAhemolyticstrepinfection(develops1014daysafter
infection)
Affectschildrenbetween26yearsofage
Isselflimitedcondition
Patientgetshematuria,edema,hypertension,andlowcomplementlevels
Somecasesmayprogresstorapidlyprogressiveglomerulonephritis

RAPIDLYPROGRESSIVEGLOMERULONEPHROPATHY

Iscrescentmoonshapedonlightmicroscopy

GOODPASTURESSYNDROME

ThereisatriadofIgGantiglomerularbasementmembraneantibodies,
pulmonaryhemorrhage,andcrescenticglomerulonephritis
Thelungfindingswilloccurbeforetherenalfindings
Patientwillhavehemoptysis,rapidlyprogressiverenalfailure,fever,and
myalgias

MEMBRANOPROLIFERATIVEGLOMERULONEPHRITIS

Onelectronmicroscopy,therearetheclassictramtracksubendothelial
humps
Hasaslowprogressiontorenalfailure

BERGERSDISEASE(IgAnephropathy)

MesangialdepositsofIgA
Isaverymilddisease
Occursafteraninfection

ALPORTSSYNDROME

Amutationoftype4collagen
Patientcanhavenervedeafnessandoculardisorders
Therearesplitbasementmembranes

NEPHROTICSYNDROMES
MEMBRANOUSGLOMERULONEPHRITIS

Verycommoncauseofadultnephroticsyndrome
Lightmicroscopeshowsbasementmembranethickening

MINIMALCHANGEDISEASE

Isthemostcommoncauseofnephroticsyndromeinchildren
Electronmicroscopyshowsfootprocesseffacement
Thisconditionresponseexceptionallywelltosteroids

FOCALSEGMENTALGLOMERULARSCLEROSIS

MorecommoninpatientswithHIV
Lightmicroscopeshowssegmentalsclerosisandhyalinosis

DIABETICNEPHROPATHY

Occursindiabetics
ThereisbasementmembranethickeningandKimmelstielWilsonlesionson
lightmicroscopy

SYSTEMICLUPUSERYTHEMATOUS

Thereare5patternsofrenalinvolvement
Lightmicroscopewillshowwireloopappearancewithgranular
subendothelialBMdepositsinmembranousglomerulonephritispattern

RENALCELLCARCINOMA
Renalcellcarcinomaisthemostcommonofallrenalmalignancies,occurringmost
commonlyinmenbetween5070yrofage,andismorecommoninsmokers.

AssociatedwithvonHippelLindau
Originatesinrenaltubulecells

Manifestsas:

Hematuria
Palpableflankmass
Secondarypolycythemia(duetoproductionoferythropoietinfromkidney)
ManyparaneoplasiasarecommonduetoproductionofProlactin,PTHrP,and
ACTH)


WILMSTUMOR
Thisisthemostcommonmalignancyseeninyoungchildrenbetween24yrofage.
ThefollowingareimportantregardingaWilmstumor:

ThereisadeletionoftheWT1genethatisfoundonchromosome11
Presentswithahuge,palpableflankmass

WilmstumorisoftenseeninconjunctionwiththeWAGRcomplex:
WWilmstumor
AAniridia(absenceoftheiris)
GGenitorurinarymalformations
RRetardation(bothmentalandmotor)

TRANSITIONALCELLCARCINOMA
Isacommoncancerseenintheurinarytract(bladder,ureters,renalpelvis,and
renalcalyces).Themostcommoncausesinclude:Smoking,AlanineDyes,
Cyclophosphamide.

PYELONEPHRITIS
Anascendinginfectionthatspreadsfromthebladdertothekidneys.Themost
commoncauseofpyelonephritisisanE.Coliinfection.
Signs/Symptoms:

Flankpains(CVAtenderness)
Fever
Nausea/vomiting
Patientwillappearquiteill

**Patientswithvesicoureteralrefluxhaveanincreasedtendencytogetting
pyelonephritis.


ACUTETUBULARNECROSIS(ATN)
Acutetubularnecrosisoccurswhenthereisaninsulttotherenaltubules.Anything
thatcanharmthekidneyscancauseATN,thingssuchas:Ischemiaduetoshock,
increasedmyoglobinsduetomusclebreakdown,drugs,toxins.
**Isthemostcommoncauseofacuterenalfailure.

ACUTERENALFAILURE
AcuterenalfailureoccursmostcommonlyfromATN(mentionedabove),andoccurs
whenadeclineinrenalfunctioncausesanincreaseinthelevelsofBUNand
Creatinine.
Thecausesofrenalfailure:
PrerenalAzotemiaiswhenthereisadecreaseinrenalbloodflow,whichleads
toadecreaseintheglomerularfiltration,andthusretentionofwaterandsodiumin
thekidneys.BUN>Cris>20
PostrenalAzotemiathisconditiononlyoccursifthereisbilateralobstruction,
thingssuchasprostatichyperplasia,neoplasia,andstone(lesslikely)willcausea
postrenalazotemia.BUN/Cris>15
IntrinsicthisisduetoATN(usually),andtheurinewillgivethiscauseawayby
havinggranularcastsorepithelialcasts.BUN/Cris<15

WHATHAPPENSWHENRENALFAILUREISPRESENT?
Renalfailureleadstoabuildupoftoxinsandleadstotheinabilitytoexcrete
nitrogenousbases.
Acuterenalfailureisusuallyduetohypoxemia,whilechronicrenalfailureis
usuallycausedbyeitherhypertensionordiabetes.
WhenthereisabuildupofBUNandCreatinine,uremiadevelops.Whenuremia
develops,thefollowingsymptomsmaybepresent:

AnemiaduetofailureofEPOproductionbythekidneys
CHF/Pulmonaryedemaduetosodiumandwaterexcess
Metabolicacidosis
Hyperkalemia
OsteodystrophyduetofailureofvitaminDproductionbythekidneys


KIDNEYSTONES
Thereareafewdifferentformsofkidneystones,theyare:
1. CALCIUMSTONESthemostcommonformofkidneystone,whichmaybe
eithercalciumoxalateorcalciumphosphate.Anydiseaseordisorderthat
leadstohypercalcemiacancauseacalciumstone.

2. STRUVITESTONESthesearemadeofammonium,magnesium,and
phosphate,andtheyarethe2ndmostcommontypeofkidneystone.Theyare
producedbyureasepositivebugssuchasProteusVulgaris.Thesehavea
tendencytoformstaghorncalculiandgetstuckintheurinarysystem.
3. URICACIDSTONESproducedasaresultofstatesofhyperuricemia,such
aswithgout.Thesestonesarealsoproducedwhenthereareconditionsof
increasedcellturnover,suchaswithleukemia.
4. CYSTINESTONEStheseoccursecondarytocystinuria.
RadiopaquestonesCalciumandStruvitestones
RadiolucentstonesUricacidandcysteinstones


ACID/BASEPHYSIOLOGY

Problem
Metabolic
Acidosis

pH

PCO2

[HCO3]

Compensation
Patientwill
hyperventilate
toblowoffCO2

Respiratory
Acidosis

Respiratory
Alkalosis
Metabolic
Acidosis

Bicarb
absorptionin
kidney
Kidney
secretesbicarb
Ptwill
hypoventilate

Causes
DKA,ASA
overdose,
lactic
acidosis
Obstruction
ofairway
Hypervent,
highalt.
vomiting


HOWDOWECOMPENSATEFORACIDBASEDISURBANCES?
Thefollowingnumbersdescribetheappropriatecompensationdependentoneach
metabolicdisturbance.
Ifpatienthasmetabolicacidosis:
PCO2=1.5(HCO3)+8+/2

Ifpatienthasmetabolicalkalosis:
Forevery1mEq/LincreaseinHCO3,thePCO2increases0.7mmHg

Ifpatienthasacuterespiratoryacidosis:
Anincreaseof1mEq/LofHCO3forevery10mmHgincreaseinPCO2

Ifpatienthaschronicrespiratoryacidosis:
Anincreaseof3.5mEq/LofHCO3forevery10mmHgincreaseinPCO2

Ifpatienthasacuterespiratoryalkalosis:
Adecreaseof2mEq/LHCO3forevery10mmHgdecreaseinPCO2

Ifpatienthaschronicrespiratoryalkalosis:
Adecreaseof5mEq/LHCO3forevery10mmHgdecreaseinPCO2

RHEUMATOLOGY

TypesofArthritis:
1.
2.
3.
4.

Osteoarthritis
RheumatoidArthritis
Gout
Pseudogout

OSTEOARTHRITIS
Osteoarthritisisthemostcommontypeofarthritisthatiscausedbythewearand
tearofjoints,whichleadstothedestructionofthearticularcartilageandthe
subchondralboneformation.Thisleadstotheformationofosteophytes,aswellas
HeberdensandBouchardsnodes.
HeberdensNodesmalformationsofthedistalinterphalangealjoints
BouchardsNodesmalformationsoftheproximalinterphalangealjoints
PresentationofOsteoarthritis:

Paininweightbearingjoints
Asymmetricinvolvement
Painworseattheendoftheday(improveswithrest)


RHEUMATOIDARTHRITIS
Isanautoimmuneconditionthatattacksthesynovialjointsofthebody.

Pannusformationinjointsleadstodeformitiesofthemetacarpophalangeal
jointsandproximalinterphalangealjoints.
Formationofsubcutaneousnodules
Ulnardeviationatthewristjoint
Seeninfemales>>>males

PresentationofRheumatoidArthritis:

Stiffnessinthemorningthatimproveswithuse
Symmetricinvolvement
Systemicsymptomsarepresent(fever,fatigue,cardiacconditions,
pulmonaryconditions)

GOUT
Aconditionwherebymonosodiumuratecrystalsprecipitateandaccumulate
insidethejoints,mostcommonlyseeninthebigtoe,whichisknownas
podagra.Ultimatelythisisaconditionthatoccursasaresultofpurine
metabolismdisorder.
Causes:

LeschNyhansyndrome
PRPPexcess
Hyperuricemia
Glucose6phosphatedeficiency

Precipitatingfactors:

Diethighinprotein
Alcoholuse
Excesscoffeeconsumption
Consumptionofdairyproducts

Diagnosisisbasedonjointaspirationandfindingofnegativelybirefringentneedle
shapedcrystalsintheaspirate.NSAIDsarebestforacutemanagement,whiledrugs
thatdecreaseuricacidinthesystemwillhelppreventrecurrences.

PSEUDOGOUT
Aconditionsimilartogout,pseudogoutiscausedbythedepositionofcalcium
pyrophosphatecrystalsinsidethejointspace.Thecrystalsformedarerhomboid
shapedandbasophilic.Thelargejointsaremostcommonlyaffected.


SERONEGATIVESPONDYLOARTHROPATHIES

Thegroupofseronegativespondyloarthropathiesinclude:
1.
2.
3.
4.
5.

AnkylosingSpondylitis
ReitersSyndrome(ReactiveArthritis)
PsoriaticArthritis
IBDArthropathy
UndifferentiatedSpondyloarthropathy

Thisgroupsofarthritistypeshasthefollowingincommon:

Theyarerheumaticfactornegative
Theyhaveextraarticularsymptoms(visual,pulmonary,cardiac,etc)
AssociationwithHLAB27antigen
Inflammatoryprocesses
Asymmetricalpresentation
Familial

ANKYLOSINGSPONDYLITIS

Lowbackpainandstiffness(patientisbentoveratthehips)
Cspinemotionislimitedduetoneckpains
Diminishedchestexpansion
Mostcommonextraarticularinvolvementisintheeyes(anterioruveitis)
Bestdiagnosticmodalityisxrayoflumbarspineandpelvis
ManagementiswithNSAIDsandphysicaltherapy

REITERSSYNDROME

Isaclinicaldiagnosisbasedonthepresentationofarthriticsymptomsthatis
precededbyaninfection(salmonella,shigella,campylobacter,Chlamydia,
andyersinia)
ClassictriadisArthritis,Urethritis,andUveitis(cantsee,cantpee,cant
climbatree)
Thereisasequentialinvolvementofnewjoints
Patientoftenhasanaccompanyingsetofsymptomssuchasfatigue,weight
loss,andoverallsenseofmalaise

PSORIATICARTHRITIS

Developsinpatientswhohavearthritis
Onsetisgradualandseenlongafterpatientdevelopsarthritis
Issimilarinpresentationtorheumatoidarthritis
ManagementiswithNSAIDs

POLYARTICULARJOINTINVOLVEMENT:RA,REITERS
MONOARTICULARJOINTINVOLVEMENT:OSTEOARTHRITIS,GOUT,
PSEUDOGOUT

SYSTEMICLUPUSERYTHEMATOUS

Anautoimmunedisorderwherebythereismultisystemandmultiorgan
inflammationandtissuedamage.
Types:

SLE
DiscoidLupus(skinmanifestationwithoutsystemicdisease)
DrugInduced
ANAnegativeLupus

Whogetsit?

90%ofcasesarefemalesofchildbearingage
AfricanAmericansareaffectedmorethanCaucasians
Severitytendstobelessinolderpatients,andmoreinyoungerpatients

Findings:

Butterflyrash
Photosensitivity
Discoidrash
Alopecia
Raynaudsphenomenon
Jointspain/arthralgias/myalgias
Pericarditis/endocarditis/myocarditis
Pleuritis/pleuraleffusion/pneumonitis
Hemolyticanemia/leucopenia/thrombocytopenia/lymphopenia
Proteinuria>0.5g/day,glomerulonephritis/pyuria/azotemia/uremia/HTN

AbnormalTcellfunction,lymphocyteautoantibodies
Nausea/vomiting/PUD/dyspepsia
Seizures/psychosis/depression/TIA/headaches/CVA
Fever,malaise,conjunctivitis

DiagnosticCriteria:

PositiveANAisseeninalmostallSLEpatients
AntidsDNAisseeninapproximately40%ofSLEpatients
AntiSmantibodiesisseeninapproximately30%ofSLEpatients

SARCOIDOSIS

Isaconditioncharacterizedbyimmunemediated,widespreadnoncaseating
granulomas.Theclassicfindingisbilateralhilaradenopathy.
Thereisalsotheincidenceof:

IncreasedlevelsofACE
Rheumatoidarthritis
Interstitialfibrosis
Gammaglobulinemia
Restrictivelungdiseases
Erythemanodosum
Hypercalcemia

AUTOIMMUNECONDITIONSOFTHESKIN

PSORIASIS
Autoimmuneconditionwheretheskindevelopsred,scalypatchesontheskin.The
plaquesthatdevelopareknownaspsoriaticplaques,andarecausedbyexcessive
productionofskinandafasterskincyclethannormalskin.

Skinappearssilverywhiteincolor
Mostcommonlypresentonextensorsurfacesofthebody(knees,elbows),
butmaybeseenonthehands,feet,genitals,andthescalp.

Thisconditionisnotcontagious*
PsoriasisisassociatedwiththeB27haplotype(HLAB27),HLA13,andHLA17.

PsoriaticPlaque

PEMPHIGUSVULGARIS
Isapotentiallyfatalconditionthatinvolvestheoralmucosaandtheskin.Itis
causedbyIgGantibodiesagainsttheepidermalcellsurface,causesbreakdownof
thecellularjunctionoftheepithelialcell.Patientwilldevelopbullaeontheskinand
oralmucosa.
IgGantibodiescanbeseenonimmunofluorescence.

BULLOUSPEMPHIGOID
IsaskindisorderwherebyIgGantibodiesworkagainsttheepidermalbasement
membrane.ThisconditionisverysimilartoPemphigusVulgarisbutismuchless
severe.

SCLERODERMA

SclerodermaorProgressiveSystemicSclerosisisanexcessivedepositionof
collagenandsubsequentlyfibrosisthroughoutthebody.Themostcommonsiteof
presentationistheskin,howeveritmayaffectthekidneys,cardiac,and
gastrointestinalsystems.

CRESTSYNDROMEAssociatedwiththeanticentromereantibody
Asyndromecomprisingof5differentconditionsthatgenerallylackanyskin
involvement.
CCalcinosis
RRaynaudsphenomenon
EEsophagealdysmotility
SSclerodactyly
TTelangiectasias

DIFFUSESCLERODERMA
ThisconditionisassociatedwiththeantiScl70antibody,wherebythereis
widespreadskininvolvement,visceralinvolvementrelativelyearly,andarapid
courseofactionandprogression.

VASCULITISCONDITIONS

LargevesselconditionsTemporalarteritis,
CONDITION
Temporal
Arteritis

Takayasus
Arteritis

ChurgStrauss

FEATURES
Severeheadache

Visualimpairment
in25%50%

Jawpains

Temporal
tenderness
Usuallyseenin
youngAsian
females

Decreasedand/or
absentperipheral
pulses

Bloodpressure
differencesinarm
vslegs

Many
complicationslike
limbischemia,
aneurysms,stroke,
HTNfromrenal
arterystenosis
Avasculitis
affectingmany
differentorgan
systems

Fatigue,weight
loss,fever

Respiratory

DIAGNOSIS
Age>50yr

Newonset
headache

ElevatedESR

Temporalartery
biopsy
Basedonclinical
symptoms

TREATMENT
Highdosesteroids

ESRfollowups
during
management

Biopsyoflung
tissue

Biopsyofskin
tissue(showshigh
eosinophils)

pANCAwillbe
found

Poorprognosis

5yrsurvivalis
only25%

Steroidscan
prolongtreatment

Steroids

HTNmanagement

Wegeners
Granulomatosis

Polyarteritis
Nodosa

symptomsandskin
findingsare
primaryfindings

Avasculitisofthe
kidneysand
respiratorytract

Upperrespiratory
symptoms

Painfuloralulcers

Eyedisease
(scleritis,
conjunctivitis)

Musculoskeletal
findings(myalgia,
arthralgia)

Trachealstenosis
Isamediumvessel
vasculitisthat
involvesthe
nervoussystem
andGItract

Causesintimal
proliferationwhich
causesadecrease
intheluminalarea,
resultingin
ischemia,
infarction,andthen
aneurysm

Livedoreticularis

Hypertension

Fever/wt
loss/arthralgia/abd
pain

CXR(nodulesor
infiltratesare
present)

ElevatedESR

Anemia

pANCAseenin
mostpatients

Confirmatorytest
isanopenlung
biopsy

Steroids+
cyclophosphamide
canhelppatients
intoremission

Withrenalfailure,
atransplantis
curative

Biopsy

ESR

pANCA

Fecaloccultblood

Steroidscan
improveprognosis,
whichispoor
withouttreatment


Behcets
Syndrome

Amultisystem
vasculitisof
unknownetiology

Recurrentoraland
genitalulcerations

Arthritis

Visualimpairment

CNSinvolvement

Fever/weightloss
BuergersDisease Seeninyoung
maleswhosmoke

Smallandmedium
sizedveinsand
arteries

Affectsarmsand
legs

Claudicationoccurs

Smokingis
imperativeinfixing
theproblem
Hypersensitivity Isa
Vasculitis
hypersensitivity
reactionthat
occursinresponse
tocertain
medications
(sulfas,PCN)

Causesskin
problems(purpura,
macules,vesicles)

Biopsyofall
involvedtissues

Steroids

Clinicallybased

Smokingcessation

Tissuebiopsyof
affectedtissues

Stopoffending
agent(s)

Remissionisoften
spontaneous

ENDOCRINEPATHOLOGY

ADRENALPATHOLOGY
1. Hyperaldosteronism
2. Addisonsdisease
3. Cushingsdisease

HYPERALDOSTERONISM
PrimaryConnsSyndrome
Causedbyanaldosteronesecretingtumorthatcauseshypertensionand
hypokalemia(rememberwhenaldosteroneincreases,potassiumdecreases),
metabolicalkalosis(rememberhypokalemia=alkalosis,hyperkalemia=acidosis),
andlowplasmarenin.
Secondaryhyperaldosteronism
Causedbyrenalarterystenosismostcommonly.Mayalsobeduetorenalfailure,
cirrhosis,nephroticsyndrome,andcongestiveheartfailure.Theseconditions
triggertheactivationoftheRAAS,whichstimulatesthekidneyseventuallytohold
ontomorewaterandsodium.Asopposedtotheprimarycause,thisconditionhas
highplasmarenin.
TreatinghyperaldosteronismAldosteroneantagonistspironolactonecaninhibit
theactivityofaldosteroneonthekidney.

ADDISONSDISEASE
Causedbyprimaryadrenalinsufficiency.Themostcommoncauseisautoimmune,
infectious,andasaresultofmetastaticdisease.
FeaturesofAddisonsdisease:

Posturalhypertension
Hypoglycemia
Weightloss
Weakness
Anorexia
Nausea
Hyperpigmentation(onlyseeninprimaryadrenalinsufficiency)
Lowaldosteronelevels(lowsodium,highpotassium)

Diagnosing:

Plasmacortisollevels
PlasmaACTHlevels

Imagingofpituitary(ifdiagnosisissecondaryadrenalinsufficiency)

CUSHINGSSYNDROME/DISEASE
CushingsSyndromethesyndromeresultsfromanexcessivelyhighlevelof
glucocorticoids(cortisolistheprimaryGC).
CushingsDiseasethediseaseoccursasaresultofapituitaryadenoma.

CausesofCushings:
1. Iatrogenicthisisthemostcommoncause,andisduetotheadministration
ofcorticosteroids.
2. ACTHsecretingadenomaofthepituitary,thisisthe2ndmostcommoncause,
leadingtobilateraladrenalhyperplasia.
3. Adenomaoftheadrenal
4. EctopicACTHproductioncanbecausedbycarcinomaofthelung(small
cell).
Features:
ThereareclassicfeaturesofCushings,theyare:

Centralobesity
Buffalohump
Hirsutism
Striaeonabdomen
Acne

Inaddition,thereisapresenceof:

Hypertension
Diabetes(glucosetolerance)
Hypogonadismcausinginfertility
Excessandrogen(masculinizesfemales)
Musculoskeletalabnormalities(musclewasting,osteoporosis,femoralhead
osteonecrosis)
Psychiatricdisturbancessuchasdepression
Impairedimmunityleadingtoincreasedchancesofinfection

TUMORSOFTHEADRENALGLAND
PHEOCROMOCYTOMA
Themostcommontumoroftheadrenalmedullainadults.Itisderivedfromthe
chromaffincells.
Signs/Symptoms:

Palpitations
Anxiety
Headache
Diaphoresis
Significanthypertension
Tachycardia

Diagnosisisbasedoncheckingurinemetanephrines,andtreatmentissurgical
removalafteradequatemanagementofthehypertension.

NEUROBLASTOMA
Isthemostcommonadrenaltumorinchildren,andisthemostcommonintracranial
tumorinchildrenaswell.Whilemostcommonlyfoundintheadrenalmedulla,it
canbefoundanywherealongthesympatheticchain.

CONGENITALADRENALHYPERPLASIA
Acongenitalconditionwherebythereareexcessiveordeficientproductionofsex
steroidsfromtheadrenalgland.
ThemostcommoncauseofCAHisdueto21hydroxylasedeficiency.Thiscondition
willcauseanexcessofandrogensandadecreaseinmineralocorticoids.Thereisan
accumulationofthesubstrate17hydroxyprogesterone.Thiscondition,whereby
thereareincreasedandrogens,willcausemasculinizationofthefemaleexternal
genitalia(internalfemalesexualorgansareintactsincenomullerianinhibiting
factorispresentnotesticles),and/orambiguousgenitalia.


THYROIDGLANDPATHOLOGY

CANCERS
PAPILLARYCARCINOMA

Presenceofgroundglassnucleiandpsammomabodies
Isthemostcommontypeofthyroidcancerandholdsthebestprognosis

FOLLICULARCARCINOMA

Thereisapresenceofuniformfollicles
Holdsagoodprognosis(betterthanmedullarybutworsethanpapillary)

MEDULLARYCARCINOMA

DerivedfromtheparafollicularCcells,thusproducescalcitonin.
IsamemberoftheMENIIandMENIIIsyndromes
Hasabadprognosis

ANAPLASTICCARCINOMA

Thisthyroidcarcinomaoccursinolderpatients
Holdsaterribleprognosisandtheworstofallthyroidcarcinomas

HYPERTHYROIDISM
TherewillbealowTSH(duetofeedbackinhibition),withahighT3/T4
Patientwillhavethefollowing:

Heatintolerance
Weightloss
Palpitations
Warm/moistskin
Arrhythmias

HYPOTHYROIDISM
TherewillbeahighTSHandlowT3/T4
Patientwillhavethefollowing:

Coldintolerance
Weightgain
Fatigue
Lethargy
Weakness
Decreasedreflexes
Dry/coolskin
Coarse/brittlehair
Myxedema

GRAVESDISEASE
Gravesdiseaseisthemostcommoncauseofhyperthyroidism,accountingforupto
80%ofallcases.

IsanautoimmunedisorderwherebyathyroidstimulatingimmunoglobulinG
antibodybindstotheTSHreceptorsonthethyroidcells,triggeringthe
synthesisofexcessthyroidhormone
Diffuseradioiodideuptakeonscan

PLUMMERSDISEASE
Alsoknownastoxicmultinodulargoiter),accountingforapproximately15%ofall
cases.

ThereareareasofhyperfunctioningthyroidtissuethatproduceexcessT3
andT4
Morecommoninolderpatients
Elderlypatientswithhyperthyroidismmaypresentsimplywithunexplained
weightloss,weakness,and/oratrialfibrillation

HASHIMOTOSTHYROIDITIS
Anautoimmuneconditionthatcauseshypothyroidism.

Presentswithamoderatelyenlarged,butnontenderthyroidgland
Thereislymphocyticinfiltrationwithgerminalcenters
Antimicrosomalantibodiesareresponsibleforthecondition

SUBACUTETHYROIDITIS(deQuervains)
Thisisatransientthyrotoxicphaselasting25monthsthatisusuallyselflimited.

Absenceofpain/tendernessofthyroidgland
Oftenfollowsaflulikesyndrome
Lowradioactiveiodineuptake

HYPERCALCEMIA
Therearemanycausesofhypercalcemia,theycanberememberedwiththe
mnemonicCHIMPANZEES
CCalciumIngestion
HHyperparathyroidism/hyperthyroidism
IIatrogeniccauses(suchasthiazidediuretics)
MMultiplemyeloma
PPagetsdisease
AAddisonsdisease
NNeoplasms
ZZollingerEllisonsyndrome
EExcessivevitaminAintake
EExcessivevitaminDintake
SSarcoidosis

Signs/SymptomsStones,Bones,Moans,Groans,andPsychiatricovertones
Stoneskidneystones
Bonesbonepain,especiallywithanincreasedPTH
Moanspsychiatricnoise
Groansconstipation
PsychiatricOvertonesconfusion,depression,etc


HYPERPARATHYROIDISM
Thereareprimaryandsecondaryformsofhyperparathyroidism.
PrimaryTheprimaryformofhyperPTHisusuallycausedbyanadenomainthe
gland.Mostofthetimetherearenosymptomsofthiscondition,howeverlab
findingswillshowthefollowing:HyperCa2+,hypercalciuria,hypophosphatemia,
increasedparathyroidhormone,andincreasecAMPintheurine.
SecondaryThesecondaryformofhyperparathyroidismiscausedbyalowserum
calcium,andisseenmostcommonlyinsomeonewithchronicrenaldisease.There
willbehypocalcemia,hyperphosphatemia,andincreasedlevelsofPTH.

HYPOPARATHYROIDISM
Hypoparathyroidismisusuallyduetoeitheraccidentalremovalduringathyroid
procedureorfromDiGeorgesyndrome.Patientwillhavehypocalcemiaandtetany.
Theeasebywhichtetanyoccurscanbetestedbycertainmaneuversthatcause
muscularspasms.
TrousseausSignisatestthatlooksforcarpalspasm,andisdonebyoccludingthe
brachialarterybypumpingupabloodpressurecuff.
ChvosteksSignisatestthatattemptstocauseaspasmofthefacialmuscles,andis
donebytappingonthefacialnerve.

ACROMEGALY
Knownasgigantisminchildren,thisisaconditionwherethereisexcessGH
secretedfromthepituitarygland.Patientwillhaveenlargementofhands,feet,
facialfeatures,deepeningofvoice,etc.Thesepatientsdieearlierthanthenormal
lifespan.
Normally,givingglucosewouldsuppressGHlevels,thusifgivingglucosedoesNOT
suppressthelevelofGH,adiagnosisofacromegalycanbemade.

CRETINISM
Cretinismisaconditionthatoccurwhenthereisalackofdietaryiodine(endemic
cretinism).AdefectinT4formationorthefailureofthyroiddevelopmentduring

developmentcausessporaticcretinism.Patientsarepuffyfaced,pale,potbellied
withprotrudingumbilicusandaprotrudingtongue.

DIABETESMELLITUS
ComparingDMtypes1and2
TYPE1DIABETES

TYPE2DIABETES

celldestruction(autoimmune)

Insulinresistance

Lifelonginsulinisrequired

DKAiscommon

Diet/exerciseisprimary
treatment

Startsinchildhood(usually)

Bodyisskinny

Associatedwithobesity
DKAisrare

InitialPresentationofDM1:
Theclassicpresentationispolyuria,polydypsia,polyphagia,andweightloss.
DKA,theadverseeffectofDM1leadstoincreasedplasmaglucose,dehydration,
acidosis,andifleftuntreatedwillleadtocomaanddeath.
ChronicEffectsofDM1:
SmallVesselDiseasethickeningofsmallvesselsleadstoamyriadofproblems
throughoutthebody.Retinopathy,nephropathy.
LargeVesselDiseasewillleadtoatherosclerosis,coronaryarterydisease,CVA,
PVD.
Neurologicalwidespreadlossofsensationthroughoutthebody.
Cataractsoccurasaresultofsorbitolaccumulation.

DIABETICKETOACIDOSIS(DKA)
DKAisalifethreateningadversereactionofDM1.Thereisanincreasedneedfor
insulinthatdoesntgetmet,andisusuallycausedbyanillness/infectionthat
increasesthestressleveloftheperson.Thisleadstoanincreaseinketogenesisand
thusproductionofketonebodies.
Signs/Symptoms:

Nauseaandvomiting
Kussmaulbreathing(attemptstocorrectmetabolicacidosis)
GIpains
Dehydration
Psychosisanddementia
Hyperglycemia
Increasedaniongapmetabolicacidosis
Increaseketonelevels
Hyperkalemiawithdepletedintracellularpotassium

Complications:

Cerebraledema
Arrhythmia
Heartfailure
Murcomycosis(causedbythefungusRhizopus)

HowisDKAmanaged?

Lotsoffluids
Insulin(giveglucoseiflevelsstarttodrop)
Potassium(whenK+levelsnormalize)

DIABETESINSIPIDUS(DI)
Alackofantidiuretichormone(ADH),duetoeitheracentralcauseora
nephrogeniccause.
CentralDIiscausedbyatumorinthepituitary,trauma,surgery
NephrogenicDIiscausedbyalackofrenalresponsetoADH

Patientwillhaveintenseneedforfluidscoupledwithpolyuria,withdiluteurinethat
isnotconcentratedduetolackofADH.
Management:CentralDI:Desmopressin(intranasal)NephrogenicDI:
hydrochlorothiazide(increasesNa+andH20absorptionindistalnephron).


SYNDROMEOFINAPPROPRIATEANTIDIURETICHORMONE(SIADH)
ToomuchADHduetoanyofthefollowingcauses:

EctopicproductionofADH(commonlyfromsmallcellcarcinomaofthelung)
Traumatotheheadand/orCNSdisordersthatreleaseexcessADH
Drugssuchascyclophosphamide

AnexcessinADHwillcausethefollowingproblems:
1. Extreme/excesswaterretention
2. Hyponatremiaduetodilutionaleffects(cancauseseizure)
3. Concentratedurine(urineosmolarity>serumosmolarity)

OSTEOPOROSIS
Osteoporosisisthereductioninthebonemasswherethereisnormal
mineralization.Therearetwotypes:
Type1Occursinpostmenopausalwomenduetodecreasedestrogenlevels.
Thereisanincreaseinboneresorption.
Type2Senileosteoporosisaffectsthosewhoareolderthan70yrofage,
affectingbothmenandwomen.
Commonproblems:

Vertebralcrushfractures
Pelvicfractures
Fracturesofthedistalradius
Vertebralwedgefractures

Management:Bisphosphonatesarerecommended,whereasestrogenreplacement
workswellbutcomeswithsideeffectsthatareconcerning.


MULTIPLEENDOCRINENEOPLASIA(MENSYNDROME)
MENsyndromesarethecategoriesofsyndromethatcompriseofcertainneoplasias.
Thesegroupsofneoplasiashaveatendencytopresentsimultaneously.
MENIPancreas(ZollingerEllison,insulinomas,VIPomas),Pituitary,Parathyroid
MENIIMedullarycarcinomaofthyroid,Pheocromocytoma,Parathyroidadenoma
MENIIIMedullarycarcinomaofthyroid,Pheocromocytoma,MucosalNeuromas

ZOLLINGERELLISONSYNDROME
ZESisagastrinsecretingtumorofthepancreasorduodenum.Thisconditionis
suspectedwhenevertherearerecurringulcersthatarenottreatedconservatively.
SuspectZESwheneverthereisapituitaryand/orparathyroidadenomaastheyare
alltogetherintheMENIsyndromecategory.

BREASTDISEASES

FIBROCYSTICDISEASE
Fibrocysticbreastdisease/changesaffectsbetween30%60%ofwomen.
Characterizedbybenignlesionsanddiffusebreastpainthatisoftenrelatedto
hormonalchangesassociatedwithhermenstrualcycle.
Thereisafibrous,lumpytexturetothelesionsofthebreast.Mammogramisnot
requiredtomakethisdiagnosis,butfineneedleaspirationiscommonlydoneto
checkthecharacteristicsofthefluid.
Treatmentisnotnecessary,howeverpainreliefshouldbedone
**Thereisnoincreasedriskofbreastcancerinfibrocysticdisease.

BREASTCANCER
RiskFactors:

Familyhistoryofa1stdegreerelativewithbreastcanceratayoungage
Ageandgender
Menarche(<12yr)isshowntoincreaserisk
Pregnancy(>30)canincreaserisk
Latemenopause(>50)

INVASIVEBREASTCARCINOMAS

Aredividedintotwomajorcategoriesbasedontheircytoarchitecturalfeatures:
INVASIVEDUCTALCARCINOMA

TubularCarcinoma

LOBULARCARCINOMA
Pleomorphic

SebaceousCarcinoma
SecretoryBreastCarcinoma

NeuroendocrineCarcinoma

MucinousCarcinoma

MicropapillaryCarcinoma

AcinicCellCarcinoma

AdenoidCysticCarcinoma

ApocrineCarcinoma

CribriformCarcinoma

GlycogenRich/ClearCell

InflammatoryCarcinoma

LipidRichCarcinoma

SignetRingCell

IntraductalPapillomasaretumorsofthelactiferousducts,theypresentwith
nippledischarge.Arisingfrommammaryductepitheliumorlobularglands,and
overexpressionofestrogen/progesteronereceptors.
DuctalCarcinomainSitu(DCIS)isearlymalignancywithoutbasement
membranepenetration
InvasiveDuctalCarcinomapresentsasafirm/fibrousmass
Comedocarcinomaisductalwithcheesyconsistencyduetocentralnecrosis
Inflammatoryhaslymphaticinvolvementandcarriesapoorprognosis
InvasiveLobularCarcinomapresentsbilaterallywithmultiplelesions
MedullaryCarcinomacarriesagoodprognosis,isfleshywithlymphocytic
infiltration

PagetsDiseaseoftheBreasteczematouspatchonthenipple

POLYCYSTICOVARIANSYNDROME
Isacommondisorderandoneofthemostcommoncausesofinfertilityinwomen.
AnincreaseinLHproductionleadstoanovulationandhyperandrogenismdueto
alteredsteroidsynthesis.
Signs/Symptoms:

Obesity
Hirsutism
Amenorrhea
Infertility

Thisconditionshouldbemanagedwithweightlossandoralcontraceptivepills
(OCPs).

OVARIANCYSTS


GERMCELLTUMORSOFTHEOVARY
TERATOMAupto90%ofgermcelltumorsoftheovary.Containsallthreegerm
layers(ectoderm,endoderm,mesoderm).Theimmatureteratomaisvery
aggressiveandmalignant.
DYSGERMINOMAisthemostcommontypeofmalignantgermcellovariantumor,
usuallyoccurringinadolescenceandearlylife.Isanalogoustothemaleseminoma.
YOLKSACTUMORproducesfetoprotein
CHORIOCARCINOMAisthesameasthetesticularversionofthegermcelltumor,
causesanincreaseinhCG.

NONGERMCELLTUMORSOFTHEOVARY
SEROUSCYSTADENOMAisbenign,comprises20%ofovariantumorsandis
frequentlybilateral.Islinedwithfallopiantubelikeepithelium.
SEROUSCYSTADENOCARCINOMAcomprises50%ofovariantumors,isfrequently
bilateralandismalignant.
MUCINOUSCYSTADENOMAisbenign,andisamultilocularcystlinedbymucus
secretingepithelium.
MUCINOUSCYSTADENOCARCINOMAismalignant,withintraperitoneal
accumulationofmucinousmaterialfromovarianorappendicealtumor.
BRENNERTUMORisabenigntumorresemblingbladderepithelium.
OVARIANFIBROMAcontainsbundlesofspindleshapedfibroblasts.Meigs
syndromeisatriadofovarianfibroma,ascites,andhydrothorax.
GRANULOSACELLTUMORsecretesestrogencausingprecociouspubertyin
children,whileinadultsitcancauseendometrialhyperplasiaorcarcinoma.
ContainsCallExnerbodies,whicharesmallfolliclesfilledwitheosinophilic
secretions.


UTERINEPATHOLOGY

ENDOMETRIALCARCINOMA
Isthemostcommongynecologicalmalignancythatpeaksbetween5565yrofage.
Themostcommoninitialpresentationisvaginalbleeding.
RiskFactorsProlongeduseofestrogen,DM,hypertension,andobesity.

ENDOMETRIOSIS
Occurswhenendometrialglandsarepresentinlocationsoutsideoftheuterus.
Presentswithseverepainrelatedtomenstruationandproduceschocolatecysts
(bloodintheovary).Maycauseinfertility.

ADENOMYOSIS
Isendometriosiswithinthemyometriumoftheuterus

LEIOMYOMA
Isthemostcommontumorseeninwomen,wheretumorsizeincreaseswith
pregnancyanddecreaseswithmenopause.Oftenpresentingwithmultipletumors
atonce.Rareprogressiontocancer.

LEIOMYOSARCOMA
Isabulkytumorwithareasofnecrosisandhemorrhage.Doesnotarisefroma
leiomyoma.Tendencytoprotrudefromcervix,ishighlyaggressiveandhasa
tendencytorecur.


CERVICALPATHOLOGY

DYSPLASIA
Isdisorderedepithelialgrowththatstartsatthebasallayerandextendsoutward.
Carcinomainsitu(CIN)isclassifiedbasedontheextentofdysplasia.Thereisan
associationwithhumanpapillomavirus.
INVASIVECARCINOMA
Mostcommonlythisissquamouscellcarcinoma.Papsmearisanessentialtoolto
catchthisbeforeitbecomestooadvanced.

COMPLICATIONSOFPREGNANCY

Fourcommonconditionsassociatedwithpregnancyinclude:
1.
2.
3.
4.

Placentalabruption(abruptioplacenta)
Placentaaccreta
Placentaprevia
Ectopicpregnancy

PLACENTALABRUPTION
Painfuluterinebleedingthatisaresultofprematureseparationoftheplacenta.Is
anemergencyconditionthatcanresultinfetaldeath.
PLACENTAACCRETA
Placentaattachesdirectlytothemyometrium,andiscausedbyadefectivedecidual
layer.
PLACENTAPREVIA
Placentalattachmenttotheloweruterinesegmentwithmayoccludethecervicalos.
Presentswithpainlessvaginalbleeding.
ECTOPICPREGNANCY
Mostcommonsiteisthefallopiantube,isseenmostcommonlyinapatientwith
historyofpelvicinflammatorydisease.Diagnosewithultrasound.

PREGNANCYINDUCEDHYPERTENSION(Preeclampsia)

Preeclampsia=Hypertension,proteinuria,andedema.
Eclampsia=Triadabove+seizure
*Ifpreeclampsiaispresent,patientrequiresbedrest,saltrestriction,and
monitoring.
AssociatedwithHELLPsyndrome,whichisanemergencysituationthatrequires
immediatedeliveryofthebaby.
HHemolysis
ELElevatedLFTs
LPLowPlatelets

HYDATIFORMMOLE

IsanovumwithoutanyDNA,whichresultsinswellingofthechorionicvilliand
proliferationofchorionicepithelium.TherewillbeelevationofhCGandthe
appearanceofaclusterofgrapes.
CompleteMole46,XXthatisofcompletepaternaloriginwithnoidentifiable
embryonicorfetaltissue.
PartialMole69,XXYor92,XXXY,whereanormaleggisfertilizedbytwoorthree
sperm.
*Maydevelopintochoriocarcinoma


BENIGNPROSTATICHYPERPLASIA
BPHisaconditionthatisquitecommoninmenovertheageof50yr.Characterized
bynodularenlargementofthelateralandmiddlelobes(ieperiurethral),which
compressestheurethraintoaverticalslit.
Signs/Symptoms:

Urinaryfrequency
Frequentnighttimeurinary
Difficultyinstarting/stoppingurination
Complicationsmaybehydronephrosis,hypertrophyofbladder,andUTI.

PROSTATICADENOCARCINOMA
Mostcommonlyseeninmenover50yrofage.Themostcommonsiteof
adenocarcinomaistheposteriorlobe(akaperipheralzone).Digitalrectalexamis
thebestwaytodetectthecancer,ashardnodulescanbedetectedonexam.PSAis
usedasawaytodetectanadenocarcinoma,aslevels>4.0areworrisome.Themost
worrisomeadverseeffectisosteoblasticmetastasis(detectbyincreasedalkaline
phosphatase).