USMLE Success Academy Course Book

2009
2012 USMLE Success Academy, all right reserved.

Part 1
Introduction/Welcome............. p.1
Vitamins & Minerals................... p.23
Membrane Physiology............... p.37
Cellular Physiology.................... p.45
Neuromuscular Physiology....... p.56
Behavioral Medicine................. p.73
Vascular Phys & The Clotting Cycle...................... p.123
Gastrointestinal Medicine......... p.150
Part 2
Acids & Bases .............. p.1
Amino Acids.................. p.12
Proteins........................ p.21
Enzymes....................... p.53
Protein Sequencing..... p.59
Catabolic Biochem...... p.61
Anabolic Biochem....... p.89
Part 3
Rheumatology....... p.1
Neurology............... p.15
Cardiology............. p.56
Pulmonology......... p.81
Endocrinology......... p.101
Nephrology.............. p.130

Part 4
Oncology............... p.1
Bacteriology........... p.38
Fungi & Parasites... p.71
Virology.................... p.100
Immunology............ p.114

WEEK 1
11/26/11
YOURJOURNEYSTARTSNOW
Teachingyoumedicineinawholenewway
Youwillbecalledupon,butthisisafriendly
safezone
Conceptstaughttodayaregoingtochangethe
wayyouseemedicineandyouregoingto
feelasthoughmedicalschoolwasahuge
ripo!
HowIliketoteach ClassroomGoals&ExpectaRons
Idontwaste,me(notyours,notmine)we Respect
aregoingtogetdowntobusinessduringclass DontbeinRmidated
hours Incorrectanswersareanotherchancetolearn
somethingnew
Iasklotsofques,onsthiswillreinforce
whatyouarelearning,thislinksclassmaterial Takeourworkseriously,buthavefundoingit!
toUSMLEstylequesRoning
1
11/26/11
TALENTvs.SKILL TALKINGABOUTSTEP1
Talentissomethingyouareeitherbornwith Atestthattestsyourabilitytotestwell
oryourarent ThisisNOTameasureofyourlevelof
Skillisdevelopedandcanhelpyoubuildon competenceinmedicine
yournaturaltalents Testtakingskillsdoesnotpredictyourability
tobeabigsuccessinmedicine
Hardworkbeatstalent,whentalentdoesnt
wanttoworkhard
TALKINGABOUTSTEP1 STEP1ANDYOURSPECIALTY
Itishowever(unfortunately)theBIGGEST Howisascoreof240requiredtogetinto
factorindeterminingyourabilitytoget plasRcswhilegeneralsurgerytakespeople
interviews withlow200s?
Moreandmoreapplicantseveryyear,theone WhytheprimarycarespecialResarenolonger
thingyouallhaveincommonistheStep1 easytoget(morecompeRRonmeansyou
youvealltakenitbytheRmeyouveapplied needthescores)
2
11/26/11
WHATITALLMEANS ORGNIZINGYOURBRAIN
Itmeansyouneedagoodscoretoatleastget Medschoolthrewhundredsofthousandsof
themtoreadyourfullresume factsatyouhowdidtheyshowyouhowto
Whetheryouhaveafailureornot,weregoing leitawayandapplyit?theydidnt
toputyourscoreintotherangethatgetsyou Thinkinginahighyieldfashion(choosingthe
interviewsthatsmypromisetoyou! 90%)
Everybodystudyingfortheboardsisstudying Wellshowyouhowtomasterthe90%
hard,butwithrealunderstandingofmedicine whichisexcellentinmedicine!
youllbelightyearsaheadofeveryone!
STARTINGATTHETOPOFTHE
THEREVERSEPYRAMIDTHEORY
PYRAMID
Inmostthingsyouwanttostartfromthe Thetopiswherethemajorconceptsareat
bofomofthepyramid Whenyouknowconceptsaboveallelse,you
Inmedicine,starRngfromthebofomis cannotbefooledever!
counterproducRve Learnaconceptanditcanhelpyoumastera
thousandsthings
Youwonthavetokeeprereadingthings,
BUTWHY? becauseyoullrecognizepafernsandyoull
knowwhatsrightandwrong,andwhich
arRcleshavemerit.
3
11/26/11
SEETHECONCEPTSFIRST ITSALLABOUTTHECONCEPTS
EverdoneaquesRonandfeltliketherewasnt Medicineisallaboutconcepts
enoughinformaRon? Youregoingtolearnhowtoapplythemto
Thisiswhatseparatestheaveragestudents everything,fromthereitisnothingbutlling
fromtheaboveaverageandexcellent intheblanks
students
No,ce:Itisntaboutintelligence,itsabout
beingproperlyequippedwiththetoolsto
succeed!
TESTWRITERSWRITETHESTUDY
GETTINGBACKTOBASICS
GUIDES
Whetheryouretakingstep1,step2ck,step EvernoRcedthatyourarelyseequesRons
3,ortheCanadianboardsthebasicsnever straightoutofyourstudyguides?
change Theyknowwhatyouguysareusingtostudy:
Atestwriterknowstheycantchange FA,B&W,SECRETS
conceptsandcluesthisiswhytheyaddextra Thatswhytheylltakethemajorconcept
uselessinformaRontotripyouup! insideandtwistitslightly10%knowthe
tricks(theygetintodermandplasRcs),while
90%areplayingadangerousguessinggame!
4
11/26/11
TESTWRITERSKNOWTHESTUDY
THEVANNAWHITETHEORY
GUIDES
Topschoolshavethetestwriters,meaning FromDr.Francis,itmeanstheypointyouto
theyalsohavetesttakingstrategysessions images,charts,labs,etc.thathaveno
fromthesource relevance
Wouldyouratherlearnhowtoshootfree IfyougetaquesRonwithlabs,oranxray,ora
throwsfromMichaelJordanorahigh
schooler? graphunlesstheyaskyoudirectlyaboutit,
ignoreit!Itsprobablynotevennecessary.
Wearegoingtohelpyouovercomethe
hurdlesandobstaclesthatareinfrontofyou
thatyoudontevenrealize.
THE3PS 4THINGSYOUNEEDFORPHARM
PHYSIOLOGY MOA(youregoingtogettonsofquesRonson
Damagenormalphysiologyandyouvegot MOAofdrugsthatswhyweregoingtodrill
PATHOLOGY theseintoyourbrains)
Wanttoxdamagedphysiologyuse ADVERSEEFFECTS
PHARMACOLOGY UNIQUEEFFECTS
Youdontrealizehowintertwinedtheyare, TREATINGANOVERDOSE
butyouwillsoon.
5
11/26/11
SAMEINFODIFFERENTTEST STEP1vs.STEP2(orMCCEE)
SomanystudentsthinktheUSMLEsare Q:A24yroldfemalepresentswithcontracRons
dierentfromonetothenexttheyarent andbeginstheiniRalstagesoflabor.During
deliveryitisnotedthatthefetusis4000g,so
ThebasicinformaRonyouhavetoknow
theOBdecidesanepisiotomyiswarranted.
remainsthesameitisonlytheangleat
whichtheyaskyouaquesRonthatseemsto
makeitdierent. Step1:Which3musclesmakeuptheurogenital
diaphragm?
Step2:Whichtypeofepisiotomyisassociated
EXAMPLE withthehighestriskofinfecRon?
BUZZWORDS INTERNALMEDICINE
Everybodysaystheyarenolongerbeingused! Theboardstestyourabilitytoknowinternal
HowarewesupposedtodierenRate andfamilymedicinethatsall.
between23commondiseases?buzzwords Surgicalprinciplesallfallbacktomedicine
TheyresRllthere,theyrejustusedona OB/GYNprinciplesallfallbacktomedicine
highermoreintellectuallevelie.Itsnot Pediatricprinciplesarejustmedicineon
straightoutofyourbooks. smallerpeople
Theclassicclueswillalwaysbearound
6
11/26/11
WHENYOUREALLYUNDERSTAND
SETTINGAGOALFORYOURSELF
MEDICINE
Nomorerereading ItisntagoalunRlyouvewrifenitdown
Youwillstarttorecognizethevastnumberof Feeltheendresult
errorsthroughouttheliterature Nothingworthhavingcomeseasyorelse
Shotgunmedicine wedallbybillionaireswith20homesand50
Howtoimpressresidents,afending,andjust cars
aboutanybodyinthewards(fromwhatIve
readandunderstand)
EXERCISENAMES
YouthinkyouknowsomethingunRlthetestis ANDFINALLY,ALOOK
infrontofyou ATSOMEDISCIPLINESPECIFIC
Drill,drill,drill TIPS&TRICKS!
Iamgoingtodrilleverythingintoyourbrain
7
11/26/11
ANATOMY BEHAVIORALSCIENCE
Detailsarenothighyield EthicsisalwaysHY
AnatomyofHYdiseases,injuries,andcommon BiostatsisnotHY,butyouwillgetafeweasy
surgicalproceduresishighyield pointsfromknowingit
Xray,CT,andMRIsarebecomingmoreand Personalityd/o,anxietyd/o,etcareallHY
morehighyield PsychpharmisHY
Neuroanatomyisveryhighyield
BIOCHEMISTRY MICRO/IMMUNOLOGY
Understandingthebasicsofbiochemistryhelp Bacteriaisthehighestyield
youallacrossmedicinesoitisallHY DisRnguishingcharacterisRcsisimportant
LinkingbiochemwithpathologyisHY Immunology/vaccines/immunodeciencies
RegulatoryenzymesareveryHY areallHYtopics
Only5%parasitology
DiagnosisisHYformicrobiology
8
11/26/11
PHYSIOLOGY PHARMACOLOGY
VeryHY ExtremelyHY
Drawitallout MOA,Prototypes,andmainsideeectsare
Masterphysiologyonceandyouwontforget HY
it Dontworryabouttradenamesordosagesfor
Highlylinkedtopatholgoy(pathophysiology) Step1
Thinkaboutpharmasasystembasedtopic,
insteadofaseparateenRtyofitsown
PATHOLOGY
Highestyieldtopic
Isintertwinedineverythingwedo
Wearegoingtodoitthroughoutthewhole
course,notasaseparateenRty
BuzzwordsaresRllinfulleect
Dontpanicwhenyougetlabsorimages,they
usuallyarentneededforansweringthe
quesRon
9
11/26/11
ENERGYDEPLETEDSTATE
WHATISTHISSTATE?
THEMOSTIMPORTANTCONCEPTS
YOUWILLEVERLEARNINMEDICINE
ENERGYDEPLETION,CELLDEATH,&
THEGABACONNECTION
ENERGYDEPLETEDSTATE ENERGYDEPLETEDSTATE
WHATISTHISSTATE? Allofthecellsofthebodyusedierentamounts
ofenergy,withsomeusingalotofenergyand
Anenergydepletedstateisaconceptwhereby someusingverylifle.
thebodyrespondstoastateofenergydepleRon
bypresenRngwithaveryspecicsetof WHATDOESTHISMEANFORTHEBODY?
symptoms..EVERYSINGLETIME!!
10
11/26/11
WHATDOESTHISMEANFORTHEBODY? WHATDOESTHISMEANFORTHEBODY?
Thecellsrequiringmoreenergywillsuer
signicantlywhilethoseneedinglessenergywill
beaectedless.
TheenergyconsumpRonhierarchy: TheenergyconsumpRonhierarchy:
#1Brain #1Brain
#2MuscleRssue
11
11/26/11
TheenergyconsumpRonhierarchy: TheenergyconsumpRonhierarchy:
#1Brain #1Brain
#2MuscleRssue #2MuscleRssue
#3ATPases(ie.AcRvetransportsystems) #3ATPases(ie.AcRvetransportsystems)
#4Heart
TheenergyconsumpRonhierarchy: The3organsthatconsumethemostenergy:
1. Thebrain
#1Brain 2. Theheart
#2MuscleRssue 3. Thebonemarrow
#3ATPases(ie.AcRvetransportsystems)
Thismeanswecanexpect,inastateofdepleted
#4Heart
energy,thebrain,theheart,andthenthebone
#5Membranemovement(endo/exocytosis) marrowtobeaected.
12
11/26/11
Sowhatdoesthisallmean? WHENADISEASEPRESENTS.
Thebodysuersandlessenergyismade.Aswe
Nomaferwhatdiseaseweencounter,allofthe nowknow,theBRAINistherstthingaected
iniRalsignsandsymptomsaretheexactsame!!
Whenthebrainlacksenergy,weexperience:
SedaRon
FaRgue
Alteredmentalstatus/decreasedarousal
Whenachilddevelopsinanenergydepleted Whenachilddevelopsinanenergydepleted
state,whatdoyouthinkwilloccur? state,whatdoyouthinkwilloccur?
MENTALRETARDATION
13
11/26/11
Whenanadultisexposedtochronicenergy Whatcanyouexpecttooccurtothemuscles?
depleRon,whatdoyouthinkoccurs? FaRgue
Lackofstrength
MENTALDETERIORATION Excessivesoreness
Intolerancetoexercise
Whatcanyouexpectwithadeciencyofthe Whatshouldyouexpectfromalackofenergyin
primaryacRvetransports?Statesofedema theheart?
Papilledema Exerciseintolerance
Pulmonaryedema Weakness(notenough02deliveredtoRssues)
Ascites Shortnessofbreath(thisisasignyouwillsee
Cerebraledema commontoalldiseasedstates)
Anasarca(fullbodyswelling)
14
11/26/11
Letsputthisintoac,on Whatarewegoingtoseewhentheyshowup?
Whataretherstimportantsymptomsthat
ThesignsyouwillALWAYSseeare:
bringsomeonetothedoctorsoce?
1Tachypnea
1Weakness(theycantperformtheirusual 2Dyspnea
acRviRes)
2Shortnessofbreath(scary,theythinktheywill
die)
Whatdowetakefromthis? Letstakethisonestepfurther.
Anydiseasethatputsthebodyintoastateof Muscleweakness+dicultybreathing+
energydepleRonwillcausetheexactsamesigns urinaryreten,on.
andsymptoms.everysingleRme!!
Whatwillalwaysoccurasaresult?
STOPGUESSING,REVERTBACKTOTHESTATE
OFENERGYDEPLETION
15
11/26/11
Someexamples
PULMONARYINFECTIONS
CANCER
AND DIABETES
CELIACSPRUE
URINARYTRACTINFECTIONS
WORRISOMECOMPLICATIONOFA
ENERGYDEPLETEDSTATE
DISEASE?
Nowletstakealookatcomplica,ons Thinkaboutwhatsmostimportantforyouto
live...
Wehavemanycellsinthebodythatarevery Brain
rapidlydividing,whenthereisnoenergythese Heart
cellsfailtodivideproperlyandwegetawide Kidneys
rangeofcomplicaRons JustlookforcomplicaRonswiththoseatthe
topofthelist
LETSTALKABOUTCOMPLICATIONS
16
11/26/11
Thefollowingaretherapidlydividingcellsofthe TakingalookatcomplicaRons
bodythatareaectedbytheenergydepleted
state
Thehairandskin
Hair Skin GItract BRITTLEANDDRY
Kidneys Bladder Endometrium
Vessels(endothelium)Breasts
Sperm Nails/cuRcles Germcells
Bonemarrow(ie.RBC,WBC,PLT)
TakingalookatcomplicaRons TakingalookatcomplicaRons
GItract TheRespiratoryTract
NAUSEA,VOMITING,ANDDIARRHEA WEAKENEDCOUGHREFLEX=INFECTIONS
17
11/26/11
IntheKidneys SpermCount
ELECTROLYTESALTERED(PCTshutsdown) LOW
TheGermCells=CANCERS TheBoneMarrow
DEPRESSED
Wheredoyouexpectcancers?
1stSKIN(exposedtothemostradiaRon)
2ndGI
18
11/26/11
THEREFORE Andnally
Noma[erwhatthediseaseorcondi,on WHATWILLBETHEMOSTCOMMONCAUSEOF
Rememberthisconceptandyouwillalwaysbe DEATHINANYDISEASEDSTATETHATRESULTS
abletoanswertheques,ons INASTATEOFENERGYDEPLETION???
Thinkabouttheconceptandmakesenseofthe Whathappensrst
quesRon.
1stBrainisaected=AMS,demenRa(not
immediatelylethal).
Thinkabouttheorgansaectedandinwhich 2ndTheheart=CHF(lethal)
ordertheyareaected,thenwhich
consequenceismostlethal Thus,inthinkingitthrough,youdonthaveto
memorizeanythingtorealizethatthemost
commoncauseofdeathwillbe
19
11/26/11
Younowhavetheability,throughthisconcept,
tounderstandwhatwillhappeninalmostevery
singlemedicalcondiRon,withouthavingto
HEARTFAILURE!!! memorizeasinglething.
Nowallthatsle\indiseasesisllinginthe
gaps!
MAKINGCONNECTIONS
DIABETESASANEXAMPLE
THROUGHOUTMEDICINE
1simpleconceptopensuptheabilityto Noinsulinmeansnoglucoseintothecells=no
explainthepresentaRonofathousandthings nrg
StopreadingthewholearRcle,lookforthe1 Werealreadyintheenergydepletedstate
uniquethingaboutit Everythingwejustcoveredts
PresentaRonsmaynotalwaysbethesame, WeaknessandSOB
butthecausesofdeatharealwaysthesame. Tachypneaanddyspnea
AlteredmentaRon,weakness,etc
20
11/26/11
YOUKNOW98%OFALLDISEASES NEXTINFLAMMATION&CELL
ALREADY DEATH
Youvejustbeengiventhekeytoknowing
almosteverydiseasepresentaRon
WesRllhavetoknowhowtollinthegaps,
whichiswhatthecourseisgoingtocoverfor
youbutweregoingtocomebacktothis
overandoveragain.
BIGPICTURECONCEPT#2 NORMALCELLSOFTHEBODY
INFLAMMATION&CELLULARDEATH NormalcellshaveNa/K+ATPase
NormalcellshaveadormantNa/Ca
exchangerforemergency
21
11/26/11
THENCOMESTHEINSULT CELLTRIESTOCORRECTTHIS
Anyinsultwilldecreasetheowofbloodand Na/Caexchangerworkstomovesodiumout
thusdecreasedthe02supply andpullcalciumin
Na/KATPaseshutsdown Nahasachargeof1+,whileCahasachargeof
K+isfreelyleakingout 2+.Cellismorelikelytodepolarize
Na+remainsinthecellwaterfollowstheN FasciculaRonandswellingseenatthesiteof
a+.Wegetswelling(1stsignofcellular injury
death)
THISCREATESAMASSEFFECT RECURRINGINJURY
Inthebrainthisleadstoamasseect Enoughtraumaforlongenoughisgoingto
CalcicaRonduetotheacRvaRonoftheNa/Ca leadtodystrophiccalcicaRons
exchangerleadstoaringenhancedlesion Hardscarsatthesiteofinjury
IsdystrophiccalcicaRon
Notamajorclue,moreofanindicaRonthat
thereissomethingcausingamasseect
WhichdrugshutsdowntheNa/Kpump?
22
11/26/11
THEGABACONNECTION
WellwaitunRlwegettobiochemistryasit
tsinbeferthere
VITAMINSANDMINERALS
WhilenotthemostexciRngtopicinmedicine,
vitaminsandmineralsplaysuchvitalrolesin
VITAMINSANDMINERALS ourhealththatthereareawiderangeof
quesRonsthatcanbeasked,letsfocusonall
SmallandPowerful ofthefollowing
23
11/26/11
VITAMINSANDMINERALS VITAMIND
VitaminsA,D,E,andK(DEKA)Fatsoluble EssenRalforproperformaRonofteethandbones
VitaminsB1,B2,B3,B4,B5,B6,B9,B12(theB SRmulatesabsorpRonandreabsorpRonofCa2+
vitamins)
andPO4
VitaminC
Calcium SRmulatesosteoblasRcacRvity(buildsbones)
Magnesium *oppositeisPTHwhichsRmulatesosteoclasRc
Zinc acRvity(breaksdownbone)
Copper **Ca2+andPO4moveinsamedirecRonwhen
Iron sRmulatedbyvitaminD(asopposedtoopposite
Traceelements(Selenium,Tin,Manganese,Fluoride) movementwhenPTHsRmulaRon)
VitaminD VitaminDdeciency
InkidsRickets
VitaminDLiver25(OH)DKidneys InadultsOsteomalacia
1,25(OH)2D VitaminDresistantricketsAdefectinthe
renalreabsorpRonofPO4,whenthePO4
leaks,Ca2+ispulledwithit.Whenyougive
vitaminD,calciummayrisetemporarilybut
thenitdropsoagain.
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11/26/11
VitaminDexcess VITAMINE
Leadstohypercalcemia: ThemainanRoxidantoftheblood
Absorbsfreeradicals(MCCbyviruses),and
1. Stones(kidneystones) helpsprotectcellsfromdamage
2. Bones(bonepain)
3. Moans(GIpainduetoexcessCa2+)
4. Groans
5. Psychicovertones(Mentalproblems)
VITAMINE VITAMINK
BecausevitaminEisourbestallyagainst RequiredforgammacarboxylaRon
oxidaRon,wearegivenprotecRonfromthe AddiRonofa3rdcarboxygivesvitaminKfactors
2,7,9,10andproteinC&S,30negaRvecharges,which
followingdiseases providesforastrongafracRontowardsclo{ng
1. Coronaryarterydisease ProteinCshortesthalflife(t1/2)of6hr(thisisa
thrombolyRc,thusitcanactuallycauseclot
2. Alzheimersdisease formaRons)**iswhyheparinisgivenbeforewarfarin
3. Cancer Factor7halflifeof2days,sinceittakes10daysfor
steadstate(t1/2x5),wekeepsomeoneinthehospital
4. HemolyRcanemias(G6PD) for10daysonhep+warfarinbeforetheyare
therapeuRc
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VITAMINK WARFARIN
Mostofitismadeupfromthegutora InhibitsvitaminKepoxidereductase(themost
BroadspectrumanRbioRcscaninhibitthe importantenzymeresponsiblefor
synthesisofvitaminK regeneraRngreducedvitK
Bleedingcanoccurwithin2days UlRmatelydecreasesthesynthesisofthe
Importanceofgivinganewborntheirvitamin vitaminKdependentfactors2,7,9,10
Kshotatbirth DecreasestheacRvityofproteinC
Requiresheparinrstduringtreatment
WARFARIN HEPARIN
IsanoralmedicaRon(akaCoumadin) IsacofactorforanRthrombin3(protects
Isteratogenic(crossestheplacenta) againstclotsinaproteinCdeciency)this
MonitorthePT(prothrombinRme) iswhywegiveheparinbeforewarfarin
Blocksthrombinandclo{ngfactors
9,10,11,12
Canbereversedbyprotaminesulfate
HalfRmeof6hr
BleedingistheMCcomplicaRon
26
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HEPARIN VITAMINA
SeriousAEisheparininduced HelpswithCSFproducRon
thrombocytopenia(HIT) Acofactorinparathyroidhormone
Ifyougetthis,switchtoLMWH ResponsibleforepithelialcellmaturaRon
AnypaRentwhohasahxofHITshouldbe (givenwhenanyorganisbeingwornaway,as
givenAgatrobannextRmetheyneedheparin itsRmulatesregeneraRonoftheepithelium)
(isadirectthrombininhibitor) AweakanRoxidant
Responsibleforvisualacuityatnight
VitaminAdeciency VitaminAexcess
Poornightvision(o|enaUSMLEquesRon) CSFoverproducRonpseudotumorcerebri
DecreaseinCSFproducRon Hyperparathyroidism=Hypercalcemia
Hypoparathyroidism(isacofactorinPTH)
FailureofmaturaRonofepithelialcells
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VitaminApseudotumorcerebri PseudotumorCerebriEvaluaRng
Papilledema CTscan=ventricularenlargement
Headache Management=SerialLPs+cessaRonof
Alwayswanttoruleoutabrainmasswhen vitaminAadministraRon
thesetwosymptomsarepresent BlindnessisthemainworrisomecomplicaRon
Commonlyseeninoverweightfemales
VITAMINB1Thiamine ThiamineDeciencyBeriBeri
Requiredformanydehydrogenaseenzymes DryBeriBeriSymptomsofalcoholism.NO
(pyruvatedehydrogenase,alphaketogluterate HeartFailure
dehydrogenase,branchedchainAAdh,and WetBeriBeriAbove+HeartFailure
transketolase).
Thiaminedeciency=lotsofenzyme
deciencies
MostcommonpopulaRonsueringfromB1
deciencyAlcoholics
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ThiaminedeciencyWernickes
VITAMINB2Riboavin
Encephalopathy
Posteriorlobesaected AnFADcofactor
RecepRveaphasia Canbedegradedbysunlight
Ataxia,opthalmoplegia,shorttermmemory Deciencyleadstoangularchelosis(lesionsin
impairment thecornersofthemouth)
WernickeKorsakoSyndromeConfusion,
nystagmus,opthalmoplegia,ataxia,psychosis
VITAMINB3Niacin NIACINdeciency
Acomponentofcofactors:NAD,NADH,NADP, ClassicUSMLEquesRon
andNADPH
Requiredindehydrogenases:Pyruvatedh, PELLEGRA:
AKGdh,andBCAAdh The4ds:Diarrhea,DermaRRs,DemenRa,and
Death(soundslikeourenergydepletedstate)
AlsocausesHartnupsDiseaserenaltransportof
tryptophanisdisrupted,leadingtosame4ds
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VITAMINB4LipoicAcid VITAMINB5PantothenicAcid
Isrequiredfordehydrogenases:Pyruvatedh, Requiredfordehydrogenases:Pyruvatedh,
AKGdh,andBCAAdh AKGdh,andBCAAdh
Thereisnostateoflipoidaciddeciency Noknowndecientstate(becauseitispresent
inalmostallfoods)
IsacomponentofcoenzymeA
VITAMINB6Pyridoxine Pyridoxinedeciency
Isanimportantpartofhemesynthesis Neuropathyisthemainsymptom
Isrequiredforalltransaminases
Isoniazidcancauseadeciency TreaRngachronicneuropathyGive
Formspyridoxylphosphatecofactor amitriptyline
TreaRngashooRngneuropathy
CarbamazepineorGabapenRn
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VITAMINB9Folate Folatedeciency
Usedtomaketetrahydrofolate(arequirement Deciencyleadstocelldeath,thusitis
fornucleoRdesynthesis) essenRalduringembryogenesisandforthe
Antagonizedbysulfadrugs maintenanceofnewcells
Istherstthingtobecomedecientduring PurposelydepleRngfolateisacornerstonein
rapidcellulardivision(cancer) mostcancerregiments
Leadstosuppressionofhematopoeisis
LeadstomegaloblasRcanemiawhy?
Folatedeciencyanemia Folatedeciency
Rememberthatfolateisresponsibleforaiding Themostcommonreasonforfolatedeciency
incellulardivision isovercookedvegetables
Iffolateisdecient,thenucleusafemptsto ThoseafempRngtogetpregnantshouldtake
divideoverandoveragain,butitcannot, folicacidsupplementsforatleast12weeks
leadingtotheenlargedcellwithamulRlobed beforebecomingpregnant
nucleusthatcouldnotdivide.
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VITAMINB12Cyanocobalamin VITAMINB12Deciency
Importantinhomocysteinemethyltransferase Leadstoneuropathy
(requiredfortetrahydrofolateproducRon) AectsthecorRcospinaltractsanddorsal
ImportantformethylmalonylCoaMutase columntracts.
(necessaryforrecyclingofoddnumbered Themostcommoncauseisperniciousanemia
fafyacidsmyelinproducRondeciency
leadstoneuropathy)
VITAMINC WhyvitaminCforacold?
NecessaryforhydroxylaRonreacRons(proline VitaminCisagreatanRoxidantagainst
andlysinecollagen,elasRnproducRon) viruses,whicharethemostcommoncauseof
VitaminCisthemainanRoxidantinthe acold.
gastrointesRnaltract
WHYISVITAMINCRECOMMENDEDWHENWE WHYDOWEINSISTINGIVINGIRON
AREBATTLINGACOLD? SUPPLEMENTSWITHORANGEJUICE??
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Iron+OrangeJuice?? Iron+OrangeJuice
Ironiseasilyoxidizedbyfreeradicals,which VitaminCpreventsoxidaRonofironandthus
rendersituseless ironisusabletoourbodies
OrangejuiceisrichinvitaminC,whichisa
greatanRoxidant
Combinethetwoand..
VITAMINCDeciency MAGNESIUM
Scurvy IsacofactorinallkinasereacRons
Classicallylinkedtopiratestravelingthehigh (phosphorylaRonreacRons),thatproduceATP
seas IsaPTHcofactor
WedontgetproperproducRonofcollagen USMLEQuesRonMagnesiumandCalcium
andelasRnbleedfrommucusmembranes, arelinkedaschronicallylowcalciumthat
hairfollicles cannotbeelevatedisalwayssuspectoflow
magnesium.*Theyarebothlinkedbywayof
PTH,lowMg2+=ineecRvePTH=lowCa2+
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ZINC COPPER
Causesdysgeusiaifdecient(abnormaltaste) RequiredforcollagenformaRon(hydroxylaRon
oflysine)
Requirementofcomplex4intheETC
COPPERDeciency COPPERExcess
Menkeskinkyhairsyndrome Wilsonsdisease
Hairisorangecolored AR
Hairfeelslikenecopperwire Ceruloplasmindeciencyleadstocopper
depositinthelenRcularnucleus,iris,and
liver..
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WilsonsDisease WilsonsDisease
Liverbleedingdisorders,esophagealvarices, EndocrinelowPTH=lowCalcium,inferRlity
cirrhosis
Neuropsychbehavioralchangesand Treatment:Penicillamine(chelatorofcopper)
Parkinsonssymptoms
EyesKayserFleisherrings(copperdepositin
theDescemetsmembraneofthecornea)
KidneysRenaltubularacidosis
Heartcardiomyopathy
IRON LetstalkaboutTraceMinerals
RequiredfortheformaRonofhemeand Tracemineralsarerequiredinverysmall
hemoglobin amounts.thuscalledtrace
Ferrousstateisrequiredforironbinding
(2+) Theyare:Chromium,Selenium,Fluoride,Tin,
RequiredforETCcomplexes3and4 Manganese,andMolebdenum
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CHROMIUM SELENIUM
PotenRatestheacRonofinsulin Requiredbytheheart
Associatedwithmanytypesofdiabetes Excesslevelscauseaspecicsmellofthe
Chromiumdeciencycanleadtodiabetes breaththatislikegarlic
Deciencycanleadtodilatedcardiomyopathy
FLUORIDE TIN
Necessaryforteethandbonegrowth Mainuseisinhairgrowth
Anexcesscanblocktheenolaseenzymein
glycolysis(2phosphoglycerate
phosphoenylpyruvate)
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MANGANESE
Requiredforxanthineoxidase(hypoxanthine
xanthineuricacid)thusimportantin
purinecatabolism.
Requiredformanyglycolysisenzymes
MEMBRANEFUNCTION
Providesshape(itsmostimportantrole)
Theyarehydrophilicandhydrophobic
MEMBRANEPHYSIOLOGY (amphipathic)
MaintainstheconcentraRongradient
Selectswhatcanandcannotpassthrough
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FATSOLUBLECOMPOUNDS WATERSOLUBLECOMPOUNDS
Dontinteractwiththemembrane,instead Arehydrophilic
passrightthroughtonucleus Mustbindtoamembranereceptorknownas
OnlylimiRngfactorforthesecompoundsis a2ndmessenger
concentraRon Mostvitaminsarewatersolublecompounds
Steroidsareimportantfatsolublehormones (exceptD,E,K,A)
Cor,solistheonlyfatsolublehormonewitha
receptorinthecytoplasm
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THEFACTORSAFFECTINGDIFFUSION MOREMEMBRANEFUNCTIONS
Concentra,ongradient(#1factor) Phagocytosis:specicformofendocytosisfor
Moleculesize internalizingsolidparRclessuchasbacteria
Charge(greatercharge=greatermovtinwater) Endocytosis:mainreasonisfornutriRonal
pH(aectamoleculescharge) needs(proteins)
Membranethickness(thicker=harder) Exocytosis:mainreasonisforeliminaRonof
Surfacearea(morearea=easiertocross) wasteproducts
Flux(movtofunitareaperunitRme) Pinocytosis:isaformofcelldrinking
Reec,oncoecient
TEMPERATUREREGULATION MEMBRANEPOTENTIALS
Conduc,on:viacontact ConcentraRongradientisalwaysyourmost
Convec,on:viamovement importantfactor
Radia,on:movementdownaconcentraRon Na+,Ca2+,Mg2+,Cl,andHC03allwanttomove
inwards,whileK+wantstomoveoutwards
gradient
Mg2+isabundantinsidethecellbutafachedto
kinases(bound),thusMg2+sRllmovesinwards
Ca2+isabundantinsidethecellbutis
sequesteredinsidetheSR
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MEMBRANEPOTENTIALS ELECTROLYTEMOVEMENT
DepolarizaRon=becomingmoreposiRve
2Rssuesthatabsorbthemostcurrentsarethe
PurkinjebersandBrain
Electricitydestroysthechargeofthe
basementmembrane,thuselectrocuRon
preventsplateletadhesion
THEELECTRICALGRADIENT DRIVINGFORCE
IsdeterminedbyanionsNernstnumber Thespeedatwhichionswillenterintoacell
Anionwillbehavesothatitbringsthecells [EionEmembrane]=drivingforce
electricalbaselineclosertoitsNernstnumber Conductance(Gion):denestheactual
Na+=+65 movementacrossamembrane
K+=95 Permeability:Smallionsmovethrough
Ca2+andMg2+=+120 channels,mediumsizedionsmovethrough
Cl=90 pores,andlargemoleculesmovethrough
proteinchannels
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TRANSPORTPROTEINS SECONDMESSENGER
Requireenergy
PrimaryAc,veTransport:theMCistheNa/K
ATPase,whichpumpseachagainsttheir
gradient
SecondaryAc,veTransport:usestheenergy
createdfromoneionmovingdownits
gradient(Na/Caexchanger)
Symport:movesinthesamedirecRonasNa
An,port:movesinoppositedirecRonofNa
SECONDMESSENGERS cAMP
Usedforthosemoleculesthatcannotpass Isthemostcommonandimportant2nd
directlythroughthemembrane messenger
TheMC2ndmessengeriscyclicAMP(cAMP) AlphareceptorissRmulatedby1stmessenger,
cAMPisthe2ndmessengerforsympatheRc GproteinsRmulatesadenylylcyclasewhich
acRvity getsacRvatedbyATP
cGMPisthe2ndmessengerfor cAMPthengetscreatedfromACandcan
parasympatheRcacRvity sRmulateproteinkinaseA(PKA)
Mg2+isthecofactorforPKA
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cGMP
GuanlyatecyclaseissRmulatedandproduces
cGMPviaGTP
cGMPthensRmulatesproteinphosphatase
PHOSPHODIESTERASE BLOCKINGPHOSPHODIESTERASE
EnzymeresponsibleforcAMPandcGMP WillelevatelevelsofcAMPandcGMP
degredaRon Atacertainpoint,cAMPwillbecome
BlockingPDEacRvitywillincreasecAMPand parasympatheRc(dontforgetthis)
cGMPlevelsandthusprolongtheir SexualarousalisparasympatheRc
physiologicaleects ThisphysiologyisthebasisforerecRle
CaeineblocksPDE dysfuncRonmedicaRons
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EDDRUGSANDNITRATES CALCIUMASA2NDMESSENGER
Combiningthesetwodrugscanprovetobe IP3DAG(usedbyallhypothalamichormones
deadly exceptforCRH,allsmoothmuscle
ThenitratesincreasecGMP,leadingtothe contracRonsbyhormoneorNE/E)
potenRalforsignicantvasodilaRonand CalciumCalmodulin(smoothmuscle
unsafedropsinbloodpressure contracRonbydistenRon)
Minimumof12hrinbetweenNitrateand Calcium(2ndmessengerforgastrin)
Viagra/Cialis/Levitra
IdeallywaiRng24hrbetween
IP3DAG CALCIUMCALMODULIN
Thereisa4:1raRoofcalciumtocalmodulin
WhenthereisdistenRon(fecesGI,foodin
esophagus,foodinstomach,fetusinuterus,
urineinthebladder)thissystemissRmulated
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CALCIUMCALMODULIN TYROSINEKINASE
Isthe2ndmessengerforallgrowthfactors
Itusesmagnesiumasacofactor
MutaRonstotyrosinekinasehavebeenlinked
tosometypesofcancer
ItsacRvitycanbeinhibitedwiththe
chemotherapydrugImaRnab
NOASA2NDMESSENGER
SRmulatesGC,leadingtoelevaRonofcGMP
levels
Usedaspartofnitratesforvasodilatory
properRes
Tachyphylaxisoccurs(rapidtolerance)
GivesbalancedvasodilaRon(veinsandarteries
equally)
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THEMOSTIMPORTANTORGANELLE
Isthenucleus
Damagetothenucleuswillresultincellular
CELLULARPHYSIOLOGY death,everysingleRme
Nucleardamageisthemostimportantsignof
irreversiblecellularinjury
PROGRAMMEDCELLULARDEATH
IRREVERSIBLECELLULARINJURY
APOPTOSIS
Programmedcellulardeath(apoptosis) Apoptosisisthetermweusetodescribe
Nonprogrammedcellulardeath(necrosis) programmedcellulardeath
Describespredeterminedplanningofacells
demise
Deathofthecellisorganized,neat,andwill
notsRmulateanyinammatoryprocesses
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NONPROGRAMMEDCELLULARDEATH
NUCLEARSUICIDE
NECROSIS
A|erthenucleushastoldthecelltodie,ittoo Necrosisistheformofnonprogrammed
mustdie cellulardeathwearedealingwithmosto|en
Karyolysisdissolvingofthenucleus Numerouswaysnecrosiscanoccur
Karyorrhexischunksofnucleusbreako Thenucleusdiesrst,sRmulaRngan
Pyknosisblebsofnucleusbreakapart inammatorymechanism
SRllusesthesamemethodsofnucleus
destrucRonaswithapoptosis
COMMONTYPESOFNECROSIS COAGULATIVENECROSIS
Ischemicnecrosis IstheMCformofnecrosis
Purulentnecrosis CausedbyischemiaorinfarcRon
Granulomatousnecrosis TheRssuediesbutitsarchitectureremains
Fibrinousnecrosis intact
Caseousnecrosis InmostRssuesischemialeadstocoagulaRve
Fatnecrosis necrosis,butintheCNSitleadstoliquefacRve
Hemorrhagicnecrosis necrosis(lackofstructuralarchitecture)
LiquefacRvenecrosis
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PURULENTNECROSIS GRANULOMATOUSNECROSIS
Thereisapresenceofpus Isanonbacterialtypeofnecrosis
Alwaysbethinkingbacteriawhenthereispus InvolvesTcellsandmacrophages
FIBRINOUSNECROSIS CASEOUSNECROSIS
AnyRmethereisadepositofbrinweworry Thisnecrosishasacheesyconsistencyasitis
aboutthefollowingproblems: awhite,so|,proteinlikesubstance
1. CollagenVascularDisease Caseousnecrosisisfrequentlyassociatedwith
2. Uremia(renalfailure) tuberculosis
3. Tuberculosis
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FATNECROSIS HEMORRHAGICNECROSIS
Occursinorganseithermademostlyoffator Whereverwehave2ormorevascularsupplies
surroundedbyfat wecangethemorrhagicnecrosis
ThebreastisacommonlocaRonis Ischemiacausesreleaseofinammatory
associatedwithtraumatothebreast mediators,thenrestoredbloodowre
Thepancreassitsonacushionoffatand introducesfreeradicalsthatleadtodamageof
whenchronicpancreaRRsoccurssodoesfat cellsstructures
necrosis MCseeninbrainandheart
LIQUEFACTIVENECROSIS CHROMOSOMALANOMALIES
CausestheformaRonofanabscessrelatedto Whenwemesswiththenuclearstructuresin
bacterialorfungalinfecRons uterowearegoingtohavemajor
TheMClocaRonisthebrain(duetohypoxic consequences
deathnotinfecRousprocesses) Mostcasesdie,the1%thatlivearetheones
Leastlikelytoforminthelungduetoits wewillseeandbetestedon
constantsupplyofoxygen MonosomiesdontdevelopenoughRssue
TrisomiesdeveloptoomuchRssue
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MONOSOMIES TURNERSYNDROME
NondisjuncRonistheMCCofmonosomies MCCisnondisjuncRonfromthefather
XO
MCRmeisduringmeiosis1
Shortstature
Basedonnumbers,theproblemusually Webbedneck
comesfromthedad(billionsofspermvs. AorRccoarctaRon(preductaltype)
limitedsupplyofeggs) Streakedgonads
Basedonodds,theproblemisusually Shieldshapedchest
transmifedviathemom CysRchygroma
Overalllooknothinggrows
COARCTATION TRISOMIES
Mostdie
Thosewholivedevelopextra,ssuebecause
therestoomanychromosomes
Patau=trisomy13
Edwards=trisomy18
Downs=trisomy21
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PATAUSYNDROME EDWARDSSYNDROME
Trisomy13 95%ofpaRentshaverockerbofomfeet
Protrudingabdomen(omphalocele) Theydiewithin3months
Polydactyly(toomanyngers)
Abdnormalpeeingsystem(GUabnormality)
Palateishigharched
Deathwithin3months
TRISOMY21 AVSD
100%ofthesepaRentshavementalretardaRon
RobertsoniantranslocaRon
AVSDistheMCcardiacanomaly
MCCofcyanoRcdiseaseatbirthistransposiRon
ofthegreatarteries
ofDownspaRenthavehypothyroidism
Duodenalatresia(doublebubblesign)
Hirschprungsdisease
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TRANSPOSITIONOFTHEGREAT
TETRALOGYOFFALLOT
ARTERIES
OTHERTRISOMIES FRAGILEXSYNROME
XXXIsanormalfemalewith2barrbodies IstheMCCofmentalretardaRoninmales
(notproblemaRc) CharacterisRcfeaturesinclude:
XXYKlinefelterssyndrome Longface
Large/protrudingears
Decreasedmuscletone/mass
Largetestes(a|erpurberty)
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THESIGNSOFIRREVERSIBLECELLULAR
DAMAGE
THEMCCISISCHEMIA
1stsignNuclearDamage
ONELASTLOOKATIRREVERSIBLE
2ndsignLysosomalDamage
CELLULARDAMAGE
3rdsignMitochondrialDamage
CONTROLLINGCELLDIVISIONWITH
MEDICATIONS
~Chemotherapy~
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CHEMOTHERAPEUTICS CHEMOTHERAPYSIDEEFFECTS
Thegoalistosloworstoprapidlydividing Thinktoourenergydepletedstate
cells Youalreadyknoweverysideeectbasedon
Leadstoirreversiblecellulardeath(afacks thatprole
nucleus)
Whydowegivechemotherapyevery7
IsnotselecRve,thuswegetsevereadverse
eects days???
ThereisnosafechemotherapeuRc
Causesnecrosiskillsnucleusrstleads
toinammaRon
CHEMOTHERAPEUTICS ANTIMETABOLITES
ForfastgrowingcancersAn,metabolites Workbestonfastgrowingcancers
2ndlingforfastgrowingcancers TheyallworkbydisrupRngtheproducRonof
MicrotubuleInhibitors metabolites,sowestoptheabilityofrapidly
ForslowgrowingcancersAlkyla,ngagents dividingcellstoregenerate
NutrientDepletorsLAspariginase
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ANTIMETABOLITES
ARAA
ARAC
Methotrexate
5Fluorouracil
6Mercaptopurine
Azothioprine
ALKYLATINGAGENTS ALKYLATINGAGENTS
Forslowergrowingcancers Bleomycin
Bigpictureisthattheyalkylatetheguanine Busulfan
nucleobasesindsDNA Doxorubacin
Thesetendtocausetheworstnauseaand CisplaRn
vomiRng(managewithOndasetron) Cyclophosphamide
AnRmycin
Melphalan
Chlorambucil
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MICROTUBULEINHIBITORS NUTRIENTDEPLETION
Are2ndlineforfastgrowingcancers Lasparaginase
VinblasRne ConvertsasparagineintoasparRcacidand
VincrisRne ammoniasothatALLcannotmakeuseof
Paclitaxel circulaRngasparagine(whichitneedsinorder
todivide)
ThusbestforALL
TendstocauseallergicreacRonsand
anaphylaxisonoccasion
IMMUNOMODULATORS
EnhancesourownNKcellskillingability
Levamisole
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THECNS
Thekeytoallneurologicalcontrol
Consistsofbrainandspinalcord
NEUROMUSCULARPHYSIOLOGY Parasympathe,cSystemcraniosacral
Sympathe,cSystemthoracolumbar
THEPARASYMPATHETICSYSTEM THEPARASYMPATHETICSYSTEM
LongpresynapRc,shortpostsynapRcbers
Acetylcholineistheneurotransmiferusedat
bothpreandpostganglionicbers
CausesdepolarizaRonofthecranialandsacral
regions(thusarecraniosacral)
2ndmessengeriscGMP
Alloftheirreceptorsaremuscarinic(except
forgangliaorNMjuncRons)theyare
nicoRnic
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THESYMPATHETICSYSTEM THESYMPATHETICSYSTEM
ShortpresynapRcandlongpostsynapRcbers
Acetylcholineisusedasthepreganglionic
neurotransmifer,NEisusedatpostganglionic
bers
CausesdepolarizaRoninthebrainand
thoracolumbarareas
2ndmessengeriscAMP
ManyarenicoRnic(exceptsweatglandsthey
aremuscarinic)
AlphaandbetareceptorsaresympatheRc
INHIBITORYNEUROTRANSMITTERS NEUROTRANSMITTERPRODUCTION
GABA:inhibitoryinthebrain
GLYCINE:inhibitoryatthespinalcord
Bothcauseachlorideioninux
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ALPHAandBETARECEPTORS ALPHA1RECEPTORS
Alpha1:smoothmusclecontracRon ContracRonofsmoothmuscles
Alpha2:smoothmusclecontracRonandNT CausesconstricRonofarteries
inhibiRon CausesRghteningofsphincters
Beta1:increasedcardiaccontracRon, Causesmydriasiswithoutcycloplegia
increasedBP
Beta2:smoothmusclerelaxaRon
ALPHAAGONISTS
Norepinephrine
Epinephrine
Ephedrine
Pseudoephedrine
Phenylephrine
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ALPHAANTAGONISTS ALPHA1BLOCKERS
Alpha1specicblockersinclude: Willlowerbloodpressure
Prazosin
Prazosin:usedforBPH,1stdose
Terazosin
phenomenon,longtermusecauses
Doxazosin
Tamsulosin orthostaRchypotension
Nonspecicalphablockers: TerazosinandDoxazosinarebothDOCsfor
Phentolamine BPH
Phenoxybenzamine Tamsulosin(Flomax):2ndlineforBPH,used
Yohimbine whentheotherscausesignicantsideeects
NONSELECTIVEALPHABLOCKERS ALPHA2RECEPTORS
Phentolamine:isshortacRngdrugusedto Foundonallpresynap,cbers(thusinhibit
diagnosepheocromocytomatendstocause
reextachycardia NErelease)
Labetalol:hasbothalphaandbetablocking FoundontheIsletcellsofthepancreas(thus
abiliRes,ispreferredoverphentolamine,is inhibitinsulinsecreRon)
excellentforHTNemergencies
Phenoxybenzamine:anirreversiblealpha1,2
blocker,isgivenbeforepheocromocytoma
surgerytopreventHTNcrisis
YohimbineandMirtazapine:arealpha2
antagonists
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ALPHA2AGONISTS BETAAGONISM
AlphaMethylDopa:DOCforpregnancy Beta1receptorswill
inducedHTN IncreaseCNSacRvity
Clonidine:primaryuseisHTN,suppresses Increasereninrelease
SNSoulowfromCNS,sRmulatesPNSoulow IncreaseHRandcontracRlity
(thusslowsHR)drawbackishighriskofHTN
SRmulateglucagonrelease(fromalphacellsof
Guanabenz:lesscommonlyused,itsmain pancreas)
sideeectisdrowsiness/sedaRon
BETAAGONISM BETA1AGONISTS
Beta2receptorswill Dobutamine:sRmulatestheheartwithout
excesstachycardia.
Relaxallsmoothmuscle(mainbenetisthe
Usedforheartfailureandcardiogenicshock
abilitytobronchodilate)
Mostworrisomesideeectisfatalarrhythmias
SRmulateinsulinreleasefromisletcellsof Isoproterenol:beta1andbeta2sRmulaRon
pancreas
Mainuseisinrefractoryheartblocksand
IncreaseheartscontracRlitybutnotitsrate bradycardia
Onceusedforasthmabecauseofbeta2
sRmulaRon,butnolongerused
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BETA2AGONISTS
Thisclassismainlyusedasasthma
medicaRons
Albuterol:theMCinhalerforasthma,
providesrapidbronchodilaRon,tis4hr) THEMUSCLES
Terbutaline:oralasthmamedicaRon,useful
forasthmaand/orbronchospasm
Salmuterol:alongacRngbetaagonist(LABA),
t12hr,usedtwiceperdaytocontrolasthma
(Advair)
STRIATEDvs.NONSTRIATED SKELETALMUSCLE
Striatedmusclescontainsarcomeres,which Appearsstriatedunderthemicroscope
givethemthestriatedappearance (arrangedinbundles,bands,sheets)
Cardiacandskeletalmuscleisstriated FuncRonsasamotorunit(1nerveber
Smoothmusclelackssarcomeresandis sRmulatesallmusclebersitinnervates)
thereforenonstriated IntracellularcalciumisusedforcontracRon
Demonstratesrecruitment
ContainsnoautonomicsorsyncyRalacRvity
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CARDIACMUSCLE
UsesintracellularcalciumforcontracRon,but
requiresextracellularcalciumtotriggerthat
intracellularrelease
CompleteautonomicsandsyncyRalacRvity
GapJuncRonsareintercellularconnecRons,
requiredtopasssignalsbetweencellssothey
reintandem
Connectedbyintercalateddiscs
SMOOTHMUSCLE
UsesintracellularcalciumforcontracRon
ExtracellularcalciumisneededtosRmulatethe2nd
messengersystems(IP3DAGandCaCalmodulin)
Hasfullautonomics
HasparRalsyncyRalacRvity(ie.GIhasperistalsis)
Containsnosarcomeres
Containsnotroponin
AcRnandmyosinareboundbyalatchingmechanism
ThereisnomyosinATPaseacRvity(MLCKandMLCP
worktogether)
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NEUROMUSCULARTRANSMISSION AXONALTRANSPORT
Howtodisruptaxonaltransport
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CONTRACTION
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THEFUNCTIONALUNITOFMUSCLEThe
Sarcomere
LENGTHvs.TENSION
THEGOLGITENDONORGAN
LocatedatthemuscleinserRons
Ensureswedontholdmaximumtensionon
ourmuscles(keepssarcomeressafe)
Willpreventmaxtensionfromgoingpast1s
OncesRmulated,amusclehasnochoicebut
torelax
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MUSCLESTRAINSvs.SPRAINS MUSCLESTRAINSvs.SPRAINS
Strain=overstretchingofamuscle Sprains=ateartothetendonorligament
Occurswhenmusclesgofromarelaxedto causedbyexcessivestretching
strainedstatetooabruptly TreatwithRICE(Rest,Ice,Compression,
TreatastrainwithNSAIDSthatalsorelaxthe ElevaRon)
muscles(Baclofen,Cyclobenzaprine)
THEFRANKSTARLINGMECHANISM
NEUROMUSCULARDISEASES
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INFLAMMATORYMYOPATHYPROFILE LISTOFINFLAMMATORYMYOPATHIES
ElevatedESR Myosi,s
ElevatedWhiteBloodCells Polymyosi,s
ElevatedAST,ALT,andAldolase Dermatomyosi,s
myoglobinemia Fibrosi,s
Polymyalgiarheuma,ca
Temporalarteri,s
MUSCULARDYSTROPHIES DUCHENNESMUSCULARDYSTROPHY
Duchennes IstheMCencounteredformofmuscular
Beckers dystrophy
Myotonic Nodystrophinismade(Xp21gene)
Isanxlinkedrecessivedisease(onsetbefore
5yrofage)
Gowerssign
Calfpseudohypertrophy
DefecRvedystrophinprotein
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BECKERSMUSCULARDYSTROPHY MYOTONICDYSTROPHY
Decreasedamountofdystrophinmade Ahighlyvariablediseasethatisslowto
Anxlinkedrecessivedisease progressandischronic
LooksjustlikeDuchennesbutonsetislaterand
progressionisslower(ie.Allndingsaresimilar) Autosomaldominant
Earlyonset(8yr)ismoreassociatedwithcardiac 2types:Type1aectsfacial/jaw/neck
involvement,whilelateronset(12yr)islesslikely muscles,andusuallypresentswithcataracts
toinvolvetheheart
ManypaRentslivenormallives,howeveratsome Type2aectstheproximalmusclesmainly
pointmostendupwalkingwithcane/crutches,or (thighs,pelvis)
needawheelchair
Managesymptomsastheycome
GUILLANBARRESYNDROME
Ascendingmuscularweakness/paralysis
Commonlybeginsaround2weeksa|eraviral
infecRon(MCCampylobacter)
NEUROLOGICALDISORDERS Isanautoimmunea[ackagainsttheperipheral
nerves(causedbyGangliosides)
INVOLVINGMUSCLES Mildcasesonlydamagemyelin(goodpx)
Severecasesmaydamageaxon(worsepx)
ThemostworrisomecomplicaRonisrespiratory
failure(intubaRonnecessaryin~30%ofcases)
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DIABETESMELLITUS SYPHILIS
MCpresentsinagloveandstocking Tabesdorsalisaectstheposteriorhornsof
distribuRon thenerves
CausedbysorbitolaccumulaRon(fromaldol ArgyllRobertsonpupil
reductasepathway),aswellasdecreased Laterstagesofsyphilismaypresentwith
bloodow shooRng/stabbingneuropathies
GoalisRghtbloodglucosecontrolthroughout TxshooRngpainwithCarbamazepine
life
MYASTHENIAGRAVIS ANTICHOLINERGICDRUGS
AutoimmuneafackagainsttheAchreceptors Atropine
MCpresenRngsymptomisamiddleaged Benztropine
femalewithptosis Glycopyrolate
PaRentsdevelopweaknessastheday Ipratropium
progresses
DiagnosewithEdrophoniumtest
TreatwithNeosRgmine
**maybeassociatedwithaThymoma
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LAMBERTEATONSYNDROME MULTIPLESCLEROSIS
AnRbodiesformedagainstthevoltagegated SeenMCinmiddleagedfemales
calciumchannelsinthepresynapRcnerve Scanningspeech,intenRontremor,nystagmus
IsaparaneoplasRcsyndrome AnRmyelinanRbodiesaectrandomareasin
Proximalmusclesaremostharshlyaected thebrain
(closesttotrunk) MRIisthebestdiagnosRctest(showsmulRple
Autonomicproblemsalsooccur areasofdemyelinaRon)
DiagnosewithEMG Acuteepisodes:IVcorRcosteroids
Treattheunderlyingcancer(ifpresent) LTManagement:DMODs
MULTIPLESCLEROSIS
4maintypes:
RelapsingRemi{ng
Primaryprogressive
Secondaryprogressive
Progressiverelapsing
Prognosisisbestwhen.Relapsingremi{ng
type,femalegender,earlyageofonset,few
afackininiRalyears,presenceofopRcneuriRs,
sensoryproblemsatonset
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MRIofMSPaRent METACHROMATICLEUKODYSTROPHY
ArylsulfataseAdeciency
AectstheG&Dofmyelin,somyelinaRonis
disrupted
LookslikeMSina510yrold
OpRcneuriRs
Internuclearopthalmoplegia
ManagementissimilartoMS(IVsteroids,IVIG,
plasmapharesiswhenrespiratoryproblems
begin)
AMYOTROPHICLATERALSCLEROSIS
AkaLouGehrigsdisease
MCseeninmales(middleage)
VentralhornandcorRcospinaltractneuron
LOWERMOTORNEURON degeneraRon
IniRalpresentaRon:fasciculaRons,muscle
DISEASES atrophy,weakness
ProgressivepresentaRon:progressiontorestof
body(usuallyindescendingfashion)
NOsensoryinvolvement
Notreatment
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WERDNIGHOFFMANDISEASE
Anxlinkedrecessivedisease
Isasevereformofspinalmuscleatrophy
Atbirth,infantspresentwithhypotonia, CHILDHOODCEREBELLAR
tonguefasciculaRons,breathingdiculRes,
poorfeeding,andaweakcry DISEASES
DiagnosewithEMG
TreatmentissupporRve,mostinfantsdieby
2yr
FRIEDREICHSATAXIA ATAXIATELANGIECTASIA
AnXlinkedrecessivetripletrepeatdisorder DisruptscoordinaRonandweakensthe
CausedbymutaRonofFXNgenethatcodesfor immunesystem(IgAdeciency)
Frataxin(onchromosome9)
Telangiectasiasaresupercial,redcolored
SclerosisanddegeneraRonofthedorsalroot spiderveinsalloverthebody
ganglion,spinocerebellartracts,lateral
corRcospinaltracts,andposteriorcolumns SupporRvemeasuresareallthatcanbe
Usuallystartsbetween515yrofage undertaken
MCsi/sxare:arm/legweakness,gaitinstability, PaRentsusuallydiebetweenteenageyears
hearingandvisualimpairment,slurredspeech, andearly20s(MCd/timmunesystem
scoliosis
dysfuncRon)
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ADRENOLEUKODYSTROPHY CEREBRALPALSY
Xlinkedrecessive Deni,on:anypermanentneurological
DefecRvecarniRneshufleresultsin damagesueredpriortotheageof21yr
accumulaRonoflongchainFAsincytoplasm Spas,cdiplegia:isamidlinecorRcalproblem
AdrenalinsuciencycancauseAddisons Spas,chemiplegia:isacorRcalproblemon1
disease sideofthebrain(contralateralsideaected)
MentaldiculResanddeterioraRonare Choreoathetosis:involvethebasalganglia
common,aswellasadrenalproblems (Kernicterus)
MostpaRentsendupincomawithin2yrof Atonic:frontalcortexisinvolved,CSFinvolved
BEHAVIORALSCIENCES
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HOWTOENSUREAHIGHSCOREIN
5AREASYOURETESTEDON
BEHAVIORAL
1. MoodandpsychoRcdisorders Focusonthesymptomsareyoumostlikelyto
2. Personalitydisorders seeontheexam.
3. Defencemechanisms Rememberthatpsychiatricillnessesputmajor
4. Sexualdeviance impairmentonsomeoneslife.
Alwayseliminatedrugsasacauseofthe
5. BiostaRsRcs
problem
MedicaRon+psychotherapyisALWAYS
superiortooneortheother.
3TIMESWHENWECANHOSPITALIZE
DSM4DISORDERCLASSIFICATIONS
AGAINSTTHEIRWILL
Theyareadangertothemselves Clinicaldisorders(Class1)
Theyareadangertoothers Personalitydisorders/mentalretardaRon
Theyaresoimpairedthattheycannotfeed (Class2)
themselves,afainshelter,orclothe MedicalcondiRons(Class3)
themselves. SocialandEnvironmentalfactors(Class4)
LeveloffuncRoning(Class5)
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PROGNOSISOFPSYCHDISORDERS MOODDISORDERS
Favorablewhen:sxareacute,insightinto Wehavetheups
theirproblemisgood,andtheyvehadhigh Wehavethedowns
premorbidlevelsoffuncRonality
Poorwhen:sxaresubacuteand/orchronic,
insightintotheirdisorderispoor,theyhad
lowlevelsofpremorbidfuncRonality
DEPRESSIVEDISORDERS STAGESOFGRIEF
Whatisnormal? Denial
Sadness Anger
Bargaining
Grief/bereavement
Depression/guilt
Acceptance
**alwaysbewaryofsomeonewhoisgrieving
withoutfuncRonality,asthisindicatesa
depressivedisorder.
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GRIEF GRIEF
Oeringempathyisthe#1waytohelp,thena TheTheoryofCompassion:
supportgroup. ApaRentfeelsyougivethemmore
Everybodygoesthrough5stages,butcan compassionandRmebasedsolelyonhowand
becomestuckincertainstages whereyouposiRonyourselfintheirroomorin
AgrievingpersonissRllfuncRonal yourclinic.
Normalgriefcanlastupto2months(a|er Si{ngattheheadofthebedvsthefootof
thatwediagnosewithmajordepressive thebedmakesyourpaRentfeellikeyoucare
disorder). more,loweringanypotenRalforbeingsued.
DISORDERSWITHFEATURESOF
BIPOLARDISORDER
DEPRESSION
DYSTHYMIA Seenin1%ofthepopulaRon
CYCLOTHYMIA Men=female
MELANCHOLY Seenmorecommonlyinyoungeragegroups
BIPOLARDISORDER Bipolar1(MDD+MANIA)
Bipolar2(MDD+HYPOMANIA)
Fordiagnosisweonlyneedtosee1episode
Ruleoutcocaineand/oramphetamineuse
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BIPOLARMANAGEMENT BIPOLARMEDICATIONS
Majorgoalsoftreatment: 1stlineisLithium(eecRveshortandlong
1. Treatandreduceseverityofmanicor termforbipolarmanagement)
depressiveepisodes. 2ndlineareanRseizuremedicaRonssuchas
ValproateandCarbamazepine(3rdline)
2. Reducethefrequencyofepisodes
3. Avoidcyclingfromonephasetoanother Whenusinglithiumbloodlevelsmustbe
4. HelpthepaRentfuncRonnormallybetween checkedfrequencyduetosmallsafetymargins
episodes WatchforpolyuriawithLithiumasitcancause
nephrogenicDI
DRUGINDUCEDMANIA MOREABOUTLITHIUM
Cocaineandamphetamines Is1stlineforbipolardisorder
Mania+tachycardia,HTN,mydriasis, Isamoodstabilizer,soitdoesntworkfor
arrhythmias acutemaniaoracutedepression
ClassicUSMLEquesRonispersonintheir20s Hyponatremia
withanMI(usuallycausedbycocaine) Hypercalcemia+hypophosphatemia
Foracutemanagement,CCBsareeecRve Nephrogenicdiabetesinsipidus
Epsteinsanomalyofthefetus
Occasionalbonemarrowsuppression
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3LEVELSOFDEPRESSION MAJORDEPRESSIVEDISORDER
Acutereac,vedepression(<2weeks) ANHEDONIA(MCsx)
Majordepressivedisorder(>or=2weeks) SIGECAPS
Bipolardisorder(combinedwithmania) FailuretofuncRondaytoday
IncidenceinthegeneralpopulaRonis13% MustconRnueatleast2weeks
(rule) 2episodesof2weeksatleast2monthsapart
Iftheyhave1riskfactorthechancesare10% isacommonpresentaRon(doathorough
history)
CATECHOLAMINETHEORYOF
MDDOTHERCOMPLAINTS
DEPRESSION
Sleepdisturbances(excessive,shortburtsof CatecholaminelevelsarelowerinpaRents
REM,excessiveREM,earlymorning whoaredepressed
awakening) Thisiswhydepressionrecurswhenuntreated
Guilt ThisiswhywegivemedicaRonstoelevate
Learnedhelplessness thesecatecholamines
Learnedhopelessness
Varioussoma,ccomplainsarecommon
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CATECHOLAMINESANDDEPRESSION CATECHOLAMINESANDDEPRESSION
Norepinephrine(apurelysympatheRc Takes~4weekstoincreasecatecholamine
catecholamine) levels
Serotonin(sympatheRcinbrain, TakespaRentminimum4(morerealisRcally
parasympatheRcintheperiphery) 68weeks)beforetheyfeelmuchbefer
Dopamine(sRmulatesCTZ,movement PaRentmustbemadeverywellawareofthis
disorders,psychosis) Suicideriskincreasesinrst90daysof
Replenishthemandyoucanexpectthese treatment(WHY?)
eects
ANTIDEPRESSIVEMEDICATIONS THESSRIS
SSRIs(1stlines,lowsideeects,anorgasmia) Citalopram(Celexa)
TCAs Escitalopram(Lexapro)
MAOIs Fluoxe,ne(Prozac)
HETEROCYCLICS Fluvoxamine(Luvox)
ATYPICALS(lowsideeectprole) Paroxe,ne(Paxil)
Sertaline(Zolo|)
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SELECTIVESEROTONINREUPTAKE
SSRISIDEEFFECTS
INHIBITORS
Blockthereuptakeof5HT(postsynapRcally) GeneralizedsideeectsoccurMCduringweeks14
(N/V,headache,drowsiness,anhedonia,apathy)
Lowernumberofsideeects MajordrawbacktouseisitslongwaiRngperiodforit
Majorsideeectisanorgasmia toreachfullpotenRal.
Anorgasmia(verycommon)
OlabeluseforprematureejaculaRonin
Diminishedlibido(common)
youngmen ErecRledysfuncRon(rare)
SSRIMAOIrequiresa2weekwait Weightgain
MAOISSRIrequiresa4weekwait(5HT IfaboveAEsaredisturbing,switchingtoBupropion
cangiverelief
crisis)
TRICYCLICANTIDEPRESSANTS TCASINUSETODAY
WerethersttypeofanRdepressant IMIPRAMINE:bedwe{ng(anRcholinergic
Notusedanymorefordepressiondueto property)
signicantsideeectprole
AMYTRIPTYLINE:chronicneuropathy/pain,
4mainaccons
diabeRcsaremainpopulaRonusingthem
1Blockreuptakeof3catecholaminespre
synapRcally. CHLOMIPRAMINEapprovedforOCDbutnot
2AnRcholingeric(strong) 1stline
3Block1receptors(causeshypotension) NORTYPTILINE:usedinelderlypopulaRon
4BlockAVconducRon(ventriculararrhythmias) DESIPRAMINE:usedinelderlypopulaRon
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MONOAMINEOXIDASEINHIBITORS
THEMAOIs
(MAOI)
Phenylzine Breaksdowncatecholamines
Tranylcypramine AsweageourlevelsofMAOrise,thus
increaseddepressionriskwithage(10%)
Isocarboxazine
SelegelinetheonlyMAOBI(usedfor
Selegeline(Parkinsonsmanagement) Parkinsonsdisease)
Cancauseserotoninsyndromeifmixedwith
SSRIs(ornotgivenenoughRmebetweenuse)
Cancauseahypertensivecrisisifingested
withtyraminerichfoods
MAOISerotoninSyndrome MAOIHypertensiveCrisis
CausedbyMAOIinteracRngwithSSRI Wineandcheesearebrokendowninto
Hyperthermia Tyramine
Musclerigidity TyramineisapotentanalogofNE
Excessiveushing NoMAOtobreakitdown
Alteredmentalstatus LeadstoexcessivespikeinBP
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HETEROCYCLICS ATYPICALANTIDEPRESSANTS
Trazadonemostworrisomeadverseeectis Bupropion(Wellbutrin)
priapism DuloxeRne(Cymbalta)
Mirtazapine(Rameron)
Venlafaxine(Eexor,ChanRx)
Trazadone
ATYPICALANTIDEPRESSANTS INTRACTABLEDEPRESSION
Havemuchlowersideeectprolesthan Electroconvulsivetherapy(ECT)
otherdrugs IsexcellentforcaseswheremedicaRonsdo
Bupropion(Wellbutrin)worksmainlyonDA, nothelpthepaRent
5HT,andNE Mainindica,onsinclude:pregnancy,
Wellbutrinsbiggestdownfallisthatitlowers unresponsivetomedicaRons,andpaRents
seizurethreshold whoareacutelysuicidal
Hasamuchlowersexualsideeectprole,
andhasbeenshowntoincreaselibido
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ANXIETY&PSYCHOTICDISORDERS TYPESOFANXIETY/PSYCHOSIS
WorrysituaRonalandcontrolled
AnxietyanoutwardmanifestaRonofyour
worry
PanicA[acksusuallysituaRonal
PhobiasirraRonalfearleadingtoavoidance
Delusionsfalselyheldbeliefsdespitethe
proofofthecontrary
TYPESOFANXIETY/PSYCHOSIS WORRY
IllusionsmispercepRonofasRmulus Issimilartosadnessinthemooddisordersis
Hallucina,onspercepRonwithouta situaRonalandwecano|enpullourselvesout
sRmulus ofit.
Psycho,cdisorderdxmadewhenthereisa Unlikeanxiety,wecantseeworryon
losswithreality someonesface
ObsessiveCompulsivedisorderrecurrent
thoughts/acRons
Posttrauma,cstressdisorderviolent
incidentthatcausesstressa|erthefact
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ANXIETY PANICATTACKS
AnoutwardmanifestaRonofyourworry TheMCtypeofanxiety
Specic:1thinginparRculariscausinganxiety UsuallysituaRonal
General:worriedaboutmanythings/ MaybeintensesympatheRcoverdrive
everything Mostpeoplefeelasthoughtheyrehavinga
Social:provokedbysocialsituaRons heartafack,thereisafeelingofimpending
Disorder:whenitcausessocialimpairmentto doom
thepointwhereyouavoidsituaRons 1ststepisalwaystoruleoutamoreserious
problem(MIsogetanEKG)
PHOBIAS DELUSION,ILLUSION,HALLUCINATION
ThereisanirraRonalfearthatleadsto Thesearecommonlyconfusedterms
avoidance Adelusioniswhenyouhaveafalselyheld
MCincludeacrophobia,arachnophobia, beliefdespitesocialproofofthecontrary
clostrophobia,agoraphobia Anillusion(thinkmagician)iswhenyou
Peoplewiththesephobiasrecognizethe misperceiveasRmulus
irraRonality Ahallucina,oniswhenyouperceive
somethingwithoutasRmulusbeingthere
(thinkofthedesertoasis)
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OBSESSIVECOMPULSIVEDISORDER POSTTRAUMATICSTRESSDISORDER
Obsessivethoughtsleadtoanxiety TheremustbeatraumaRc/violenteventthat
Compulsionsacttotemporarilyrelievethe scarsthem(classicexampleisawarveteran)
anxiety PaRentsrelivesincidentviasubconsciousorina
ObsessionscommonlyinvolvecontaminaRons dream
andcleanliness,doubt,symmetry
Thestressofanythingthattriggersthisleads
Reliefistemporary(veryshortlasRng) themtoavoidstressors(placesandacRviRes)
Thispersonrecognizestheabsurdityoftheir
disorder,wheraspeoplewithOCpersonalitysee Detachmentfromothersiscommon
nothingwrong Depressioniscommon
TreatwithSSRIs+psychotherapy Acutestressdisorder(within4weeksand<4wk)
PSYCHOSIS SIGNSOFPSYCHOSIS
ApsychoRcpersonhaslosttouchwithreality Disordersofthethoughtpa[erns(ightofideas,
Timeframesareveryimportantfordx ideasofreference)
Iftheepisodeis<2weeks,wecallitBrief Disordersofspeech(pressure,nonsensical)
reaccvepsychosisthisisusuallytriggeredby Tangen,ality(theygooontangentsthatmake
something
nosense)
Ifepisodelasts2weeksbut<6months,wecallit
Schizophreniformtheyreusuallyontheirway Neologisms(makingupnewwords)
toschizophrenia Clangassocia,ons(rhymingtowhatyousay)
>6monthsandwecallitSchizophrenia Thoughtblocking(movingfromonethoughtto
Schizophrenia+mooddisorder=SchizoaecRve thenextwithoutcompleRon)
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SIGNSOFPSYCHOSIS MANAGEMENTOFPSYCHOSIS
Hallucina,ons(MCareauditory),canbe Dopamineisthemainplayerinpsychosis
tacRle(formicaRon) Alltreatmentregimensinvolveloweringthe
Socialwithdrawal(isanegaRvesymptoms levelsofdopamine
theytakethemselvesawayfrompeopleand ToomuchDA=psychosis,CTZsRmulaRon(N/
situaRons) V)
Presenceofnegacvesymptomsareusuallyan ToolifleDA=movementdisorders(extra
indicatorofaworseprognosis pyrimidalsymptoms)
NEUROLEPTICMALIGNANT
EXTRAPYRIMIDALSIDEEFFECTS
SYNDROME
DystoniasustainedcontracRonofagroupof Isthesameasmalignanthyperthermiathat
muscles(torRcollisisacommonlyencountered
formofdystonia) occurswithanestheRcs(MCHalothane)
TardiveDyskinesiawithlongtermmedicaRon Severemusclerigidity
repeRRve,involuntary,purposelessmovements
Hyperthermia
AkisthesiapaRentexperiencesnonstop
movements(restlessness) Treatmentisthesameasformalignant
ParkinsonsSyndromesxofParkinsonsdisease hyperthermia(Dantrolene)
(ifthereisalsoautonomicdysfuncRonwecallit
ShyDragerSyndrome)
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DOPAMINEANDTHEHYPOTHALAMUS ANTIPSYCHOTICMEDICATIONS
DopamineinhibitsthereleaseofprolacRn Phenothiazines
UndernormalcondiRonswedontlactate
Thioxanthines
IfyoublockDAthenyouincreaseprolacRn
release Butyrephenols
ThiscancauselactaRoninmaleswhoareonanR Atypicals
psychoRcs(galactorrhea)
Thiscanalsoleadtoamenorrheainfemalesas
prolacRninhibitsGnRHreleasefrom
hypothalamus
HighprolacRnalsoblocksTRH
PHENOTHIAZINES THIOXANTHINES
WeakDAblockade,stronganRcholinergics Weakdopamineblockade,stronganR
Chlorpromazine:blocks1receptors(orthostaRc cholinergics
hypotension)
Perchlorperazine:anRemeRcinadults LongeracRngdepoform
Promethazine(Phenergen):anRemeRcin BestforpaRentswithmildpsychoRc
children symptomswhohavetroublesleeping(strong
Fluphenazine:mainlyusedaslongacRngdepo anRcholingeric)
shot
Thioridazine:causespigmentreRnopathy(dark Idealforpa,entswhoarehomelessand/or
spotsonreRna,doesntleadtoblindness) noncompliant
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BUTYREPHENOLS ATYPICALANTIPSYCHOTICS
Highlypotentdopamineblockers UsedwhentherearenegaRvesymptoms
Havethehighestrateofextrapyrimidalside UsedwhenpaRentisrefracRvetoother
eects treatments
1stlineforacutelypsychoRcpaRents UsedwhenpaRentssuerfromtoomany
adversereacRonstootherformsof
Haldol:highlypotent,movementdisorders medicaRon
likely,loweranRcholinergiceects Lowsideeectprolebecausetheyonlyblock
Droperidol: D4receptors
AreNEVER1stlinetreatment
ANTIPSYCHOTICMEDICATIONSAND
ATYPICALANTIPSYCHOTICS
MOVEMENTDISORDERS
DISORDER TIMECOURSE CHARACTERISTICS
Clozapine:usedforrefractorypsychosis,has
riskofagranulocytosis(requiresweeklyCBC) ACUTEDYSTONIA 4HRTO4DAYS Sustainedmusclespasms,
giveIVdiphenhydramine
Risperidone:usedinanesthesiawithfentanyl
PARKINSONISM 4DAYSTO4MONTHS Cogwheelrigidity,
(Neurolepthanesthesia) shuinggait,resttremor
GiveBenztropine
Olanzapine:hasahighrateofweightgainand TARDIVEDYSKINESIA 4MONTHSTO4YEARS Involuntaryirregularmovt
causingdiabetes Changemedsordoses
AKATHISIA CANOCCURATANYTIME AsubjecRvesenseof

restlessness
LowermedicaRondose
NEUROLEPTICMALIGNANT CANOCCURATANYTIME Lifethreatrigidity
SYNDROME Stopmeds,give
dantrolene,coolthemo
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PERSONALITYDISORDERS CLUSTERADISORDERS
ClusterA Theseareoddoreccentricpeople
ClusterB ParanoiduntrusRngofothers,use
ClusterC projecRonasadefensemechanism
Somatoformdisorders Schizoidhaveavoluntarysocialwithdrawal
DissociaRondisorders inaddiRontolimitedemoRonalexpression
Schizotypalhaveinnerawkwardnessin
Malingeringdisorders
addiRontoanoddappearanceandthought
pafern
CLUSTERBDISORDERS CLUSTERBDISORDERS
ThesepeopleareemoRonal,dramaRc,and/ Histrionicthispersonisexcessively
orerraRc emoRonal/dramaRc,o|ensexually
provocaRve,theyareconstantlyseeking
An,socialpaRentshaveadisregardfor
afenRon
otherpeople(violaterights,males>females,
Narcissis,csenseofenRtlement,feelingsof
<18calledConductdisorder) grandiosity,believetheyalwaysdeservethe
Borderlinefemales>males,unstablemoods, bestoverothers.Thispersonthinkstheworld
impulsive(notinagoodway).Spli{ngisseen revolvesaroundthem,theyaresensiRveto
(ie.Eitherloveorhate,blackorwhite,etc) criRcism,andneverbelievetheyarewrong
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SOMATOFORM&FACTITIOUS
CLUSTERCDISORDERS
DISORDERS
Thesepeopleareconstantlyanxiousorfearful Somatoformdisorderstheydonotrealize
Avoidantfeelinadequatetoothers,is thattheyarefaking
excessivelysensiRvetorejecRon,veryRmid. FacccousdisorderspaRentisfaking
Obsessivecompulsivepreoccupiedwith consciouslyormanipulaRngsymptomsto
perfecRon,arealwaysorganizedandneedtobe assumethesickrole.Notformaterialgain
incontrol.
MalingeringdisorderspaRentconsciously
Dependentthispersonalwaysseeksapproval, fakesbeingsickforthepurposeofmaterial
needsotherstocareforthem,haslowself gain
condence,issubmissive,isclingy.
SOMATOFORMDISORDERS FACTITIOUSDISORDERS
Conversiondisorder PaRentcanmimiceitherphysicalorpsychological
SomaRzaRondisorder symptomsinordertoassumeasickrole
Hypochondriasis PaRentisconsciouslyfaking,butnotforany
parRculargain,onlytoassumethesickrole.
Bodydysmorphicdisorder
MunchhausensyndromefacRRousdisorder
Pseudocyesis thatisusuallyphysical
MunchhausenbyproxypaRentclaimsnon
existentsymptomsinsomeoneelse(classicallyin
theirchildren)
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MALINGERINGDISORDER DISSOCIATIONDISORDERS
ThepaRentispurposelyfakingtheirsickness Disorderswherepeoplebecomedetachedfrom
themselvesinsomeway
inordertogetsomesortofmaterialgain(to Depersonaliza,onpaRentfeelsdetachedwhile
avoidwork,towincompensaRon,etc) maintainingawareness
Dissocia,veamnesiaemoRonaltraumaimpairsabilityto
remembercertainthings
Dissocia,vefuguepaRentassumesnewidenRtyand
desertstheirlife
Dissocia,veiden,tydisorder2ormorepersonality
states
Dissocia,vedisorderNOSdoesnttabovecriteriabutis
dissociaRve
BEHAVIORALPHARMACOLOGY BENZODIZEPINES
Iftheyredownwewanttobringthemup(ie. Workbyincreasingthefrequencyofchloride
Depressionincreasecatecholamines) channelopening
Iftheyreupwewanttobringthemdown(ie. Thesedrugsalwaysendinpamorlam
BywayofGABA) Usedforanxiety,seizures,insomnia,and
WevealreadydiscussedhowanRdepressants musclecramping
bringpeoplebackup,nowletslookathow Seda,ve=calming
webringthemdown. Hypno,c=inducessleep
BenzodiazepinesandBarbiturates
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BENZOS,BARBS,OPIATES,AND
BARBITURATES
ALCOHOL
WorkbyincreasingtheduraRonofchloride Overdoseofthose4lookthesame,theonly
channelopening dierenceismiosisseenwithopiates
Mostdrugsendintal Withdrawalfromtheseareallthesame,except
immediateETOHwithdrawalseesformicaRon
YoumaythinkyoureseeingDTs,buttheycanbe
justsympatheRcoversRmulaRon
OpiatewithdrawalmanagedoutpaRent
(methadone),otherthreerequirehospitalizaRon
OVERDOSE,WITHDRAWAL,
THEBENZODIAZEPINES
COMPLICATIONS
OverdosesleadtoexcessivesedaRon Fluorazepam
Alprazolam
NeurologicalcomplicaRonsarethemost Oxazepam
worrisome(CNSdepressionrespiratory Triazolam
depressiondeath) Tamazepam
WithdrawalfromanysedaRngdrugleadsto Diazepam
theoppositeeectsympatheRc Lorazepam
oversRmulaRon Clonazepam
Benzodiazepineoverdoseistreatedwith Midazolam
chlordiazepoxide
Flumazenil
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THEBENZODIAZEPINES THEBENZODIAZEPINES
Itisimportantthatweknowthemostimportant Diazepam(Valium)1stlineforstatus
factsabouteachone epilepRcus,anxiolyRc,presurgicalsedaRon/
Alpralozam(Xanax)istheshortestacRngandis amnesia
used1stlineforanxietyandpanicafacks Lorazepam(ARvan)2ndlineforstatus
Oxazepamisthe2ndshortestacRng epilepRcus
Triazolamisthe3rdshortestacRng,causes15 Midazolam(Versed)provides45minutesof
minutesofamnesiawhilefallingasleep(thisis anteriogradeamnesia,thusexcellentforshort
whytheydontrememberfallingasleep) procedures
FluorazepamisthelongestacRngbenzo Chlordiazepoxidetheonlybenzothatdoesnt
Temazepamhelpspeoplestayasleep endinpamorlam.UsedforacuteETOH
withdrawalandshorttermanRanxiety.
THEBARBITURATES THEBARBITURATES
WorkbyincreasingtheduraRonofthe PhenobarbitalthelongestacRngbarbiturate,
1stlinetreatmentforgeneralizedseizuresin
chloridechannelopening children
Dosesof1gareharmfultomostpeople,while Primidoneistheparentcompoundof
dosesof210garefataltomost. phenobarbitalbutislesseecRve(justknowthat
theyarerelated)
Overdoseismanagedwith1g/kgofacRvated ThiopentalistheshortestacRngbarb,usedin
charcoal,thenalkalinizaRonoftheurine anesthesiatomildlysedateandrelax
sodiumbicarbonate Secobarbitalisthemostabusedbarbonthe
street,commonlyknownasdownersonthe
street.
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DEFENSEMECHANISMS MATUREDEFENSEMECHANISMS
Arethesubconscioustryingtoprotectthe Altruismaselessconcernforthewelfareof
conscious others
Therearebothmatureandimmature Humorusingjokeswhenfeelinganxious
defensemechanisms Suppressionconsciouslyblockingsomething
out
Sublima,onturningsomethingnegaRveinto
somethingposiRve
IMMATUREDEFENSEMECHANISMS IMMATUREDEFENSEMECHANISMS
Ac,ngoutdisplayingfeelingsinanoutwardmanner Projec,onpu{ngyourowninternalfeelingsonto
Denialpurposelyavoidingapainfulreality somethingsimilar
Displacementtakingsomethingoutonsomeoneother Ra,onaliza,onmakingexcusesforyourbehaviorsoit
thanthesourceofyouranger doesntseemasbad
Dissocia,onatemporarychangeinpersonality Reac,onforma,ondoinganacRonoppositetohowyou
Fixa,onremainingatamorechildishlevelof feel
development RegressionreverRngbacktostressmanagementasifyou
Isola,onseparaRonoffeelingfromideas/events wereinayoungerstate
Iden,ca,onafempRngtolooklikesomeoneyoudesire Repressioninvoluntarywithholdingofidea/feelingsfrom
yourconscious
Intellecutaliza,onacRngasifyouknoweverythingto Splipngseeingthingsasonedenitewayoranother
makeupforyourignorance
Undoingdoingtheexactoppositeofwhatyouusedtodo
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TRANSFERENCE&
CONDITIONING
COUNTERTRANSFERENCE
TransferencewhenapaRentprojects Classiccondiconinganaturalresponsethatis
learnedbythepresenceofacondiRoned/learned
feelingsfromtheirpersonallifeontothe sRmulus.Ex.Pavlovsdog
physician OperantcondiconinglearninganacRonbythe
Countertransferencewhenthephysician presenceofareward(posiRveandnegaRve
reinforcement)
projectsfeelingsfromtheirpersonallifeonto
Posi,vereinforcementadesiredreward
thepaRent producesanacRon
Nega,vereinforcementremovalofan
unwantedsRmulusproducesbehavior
REINFORCEMENT SEXUALDEVIANCES
Determineshowquicklycertainbehaviorsare Deviancesnevergoaway,theyarelifelong
eitherlearnedorabandoned condiRons
Concnuousreinforcementarewardisgiven Acouplebehindcloseddoorsarenever
a|ereveryresponse(vendingmachine) consideredtobedeviants
Variableracoarewardisgivenonlya|er Followingisalistofhighlytestedsexual
certainnumberofafempts(slotmachine) deviances
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SEXUALDEVIANCES SEXUALDEVIANCES
Fe,shesderivingpleasurefrominanimate Fro[eurismderivingsexualpleasureby
objects rubbingagainstsomeonewhoisfullyclothed
Pedopheliaderivingsexualpleasurefrom SadismderivingsexualpleasurebyinicRng
children(images,videos,reallife) painonsomeone
Voyeurismderivingsexualpleasurefrom
Masochismderivingsexualpleasureby
watchingotherpeoplehavingsex
receivingpain
Exhibi,onismderivingsexualpleasurefrom
beingwatchedinsexualactsorhaving
someoneseeyourgenitals(ashing)
SEXUALDEVIANCES ETHICALPRINCIPLES
Necrophiliaderivingsexualpleasurefroma Ethicalprinciplescanbethrownatyouina
deadcorpse widevarietyofways
Urophiliasexualpleasurefrombeing Yourgoalistounderstandthebasicprinciples
uriantedon andbeabletoapplythemtoanycircumstance
Coprophiliasexualpleasurefrombeing
poopedon
Beastophiliasexualpleasurederivedfrom
animals
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CONFIDENTIALITY CONFIDENTIALITYEXCEPTIONS
IstorespectapaRentsautonomyandprivacy ThereareafewRmeswhenyoudonothave
PaRentshavearighttowaivetheirrightto tomaintainthepaRentdoctorcondenRality
condenRality IfpaRentislikelytohardthemselvesorothers
YoucannotdiscloseinformaRontofamily/ Ifthereisnowaytoprotectorwarnsomeone
friendsthatthepaRentdoesnotgiveyou oftheirpotenRalharm(theTarasodecision)
permissiontorelease IfthereisareportableinfecRousdisease
Ifthereischildorelderlyabuse
IfpaRentisintoxicatedandcannotdrive
REPORTABLEINFECTIOUSDISEASES INFORMEDCONSENT
UsethemnemonicB.A.SSSMMARTChickenoryoure Thereare3criteriathatmustbemet,they
Gone
BhepB are:
AhepA
1. DiscussionofperRnentinformaRonrelaRng
SSSsalmonella,shigella,syphillis
MMmeaslesandmumps tothetreatmentinquesRon
AAIDS 2. PaRentmustagreetotheplanofcare
Rrubella
Ttuberculosis 3. ThepaRentshallnotbecoercedintoany
Cchickenpox decision
Ggonorrhea
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WHATCONSTITUTESDECISION
EXCEPTIONSTOINFORMEDCONSENT
MAKINGCAPACITY?
IfpaRentlacksthecapacitytomakea PaRentiscorrectlyinformed
decision(ie.Legallytheyarenotcompetent) ThedecisionremainsstableoverRme
Ifthesitua,onisanemergencyandwaiRngis
PaRentmakesandcorrectlycommunicates
dangerous
theirchoice
IfpaRentwaivestheirrighttoinformed
consent DecisionisconsistentwiththepaRentsvalues
Caseoftherapeu,cprivilege(towithhold andgoals
informaRonthatwouldotherwiseseverely Decisionmadewithoutpresenceofdelusions
harmthepaRent) orillusions
3DEFINITIONS ADVANCEDIRECTIVE
AutonomyyourlegalandmoralobligaRonto Wri[enlivingwills,durablepowerof
respecteachpaRentisanindividualandto aforney
honortheirpreferences(eveniftheyare
Oraltheoralstatementfromanow
dierentfromyours)
incapacitatedpaRent
Nonmalecencetodonoharm(onlydowe
doharmifthebenetsofintervenRon
outweightherisks)
Benecencetoactinthebestinterestof
yourpaRent
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MALPRACTICE BIOSTATISTICS
The3Ds SensiRvity/Specicity
Derelic,onphysicianbreachestheirdutyto PosiRveandNegaRvePredicRveValues
thepaRent
AfributableandRelaRverisk
DamagepaRenthassueredfromthis
negligence OddsraRo
Directbreachofdutyhascausedharm StandarddeviaRon
The#1reasonforbeingsuedisactuallypoor Mean,median,mode
communicaRonbetweenyouandyour SkeweddistribuRon
paRent.
BIOSTATISTICS INCIDENCEvs.PREVALENCE
Reliability,validity Incidenceisthenumberofnewcasesofa
CorrelaRoncoecient diseaseinaspecicunitofRme(ex.1yr)
Typesofstudies Prevalenceisthetotalnumberofcasesofa
PValue disease(bothnewandold)atacertainpoint
inRme.
Confoundingvariables
Bias
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EPIDEMIC,ENDEMIC,PANDEMIC THEUSEFUL2X2BOX
Epidemicnewcasesofadiseasegreatly Drawingouta2x2boxwithrepresentaRve
exceedwhatisexpected. valuescanhelpyouwithbiostaRsRcs
Endemicnewcasesareexclusivetoacertain quesRonsontheexam
place,region,populaRon. Onthenextpageyoullseehowthisisdone
PandemicthespreadofinfecRousdisease
acrossalargegeographicregion(ex.Inuenza)
2X2BOX SENSITIVITY
Sensi,vityisthetestsabilitytodetecta
disease.
TestswithhighsensiRviResareusedas
screeningtools(colonoscopy,Papsmear,
mammography)lowfalseverate.
FalseposiRvesmayoccur,butahighly
sensiRvetestwontmisspeoplewiththe
disease
Equa,on:A/(A+C)
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CALCULATINGSENSITIVITY SPECIFICITY
Specicityisatestsabilitytodetecthealthy
individuals
WeusehighlyspecictestsasconrmaRon
testsbecausetheywontidenRfysomeoneas
sickwhoisactuallyhealthy(lowfalse+rate)
Ideallyconrmatorytestsshouldhavebotha
highsensiRvityandspecicity,otherwisewe
wouldidenRfysickpeopleashealthy
HIGHYIELDSENSITIVITYVS.
CALCULATINGSPECIFICITY
SPECIFICITYQUESTION
ThetradeobetweensensiRvityand
specicityisalwaysasked
Isconfusingtograspunlessyouunderstand
whattheyareasking
WecanalsobeaskedaboutPPV(posiRve
predicRvevalue)andNPV(negaRvepredicRve
value)soletstakealookatthosebeforewe
jumpintothegraphicalanalysis
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POSITIVEPREDICTIVEVALUE NEGATIVEPREDICTIVEVALUE
Posi,vePredic,veValuemeasuresthe Nega,vePredic,veValuemeasuresthe
probabilityofhavingthediseasewhenthey likelihoodthatapaRentdoesnthavethe
testposiRveforit. condiRonforwhichtheytestednegaRvely)
Measurebytakingthe#oftrueposiRves MeasuredbydividingthetruenegaRvesby
dividedbythe#ofallposiRves thetotalnegaRves
A/(A+B) D/(C+D)
Directlyrelatedtoprevalence(ie.Increased Inverselyrelatedtoprevalence(ie.Higher
prevalence=increasePPV) prevalence=lowerNPV)
TRADEOFFS CUTOFFATA
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CUTOFFATB ATTRIBUTABLERISK
Dontforgetourrules.
Ifpersonhas0riskfactors,theirriskof
diseaseis13%
Ifpersonhas1RF,theirriskofdiseaseis10%
Theafributableriskissimplytheriskthatis
afributedtotheriskfactorie.10%13%=
79/100
OryoucanusethecomplexcalculaRon:[A/(A
+B)][C(C+D)]
RELATIVERISK ODDSRATIO
TheRRcomparesthediseaseriskinpeople Iscalculatedfromaretrospec,vestudy(as
exposedtoacertainRFcomparedtopeople opposedtoRRwhichcanonlybecalculatedfrom
prospecRvestudies)
notexposedtothatsameRF.
Looksattheincidenceofdiseaseinpplexposed
Canonlycalculatethisa|eraprospecRveor toRFvs.incidenceofnondiseaseinpplnot
experimentalstudy,notfromaretrospecRve exposedtotheriskfactor
study. Goalistoseeifthereisadierencebetweenthe
ArelaRveriskof1isinsignicant,only twopopulaRons
numbersaboveorbelowareworthy [(AxD)/(BxC)]
Valueof1isinsignicant(likerelaRverisk)
[A/(A+B)]/[C/(C+D)]
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STANDARDDEVIATION MEAN,MEDIAN,&MODE
VerysimpledeniRons
MEAN=averagevalue
MEDIAN=themiddlevalue
MODE=themostcommonvalue
SKEWEDDISTRIBUTIONS POSITIVELYSKEWEDCURVE
SkeweddistribuRonssimplyindicatethatthe
valuesgivenwereuneven(ie.Thecurveisntbell
shaped)
PosicvelySkewedmeansthevaluesare
excessivelyhighinthiscasethemean>median
>mode
NegacvelySkewedmeansthevaluesare
exccesivelylowinthiscasethemean<median
<mode
StandarddeviaRonsandmeanareofless
signicancebecauseoftheseskewedvalues
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NEGATIVELYSKEWEDCURVE RELIABILITYOFATEST
Measuresthereproducibilityandconsistency
ofatest
Akaprecisionofatest
Areliabletestwillproducesameresultsno
maferhowmanydierentpeoplearegivingit
Reliabilityisreducedbyrandomerror
VALIDITYOFATEST CORRELATION
Validitymeansthetestmeasureswhatitsays DeterminesthestrengthofarelaRonship
itwill between2variables
Akaaccuracy Weusethedistancefrom0asthestrengthof
AgoodexampleisanIQtest(ifptismentally thecorrelaRon
retardeditwillshowusthat) +1meansperfectposi,vecorrela,on(1value
ValidityisdisturbedwithsystemaRcerrors increasessodoestheother)
1meansperfectnega,vecorrela,on(1
valueincreasestheotherdecresaes)
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THECONFIDENCEINTERVAL PVALUE
TakingdatafromapopulaRonssubsetmeans Isusedtodeterminethesignicanceofdata
thatyourmeanswillneverbeidenRcal obtained
Weusethecondenceintervalto Ifwesayp<0.05,thismeansthereis<5%
demonstratehowsurewearethatourmeans chancethatdatawasobtainedbyrandom
arewithinacertainrangeofeachother chanceorerror
95%CIisusuallytheacceptedvalue P<0.05isourcutoforstaRsRcalsignicance,
WemustindicatestandarddeviaRoninourCI althoughthisdoesntruleoutawsinthe
aswell study,nordoesitimplyclinicalsignicance
PVALUEANDNULLHYPOTHESIS TYPE1AND2ERRORS
Anullhypothesismeansthatsomething Type1error:meansyouveclaimedsignicance
doesntwork(ex.AdrugbeinginvesRgated) whennoneexists,ORyouverejectedthenull
hypothesiswhenitwastrue(falseposiRve)
AnullhypothesisthatshowsstaRsRcal Type2error:meansyouveeitherclaimedno
evidencesuggesRngotherwiseissaidtobe signicanceexistsinyourresultsORyouve
duetorandomerrororchance acceptedthenullhypothesiswhenitwasinfact
IfstaRsRcalevidencesuggestsmuch wrong(falsenegaRve)
dierentlyfromthenullhypothesis,wehave POWERtheprobabilityofrejecRngthenull
hypothesiswhenitisfalse..Idealwaytoincrease
torejectit
poweristoincreasesamplesize.
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CONFOUNDINGVARIABLES STUDIES
Areunmeasuredvariablesthataectthe EXPERIMENTALSTUDIES(goldstandard)
independentanddependentvariables PROSPECTIVESTUDIES(akacohort,follow
Areusuallyextraneousvariablesthatareofno up,observaRonal,andincidence)
signicancethatareinsertedintoastudyand RETROSPECTIVESTUDIES(akacasecontrol)
alterresults CASESERIESSTUDY
Wecontroltheseconfoundingvariablesby PREVALENCESURVEYS(akacrosssecRonal)
usingdierentformsofcontrolledstudies
TYPESOFBIAS CHISQUARED,TTEST,ANOVA
NONRESPONSEBIAS Chisquaredtestisusedtocompare
LEADTIMEBIAS proporRons/percentages
ADMISSIONRATEBIAS Ttesttocompare2dierentmeans
RECALLBIAS ANOVA(analysisofvariance)tocompare3
INTERVIEWERBIAS ormoremeans
UNACCEPTABILITYBIAS
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SLEEPCYCLES
BETAWAVES:awake(eyesopen)
ALPHAWAVES:eyesclosebutsRllawake
THETAWAVES:Kcomplexes,sleepspindles,
lightwaves(stages1and2)
DELTAWAVES:largewavesduringdeepsleep
BETAWAVES:REMsleep,occursevery90
minutes,experience57pernight,
parasympathic,dreams
HIGHYIELDANATOMYNUGGETS
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115
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116
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AUTOREGULATION
BPmaintainedbetween60160systolic
Above160=HemorrhagicInfarct
VASCULARPHYSIOLOGY Below60=IschemicInfarct
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SMOOTHMUSCLES
Mostsmoothmusclebyareaisfoundinthe
arterioles(forvasodilaRonand
vasoconstricRon)givestheabilitytocontrol
ow
Leastsmoothmusclebyareafoundinveins
andvenules(theyarecapacitancestructures)
ThickestlayerofSMisfoundintheaorta
(manyreasonsforthis)
AnatomyofVeins/Arteries VEINS/VENULES
Designedforcapacitance(abilityto
holdontoblood)
Havetheleastamountofsmooth
muscleofallvasculature
Skeletalmusclemustpropel
bloodforward
Onewayvalvespreventbackow
ofblood
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CONTROLOFTHEVEINS CONTROLOFTHEARTERIES
Underparasympathe,ccontrol(ie. Undersympathe,ccontrol(ie.
VasodilaRon) VasoconstricRon)
TheyareunderparasympatheRccontrolmost TheyareundersympatheRccontrolmostof
oftheRme(ie.Remaindilatedmostofthe theRme(ie.Usuallyconstricted)
Rme) Controlledby1receptors(IP3/DAG)
VenoconstricRoncontrolledby1sRmulaRon vasocontricRon
(IP3/DAG)venoconstricRon
THEARTERIOLES CAPILLARIES
MaintainBPbyautoregulaRon(theirabilityto Thinnest+greatestsurfacearea
constrictanddilatewell) Those2thingsmakethemidealfordiusion
Mostsmoothmusclebysurfacearea (theirmainrole)
Controlledby2receptors(cAMP)
vasdilaRon
FF=(Hv+int)(Hint+v)
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FLUIDACCUMULATIONOUTSIDETHE
ImportanceofAVAnastomoses
VESSELS
HelptoshuntbloodawayfromnonessenRal Transudate=mostlywater
structuresatRmesofneed Exudate=mostlyprotein
Theyaremostsignicantinthengers,toes,
nose,lips,andearlobes(iswhytheseareasget
redwhencold)
TRANSUDATE EXUDATE
Mostlywater(lowprotein,normalglucose, Mostlyprotein(highLDH,highWBC,lowglucose,
lowLDH,lowWBC,highpH) lowpH)
Proteinrichuidsoozeintoanareaof
CausedbyadisturbanceineitherhydrostaRc inammaRon/lesion
oroncoRcpressureinthevessel
Purulent
Fibrinous
Dieren,alsfortransudate?? Serous
Malignant
Catarrhal
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ASCITES
Canbetransudateorexudate
UseSerumAscitesAlbuminGradient(SAAG)
SidenoteWhatifweseeAscites?
SAAG=[serumalbumin][asciccuidalbumin]
Highgradient(>1.1g/dL)=increasedhydrostaRc
pressure(MCCisportalHTN)
Lowgradient(<1.1g/dL)=notd/tincreased
hydrostaRcpressure(nephroRcsyndr,TB,cancer)
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MEASURINGPRESSUREINAVESSEL
Pressureismeasuredasbothlinearand Whathappensasavesselnarrows?
transmural. (aortaarteriesarteriolescapillaries)
TherelaRonshipbetweenlinearand
Velocityincreases
transmuralpressureisinversed
Flowdecreases
Resistanceincreases
Bloodpressurerises
WhatshappeningduringSYSTOLE?
Ventricularcontrac,on
AorRcvalveisopen
AorRcvelocityishigh,transmuralpressureis
quitelow
Veryhighresistanceinthecoronaries=no
coronarybloodow
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WhatshappeningduringDIASTOLE? AV02DIFFERENCE
Ventricularrelaxa,on Isthe%of02extractedbytheRssues
AorRcvalveisclosed
ItincreaseswhenRssueismetabolicallyacRve
AorRcvelocityislow,transmuralpressureisquite
high ORthereisdecreasedow
Verylowresistanceinthecoronaries=high
coronarybloodow
**AV02dierenceisgreatestduringsystole(~
97%)
REMEMBER:AV02dierence=%02extracted
THEEFFECTOFRADIUSCHANGES
THROUGHOUTTHEBODY
CNS:pC02p02
LUNGS:p02
FLOW MUSCLES:pHpC02
CV:Adenosine
SKIN:pC02TEMP
GI:Food
RENAL:ANPDAPGE2
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NEUROLOGICCONTROLOFTHE
BLOODPRESSURE
AUTONOMICDYSFUNCTION VASOVAGALSYNCOPE
Inabilityrespondappropriatelytoasuddendrop AcutestretchingofthecaroRdleadsto
inBP(HRdoesntraiseatleast5bpm) passingout
MCCisdiabetesmellitus
Causedwhentheresasuddenincreasein
PaRentlosesconsciousnessassoonasthey
intraabdominalpressure,whichcausesa
standup(orthostaRchypotensionwithinafew
seconds,dontalwayspassout) rapidengorgementofthecaroRds
Newborns:RileyDaysyndrome
Elderly:Sicksinussyndrome
Parkinsonism:ShyDraggersyndrome
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CAROTIDMASSAGE ORTHOSTATICHYPOTENSION
SRmulaRonofthecaroRdswilltrickthesinus Duetohypovolemia
intobelievingthereismorevolumethanthere Systolicwilldropby20mmHgormoreOR
actuallyis Diastolicwilldropby10mmHgormoreORHR
LeadstoslowingoftheHR goesupbymorethan1020bpm
Uponstandingautonomicstakeover(theyll
bene),withinafewsecondstheyfeellight
headedandblackout(notpassout)
OrderofBPregulaRon LOWVOLUMESTATE
02seconds:autonomicstakeover Howwilltheautonomicnervoussystemrespondtoa
lowvolumestate?
2sec20min:NEtakesover(sRm1
receptors) Lowstrokevolume
LowcaroRdstretch
20minandon:Renalsystemtakesover LowCN9ring
LowCN10ring
IncreasedHR
IncreasedNErelease
IncreasedTPR
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Decreasedrenalbloodow
DecreasedGFR
IncreasedReninsecreRon HowtoblocktheeectsofAldosterone?
RAASAldosteronesRmulatesCollecRng
tubules GiveanAceInhibitor
IncreasedNa+/H20reabsorpRon
IncreasedK+andH+excreRon
Whattoswitchyourpa,enttoifthey HIGHYIELDVASCULITIS
experienceadisrup,vecough?
AngiotensinReceptorBlocker
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VASCULITIS IgANephropathies
InammaRonofthevessels AretheMCglomerulonephriRsintheworld
1stchangewellsee:Swelling(PMNsearly,T
cells&Macrophageslater,brosisevenlater)
ThreecommonIgAnephropathies:
Whatwillwesee? BergersIgA
Schistocytes(tornRBCsandPLTs)
HenochSchonleinPurpura
Lowenergy/lowvolumestate
Alportssyndrome
**allvasculi,shavethesameunderlying
featuresjustknowthe1uniquefeature!**
BERGERSDISEASE HENOCHSCHONLEINPURPURA
2weeksa|eracommoncold SerumIgAlevelsareelevatedleadstoclassictriad:
PalpablePurpura+Arthrics+AbdominalPain
developrenalfailure OnlyvasculiRsthatmovesfrom
FollowtheurinalysisunRlitclears thewaistdown(classic
presentaRonontheglutes)
Highassocia,onwith
intussuscep,on(watchforsigns
currantjellystool,
sausageshapedmass,
severeabdominalpain)
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ALPORTSSYNDROME
IsahereditarynephriRs
Associatedwithcataractsandhearing
disabili,es MOREHIGHYIELDVASCULITIS
Presentsinchildhoodbuttakes~15yrfor
renalfailuretodevelop
DISSEMINATEDINTRAVASCULAR
BUERGERSDISEAE
COAGULOPATHY(DIC)
Akathrombosisobliterans PathologicalacRvaRonofcoagulaRon
mechanismsinresponsetodisease(smallblood
Associatedwithtobacco clotsthroughoutthebody)
ProgressiveandrecurringinammaRonand MCCissepsis
thrombosisofthesmall/mediumvesselsof PaRenthasabnormalbleedingfromskin,GItract,
thehandsandfeet respiratorytract,wounds,etc
PT/PTTareelevated
Fibrinsplitproductselevated
Tx:GivepaRentFreshFrozenPlasma
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THROMBOTICTHROMBOCYTOPENIC
HEMOLYTICUREMICSYNDROME
PURPURA
IstheMCCofrenalfailureinchildren Clo{ngthroughoutthebody,buta[acksthe
Occurs2weeksa|eraboutofgastroenteriRs cerebralvesselsrst(neurosymptoms)
(E.Coli0157:H7)assdwithundercooked Thrombocytopenia
hamburger Associatedwithclopidogreluse
StartswithVomiRngandBloodyDiarrhea VonWillebrandfactoresterasedeciency
Oliguriaandanuriamaydevelop PlasmapharesisisbestiniRalmgmt
Requiressteroids,dialysis,packedRBCsand
PLTs
DIABETES SYPHILIS
VasculiRsd/tincreasedviscosityoftheblood TerRarysyphilisleadstohyperplasRc
Gloveandstockingdistribu,onisclassicof thickeningoftheaorRcwalls
DM Ischemiatoouter2/3ofthewallleadsto
Sorbitolisthesugarcausingneuropathy treebarkappearanceanddestrucRonofthe
vasovasorum(bloodsupplytoaorRcwall)
Leadstoaor,caneurysm
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TAKAYASUSARTERITIS KAWASAKISDISEASE
AorRcarchsyndromeorPulselessdisease Criteriafordiagnosis:
Isalargevessel Presenceoffeverfor5ormoredays+4ofthe
granulomatousvasculu,s following:
thatleadstoinRmal
Cervicallymphadenopathy
brosisandvascular
narrowing Polymorphousrash(mainlytruncal)
MCaectsAsianfemales Generalizedorlocalizeddesquamacon
between1530yr
Bilateralnonsuppuracveconjunccvics
BestindicaRonontheexamis
thepresenceofweakened Changesinmucusmembranes(MClipsand/or
pulses+veryelevatedESR tongue)
KAWASAKISMGMT
IVIGusuallyimprovescondiRongreatly
within24hr
HighdoseaspirinunRlfeversubsides
Lowdoseaspirinfor23monthstoprevent
clo{ng
Immuniza,onforVaricellaandInuenza
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ComplicaRonsofKawasakis TEMPORALARTERITIS
MCandmostworrisomecomplicaRonis InammaRonofthevesselsthatsupplythe
cardiac(coronaryarteryaneurysms) head
CoronaryarteryaneurysmscanleadtoMI Commonlyassociatedwithpolymyalgia
(eveninchildren) rheumaRca
MCseeninpeople>60yrwithjawpainor
**KawasakisdiseaseandRheuma,cFeverare headache+highlyelevatedESR(>60)
the2MCCofacquiredheartdiseasein Ifvisualdisturbancespresent,givesteroids
children** rst,getbiopsy2nd
ANKYLOSINGSPONDYLITIS PSORIATICARTHRITIS
Oneofthe3HLAB27diseases Silverplaquesonextensorsurfaces+arthriRs
Startswithsacroilii,s(lowbackpain)get oftheDIPjoints
xray IfarthriRspresentisHLAB27,ifonarthriRsit
Bamboospine(scarringandbrosisofthe isHLAB13
lumbarspine) Pi{ngofthenailsisamajornding
+veSchoebertest(bendover,lumbarspine Increasesgoutincidencebecauseofgreater
barelymoves) uricacidproducRon
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REITERSSYNDROME POLYARTERITISNODOSA(PAN)
HLAB27(the3rdofthegroup) Aectsmediumsizedvessel(espinGIand
IsapostinfecRousarthriRswiththeclassictriad: renal)
Urethri,s,Conjunc,vi,s,Arthri,s
40%ofcasesareseeninconjuncRonwithHep
B(bigclue)
Urethrics:MCCbychlamydialinfecRon(cant
pee) MostimportantdiagnosRcclueisthe
presenceofpANCA
Tx:TreatunderlyinginfecRon+NSAIDfor
arthriRs
WEGENERSGRANULOMATOSIS GOODPASTURESSYNDROME
Aectsthekidney,lungs,andnosa/sinuses TheMCCofrapidlyprogressive
cANCAisthemarkerANCAsagainstsmalland
mediumsizedvessels glomerulonephrics
CausesrapidlyprogressivegN,whichleadstochronic Aectslungsandkidneys
renalfailure(crescents)(seeninmanycases)
Causesepistaxis,rhiniRs,perforaRon An,glomerularBMan,bodies
Causespulmonary(coinlesions),inltrates,cavitary
lesions,andpulmonaryhemorrhage
**willseelinearancbodiesonElectron
**lifethreateningcondi,onthatrequireslongterm Microscope
immunosuppression**
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LEUKOCYTOCLASTICVASCULITIS CHURGSTRAUSS
VasculiRscausedbydrugallergy IsapulmonaryinltraRonwitheosinophilia
LookforpaRentwhousedsulfaorpenicillin syndrome(PIEsyndrome)
Verynonspecic Seeninchildren,looksexactlylikeasthma
Isthe3rdMCCofPIEsyndrome
CRESTSYNDROMES
Themildestformofscleroderma(involvementis
patchy)
CCalcinosis
COLLAGENVASCULARDISEASES RRaynauds
EEsoophagealdysmoRlity
SSclerodactyly
TTelangiectasis
An,centromerean,bodies(uniquetoCREST
syndromes)
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SCLERODERMA PROGRESSIVESYSTEMICSCLEROSIS
SevereformofCRESTsyndrome,aects Severeformofsclerosisthatleadstoscarring
widespreadareasoftheskinandoneormore oftheliverandotherorgans
internalorgans(bloodvessels,GI,GU) AnRtopoisomeraseanRbody(uniquetoPSS)
Canonlytreatsymptomsastheyoccur
An,smoothmusclean,bodies(anRSCL70)
Kidneysdeveloponionskinningdueto
intermifentHTN
JUVENILERHEUMATOIDARTHRITIS
MIXEDCONNECTIVETISSUEDISEASE
(JRA)
WidevarietyofconnecRveRssuesareaected KnownasSRllsdisease
Thereare2types(RFnegaRvefavorable
Mostimportantndingisthepresenceof prognosis,RFposiRverapidlyprogressing
an,ribonuclearproteinan,body disease)
RFNegacve:2/3ofcasesareRF,onlyaectsa
fewjoints(oligoarRculuar)majorcomplicaRon
isiridocycliRs
RFPosicve:1/3ofcasesareRF+,progresses
rapidlytodebilitaRngdisease,willbewheelchair
bound
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FELTYSDISEASE
FeltysDisease:RA+Leukopenia+
Splenomegaly
BecetsDisease:RA+GIulceraRons(mouthto COLLAGENVASCULARDISEASESw/LOW
anus) COMPLEMENTLEVELS
SjorgensDisease:RA+Xerophthalmia+
Xerostomia
RoAnRbody(ROLaSSA)
POSTSTREPgN
PostStrepGlomerulonephri,s 2weeksa|eraS.PyogenesinfecRon
SerumSickness Mayoccura|erbothastrepthroatANDskin
SubacuteBacterialEndocardi,s strep
SystemicLupusErythematous Producessubepithelialhumps
Membranoprolifera,veGlomerulonephri,s
Cryoglobulinemia
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SERUMSICKNESS SUBACUTEBACTERIALENDOCARDITIS
Ameasleslikeillness MCCpresentsonthemitralvalve
Occurs2weeksa|ervaccinaRon(espMMR MCCbyStrepViridans
vaccine) Seencommonlya|erinvasionofmucosal
surfaces
Requiresprophylaxisbeforedentalsurgery
(Amoxicillinisbest)
5BIGCluestodiagnosing
SYSTEMICLUPUSERYTHEMATOUS MEMBRANOPROLIFERATIVEgN
2ndMCarthriRcdiseaseinmiddleagedfemales MPGNisatermdescribingcomplexdeposits
(a|erRA)
inthekidney
An,bodies:anRSmith,anRdsDNA,anR
cardiolipin Type1hasnormalcomplement(C3nephriRc
An,cardiolipin:CansRmulatetheintrinsic factor)
clo{ngsystem,cancausemulRplespontaneous
aborRonsbyclo{ngtheplacenta,andcanblock Type2haslowcomplement(causesdense
vWF(leadstobleeding) depositdisease)
LUPUSistheONLYvasculiRswithMCCofdeath Tramtrackappearance(membranesplitinto
beingnoncardiacrelated(isd/tkidneyfailure)
twobydeposiRon)
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CRYOGLOBULINEMIA
AnRbodydeposiRonthatcanaectanyvessel
intheenRrebody
UniquefeatureiscoldaggluRninsandIgM
only
Mainndingsinthevigne[e:IgMonly,non
bacterialcause,acuteinammaRononly(ie.
IgM)
PLATELETS
Bleedingfromtheskinormucosalsurfaces=
Problemwithplatelets
Normalcount:150,000350,000
THECLOTTINGCYCLE PLTslast47daysincirculaRon
BleedingintocaviRes=Clopngfactordefects
Intheskinwegetdothemorrhages,aka
Petechiae
Ifpalpableontheskin,itiscalledPurpura
Ifitcausesabruise,itiscalledEcchymoses
Todetectaplateletproblem,testBLEEDINGTIME
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CLOTTINGFACTORS COMPARTMENTSYNDROME
DefectleadstobleedingintocaviRes Bleedingintoaxedspaceleadsto
8caviResintowhichwecanbleed compressionofvasculature
Compartmentsyndrome(swellinginsideaxed Causesthe5Ps:
compartment)5Ps Pain
ClotformaRoninaveinrequiresyoutolookfor Pallor
Virchovstriad(Stasis,Hypercoagulability,
Endothelialdamage) Pulselessness
3MCCofsuddenclotforma,on:FactorVLeiden Poikylothermia(coldlimb)
deciency,Gramvesepsis,Trauma Parasthesia
VIRCHOVSTRIAD 3MCCOFACUTECLOTFORMATION
3thingsthatincreasetheriskofsuddenclot FactorVLeidendeciency(theMCCof
formaRon suddenonsetofclotformaRon)
Hypercoagulablestate Gramnega,vesepsis
Stasis Trama
EndothelialDamage(isthe#1causeofclot
formaRon)
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PRIMARYHEMOSTASIS
Ac,va,onofplatelets:
EndotheliumreleasesvWFandFactorVIII
vWFhelpsendothelialcellsadheretocollagen
onbasementmembrane
vWF,collagen,andRssuefactorwithinthe
endotheliumareexposedtobloodstream
PlateletscontactcollagenorvWF,become
acRve,andclumptogether
PRIMARYHEMOSTASIS SECONDARYHEMOSTASIS
AdhesionandAggrega,on: Coagula,oncascade
PlateletaggregaRonreceptorglycoproteinIIB/IIIa Intrinsicpathway(contactacRvaRonpathway)
(calciumdependentreceptorforbrinogen, measurewithPTT
bronecRn,andvWF) Extrinsicpathway(Rssuefactorpathway)
AcRvatedplateletwilladhereviaglycoproteinIa measurewithPT
tocollagenthatbecomesexposedwith Goal:totakeinacRveenzymeprecursorsand
endothelialdamage theirglycoproteincofactorsandacRvatethemso
AggregaRonandadhesionacttogethertoforma theycancatalyzethefollowingreacRoninthe
plateletplug cascade,withulRmategoalbeingtocreatecross
MyosinandacRnlamentaresRmulatedto linksofbrin
contractduringaggregaRon(reinforcingtheplug)
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INTRINSICPATHWAY EXTRINSICPATHWAY
Startswhenthereisdamagetothevessel AlsoknownastheRssuefactorpathway
COMMONPATHWAY FINALCOMMONPATHWAY
OnceXaismadefromeithertheintrinsicor
extrinsicpathways,itundergoesaseriesof
changesunRlbrinismade
FibrinisthebuildingblockofthehemostaRc
plug
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Oncebrinislaiddown IMPORTANTCOFACTORS
TherearesRllendothelialholesneeding VitaminK
patchingup Calcium/Phospholipid
Endotheliumreleasesendotheliumderived
growthfactors,plateletsreleasePLTderived
growthfactors
GFssRmulatebroblasts,whichrelease
collagentosealupthegaps(requiresATP)
Bradykinindilatesvasculaturetobringmore
ATPsobroblastscanlaydownthecollagen
IMPORTANTREGULATORS VonWillebrandDisease
ProteinC AnchorsfactorVIIItoplatelets
HelpsplateletsanchortotheIbglycoprotein
TissueFactorPathwayInhibitor(TFPI)
vWDisanADdisease
Plasmin vWDinfemalealmostalwayspresentswithheavy
Prostacyclin menstrualbleeding
MildbleedingismanagedwithDDAVP(causing
An,thrombin endotheliumtosecretevWF)
ModeratebleedingismanagedwithCryoprecipitate
SeverebleedingismanagedwithFFP
TestfuncRonwithRistoceRnAggregaRonTest
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HemophiliaA(Factor8) HemophiliaB(Factor9)
Xlinkedrecessive Xlinkedrecessive
PaRentsarelackingfactorVIII
MissingfactorIX
BleedingintocaviRes
PTTiselevated BleedingintocaviRes
MildbleedingismanagedwithDDAVP PTTincreased
Moderatebleedingismanagedwithcryoprecipitate
TestbycheckingthelevelsoffactorIX
Severeorlifethreateningbleedingrequires
concentratedfactor8 AnybleedingrequiresFreshFrozenPlamsa
Testforhemophiliawithfactor8acRvitylevel(<40%is
worrisome)
FIBRINDefects PLASMIN
Clo{ngwillsRlloccur MostpowerfulthrombolyRcinthebody
IsconvertedfromplasminogenviatPA
Woundswillfallapart(dysbrinogenemia)
tPA/Streptokinase/Urokinaseallconvert
MCCisadefectinthebrinstabilizaRonfactor plasminogentoplasmin(bustupclots)
MCpresentaRonisrecurringbleedingfrom Mainlyafacksbrin
theumbilicalcordstump tPAisMCusedbecauseitissaferthantheothers
Streptokinasebindsbrinogen,causesexcessive
Managewithcryoprecipitate bleeding
Urokinaseisusedtokeepfeedingtubesand/or
stulasopen
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FACTORVLEIDENDEFICIENCY DRUGSALTERINGTHEPATHWAY
Autosomaldominant Agatrobanblocksthrombin
IsafactorVvariantthatcannotbeinacRvated CilastazolelevatescAMPintheplatelet
byacRvatedproteinC (decreasingclo{ngability)
LeadstooverproducRonofthrombin,this AspirinirriversiblyblocksCOX1and2
leadstoexcessbringeneraRonandexcessive (blocksthromboxaneproducRon,PLTs
clo{ng renderednonfuncRonal)
Limitedtotheveins(DVTs) Dipyridamole,Clopidogrel,Ticlopidine
IncreasedriskofPEs blocksADPreceptoronplatelet
SIMPLIFIEDOVERVIEWOFTHE
PLATELETMANAGEMENT
CLOTTINGCYCLE
Normalis150,000350,000
Higher=thrombocytosis
Lower=thrombocytopenia
PLT<40,000.Startsteroidtreatment
PLT<20,000.Spontaneousbleedingbegins
PLT<10,000Spontaneousintracerebral
hemorrhages(requiresplenectomy)
Transfuseonlywhentherearesymptomsand/or
BMsuppression
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FOREGUT
Frommouthtobeginningofthe2ndpartof
theduodenum
GASTROINTESTINAL Alsoincludestherespiratorytract(comefrom
samelaminardisc)
Anatomy,Physiology,Pathology Bloodsupply:Celiacartery
Parasympathe,cinnerva,on:Vagusnerve
Sympathe,cinnerva,on:Splancnicnerves
(T5T9)
MIDGUT MIDGUT
From2ndpartofduodenumtosplenicexure RotaRonrequiresacRonofcilia
Developsintheyolksac Primaryciliarydyskinesia(PCD)leadstositus
Undergoesa270rotaRonasitmigratesfromthe inversus50%oftheRme
yolksacintotheabdominalcavity(requiresciliary Kartageners
acRon)
Majororgansaremirrorimaged,andsiton
Bloodsupply:SuperiorMesentericArtery thewrongsideofthethoraciccavity
Parasympathe,cinnerva,on:Vagusnerve
Usuallynotasignicantproblem,but
Sympathe,cinnerva,on:Splancnicnerves(T9 someRmecongenitalcardiacproblemsare
T12) present
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WatershedareaSplenicFlexure HINDGUT
FromSplenicFlexuretotheAnus
Watershedareaatbeginningofthehindgut
Bloodsupply:InferiorMesentericArtery
Parasympathe,cinnerva,on:Pelvic
Splancnicnerve
Sympathe,cinnerva,on:LumbarSplancnic
nerves(L1L2)
THESEQUENCEOFEVENTS IntheBRAIN
Sensoryinforma,onaboutfoodreachesyour
cortex(thought,hearing,smelling,touching,
andtasRngfood)
ResponsetothissensoryinformaRonissent
throughtheCor,cobulbarPathwaybywayof
theVagusnerve
Allbasicurges(notjustfood),canbeover
ridenbythecortex
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ThePinealGlandandFood THEHYPOTHALAMUS
Pinealglandsecretesmelatonin ContainstheHungercenterandtheSaRety
Helpsmaintainapropercircadianrhythm center
Highduringthenight,lowduringtheday Hunger/Feedingcenterinthelateral
TheAAtryptophanisaprecursorfor hypothalamus
Melatonin SaRetycenterlocatedintheventromedial
Foodsrichintryptophanincreasemelatonin nucleusofthalamus
andthustrickthebodyintothinkingitis
nigh{me(ie.Webecomesleepy)
TheHUNGERCENTER THESATIETYCENTER
Lateralhypothalamus Locatedintheventromedialnucleusofthe
SRmulatedwhenthebloodglucoseislow hypothalamus
Damagetothearea=nohunger(anorexia) 2thingss,mulatethiscenter:Elevated
glucoselevelsandmechanicalstretchingof
thestomach
DestrucRonleadstohypothalamicobesity
syndrome(PraderWilli)
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AVERAGEBODYWEIGHTS HYPOTHALAMUS,cont.
At5feet Anteriorhypothalamuscools(viainhibiRonof
Malesshouldaverage106lbs
Femalesshouldaverage100lbs NE)lesiontoanteriorhypothalamuscan
resultinlifethreateninghyperthermia
Forevery1a|er5,weadd5lbs
Ifsmallframeadd15,iflargeframeadd30
Posteriorhypothalamuswarms(damagecan
leadtolifethreateninghypothermia)
NormalBMI18.524.9 ControlsmensescontrolsProgesterone
Overweight:2529
Obese:>30 (progesteroneinuenceshungerweird
MorbidObesity:35 cravingsduringmensesand/orpregnancy)
GIMOTILITYANDSTRESS
Responsetostressisalwaysthesame1st
ParasympatheRcrelease,2ndSympatheRc
release
Parasympathe,c:GImoRlityincrease,
THEORALPHASE
increasedgastricacidproducRon
Sympathe,c:GImoRlitydecreases,
decreasedgastricacidproducRon
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THEORALPHASE PRODUCTIONOFHYPOTONICSALIVA
Salivaryglandsrespondtofoodinthemouth
Paro,dglands(serousCN9)
Lingualglands(mainlyserousCN7)
Sublingualglands(mainlymucinousCN7)
Submandibularglands(allmucinousCN7)
Inputtothesalivaryglands SALIVA
BothsympatheRcandparasympathaRcinputs The1ststepinthedigesRveprocess
Parasympathe,cdrugsincreasesecreRon RichinIgA(isthemainIginmucoussecreRons)
Sympathe,cdrugsdecreasesecreRon Lipasebeginsbreakdownoffats
Amylasebeginscarbbreakdown(breaksalpha
1,4bonds)
LysozymedetergentacRvity
HC03protecRonagainstacidfromfood,drinks,
andreux
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CYSTICFIBROSIS
CFTRgeneonchromosome7,ismutated,
rendersthechloridechanneltransportnon
funcRonal
WHILEWERETALKINGABOUTCREATING
MutaRonaectschloridelevelsinthesweat
HYPOTONICSALIVALETSDISCUSSCYSTIC glands,aswellasthelungs,pancreas,sinuses,
FIBROSIS andGI
Chronicsinopulmonaryinfec,ons
ChronicGImanifesta,ons
Simplestdiagnoscctest:Chloridesweatlevel
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THETEETH MUSCLESOFMASTICATION
Incisors:forcu{ng(seenby1015mnth)
Bicuspids:forchopping(seenby1518mnth)
Molars:forgrinding(seenby1824mnth)
SWALLOWING SWALLOWINGPharyngealPhase
2PHASES:1stphasegoesfromfoodtouching A\ermas,ca,oniscompleted
TroughformaRon
thelipstothebolusoffooddroppingintothe Startofpharyngealphase
esophagus,2ndphasegoesfrombolus Closureofnasopharynx
droppingintoesophagustoreachingthe Pharynxpreparestoreceivebolus
Auditorytubesopen(aconsequence)
stomach Closureoforopharynx
Closureoflarynx
HyoidelevaRon
Bolustransitthroughpharynx
Esophagealphasebegins
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SWALLOWINGEsophagealPhase ESOPHAGEALANATOMY
EsophagealPeristalsis:
TheUESrelaxesallowingbolustoenter
BoluspropelleddownwardiniRallybyskeletal
muscle(CNX),thensmoothmuscle.
BoluseventuallymovesthrougharelaxedLES
RelaxaconPhase:
Oncefoodentersstomach,thepharynxand
larynxrelaxviarecoilmechanism
ESOPHAGEALPATHOLOGY
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ODYNOPHAGIA DYSPHAGIA
ODYNOPHAGIA:painfulswallowing DYSPHAGIA:dicultyswallowing(not
O|enduetoinammaRon painful)
Seeninimmunosuppression(MCCandida, Progressiveworseningislikelyesophageal
CMVis2ndMCC) cancer(ie.Solidsrst,liquidssecond)
HSVmaybeacause(willseeCowdryAbodies ChronicdysphagiaislikelyAchalasia
intracytoplasmicinclusionswitheosinophils) Paradoxicaldysphagia(problemonlywith
Inahealthyindividual,theMCCof liquids),likelyAchalasia
Odynophagiaisdrugs
ACHALASIA
FailureoftheLEStorelax
DuetolossofAuerbachsplexus(myentericplexus)
MaybecausedbyChagasdisease
BirdBeaksignonbariumswallowduetodistalstenosis
Dysphagiadevelopsprogressivelyandbecomeschronic
Isassociatedwithanincreasedriskofesophageal
carcinoma
CantreatwithCCBsorNitrates(increaseriskofGERD)
CangiveBotox,whichmaintainsrelaxaRonfor46months
(lessriskofGERD)
Cantreatsurgicallywithmechanicaldila,on(riskof
Boerhaavessyndrome)
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MalloryWeisTearsvs.Boerhaaves
BARRETTSESOPHAGUS Syndrome
MalloryWeisSyndrome:tearingofthemucosaatthegastro
Metaplasiaofcolumnarepitheliuminto esophagealjuncRon,causedbysevereretching,coughing,or
squamousepitheliuminthedistalesophagus vomiRng.
Associatedwithalcoholism,eaRngdisorders,andhiatalhernias
Chronicexposuretogastricacidcausesthis Stopsabruptlyin2448hr
change(GERD) BoerhaavesSyndrome:esophagealrupture
Increasesriskof Isamedicalemergency
ofcasesareduetomedicalinstrumenterror(endoscopy),are
adenocarcinoma duetosuddenincreaseinintraesophagealpressure
Hammanssign(crunchheardoverprecordium,synchronouswith
eachheartbeat)
ZENKERSDIVERTICULUM
AfalsediverRculumthatsitsrightabovethe
UES(ie.Isinthelowerpharynx,abovethe
cricopharyngealmuscle)
O|encongenital,o|encausedbyexcessive
pressureinthelowerpharynx(weakest
porRonofthepharyngealwall)
Dysphagia,halitosis,andcoughingup
undigestedfoodaremajorclues
ManypaRentsremainAsx
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ESOPHAGEALWEBS PlummerVinsonSyndrome
PlummerVinsonSyndrome(upper AcondiRonthatpresentswithacommontriad:
Dysphagia,Irondeciencyanemia,andGlossi,s
esophagus)
MCinmiddleagedfemales
SchatzkiRings(loweresophagus) Dysphagia/Odynophagia:intermifent,usually
onlytosolid
Iso|enconsideredtobeapremalignant
condiRon
Treatunderlyingcauseofanemia,modifythediet
tomakepaRentcomfortable,resectringsonlyif
severeodynophagia
SchatzkiRings
Esophagealwebsintheloweresophagus
(fewcmaboveloweresophagealjuncRon)
MCndingsareintermifentdysphagiaand/or
feelingsoffoodsRckingwhenswallowing
SteakhouseSyndrome=whenbolusgets
stuck
MostcasesareAsxanddonotworsenover
Rme
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DIFFUSEESOPHAGEALSPASM
UncoordinatedcontracRonsofthewhole
esophagealbody(LESremainsintactand
relaxed)
CausesdysphagiaandregurgitaRon
SeverechestpainthatmimicsanMI
TriggeredbyverycoldorHOTbeverages
LookslikeaCorkscrewonimaging
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CHOANALATRESIA
CongenitalcondiRonwherebyRssueobstructs
oneorbothofthenasalpassages(so|Rssueor
bonyRssue)
Unilateralchoanalatresiamaygoundetected
unRllaterinlife,whilebilateralchoanalatresia
isevidentimmediatelyoncebabystopscrying
Cyanosiswhentheyarefeedingisclassicclue
DxatbirthbyinserRonofnasalcatheter(cannot
penetrate),conrmwithCT
ESPHAGEALATRESIAWITHFISTULAS
Failureoffusionofthetracheoesophageal
ridgesduringthe3rdweekofembryogenesis
RiskofaspiraRonorairinthestomach
MCpresentswithvomiRng/chokingonthe
rstfeeding(typeCismostcommon)
TypeE(orH)hasapatentesophaguswitha
stulatothetrachea(chokingandcoughing
withfeeding,notvomiRng)
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GERD ESOPHAGEALTESTING
AbnormalrelaxaRonofLESallowsstomach WhenisanUpperEndoscopytherightchoice?
contents/acidstomoveintotheloweresophagus
Associatedwithhiatalhernia WhenisaBariumSwallowtherightchoice?
MCsi/sx:heartburn,regurgitaRonofstomach WhenisEsophagealManometrytheright
contents,chroniccough,erosionofdental choice?
enamel,laryngiRs/pharyngiRs
Complica,ons:EsophagiRs,Strictures,Barrefs
esophagus,Adenocarcinoma
PPIsarebothdiagnosRcandtherapeuRc
GoldStandard:pHmonitoring
THESTOMACH/UPPERGI
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RECEPTIVERELAXATIONOFTHESTOMACH GASTRICEMPTYING
Mechanoreceptorsdetectstretch Takesapprox3hr(avg)
Vasovagalreex(AerentEerent) RateofemptyingisRghtlyregulatedtoallow
enoughneutralizaRonofduodenalacidto
VIPreleasedfrompostganglionicvagalnerve
allowforopRmalabsorpRon
bers
2mainfactorsthatslowgastricemptying:
Acid(H+)induodenum,FATSinthestomach
FATismediatedbyCCK(secretedin
duodenum)
H+ismediatedbymyentericplexusreexes
IMPORTANTDIGESTIVETOOLS
HydrochloricAcid:workstoreducepHso
pepsinogenisacRvatedtopepsin
Pepsinogen:isaninacRveenzyme,needs
highacidicenvironmenttoconverttothe
acRveformpepsin,whichisnecessaryfor
proteindigesRon
IntrinsicFactor:forB12absorpRoninIleum
Mucus:protectsthestomachliningfromHCl
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BODYOFSTOMACH
ANTRUMOFSTOMACH
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PROTECTINGTHESTOMACH
Mucus:fromthegobletcells Misoprostyl:replacesprostaglandinsthatgo
Prostaglandins:fromthearachidonicacid missingwhentakingNSAID
pathway Alprostadil:vasodilatoryproperResthat
HC03 keepsaPDAopeninanewborn
COX2inhibitorsinclude
Celecoxibonlyonele|onthemarket
PARIETALCELLS
ReleaseHClandIntrinsicFactor
CanbesRmulatedby3mechanisms:Vagus,Mast
cells,andGcells
VagussecretesAchtosRmulatethemuscarinic
receptorssRmulatesparietalcellsreleases
HCl
MastCellsreleasehistaminesRmulatesH2
receptors(inhibitwithCimeRdine)
GCellsreleasegastrinsRmulatesHCl
secreRon
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STOMACHPATHOLOGY
GASTRITIS
IstheMCCofupperGIbleedsinolder
children,teens,andadults
Duetosupercialerosions
TYPEAlocatedinbodyofstomach(4As)
TYPEBlocatedinantrumofstomach
(breakdowninbarrierprotecRon)
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PEPTICULCERDISEASE PUD,cont.
GastricUlcer:painisworseduringameal DuodenalUlcer:painimproveswithmeal
Locatedantheantrumofthestomach Painworsens3045minutesa|erameal
AssociatedwithH.Pylori70%oftheRme Painworsensatnight(d/tMoRlin)
Associatedwithcancer20%oftheRme AssociatedwithH.Pylori95%oftheRme
Endoscopyisrequiredtor/ocancer Cancerriskextremelylow(<1%)
H.PyloritesRngwitheitherbloodtestsfor Weightgainwithduodenalulcerisnot
anRbodies,ureasebreathtest,orstoolsample uncommon
test.
H.PYLORITREATMENT SurgeryforPUD??
2An,bio,cs+ProtonPumpInhibitor Surgeryisindicatedforthefollowing4
Requiredfor2weeks reasons(IHOP)
PPIusedtodecreaseacidtohelpthe Intractablepain
damagedRssueheal Hemorrhage
2AbsweuseamulRdrugregimento Obstruccon(r/owithxray,airuidlevels)
preventresistance,aswellstudiesshowthat Perforacon(r/owithxray,airunder
recurrenceisveryhighwithsingledrug diaphragm)
regimens
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BEZOARmassofindigesRblematerial
25yroldfemalehastrichophagia(eacnghair), IsMChair
presentstotheERwithsevereupperGIpain. MaycausegastricoutletobstrucRon
Endoscopyrevealsagastricoutlet Treatment:Endoscopicremoval
obstruc,on.Whatisthetechnicaltermfor
thisproblem?
HIATALHERNIAS
Partofthestomachmovesabovethediaphragm
SlidingHernia:MCtype(95%),thewhole
gastroesophagealjuncRonmovesabovethediaphgram
alongwiththestomach
MCproblemencounteredisGERD
Notreatmentisnecessary
RollingHernia:defectindiaphgramallowspartof
stomachtoherniateabovediaphragm
AkaParaesophageal
RequiressurgicalcorrecRonastheresariskof
strangulaRonand/orcompressionofesophagus
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MENETRIERESDISEASE
MCCofHypoalbuminemia MCCofHyperalbuminemia
CondiRonwherethestomachhasgobletcell
hyperplasia+enlargedrugalfolds Liverdisease DehydraRon(istheMCC)
NephroRcsyndrome VitaminAtoxicity
ProteinsleakthroughtheGI Proteinlosingenteropathy
MalabsorpRon
LookslikeanephroRcsyndromewithlow MalnutriRon
Laterinpregnancy
albumin
Lowalbuminleadstoincreasein
unconjugatedbilirubin,decreaseintotalT4,
lowcalcium
PYLORICSTENOSIS HormonesoftheDuodenum
Hypertrophyofthepylorus SecreRn
MCpresentsinthe3rd4thweekoflifewith CCK
projecRlevomiRng MoRlin
PathognomonicOliveSign(palpableupper GIP
abdominalmass) VIP
Uponsuspicion,doanU/S
SomatostaRn
Treatment:correctuids/electrolytes,then Enterokinase
gotosurgery(pyloromyotomy)
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PANCREATICENZYMES
Zymogens:areinacRveenzymesthatrequire
acRvaRon(inacRvetokeepthepancreassafe)
AMYLASE:breaksthe1,4glucosidicbonds
inlactose,sucrose,maltose,andalpha
dextrins(fructosehasowntransportsystem)
DISACCHARIDASES:lactase,sucrase,maltase,
alphadextrinase
PANCREATITIS RansonsCriteria
IstheMCCofsevereabdominalpain Asetofcriteriathathelpuspredictthe
Presentsasmidepigastricpainthatradiates prognosisofpancreaRRs(atadmission,at2
totheback days)
MCCinadults:Alcohol,thenGallstones
MCCinchildren:Abdtrauma,theninfecRons
Dx:Serumlipase/amylase,abdominalxray
Mgmt:NPO,NGtube,IVNS,Opioid,Abdxray
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PANCREATITISComplicaRons ComplicaRons,cont.
PSEUDOCYST:acollecRonofpancreaRc HEMORRHAGICPANCREATITIS:
enzymes,necroRcdebris,andhemolyzed Bleedingintotheretroperitonealspace
bloodinapseudocyst Mayseeeitherofthefollowing:GreyTurner
Pseudocystcontainsnoepitheliallining signand/orCullensign
RecurringboutsofpancreaRRsmimicking GreyTurnerankbruising
symptomswarrantsinvesRgaRon Cullensignperiumbilicalbruising
Dx:U/Sisbestandeasiestimagingtest Dx:CTscan
Mgmt:DrainageifsymptomaRc
GALLSTONES
RUQpain(colicky)istheMCsymptom
GALLSTONES 4Fs(female,ferRle,fat,forty)
Murphyssignposi,ve(inspiratoryarrestupon
RUQpalpaRon)
80%ofstonesarecholesterolstones(d/texcess
bilirubin),20%aremadeofcalciumbilirubinate
(d/texcessbilirubin)
90%ofstonesarelodgedinthecys,cduct(Alk
Phosphisnormal),10%lodgedinthecommon
bileduct(AlkPhosphincreased)
172
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GALLSTONESMgmt
Ifnosymptoms,donothing
Minorcasescanbemanagedwith
UrsodeoxycholicAcid(breaksupthestone)
Diagnosis:1stU/S,ifinconclusivedoHIDA
scan(injectsradioacRvedye,visualizetheGB)
Treatment:MCsurgicalprocedureisa
laparoscopiccholecystectomy,lesscommonly
usedistheERCP
FATDIGESTION
Noneinthemouth
MostinthesmallintesRne
LecithinandBileSaltshelpemulsifyfats
BILESALTS:80%forfatemulsicaRon,20%
reabsorbedintrahepaRcally
173
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LinkingTGstoDKA deNOVOCHOLESTEROLSYNTHESIS
174
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FAMILIALHYPERCHOLESTEROLEMIA FAMILIALHYPERCHOLESTEROLEMIAS
CausedbyveryhighLDLlevels(LDLreceptor Class1:LDLreceptorabsent
defectorApoB(B100)defect) Class2:LDLreceptornottransportedto
appropriateplace(fromERtoGolgitocells
PaRentsareatriskofearlycardiovascular surface)
disease
Class3:LDLcantbindreceptord/tB100defect
Xanthelasmas Class4:LDLboundtoclathrinpitsdoesntwork
Atherosclerosisatearlyages appropriately
Class5:LDLreceptorsarenotrecycledtothecell
surface
HYPERLIPIDEMIAS
Occursbecausetheresadefectinlipoprotein
metabolism
MaygetelevaRonofTGsorcholesterol,or
BOTH
IstheMCdyslipidemia
Primary:geneRc
Secondary:duetounderlyingcause(DM)
175
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FAMILIALHYPERLIPIDEMIAS HYPERTRIGLYCERIDEMIA
Type1:ElevatedChylomicronsd/tdefecRve ElevatedlevelsofTGs
LipoproteinLipase Mild/moderatecasesareusuallyAsx
Type2a:IncreasedLDLd/tnonfuncRonalB100 SeverecasesmaypresentwithLipemiaReRnalis
Type2b:MCform,IncreasedLDLandVLDLd/t anderupRvexanthomas
receptorineciency(obesityrelated) Iscausedbylifestylefactors(diet,obesity,alcohol
Type3:IDLelevatedd/tlackofAPOE use,autoimmunediseases)
Type4:IncreasedVLDLd/tLipoproteinLipase Primarypreven,oninvolvesdietary
problem modicaRons,includingomega3FAs
Type5:IncreasedVLDLandChylomicronsd/t Secondarypreven,oninvolvestheuseof
decreaseinC2 medicaRons(Gembrozil,StaRn,orNiacin)
BILIRUBIN INTRAVASCULARHEMOLYSIS
Thebreakdownproductofhememetabolism VasculiRs
Unconjucated(indirect):hemeisturnedinto Schistocytes
unconjugatedbilirubininthereRculoendothelial
cellsofthespleen Haptoglobinlow
Notsolubleinwater
CancrossBBB(istoxictoCNS)
Conjucated(direct):conjugatedintheliverby
addiRonofglucuronicacid
Iswatersoluble
176
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EXTRAVASCULARHEMOLYSIS TheConjugaRonCycle
Splenomegaly
RBCmembranedefect
Autoimmuneprocess
JAUNDICE JAUNDICE
increasedbilirubinduetoavarietyof UNCONJUAGEDBILIRUBIN:
potenRalcauses HemolyRccauses
Gilbertssyndrome
Prehepa,c:increasedhemolysisofRBCs CrigglerNajjarType1(fatalearlyinlife)
(unconjugatedbilirubin)
Intrahepa,c:liverhasreducedabilityto CONJUGATEDBILIRUBIN:
metabolizeandexcretebilirubin,leadingto ObstrucRvejaundice
increaseinunconjugatedbilirubin CrigglerNajjarType2
Posthepa,c:obstrucRonpreventsdrainage DubinJohnsonSyndrome
RotorsSyndrome
frombiliarysystem
177
11/26/11
CHOLESTATICJAUNDICE THECOLON
NewbornscholeductalcystORbiliaryatresia
ChildrenandadultspancreaRRs,gallstones,
sclerosingcholangiRs,primarybiliarycirrhosis
OlderadultspancreaRccancer
VOLVULUS
Twis,ngofasegmentofbowelaroundits
mesentery
ChildrenMCintheileum(congenitalmalrotaRon)
AdultsMCinthesigmoid
Xrayshowsakidneybeanshape,withproximal
dilaRonofintesRnes
Currantjellystool
Treatwithbariumenema
178
11/26/11
DIVERTICULOSIS/DIVERTICULITIS
DIVERTICULOSIS:presenceofsevereal DIVERTICULITIS:diverRcularinammaRon
diverRculainthecolon Causedbyfecolithcaughtintheoutpouching
SeenMCinpaRents>60yrofage InammaRonleadstoLLQpain
Increasedintraluminalpressure+focal PossiblecomplicaRonsincludePerforaRon,
weaknessesofthecolonicwall PeritoniRs,formaRonofAbscess,orStenosis
Associatedwithalowberdiet oftheBowel
Commoncauseofpainlessbleeding
INTUSSUSCEPTION
Telescopingofonesegmentofbowelinto
another
MClocaRonisattheileocecaljuncRon
N/V,andsausageshapedmassisMC
presentaRon
Treatwithsigmoidocopyandrectaltube
placement
179
11/26/11
THEAPPENDIX THECOLON
Smallappendageafachedtothececum CECUM:rstandlargestpartofthecolon
AsofnowithasnoknownfuncRon Cancerherecarriesthepoorestprognosis
ASCENDING:lastareawhereuidsandelectrolytes
areabsorbed(manyNa/Kpumps)
APPENDICITIS:inammaRoncausedbyfecolith TRANSVERSE:containshaustraRons(primary
Beginsasperiumbilicalpain,seflesintheRLQat peristalsis),massmovementbasedonstretch,splenic
McBurneyspoint exure(watershedarea)
Mgmt:NPO,NGtube,IVNS,Meperidine, DESCENDING:haustraRonsandmassmovement
Imaging) SIGMOID:sitsata90anglewithdescendingcolon
Ifnecessary,appendectomyshouldbedone andrectum(formedbypubococcygeusmuscle)
ABSORPTIONREVIEW HEMORRHOIDS
INTERNAL:sitabovethepecRnateline
Nopain
Commoncauseofpainlessrectalbleeding
EXTERNAL:sitbelowthepecRnateline
Painful/itchy
Mgmt:Sitzbath,increasedberdiet,
hemorrhoidalcream
180
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INFLAMMATORYBOWELDISEASES GIPHARMACOLOGY
CROHNSDISEASE ULCERATIVECOLITIS
QuickReview
Morecommoninwomen Morecommoninmen
Transmural Hematochezia PPIs
Granulomatous Mucosal H2blockers
Creepingfat Startsinrectum(movingproximally)
Cobblestoning Pseudopolyps Calciumcarbonate
Skiplesions ConRnuous SucralfateandBismuth
CompleteGItract(mouthtoanus) HLAB27 Simethicone
Startsinileum Toxicmegacolon Loperamide
Melena Leadpipecolon
Fistulas 10%riskofcancerat10yr
Bulkingagents
Pseudopolyps Mineraloil
Cissapride/Metachlopramide
Sulfasalazine
MCCofupperGIbleeds
Newbornsswallowedmaternalblood
Childrensepistaxis
HIGHYIELDGINUGGETS AdultsgastriRs
MassiveupperGIbleedChildren:Meckels
diverRculum,Adults:PUD
181
11/26/11
MCCoflowerGIbleeds MCCofupperGIobstrucRon
Newbornsswallowedmaternalblood Newborns:
Choanalatresia(cyanoRcwithfeeding)
Infantsanalssures
TEstula(ctypemostcommon)
Childrenpolyps Duodenalatresia(Downs,doublebubblesign)
AdultsIBD
Elderlyangiodysplasiasorcancer At34wksofage:
Pyloricstenosis(projecRlevomiRnga|erfeeding,
Olivesigninupperabdomen
Correctelectrolytesrst,surgerysecond
MCCoflowerGIobstrucRon
At46mnthofageAchalasia In1styroflifeHirschsprungsdisease(Absent
myentericplexus),getdistalbowelenlargement
(megacolon)
6mnth2yrIntussuscepRon(sausage
shapedmass) 1yr40yrAdhesions
>40yrAdhesions
2yr40yrAdesions(*MCCpostsurgical) ObsRpaRon(infrequentpassageofhardstool)
DiverRculiRs(inammaRonleadingtoscarring)
cancer
182
11/26/11
AtaxiaTelangiectasia
Cerebellarproblemsinboys510yr+spider
angiomasintheGItract(givesbloodinstool)
HIGHYIELDGINUGGETS
HeavyChainDisease CeliacSprue
VeryhighIgAonbowelbiopsy MalabsorpRonleadingtosteatorrhea
AnRgliadin
AnRgluten
Injejunum
183
11/26/11
TropicalSprue NecroRzingEnterocoliRs
Usuallyinileum(difromCeliacwhichis Excessivebleedingatthesplenicexure
jejunum)
Willhavefatsolublevitamindeciencies
WillhavevitaminB12deciency
IrritableBowelSyndrome SpasRcColon
Femalesintheir20s Frequentboutofdiarrhea
Usuallyastressed/anxiouspersonality
AlternaRngboutsofconsRpaRonanddiarrhea
Adiagnosisofexclusion
Prescribebersupplement
184
11/26/11
WhipplesDisease ToxicMegacolon
SmallintesRnescantabsorbnutrients ComplicaRonMCofIBDs
CausedbytrophymaWhippelii CanbeduetoC.Dicile
Jointpainisrstsymptom Treatwithdecompressiontechniques
Mainlyinmiddleagedmen
BowelIschemia
SplenicexureisMClocaRon
MCCisatherosclerosis
HIGHYIELDGIMANAGEMENT
185
11/26/11
UreaBreathTest SudanBlackStain
ForconrmaRonofH.PylorieradicaRon ForthedetecRonoffatinthestool
Neverthebesttest WhenmalabsorpRonissuspected
Whenstoolisgreasy,pale,ormalodorous
AnRGliadinanRbodies SerumTrypsinogenConcentraRon
Todetectwheatorglutenallergies Checkthisa|erdoingSudanBlackhas
ForthedetecRonofCeliacdisease(aectsthe conrmedfatmalabsorpRon
jejunum) Lowlevelsoftrypsinogenfromaburnedout
Goldstandardforceliacdiseaseisbiopsy pancreas
186
11/26/11
DXylosetest Ceruloplasmin
Teststhesmallbowelsabilitytoabsorb(ie. BestiniRaltestforWilsonsdisease
Microvilliworking) Lowceruloplasmin=Wilsons
Ifabsorbedlevelsarehighintheurine,and ConsiderthiswhentherearebothhepaRc+
micmrovilliareworking psychsymptomstogether
Ifimproperlyabsorbeditwillmovethrough Goldstandardisliverbiopsy
andoutthefeces(lowurinelevels)
GoodfordetecRonofWhipplesdisease,
Celiacdisease,orTropicalSprue
Lipase/Amylase AnRSmoothMuscleAnRbodies
BestiniRaltestforacutepancreaRRs BestiniRaltestforautoimmunehepaRRs
LipaseismorespecicforpancreaRRs Goldstandarisliverbiopsy
MostaccuratetestforpancreaRRsis
abdominalCT
187
11/26/11
AnRMitochondrialAnRbodies PeriodicAcidShi|(PAS)Staining
BestiniRaltestforprimarybiliarycirrhosis Mostaccuratestaintoapplytoasmallbowel
Mostaccuratetestisabiopsyoftheliver biopsy
UsedwhenWhipplesdiseaseissuspected
ENDOFGI
188

WEEK 2
9/17/11
SOURCESOFENERGY
PROTEINS
FATS
BIOCHEMISTRY SUGARS
PROTEINS FATSANDSUGARS
Mainintracellularbuer Moreonthemlater
Madeofaminogroup(NH3+)andacarboxyl
group(COOH)
ExcepJon:Prolineisanimino
Proline=kinks,bends,twists,andturns
Findlotsofprolineinhair,bloodvessels,and
theGItract
1
9/17/11
MASTERINGACIDS&BASES ACIDS&BASES
WearegoingtoactuallyLEARNwhatitall ACID:pKa<7
meanssoyoucanunderstandhowtoapplyit StartsasCOOH(neutral)
allacrossmedicine
WhenitlosesaH+itbecomescharged
Wecanapplytheseprinciplesto
pharmacology,paJentmanagement,and Strongacid:pKa13
preventaJvemedicine Weakacid:pKa47
Ifwehave2acids,theonethatismoreacidic
willbehavelikeanacidandtheotherbehaves
morebasic(anviceversa)
ACIDS&BASES ACIDS&BASES
BASE:pKa>7 Acoupleimportantpointstounderstand
StartsasNH3+(charged) Chargedmoleculescannotcrossmembranes
WhenitlosesanH+itbecomesneutral (theylosebioavailability)
Weakbase:pKa710 Neutralmoleculescancrossmembranes
Strongbase:pKa>10 (havegoodbioavailability)
ThemostimportantbaseinmedicineisHC03
(bicarb)whichisourmainextracellular
buer
2
9/17/11
3IMPORTANTBIOCHEMISTRYMUST
THEMAJORITYOFDRUGS
UNDERSTANDDEFINITIONS
1. Dissocia:onmeanstoloseanH+(lose HavepKrangingfrom49
proton) Areacids
2. Solublemeansitischarged/polar(water Theimportanceofknowingthiswillcomeinto
soluble) playshortly
3. Bioavailablemeansitisneutral
**onceyouunderstandthese,youllhave
masteredmanythingswithoutknowingit**
ACIDSINTHEBEGINNING ACIDSONCETHEYDISSOCIATE
Theystartoutneutral(COOH) GainanegaJvecharge(COO)
Havealonghalflife Gainssolubility
Easilycrossmembranes Losesitsbioavailability
EasilyabsorbedintotheJssues
HighCNStoxicity(duetoeasyabsorpJon)
CYP450metabolismtoxictotheliver
3
9/17/11
BASESINTHEBEGINNING BASESONCETHEYDISSOCIATE
Startoutcharged(NH3+) Theylosetheir+vechargeandbecome
Haveshorthalflife neutral
HaveahardJmecrossingmembranes Losesolubility(nolongersolubleinwater)
LowCNSandlivertoxiciJes Gainbioavailability(cancrossmembranes)
Metabolizedinthekidney
Eliminatebygivinguidstoushitout
HENDERSONHASSELBALCH
ONTOEVERYBODYSFAVORITE.. Wedonthavetoknowhowtoderiveit
Wejusthavetobeabletoapplyit
THEHENDERSONHASSELBALCHEQUATION ItwontbegiventoyouontheUSMLE,butif
youunderstandwhatitsallaboutyoullsee
thattheapplicaJonisallovertheexam!
4
9/17/11
HENDERSONHASSELBALCHEQUATION HENDERSONHASSELBALCHEQUATION
Whatiftheydontgiveyousuchasstraight
forwardquesJon?
5
9/17/11
Butwaitwhatdothesepercentages
represent??
Arewedealingwithanacidtheyrepresent
thechargedform(keepitavailablebykeeping
pH2belowpK)
Arewedealingwithabasetheyrepresent
theneutralform(keepitavailablebykeeping
pH2abovepK)
LETSAPPLYIT LETSAPPLYIT
AspirinhasapKofapproximately4howare Whydowetellpeopletoeatanaspirinatthe
wegoingtoensureitgetsmaximally rstsignofstrokeorMI?
absorbed?
6
9/17/11
LETSAPPLYIT LETSAPPLYIT
PaJentwhoisonregulardosesofaspirin PaJentwhoisonregulardosesofaspirin
comesintodayandheappearstoxic,whathas comesintodayandheappearstoxic,whathas
probablyhappenedrelaJngtohismedicaJon? probablyhappenedrelaJngtohismedicaJon?
CAUSTICINGESTION CAUSTICINGESTION
Mixingofastrongacidorstrongbasewiththe StrongbaseingesJon
oppositecausesastrongreacJon AcuteconcernsareperforaJonandbleeding
Below4orabove9dontmix Chronicconcernsarescarringandstricture
Mixingacidwithstrongbase,orbasewith formaJons(aper36months)
strongacidwillcausemassiveheatrelease Strongbases:Drano,LiquidPlumr,Hair
Strongbasewithanacidistheworst products
StrongbaseingesJonendoscopy
7
9/17/11
TAKETHEDRUGONANEMPTY
ANTIBIOTICS
STOMACH
Youvebeentoldtotakeadrugonanempty WhatifweputourpaJentonanacidic
stomachisitanacidorabase? anJbioJc,andhecomesbacktoseeusandhe
Youvebeentoldtotakeadrugwithfoodis isntgernganybeser?
itanacidorabase? Tetracyclinesanduoroquinolonesarestrong
acidsmustbetakenonanemptystomach
ENTERICCOATEDASPIRIN MIXINGDRUGSANDALCOHOL
WeallknowhowaspirincancauseGIproblems Alcoholisanacid
Sowedevelopawaytobypassthestomach Mixingdrugsandalcoholmeansgreater
Wraptheaspirininabasewhy? absorpJon
Basesremainchargedintheacidicstomach Remembermostdrugsareacidsthisiswhy
TheypassintotheGIanddontlosechargesunJl weshouldnevermixdrugswithalcohol
thejejunum (especiallystrongerprescripJondrugs)
OuterlayerisnowfatsolubleandsJckstotheGI
wallallowingtheaspirintoabsorbintact
8
9/17/11
INGESTIONOFANUNKNOWNDRUG ACIDSWENEEDTOKNOW
Whenthisoccurs,wehavetogowiththe Aspirin
mostlikelyoccurrenceacids Barbiturates
WhatwethendoishavethepaJentingest TricyclicanJdepressants
acJvatedcharcoal(itisabase) myoglobin
Since90%ofdrugsareacids,wellsave90%of
ourpaJentswhoingestanunknowndrug
Youneverwanttotakethechanceofdoing
NOTHING
3BLOODGASESWEMUST BLOODGASCHANGESWITHASPIRIN
UNDERSTANDFROMASAINGESTION INGESTION
1strespiratoryalkalosis
2ndmetabolicacidosis
Calledcombinedrespiratoryalkalosisand
metabolicacidosis
Lateconsequence:MixedAcidosis
TreatmentforanaspirinODgivethembases
(milk,alkaseltzer,bakingsoda)
9
9/17/11
BARBITURATES BASESWEMUSTKNOW
Barbituratesworkbyincreasingtheamountof Amphetamines
GABA(increasethefrequencyofchloride Hallucinogens:LSD,PCP,ECSTACY
channelopening) Methylphenidate(Ritalin)
THEISOELECTRICPOINT
IsthepHatwhichthereisnonetchargeona
molecule(Zwiserion)
NomovementtowardcathodeORanode
Thereisnoneedtocomplicatethiswhole
process,soletsgetinto3strategiesbasedon
simpleandcomplexisoelectricgraphs
10
9/17/11
THEISOELECTRICPOINT THEEASYISOELECTRICPOINT
Step1countthe#ofNH2s
Step2movetothefarlepoftheCOOs
Step3countfromRLthe#ofNH2syou
have
Step4Addthevalueofthe2COOsand
divideby2
THEEASYISOELECTRICPOINT THECOMPLEXISOELECTRICPOINT
11
9/17/11
THEAMINOACIDS GLYCINE
Size Isthesmallestaminoacid
Structures HasNOchiralcarbon(isassymetric)
Charges GlycineistheinhibitoryNTinthespinalcord
Specialfeatures
ImportantmedicalconnecJons
DontwasteJmememorizingstructures(just
knowtheexcepJons)
AROMATICAMINOACIDS AROMATICAMINOACIDS
Phenylalanine(Phe)
Tryptophan(Trp)
Tyrosine(Tyr)
TheyhavearomaJcrings
TheyarerecognizedbytherestricJonenzyme
chymotrypsin(moreonthislater)
12
9/17/11
BASICAMINOACIDS
Lysine(Lys)
Arganine(Arg)
TheycontainanextrachargeviaNH3+(so
theymovetowardsthecathode)
RecognizedbytherestricJonenzyme
trypsin
ACIDICAMINOACIDS
Aspar:cAcid(Asp)NMDApathway
GlutamicAcid(Glu)NMDApathway
TheseAAshaveanextranegaJvecharge
(COO)
13
9/17/11
SULFURCONTAININGAAS
Cysteine(Cys)
Methionine(Met)
Theycontainsulfur
Theyhelpformdisuldebonds
4hormoneshighindisuldebonds
AMINOACIDSFORMINGNITROGEN
BONDS
Asparagine(Asn)
Glutamine(Gln)
14
9/17/11
AMINOACIDSINVOLVEDINOBONDS
Serine(Ser)
Threonine(Thr)
Tyrosine(Tyr)
TheyareinvolvedinObonds(asachto
oxygen)
SerineissmallandinvolvedinmanyacJve
sites
Thereisaserineprotease
BRACHEDCHAINAMINOACIDS
Leucine(Leu)
Isoleucine(Ile)
Valine(Val)
3ofthe9essenJalAAs
Absenceofbranchedchainalphaketoacid
DHcomplexleadstobuildupofBCAAs
MapleSyrupUrineDisease
15
9/17/11
TRYPTOPHAN(TRP)
IstheprecursorforSerotonin(5HT)and
Niacin
5HTcanconverttomelatonin(Turkeydinner?)
Serotoninsyndrome(ushing),Niacin
(Flushing)
Triptandrugsmimictheeectsof5HT
Sumatriptan
AnessenJalaminoacid
TYROSINE(TYR)
Precursorforcatecholamines(NE,Epi,DA)
Isaproteogenicaminoacid
InvolvedinsignaltransducJoninproteins
Canbesynthesizedfromphenylalanin
BreakdownofcatecholaminesbyMAOand
COMT(toomuchassociatedwithdepression)
16
9/17/11
KETOGENICAMINOACIDS GABA
Leucine(Leu) H+(acidosis)
Lysine(Lys) NH3(urea)
Thesecanbeconvertedintoketonebodiesvia NH4+(ammonia)
ketogenesis(pHdecreases)
Ketonesusedby:brain,heart,andkidneys NH3+H+NH4++AKGGlutamateGABA
BrokendowntoormadefromAcetylCoA
INDICATIONSFORDIALYSIS GLUCOGENICAMINOACIDS
1. Hyperkalemia(EKGchanges) AAsthatcanbeconvertedtoglucosevia
2. SymptomaBcUremia(NH3GABA) gluconeogenesis
3. SymptomaBcAcidosis(H+GABA) Thereare13(noneedtomemorize)
*WeknowGABAcankillourpaJentsthus
whenwehaveanexcessofH+,NH3,orNH4+
wehavetodialyzethem*
17
9/17/11
AMINOACIDSTHATAREKETOGENIC ESSENTIALvs.NONESSENTIALAMINO
ANDGLUCOGENIC ACIDS
Canbeconvertedtobothketonesandglucose NonessenJalaminoacidsarethosethatour
Phenylalanine(Phe) bodymakesforussowedonthavetoget
Isoleucine(Ile) themthroughthediet
Tryptophan(Trp) EssenJalaminoacidsarerequiredbythediet
becausewehavenocyclesthatcanmake
Tyrosine(Tyr) them
Threonine(Thr) DeciencyofessenJalAAsleadstoastateof
MnemonicPITTT starvaJonandcanleadtodisease
THEESSENTIALAMINOACIDS WHENAMINOACIDSGOMISSING
MnemonicPVTTIMHALL 1stMusclestartsbreakingdown
Phenylalanine
Valine 2ndBreathinggetsrestricted
Threonine
3rdPC02increases
Tryptophan
Isoleucine 4thRespiratoryrateincreases
Methionine
His:dine
5thWehavetroublebreathing
Arginine Consequences:
Lysine
Leucine Sequelae:
18
9/17/11
AMINOACIDRELATEDPATHOLOGIES PHENYLKETONURIA
PKU Deciencyofphenylalaninehydroxylase
ALBINISM (cannotconvertphenylalaninetyrosine)
ALCAPTONURIA Cannotmaketyrosine(wontgetDA,NE,EPI)
MAPLESYRUPURINEDISEASE Cannotmakemelanin(lightskin,blondehair,
CYSTINURIA blueeyes)
Phenylacetate,pheylpyruvate,and
phenethylamineaccumulate(mustyodor)
EliminatePhefromthediet,includetyrosine
PKUSCREENING ALBINISM
Allnewbornsarescreenedat48hrsusingthe AnARdisorder
Guthrietestspillingofphenylketonesinthe IsadeciencyofTyrosinase(convertstyrosine
urine melanin)
Avoidnutrasweet Oculocutaneousinvolvestheeyesandthe
AnypregnantpaJentwhohasPKUmustbe skin
verystricttoavoidphenylalanine,especially Ocularonlytheeyeslackpigment
duringrst8weeks Predisposedtoskincancer
19
9/17/11
ALCAPTONURIA MAPLESYRUPURINEDISEASE
Deciencyofhomogen:sicoxidase ARdisease
Bodycannotproperlybreakdowntyrosine Deciencyofthebranchedchainalphaketo
andphenylalanine,leadingtohomogenJsic aciddehydrogenasecomplex
acidaccumulaJon BuildupofBCAAs(leucine,isoleucine,valine)
Classicsignisblackeningofurinewhen CharacterisJcpresentaJonissweetsmelling
exposedtoair urine
Maypresentininfancy,maypresentin Mayrangefrommildtosevere
adulthood
CYSTINURIA
AnARdisease
AdefecJverenaltransportofaminoacids
COLA:cysteine,ornithine,lysine,arginine
Causespersistentkidneystones
PaJentsusuallyhavehexagonalcrystalsthat
aretranslucent
20
9/17/11
4TYPESOFPROTEINS
Primary
Secondary
BIOCHEMISTRY TerJary
Quaternary
PROTEINSTRUCTURE&FUNCTION
PRIMARYPROTEINSTRUCTURE 3PEPTIDEBONDFEATURES
Thismeanstheaminoacidsaresequencedas Theyareplanar(at)
chains Mobilityisrestricted(preventsthemfrom
LinkagesaremadebypepJdebonds excessivemovement)
Theseaminoacidsequencesarethebackbone RgroupsareintransconguraJon
ofpepJdechainsorproteins
21
9/17/11
PEPTIDEBONDSTRUCTURE PEPTIDEBONDS
PRIMARYPROTEINSTRUCTURE SEQUENCINGAMINOACIDS
Acidhydrolysis
Gelelectrophoresis
NinhydrinreacJon
EdmansdegredaJon
RestricJonpepJdases
22
9/17/11
ACIDHYDROLYSIS GELELECTROPHORESIS
Wediptheproteinintoacidinorderto Weuseanagarosegeltoseparatethe
denaturetheprotein proteinsbysizeandcharge
Thiswontsequenceaprotein,justbreakit Smallerproteinswillmigratefurtherdownthe
intosmallcomponents(AA) gel,whilelargerproteinswillstaycloserto
AcidicaJonturnsAsparagineAsparaJc wheretheystart
acid,andGlutamineGlutamicacid Doesntsequence,justseparatesbasedon
Forthatreasonwedontusethis sizeandcharge
NINHYDRINREACTION EDMANSDEGREDATION
Reactswithaminoacidsattheamino Thisusesthechemicalphenylisothiocyanate,
terminal,givingitapurplecolor(Ruhemanns whichreactswithaminoacidsstarJngatthe
purple) aminoterminal(lepside)
MCuseistodetectngerprints,asthe Thenweusespectrophotometry(light
terminalamineoflysineissloughedoofthe transmission)toidenJfythepasernofAAs
ngers(lepintheprint) Goodforsequencesupto100AAlong
AAsturnpurple,exceptforProlinewhich
turnsyellow(ithasaniminogroupC=NH)
Itcanonlycountproline
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IMPORTANTRESTRICTION
RESTRICTIONPEPTIDASES
ENZYMES
ForAAsequenceslongerthan100AAs Carboxypep:daseistheonlyonethatcuts
Thisprocedurewillactuallyallowusto tothele]oftheAAonthecarboxyterminal
sequencesproteins Trypsincutstotherightoflysineand
RestricJonenzymescutatspecicareasand arginine
helpusgureoutwhichAAsarewhere ChymotrypsincutstotherightofaromaJc
aminoacids(Phe,Trp,Tyr)
ElastasecutstotherightofGly,Ala,Ser
CNBrcutstotherightofMet
IMPORTANTRESTRICTION
HOWTOSEQUENCE
ENZYMES
Aminopep:dasecutstotherightoftheAA
terminalsequence
Mercaptoethanolbreaksupdisuldebonds
(Cys,hormoneswithsuldebonds)
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SEQUENCING SEQUENCING
SEQUENCING SECONDARYPROTEINSTRUCTURE
Thealphahelix
Thebetapleatedsheet
EveryJssuehasalislebitofbothstructures
25
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SERUMPROTEINS
FuncJonal
Acutephasereactants
HOWTODETECTEXCESSIVE WHATIFTHERESTOOMANY
PLASMAPROTEINS ACUTEPHASEPROTEINS???
WedoatestcalledCreacJveproteinORESR Inthiscasewedevelopadiseaseknownas
TheybothindicatenonspecicinammaJon Amyloidosis
Acutephasereactantsarereleasedbythe Primaryamyloidosis(AD)
liverinresponsetoinammaJon(IL6 Secondaryamyloidosis(chronicdisease)
mediated) StainedwithCongoRed
ESRfalselyhigh?Thinkanemia Hasapplegreenbirefringence
ESRfalselylow?Thinkpolycythemia,sickle
cellanemia
26
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SECONDARYAMYLOIDOSIS TERTIARYSTRUCTURE
Therearemanytypes,hereisalistofthemost Isa3dimensionalstructureoftheprotein
important Themostimportantthingiswhetherthe
AAindicaJonofchronicinammatory interacJonsarehydrophilicorhydrophobic
disease asthisdeterminestheoverallstructure
ABAlzheimersdisease Bondsarecovalent
AB2Chronicrenalfaiilure
AE/AFMEN2
ALMulJplemyeloma
ALOOKATTHEALLOSTERIC
QUATERNARYSTRUCTURE
ENZYMES
Weget2ormoreproteinsthatinteractwith 1storderkineBcs:substrateconcentraJonis
eachother proporJonaltoVmax
EnzymescooperaJvityorallosterism IncreasesubstrateandVmaxincreases
Allostericenzyme=ratelimiJngenzyme proporJonally
(important) AcJvesitesarenotallsaturatedyet(canthus
addmore)
KineJccurveislinear
MetabolizingaconstantfracJon(%)
MostmedicaJonsare1storder
27
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ZEROORDERKINETICS
AcJvesitesarefullysaturated
The#ofparJclesbeingmetabolizedis
constant
Vmaxdoesntchangenomaserhowmuch
saturaJonisgiven
Wemustgothrough1stordertogetintozero
order(itisjustveryshort)
ALCOHOLANDZEROORDER
ZEROORDERKINETICS
KINETICS
FlatlineonthekineJcgraph ThereisNOWAYtosoberupfaster
Lethaldrugsareallzeroorder Alcoholisanacid,drinkingonanempty
Alcoholiszeroorder stomachgetsyoudrunkfasterbecauseacidic
stomachabsorbsbeser(metabolicacidosis)
AlcoholacidGABAsedaJon/lowered
inhibiJons
Crosstolerance(barbandbenzotolerance)
Tolerancebuiltupenzymestokeepyouin
1storderlonger(alcoholdehydrogenase)
28
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HOWTOCHECKFORDRUG
THETHERAPEUTICWINDOW
TOXICITIES
Toxicdose/therapeu:cdose(thegreaterthe Watersolubledrugs(excretedrenally)
windowthebeser) Fatsolubledrugs(excretedhepaJcally)
DrugswithnarrowtherapeuJcwindowsmust
bechecked(bloodlevels)
NEPHROTOXICTHERAPEUTIC HEPATOTOXICTHERAPEUTIC
WINDOWS WINDOWS
Rememberwatersolubledrugscanbetoxicto Rememberfatsolubledrugscanbetoxicto
thekidneys theliver
Doapeakandtroughlevel Twowaystoclearhepatotoxicdrugs(make
Peakleveltaken4hraperdose(iftoohigh thempolar,conjugatethem)
lowerthedose) Makethempolarbyaddingoxygen,sulfur,or
Troughleveltaken2hrbeforenextdose(if nitrogen
toolowincreasefrequencyofdosage) Makethemconjugatedbyaddingglucose,
phosphate,sulfate,oracetylgroups
(acetylaJonisthe#1way)
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Km,Vmax,&AFFINITY HEMOGLOBIN
Km=substrateconcentraJonwherewehave Wasthe1stquaternaryproteintobe
Vmax discovered
Kmisinverselyrelatedtoanity(Kmhigh,
anitylowKmlow,anityhigh)
Anityisdirectlyrelatedtopotency(high
potency=highanity)
Vmax=Ecacy(ecacymeansthemaximum
response)
THREETYPESOFHEMOGLOBIN HEMOGLOBINF
A2chains,2chains Isfoundinthefetus
A22chains,2chains Isgonebythe6thmonthofage
F2chains,2chains HasaHIGHanityfor02
HasaLOWanityfor2,3DPG
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HgAvs.HgF
Howdowemeasuresatura:on?
HgAvs.HgF
But,whatifwekeepexercisingbeyondour
capacity?
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HgAvs.HgF FETALCIRCULATIONANDHgF
FETALCIRCULATIONANDHgF HgFANDSICKLECELLANEMIA
HypoxiacausesanRBCtosickle
HgFwilltrickanRBCintothinkingthereis
plentyof02onboard
ThusHgFpreventssicklingcrisisinasicklecell
paJent
HowdoweinduceHgFformaBon?
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OURACUTERESPONSETO OURCHRONICRESPONSETO
HYPOXIA HYPOXIA
Sx:Weaknessandshortnessofbreath(sound 1stIncreasedmitochondriaintheskeletal
familiar) musclemakesusmoreecientatATP
Si:Tachypneaanddyspnea(soundfamiliar) producJon
2ndHematocritgoesupduetosJmulaJonof
erythropoieJn
Thisiswhathappenswhenyoutrainyourbody
tobephysicallyt!
ERYTHROPOIESIS ERYTHROPOIESIS
Startsat4monthsgestaJonintheyolksac AbabycanmakeRBCsintheliver,spleen,and
At6monthsgestaJonitmovestothespleen, atbonesupunJl1yrofage
atbones,andliver Ababywhoexperiencesaneedforincreased
At8monthsgestaJonitmovestothelong erythropoiesiswillhaveincreasedskull,
bones sternum,etc.
AtbirthwehavesomanythingsmakingRBCs Ifyouloseerythropoiesisinthelongbones,
thatababysHcTcanbedoublethenorm thespleentakesoverandmassive
splenomegalyensues
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PATHWAYS PATHWAYS
Ifweneedtoknoweverystepwellcover Anabolicprocessesoccursincytoplasm
them,ifnotwewont! Catabolicprocessesoccurinmitochondria
Thereare3importantthingstoknowabout ExcepJon:Glycolysis(onlycatabolicprocess
eachpathway: thatoccursincytoplasm)
1. ThestarJngmaterials Thereare3pathwaysthatoccurinboth:
2. TheRLE 1. Ureacycle
3. Theendresult 2. Hemesynthesis
3. Gluconeogenesis
HEMESYNTHESIS HEMESYNTHESIS
TheRLEisaminolevulinicacidsynthase
Startswithsuccinylcoa(fromkrebscycle)
UsestheAAglycine
Requiresthevitaminpyridoxine(B6)
FerrochetolaseaddstheFe2+tothemiddleof
thefourporphyrinringsmakingitheme
34
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HOWAREFREERADICALS
METHEMOGLOBINEMIA
FORMED?
Viralinfec:onsarethe#1cause WhenFe2+(ferrousiron)isoxidizedintoFe3+
(ferriciron)
Drugs Hgisne,itjustcannotpickupoxygen
Willnotbeabletopickupoxygen
02saturaJonwillbelow
P02willappearnormal(rememberwesaidp02
doesnthavetomeanboundoxygen)
PaJentswontimprovewithoxygenmask
ReversewithMethyleneBlue(Fe3+Fe2+)
Primary:rareSecondary:common
PORPHYRIAS ACUTEINTERMITTENTPORPHYRIA
ARdeciencies(enzymedeciency25%risk IstheMCtypeofporphyria,leadstodefecJve
ofgerngit) hememetabolism
CausedbyalackofUroporphyringen1Synthase
Thereiseithertoomanyporphyrinrings requiredforthe3rdstepofporphyrin
syntheJzedorinadequatemetabolismto metabolism
degradetherings GetexcessivesecreJonofporphyrinsand
Excessiveringscausestheproblem porphyrinprecursors
Acuteintermieentandporphyriacutanea Recurrentabdominalpainandneuropathyoccur
tardaarethe2mustknowporphyrias NORASH
35
9/17/11
ACUTEINTERMITTENDPORPHYRIA PORPHYRIACUTANEATARDA
TheMCCofanoutbreakisSTRESS IfpaJentis<1yrofage=erythrocy:c
protoporphyria
Barbituratescancauseareupofporphyria
IfpaJentis>1yrofage=porphyriacutanea
GiveHemaJntodecrease#ofporphyrin tarda
ringsmade Porphyrinringsdepositedunderneaththeskin
Lightexposureleadstoheatreleasefromrings=
blistering
Babywiththishasjaundice(canbecomedeadly)
MCCofdeathisskininfecJons
PORPHYRIACUTANEATARDA RECOGNIZINGBURNS
VitaminDdeciencyisseeninthispaJent 1stdegreelimitedtotheepidermis(redness)
AbabyMUSThavelighthitthereJnaby3 2nddegreeepidermisandbeneath
monthsofagetopreservevision (blistering)
3rddegreetodermis,involvesnerves(black,
charred,painless)
36
9/17/11
GIPAINRELIEFOPIATES OPIATES
Sincewereinthemiddleofdiscussingpain Have3mainacJons
reliefforGIproblemsletstalkabout Analgesia
OPIATES CNSdepression
MusclereleaxaJon
MOA:sodiumchannelblockers
OPIATES OPIATES
HeroinistheMCabusedopiateonthestreets Codeineisaddedtotylenolformoderate
Methadonelongert1/2,usedforwithdrawinga painrelief(T3s),mildlyanJtussive
paJentfromheroin
Morphineexcellentforseverepain(sicklecell, DextromethorphanisananJJssive(in
porphyria,cancer) coughmedicine)
Fentanylverystrong,patchformforslowrelease. Loperamidetreatmentfordiarrhea
Alsousedforanesthesia
Meperidineleasteectonthesphinctorofoddi,not
(Immodium)worksbyslowingtheGI
usedinacutelypainfulGIproblem withoutaecJngtheCNS
Oxycodoneformoderatepain,popularonthestreets
37
9/17/11
ADVERSEEFFECTSOFOPIATES COMPLICATIONSOFOPIATEUSE
Bradycardia Opiatewithdrawalhasatendendytocause
Bradypnea seizures(isthemaincomplicaJon)
ConsJpaJon Withdrawalleadstoseveresympathe:c
Miosis(MCgivenontestsduetosJmulaJon symptoms
ofEdingerWestphalnucleusCN3) Naloxone(IV)
Weakness Naltrexone(oral)
SOB HowtodecipheranETOHwithdrawalfroman
opiatewithdrawal?
ANEMIAWHATYOUNEEDTO
ANEMIAORGNIZATION
KNOWFIRST
Weneedtounderstandafewofthekeytests
usedtodecipherbetweenthedierentcausesof
anemia
HEMOGLOBIN
HEMATOCRIT
MCV
FERRITIN
HEMOGLOBINELECTROPHORESIS
RETICULOCYTECOUNT
COOMBSTEST
38
9/17/11
WHATYOUHAVETOKNOWABOUT
IRONDEFICIENCYANEMIA
ANEMIA
Irondeciencyanemia IstheMCCofhypochromicanemia
Sicklecelldisease
Thalassemias SerumironandferriJnaredecreased
Leadpoisoning
TIBCincreases
SideroblasJcanemia
Anemiaofchronicdisease Inchildrenandyoungadultsinadequate
Autoimmunehemolysis intake
Hereditaryspherocytosis
Elliptocytosis 2040yrolds,theMCCisinammatorybowel
G6PDHdeciency disease
MegaloblasJcanemia(B12orfolate)
>40yrmucosalbleedingistheMCCofanemia
HEMOGLOBINSANDCDISEASE SICKLECELLDISEASESI/SX
HemoglobinSdiseaseisakaSickleCellDisease Sicklecellcrisis(termtodescribethe
QualitaJveproblemwithsynthesisofincorrectly consequencesofsickling)
funcJoningglobin(pointsubsJtuJon:valine
subs:tutedforglutamineat6thposi:onofbetachain) Vasooclusivecrisis(4thingsweworryabout)
ARdisease AplasBccrisis(ParvovirusB19)
Onsetisat6monthsofage(whenwerunoutofHbF)
HemolyBccrisis(openduetocoexisJng
Hypoxiacausessickling,whichleadstovasoocclusion
DactyliJs(earlysymptom)
G6PDdeciency)
39
9/17/11
MANAGEMENTOFSICKLECELL
SICKLECELLDISEASE
DISEASE
Anemiaiscausedbyhemolysis Oxygen
BonemarrowcompensaJondoesntmeetthe Exchangetransfusion
rateofdestrucJon Hydroxyurea
Sicklecellsonlysurvive1020days LifeJmefolatesupplementaJon
#1reasonforvasoocclusionishypoxia Penicillinfrom05yr
1sttesttorunisreJculocytecount Opiatesforpain
Bonemarrowtransplants
SICKLECELLDISEASEAND
SICKLECELLTRAIT
MALARIA
PaJenthashalfHbSandhalfHbA Fitness
SicklingonlyinseverelyhypoxicsituaJons 1gene=moretolerant
Bothgenes=immune
Whatisthebenetofhavingsicklecelltrait
vs.sicklecelldiseasewhenitcomesto
malaria?
40
9/17/11
HEMOGLOBINCDISEASE THALASSEMIAS
LysineissubsJtutedforglutamateatthe6thposiJonof Involveandglobinchains
thebetachain
Theyareinheritedinanautosomalrecessive
FormaJonofcrystalsleadstobloodcelldeformity/
increasedbloodviscosity fashion
NosicklingbecausebothAasarehydrophilic TheyarecommoninMediterraneanindividuals
IsbenignandopennotseenunJladulthood RememberHgA(22),HgA2(22),and
MildhemolyJcanemia HgF(22)
SporaJcepisodesofmusculoskeletaljointpain
Minorforms=atleast1geneisremaining
Pigmentedgallsteones
ManageasoutpaJent,performingregulareyeexams
Majorforms=nogenesareremaining
ALPHATHALASSEMIAMINOR ALPHATHALASSEMIAMAJOR
2genelocimaking4allelesintheglobinchain All4genesaremissingsonohemoglobincanbe
If1geneismissing,paJentisasymptomaJc(Hg made
isaround12)75%ofhemoglobinsJllmade Hydropsfetalis(babydiesinuteroby4months
ofagewhy?)
If2genesaremissing50%ofhemoglobinis HemoglobinBart(4chains)seeninHydrops
sJllmade(ifptacJve:symptomaJc,ifnon Fetalis
acJve:notsymptomaJc)
HemoglobinH(4chains)
If3genesaremissing25%ofhemoglobinis Treatmentinvolveschronicbloodtransfusion
sJllmade(allpaJentaresymptomaJc) therapy,ironchelaJon,splenectomy,stemcell
Thereisusuallynospecictreatmentnecessary transplantaJon
41
9/17/11
BETATHALASSEMIAS BETATHALASSEMIAMINOR
HBBgeneonchromosome11(2alleles) 1geneismissing
If1geneismissing=Betathalassemiaminor PaJentsusuallyhaveHbaround7.5
If2genesmissing=Betathalassemiamajor IfpaJentisacJvesymptomsoccur
IfpaJentisinacJvetheyareasymptomaJc
IncreasedfracJonofHbA2,decreasedfracJon
ofHbA
MildmicrocyJcanemia
BETATHALASSEMIAMAJOR BLOODTRANSFUSIONS
Bothgenesaremissing WedothemonlyifpaJentsaresymptomaJc
PaJentcanonlymakeHbA2andHbF
1unitofpRBCsincreasesHbby12g(andHcT
TheyremainasymptomaJcunJl6monthsofage
(HbF),whentheyneedtransfusionstoremain by36)
alive 1unitpRBCsdelivers3.4gofiron
PaJentexperiencesseveremicrocyJc,
hypochromicanemia WholebloodisonlygivenwhenpaJenthas
Chronictransfusionscauseironoverload,so experiencedacutetrauma
chelaJontherapyisrequiredaswell pRBCsareusedforananemicpaJent
Deathopenbefore20yr
42
9/17/11
COMMONTRANSFUSIONRELATED
BLOODTRANSFUSIONS
REACTIONS
Ruleofthumb:forevery2unitsofpRBCs,give1unit FebrileReac:on
ofFFP
FFP:containsallclorngfactors(willstopbleeding Anaplyaxis
immediately)
Cryoprecipitate:containsfactor8,vWF,andbrinogen
ABOReac:on
(usedforHemophiliaAandvWDbothmildbleeding)
Immunoglobulins:fordeciencies(ie.PaJentis
sepJc),ortoblockanotherprocess
Albumin(5%):forcaseswheresignicantproteinislost
(neprhoJcsyndrome,cirrhosis,kwashiorkor,
Menetrieresdisease)
FEBRILEREACTION ANAPHYLAXIS
PaJentgetsafever(canbeshortlivedor PaJentexperiencesushing,swelling,
longerlived),andiscausedbywhitecell wheezing
anJgens. CausedbyIgAdeciency
Wecanavoidafutureoccurrenceby FirststepistoSTOPthetransfusion,thengive
washingthecellstoremoveanJgens subcutaneousepinephrine
Treatment:acetaminophen Inthefuturespeciallterorbloodfroman
IgAdecientpaJent
43
9/17/11
TRANSFUSIONRELATED
ABOREACTION
INFECTIONS
RBCsgetlysed HIV
HepaJJsB,C,andD
PaJentexperiencesfeverandpaininthe
EBV
lowerback(RBCsgotokidneys)
CMV
Firststepistosimplystopthetransfusion Hemorrhagicviruses
BacterialinfecJons(staph,strep)
Malaria
Babesiosis
syphilis
IRONOVERLOAD LEADPOISONING
HemosiderosisisthedeposiJonof ElevatedPb2+levelswillinhibitthe
hemosiderin,andhemochromatosisthe aminolevulinicaciddehydratase(2ndenzyme
diseasethatwegetfromironoverloadinthe inhemesynthesis),aswellasferrochetolase
Jssues. Porphyrinringsthenbecomestucktothe
Bronzediabetesmicronodularcirrhosis, insidewalloftheRBC(basophilicsJppling)
pancreaJcbrosis,andpigmentaJonofthe TheMCCofleadpoisoningisfromeaJng
skin leadbasedpaintchips
Primaryautosomalrecessive Leadpoisoningaectsallorgansystems(brain
Secondarychronictransfusiontherapy ismostsensiJve)
44
9/17/11
LEADPOISONINGSIGNSAND
LEADPOISONING
SYMPTOMS
Leadisstoredmainlyintheblood,sopJssues, Learningdisability
andbones Neurologicndings(numbness,Jngling)
Inadultsitstaysinthebones,hair,nails,andis Abdominallpain
unavailabletootherJssues,whereasin ConsJpaJon
childrenitdoesntoccurthisway
LossofappeJte
Leadlevels>10ug/dListhecutofor
intervenJon Irritability
Psychosis/depression(mainlyinadults)
MANAGEMENTOFLEAD MANAGEMENTOFLEAD
POISONING POISONING
Normallevelis<10ug/dL 4569ug/dLallpreviouslymenJoned+
1ststepistodeterminesourceandeliminateit chelaJontherapyisnowindicated
1014ug/dLeducateyourpaJentaboutlead,
eliminatesource,F/Ubloodmonitoring >79ug/dLhospitalizaJon+chelaJon
1519ug/dLeducateyourpaJent,F/Ublood therapy
monitoring3monthsaperiniJalvisit
2044ug/dLHx/PE,labs(Hb,Fe2+),
environmentalinvesJgaJon,leadreducJon,
monitorneurodevelopment,AXR(bowel
decontaminaJon)
45
9/17/11
ANEMIAOFCHRONICDISEASE COOMBSTESTPOSITIVE
AnychronicinfecJousorinammatory PerformedwhenMCVisnormalbutreJculocytecount
isincreased
process AposiJvetestwouldindicateanautoimmuneprocess
DecreasedTIBC isdestroyingtheRBCs
Howitsdone:
IncreasedFerriJn Step1:Getbloodsample
Ironisstoredinincreasedamountsinthe Step2:AddCoombsreagent(anJhumananJbodies)
marrowmarcophages Step3:CheckforbindingofCoombsreagent
PosiJveresultmeansanimmunmediatedmechanismis
asackingthepaJentsRBCs(autoimmune,
alloimmune,druginduced)
AUTOIMMUNEHEMOLYTIC
ANEMIA
PrematureRBCdestrucJonthatleadsto
anemiawhentheBMcannotcompensate
Intravascular(complementsystem)and
extravascular(RBCscoatedwithanJbodies
anddestroyedbymacrophages)
WillseereJculocytosis,increasedLDH(non
specic),reducedplasmahaptoglobin"
46
9/17/11
HEREDITARYSPHEROCYTOSIS
AnADdisorderthatisCoombsve
Intrinsicand/orextravascularhemolysisdue
tospectrinproteindefect
Alsoincludeselliptocytosis(ovalshapedRBC)
RBCissmall/roundwithnocentralpallor
PresenceofreJculocytosis,increasedRDW,
andincreasedMCHC
Conrmatorytestistheosmo:cfragilitytest
GLUCOSE6PHOSPHATEDH RBCSHAPESANDTHEIR
DEFICIENCY MEANINGS
Xlinkedrecessive HowellJollyBodies:tellsusthereisnuclear
DeciencymeansRBCsareatriskofofoxidaJve remnantsintheRBC(hemolyJcanemia,defectin
damage(noNADPHtomaintainreducedglutathione) thespleen)
ManyareasymptomaJcunJlastressfulortriggering Heinzbody:G6PDdeciency
event(infecJon,drugs) Basophilics:ppling:leadpoisoning
Neonataljaundiceleadingtokernicterus Teardropcell:hemolyJcanemiaorcancer
HemolyJccrisis Targetcells:missinghemoglobin(allmicrocyJc
Sulfas,anJmalarials,methyleneblue,naphthalene anemias)
Favabeans Poikilocytes:cellsindierentstagesof
development
47
9/17/11
MACROCYTICANEMIAS COLLAGEN
MCV>100
EitherduetoB12deciencyorfolate
deciency
B12deciencycomeswithneurological
sequelae
COLLAGEN COLLAGEN
Isthemostabundantproteininthebody Glycineisfoundatevery1/3residue(thusit
4types,usetheSCABmnemonic makesup33%ofcollagen)
Type1:SKIN VitaminCrequiredtohydroxylateprolineand
lysine
Type2:CONNECTIVETISSUE Copperisrequiredtohydroxylatelysine
Type3:ARTERIES HydroxylaJon:inRER(givespreprocollagen)
Type4:BASEMENTMEMBRANE GlycosylaJon:inGolgi
Fibroblastsuseitforsimplescarring AperglycosylaJonprocollagen(triplehelix)
MyobroblastsforwoundcontracJon
48
9/17/11
COLLAGENPRODUCTION KELOIDS
Woundcontrac:onMyobrils
Simplescarringbroblasts
Desmoplasia:collagenousreacJonpost
injury/insult
Keloid:excessivecollagendeposiJonpost
insult
SCURVY EHLERSDANLOSSYNDROME
VitaminCdeciency,leadstobleedingofthe Faultycollagensynthesisleadstohighly
gingivaandthehairfollicles. stretchableskin(mainsign)
VitaminCisneededforhydroxylaJon,no Therearemanytypes(10)
hydroxylaJon=scurvy
49
9/17/11
OSTEOGENESISIMPERFECTA OSTEOGENESISIMPERFECTA
AnADdisease,exhibitspleiotropy Type1normalcollagenproducedin
Therearemanygenedefectsthatleadto insucientamounts
abnormalcollagensynthesis
GlycineisreplacedwithbulkierAAs(lowers Type2collagenismadepoorlyandin
tensilestrength) insucientamounts
Skinisverythin(canseethroughit) Type3collagenisformedimproperly
Bonesareverybrisle
Bluesclera(mostuniquending)
Severaltypes(type1ismild,type2islethalin
utero)
COLLAGENVASCULARDISEASES KERATIN
CREST Aproteinmadeforitstensilestrength
SCLERODERMA Haslotsofcysteins(fortheirdisuldebonds)
PROGRESSIVESYSTEMICSCLEROSIS Foundinhair,nails,bones,carJlage,tendons,
SLE andligaments
RHEUMATOIDARTHRITIS Alcohol,water,andheatcanbreakdisulde
bonds(hairstraighteners,curlingirons)
50
9/17/11
ELASTIN ELASTIN
Aproteinthatgivesustheabilitytostretch Importantforarteries
andrecoil Lungs
Richinglycine,proline,lysine
Skin
Hasthesamehydroxyprolinesascollagenbut
doesNOThavethehydroxylysines Bladder
MadebylinkingtropelasJnproteinmolecules ElasJcligaments/carJlage
viaalysyloxidasereacJon
Desmosineandisodesmosidearethetypesof
linksinthetropoelasJnmolecules
MARFANSSYNDROME HOMOCYSTEINURIA
CausedbymutaJonoftheFBN1gene(chrom AppearslikeMarfanoidsyndrome
15)whichencodesbrillin Problemisthatinterferencewithlysine
Mainsignisthatthewingspaniswiderthan hydroxylaJonleadstoacollagenproducJon
thepa:entsheight problem
Arachnodactyly(spikerlikengers) Clolngdiseaseinchildreniso]enseen(DVT,
ReJnaldetachmentoccurfromthebosom MI,stroke)
(whyisthisimportant?) ReJnaldetachmentfromthetop,sotheyhave
theoppositeproblem
51
9/17/11
ELASTASE EMPHYSEMA
IsanenzymethatdestroyselasJn Occursasaresultofelastasedestroyingthe
WegetprotecJonfromelastasevia1 recoilingabilityofourlungs(lostcompliance)
anJtrypsin(inhibitselastase),whichisfound Thereare4typesofemphysemawehaveto
inmonocytesandneutrophils(aswellas worryabout:
bacterialS.AureusandPseudomonas) 1. Panacinar:
1anJtrypsinisdestroyedbysmoke 2. Centroacinar:
1anJtrypsindecreasesasweage 3. Distoacinar:
4. Bullous:
ALPHA1ANTITRYPSIN
NoJcethewordtrypsin
Trypsinisprevalentinthelung,liverand
pancreas
Ifwehaveanalpha1anJtrypsindeciency
thenweloseprotecJonfromdestrucJonof
theliverandthepancreas
WatchforanobstrucJvelungdiseasein
addiJontohepaJJsand/orpancreaJJsina
veryyoungchild(<1yr)
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ENZYMES
THEROLEOFTHEENZYME
Bringthesubstratestogetherinspaceand
Jme
LowerthefreeenergyofacJvaJon
Stabilizethehighenergyintermediate
*Anenzymedoesnotgetconsumedina
reacJon
53
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ENZYMEBINDINGSITES COMPETITIVEINHIBITION
Ac:vesiteiswherethesubstratebinds Thebigthingtorealizeisthatcompe::ve
inhibitorshavetolookliketheirsubstrates
Regulatorysiteiswheretheregulatorbinds TheycompeteforthesameACTIVESITEasthe
Km=thesubstrateconcentraJonatwhichyou substrate
haveVmax Ifyouarebumpingyoursubstrateothesite,the
anitydecreases
Km=1/anity=1/potency Ifanitydecreases.Kmhastoincrease
Thusanity=potency Vmaxremainsthesamebecausemoresubstrate
isallweneedtoaddtoovercomethecompeJtor
Andlowanity=highanity,lowanity=
Potencydecreases(Kmrises)
highKm
FAVORABLEANDSPONTANEOUS
NONCOMPETITIVEINHIBITION
NATUREOFREACTIONS
Whenaninhibitorisnotsimilartothe AreacJonwillonlybefavorableand
substrate spontaneousiftheGisnegaJve
Itbindstotheregulatorysite,turningthe WhenwehaveaG,energyisgiveno
enzymeOFFirreversibly GsareaddiJve,theoverallreacJoncan
WedontaectanitysoKmremainsthe proceedaslongasoverallisaG
same
Vmaxdecreases
G=HTS
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REACTIONS ISTHISREACTIONFAVORABLE?
G=freeenergyofthereacJon(wewantit
negaJvetoproceed)
H=enthalpy=heat
S=entropy
TEMPERATURE
TemperaturewillincreaseyourVmaxunJlit
reachesacertainpoint
Onceitpeaks,yourenzymeswillstartto
denatureandyourVmaxdropssignicantly
Iftemperaturedenaturesanenzyme,itwill
alsodenatureyourbodysproteins(muscle,
organs,heart)
55
9/17/11
REDOXPOTENTIAL REDOXPOTENTIAL
IsrepresentedbyE Whenyougiveawayelectronsyoureduce
IfwehaveaE,ithaselectronstogiveaway it
Ifwehavea+E,itwantstoacceptelectrons Whenyougiveelectronsyouarethereducing
agentandyoubecomeoxidized
WewantourEtobenega:ve
Whenyouacceptelectronsyoubecome
reducedandaretheoxidizingagent(because
youmadetheotheragentoxidized)
AREDUCINGAGENT ANOXIDIZINGAGENT
HasanegaJveE HasaposiJveE
Wantstogiveawayitselectrons Wantstoacceptelectronsfromsomeone
Isthereducingagent Istheoxidizingagent
BecomesoxidizedaperthereacJon BecomesreducedaperthereacJon
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THEELECTRONTRANSPORTCHAIN THEETCCHEMIOSMOTICTHEORY
THEETCINHIBITORS/UNCOUPLERS INHIBITORSvs.UNCOUPLERS
InhibitorswillstoptheETCfromoccurring
UncouplerswillconJnuetolettheETC
funcJonwithouttheproducJonofATP
Carbonmonoxide(CO)inhibitsatcomplex4
howcanweapplythisinformaJon???
57
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CYANIDEPOISONING CHLORAMPHENICOL
Complex4inhibitor Complex4inhibitor
NoncompeJJveinhibitorofhemoglobin IsananJbioJc
Low02saturaJonwithnormalp02
ItsuniqueadverseeectisBONEMARROW
Sodiumnitroprussideistheonlydrugweusethat
containscyanide(veryimportant!!!)
SUPPRESSION
Looksjustlikemethemoglobinemia Howcanweexplainthisbasedonwhatwe
nowknowaboutATPgeneraJon???
AmylnitriteSodiumThiosulfateMethylene
BluepackedRBCs
UNCOUPLERS
DontstoptheETC,justpreventATPfrom
beinggenerated
EnergycreatedgetsreleasedasHEAT
NoATPmeanswelltapintoourenergystores
andusethemupquickly
DNP,Aspirin,andFFAsaretheuncouplers
58
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FOURIMPORTANTPROTEIN
SEQUENCES
1. Presequence
2. Prosequence
PROTEINSEQUENCES 3. Mannose6Phosphatesequence
4. ShortNterminalsequence
THEBIGPICTURE THEPRESEQUENCE
59
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THEPROSEQUENCE PRE&PROSEQUENCEDEGREDATION
Bothlabelsaredegraded
Prelabelisdegradedaperproteinentersthe
RER
Prolabelisdegradedaperproteinenterthe
Golgi
Only1JmewhentheProlabelisnot
degradedINSULIN
ADDITIONOFMANNOSE6 ADDINGSHORTNTERMINAL
PHOSPHATE SEQUENCE
60
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CATABOLICMETABOLISM
Breakingthingsdown
ANABOLICvs.CATABOLIC CATABOLICPATHWAYS
Asarule Catabolicpathwaysareturnedonwhenwere
Anabolicpathwaysaredoneinthecytoplasm inastateofenergydeciency(starvaJon)
Catabolicpathwaysaredoneinthe Catabolicpathwaysaredoneexclusivelyinthe
mitochondria mitochondria(exc:Glycolysis)
61
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HOWWEUSETHEENERGYAVAILABLE
SOURCESOFENERGY
TOUS
Glucose40%ofourenergy
Protein/Fat30%each
Ketoneslastresort
Glucose=4caloriespergram
Protein=4caloriespergram
Fat=9caloriespergram
THEHOURLYENERGYUSAGE THECATABOLICSTATE
Plasmaglucoselasts24hr Hormonesepinephrineandglucagonarethe
Liverglycogenlasts2448hr controlmechanisms
Proteolysisstartsaround36hr Catabolicstateiscontrolledbythe
Lipolysisstartsaround36hr sympatheJcsystem
cAMPisthe2ndmessenger
Ketogenesisstartsaper36hr
62
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GLYCOLYSIS GLYCOLYSIS
Itallstartswithglycolysis
Glycolysisisthemostac:vepathwayinthebody
Istheonlypurelycatabolicpathwaythatoccursinthe
cytoplasm
Catabolicinallcellsexceptintheliver,whereitis
anabolic(veryimportantdetail)
Thebodylikesglycolysisbecauseitgivesus2ATPs
immediately(ontopofthepyruvate)
Which3pathwaysoccurinbothcytoplasmaand
mitochondria?
GlucoseGlucose6Phosphate Glucose6PhosphateFructose6Phosphate
RequiresATP Enzyme:G6Pisomerase
Usesglucokinase(liverandpancreas)
Useshexokinaseeverywhereelse
63
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GLYCOLYSIS ALLOSTERICACTIVATIONOFPFK1
Fructose6PhosphateFructose1,6
Bisphosphate
RLE:Phosphofructokinase1(PFK1)
UsesanATP
AtthispointwevecreatedF1,6BP
Weveused2ATPs
WevealreadypassedourRLE(whichisPFK1)
64
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MERCURYPOISONINGAND
GLYCOLYSIS
GLYCOLYSIS
InhibitstheenzymeGlyceraldehye3
phosphatedehydrogenase
MCCinadultsisTuna(eateninexcess)
MCCinchildrenisbiJngintoathermometer
RBCsareaectedrst
Thebrain/heart/kidneysuerthemostsevere
consequences
THE2NDHALFOFGLYCOLYSIS SHUNTINGOFG1,3BP2,3BPG
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REVIEWOFTHEIMPORTANTPOINTS
GLYCOLYSIS
INGLYCOLYSIS
66
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REVIEWOFTHEIMPORTANTPOINTS
GLUCONEOGENESIS
INGLYCOLYSIS
Responsibleforfeedingglucoseintothe
glycoly:cpathway(nomaserwhere
glycolysisisoccurring)
90%occursintheliver,10%inadrenal
medulla
Controlledbyepinephrineandglucagon
2ndmessengeriscAMP(sympethaJc)
gNis1ofthe3pathwaysthatoccurinthe
cytoplasmANDmitochondria
THEGLUCONEOGENESISPATHWAY THEGLUCONEOGENESISPATHWAY
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FEEDINGINTOTHEGLUCONEOGENIC
AQUICKLOOKATTHECORICYCLE
PATHWAY
Pyruvate
Lactate(viaCoriCycle)
Glycerol
Glucogenicaminoacids(alanine,glutamine)
GLUCONEOGENESIS MECHANISM1:OAAPEP
Livergetssignaltomakemoreglucose Thismechanisminvolvesasimpleconversion
Thissignalsthemitochondriatoblock ofOAAPEP,viamitochondrialPEPCK
pyruvatefromentering(somesJllenters) Pyruvatecarboxylase(PyrOAA)istheRLEof
Ifpyruvategetsintothemitochondria,then gluconeogenesis
wehavetogetitout
OAAPEP(phosphoenylpyruvate
Pyruvatecannotcrossthemitochondrial carboxykinase)
membrane,sowehave3mechanismsby
whichwegetthenecessarysubstratesback PEPjumpsintogNasasubstrateannothing
intothecytosol furtherisrequired
68
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MECHANISM2:OAAASPARTATE
AtransaminaJonofOAAAspartate
Aspartateisthentransportedintothecytosol
wherereversetransaminaJonyieldsOAA
ThismechanismrequiresconJnuoustransport
ofglutamateintoandalphaKGoutofthe
mitochondria,thusthismechanismislimited
bythesubstrateavailability
MECHANISM3:OAAMALATE
Occursbyreversing1stepintheTCA
CatalyzedbyMalatedehydrogenase
RequirescofactorNADH
Malatetransportedtocytosolwhereitis
oxidizedtoOAAviacytosolicMalateDH(uses
NAD+)yieldsNADH
CouplingthesetwooxidaJonreducJon
reacJonskeepsgNfuncJonalwhenpyruvate
isthesourceofyourcarbonatoms
69
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GALACTOSEMETABOLISM
GALACTOKINASEDEFICIENCY GALACTOKINASEDEFICIENCY
70
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GALACTOSEMIA
DeciencyofGal1PUridyltransferase
AectsRBCsrst,thenthebrain/heart/
kidneys
KeyistonoJcesymptomsbetweenfeedings
(whileabsorpJonistakingplace)
PaJentmustbeswitchedtosoymilk
Screeningnowtakesplacebecauseweworry
aboutconversiontosorbitolorgalac:col
FRUCTOSEMETABOLISM FRUCTOSURIA
Causedbydeciencyoffructokinase
Hexokinasecanllinandthusthisisabenign
condi:on
Spillingoffructoseintotheurineisseen
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FRUCTOSEMIA THE5FATESOFPYRUVATE
DeciencyofAldolaseB
Ismoreseverethanfructosuria
AccumulaJonofF1Pleadstoaectson
RBCsrst,thenbrain/heart/kidney
PaJentexperiencesthesameenergydeprived
symptomsasthosewithgalactosemia
OnsetwhenstarJngtofeedthebabyfruits
(wontseeunJl6monthsorlater)
PyruvateLacJcAcid PyruvateAcetylCoA
72
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PyruvateAcetylCoA PYRUVATEDEHYDROGENASE
AcetylCoAisneededfortheKrebsCycle Oneoftherstquaternaryenzymes
(moreontheTCAlater) discovered(contains3proteins)
Requirespyruvatedehydrogenase(moreon 5cofactorsrequired
thisrightnow) TPPThiamine(vitaminB1)
3enzymesthatchangepyruvatetoAcoA(E1, LipoicAcid(vitaminB4)
E2,E3) CoAPantothenicAcid(vitaminB5)
5cofactorsrequired FADRiboavin(VitaminB2)
NADNiacin(VitaminB3)
73
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PYRUVATEDHCoFactorFuncJons ALCOHOLANDPYRUVATEDH
TPP:Decarboxylates Alcoholicsarethiaminedecient(B1)
LipoicAcid:Acceptsthe2cunitandgets Nothymine=noE1funcJon=pyruvatestays
reduced inthecytoplasm
CoA:nal2cacceptor(=AcoA) Pyruvatestaysincytoplasmandconvertsto
FAD:oxidizeslipoicacid(givesusFADH2) lacJcacid
NAD:oxidizesFADH2(givesNADH+H) WhathappenswhenwegettoomuchlacJc
acid?
BVITAMINDEFICIENCIESANDTHE
SEQUELAE
HowdowemanageanalcoholicintheER? B1(Thiamine)
BeriBeri(dryandwet)
WernickesEncephalopathy
Korsakossyndrome
74
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BVITAMINDEFICIENCIESANDTHE BVITAMINDEFICIENCIESANDTHE
SEQUELAE SEQUELAE
B2(Riboavin) B3(Niacin)
Angularchelosis Pellagra(4Ds)
Hartnupsdisease
PyruvateETOH PyruvateETOH
FermentaJonintoalcohol
ETOHAcetaldehydeacetate
ETOHleadstoNADHexcess,shurngdown
gluconeogenesis(andturnstoproteinsfor
energy)
75
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ALCOHOLDEHYDROGENASE
IstheenzymeusedinETOH,Methanol,and
EthyleneGlycolmetabolism
Methanolformicacid(visualtoxicity)
EthyleneGlycolGlycoxylate(oxalatekidney
stones)
Treatmentforbothisethanoldrip
PyruvateOAA PyruvateAlanine
Occursanaerobically
ViaAST
76
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KREBSCYCLE KREBSCYCLE
2ACoAforevery1moleculeofglucose(thus
doubleyourproducts)
3NADHperturn(1NADH=2.5ATP)
1FADH2perturn(1FADH2=1.5ATP)
1GTPperturn(1GTP=1ATP)
TotalATPgeneratedperturn?10ATP
ATPGENERATEDPERMOLECULEOF MOVINGNADHFROMCYTOSOLINTO
GLUCOSE MITOCHONDRIA
10ATPsperturnoftheKrebsCycle(20ATP NADHisalargemoleculeandwontcrossthe
totalperGlucose) membrane,sowehavetotransferthe
2NADHmadeinglycolysis(5ATP) electronssomehow
2NADHfrompyruvate(5ATP) Wehave2shuslesthathelpustransport
2netATPsgeneratedinglycolysisproper NADHfromcytosoltomitochondria
TotalATPper1moleculeofglucose=32ATP MalateAspartateshusle
Glycerol3Phosphateshusle
77
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MALATEASPARTATESHUTTLE MALATEASPARTATESHUTTLE
OAAisconvertedintomalateusingNADHand
malatedehydrogenase
Malatethencrossesthemitochondrial
membraneandisconvertedrightintoOAA,
yieldingNADH
Importantplayersinthisprocessinclude:
aspartate,glutamate,andalphaKG
ThisshuslerequiresnoATP
GLYCEROL3PHOSPHATESHUTTLE GLYCEROLPHOSPHATESHUTTLE
Thisshusleuses2ATPs,asopposedtothe
malateshuslewhichusesnone
FADH2isusedatcomplex2intheETCdirectly
Weusethisonlyincaseswhereourbodyisin
needofextraNADHquickly(aroundbirth,
duringchildhoodgrowthspurt,andduring
puberty)ie.Whenwereundergoingrapid
cellulardivision
78
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AMINOACIDCATABOLISM
Whenglucoseisusedup,weturntoamino
acidsforenergy
AMINOACIDCATABOLISM Thereare20aminoacids,andwehavea
transaminaseforeach
The3mostimportanttransaminasesareGGT,
AST,andALT
GGTisonlyinthemitochondria(important)
AlltransaminasesuseB6asacofactor
THEORIGINOFALCOHOLICHEPATITIS
LABVALUES
WHEREDOTHEDIFFERENCESINAST:ALTFOR
VIRALvs.ALCOHOLICHEPATITISCOMEFROM
79
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FATTYLIVERMicrovs.Macro AMINOACIDCATABOLISM
Microsteatosis(ReyeSyndrome,
Acetaminophentoxicity,Pregnancy)
Macrosteatosis(Alcohol,Obesity)
AMINOACIDCATABOLISM
FATTYACIDBREAKDOWN
80
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GOALOFFATTYACIDCATABOLISM FATTYACIDCATABOLISM
Breakdownchainsofcarbons,2cataJme, Howmanyroundswillittaketobreakdowna
unJlwehaveonly2carbonslep FAchain?[(C/2)1]
PurposeistocreateAcetylCoAthatwillfeed #ofNADHPscosttomakeaFAchain?[C2]
intotheTCA #ofATPscosttomakeaFAchain?[C1]
EveryJmewebreakdownalongchainitcosts
us2ATPs
FAbreakdownyieldsalotofenergyviaNADH,
FADH2,andAcetylCoA
12CFACHAINBREAKDOWN FATTYACIDCATABOLISM
SJmulatedbyglucagon
GlucagonsJmulateshormonesensiJvelipase
(HSL)
HSLmobilizesfreeFAsandsendsthemtothe
liver
ShortandmediumchainFAscancross,long
chainsrequireCAT1andCAT2
Costs2ATPsiniJallytostartbreakingthem
downintheliver
81
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CARNITINESHUTTLEDEFICIENCIES
Carni:neorCAT1problemsmeanFFasstay
inthecytoplasm
WecallthisAdrenoleukodystrophy
Xlinkedrecessive
Adrenalglandfailureoccurs(doesntget
myelinatedproperly)
Earlywhitemaserinvolvement
BETAOXIDATION BETAOXIDATION
A4stepprocessrepeatsunJlwecometothe
last2carbons
MnemonicOHOTtorememberthesteps
O=oxidaJon(FADH2)
H=hydrolysis(H20)
O=oxidaJon(NADH)
T=thiolysis(viaThiolaseyieldsACoA)
82
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FATTYACIDCATABOLISMOFODD
CHAINFATTYACIDS
IfbetaoxidaJonleavesuswitha3carbon
chainattheend(propionylCoA),afewsteps
mustbeundertakentoxthisproblem
Wewillcreatea4cintermediateknownas
succinylcoa,whichwillthengotoreplenish
theTCA(AnapleroBcreacBon)
RequiresPropionylCoACarboxylase,and
MethylmalonylCoAMutase
Bio:nandB12arecofactorsofthisreacJon
KETOGENESIS
Ketonesarealastresortsourceofenergy
Controlledonlybyglucagon
TheRLEisHMGCoAsynthase
Ketonesaremostimportantforthebrain
3ketones(acetoacetate,acetone,OHbutyrate)
Acetonehasastrongsmell
OHbutyratecrossestheBBB,makesupthe
majorityofcirculaJngketones
Ketonesarecon:nuoustheycanmoveinany
direcJon
83
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DIABETICKETOACIDOSIS DKACOMPLICATIONS
IsacomplicaJonofDM1,notDM2 Polyuria
DM1isanautoimmunecondi:onagainsttheislet
cells(anJisletcellanJbody) Polydypsia
SymptomsofDM1dontstartunJl~90%oftheislet Hypovolemia
cellsaredestroyed
Hyperkalemia
Remaining10%undergohyperplasiatocounteractthe
loss(causeshoneymoonperiodduring1styearofDM1) Hypophosphatemia
Commonlyoccurs2weekspostviralinfecJon Hyponatremia
(CoxsackieB)
IsassociatedwithHLADR3andDR4
DKAMAKINGELECTROLYTE
DKACOMPLICATIONS
CORRECTIONSPROPERLY
Pain Determiningthecorrectvalueforsodium
Forevery100mg/dLglucoseisabove100,the
ElevatedcreaJnine sodiumlevelisdiluted1.6mEq/L..Calculateand
determinethecorrectsodium.
Correc:ngsodiumlevels
PonsissensiJDontcorrect>10mEq/Lover24hr
period
vetoosmoJcship=demyelinaJon(central
pon:nemyelinolysis)
84
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DKAMAKINGELECTROLYTE
CORRECTINGACIDOSIS
CORRECTIONSPROPERLY
Correc:ngforglucose NevergiveHC03toapaJentinDKA
Donotcorrectglucoseanymorethan100mg/ Fluidsaremainstayoftreatment(NS)
dLinasinglehour AddK+totheuidsonlyapertheyvebegun
Addphosphateifhypophosphatemia
Insulindrip Monitorclosely
Apergivinguids,K+,andPO4,drip0.1mg/
kgofbodyweight(adult),childneeds1unit/kg
total
MAJORREASONWHYYOUNEVER NONINSULINDEPENDENTDIABETES
GIVEBICARBTOAPATIENTINDKA MELLITUS(TYPE2)
#1Itonlymaskstheunderlyingproblem Lateronset(usedtobeadultonset,todaycan
#2Itdecreasescardiacoutput happeninobeseyoungerpeople)
#3Leadstoarealhypokalemia Theresanobesityconnec:on
#4CausesalepshipoftheHbdissociaJon Insulinreceptordownregula:on
curve Hyperinsulinemiapresent
#5HC03doesntgetintothebrain(only Noketonebodiesdeveloped
correctsplasmapHnotbrainpH) HyperglycemicnonketoJccome
85
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COMPLICATIONSASSOCIATEDWITH
MANAGEMENTOFDM1ANDDM2
DM2
Vasculi:s Type1diabeJcsalwaysrequireinsulin
Nephropathy(microalbuminuria,nodular Type2diabeJcsshouldalwaysstartby
glomerulosclerosis) asempJngtoloseweightmedicaJonsifno
Neuropathy improvementinsulin
Bleeding/clolng
Shortle]colonsyndrome
DIABETICMEDICATIONS
DIABETICMEDICATIONS
SECRETAGOGUES
Secretagogues(Sulfonylureas) ThesecretagoguesworkbysJmulaJngthe
Sensi:zers(Biguanides,Thiazolidinediones) releaseofinsulin
MOA:theyblockthevoltagesensiJveK+
glucosidaseinhibitors(Acarbose,Miglitol)
channelonthepancreaJccellmembrane,
leadstodepolarizaJonwhichopensCa2+
channelswhichleadtoincreasedfusionof
insulinwithcellsmembrane
Sideeects:Weightgain,hypoglycemia,sulfa
allergies
86
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SULFONYLUREAS DIABETESMEDICATIONSSENSITIZERS
1stgeneraBon: Biguanides(Meormin)
Chlorpropramide:SIADH Thiazolidinediones(Glitazones)
Tolbutamide
2ndgeneraBon:
Glypizide
Glyburide
BIGUANIDES(METFORMIN) THIAZOLIDINEDIONES(GLITAZONES)
Isused1stlineinconjuncJonwithdiet MOA:enhancetranscripJonoftheproteins
modicaJonandweightloss thatassembleinsulinreceptors(thus
MOA:decreasesthehepaJcglucoseoutput enhancinginsulinsensiJvity)
andincreasesuptakeofglucosebyperipheral Sideeects:theMCconcerniscardiacdisease
Jssuesandskeletalmuscle (soavoidiftheresapreexisJngcardiac
SideEects:GIupsetistheMCcomplain(N/V, problem)
diarrhea,atulence) Rosiglitazone(Avandia)
Pioglitazone(Actos0
87
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DIABETESMEDICATIONS
INSULIN
GLUCOSIDASEINHIBITORS
ONSET PEAK WEARSOFF
MOA:decreaseabsorpJonofcarbohydratesin
thesmallintesJnesoinsulinhasmoreJmeto
respond Regular 30MINUTES 4HOURS 6HOURS
SideEects:severebloaJngandatulence,
weightloss
23HOURS 6HOURS 8HOURS
Acarbose NPH/
SemiLente
Miglitol
THESAMOJIEFFECT THEDAWNEFFECT
Earlymorninghypoglycemialeadstoa Isanautoinducedhyperglycemiacausedby
reac:vehyperglycemialateinthemorning normalincreasesinepinephrine,glucagon,
(7am) andcorJsol
Earlymorninghypoglycemialeadsto Simplyincreasethemorningregularinsulinto
s:mula:onofepinephrineandglucagonto counteractthiseect
increaseglucoseintheblood
LowereveningNPHtopreventhypoglycemia
intheearlymorning
88
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ANABOLICMETABOLISM
Buildingitbackup
AQUICKREVIEWOFENERGY
GLYCOGENSYNTHESIS
SOURCES
Plasmaglucose(lasts24hr) SJmulatedinawellfedstate
Liverglycogen(lasts2448hr) Controlledrstbyinsulin,thenbycGMP
Proteins RatelimiJngenzymeofglycogensynthesisis
Fats GlycogenSynthetase
Ketones Glycogenlasts2448hr
89
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GLYCOGENSYNTHESIS5LOCATIONS GLYCOGENSYNTHESIS
Liverusedforplasmaglucose GlycogensynthetaseistheRLE
Adrenalcortexusedforplasmaglucose Glycogensynthetasecanonlyadd810
Skeletalmuscleusesglycogenforitself glucosemoleculesataJme(via1,4)
Cardiacmuscleusesglycogenforitself Branchingenzymeneededtochange1,4
Intes:nalwallusesglycogenforitself 1,6(thisensuresplentyofOHgroupsto
makeitmorewatersoluble)
StarJngproductisGlycogeninOH
UNDERSTANDINGBASICSOFGLUCOSE
GLYCOGENSYNTHESIS
MOLECULES&BONDING
90
9/17/11
COUNTINGCARBONS LINKAGESINGLYCOGENSYNTHESIS
GLYCOGENSYNTHESIS GLYCOGENBREAKDOWN
Requirestheenzymephosphorylase
PhosphorylasecutsatC1,releasinga
glucose1phosphate
Requiresdebranchingezymestoremovethe
1,6linkages(givesfreeglucose)
Cardiacmuscleusesan1,6glucosidaseto
releasefreeglucoseimmediately
91
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EACHINDIVIDUALMOLECULEOF
BREAKINGDOWNGLYCOGEN
GLUCOSE
BREAKINGDOWNGLYCOGEN BREAKINGDOWNGLYCOGEN
92
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BREAKINGDOWNGLYCOGEN TROUBLEBREAKINGDOWNGLYCOGEN
Weendupwithglycogenstoragediseases
Mustknowwhichenzymesareaected
MustknowthedeningcharacterisJcofeach
specicpathology
GLYCOGENSTORAGEDISEASES VONGIERKESDISEASE
VonGierkes(Glucose6Phosphatase) Glucose6phosphatasedeciency
Andersons(BranchingEnzyme) Thisenzymeisusuallymostabundantinliver
Corys(DebranchingEnzyme) andkidney,thusweaccumulateG6Pand
Pompes(Cardiac1,4glucosidase) theseorgansenlarge
Noglucosereleased=severehypoglycemia
McArdles(MusclePhosphorylase)
Hers(LiverPhosphorylase)
93
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ANDERSONSDISEASE CORYSDISEASE
Branchingenzymedeciency Deciencyofdebranchingenzyme
Istheonlyproblemwithglycogensynthesis Wecannotshortenourglycogenbeyond4
Liverllswithstraightchainsofglycogen(no moleculestothebranchpoint
longerthan810moleculeslong) Liverbiopsywillshowmanyshortbranches
HERSDISEASE McARDLESDISEASE
Deciencyofliverphosphorylase Deciencyofmusclephosphorylase
Wecannotbreakdownglycogendoreplenish Muscleusesitsownphosphorylaseforitsown
plasmaglucose glucoseproducJon
Enlargedliverisevidentbecauseofglycogen Severecrampingduringexerciseoccurs(not
accumulaJon whenatrestthough)
MuscleJssuebreaksdownduetotrauma(K+
leaksout)
94
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POMPESDISEASE
Deciencyofcardiac1,4glucosidase
Cardiacmuscleusesitsownglucosesupply
Noglucose=nocardiacenergy
Heartdiseasedevelopsinutero PENTOSEPHOSPHATEPATHWAY
Deathin1styearoflifeviaheartfailure
(HMPSHUNT)
TOMOVEINTOTHEPENTOSE
PENTOSEPHOSPHATEPATHWAY
PHOSPHATEPATHWAY
ProducesNADPH Plasmaglucosemustbehigh
ProducesRibose5phosphate Theremustbelotsofglycogensynthesis
PathwayisonlyacJvatedwheninthewellfed alreadyhappening
state ThereisanoxidaJvephase(generates
RLEisglucose6phosphateDH NADPH)
AllostericacBvatorisglucose6phosphate ThereisanonoxidaJvephase(givesusthe
Allostericinhibitorisribose5phosphate ribose5phosphateneededfornucleoJde
synthesis)
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PENTOSEPHOSPHATEPATHWAY
2PROBLEMSOCCURINTHENON LINKING4AND7CARBONSUGARSTO
OXIDATIVEPORTIONOFTHEPATHWAY PATHOLOGY
TheotherhalfofthenonoxidaJveporJonof Theresanareaofthebrainthatcontainsonly
thepathwayleavesuswitha4carbonanda transketolase
7carbonsugar
Normallytransketolasecanmanagetochange
Weuse2enzymestoremove1carbonfrom a4carbonand7carbonsugarintousable3
eachofthesesugars
carbonand6carbonsugars
Transketolase(TPPcofactor)and
Transaldolase(PLPcofactor) Whatsgoingtohappenifwecannoteliminate
Createa3Canda6Csugar(G3PandG6P) unusablesugarsfromaparJcularareaofthe
brain?
Thosethengetshueledintoglycolysis
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GLUCOSE6PHOSPHATEDH
DEFICIENCY
Anxlinkedrecessivedisease
IsseenmorecommoninMediterraneansasit
helpedprotectthemfrommalaria
AMINOACIDSYNTHESIS
LeadstooxidaJonofRBCandhemolysis
InfecJons,drugs,andsomefoodscan
exacerbatetheproblem
AMINOACIDSYNTHESIS AMINOACIDSYNTHESIS
Plasmaglucosehastobenormal ManyofthenonessenJalaminoacidsare
Liverhastohaveplentyofglycogen deriveddirectlyfromTCAandglycolysis
Thepentosephosphatepathwayhastobe intermediates
working Transamina:on:AA+ketoacidketo
Thenwecanstartmakingaminoacids acid+newAA
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TRANSAMINASES AMINOACIDSYNTHESIS
Therearemany,wehavetoknowofthe3
mostimportantones
AST
ALT
GGT
CofactorusedintransaminasesisvitaminB6
AASYNTHESISWheretheAAscome
from
FATTYACIDSYNTHESIS
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ABOUTFATTYACIDS FATTYACIDRULES
OurmainproducedFAisPalmi:cAcid,which Anythingbeyond16carbonsisnotmadeby
is16carbonslong ourbody(ie.TheybecomeessenJal)
AsaturatedFAhasnodoublebonds Adoublebondmustbeatleast3carbons
AnunsaturatedFAhassomedoublebonds apartfromanotherone
OmegaFAsarenamedbasedonthelocaJon Aperthe10thcarbontherearenodouble
ofthedoublebond(omega3,omega6) bonds
NAMINGOMEGAFATTYACIDS
Wrisenasfollows:#C:#dblbonds,locaJon1st
dblbond
Ex:20:3,omega3
Meansthereare20carbons,3doublebonds,
1stdoublebondis3carbonsfromC1
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FATTYACIDSYNTHESIS CITRATEACCUMULATION
AsweaccumulateNADH,FADH2,andGTPin AllostericinhibiJonofPFK1
theTCAweinhibittheRLEofTCA(Isocitrate AcJvaJonoftheRLEoffasyacidsynthesis
DH) (AcetylCoAcarboxylase)
TheseaccumulaJonsalsoinhibitPyruvate GetsdividedintoAcetylCoAandOAAvia
Dehydrogenase lyaserequiresATP
Citrateaccumulatesandmovesintothe
cytoplasmandhasafewspecicfuncJons CitrateAcetylCoA+OAA
ENZYMESBLOCKEDBYEXCESSIVE
ATPS
Pyruvatedehydrogenase
Isocitratedehydrogenase
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FATTYACIDSYNTHESIS
EachAcetylCoAcontains2carbons
EachAcetylCoAcomesfromcitrate
90%oftheNADPHusedinfaeyacid
synthesiscomesfromthepentosephosphate
pathway,theother10%comesfrom
WeneedamalonylCoAtostarteveryround
ofFAsynthesis
STEPSTOMAKINGFATTYACIDS FATTYACIDSYNTHESIS
Therearemanysteps
WeneedtoknowandunderstandonlyFOURof
thesesteps
ItcostsusTWONADPHperround
EachroundaddsTWOCARBONS
Aperthe1stroundwehaveFOURCARBONS
NADPHsneededperround=(#Carbons2)
#ofroundsrequiredtomakeacertain#chain=
[(#carbons/2)1]
#ATPrequiredforwholemolecule=C1
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ESSENTIALFATTYACIDS LINOLEICACID
LinolenicAcid(omega3)
LinoleicAcid(omega6)
Importantinmakingmodiedproductsthat
helpwithinammaJon,behavior,andmood
Linoleicacidisresponsibleformaking
ArachidonicAcid
LINOLEICACID ARACHIDONICACID
Anomega6fasyacid
Makesarachidonicacid
Componentoflipidcellmembranes
Foundinvegetableoils
Adeciencyleadstodryhair/skin,hairloss,
andpoorwoundhealing
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THECYCLOOXYGENASEPATHWAY THELIPOXYGENASEPATHWAY
Thromboxane(PGA2):Increases Producesleukotrienes
vasoconstricJon,increasesplateletaggregaJon LeukotrienecombinaJon(LTC4D4E4)creates
PGE2:vasodilaJon,keepsaPDAopen SRSA(slowreacJngsubstanceofanaphylaxis)
PGF2:causesvasoconstricJon,causespain,helps
SRSAreleased48hrsaperanallergic
separateplacentaaperdelivery
response
PGI2:prostacyclin,madeprimarilyby
endothelialJssue,decreasesplatelet CausessmoothmuscleconstricJon(MC
aggregaJon,causesvasodilaJon,mademoreso bronchioles)
byCOX2 SRSAdegradedbyArylsulfatase
IRRIVERSIBLECOXINHIBITION ADVERSECONSEQUENCESOFASPIRIN
AspirinisanirreversibleblockeroftheCOX GastriculceraJon/bleeding/gastriJs
pathway Thrombocytopenia
MOA:acetylaJonoftheCOXenzymedestroys Cinchonism(Jnnitus,hearingloss)
itsabilitytofuncJon Reyesyndrome
Func:onsinallofthefollowing:AnJ
IntersJJalnephriJs
inammatory,anJpyreJc,anJplatelet
ManagementofoverdoseisopenHC03
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NSAIDSANDTHECOXPATHWAY STEROIDS
Indomethacin ArethemostpotentanJinammatoryagents
Ibuprofen usedinmedicine
Naproxen HavemanyimportantacJonswhichmake
thembothpotentanddangerous
Importanttobeabletodecipherbetween
*Plateletsarentaectedaswithaspirinuse
dierentsteroidsusedthroughoutmedicine
COMMONLYUSEDSTEROIDSIN
STEROIDSMECHANISMOFACTION
MEDICINE
Thefollowingarethebigpictureac:onsofsteroids: Prednisone
Inhibi:onofPhospholipaseA(inhibitsarachidonicacid
breakdownandallproductsofit) Methylprednisolone
KillseosinophilsandTcells Beclamethasone
Inhibi:onofmacrophagemigra:on Betamethasone
Mastcellstabiliza:on
Stabilizesendothelium
HydrocorJsone
Causeproteinbreakdown Dexamethasone
S:mulategluconeogenesis
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COMMONLYUSEDSTEROIDSIN
STEROIDS
MEDICINE
Triamcinolone Anyadultwhousestheir2agonistinhaler
FludrocorJsone morethan1xperdayshouldalsobeusinga
Megesterol steroid
FluJcasone
Mometasone
Danazol
LEUKOTRIENERECEPTOR
MASTCELLSTABILIZERS
ANTAGONISTS
Stabilizingthemastcellmeansitwillnot Montelukast,Zarlukast,Zileuton
degranulate Eitherblocktheleukotrienereceptoror
TheseareusedMCinchildren inhibitthelipoxygenasepathway
MCisCromolyn MCusedisMontelukast(blocksreceptor)
Cromolyncomesinmanyformsandisvery Zileutonblocksthelipoxygenasepathway
safewithGIupsetastheonlycommonly
encounteredsideeect
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TRIGLYCERIDESYNTHESIS
Thisallowsustostorechainsoffasyacids
Occursonlyintheliver
TRIGLYCERIDESYNTHESIS WestartwithGlycerol3Phosphateandadd
16carbonchainstoit
ChainonC1issaturated
ChainonC2musthave1doublebond
TRIGLYCERIDESYNTHESIS
AddiJonofthe1stC16=Lysophospha:dic
Acid
AddiJonofthe2ndC16=Phospha:dicAcid
PhosphaJdicacidisthebackboneonwhich
complexphospholipidsaremade
AddiJonofthe3rdC16=Triglyceride
(Triacylglycerol)
LipidmodicaJonrequiresCDPcarrier
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LYSOPHOSPHATIDICACID PHOSPHATIDYLCHOLINICACID
TRIACYLGLYCEROL LIPIDMODIFICATION
UsuallyrequiresthecarriedCDP
Serine,choline,andethanolaminerequireCDP
Examples:
PhosphaJdylcholine
PhosphaJdylserine
PhosphaJdylinositol
PhosphaJdylethanolamine
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PHOSPHATIDYLCHOLINE PHOSPHATIDYLSERINE
TRIGLYCERIDETRANSPORT SIGNSOFHYPERTRIGLYCERIDEMIA
Chylomicrons:transportTGsfromGIto Pancrea::sduetorecurrentfatnecrosis
endothelialJssue Xanthelasmasyellowpatchesontheeyelids
VLDL:madeinliver,takesTGsfromliverto
adiposeJssueforstorage
IDL:transportaJonofTGsfromadiposeJssue
throughoutthebodytoallJssues
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SPHINGOLIPIDS CERAMIDEASABACKBONE
A16carbonmoleculewithanSCoAasached Ceramide+1sugar=Cerebroside
toit Ceramide+groupofsugars=Ganglioside
IsusedbyneuronalJssues
CarrierforcomplexlipidsisCDP
Sphingosine=CoASerine
Sphingomyelin=(CoASer)(CoASer)
Ceramide=CoASerineC16(becomesthe
backboneforcomplexsphingolipids)
BREAKINGDOWNSPHINGOLIPIDS LYSOSOMALSTORAGEDISEASES
LysosomesPhagosomes Themostimportantthingistheenzymethatis
Acidhydrolases(enzymesofthelysosome) missing
Lysosomalstoragediseases(lysosomal
inclusions)
Lysosomalinclusions=unusableenergy=
stateofenergydeciency
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LYSOSOMALSTORAGEDISEASES LYSOSOMALSTORAGEDISEASES
GAUCHERSDISEASE FABRYSDISEASE
Isthemostcommonlysosomalstorage Deciencyofgalactosidase
disease,isAR Isxlinkedrecessive
Glucocerebrosidasedeciency(aka PaJentsdevelopcataracts
glucosidase) PaJentsdeveloprenalfailureearlyinlife(1st
Gargoylelikefeatures signisproteinuria)
Macrophagesshowawrinkledappearance
Pseudohypertrophyofthelegsiscommon
SeeninAshkenaziJews
LYSOSOMALSTORAGEDISEASES LYSOSOMALSTORAGEDISEASESTAY
KRABBESDISEASE SACHSDISEASE
Deciencyofgalactocerebrosidase Autosomalrecessive
Youwillseemacrophageswithevidenceof DeciencyofHexosaminidaseA
thisenzymeinsideknownasGloboid SeeninAshkenaziJews
Bodies Maydevelopininfants,children,orasadults
InfanJlepresentsaround4monthswithrapid
onsetofmental/physicaldeterioraJon
Cherryredmaculaisseen
NOhepatomegaly(whereasmostothershaveit)
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LYSOSOMALSTORAGEDISEASES LYSOSOMALSTORAGEDISEASES
SANDHOFFSDISEASE NIEMANNPICKDISEASE
DeciencyofHexosaminidaseAandB DeciencyofSphingomyelinase
Autosomalrecessive NervesdemonstratealternaJngdarkandlight
LooksexactlylikeTaySachs areas(Zebrabodies)
Watchforachildwhoregressesaround6
monthsintheirdevelopment
LYSOSOMALSTORAGEDISEASES
HURLERSANDHUNTERS
METACHROMATICLEUKODYSTROPHY
DeciencyofArylsulfatase Hurlers:LIduronidasedeciency
CannotbreakdownslowreacJngsubstanceof Hunters:Iduronate2Sulfatasedeciency
anaphylaxis(SRSA) BothhaveGAGbuildup
PresentslikemulJplesclerosisina510yrold Gargoylismseeninboth
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CHOLESTEROLSYNTHESIS
Cholesterolisanimportantcomponentof
membranes
CHOLESTEROLSYNTHESIS TheRLEforcholesterolsynthesisisHMGCoA
Reductase
AllostericacJvaJonbyHMGCoA
AllostericinhibiJonbydietarycholesterol
CHOLESTEROLSYNTHESIS MANAGINGHYPERCHOLESTEROLEMIA
BlockingcholesterolabsorpJonbyblocking
pancreaJclipase
BlockcholesterolabsorpJonbyblocking
intesJnalabsorpJon
PreventsynthesisbyinhibiJngtheRLE
Bindingagentstobindandexcreteinthefeces
InhibiJonofVLDL
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ORLISTAT EZETIMIBE
OrlistatisadrugusedtoblocktheabsorpJon DecreasescholesterolabsorpJonbyinhibiJon
ofcholesterolbyinhibiJonpancreaJclipase itfromcrossingatthebrushborderofthe
MarketedasAlli smallintesJne
MajorproblemismalabsorpJonleadingto AlsoleadstoupregulaJonofLDLreceptors
greasystoolsandanalleakage(steatorrhea) andthuslowerscirculaJnglevels
CancausesteathorrheajustlikeOrlistat
STATINS STATINSPECIFICEFFECTS
Mostpopularandwidelyusedcholesterol Simvasta:n:excellentfordiabeJcsasitslows
medicaJon atherosclerosis
InhibitstheRLEHMGCoAReductase Atorvasta:n(Lipitor):iscardioprotecJve,
AlldrugsendinStaJn loweringriskofcardiovasculardisease
VeryeecJveatloweringLDL(upto40% Rosuvasta:n(Crestor):whencombinedwith
reducJon) othercholesterolloweringdrugshashigh
Adjunct:cholestyramineorcholesJpol incidenceofrhabdomyolysis(toxictokidneys)
CommonsideeectsincludemyosiJs,hepaJJs, Provasta:n:istheleastfatsolubleofthe
cataracts,anddemenJa group,bestforpaJentswithneuroproblems
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NIACIN
IsalastresortwhenothermedicaJonsfailto
producesaJsfactoryresults
Workbyinhibi:ngVLDLproduc:oninthe
THEUREACYCLE
liver
Maycauseushing/pruriJsduetohistamine
release
HasstrongabilitytoincreaseHDLbyover40%
THEUREACYCLE THEUREACYCLE
Canworkduringbothanabolicandcatabolic
states
Isoneofthe3processesthatoccursinboth
themitochondriaandthecytosol
TheRLEisCarbamoylPhosphateSynthetase
1
AllostericacBvators:NH4+andN
acetylglutamate
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THEUREACYCLE THEUREACYCLE
Nacetylglutamateisyourmostimportant
allostericacJvator
Reasonisbecauseifwegetthismoleculeit
meanstherewereexcessiveamountsof
transaminaJonreacJonsoccurring
ToomanytransaminaJonreacJonswillsignal
CPS1thatthereistoomuchammoniumand
weneedtoeliminatesome
THEUREACYCLE THEUREACYCLELIVERFAILURE
90%oftheureacycleoccursintheliver 1stthingwedoislimitproteinintake
10%oftheureacycleoccursinthecollecJng 2ndthingwedoisgivethepaJentNeomycin
ductofthekidney tokillureaseposiJveGIbacteria
IfpaJentisdemonstraJngsignsof
encephalopathygiveLactulose
115
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WHATELSETOAVOIDINLIVER
UREACYCLEDEFECTSINANEWBORNS
FAILURE
Anythingthatrequiresmetabolismbytheliver: ImportanttounderstandthatelevatedNH4+
levelsindicateaproblemearlierinthecycle
Anyfatsolubledrug pHwillbeelevatedbecauseNH3+picksup
AnydrugthataectstheP450system freeH+andconvertsintoNH4+
2typesoftrickstheyllthrowatyouonthe
Alcohol
boards
Barbituratesandbenzodiazepines(willkill
yourpaJentveryquickly)
NUCLEOTIDES
Arethebuildingblocksofnucleicacids
ForDNA,RNA
NUCLEOTIDES Forcarriers:UDP,CDP
Formethylgroupcarrier(SAM)
For2ndmessengers(cAMP,cGMP)
Forenergy
116
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PURINES PYRIMIDINES
AdenineandGuanine Cytosine,Thymine,Uracil
Suxofineisabase ThymineisonlyfoundinDNA
Suxofsideisasugar UracilisonlyfoundinRNA
Suxof:deisaphosphate Pyrimidinedimerscausedbyultravioletlight
(thymineismoresensiJvetoUVlight)
EndonucleaseshelprepairTdimers,butif
weremissingtheenzymewegetlotsof
thyminedimersXerodermaPigmentosa
NUCLEOTIDEEXCISIONREPAIR XERODERMAPIGMENTOSUM
UVdamagepyrimidinedimers AnARdiseasewherethereisaninabilitytorepair
damagecausedbyUVlight
Excisionofdamagedareaoccursvia MutaJonorabsenceofNucleo:deexcisionrepair
endonucleases enzymesaretheproblem
PaJentsdemonstrateextremephotosensi:vityand
DNApolymeraserepairsthemissingsequence changesinpigmenta:on
ThenewporJonissealedwithenzymeligase MulJpleareasofbasalcellcarcinomaarenormalata
youngage
The2MCCofdeathinanXPpaJentaresquamouscell
CAandmetasta:cmalignantmelanoma
Deathiscommonby20yrofage(opensooner)
117
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NUCLEOTIDES NUCLEOTIDES
Euchroma:n(looseDNA)
Heterochroma:n(JghtDNA)
TESTSFORDETECTION
SouthernBlotDNA
NorthernBlotRNA
WesternBlotProteins PURINESYNTHESIS
ELIZAdetectsanJbodies
PCRusedtoamplifysmallquanJJesof
DNAorRNA
118
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PURINESYNTHESIS PURINESYNTHESIS
PURINESALVAGEPATHWAY SALVAGEOFADENINE
NeedtheSalvagePathwaywheneverPRPP
islow(rememberPRPPisacJvatorofdeNovo
RLEstep)
ThispathwaywillborrownucleoJdesfrom
dyingcellsandusetheirhypoxanthine
HypoxanthineisreadilyconvertedintoIMPvia
HGPRT
AdenineisconvertedtoAMPviaAPRT
GuanineisconvertedtoGMPviaHGPRT
119
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SALVAGEOFGUANINE SALVAGEOFHYPOXANTHINE
PROBLEMSWITHTHESALVAGE
HGPRTDEFICIENCY
PATHWAY
TheMCproblemisadeciencyofHGPRT
ThisshuntssalvagedproductsintoproducJon
ofxanthineandthenuricacid.
LeadstoaccumulaJonofPRPPwhich
sJmulatesthedeNovopathway
LeschNyhannSyndromeisaresultofHGPRT
deciencyandaccumulaJonofuricacid
throughoutthebodyuids
120
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LESCHNYHANNSYNDROME GOUT
Anxlinkedrecessivediseasethatcausesa AcondiJoncausedbyhyperuricemia
deciencyofHGPRT MCpresentaJonisanacutelyinamedbigtoe
LeadstoaccumulaJonandbuildupofuric (Podagra)
acid(hyperuricemia,hyperuricuria) DeposiJonofuricacidisnotwithinthejoint,
Onsetisinthe1styearoflife(crystalsin butundertheskinandaroundthejoin
diaper,poormuscletone,irritability) (periarJcular)
2ndyearoflifeandbeyondpaJenthasclassic Pathognomonicndingisnega:vely
selfmuJlaJngbehavior birefringentcrystalsofuidaspirate
GOUT GOUTMANAGEMENT
ETOHandproteinarecommondietarycauses ForacutegoutyaeacksweuseColchisine
GeneJcmayplayaroleinalteringuricacid IfpaJenthasrenalorbonemarrowproblems
levels useindomethacin
MedicalcondiJonssuchasHTN,DM, Forchronic/recurringgoutyaeacksweuse
hypertriglyceridemiaareopenseenin Allopurinol+Probenecid
paJentswithgout
Gouthasatendencytoexacerbatemany
medicalproblems
121
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PYRIMIDINESYNTHESIS PYRIMIDINESYNTHESIS
Carbamoylphosphate2isrequiredbutthis
Jmeweareinthecytosol
CarbamoylphosphateOro:cacid
OroJcacid+PRPPUMP(uracilonlyinRNA)
UMPTMPorCMP
TMP=UMP+Methylgroup(TMPonlyin
DNA)
CMP=UMP+aminegroup
REGULATIONOFDNAPRODUCTION RIBONUCLETIDEREDUCTASE
RequirestheenzymeRibonucleoJde
Reductase
RNRisresponsibleforensuringwedontmake
toomuchDNA(maintainsaconstantraJoof
DNA:Cellmass)forcelldivisionandDNA
repair
AtthispointweveonlymaderibonucleoJdes,
sowehavetomadedeoxyribonucleoJdes
usingRNR
122
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RIBONUCLEOTIDEREDUCTASE SCID
DuetoadeciencyofAdenosineDeaminase
ThisallowsdATPtoaccumulateandshutdown
DNAproducJontooearly
Allrapidlydividingcellsareaected
EarlyinlifepaJentsaremostsuscepJbleto
infecJons(MCCofdeathinrst2yearsoflife)
HISTONES
HelppackageourDNAintomorecompact
products(DNAhelix)
5types(H1,H2a,H2b,H3,andH4)
Nucleosomeisanoctomerofnucleo:des(2of
eachtype)andiswrappedinDNA
H1isalinkerproteinthatlinkseachoctamer
HistonescontainposiJvelychargedbases
becauseitmustinteractwellwithphosphate
123
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THECELLCYCLE
Isaseriesofeventsthatleadstocellular
division
G1makesproteinsthatwillberequiredfor
replicaJon
SDNAsynthesisandcentrioles
G2makesproteinsspecicformitosis
Mmitosis
GoresJngphase
DNAREPLICATION
IssemiconservaJve
Isdegenerate
Wereadinthe35direcJon
Wedoeverythingelseinthe53direcJon
124
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DNAREPLICATION TELOMERASE
OKAZAKIFRAGMENT:ashortDNAfragment
onthelaggingstrand
Nascentstrand:istheoldstrand
Daughterstrand:isthenewstrand
125
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TRANSCRIPTION
DNARNA
MainenzymeusedisRNApolymerase
Twozonesofrecogni:on(35recognizedby
coreenzyme,10recognizedbysigmafactor)
CAATbox:signalsbindingsiteforRNA
transcripJonfactors
TATAbox:isacorepromotersequenceandis
thebindingsiteforgeneraltranscripJon
factors
REPRESSORANDENHANCERGENES MODIFICATIONS
REPRESSORGENES:notstaJonaryonyour Intronsgetremoved,exonsremain
chromosomes SplicingoccursviaSNRPS(smallnuclear
ENHANCERGENES:staJonaryonthesame ribonucleoproteins)
chromosome
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TRANSCRIPTION
1stproductitmakesispremRNA
PremRNAmustbemodiedsothatitisready
fortranslaJon
ModicaJonsincluderemovingintrons,
addingaPolyAtail,andaddingaguanosine
captothe5endofthemRNA
SPLICINGOFmRNA ADDITIONOFPOLYATAIL
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ADDITIONOF5METHYLGUANOSINE
TRANSLATION
CAP
CreaJonofproteinfromourmRNA
SeveraltypesofRNAarerequiredtomakeitall
work
mRNAfromtranscripJon,madefromRNA
polymerase2(isthebiggesttypeofRNA)
rRNAcomesfromthenucleolusandismade
fromRNApolymemrase1(isthemostabundant
typeofRNA)
tRNAtransferRNAfromRNApolymerase3(is
thesmallesttypeofRNA)
TRANSLATIONSTEP1INITIATION
ThesmallribosomalsubunitasachestothemRNA
fromthe5capandmovestotheiniJaJonsite
ThetRNAwiththeanJcodontothestartcodon(AUG)
binds
Thelargeribosomalsubunitbinds,creaJngtherstP
site
ThenexttRNAenterstheAsiteandthe1staminoacid
istransferredfromPsitetoAsite
tRNAinthePsiteisreleasedandthetRNAintheAsite
movesintothevacantPsite,makingroomforthenext
tRNAtoenterintotheAsite
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TRANSLATIONSTEP2ELONGATION TRANSLATIONSTEP3TERMINATION
AseachnewtRNAentersintotheAsite,it Stopcodonisencounteredandarelease
receivesthechainthatisbuildingandis factorentersintotheAsite,signalingthe
boundtothetRNAinthePsite terminaJonoftranslaJon
ThisconJnuesunJlastopcodonis Theribosomedissociatesandthenewly
encountered formedpepJdeisreleased
Whenencountered,areleasefactorwillcome
inandterminatethetranslaJon
ENERGYREQUIREMENTSFOR HIGHYIELDFACTSABOUT
TRANSLATION TRANSLATION
ForeachAAthatisasached,4GTPsare Thereare64tRNAs(1start,3stop,restforAAs)
EachAAasachedrequires4GTPs
required
EnzymeforasachingnewAAisPepJdylTransferase
2GTPstoasachtheAAtothetRNA SmallribosomalsubunitreleasesiniJaJonfactors(IF1,
IF2,IF3)IF2recruitsthelargeribosomalsubunit
1GTPtondeachcodon LargeribosomalsubunitreleasesIF2aswell,thisJme
1GTPforthemovementofthetRNAfromA itisresponsibleforndingthenextcorresponding
tRNA
siteintoPsite AminoacetyltRNAsynthetaseaddseachAAtothe
3OHendofthetRNA,givingittheenergyneededto
addtheAAtothegrowingpepJdechain
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MUTATIONS
FrameshipmutaJon
PointmutaJon(TransiJonorTransversion)
SilentmutaJon
MissensemutaJon
nonsense
130

WEEK 3
9/17/11
STEPSTOFIGURINGITALLOUT
Step1Distribu.on
Wheredoestheproblemgoorpresent
RHEUMATOLOGY Singlejoint=monoar'cular
Afewjoints=oligoar'cular
Manyjoints=polyar'cular
Movesaround=migratory
MONOARTICULARINVOLVEMENT OLIGOARTICULARINVOLVEMENT
Osteoarthri's(causedbytoomuchacOvity) Spondyloarthropathies(Ankylosing
Gout(toomuchuricacid,negaOvely spondyliOs,reacOvearthriOs,psoriaOc
birefringentneedleshapedcrystals,podagra) arthriOs)
Sep'carthri's(elevatedWBCs,oTen>
50,000)
1
9/17/11
POLYARTICULARINVOLVEMENT MIGRATORYARTHROPATHIES
RheumatoidArthri's Rheuma'cFever(mitralvalveaectedrst)
SystemicLupusErythematous GonococcalArthri's(disseminaOon)
Viraldiseases(HepaOOs,ParvoB19,CMV) LymeDisease(fromtheIxodesOck)
STEPSTOFIGURINGITALLOUT STEPSTOFIGURINGITALLOUT
Step2Acutevs.Chronic Step3Aretheresystemicsymptoms?
Acutecondi'onsarecausedbysomething Pulmonary:pleuraleusioncausedbySLE
thathasrecentlyhappened(crystalinduced, Renal:proteinuriacausedbyRF
sepsis,gout) CNS:vasculiOs,strokes,changesinpersonality
Chroniccondi'onsdevelopoverOme
Skin:malarrash,photosensiOvityrash(Lupus)
(OsteoarthriOs)
Hematologic:anemias(immunemediated)
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STEPSTOFIGURINGITALLOUT JointsoftheHand
Step4Isthereevidenceofinamma.on?
Noinamma'on:OsteoarthriOs
Inamma'on:RheumatoidarthriOs
JointAspiraOon
AnyOmethereisuidinajoint
Isthenextbeststep(notthebest
conrmatorystepthatisbiopsy)
THETESTS/LABSWEUSETO
NeveraspirateajointinapaOentwith
DETERMINERHEUMATOLOGICAL bleedingdyscriacies,overlyingcelluliOs,or
DISORDERS paOentwithabnormalINRs(d/theparin,
warfarin)
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Next WBCRanges
ATeraspiraOon,alwaysorderthe3Cs
WBCs
Cultures
Crystals
CRYSTALS ANTIBODIES
SEPTICARTHRITIS= AnONuclearAnObodies
GOUT= AnONeutrophilCytoplasmicAnObodies
PSEUDOGOUT= AnOdsDNA
RHEUMATOIDARTHRITIS= AnOSmith
OSTEOARTHRITIS= AnOphospholipid/AnOcardiolipinanObodies
TRAUMA= Rheumatoidfactor(RF)
SLE=
4
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AnONeutrophiliCytoplasmic
AnONuclearAnObodies(ANA)
AnObodies(ANCA)
10%ofthepopulaOonwilltestposiOvefor AnanObodyagainstspecicneutrophil
ANA cytoplasmicproteins
97%ofallSLEpaOentswillhaveaposiOve cANCA:foundinWegenersgranulomatosis,
ANA aectskidneysandlungs
IfANAis+ve,checkanOSmithandanOdsDNA cANCAhasadiusestainingpagern
pANCA:seeninpolyarthriOs
Likestoagackmyeloperoxidase
AnOdsDNA,AnOSmith
BotharehighlyspecicforSLE
5
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AnOPhospholipidAnObody RheumatoidFactor
AnObodiesagainstthephospholipidlayerofa IsanautoanObodythatactsagainsttheFc
cellsmembrane porOonofIgG(alsoananObody)
PosiOveinanOphospholipidsyndrome TheyformanimmunecomplexthatcausesRA
Leadstothrombosisofarteriesandveins ThemoreRFpresent,themoreseverethe
PregnancyrelatedcomplicaOonsarecommon destrucOonofthedisease
AlsoseeanOcardiolipinanObodies MaybeelevatedinothercondiOons(butnot
(componentoftheinnermitochondrial ashighasinRA)
membrane)
HIGHYIELDRHEUMATOLOGYDISEASES RHEUMATOIDARTHRITIS
RHEUMATOIDARTHRITIS Achronic,systemicinammatorydisease
SYSTEMICLUPUSERYTHEMATOUS MayaectanyOssueororgan,butmainly
SCLERODERMA aectsthesynovialjoints
SJORGENSYNDROME SymmetricdistribuOon
SPONDYLOARTHROPATHIES 1520%ofRApaOentshaveextraarOcular
OSTEOARTHRITIS manifestaOons
GOUT/PSEUDOGOUT
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Anyofthefollowingfor6weeks CommonhanddeformiOes
MorningsOnessthatlastsmorethan1hr
Symmetricjointswelling
Swellingofatleast3joints
Swellingofthewrist,MCPorPIPjoints
ExtraarOcularmanifestaOons LabndingsinRA
Skin:rheumatoidnodules RFisincreased
Lungs:brosis,pleuraleusions ESRisincreased
Renal:renalamyloidosis,glomerulardamage Xraymayshowbonyerosions(laterstages)
Cardiac:increasedriskofatherosclerosis Analysisofsynovialuid(WBC=2,000
increasesriskofstrokeandMI 50,000)
Eyes:keratoconjuncOviOssicca
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ManagementofRA SYSTEMICLUPUSERYTHEMATOUS
1stline=Methotrexatefor1week AsystemicdiseaseaecOngmulOpleorgans
FollowMTXwithPrednisonefor1week DamagecausedbyanObodiesandimmune
ConOnuePrednisoneonlywhenareups complexesagainsttheOssues
occur AnOnuclearanObodyMUSTbeposiOveto
makediagnosis
**ifptcannottolerateMTX, Diagnosis:1stcheckANA,conrmwithanO
Hydroxychloroquinecanbeused dsDNAandanOSmith
OrgansaectedinSLE
SKIN:malarrash,discoidrash,
photosensiOvity
RENAL:endstagerenaldisease
LUNGS:intersOOallungdisease
CNS:alteredmentalstatus(confusion),
personalitychanges
HEMATOLOGIC:autoimmunehemolysis
BONES:bonyerosions
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SLEManagement DRUGINDUCEDLUPUS
NSAIDS:forarthirOcpain Doesntcausemajororganinvolvement
STEROIDS:formajororganinvolvement IsalimitedformthatisduesolelytoingesOon
ANTIMALARIALS:chloroquine ofaprecipitaOngdrug
CYTOTOXINS:azathioprinetoinhibittcells, DiagnosisbasedonpresenceofRASH+anO
cyclophosphamideforcrosslinkingofDNA histoneanObodies(withnormalcomplement
levels)
DisconOnuetheoendingagent
PregnancyandLUPUS
FerOlityratesarenowaectedinpaOentswith
Lupus
PresenceofspontaneousaborOonsandsOllbirths
isanindicaOonthatanOphospholipid/anO
cardiolipinanObodiesarepresent(putthemon
LMWHtodecreasecloong)
ExacerbaOonsrequiresteroids
ScreenallpregnantpaOentswithLupusforSSA/
AnORoanObodies
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SCLERODERMA SJORGENSYNDROME
Achronicsystemicautoimmunedisease Chronicautoimmunedisease
MainmanifestaOonisbrosisoftheskin
(thickening,hardening) Autoimmuneagackofthelacrimaland
90%ofcasespresentwithRaynauds salivaryglands(dryeyes,drymouth)
phenomenon MCseeninfemalesintheir40s
2types:Limited(CRESTSyndrome),andDiuse
Systemic(skin+1ormoreorgans) Labs:ANA,RF,SSA/La
Diagnosis:basedonndings,anO Diagnose:Schirmertest,SlitLamptest,
topoisomeraseand/oranOcentromere salivaryglandultrasoundiseasiestdiagnosOc
anObodies
test
SPONDYLOARTHROPATHIES ANKYLOSINGSPONDYLITIS
Inammatorydiseaseoftheaxialskeletonand
AnkylosingSpondyli.s peripheraljoints
Reac.veArthri.s MCseeninyoungmales(intheir20s)
Psoria.cArthri.s Chroniclowerbackpain,morningsOness
EnteropathicArthropathy lasOngmorethan1hr,improveswithexercise
90%ofpaOentswilltest+veforHLAB27
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ASExtraarOcularmanifestaOons REACTIVEARTHRITIS
SKIN:erythemanodosum(tenderrednodules AcomplicaOonofaninfecOonsomewherein
undertheskin,MConshins) thebody
CARDIAC:aorOcinsuciency MCCinclude:Nongonococcalurethri's
SPINE:decreasedmoOlity (Chlamydia,Ureaplasma),andInfec'ous
EYES:conjuncOviOs/anterioruveiOs Diarrhea(Campylobacter,Shigella,
Salmonella)
PSORIATICARTHRITIS ENTEROPATHICARTHROPATHY
ArthriOs+PsoriaOcsymptoms SeeninulceraOvecoliOsandCrohnsdisease
AectstheDistalinterphalangealjoints Pyodermagangrenosum(deep,necroOc
Piongofthenails(specic) ulcers)
Sausageshapeddigits(nonspecic) Erythemanodosum(subQrednodulesMC
seenontheshins)
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OSTEOARTHRITIS
DegeneraOvejointdiseasethatdestroys
arOcularcarOlageandsubchondralbone
Mayaectanyjoint,butMCaectshands,
OSTEOARTHRITIS feet,spine,andweightbearingjoints(hips,
knees)
PrimaryForm:relatedtoaging
SecondaryForm:relatedtonumerous
disorders(DM,obesity,inammatory
diseases)
OSTEOARTHRITIS
Symptoms:jointpain,tenderness,sOness,
jointlocking
HeberdensnodesaectDIPs
BouchardsnodesaectPIPs
Bunyons=OsteoarthriOsofthetoes
Diagnosis:basedonPEandxrayndings,normal
ESRandCRP
Treatment:lifestylemodicaOons(exercise,wt
loss),andAcetaminophen
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Osteophytes CRYSTALINDUCEDARTHROPATHIES
GOUT
PSEUDOGOUT
GOUT GOUTCauses
AcutemonoarthriOscausedbyexcessiveuric Excessiveintakeofalcoholorredmeat
acidaccumulaOon UseofdiureOcssuchasHCTZandFurosemide
Tophi=DeposiOonofmonosodiumuratein AnOTBmedssuchasPyrazinamideand
theOssues Ethambutol
Podagra=Tophiinbigtoe Trauma
(metatarsophalangealjoint) InfecOons
Allofthesecanleadstoincreaseduricacid
levelsintheblood
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GOUTDiagnosis/Mgmt HYPOURICEMIA
Analysisofthejointuid Chronicallylowlevelsofuricacidintheurine
NegaOvelybirefringent,needleshaped PaOentsrequirelifelongtherapyandmust
crystals followuricacidlevelsconstantly
WBCsareintheinammatoryrange(5,000 ForthosewhoarenotsecreOngtheiruricacid
50,000)
properly,wegiveProbenecid(forceskidneys
NSAIDsaremainstayofmanagement tosecretemoreuricacid)UA<600
(Indomethacin50mgOd)
GiveColchisineeveryhourunOlsymptom Forthosewhoareoverproducinguricacid,
resolve wegiveAllopurinolUA>700
PSEUDOGOUT
CausedbyaccumulaOonofasalt(Calcium
PyrophosphateDihydrate),noturicacid
IsacommoncauseofacutearthriOsinasingle
joint(amongadults) Andnally
MCaectsthekneejoint
Crystalsare+vebirefringent,rhomboid
shaped,andlooklikealinearradiodense
depositinthemenisciofthejoints
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SEPTICARTHRITIS
MCCbygonorrheainfecOons
IntheelderlypopulaOontheMCCisStaphAureus
Musttapthejointandgramstaintheuidto
determinethecause(mostcasesshowWBCs>
50,000)
StaphAureustx=IVVancomycin
Gonococcaltx=IVCeTriaxone
Removalofinfecteduidfromthejointtendsto
decreasethepain
BRAINEMBRYOLOGY
Prosencephalon(forebrain)
Mesencephalon(midbrain)
NEUROLOGY Rhombencephalon(hindbrain)
Anatomy,Physiology,andPathology
oftheNeurologicalsystem.
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BRAINEMBRYOLOGY
Primi.veStreakNotochordSpinalCord
Notochordstartstoforminthe2ndweeks
Notochordisvisiblebythe3rdweek
Notochordiscompletelydevelopedbythe4th
week
BRAINEMBRYOLOGY
Therefore..
By3weeksthenotochordisvisibleandby4
weeksitisdone
By8weeksthebrainisfullyformed
ThebrainisacOveearlyon,especiallywith
reexes(importantforprocessingamnioOc
uid)
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AMNIOTICFLUID AMNIOTICFLUIDINDEX
Mostisaltratefromthemothersplasma
Fetususesswallowingreextosubtractsome
ofit(isabsorbed/digested)
Fetusadds20%byurinaOonofthefetus
HowdowemeasuretheamnioOcuid?
POLYHYDRAMNIOS RileyDaySyndrome(Polyhydramnios)
AmnioOcuidof>2024 KnownasFamilialDysautonomia
Maternalcause=diabetes SeenmainlyinAshkenaziJews,isamutaOon
Fetalcause=obstrucOon toIKBKAPgeneonchromosome9
RileyDaysyndrome ANSdysfuncOonleadstovariousautonomic
WerdnigHomansyndrome problems
IniOalndingisusuallylackoftearswhen
crying(xerophthalmia)mustgivearOcial
tears
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SPINALCORD
MotorneuronsdevelopfromSHH
SensoryneuronsdevelopfromBMP
StartsattheoccipitalboneandendsbetweenL1
THESPINALCORD L2
EndsattheConusMedullaris
NerveshangingfromcordaretheCaudaEquina
FilumTerminalisanchorsthestructuretothe
sacrum
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THEVERTEBRAE
7cervical,12thoracic,5lumbar,sacrum
consistsof5fusedvertebrae(fusedby
1618yr)
Fusionofvertebralarchesstartsventrallyand
movesdorsally(bidirecOonally)
Prematurebirthsmayresultinincomplete
fusion,resulOnginholesatthetoporbogom
Failuretofuse=SpinaBida
Abnormalspinalcolumncurvaturescanoccur
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SPINABIFIDA SPINABIFIDAOCCULUTA
Congenitaldisorderwherebytheresan Vertebralarchdefect
incompleteclosureofeithertheneuraltube Outervertebrafailstoclosecompletely,butis
ortheoverlyingvertebrae toosmallforcordtopassthrough
3maincategories:Occulta,Meningocele, Maybebirthmark,hair,ordimpleovertopof
Meningomyelocele theerror
Associatedwithinadequatefolateintake MostareAsx(upto10%ofthepopulaOonis
duringpregnancy thoughttohavethisdiscoveredwhendoing
ElevatedlevelsofFPandAchE lumbarimagingforsomethingelse)
MENINGOCELE
Meningesherniatebeforethevertebralarch
closes
Thespinalcordremaininthevertebralcanal
Isthemostrareformofspinabida
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MENINGOMYELOCELE
MCandmostseriousofallspinabidatypes
Bothmeninges+spineherniatethroughthevertebral
defect
ProblemiseitherdamagetoSCortodevelopmentof
SC
AssociatedwithArnoldChiariMalformaOon2
MCiniOalsymptomishydrocephalus
ParalysisandlossofsensorypercepOonoccursbelow
thelesion
FolateduringpregnancyisessenOaltopreventthis
fromoccurring
NEURALTUBEDEFECTS
Anencephaly
Encephalocele
Encephalomeningocele
Encephalmeningomyelocele
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ANENCEPHALY
Failureofthecephalicendoftheneuraltube
resultsinabsenceoftheforebrain
FPishighinmaternalserum
Mostbabieswontsurvivepastbirth,those
whodocanbreathe810breathsperminute
(medullaispresent)
PrognosisisdeathshortlyaTerbirth
ENCEPHALOCELE
Neuraltubedefectwherebythebrainand
meningesprotrudethroughopeningsinthe
skull
Failureofneuraltubetocloseduring
development
Ismidline(middleofskull,foreheadtonose,
orocciputoftheskull)
Accompaniedby
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CEREBROSPINALFLUID FUNCTIONSOFTHECSF
Howisitmade? Protec'onfromtrauma
Whichvitaminisrequiredtomakeit? Buoyancy(decreasesweightofbrainthrough
Whichenzymeisrequired? buoyancy)
WhichcellslinetheenOretracttakenbyCSF? Preventsbrainischemia
HowdoesCSFgetbackedup? Provideschemicalinstability
THEFLOWOFCSF CHEMOTACTICTRIGGERZONE(CTZ)
Locatedatthebaseofthe4thventricle
RespondstoDAandincreasedICP
SOmulatesbothnauseaandvomiOng
AreaPostrema:locatedonthebloodsideof
theBBB,respondstosmellsortasteswend
oensive(sOmulatedbyDA)
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HYDROCEPHALUS COMMUNICATINGHYDROCEPHALUS
Communica'ng:duetoaCSFoverproducOon ExcessCSFproducOonorimpairedresorpOoninthe
absenceofanyowobstrucOonbetweenthe
orlackofreabsorpOon ventriclesandsubarachnoidspace
Noncommunica'ng:duetoanobstrucOonof Newbornsprematurenewbornstendtodevelop
intraventricularhemorrhage,addingtotheexisOngCSF
normalCSFow volume
ChildrenMCduetoinammaOonwhichblocks
reabsorpOon
AdultsMCCispseudotumorcerebri(obesefemaleon
reOnoicacid)
ElderlyMCCisatrophyofthebrain
NONCOMMUNICATINGHYDROCEPHALUS
DuetosomeformofobstrucOon
NewbornsstenosisistheMCC(Cerebral
Aqueduct),CystisthenextMCC(4thventricle)
NEUROCUTANEOUSSYNDROMES
ChildrenMeningiOsandTB
AdultsCanceristheMCC
ElderlyCanceristheMCC
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STURGEWEBERSYNDROME OSLERWEBERRENDUSYNDROME
Portwinestainontheface(d/texcessof Smallaneurysmaltelangiectasiasontheskin
capillariesaroundV1ofCN5) andmucusmembranes
Glaucoma CanleadtoGIbleeding
Seizuresatbirth CancausepulmonaryAVstulas
MentalretardaOon
MainconcernismonitoringICP
TUBEROUSSCLEROSIS VONHIPPELLINDAU
ADcondiOonseeninchildren510yrofage FrommutaOoninVHLsuppressorgene
Presentswithbenigntumorsthatlooklike ADcondiOonswherehemangioblastomasare
acne foundinanyofthefollowing
Benigntumorsofanyand/orallorgans Cerebellum
Mostcasespresentwithacoloboma(big KidneyandAdrenals
idenOfyingclue) ReOna
Spinalcord
PresenceofCafauLaitspots
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MIGRAINEHEADACHES
Females>males(raOoof3:1)
Maylastanywherefrom472hr
HEADACHES StronggeneOccomponent(upto80%of
migrainesuerersalsohaverelaOvewho
suer)
MIGRAINEDiagnosis MIGRAINEManagement
Mustseeatleast2ofthefollowing Acutemanagement:Triptandrugs(5HT
Unilateral agonistsleadtovasoconstricOon)
PulsaOlequality
Aggravatedbymovement
Moderatetosevereinintensity(oTendebilitaOng) Prophylaxis:Betablockers(preventexcess
Andmustsee1ofthefollowing vasodilaOon)
Nauseaand/orvomiOng
Photophobia
Phonophobia
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TENSIONHEADACHE CLUSTERHEADACHE
Isamild/moderateheadache Asevereunilateralheadache
Localizedtothetemporal/periorbitalarea
Isusuallybilateralandlocatedinthefrontal Theycomeinclustersof18smallheadachesperday(last
and/oroccipitalarea 1590min)
Comeandgoforperiodsof46weeks
Hasabandlikequality Muchmorecommoninmen(8:1)
Maybeaccompaniedbyanyofthefollowing
OTenstressrelated Ipsilateralrhinorrhea
NotdebilitaOng Miosis
NasalcongesOon
NotassociatedwithnauseaorvomiOng Eyelidedema
ANATOMYOFTHEEYE
THEEYES
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ANATOMYOFTHEEYEMUSCLES VISION
20/20vision
20/1620/12isconsideredperfectvision
20/200islegallyblind
Childrenarebornwith20/400
NearSightednessvs.FarSightedness ANISOCORIA
Myopia:nearsightedness(ie.Theycannotseefromfar Unequalpupilsize
away)
ThefocusoflighthappensbeforethereOna,weneed InchildhoodtheMCCisincreasedICP(UnOl
concavelensestodispersethelight
Hyperopia:farsightedness(ie.Theyhavetroubleseeing provenotherwise)
objectscloseup) IsacongenitalADdisorderifnopathologyis
FocusoflightisbehindthereOna,treatwithconvexlenses
tofocuslightearlier found
Presbyopia:lossofaccomodaOonthatoccurswithaging
Duetomuscleweakening
Troublefocusingonobjectsapproachingthem
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Anisocoria AMBLYOPIA
LazyEye
Theresadierenceineacheyesacquity
WeakeningofCNs3,4,and6
Treatmentinvolvespatchingthestrongereye
sotheweakonewillcatchuptoit
AllamblyopiapaOentsneedregular
ophthalmicexams
STRABISMUS
Misalignmentoftheeyes
Extraocularmusclesarentinsync,canbe
neurologicalorcanbeweakenedmuscles(CN3,
4,6)
Esotropia:eyesdeviatedmedially
Exotropia:eyesdeviatedlaterally
Hypertropia:eyesdeviatedsuperiorly
Hypotropia:eyesdeviatedinferiorly
Treatmentinvolvesspecializedeyeglasses,vision
therapy,andcorrecOvesurgery
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ASTIGMATISM
IstheMCreasonwhysomeonevisitstheeye
doctor
Abnormalcurvatureofthecornealeadsto
blurryvision(refracOveerror)
Eyeglassescancorrectmostcases,otherwise
alaserkeratotomyiscorrecOve
THEWHITEREFLEX
IssuggesOveofcataractsorreOnoblastoma
Cataracts:opacicaOonofthelens
LightcannotgettothereOna
Mustberemoved
Re'noblastoma:rarecancerofthereOna
MutatedRB1gene
MCsignisleukocoria(whitereecOonfrom
reOna)
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UNDERSTANDINGTHEVISUAL
FIELDANDITSDEFICITS
OpOcRadiaOon/MeyersLoop MONOCULARVISUALLOSS
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SCOTOMA BITEMPORALHEMIANOPSIA
CONTRALATERALSUPERIOR
CONTRALATERALHEMIANOPSIA QUADRANTANOPIA
32
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CONTRALATERALINFERIOR ContralateralHomonymousHemianopsia
QUADRANTANOPIA w/MacularSparing
THECRANIALNERVES THECRANIALNERVES15
CN1OLFACTORY:senseofsmell
CN2OPTIC:vision
CN3OCCULOMOTOR:innervatesLevator
Palpebraesuperioris,SuperiorRectus,Medial
Rectus,InferiorRectus,andInferiorOblique
CN4TROCHLEAR:innervatesSuperiorOblique
CN5TRIGEMINAL:sensaOontotheface,
innervatesmusclesofmasOcaOon(V1
Ophthalmic,V2Maxillary,V3Mandibular)
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THECRANIALNERVES69 THECRANIALNERVES1012
CN6ABDUCENS:Innervateslateralrectus CN10VAGUS:MotorinnervaOontomost
laryngealandallpharyngealmuscles,
CN7FACIAL:Tastetoanterior2/3oftongue, parasympatheOcinnervaOontomostabdominal
musclesoffacialexpression,secretomotor andthoracicviscerauptosplenicexure,
innervaOontosalivaryandlacrimalglands sensaOonfromepigloos
CN8VESTIBULOCOCCLEAR:Sensessound, CN11ACCESSORY:MotorinnervaOonto
sternocleidomastoidandtrapezius
gravity,androtaOonofthehead/body
CN12HYPOGLOSSAL:MotorinnervaOontoall
CN9GLOSSOPHARYNGEAL:Tastetoposterior tonguemuscles(exceptPalatoglossus),
1/3oftongue,secretomotortoparoOdgland, importantforbolusformaOon/swallowing,and
motorinnervaOontostylopharyngeus speecharOculaOon
FORAMINAOFTHESKULL
GROSSANATOMYOFTHEBRAIN
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THEFRONTALLOBE
35
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THEFRONTALLOBE ProblemsoftheFRONTALLOBE
Determinespersonality DemenOa(Alzheimers,Picksdisease)
HighercogniOvefuncOon/abstractreasoning Atonicseizures
Consistsofthepremotorandmotorareas Schizophrenia(leadstobrainasymmetry)
(originofcorOcospinaltract)
THEPARIETALLOBE MAJORBRAINVASCULATURE
Thedominantlobe(istheleTsidein90%of
thepopn)
Responsibleforlongtermmemory
DestrucOonleadstolossofabilitytodobasic
tasks
Thenondominantlobe(istherightsidein
90%ofthepopn)
DestrucOonleadstoapraxiaandhemineglect
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LATERALPONTINESYNDROME
AlsocalledAICASyndrome
AnocclusionoftheAnteriorInferior
CerebellarArtery
AcuteonsetN/V,verOgo,nystagmus,fallingto
sideofinjury
IpsilaterallossoffacialsensaOon
Ipsilateralfacialparalysis
IpsilateralhearinglossandOnnitus
LATERALMEDULLARYSYNDROME
PosteriorInferiorCerebellarArteryocclusion
Aectscerebellarpeduncle(causesipsilateral
limbataxia)
Aectsdescendinghypothalamics(causing
ipsilateralHornerssyndrome)
Aectsnucleusambiguous(causesdysphagia)
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MEDIALMEDULLARYSYNDROME
OcclusionofoneorbothoftheVertebral
arteries
CN12injuryleadstotonguedeviaOon
(towardsthesideofthelesion)
PyramidsleadstocontralateralspasOc
hemiparesis
MEDIANMIDBRAINSYNDROME
Posteriorcerebralarteryocclusion
CN3aected(eyedeviatesdownandout)
CorOcobulbartractaectslowerface
CorOcospinaltractaectsupperlimb
(contralateralspasOchemiparesis)
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EPIDURALHEMATOMA
Middlemeningealarterytear
Commonlycausedbyfracturetothetemporal
bone
HIGHYIELDBLEEDSTOTHEBRAIN
Lucidinterval
Lensshapedbleed
CTifrststepindiagnosis(lookatshape,+/
midlineshiT)
SUBDURALHEMATOMA
Causedbytearingofthebridgingveins
Slowleaks=slowonsetofsymptoms
Crescentshapedbleedbetweenduraand
arachnoidmater
1ststepistogetaCT
2ndstepistodoanLP(lookingfor
xanthocromia)
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SUBARACHNOIDHEMORRHAGE
Rupturedaneurysmisthemostlikelycause
(Berryaneurysm)
OthercausesmaybeAVM
Bleedingbetweenthearachnoidandpia
mater
PaOentc/oworstheadacheoftheirlives
CTisusuallydiagnosOc,ifnegaOveanLPis
mandatory
THALAMUS&HYPOTHALAMUS
40
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THALAMUS
SensoryrelaybetweenthecortexandmulOple
subcorOcalareas
Allsensorysystemscontainthalamicnuclei
(excepOonistheolfactorysystem)
MedialthalamusrelaysinformaOonaboutthe
lowerbody
LateralthalamusrelaysinformaOonaboutthe
arms
HYPOTHALAMUS
Majorcontrolcenterforthebody
Controlsallofthefollowing.
Hunger/Thirst
Autonomicregula'on(stressresponse)
Temperature
Sexualbehavior
Adenohypophysisviareleasingfactors
Neurohypophysisviareleaseofsynthesizedhormones
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THALAMICNUCLEI
THERETICULARACTIVATINGSYSTEM
RETICULARACTIVATINGSYSTEM THEBASALGANGLIA
Caudatenucleus
Putamen
Globuspallidus(internalandexternal
segment)
Subthalamicnucleus
Substan'anigra
42
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SUBSTANTIANIGRA
ResponsibleforiniOaOonofmovement
Dopamineisitsneurotransmiger
InhibiOonfromotherbasalgangliastructures
(GABA,Ach)
LossofDAbers=Parkinsonsdisease
ParkinsonsDisease Parkinsonsmanagement
IscausedbyalossofDAbersfromsubstanOa 1stline:Levedopa/Carbidopa
nigratothestriatum(caudateandputamen)
UnabletoiniOateacOon,alsodicultystopping 2ndline:BromocripOne(DAagonist)
oncemoving Amantadine(inuenzaA,increasesDArelease
Telltalesxinclude fromnerveterminals)
Pillrollingtremor
Selegeline(MAOBI,preventsDAbreakdown)
Bradykinesia
Shuinggait Tolcapone(COMTinhibitor,increases
Masklikefacies levedopabioavailability)
AutonomicdysfuncOon
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HUNTINGTONSDISEASE WILSONSDISEASE
ADtrinucleoOderepeatdisorder ARdisorder
AectsHunOngOngeneonchromosome4 TheceruloplasminproteinisdefecOve,leadingto
excesscopperintheserum
LackofGABAergicneuronsinthecaudate DeposiOonintheliver,kidneys,eyes,andbrain
nucleusleadstoinvoluntarymovement leadtoamyriadofsymptoms
(chorea) Movementdisordersandpsychologicaldisorders
ShowsanOcipaOon(worsewitheach areprominent
generaOonatyoungerage) KayserFleischerringsarepathognomonic
ManagewithDAblockers TreatwithPenicillamine
THEINTERNALCAPSULE
Sitsinbetweenthecaudate/thalamusandthe
lenOcularnucleus
Containsallmotorbersthatrunintoandout
ofthebrain
MIDBRAIN
AectedbyaLacunarhemorrhage(leadsto
motordefects)
SuppliedbytheLenOculostriatearteries
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THEREFLEXARC
CORTICOSPINALTRACT
Responsiblefornemotorac'vity
Mustinhibitexion/extensionsotheopposite
canoccurinanemotorfashion
Fibersfromthistractoriginatefromfrontal
lobe/precentralgyri
Fibersdescendthroughinternalcapsule,cross
atmedullarypyramids,anddescendthrough
spinalcord
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CORTICOSPINALTRACTPATHOLOGY DecorOcatevs.DecerebratePosturing
ALSmotorneurondegeneraOon
VitaminB12deciencyaectstheCStract
inaddiOontothedorsalcolumn
Seizuresatonicseizures
DORSALCOLUMNS
ResponsibleforvibraOonsense
2pointdiscriminaOon
ConsciouspropriocepOon
PosiOonsense
Twoimportantparts:GracilisandCuneatus
Gracilis:fromlegs,locatedmedially
Cuneatus:fromarms,locatedlaterally
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DORSALCOLUMNPATHOLOGY SPINOTHALAMICTRACT
VitaminB12deciency Sensespainandtemperature
Syphilis(tabesdorsalis) Crossesinthespinalcord(notinthebrain)
BrownSequardSyndrome(hemisecOonofthe Fibersenterspinalcord,ascend2levels,then
cord) crosstotheoppositesideviawhite
commissure
SPINOTHALAMICPATHOLOGY
Syringomyelia:thisisaformaOonofauid
lledcavitywithinthecenterofthecord
Canexpandanddisruptthewhitecommissure
=lossofpain/tempsensaOoninacapelike
distribuOon
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SPINOCEREBELLARTRACT
Responsibleforpropriocep'on(limbandjoint
posiOon)
UsedbyGolgitendonsandmusclespindles
Onlypathwayinspinalcordwith2
decussaOons(maintaininganipsilateral
nding)
Pathway:DorsalrootganglionThalamus
Cerebellum(doesntreachthecortex)
SPINOCEREBELLARPATHOLOGY
Alcohol(aectsthevermis,whichismidline),
allotherdiseasesaectthehemispheresof
thecerebellum)
FriedreichsAtaxia
THEPONSANDMEDULLA
AtaxiaTelangiectasia
Adrenoleukodystrophy
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THEPONS PONSPathology
Respondstothesurroundingenvironment LockedinSyndrome:rapidosmoOcshiTleads
toasyndromewherebypaOentcannot
Containsthefollowing moveonlyblinkingispossibleinthis
Pneumotac'ccenter(ponOnerespiratorygroup): syndrome.
locateddorsally/laterally,antagonizesapneusOc
CentralPon'neMyelinolysis:isMCdueto
center,cyclicallyinhibitsinspiraOon
rapidcorrecOonofhyponatremia,andmay
Apneus'ccenter:locatedinlowerpons,controls
intensityofbreathing alsobeassociatedwithalcoholism
CranialNerves5,6,7,8
THEMEDULLA
ControlsallbasicfuncOons
SOllpresentinanencephaly
Providesourbasalrespiratoryrate(810) Andnally
Cranialnerves9,10,11,12
HowcanIgureouteverylesion?
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Isaspinalcordlesionwhen IsaCNSlesionwhen
Painandtemperaturelossisoppositetoall UMNsignsareononesideofthebody
otherdecits Thenthelesionisontheoppositesideofthe
Thelevelofthelesionis2dermatomesabove brain
wherepainandtemperaturelossbeginsand UsetheCNstolocatethelevelofthelesion
onoppositeside(ex.LesionatL4,lossatL6)
CARDIACMEDICINE
Physiology&PathologyoftheHeart
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ELECTROLYTEBEHAVIOR ELECTROLYTEMOVEMENT
ConcentraOongradient Depolariza'on:tobecomemoreposiOve
Electricalgradient Repolariza'on:tobecomemorenegaOve
Drivingforce Overshoot:tobemoreposiOvethanthe
Conductance(Gion) thresholdpotenOal
Nernstnumber(Eion) Hyperpolariza'on:tobecomemorenegaOve
thanbaselinepotenOal(undershoot)
ELECTROLYTEMOVEMENT
AbsoluteRefractoryPeriod:Omeduring
whichnoacOonpotenOalcanpropogate
Rela'veRefractoryPeriod:Omeduringwhich
anAPcanbepropogatedwithextrasOmulus
Threshold:theminimumsOmulusthatis
requiredtogetafulldepolarizaOon
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REESTABLISHINGTHEGRADIENT
GradientisreestablishedbytheNa/Kpump
ResOngmembranepotenOalisestablishedby
theNa/Caexchange
DepolarizaOon(Na+movesin)phase0
RepolarizaOon(K+movesout)phase3
ResOngmembranepotenOal(automaOcity)
phase4
THEHEART THESANODETRACING
Atriumconsistsmainlyofslowcalcium
channels
TheSAnodeislocatedhighupintheRA,
wherethesuperior/inferiorvenacavameet
TheAVnodeislocatedinthelowermedial
walloftherightatrium,istheslowest
conducOngsiteintheheart
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THEAVNODETRACING HEARTBLOCKS
2:1,3:1,4:1
TheyaresimplytheAVnodeprevenOngatrial
arrhythmiasfromhurOngtheventricles
Duringatrialarrhythmias,youmainconcernis
sOlltheventriles
Ifventricularrateiscontrolled,everythingis
ne
THEVENTRICLES
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UNDERSTANDINGTHEEKG
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MOREANATOMYOFTHEHEART
RIGHTvs.LEFTSIDECORONARYINFARCT UNDERSTANDINGTHE12LEADEKG
Heartblock(right)
Ventriculararrhythmia(leT)
HeartfailurefollowingMI(leT)
Suddendeath(leT)
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12LEADEKG 12LEADEKG
BipolarLeads:3oftheseleads Sta.onaryLeads:AVR,AVL,AVF
Theystartatonespotandendatanother AVR:looksattherightatrium
(hencebipolar) AVL:looksattheleTatrium
Wheretheystopiswheretheylookatthe AVF:looksattheapex
heartfrom
Theyarelead1,lead2,andlead3
12LEADEKG Remember
AnteriorLeads:6ofthese
TheyarelocatedoverparOcularareasoftheheart
V1:sitsattheRanteriorsternalborder,seestheright
atrium
V2:sitsattheLuppersternalborder,seestheleTatrium
V3:
V4:sitsattheLlowersternalborder,seestheanterior
surfaceoftheapexbest
V5:sitsattheLlowersternalborderatthemidclavicular
line,seestheleTventriclebest
V6:sitsattheLlowersternalborderatthemidaxillaryline,
seestheleTventriclebest
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WhatwillAVRlooklike? WhatwillV3looklike?
TWAVEINVERSIONS INFARCTEDTISSUE
WhentheTwavedeectsintheopposite PresenceofnegaOvedeecOonsseen
direcOonasyourQRS consistentlyindicatesdeadOssue
ItmeansrepolarizaOonsaremovinginthe NegaOvedeecOonsinV5andV6tellusleT
wrongdirecOon ventricledamageispresent
Theheartselectricalcurrentswillcanceleach
otherout
VentricularbrillaOonsarethemainconcern
Startlidocainedrip
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HEARTBLOCKS 1STDEGREEHEARTBLOCK
NormalPRintervalis<0.2seconds AxedandprolongedPRinterval
1stdegreeblocks(xedandprolongedPR ProblemlieseitherattheSAnodeorbetween
interval) theSAandAVnode
2nddegreeblocks(twopossibleproblems) Signalisprolongedbutventriclesbeat
3rddegreeblocks(completedissociaOonof normally
theSAandAVnodes) Notreatmentisnecessary
2NDDEGREEHEARTBLOCK 3RDDEGREEHEARTBLOCK
2types TheresacompletedissociaOonbetweenthe
MobitzType1:aprogressivelengtheningof SAandAVnode
thePRintervalunOlaQRSisdropped AVnodehasinfarcted
TreatmentifsymptomaOc ThereisnorelaOonshipbetweenthePwaves
andtheQRS
MobitzType2:anormalPRintervalwith Treatmentispacemaker
droppedQRScomplexes
Treatmentisplacementofpacemaker
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PREMATUREVENTRICULARCOMPLEXES
/CONTRACTIONS
AlwaysapauseaTeraprematurebeat
VentriclesarespendingtoomuchOmeintheRRP
NoPwave,widenedQRScomplex,pause
followingQRScomplex
PVCeveryotherbeat=Bigeminy
PVCevery3rdbeat=Trigeminy
Vb:therearenorecognizableQRScomoplexes
Vtach:thereare3ormoreconsecuOvePVCs
andaminimumHRof150
VTACH VFIB
Ifstable,treatwithmedicaOon Epinephrine
Ifunstable,shock ThenshockthemasinVtach
ApaOentwhoshowsupwithalife
threateningarrhythmiawarrantsAmiodarone
rst(willneedintubaOonandICUplacement)
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IMPORTANTELECTROLYTESAFFECTING
ATRIALARRHYTHMIAS DEPOLARIZATION
PrematureAtrialContracOons(PAC) SODIUM
MulOfocalAtrialTachycardia(MAT) CALCIUM
ParoxysmalSupraventricularTachycardia MAGNESIUM
Atrialuger POTASSIUM
AtrialbrillaOon
SODIUMHYPERNATREMIA SODIUMHYPONATREMIA
Normalsodiumlevelis135145mEq/L Morelikelytodepolarizebecausesodium
Cellsaremorelikelytodepolarize leaksoutandcalciumleaksin
CorrectslowlywithnormalsalineandHCTZ Canbeinducedbyexercising
Treatwith3%salinewhenlevelsare<
120mEq/L
CorrectslowlytopreventcentralponOne
myelinolysis
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CALCIUMHYPERCALCEMIA CALCIUMHYPERCALCEMIA
Intheatriumtheyaremorelikelyto MorelikelytoseedepolarizaOoneverywhere
depolarize (exceptintheatrium)
Everywhereelseinthebodytheyareless Willaectthe2ndmessengersystems
likelytodepolarize Chvostekssign(facialspasmontappingfacial
TreatwithIVnormalsalineandloopdiureOcs nerve)
Trousseaussign(carpalpedalspasmwhen
inaOngaBPcu)
MAGNESIUMHYPERMAGNESEMIA MAGNESIUMHYPOMAGNESEMIA
Lesslikelytodepolarize(strongerdrivingforce MorelikelytogetdepolarizaOons
thanSodium) Aectsallkinases(isacofactorinkinase
Excellentinslowingseizuresbecauseitbeats reacOons)
sodium Aectscalciumandpotassium
LowerelevatedMg2+bydiluOngitthengiving Treatwithmagnesiumsulfate
aloopdiureOc
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POTASSIUMHYPERKALEMIA POTASSIUMHYPOKALEMIA
Morelikelytodepolarize(iniOally) LesslikelytodepolarizesinceK+isgoingto
PeakedandwidenedTwaves rushoutofthecells
ProlongedQTintervals FasterrepolarizaOon(narrowTwaves,
Treatment:calciumgluconate,insulin, invertedTwaves)
glucose,HC03 PresenceofUwave
BRICKLE
HEARTSOUNDS
HEARTSOUNDS
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HEARTSOUNDS HEARTSOUNDS
S1:closureofthemitralandtricuspidvalves Isovolumetriccontrac'on:thesamevolume
Mitralvalveclosesrst(greaterpressureonrt intheventriclesbetweentheclosureofthe
side) tricuspidandmitralvalvesandtheopeningof
Tricuspidvalveclosessecond(lesspressureonlt thepulmonaryandaorOcvalves
side)
Isovolumetricrelaxa'on:theperiodbetween
S2:closureofpulmonaryandaorOcvalves
S2andS3whentheaorOcandpulmonic
Pulmonaryresistanceislessthantotalbody
resistance,sothepulmonaryvalvewillcloserst valvesshutandthemitralandtricuspidre
AorOcvalvewillclosesecond open
OPENINGSNAP EJECTIONCLICK
Soundmadebyforcingavalveopenduring Thissoundismadebyforcingavalveopen
diastole duringsystole
Eithertricuspidormitralstenosis MustbestenosisofaorOcorpulmonicvalve
AvalvebeingforcedopenmustbestenoOc
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MIDSYSTOLICCLICK SOFTvs.LOUDS1
Bloodmovingathighvelocityslapsthemitral Involveeithermitralortricuspidvalve
valve Sod:oneofthesevalvesisnotclosing
ClosertoS1whenstanding Loud:oneofthesevalvesiseithersOand
ClosertoS2whenlyingdown bangsshut,ortheventricle(s)arecontracOng
Mitralvalveprolapse(MVP) harder
SOFTS2 LOUDS2
Aor'corpulmonicvalveiseithernotclosing OneofthevalvescontribuOngtoS2aresO
properlyorthevalveismissing ORthereshighpressureinfrontofthevalves
Notclosingregurgita'on (eithersystemicorpulmonaryHTN)
Notpresentatresia(botharecyanoOcat AorOcstenosis
birth) Pulmonarystenosis
PulmonaryHTN
SystemicHTN
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INSPIRATIONANDBLOODFLOWTO
S2SPLITTING
THEHEART
AdierenceinOmebetweenclosureofaorOc InspiraOonincreasesnegaOvepressureinthe
andpulmonaryvalves thoraciccavity
Increaseswhenyouinhale(physiologic VacuumformaOonpullsbloodintotheright
spliong) sideoftheheart
3reasonswhyS2spliengoccurs:More02
InspiraOonwillmakepathologyontheright
deliverytolungs,increasedvolumeinlungs,
delayedopeningofpulmonaryvalve sidesoundlouder
CannarrowS2byincreasingthepressurein ExpiraOonwillmakepathologyontheleTside
thelungs(pulmonaryvalveshutssooner) soundlouder
S3 S4
MCmeanstheresadilatedventricle DuetoatriacontracOngagainstanabnormally
Volumeoverload sOorhypertrophiedventricle
DecompensaOon PressureoverloadandexcesscompensaOon
NormalONLYinanadolescentfemales(higher Atrialkick
estrogenlevels) Leadstoagallopcausedbyatherosclerosis
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RESISTANCEANDVOLUME
Systolic=Resistance
Diastolic=Volume
StressfulsituaOons/individualsusuallyresultin
systolicHTN
DietshighinsaltusuallyresultindiastolicHTN
BLOODPRESSURE DIAGNOSINGHTN
NormalBPis<120/80 Asinglereadingabove200systolicor2
SDis20forsystolic,15fordiastolic readings>135systolic=Hypertension
MildsystolicHTNis135155 >135/85on2ormoreoccasionsatleast1
ModeratesystolicHTNis155175 weekapartisdiagnosOccriteria
SeveresystolicHTNis175195
MilddiastolicHTNis85100
ModeratediastolicHTNis100115
SeverediastolicHTNis115130
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SYSTOLICvs.DIASTOLICDYSFUNCTION AV02
SystolicdysfuncOonmeansthereisa Isthedierencebetweentheoxygeninthe
resistanceproblems(toomuchdilaOon) arteryandtheoxygenintheblood
DiastolicdysfuncOonisavolumeproblem(too Atresttheheartextractsthemost02owing
muchhypertrophy) throughit(~97%)
Themore02usedbyOssues,thegreaterwe
saytheAVO2dierence
ThekidneyhasthelowestAV02dierenceof
allorgansalltheOme
ESSENTIALCARDIOVASCULAR
HOWTOLOWERICP
EQUATIONS
SV=EDVESV Step1:hypervenOlaOon
CO=SVxHR Step2:IVMannitol
BP=COxTPR=SVxHRxTP Step3:IVAcetazolamide
MeanArterialPressure=1/3Systolic+2/3 Step4:Burrhole(ifsteps13fail()
Diastolic
CerebralPerfusionPressure=MAPICP
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MURMURGRADES
Grade1:BarelyaudibleonauscultaOon
Grade2:EasilyaudibleonauscultaOon
MURMURS Grade3:Pregyloud
Grade4:Palpablethrill
Grade5:Hearwithstethoscopeothechest
Grade6:Abletohearwithoutastethoscope
SYSTOLICMURMURS SYSTOLICMURMUS
ValvesthatshouldbeopenarestenoOcOR Aor'cstenosis
valvesthatshouldbeclosedarenotclosing Pulmonarystenosis
AorOcandpulmonicvalvesshouldbeopen Mitralregurgita'on
Mitralandtricuspidvalvesshouldbeclosed Tricuspidregurgita'on
Pansystolic:sameasholosystolic,theygoall Ventricularseptaldefect
thewayacrossS1andS2
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PANSYSTOLICMURMURS SYSTOLICEJECTIONMURMURS
MurmurgoesacrossbothS1andS2 AorOcstenosis
Tricuspidregurgita'on Pulmonarystenosis
Mitralregurgita'on CausesaloudeningofS2becauseitisa
VSD resistanceproblem
LouderonrightsideduringinhalaOon
LouderonleTsideduringexhalaOon
IDIOPATHICHYPERTROPHIC
AORTICSTENOSIS
SUBAORTICSTENOSIS(IHSS)
AkaCOMH
Autosomaldominant
IstheMCCofsuddendeathinyoungathletes
Musclebersarehypertrophiedand
disorganized,leadingtosubaorOcstenosis
MurmurislouderwhenlessbloodintheleT
sideoftheheart(standing,valsalva)
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DIAGNOSINGIHSS MANAGINGIHSS
BestdiagnosOctestisECHO GoalistoensureadequateOmeindiastole
Valsalvamaneuverinthecliniccanhelpyou Giveabetablocker
idenOfyanIHSS Banthemfromorganizedsports
IHSSgetslouderwithvalsalvabecausethere Adequateuidintakeisessen'al
isntenoughbloodintheleTventricletokeep ThewholefamilymustgetanECHObecauseit
theasymmetricseptumfromfallingintothe
isanADdisorder
ventricle
DIASTOLICMURMUS AORTICREGURGITATION
ValvesthatshouldbeopenarestenoOcOR IslouderonexpiraOon/leaningforward
valvesthatshouldbeclosedareregurgitant /squaong
AorOcregurgitaOon ESVwillbeincreased
PulmonaryregurgitaOon RadiatestothecaroOds
Mitralstenosis Widepulsepressureisalwaysseen(high
Tricuspidstenosis systolic+lowdiastolic)
PaOentmayc/odyspneaonexerOon,
orthopnea,orparoxysmalnocturnaldyspnea
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AORTICREGURGITATION PULMONARYREGURGITATION
Radiatestotheback
IslouderoninspiraOon
DIASTOLICRUMBLES
Tricuspidstenosis(louderwithinspiraOon)
Mitralstenosis(louderwithexpiraOon)
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CARDIOMYOPATHIES
DILATEDCARDIOMYOPATHY
RESTRICTIVECARDIOMYOPATHY
CollagenVascularDisease
CARDIACPATHOLOGY Hemochromatosis
Amyloidosis
HYPERTROPHICCARDIOMYOPATHY
CONSTRICTIVECARDIOMYOPATHY
Tamponade
TYPESOFEFFUSIONS
Transudate:isauidmademostlyofwater
SINCEWEVEDISCUSSEDFLUIDBUILDUPIN Specicgravity<1.012
THEHEARTLETSDISCUSSEFFUSIONS Protein<2g
Exudate:isauidmademostlyofprotein
Specicgravity>1.012
Protein>2g
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CONGENITALHEARTDISORDERS
InorderofMCoccurrence,thecongenital
heartcondiOonsare
VSD
ASD
PDA
COARCTATION
VSD ASD
Isthemostcommoncongenitalheartdefect MCCisaseptumprimumdefect
CommunicaOonbetweentheventricles LeadstoaxedwidespliongS2
Holosystolicmurmurcanbeheard
WithlargedefectathrillcansomeOmesbefelt
CreatesaleTtorightshunt
Mostcaseswillxthemselves
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PDA COARCTATIONOFTHEAORTA
Normallyductusarteriosuscloseswithin Preductalandpostductaltypes
1224hraTerbirth Preductalformisseenin5%ofTurners
PDAallowsaconnecOonbetweentheaorta syndrome
andpulmonaryartery Postductalformisseeninadults
ClosewithNSAIDS(Indomethacin) PostductalformisassociatedMCwithrib
OnauscultaOonwehearaconOnuous notching
machinelikemurmur UpperextremityHTN,weakpulsesinthe
lowerextremiOes
CYANOTICCONGENITALHEART
LISTOFCYANOTICHEARTCONDITIONS
DISEASES
ThesecondiOonsareAsxunOlthePDAcloses TetralogyofFallot
Transposi'onoftheGreatArteries
IdenOfyingacyanoOcheartcondiOonand
Tricuspidatresia
keepingthePDAopenwithprostaglandins
Truncusarteriosus
Totalanomalouspulmonaryvenousreturn
Aor'catresia
Pulmonaryatresia
Ebsteinsanomaly
Hypoplas'cledheart
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TRANSPOSITIONOFTHEGREAT
TETRALOGYOFFALLOT
ARTERIES
TheMCcyanoOcheartdiseaseinaninfant Aortaandpulmonaryarteryareswitched
(112months) Severecyanosis,poorfeeding,andSOB
Overridingaorta FirststepinmgmtiskeepingthePDAopen
Pulmonaryarterystenosis withprostaglandins
Rightventricularhypertrophy Secondstepisaballoonatrialseptostomyto
VSD allowshunOngofblood
Thirdstepissurgicalswitchingofthegreat
arteries
TRICUSPIDATRESIA TRUNCUSARTERIOSUS
Notricuspidvalve,insteadjustapieceof Pulmonaryarteryandaortaareasinglevessel
Ossue Alsojust1bigvalve
SoTS1 OnauscultaOonyouwillonlyhearasingleS2
CVPrisesbecausebloodbacksup
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TAPVR AORTICATRESIA
Totalanomalouspulmonaryvenousreturn NoclearpathwayfromLVtotheaorta
Pulmonaryveinsreturnonlytotheright Onlysourceofsystemicbloodowisthrough
atrium theductusarteriosus
BloodiscaughtinaconOnuouspathway OTenoccursincombinaOonwithhypoplasOc
(showsagureeightonxray) leTheartsyndrome
NotcompaOblewithlife Usuallyresultsindeath
PULMONARYATRESIA EBSTEINSANOMALY
NarrowS2spliongduetodecreasedblood Tricuspidvalvedevelopstoolowintheright
owtothelungs ventricle
SoTS2 Valvesarealsoabnormallylarge
RightventriculardilaOon Resultsinaregurgitantvalve
CanbecausedbyusingLithiumduring
pregnancy
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HYPOPLASTICLEFTHEART
THEMCCOFVALVULARDISEASES
SYNDROME
LeTventricleistoosmall Aor'cstenosis:DystrophiccalcicaOon(dueto
aging)
HRwillbeveryhighbecausestrokevolumeis Aor'cregurgita'on:DystrophiccalcicaOon
verylow (duetoaging)
PaOentrequiresaseriesofsurgeriestore Mitralstenosis:RheumaOcfever
arrangetheconnecOonsbetweentheSVC, Mitralregurgita'on:MVP,SBE,Collagen
Diseases
IVC,andpulmonaryarteries TricuspidStenosis:RF,carcinoidsyndrome
Tricuspidregurgita'on:AcuteendocardiOs(IV
drugs)
FLOWVOLUMELOOPS DILATIONOFVENTRICLE
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CONSTRICTIONOFVENTRICLE WOLFPARKINSONWHITESYNDROME
Ventriclesarepreexcitedduetoanaccessory
pathwayknownastheBundleofKent
Mostpeoplewiththisaccessorypathwayare
Asx
IstheMCCofpalpidaOons(SVTs)inyoung
people
EKGdemonstratesadeltawave(aposiOve
slantthatcomesbeforeanarrowedQRS)
ANTIARRHYTHMICS
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CLASS1SodiumChannelBlockers
Blocktheventricles,aectsQRS(lowerheight,
wider)
Class1Ablockssodiumchannelsintheopen
state,slowlyrecover
Class1Bblockssodiumchannelsinthe
closedstate,hasafastrecovery
Class1Cblockssodiumchannelsintheopen
state,veryfastrecovery
SODIUMCHANNELBLOCKERS SODIUMCHANNELBLOCKERS
Class1A:Quinidine,Procainamide, Class1B:Lidocaine,Phenytoin
Disepyramide
Lidocaine:haslowtoxicity,isDOCforpostMI
Quinidine:hasstronganOcholinergic arrhythmias
properOes,cancausecinchonism MaycauseCNSsOmulaOonordepression,as
wellascardiacdepression
Procainamide:ananestheOc(canhelpwith
Phenytoin:usedmainlyforseizuredisorder,
neuropathies),causesdruginducedlupus,
cancausemegaloblasOcanemiaandgingival
canalsoblockK+channels hyperplasia
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SODIUMCHANNLEBLOCKERS CLASS2BetaBlockers
ClassIC:Flecainide,Ecainide,Propafenone Decreasetheslopeofphase4,increasingPR
Flecainide:bestusedforlifethreatening interval
ventriculararrhythmias(asalastresort)..Do Decreasecalcium
notusepostMIasitisaproarrhythmic DecreasecAMP
Propafenone:maycausehypersensiOvity
reacOons Includes:Metoprolol,Esmolol,Atenolol,
Propranolol
CLASS3K+channelblockers CLASS4
Blocksthephase3ofventricular
repolarizaOon
DemonstratesReverseUseDependence,thus
begeratprevenOngarrhythmias
MainK+channelblockerisAmiodarone
Amiodarone:isDOCforlethalarrhythmias
CausessignicantprolongaOonofPRinterval
Toxictolungs,liver,andthyroid
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PULMONARYMEDICINE
Pulmonaryphysiology&Pathology
EMBRYOLOGYOFTHELUNGS FormaOonofNeuralCrestCells
Endodermgivesrisetothelungs
TracheaandlaryngealcarOlageisderivedfrom
neuralcrestcells
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EMBRYOLOGYOFTHELUNGS Whenarethelungsready?
Lungsdevelopin1sttrimester Lecithin/Sphingomyelinra'oisatleast2:1
SurfactantproducOonisntcompleteunOl Toomuchsphingomyelintellsusthenervous
3234weeks systemissOllbusymyelinaOng
Surfactantsrole:Decreaseatmospheric Surfactantisamodiedformoflecithin
pressureseectonalveoli,increasethe PhosphaOdylglycerolisabreakdownproduct
alveolarcompliance ofsurfactant(tellsusthebabywillbeableto
breatheonitsown)
WithoutSurfactant RDSvs.ARDS
Wegetatelectasis RespiratoryDistressSyndrome(RDS)occursin
Poorcomplianceensues infantsduetolackofsurfactant
Aagradientincreases AdultRespiratoryDistressSyndrome(ARDS)
02cannotproperlydiuse occursinadultsbecausesomethinghas
washedawaythesurfactant
02buildsupandfreeradicalformaOonensues
MCCofRDSisprematurity
DevelopmentofprotecOvehyalinemembrane
MCCofARDSissepsis(followedbytrauma)
Respiratorydistresssyndromecandevelop
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THEAaGRADIENT HYALINEMEMBRANEDISEASE
Measuresthedierencebetweenthealveolar IstherstrestricOvelungdisease
[02]andthearterial[02] Needsmore02,getcomplicaOonsassociated
Normalis10mmHgorless withdeliveringthis02
Anythingabovethismeanssomethingis PneumothoraxisapossiblecomplicaOons
disrupOngthemovementofexternal02tothe
blood (spontaneous,traumaOc)
PossiblecausesofincreasedAagradient: Kussmaulsign
FluidinintersOOum,Alveolaredema,V/Q Pulsusparadoxus
mismatch,RLshunts Hammanssign
PNEUMOTHORAX PNEUMOTHORAX
Spontaneous:blebspop IfasymptomaOcandoccupying<25%ofthe
MCinwomenonOCPs pleuralcavity,notreatmentisnecessary
CommoninMarfanspaOents SymptomaOcatanylevel/ormorethan25%
ofpleuralcavityoccupied,insertachesttube
Trauma'c:MCCisstabwoundtothechest
Ifsymptoma'c:stablevs.unstable
StabwoundtoleTsidechesttamponadeis
MCCofdeath
StabwoundtorightsidechestPTXisMCCof
death
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OBSTRUCTIVELUNGDISEASES OBSTRUCTIVELUNGDISEASES
Mainproblemistheinabilitytoexhale ChronicBronchiOs
adequately(FEV1/FVCraOoisdecreased,<80%)
BacterialinfecOonsMCaecttheairway(thus Emphysema
bacteria=obstrucOve) Asthma
AirwayproblemsleadtovenOlaOonproblems
Bronchiectasis
Excessiveairwaymucusleadstoairway
thickening
IncreasedREIDINDEX
p02low,pC02high,pHlow
MCCdeathisbronchiectasis
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RESTRICTIVELUNGDISEASES
Extrapulmonarycauses(poormusculareort,
poorsupport)
Inters''aldiseasesinclude:
RDSandARDS
Pulmonarybrosis
Sarcoidosis
Pneumoconioses
Goodpastures&Wegeners
Granulomas
RestricOvevs.ObstrucOve THEROLEOFAMNIOTICFLUID
RESTRICTIVE OBSTRUCTIVE
Problemwithbreathingin(intersOOum Problemwithbreathingout(airway
Mainroleistoactasashockabsorber
problem)diusionproblem problem)venOlaOonproblem Anotherimportantroleistopreventthe
Poorcompliance p02isnormalorhigh
Poordiusion pC02ishigh
atmosphericpressurefromcollapsingthe
Aagradientincreased pHislow baby
p02islow Airwayisthickened
pC02islow REIDindexiselevated
ToomuchamnioOcuid=polyhydramnios
pHishigh MCCofdeathisBRONCHIECTASIS TooligleamnioOcuid=oligohydramnios
MCCofdeathisCorPulmonale
FEV1/FVC>80% FEV1/FVC<80%
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POLYHYDRAMNIOS OLIGOHYDRAMNIOS
ToomuchamnioOcuid,seenwhenthebaby DecreaseinamnioOcuid
cannotswallowordigest
Causesinclude.
Causesmayinclude. Renalagenesis
AutonomicDysfuncOon(RileyDaysyndrome) RenalobstrucOon
Neuromusculardisease(WerdnigHoman
syndrome) Leadingto
Pogerssyndrome
UpperGIatresia(esophageal,duodenal)
Prunebellysyndrome
DIAPHRAGMATICHERNIAS
Diaphragmdevelopsfromfronttoback
Prematurebirthsresultinreardefects90%of
theOme
ANATOMYOFTHEAIRWAY
ReardefectknownasBochtalekDefect
Anterior/MidlinedefectknownasMorgagni
Defect
IntesOnesmovingintothoraciccavitycanlead
topulmonaryhypoplasia
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THETRACHEA AIRWAYANATOMY
PNEUMOCYTES
Type1:makesupmostofthepneumocyte
populaOon(95%)
Mosttype1pneumocytesarefoundinthe
terminalbronchiole
HISTOLOGYOFTHELUNGS
Type2:thispneumocyteisresponsiblefor
producingsurfactant
Isfoundinthealveoli
Canbecometype1pneumocytesiftheyare
needed
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GOBLETCELLS DUSTCELLS
Producemucus KnownasClaracells
Arethemostabundantofallcellsinthe Aremacrophagesthatspecializeinrounding
airway updustparOcles
ObstrucOvelungcondiOonsleadtoincreased Mostabundantintheterminalbronchioles
gobletcells
SMOOTHMUSCLE AIRWAYEPITHELIUM
Throughouttheairway StraOedsquamouslinestheupper1/3ofthe
Mostabundantinmediumsizedbronchioles trachea
Lower1/3ofthetracheaislinedwithciliated
columnar
Middle1/3isamixofbothsquamousand
columnar
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CILIA
LinestheenOreairway
TheyonlymoveinasingledirecOon,whichis
towardsthemouth
9+2conguraOon
Dyneinarmgivesexibility
DefectofdyneinarmleadstoKartageners
syndrome
PHYSIOLOGYOFTHELUNGS
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LUNGVOLUMES MINUTEVENTILATION
AnatomicalDeadSpace:areasthatcannot IsTIDALVOLUMExRESPIRATORYRATE
exchange02(frommouthtorespiratoryunit) VenOlatorseongsusually10ccperKgof
RespiratoryUnit:areasthatareusedto bodyweight
exchange02(bronchiole,alveolarduct,
alveolus)
TotalVen.la.on=VDeadSpace+Valveoli
LUNGVOLUMES
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COMPLIANCEANDAIRFLOW INSPIRATION
DuringinspiraOonthechestwallhasa
strongerexpansileforcethanthelungs
Duringrstofinspira'on,thechestwall
hasmoreexpansileforces
Duringsecondofinspira'onthelunghas
moreexpansileforces
Attheend,therecoilforceofthechestwallis
equaltotheexpansileforceofthelung
EXPIRATION INTRATHORACICPRESSURE
Recoilforcesinthechestwallisgreatestin
therstofexpiraOon
Recoilforcesinthelungsaregreatestinthe
secondofexpiraOon
UponcompleOonofexpiraOon,therecoil
forcesofthelungareequaltotheexpansile
forcesofthechestwall
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POSITIVEINTRATHORACICPRESSURE
MCCarePTXand/orPericardialTamponade
Kussmaulsign(increasedJVDoninspiraOon)
Pulsusparadoxicus(exaggerateddropinBP>
10mmHgORdropinpulse>10bpmon
inspiraOon)
FLOW(Q) VENTILATION(V)
Themovementofairthroughtherespiratory IsameasureofthepC02thatisescaping
tract circulaOonthroughthealveoli
Moreow=more02=morevasodilaOon= Apatentairwaymustbeinplaceforproper
moreow venOlaOon
Keepingpulmonaryvesselsopenlongerwill VenOlaOonishighatthebogomofthelung
increaseS2spliong onlyduringinspiraOon,themostvenOlaOon
occursatthetopofthelungs
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VENTILATION/PERFUSION RECEPTORSINTHELUNGS/CHEST
AnidealV/QraOois0.95 Jreceptors:foundinthelungsintersOOum
AnythingfoundintheintersOOumwillsOmulatetheJ
V/Qisgreatestatthetopofthelungandthe receptors
lowestinthebaseofthelung SOmulaOonofthesereceptorsincreasesthe
V/QmismatcheslooklikerestricOvelung respiratoryrate
diseasepagerns(lowp02,lowpC02,highpH)
Slowadap'ngreceptors:foundatthesternocostal
juncOonsoftheribs
RecognizestretchandinaOonofthethoraciccavity
ResponsibleforexhalaOon
GRAPHICALANALYSISOFPULMONARY
PRESSURES
NegaOvepressure=InspiraOon
PosiOvepressure=ExhalaOon
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THEFACIALSINUSES
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THESINUSES THESINUSES
MaxillarySinuses: EthmoidSinus:
Arethelargestoftheparanasalsinuses 3groups(anterior,middle,posterior)
Drainintothemouth Posteriordrainsintothesuperiormeatus
AretheMCsiteofsinusinfecOonbecauseof Middleandanteriordrainintothemiddle
theirdrainagepathway meatusofthenose(anteriordrainsviathe
infundibulum)
THESINUSES
Sphenoidalsinus:
Developsaround2yrofage
Itopensintotheroofofthenasalcavity
throughanopeningontheposteriorwallof
thesphenoethmoidalrecess
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THESINUSES CHEMORECEPTORS
Frontalsinuses: AorOcbody
Developaround46yrofageandarefully CaroOdbody
developedbypuberty
Drainanteriorlyintothecorrespondingmiddle Brain
meatusofthenoseviathefrontalnasalduct Pons
Linedwithmucusmembranesthatareinnervated Medulla
bythesupraorbitalnerve(controlssecreOons)
FrontalsinusishighlyresponsibleforltraOonof
thingsthatpassthroughthenose
THEPONS THEMEDULLA
Apneus'ccenterdetectslackofp02(hypoxia) ResponsibleforbasicfuncOonssuchas
andsOmulatesrespiraOon respiraOon
Pneumotac'ccenterdetectshypercarbia LocaOonofmanyreexcentersvomiOng,
(pC02)andsOmulatesexhalaOon sneezing,swallowing,coughing
CNs5,6,7,8 CNs9,10,11,12
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SubclavianStealSyndrome
LUNGSOUNDS
WHEEZING STRIDOR
MCduetoexpiraOonthroughanarrowingof Narrowingofextrathoracicairway(mouthto
theintrathoracicairway gloos)
Seenonxray Soundslikeahighpitchedwheeze
WheezingoninspiraOonisindicaOveof
bronchospasmorsomethinginthewayof
inhalaOon
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RHONCHI CRACKLES
Thesoundmadewhenairtravelsovermucus Thesoundmadebycollapsedairwayopening
Soundiscoarse Surfactantmaybemissing
MCseeninobstrucOvelungdiseases Alveolimaybescarred
SeeninconjuncOonwithaproducOvecough MCseeninrestricOvedisease,butmore
commoninlaterstageobstrucOvedisease
PERCUSSION
Dullnessindicatessomethingisinthelungs
(uid,mass,etc)
Typanyindicatesthereisopenspace
(pneumothorax)
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MCUPPERAIRWAYINFECTIONS
Epigloe's:causedbyH.InuenzaB
Trachei's:causedbyStaphAureus
COMMONINFECTIONSOFTHE
LUNGSANDAIRWAY
MCLOWERAIRWAYINFECTIONS
BronchioliOs:
BronchiOs
Croup:
Pneumonia:
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PNEUMOCONIOSES LUNGMASSES
Allpredisposetolungcancerexceptfor Inchildren,theMCmassisahamartoma
Anthracosis(coalminerslung) Inadults,theMCmassisagranuloma
Asbestosis:shipyard,pipegers,break Overall,theMCtumoristheAdenoma(of
mechanism,insulaOontechnicians glandularorigin)
Berrylliosis:fromweldingofmetalsfoundin
TVandradiodevices
Bissinosis:fromcogonbers
Silicosis:fromsandblasOng,glassblowing
PERIPHERALLYLOCATEDLUNG
CENTRALLYLOCATEDLUNGCANCERS
CANCERS
Squamouscellcarcinoma(producesPTHrP) Largecelladenocarcinoma
Smallcellcarcinoma(producesACTH,ADH, Bronchogenicadenocarcinoma
PTH,andTSH) Bronchoalveolaradenocarcinoma
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RISKFACTORSASSOCIATEDWITH
PANCOASTSTUMOR
LUNGCANCER
#1SMOKING Acarcinomaattheapexofthelung
#2RADON AectsthecervicalsympatheOcplexus
#3SECONDHANDSMOKE CausesHornerssyndrome(Ptosis,Anhydrosis,
#4PNEUMOCONIOSES Miosis)
ENDOCRINOLOGY
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Exocrine:secreOonintoacavity
Endocrine:secreOonintotheblood
Paracrine:secreted,workintheviscinity
Autocrine:secretedbythesamecellitworkson
Apocrine:OpofcellissecreOngthesubstance
(sweatglands)
Holocrine:enOrecellissecretedwithsubstance
(sweatglandinaxilla,groin)
HORMONESWhattoknow? WATERSOLBHORMONES
Thenameandwhereitcomesfrom Comemainlyfromtheanteriorpituitary
ItsmainsOmulus Theyusea2ndmessengertogettothe
Itsmaininhibitor nucleusofthecell
Whereitgoes Proteinsarewatersoluble
ItsmainacOon
Its2ndmessenger
Miscellaneoussymptomsassociated
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1STEROIDWITHCYTOPLASMIC
FATSOLBHORMONES
RECEPTOR
Steroidsarethemainfatsolublehormones CORTISOL
Theycrossrightthroughmembraneandhead
tothenucleus(thensOmulatetranscripOon)
Theyhavenuclearmembranereceptors
AectDNAreplicaOon,transcripOon,and
translaOon
Theydontusea2ndmessenger,justworkvia
proteins
ThePituitary
Sitsatthebaseofthebrain(bogomofthe
hypothalamus)
Restsinthesellatursica
THEPITUITARY Coveredbythediaphgragmasella
Connectedtohypothalamusviapituitarystalk
Secretes9hormones
ReceivessOmulaOonorinhibiOonsignalfrom
thehypothalamus
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AnteriorLobeofPituitary
3PARTS
Part1ParsDistalis(makesupmajorityofthe
anteriorpituitary,iswherethebulkofhormone
producOonoccurs)
Part2ParsTuberalis(formsasheathextending
upfromtheparsdistalisandwrapsaroundthe
pituitarystalk)
Part3ParsIntermedia(sitsbetweenthepars
distalisandposteriorpituitaryisverysmall)
AnteriorLobe AnteriorLobeHormones
Secretes7hormones(ACTH,TSH,GH,
ProlalcOn,LH,FSH,MSH)
Receivessignalsfromthehypothalamus
throughanetworkofcapillariesknownasthe
HypothalamoHypophysialPortalSystem
Allstainbasophilic(except:GHandprolacOn
stainacidophilic)
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PosteriorLobeofPituitary PosteriorLobeofPituitary
AlsocalledNeurohypophysis 3PARTS
IsNOTagland,isacollecOonofaxonal Part1:ParsNervosa(makesupmajorityof
projecOonsfromthehypothalamus theposteriorlobe)
TheneuronalprojecOonsextendfromthe Part2:InfundibularStalk(akaPituitaryStalk
supraopOcandparaventricularnucleiofthe isthebridgebetweenthehypothalamicand
hypothalamusthenreleasepepOde hypophysealsystem)
hormonesintothecapillariesofthe Part3:MedianEminence
hypophyealcirculaOon
PosteriorLobeHormones PROLACTIN
Secretes2hormones(Oxytocinand Nipples'mula'onsOmulatesprolacOn
Vasopressin) release
Oxytocin:responsibleforuterinecontracOon CanbeinhibitedbyDA(relaOonshipbetween
andmilkletdown(ProlacOnmakesit,oxytocin DAandProlacOnisveryimportant)
releasesit) AllDopamineagonistscaninhibitlactaOon
Vasopressin:targetskidneysandarterioles (BromocripOnewasanolderDAagonistused
SOmulateswaterretenOonandincreasesBP tostoplactaOon)
viacontracOonofarterioles
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PituitaryTumors
Prolac'noma:istheMCfuncOonaltumorof
thepituitary
WHYAREALLPITUITARYTUMORSASSOCIATED Chromophobicadenoma:istheMCpituitary
WITHHIGHPROLACTINLEVELS? tumor,andisanonfuncOonaltumor
Malesgetmacroadenoma
Femalesgetmicroadenomas
EmbryologyoftheThyroid
Seenat34weeksintheoorofthepharynxatthe
baseofthetongue
THETHYROIDGLAND Descendsthroughthethyroglossalductasitmigrates
tothebaseoftheneck
Asitmigratesitremainsconnectedtothetongueby
thethyroglossalduct
TRHandTSHbeginsecreOonfromthefetal
hypothalamusbetween1620weeksgestaOon
T4(thyroxin)levelsareclinicallysignicantat1820
weeks,whilefetaltriiodothyroxine(T3)stayslowunOl
30weeks,risingsharplyatterm
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HistologyoftheThyroid RoleofThyroidHormone
3mainfeatures: RegulatesBMR
FolliclessphericalfolliclesthatselecOvely Aectsproteinsynthesis
absorbIodide(I) Regulatesbonegrowth(alongw/GH)
Follicularcells(thyroidepithelialcells)single IncreasessensiOvitytocatecholamines
layerofthyroidepitheliumsecreteT3&T4 HeatgeneraOon
Parafollicularcells(Ccells)secrete
RegulaOonofprotein,carb,andfat
calcitonin(counterregulatesPTH) metabolism
MCDiseasesoftheThyroid HYPERTHYROIDISM
HYPERTHYROIDISM CausedbyoverproducOonofthyroid
Gravesdisease hormone(TSH,T3andT4)
ToxicMul'nodulargoiter SympatheOchyperacOvity
Toxicthyroidadenoma
Weightloss+increasedappeOte
HYPOTHYROIDISM Heatintolerance
Hashimotosdisease Tremors
DeQuarvainsdisease PreObialmyxedema
Lymphocy'cthyroidi's Myopathy
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GRAVESDISEASE
Gravesdisease(enOreglandoverproducing MCCofhyperthyroidism
thyroidhormone) AutoimmuneautoanObodiesagainsttheTSH
ToxicMul.nodularGoiter(singlenodules receptors,leadstosOmulaOonofthyroid
overproducingthyroidhormone) hormoneandgrowthofthethyroid
ToxicThyroidAdenoma(maybeeither StronggeneOccomponent
asymptomaOcorsymptomaOc) Seeninpeople<50yrofage
Exophthalmosisseen(protrusionoftheeyes)
TOXICMULTINODULARGOITER TOXICTHYROIDADENOMA
The2ndMCCofhyperthyroidism Usuallyanadenomaofthefollicularcells
Isolatednodulesdevelopthatsecrete HasdierentlevelsoffuncOoning(cold,warm,
excessiveamountofthyroidhormone orhot)
Hotnodulestakeupiodineandare Itisasolitaryneoplasm(asopposedtotoxic
indicaOveofafuncOoningnodule mulOnodular)
CausedbyageneOcmutaOon
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SUBACUTETHYROIDITIS Makingadiagnosis
Abruptonsetofhyperthyroidsymptoms
Duetoleakingofthyroidhormonefroman
inammedthyroidgland
Usuallyfollowsaviralillnessandsymptoms
resolveontheirown
RAIUResults MgmtofHyperthyroidism
Controlthesympathe'csymptomswith
beta1blockers(Propranolol)
BlockperipheralconversionofT4T3using
PTUorMethimazole
RadioacOveIodinegivenasasingledosecan
curehyperthyroidisminpeople>40yr
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HYPOTHYROIDISM TypesofHypothyroidism
Thyroidglandcannotproduceenoughthyroid Hashimotosdisease:Autoimmuneagack
hormone(MCC) againstthethyroidperoxidaseand/or
FaOgue thyroglobulin
Coldinterolerance
GradualdestrucOonoffolliclesinthethyroid
Weightgain
Coarse/briglehairandnails Hypothyroidsigns+rm/large/lobulatedthyroid
Primary:Thyroid gland(d/tlymphocyOcinltraOonandbrosis)
Secondary:Pituitary DeQuervainsthyroidi's:Isasubacute
Ter'ary:Hypothalamus thyroidiOs(rstlookshyperthyroid,thenlooks
hypothyroid)
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TypesofHypothyroidism
Lymphocy'cthyroidi's:Occurspostpartum
Isselflimited
CANCERSOFTHETHYROIDGLAND
Cre'nism:maternalhypothyroidismleadsto
congenitalhypothyroidism,resulOngin
stuntedphysicalandmentaldevelopment
Earlydiagnosisandreplacementwith
thyroxineprovidesgoodpx,latediagnosis
resultsinmentalretardaOon
PAPILLARY FOLLICULAR
IstheMCtype SeeninolderpaOents
Responsiblefor75%ofallthyroidcancers METStothebones
SeenmoreoTeninyoungerpaOents
METStotheLNs
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MEDULLARY ANAPLASTIC
Aectstheparafollicularcells SeenMCinolderpaOents
AssociatedwithMEN2andMEN3 Carriestheworstprognosisofallthyroid
Isanisolatedcancer cancers
DoesNOTmetastasize(onlyone)
InltraOonofthevascularsupplyisso
tremendousthatsurgeryisnotpossible
(reasonwhypxissobad)
LABVALUES
THEADRENALGLANDS
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AdrenalAnatomy ZONAGLOMERULOSA
ProducesAldosterone(sOmulatedbythe
RAAS)
S.mulatedby:Hypovolemia,Hyponatremia,
andHyperkalemia
Inhibitedby:Hypervolemia
Whereitacts:LateintheDCT
Whatitdoes:SOmulatestheNa/Kpumps
ALDOSTERONE CONNSSYNDROME
Toomuch=Connssyndrome AkaPrimaryHyperaldosteronism
Hypernatremiaasaresultofthebodys
Tooligle=Adrenalinsuciency compensaOonmechanismforexcesswater
reabsorpOon
HypokalemiabecauseK+canfreelyleakout
ofcells
AlkalosisduetotheK+/H+exchange
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ADRENALINSUFFICIENCY
ResultsintooliglealdosteronesecreOon
Congenitaladrenalhyperplasia:
MCCis21hydroxylasedeciency(90%ofthe
Ome)
Lesscommonly11hydroxylasedeciency
Abruptcessa'onofsteroidusagecanresultin
autoimmuneadrenaliOs.
21hydroxylasedeciency:
Decreasedaldosterone(mineralocorOcoid)
wegetNa+wasOng(leadingtohypotension)
DecreasedcorOsol(glucocorOcoid)noACTH
feedback
Increasedandrogens=virilizaOon
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ZONAFASCICULATA
11hydroxylasedeciency: ProducesCor'sol(ourstresshormone)
Excess11deoxycorOcosteronemimicsthe S.mulatedby:Stress,Hypoglycemia
eectsofaldosterone(retainsalt=HTN) Inhibitedby:Hyperglycemia
Decreasedaldosterone Whereitacts:Everywhere
DecreasedcorOsol(noACTHfeedback) Whatitdoes:UpregulaOonofallreceptors
IncreasedandrogenproducOonleadsto duringstress
virilizaOon
PhysiologicaleectsofCorOsol
Proteolysis(breakdownofproteins)
Gluconeogenic(madefromproteinbreakdown)
AnOinammatory
InhibiOonofmacrophagemigraOon
StabilizaOonofendothelium,
StabilizaOonofmastcells
InhibiOonofphospholipaseA
KillsTcellsandeosinophils
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CUSHINGSDISEASE
ToomuchcorOsol=Cushingssyndrome Cushingsdiseasewhenproblemisectopic
(pituitaryadenoma,smallcellcarcinoma)
TooliglecorOsol=Adrenalinsuciency Cushingssyndromewhenproblemisinthe
(Addisonsdisease) adrenalgland
Pathognomonicndings:
Bualohump
Truncalobesity
Striae
Diagnosis:Dexamethasonesuppressiontest
(lowdoserst=12mg,highdose=8mg)
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ResultsoftheDexamethasone
AbnormalDexatestresults
Suppressiontest
NORMALVALUES: Cushingssyndrome(adrenaltumor):isnot
suppressedbyloworhighdoses
Lowdose:OvernightplasmacorOsol<5cmg/
dL Cushingssyndromed/tectopicACTHproducing
Highdose:Overnight>50%reducOonin tumor:isnotsuppressedbyloworhighdoses
plasmacorOsol **dierenOatebetweenthetwobycheckingACTHlevel
(highinectopicsource,lowinadrenalsource)
Cushingsdisease(pituitary):issuppressedonlybyhigh
dosedexamethasone
ADDISONSDISEASE
Adrenalinsuciency/hypocorOsolism AddisonianCrisis:
TooliglecorOsolforcesthepituitarytosecreteexces
ACTH LifethreateningcondiOon
ExcessACTHgoesthroughthebetalipotropinpathway UsuallysOmulatedbytraumaorinfecOon
sOmulatesMSHandendorphins
SevereN/VleadingtodehydraOon
Si/Sx:faOgue/weakness,orthostaOchypotension, Syncope
changeinpersonality,pigmentchanges(darkening PenetraOngpaininthelowerbody/lowerback
MSH)
Dx:ACTHsOmulaOontest
Tx:LifelongglucocorOcoidreplacement Isanemergency!RequiresIVglucocorOcoids
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ZONARETICULARIS
ProducesTestosterone/Androgens
S.mulatedby:ACTH
Whatitdoes:controlsmaleexternalgenitaliain
utero,sOmulatesappeOte,sOmulateslibido
DHTamoreacOveformoftestosterone,made
inthetestesby5reductase
Responsibleforhairgrowth(andhairlosswhen
therestoomuch)
ADRENALMEDULLA
ProducesEpinephrineandNorepinephrine
S.mulatedby:Stress,Hypoglycemia
Inhibitedby:Hyperglycemia PHEOCROMOCYTOMA&NEUROBLASTOMA
Whereitacts:Liverandadrenalcortex
Whatitdoes:Glycogenolysisand
Gluconeogenesis
Hasa2ndmessenger:cAMP
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NEUROBLASTOMA PHEOCROMOCYTOMA
MCcancerininfancy,MCextracranialsolid ExcessofNEandE
cancerinchildhood PalpitaOons,HA,intermigentspikesinBP
Neuroendocrinetumorarisingfromneuralcrest Ruleof10s
cells
MCfoundintheadrenals Dx:24hrurinaryVMAandmetanephrinelevels,
Si/Sx:abdominalswelling/tenderness(mass ifposiOvedoMRI(ifMRIneg,doMIBG
scinOgraphy)
eect),palpitaOons,HTN,diaphoresis,HA
Mgmt/Tx:Requiresremoval,alphablockaderst
Weaknessifcompressingspinalcord (preventsHTNcrisis),betablockadesecond
Dx:Catecholaminesareelevated,imaging(MRI) (keeps02deliverytotheheart)
ERYTHROPOIETIN
Source:Renalparenchymacells
S.mulatedby:Hypoxia
HORMONESOFTHEKIDNEY Inhibitedby:Increasedoxygen
Whereitgoes:Bonemarrow
Whatitdoes:Erythropoiesis
Its2ndmessenger:Tyrosinekinase
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Polycythemia
Polycythemia+EPOeleva'on=Hypoxiaor
Tumor
PolycythemiawithoutEPOeleva'on=Bone
marrowproblem
THEPANCREAS
PancreaOcHormones INSULIN
Insulinreleasedfrombetacells BeginsasProInsulin,whichisacombinaOonof
insulin+Cpep.de(clinicallyimportant)
Glucagonreleasedfromalphacells
SOmulus:Glucose
Somatosta.nreleasedfromdeltacells
Pancrea.cpolypep.defromFcells Howcanwes'mulateinsulinwithoutglucose?
Insulinoma
Sulfonylureas
ExogenousadministraOon(doesntcontainC
pepOde)
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INSULIN
Source:PancreaOcisletbetacells(2,2
receptors)
S.mulatedby:Hyperglycemia
Inhibitedby:Hypoglycemia
Whereitgoes:allcellsexceptBRICKLE
Whatitdoes:increasesallanabolicprocesses
Its2ndmessenger:TyrosineKinase
INSULINSulfonylureas INSULINOMA
DM2drugsthatworkbyincreasinginsulin Hypoglycemiainanadultwhodoesnthave
releasefromthebetacellsofthepancreas diabetes
MCuse2ndgeneraOons:Glipizide,Glyburide Seenmostlyinadults
Willseehighinsulin+highCpep'delevels
MOA:BindtoATPdependentK+channelon
thebetacellsmembrane,leadstoopeningof
voltagegatedCa2+channels,leadsto Dx:Labs+CT
incresaedfusionofinsulingranulesontocell Tx:Removethetumorsurgically
membrane(secretesproinsulin)
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GLUCAGON Glucagonoma
Source:PancreaOcalphacells(1receptor) TumorofthepancreaOcalphacells
S.mulatedby:HypoglycemiaandStress Causesa1000foldincreaseinserumglucagonlevels
(throughgluconeogenesisandlipolysis)
Inhibitedby:Hyperglycemia
Whereitgoes:Adrenalcortex,liver,adipose Si/Sx:Severelyelevatedglucose,N/V/D,NME,
Ossue developmentofDMinmostcases
Dx:SevereelevaOoninglucagonlevels(>1000pg/mL,
Whatitdoes:Gluconeogenesis,Glycogenolysis, N:50200)
Lipolysis,Ketogenesis Tx:Octreo'de(somatostaOnanalogthatinhibits
glucagonrelease)
Its2ndmessenger:cAMP(watersoluble) SurgeryistheonlycuraOvetherapy
SOMATOSTATIN
Sidenote..MENSyndromes Source:PancreaOcdeltacells
MEN1(Wermer):Pituitary,Parathyroid,Pancreas S.mulatedby:InsulinandGlucagon
(glucagonoma,gastrinoma,VIPoma,insulinoma) Inhibitedby:Lowinsulinandglucagon
MEN2a(Sipple):Parathyroid,MedullaThyroid Whereitgoes:Paracrine(worksinviscinity)
Carcinoma,Pheocromocytoma
Whatitdoes:InhibiOonofinsulinand
MEN2b:Medullarythyroidcarcinoma, glucagon
Pheocromocytoma,Marfanoidbodies,Mucosal
neuromas
Its2ndmessenger:cAMP
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PANCREATICPOLYPEPTIDE
Source:PancreaOcPPcells(headofpancreas)
S.mulatedby:Highproteinmeal,exercise,
fasOng,acutehypoglycemia HORMONESOFTHEGITRACT
Inhibitedby:SomatostaOn,IVglucose
Whereitgoes:Liver,Pancreas(autocrine)
Whatitdoes:Glycogenolysisandself
regulaOonofpancreaOcsecreOons
GASTRIN SECRETIN
Source:Stomach Source:Duodenum
S.mulatedby:HighpH S.mulatedby:LowpH
Inhibitedby:LowpH Inhibitedby:HighpH
Whereitgoes:Parietalcellsofthestomach Whereitgoes:Pancreasandbladder(making
(bodyofstomachmainly) itparacrine)
Whatitdoes:ProducOonofHClandIntrinsic Whatitdoes:SOmulatesproducOon/
factor(forB12absorpOon) secreOonofHC03frompancreasandGB
Its2ndmessenger:calcium Its2ndmessenger:cAMP
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CCK MOTILIN
Source:Duodenum Source:Mcellsofduodenumandjejunum
S.mulatedby:LowpH S.mulatedby:HighpH
Inhibitedby:HighpH Inhibitedby:LowpH
Whereitgoes:PancreasandGB(paracrine) Whereitgoes:EnOreGI
Whatitdoes:FatandproteindigesOon Whatitdoes:SOmulatesgastricmoOlity,
Its2ndmessenger:IP3/DAG sOmulatespepsinproducOon,clearstheGIin
prepfornextmeal
GASTROINTESTINALPEPTIDE(GIP) VASOINTESTINALPEPTIDE(VIP)
Source:Duodenum Source:Duodenum
S.mulatedby:Glucose S.mulatedby:Otherduodenalhormones
Inhibitedby:HighpH Inhibitedby:HighpH
Whereitgoes:PancreaOcIsletCells Whereitgoes:Paracrine
Whatitdoes:EnhancesthesecreOonof Whatitdoes:InhibitsgastricacidsecreOon,
insulin secreOonofwater/electrolytesinsmall
Its2ndmessenger:cGMP intesOne,pancreaOcHC03secreOon
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SOMATOSTATIN
Source:Duodenum
S.mulatedby:LowpH
Inhibitedby:HighpH CALCIUMMETABOLISM
Whereitgoes:Paracrine
Whatitdoes:InhibiOon
PARATHYROIDHORMONE(PTH)
OSTEOBLASTS:Buildbone(lowersserum
calcium)
OSTEOCLASTS:Crumblebone(toincrease
serumcalcium)sOmulatedbyPTH
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PTH
Source:Chiefcellsoftheparathyroid
S.mulatedby:Lowserumcalcium,mild
decreasedinMg2+,highserumPO4
Inhibitedby:Highserumcalcium,severe
decreaseinMg2+,lowerserumPO4
Whereitgoes:Osteoclastsofbone,lateDCT
Whatitdoes:SOmulatesosteoclastacOvity
(increasescalcium),increasessecreOonof
phosphate
HYPERPARATHYROIDISM
PrimaryHyperPTH:MCCbyaparathyroid
adenoma(probleminthegland)
HYPERPARATHYROIDvsHYPOPARATHYROID PTH,Ca2+,PO4
SecondaryHyperPTH:IncreasedPTHin
responsetolowcalcium
PTH,Ca2+,PO4
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HYPERPARATHYROIDISM HYPOPARATHYROIDISM
OTenasymptomaOc PrimaryHypoPTH:MCCbysurgicalmistake
WithincreasedosteoclasOcacOvitywegetdestrucOon
ofnormalbonecontrucOon (removalofparathyroidsaccidentally)
PTH,Ca2+,PO4
Osteopenia:Decreasedbonedensity(osteoporosis
precursor)
Osteomalacia:NutriOonaldeciencyleadingto SecondaryHypoPTH:MCCbyincreased
soTeningofthebones(MCCisvitaminDdeciency)
thisisknownasRicketsinchildren. levelsofvitaminD
Osteosclerosis:Trauma(causesincreaseddensityof PTH,Ca2+,PO4
bones)
Osteoporosis TScoreandZScore
Decreasedmicroarchitectureofthebone(decreased DEXAscan(1stdiagnosOctestfor
bonemineraldensity)
osteoporosis)
Atleast2.5SDsbelowtheaverage30yrold(DEXA
scan) Tscore:ComparisonofpaOentsbonemineral
Primarytype1:Postmenopausalwomen densitytoahealthy30yroldofthesamesex
Primarytype2:Senile(F:M2:1),seenaTer75yrof
age
Secondary:Seenatanyage(prolongeddisease, Zscore:ComparisonofapaOentsBMDtothe
prolongedglucocorOcoiduse) averageofthesameage,sex,andrace
Tx:1stline:Lifestylemods/Calcium/VitaminD,2nd
line:Bisophosphonates Usedinpremenopausalfemales,males<
50yr,andchildren
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Bisphosphonates
Inhibitosteoclas.cac.vity(mimiccalcitonin)
TheyshutdownosteoclasOcacOvitybyforcing
themtoundergoapoptosis
VITAMIND
Preventlossofbonemassandreplenishbone
masslostinosteoporosis
2ndlineforosteoporosis(1stcalcium)
Alendronate,Elandronate,EOdranate
OSTEOMALACIA&RICKETS
Source:Absorbedthroughskinliver Rickets:bonesoTeninginchildrend/t
kidney impairedmetabolismofvitD,PO4,orCa2+
S.mulatedby:Lowcalcium,lowPO4 Osteomalacia:bonesoTeningd/tdefecOve
Inhibitedby:Highcalcium,highPO4 bonemineralizaOonsecondarytoinadequate
Whereitgoes:KidneyandGI amtofavailablePO4andCa2+
Whatitdoes:ProducOonofCaATPase,
ProducOonofcalciumbindingprotein,and
sOmulaOonofosteoblasOcacOvity
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GreensOckFractureCommonto
Rickets
CALCITONIN
CALCITONIN
Source:Parafollicularcells
S.mulatedby:Highcalcium
Inhibitedby:Lowcalcium
Whereitgoes:Bone
Whatitdoes:InhibiOonofosteoclasOc
acOvity
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EmbryologyoftheKidney
Metanephros:by5thweek
Givesrisetothekidneyproper
RENALMEDICINE Developsoutpouchingcalleduretericbud
Everythingaboutthekidneys UretericBud:givesrisetothecollecOng
system(ducts,calixes,hilum,ureters)
DevelopmentofMalevs.Female
Around8thweek,agenotypicmalewillsecrete
MullerianInhibiOngFactor(MIF)
IfnoMIF,theMullerianductsdevelopby
default(weareallfemalebydefault)andthe
Wolanductsdie(apoptosis)
IfMIFpresent,Mullerianductsdieby
apoptosis
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ParamesonephricDucts(Mullerian
MesonephricDucts(WolanDucts)
Ducts)
Developinto: Developsinto:
Ovaries Testes
FallopianTubes Epidydimus
Uterus Vasdeferens
Cervix
Seminalvesicle
Upper1/3ofvagina
Lower2/3ofvaginadevelopsfromurogenital Penisdevelopsfromurogenitaltubercle
sinus Prostate,prostaOcurethra,andbulbourethral
Clitorisdevelopsfromurogenitaltubercle (Cowpers)glandsdevelopfromurogenitalsinus
RenalEmbryocont.
VitellineDuct(OmphalomesentericDuct)
Allantois
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Allantois
Allowstheembryotohandlegasexchange
andliquidwaste
AnendodermalevaginaOonofthehindgut
thatbecomessurroundedbythemesodermal
connecOngstalk
Bladderisconnectedtotheallantoisviathe
urachus,allowingremovalofnitrogenous
compoundsfromthefetalbladder
Ifremainspatenturachalcystforms
UrachalCyst
Acystbetweentheumbilicusandbladder
Isanextraperitonealmassintheumbilical
region
Abdominalpain,painwithurinaOon,
persistentumbilicaldischarge,andfrequent
UTIsarethecommonsequelae.
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TheVitellineDuct VitellineDuct
AkaOmphalomesentericDuct
Joinstheyolksactothemidgutlumen
around4thweekgestaOon
Failuretoobliteratearoundthe9thweek
resultsinadiverOculuminsmallintesOne
(MeckelsdiverOculum)
Seenin2%offetuses,is2T.fromileocecal
valve,is2long(ruleof2s)
ANATOMYOFTHERENALSYSTEM
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RenalAnatomy
LeTkidneyL1
RightkidneyL2(lowerduetopresenceof
liveronthisside)
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BLOODSUPPLYTOTHEKIDNEYS THEGLOMERULUS
ProximalConvolutedTubule
CompletereabsorpOonofglucose
CompletereabsorpOonofAAs
THETUBULES SecreOonofammonia
NearcompletereabsorpOonofSodium,Water,
andBicarb
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PCT LoopofHenle
ThickDescendingLoop:highwaterpermeability,low
solutepermeability
ThinDescendingLoop:highwaterpermeability,low
solutepermeability
ThinAscendingLoop:nowaterpermeability,passive
NaClpermeability
ThickAscendingLoop:AcOvetripletransportofNa/
K/2Cl
PassiveK+secreOon(generatesanelectrochemical
gradientforreabsorpOonofNa,Mg2+,andCa2+)
ThickAscendingLoop
AcOveSodiumreabsorpOon
AcOvePotassiumreabsorpOon
AcOveChloridereabsorpOon
PassiveMagnesiumreabsorpOon
PassiveCalciumreabsorpOon
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ThickAscendingLoopofHenle DistalConvolutedTubule
AcOveSodiumreabsorpOon
AcOveChloridereabsorpOon
CalciumreabsorpOonifPTHpresent
AcOveBicarbreabsorpOon
DCT CollecOngDucts
SodiumreabsorpOonwhenAldosterone
present
WaterreabsorpOonwhenADHpresent
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CollecOngDucts
DIURETICS
InthePCTAcetazolamide,
InthePCT
Dorzolamide
InhibitCarbonicAnhydrase
DecreasestheamountofH+inPCT
ThusdecreasingtheNa+/H+anOport
IncreasedSodiumandBicarbintheurine
waterfollowsthesodium
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LOOPSThickAscendingLoop
IntheLoopofHenleLOOP
LOOPDIURETICS
DIURETICS
Furosemide MOA:InhibiOonoftheNa/K/2Clcotransport
Ethacrynicacid(nonsulfa) systeminthethickascendingloop
Usedforstatesofexcessiveedema(CHF, OHDANGOtoxtoxicity,Hypokalemia,
Cirrhosis,PulmonaryEdema,NephriOc DehydraOon,Allergy,NephriOs,gout
syndromes)
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BargersSyndrome
Mutatedgeneencodingproteinsinthethick
ascendingLoopofHenle
Thetripletransporter(Na/K/2Cl)isineecOve
TheylookasiftheyareusingaLOOPdiureOc,
buttheyarent
Hypokalemia,hyponatremia,metabolic
alkalosis
BPisnormalorlow
THIAZIDESDCT IntheDCTHCTZ
Hydrochlorothiazide(thiazidediureOcs)
MOA:shutsdowntheNa/Clcotransportin
thedistalconvolutedtubule(thuswelose
sodiumandchloride)
USES:HTN,CHF,Nephrolithiasisdueto
calciumstones,nephrogenicDI
A/Es:hyperGLUC(glycemia,lipidemia,
uricemia,calcemia)
**pa'entsknowtheseaswaterpills
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Thiazidesandhyperglycemia
IntheCollecOngDucts
Spironolactone:acompeOOvealdosterone
receptorantagonist
DecreasedNa+reabsopOonpreventsK+
secreOon
ConsideredaPotassiumsparingdiureOc
AnOandrogeniceects(causesgynecomasOa
inmen)
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Amiloride:blocksNa+channelsonthelumen
side
Decreasedsodiumintotheprinciplecell
meanslessK+getsexcreted
DIABETESINSIPIDUS
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DIABETESINSIPIDUS
22y/ofemalepresentswithpolyuriaand PsychogenicDI:
polydypsia Duetoexcessiveuidintake
Urineosmolalitywillbe<200mOsm/kg
WhatisatthetopofthedierenOaldx? RestricOnguidfor24hrwillconcentratethe
Whatisyournextstepinmgmt? urine
Glucosecomesback,whatnow?
CentralDI: NephrogenicDI:
LackofanOdiureOchormonereleasedfrom KidneysdonotrespondtoADH
theposteriorpitutary Urinedoesntconcentratewithuid
AdministraOonofsyntheOcADHwill restricOonORwithadministraOonofsyntheOc
concentratetheurine,andisthemanagement ADH
ofchoice(Desmopressin) GivingathiazidediureOcwillparadoxically
leadtouidconservaOon
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HowdoesaThiazidediure'chelpconserveuids
inNephrogenicDI?
Ithasaparadoxicaleectinthatitwillleadto
excessuidremovalviaitsnormalmechanismin
theDCT.Thisleadstoadecreaseinplasma
volumewhichlowerstheGFR,whichwill
sOmulatethereabsorpOonofmoresodiumand
waterinthePCTLessuidcanactuallyreach
theDCTsonotasmuchcanescape,thus
normalizingtheplasmaandurineosmolaliOes.
BODYWATER
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Stepstoansweringbodywater
LOSSOFISOTONICFLUID
quesOons
VomiOng,Diarrhea,Hemorrhage
Step1Lookattheosmolarity(topline) Onlyvascularvolumeisaected
Step2Lookatthevascularspace(gainsuid
rst)
GAINOFISOTONICFLUID LOSSOFHYPOTONICFLUID
AdministraOonofisotonicsaline DehydraOon,DI,Alcoholism
Onlyvascularspaceisaected Osmolarityincreases,lossofvascularandICF
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GAINOFHYPOTONICFLUID GAINOFHYPERTONICFLUID
WaterintoxicaOon,administraOonof HypertonicsalineadministraOon,mannitoluse
hypotonicsaline Increasedosmolarity,uidpulledfromICFinto
FluidgaininvascularandICF vascularspace
TheParklandFormula
4ccxWt(inKg)x%burned
RULESFORFLUIDREPLACEMENT
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Fluidreplacement
Replaceofdecitintherst8hrfromthe
Omeoftrauma(notfromtheOmeofexam)
Replacethesecondofthedecitoverthe
next16hr
RAAS
ThispathwayissOmulatedwhenweareina
lowvolumestate
THERENINANGIOTENSINALDOSTERONE Resultsinaseriesofeventsleadingto
SYSTEM(RAAS) retenOonofNa,Cl,andH20,whichulOmately
increasesvolumeandthusBP
AldosteronelowersK+levels
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HOWCANWELIMITTHISPATHWAY?
ACEInhibitorsandARBs
ACEINHIBITORS ANGIOTENSINRECEPTORBLOCKERS
Captopril,Enalapril,Lisinopril Candesartan,Losartan,Omisartan,
BlockconversionofA1A2byinhibi'ngthe Telmisartan,Valsartan
angiotensinconver'ngenzyme Angiotensin2receptorantagonists
UsedinHTN,CHF,DiabeOcnephropathy,renal MainlyusedforHTN,CHF,diabeOc
disease,andleTventricularhypertophy nephropathy
PreventsdegredaOonofBradykinin,whichcan OTengivenwhenpaOentsusingACEIs
causeabadcough(switchtoanARB) experienceasignicantcough(noeecton
A/Es:CAPTOPRILMnemonic Bradykinin)
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NormalRanges
pH:7.357.45
ACIDBASEDISORDERS pC02:3545
p02:80100
HC03:2228
StepstoagackingAcid/Base
ResponsestoalteredpH
problems
Respiratorychangesareimmediate Step1CheckpH(acidosisoralkalosis?)
Kidneystake23daystorespond Step2CheckC02/HC03todeterminemetabolicor
respiratorycause
Step3DeterminewhethercompensaOonisappropriate
Step4Calculatetheaniongap(formetacidosisonly)
Step5ChecktoseeifHC03changematchesaniongap
change(onlyformetacidosis)
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METABOLICACIDOSIS INCREASEANIONGAPMet.Acidosis
PrimarydecreaseinplasmaHC03,dueto MMethanol
overproducOonofacidsorinadequate UUremia
removalbythekidneys DDKA
Mustcheckaniongap(N:816)todetermine
cause(s).Eqn:Na(Cl+HC03)=AG PParaldehyde
IncreasedAG:thinkMUDPILES IIsoniazid
LLacOcacid
NormalAG:thinkHARDUP
EEthanol,EthyleneGlycol
Compensa'on:respiratoryrateincreases, SSalicylates
shouldseea1:1C02:HC03decrease
NORMALANIONGAPMet.Acidosis METABOLICALKALOSIS
AlargenetHC03lossisaccompaniedbyalossof Reectsanincreaseinplasma[HC03]
caOonsaswell,sotheresnochangeinAG
DuetoeitheragainofHC03ORan
HHyperalimentaOon extracellularvolumecontracOon
AAcetazolamide
RRenaltubularacidosis
Salineresponsivevs.Nonsalineresponsive
DDiarrhea (nextslide)
Compensa'on:Bradypneatoincrease
UUremia C02:HC031:1
PPostintubaOonhypocapnia
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RESPIRATORYACIDOSIS
TheresaprimaryincreaseinC02,almostalways
duetoalveolarhypovenOlaOon
Causesinclude:
Respiratorycenterdepression
Neuromusculardisorders
Upperairwayobstruc'on
Pulmonarydiseases
Mechanicalhypoven'la'on
CompensaOonforRESPIRATORY
RESPIRATORYALKALOSIS
ACIDOSIS
KidneycompensatesforincreasedC02by HypervenOlaOonleadstoadecreaseinC02
increasingtheamountofHC03itmakes
CompensaOonisdierentforacuteand Causes:
chroniccases Hypoxemia(anycause)
Acute:Forevery10C02sincreased,thereis1
S'mula'onofrespiratorycenter
HC03increased
Mechanicalhyperven'la'on
Chronic:Forevery10C02sincreased,thereis
3HC03increased
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MIXEDACID/BASEDISORDERS
Thereis>1primaryacid/basedisturbancepresentsimultaneously
Whentosuspectamixeddisorder:
1.
2.
TheexpectedcompensaOondoesntoccur
ThereisinadequateorextremecompensaOon
DIABETICKETOACIDOSIS(DKA)
3. IfPC02andHC03moveinoppositedirecOons
4. IfpHisnormalbutpC02orHC03areabnormal
5. IfchangeinHC03isntproporOonaltoaniongap(onlyforanion
gapmetabolicacidosis)
6. IfpHisreturnedtonormalwithcompensaOon(shouldnthappen)
DKA
Severelackofinsulinandsignicantblood
glucoseelevaOon
Leadstoametabolicacidosis
Signicantlossofbodywater(3L) RENALTUBULARACIDOSIS
PotassiumlevelsuctuatefalselyduetoK+/H+
exchangeincells(pseudohyperkalemia)
Fluidreplacementisrststepinmanagement,
followedbyinsulinandclosemonitoringofK+
levels
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TYPE1DistalRTA TYPE2ProximalRTA
Themostcommonform FailureofthePCTtoreabsorbHC03,leading
Afailureofthecollec'ngductstosecreteacid tourinarywasOngofHC03anddevelopment
ofacidemia
Producesanormalaniongapmetabolicacidosis
Lessseverethantype1becausethecollecOng
Urinarytractstones
ductssOllsecreteH+
BonedemineralizaOon(lateconsequence AssociatedwithFanconissyndrome(defecOve
Rickegs) reabsorpOonintheproximaltubule)
Treatment:OralSodiumHC03,PotassiumCitrate Treatment:HighdoseoralSodiumHC03to
forthestones overcomeurinaryHC03wasOng.
TYPE4HyporeninHypoaldosterone
TYPE3CombinedType1and2
syndrome
Veryrare DecreasedsecreOonofreninand
Overlappingfeaturesoftypes1and2RTA subsequentlyaldosterone
CarbonicAnhydrasedeciency UsuallyseenindiabeOcsduetodiabeOc
nephropathy
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FANCONISSYNDROME
InabilitytoreabsorbviathePCT
Glucose,AAs,uricacid,phosphate,andHC03
allpassintotheurine
GLOMERULARFILTRATIONRATE
MajorproblemsaredehydraOonand
hypophosphatemia(Ricketsinkids,
Osteomalaciainadults)
Treatment:Replacelostelectrolytesand
uids
GFR
RateatwhichplasmaislteredintoBowmans
capsule
GFR=Kf[(PGCPBC)(GCBC)]
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WhatdeterminesltraOon THEBASEMENTMEMBRANE
ParaAminohippuricAcid(PAH)
Isasubstancethatisnotabsorbedatallby
thebody
ItistheGoldStandardtestfordetermining
GFRandrenalplasmaow
20%willalwaysbelteredintotheBC,the
restwillalwaysbesecretedbythePTCs
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FiltraOonFracOon RESISTANCE
IsthefracOonofmaterialthatisltered Increaseordecreasedresistanceofthe
throughthekidney(GFR/RPF) aerentoreerentarterioleswillchangeGFR,
AhealthykidneyshouldalwayshaveaFFof PTCpressure,andoverallrenalbloodow.
20%(GFRshouldbe120ml/min,renalplasma
owshouldbe600ml/min)
Thus,anyOmesomethinggoesintothekidney,
20%shouldgetacross
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CLEARANCE
Thevolumeofplasmafromwhichasubstance
isremovedoveraperiodofOme
Clearance=[UsXV]/Px
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ACUTERENALFAILURE
BUNandCrea'ninelevelsrise
Urineoutputdecreases:
RENALFAILURE Oliguria<400cc/day
Anuria<100cc/day
Thetermacuterenalfailureusuallymeans
damagetothekidneyproper(Intrarenal)
PRERENALAZOTEMIA PRERENALLabFindings
ProblemrelaOngtotheinowtothekidneys BUN:Cr>20:1(BUNelevateswhenwecannot
(IE.Somethingbeforethekidneys) lterproperly)
Volumedeple'on UrineSodium<10(lowvolumestate=
Cardiovascularcauses sodiumretenOon)
Decreasedonco'cpressure Frac.onalexcre.onofSodiumis<1%
Renalarteryvasoconstric'on (hangingontosodium)
Decreasedvascularresistance(shock) Urineosmolarity>500mOsm/L(lowvolume
state)
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INTRARENALAZOTEMIA INTRARENALLabFindings
MCCofintrarenalkidneyfailureisAcute BUN:Cr<20:1
TubularNecrosis Urinesodium>20
MCCduetoDRUGS,CRYSTALS,ORCRUSH Frac.onalexcre.onofsodium>2%
INJURIES Therewillbealowspecicgravity
Drugs:AmphoB,CisplasOn,Aminoglycosides
Crystals:Uricacidstones,Oxalatestones
CrushInjuries:Myoglobindamagesthe
kidney(rhabdomyolysis)
POSTRENALAZOTEMIA RENALFAILUREMakingadiagnosis
ThereisanoulowobstrucOon Urinalysis
Bothsidesmustbeaectedinordertosee FracOonalexcreOonofsodium
symptoms
MCpresentaOonishydronephrosis,leadingto PostrenalazotemiarequiresaDRE
increasedpostvoidingresidualvolume Ifcausecannotbedetermined,biopsyshould
bedone
BladderObstruc'on:Prostateenlargement,
tumorsofthepelvis,urethralstrictures
UrethralObstruc'on:StonesorTumors
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RenalFailureTreatment
Correct/balancealluidsandelectrolytes
DisconOnuealloendingmedicaOons
Dialysisif:hyperkalemia,metabolicacidosis, GLOMERULARDISEASES
uidoverload,encephalopathy,orpericardiOs
NEPHRITICvs.NEPHROTIC
NEPHRITICSYNDROMES
NEPHRITICSYNDROMES
Diagnosing
MAINFINDINGS Bestini'alstep:24hrurinalysis(lookingfor
hematuriaand/orproteinuria)
Hypertension
Macroscopic/Microscopichematuria Bestdiagnos'ctest/GoldStandard:Biopsyof
Oliguria kidney
Edema(d/tdecreasedvascularprotein)
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NEPHRITICSYNDROMESMgmt THENEPHRITICSYNDROMES
TreatmentofsequelaewithdiureOcsand/or Poststrepglomerulonephri's
dialysisifneeded Goodpasturesglomerulonephri's
ControluidoverloadbyrestricOonofwater Rapidlyprogressingglomerulonephri's
andsalt(renaldiet) IgAnephropathy
IfinammaOonispresent,treatwith
Membranoprolifera'veglomerulonephri's
corOcosteroids
PostStrepGlomerulonephriOs GoodpasturesSyndrome
MCCbyGroupAstreptococcus MCinmales2040whopresentwithhemoptysis
95%ofthoseaectedrecovercompletely Agacksthetype4collagen
MCsignisperipheralandperiorbitaledema Isatype2hypersensiOvity
EM:Showssubepitheliallumpy/bumby UsuallyprogressestoRPGN
deposits LM:Showshypercullularity,mayormaynot
showcrescents
LM:Showshypercellularity,lotsofPMNs
IF:IgG/C3,lineardepositsalongthebasement
IF:Showsgranulardepositsinanonlinear
membrane
distribuOon,showsIgG/C3
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RapidlyProgressivegN IgANephropathy
MCpresentswithhematuria,proteinuria,HTN,andedema MCpresentaOonisgrosshematuria
Proteinuriamayexceed3.5g/day
AssociatedwithWegenersandGoodpastures OTenassociatedwithotherIgAdiseasessuch
Progressesrapidlytorenalfailure(w/inweeksmonths) asDermaOOsHerpeOformisandCeliacSprue
Type1:d/tanObodiesagainstBM(Goodpastures)
Type2:d/tdepositofimmunecomplexesinglomerulus LM:Showshypercellularity+mesangialcell
Type3:d/tanObodiesagainstPMNs(anOneutrophil proliferaOon
cytoplasmicanObody)
LM:Hypercellularity,crescentshapeddeposits IF:ShowsIgAmesangialcelldeposits
IF:IgGcrescentshapeddeposits
MembranoproliferaOvegN
MCpresentaOonishematuria(alsoseecolacolored
and/orcloudyurine)
CausedbymesangialdepositsandGBMthickening
ClassicTramTrackappearance
Type1:MCform,immunecomplexesdepositedsub
endothelialandmesangial(Classiccomplementsystem
associaOon)
Type2:Similartotype1butassocaitedwiththe
alternatecomplementpathway
Type3:Rare,seeamixtureofsubepithelialdeposits.
Seecomplementcomponent3(C3)onIM
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NEPHROTICSYNDROMES
MAINFINDINGS
Proteinuria>3.5g/day
Generalizededema
Hypoalbuminemia
Hyperlipidemia
NEPHROTICSYNDROMES,cont. NEPHROTICSYNDROMESDiagnosis
A1/3ofallcasesarecausedbysystemic Urinalysisdemonstratesproteinuriaof>3.5g/
diseasessuchasDiabetes,Lupus,or day
Amyloidosis CBCdemonstrateshypoalbuminemia(<3g/
IflasOng>2wk,wecallitchronic day)
GoldStandardfordiagnosis:RenalBiopsy
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NEPHROTICSYNDROMES
THENEPHROTICSYNDROMES
Treatment
Proteinandsaltrestricteddiet MembranousgN
DiureOcs MinimalChangeDisease
Hyperlipidemicdrugs FocalSegmentalgN
ACEIsfordiabeOcpaOents(alwaysgiveACEIs Amyloidosis
attherstsignofproteinuria) NodularSclerosinggN
AdministerthepneumococcalvaccinaOon
MembranousGlomerulonephriOs MinimalChangeDisease
MCnephroOcsyndromeinadults IstheMCnephroOcsyndromeseeninchildren
Primary:MCtype,85%ofcasesareidiopathic (peakincidencein23yrolds)commonfrom
Secondary:Autoimmune,InfecOous,Drug 17yr,andmaybeseeninteens
induced,Cancer EM:Showsfootprocesseacementand
EM:Subepithelialdeposits(spikesand vacuolizaOon
domes) Treatment:ACEIsandPrednisone
LM:verydensethickeningoftheBM
IF:GranularandlinearIgGdeposits
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FocalSegmentalgN Amyloidosis
Onlysmallfocioftheglomerulusareaected Usuallyanunderlyingcauseofamyloidosisis
LM:Showsthesclerosisoftheglomerulus present
AssociatedwithdiseasessuchasAIDSand Amyloidproteinsdepositinthemesangium
Sicklecelldisease andGBM
5variantsinprimaryform(Collapsing=high LM:Congoredstainofextracellular
riskofESRD,GlomerularTipLesion=lowrisk amorphousproteins
ofESRD)
NodularSclerosingGlomerulosclerosis
Historyofdiabetes
Willseered/pinkdepositsintheglomeruli
LM:Showsnodularsclerosisofthe
glomeruluswithBMthickening
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EOSINOPHILSINTHEURINE
THEURINALYSIS LookforDrugInducedHypersensiOvity
TheMCCisacephalosporin
RBCCASTS WBCSANDBACTERIA
LookforGlomerularNephriOs LookforInfecOon
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CRYSTALS BENCEJONESPROTEINS
Lookforbirefringence,likelyGOUT LookforMulOpleMyeloma
POSITIVEFORBLOOD,NEGATIVEFORRBCS FATCASTS+>3.5gPROTEIN/DAY
LookforMyoglobinuria LookforNeprhoOcSyndrome
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CASTS
**onlythenephroncanformacast**
WBCcastsAcutePyelonephriOs
RBCcastsGlomerulonephriOs
EosinophilcastsIntersOOalnephriOs HIGHYIELDRENALPATHOLOGY
FatcastsNephroOcsyndrome
Waxycastschronicendstagerenalfailure
Hyalineandepithelialcellsnormalnding
(sloughedoPCTcells)
CrescentshapedcastsRPGN,Goodpastures/
Wegeners
HORSESHOEKIDNEY
CommoncongenitalcondiOon,usuallyonly
seenonautopsy
CentralporOonofkidneysremainfusedduring
embryogenesis
MiddleporOongetscaughtundertheIMA
UsuallyAsx,thoughmaypresentwith
abdominaldiscomfort
IncreasedriskofUTIsandkidneystones
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Ifkidneyistoosmall,theMCCisrenalartery
stenosis
Ifkidneyistoobig,itisusually1of3
ABNORMALKIDNEYSIZES
condiOons.Polycys'c,MedullaryCys'c,or
MedullarySpongekidneydiseases
RenalArteryStenosis EnlargedKidneyDiseases
MCCincludeatherosclerosisandbromuscular Polycys'cKidneyDisease
dysplasia MedullarySpongeKidneys
Almostalwaysunilateral MedullaryCys'cKidneys
SymptomsdontstartunOlatleast50%stenosis
AbdominalbruitcanbehearteitherrightorleT
ofthemidline
Dx:Ultrasoundandreninlevels
Treatment:Atherectomy(AvoidACEIs)
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POLYCYSTICKIDNEYDISEASE
2types:AdultandInfanOle
Adulttype:AD(PKD1,2,and3gene),
bilateral,presentswithHTNandrenalfailure
Requiresakidneytransplant
Infan'letype:AR,unilateral,noHTNandno
renalfailure
DiagnosewithU/S
Treatment:SupporOve,targetBP<130/85
MEDULLARYSPONGEKIDNEY
CysOcdilaOonsofthecollecOngtubules
Manycasesarebilateral(~70%)
OTenpresentswithhematuria
IncreasedriskofkidneystonesandUTIs(seen
aTerage30maybeiniOalpresentaOon)
Diagnosewithanultrasound
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MEDULLARYCYSTICKIDNEYDISEASE
ADdiseasewhenpresenOnglaterinlife,AR
diseasewhenpresenOngearlyinlife
MulOplecystsdevelopinthemedulla
Earlysymptomsinclude:Polyuriaandpolydypsia
becausetheylosetheabilitytoconcentrateurine
(medullaryprocess)
Laterinlifeendstagerenaldiseaseoccursin
most
Diagnosewithultrasound
Notreatmentknown
ANATOMYOFTHEURETER
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KIDNEYSTONES
Calciumstones
Struvitestones
UricAcidstones
Cysteinestones
Oxalatestones
Si/Sx:Hematuria,N/V,radiaOngankpain(to
thegroin)
Mgmt:NS+Opiates(theneachtypehasanother
specicmgmtcriteria)
RadiaOnganktogroinpainofa
CalciumStones
kidneystone
AretheMCtypeofkidneystones,theyare
radioopaque
MCCbyhypercalcemia
Presenta'on:Flankpain,hematuria,N/V
GiveNS(toush),morphine(forpain),and
addathiazidediure'c(lowersurinary
calcium)
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StruviteStones UricAcidStones
TheseareStaghornCalculi
AreatriplephosphatestonecontainingCalciumMagnesium
AssociatedwithcondiOonswherebythereis
AmmoniumPhosphate rapidcellulardivision(cancer,burns,trauma)
CausedbyUreasePosiOvebugs:PPUNCHSB
PProteus Theyareradiolucenet,thusmustbeseenwith
PPseudomonas
UUreaplasma
anultrasound
NNocardia NS+Morphineisthestandardoftreatment
CCryptococcus
HH.Pylori
SStaphSaprophyOcus
BBrucellosis
CysteineStones/Crystals OxalateStones
AnADdisorderduetodefecOverenal Formedwhentheresamalabsorp'on
transportof4aminoacids(COLA) problem
COLA:Cysteine,Ornithine,Lysine,Arginine Arehexagonalinshape
Crystalsareenvelopeshaped NS+Morphine
NS+Morphine
Reducesaltandproteinfromdiet,alkalinize **sametypeofcrystalcanformbyingesOng
theurine(citrate) ethyleneglycol
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PYELONEPHRITIS
InammaOonofthekidneycausedbyan
ascendingUTI
MCCareE.ColiandE.Faecalis
Si/Sx:Fever,N/V,severeCVAtenderness,pain
onurinaOon
MayprogresstosepOcshock
Riskincreaseswiththefollowing:Mechanical
obstrucOon,immunocompromisedstates,
increased#ofsexualpartners.
PYELONEPHRITIS,Cont. HYDRONEPHROSIS
Diagnosis:1stKUB(kidney,ureter,bladder) ObstrucOonsomewherealongtheurinespath
2ndifKUBisntconclusive,doaspiralCT causesabackupofuidintothekidney
3rdifCTisinconclusivedoanIVP AcutecasesareMCd/tkidneystones(thus
IfhydronephrosisdevelopsdoanU/S presentasapainfulincident)
ChroniccasesareoTenAsx,orpresenOng
Ifthereisastoneinthemiddleorlower1/3of
withmildabdominaldiscomfort
theureter,wecanremoveitviaureteroscopy
RequiresempiricalanObioOctreatment+ StasisofurineleadstoincreasedriskforUTIs
percutaneousnephrostomystenttodrainpus
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HYDRONEPHROSISMCCs
Newborns:MCCisposteriorurethralvalves
(retrogradeejaculaOon)and/or
malimplantaOonoftheureters(no90angle)
Children:MCCisUTI
Teens:MCCisurethralvalvestricture(STDs)
Adultmales:BenignProstaOcHypertrophy
Adultfemales:MCCiscystoceleoruterine
prolapse(causedbymulOplevaginal
deliveries)
BENIGNPROSTATICHYPERTOPHY BPH
IstheMCCofurinaryobstrucOoninadultmen
HyperplasiaoftheprostaOcstromaand
epitheliumleadstoformaOonofnodulesinthe
periurethral(central)porOonoftheprostate
OvergrowthofOssuecancompressurineoulow,
leadingtocommonsymptoms:
Si/Sx:urinaryhesitancy,urinaryfrequency,
dysuria,increasedriskofUTI,urinaryretenOon
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TURP(TransurethralresecOonof
BPH,cont.
prostate)
Causes:Androgensmayplayrole ResecOonofprostaOcOssuebyelectrocauteryorsharp
DHT(metaboliteoftesosterone)playsarole dissecOon
A/E:TURPsyndrome(hyponatremiacausedbywater
Diagnosis:DREisbestiniOaltest(aswellasbest intoxicaOon),becauseofanoverloadofuid
screeningtest) absorpOonfromtheopenprostaOcsinusoidsduring
theprocedure
Treatment:1blockers(Prazosin,Terazosin, Pudendalnervecanbeinjured(leadingtoimpotence)
Doxazosin) Urinaryincon'nenceifexternalsphincterisinjured
5reductaseblockers(blockDHTformaOon) Retrogradeejacula'onifinjurytoperiprostaOc
sphincter(internalsphincter)
Surgicaltreatment:TURP
ABDOMINALAORTICANEURYSM AAA,cont.
MCCbyatherosclerosis SizeoftheAAAisthemainfactorin
90%ofAAAsoccurbelowtherenalarteries determininghowyouwillmanagethepaOent
If<4cmindiameter=controlBPandmonitor
Presenta'on:paOentmayc/oatearingpain regularlyforchanges
inthelowerback,aswellasapulsaOlemassin If46cm,surgeryisopOon(mustbedoneby
theabdomen vascularsurgeon)watchBP
If>6cmindiameter=controlHTNandbring
Diagnosis:U/SthenconrmwithCT tosurgery
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URACHALCYST
Remnantsoftheallantois
THEBLADDER MainpresenOngsignwillbedrainingofurine
fromtheumbilicus
Requiressurgery
EXSTROPHYOFTHEBLADDER
Rarecongenitaldefectcausedbyfailureof
closureoftheabdominalwallduringfetal
development
Presentswithagroupofanomaliesinthe
lowerabdominalwall,bladder,anteriorbony
pelvis,andtheexternalgenitalia
Treatment:surgicalcorrecOon
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CYSTOCELE CYSTOCELE,Cont.
HerniaOonofthebladderintothevaginad/tlossof Diagnosis:Voidingcystourethrogram
supporOvePubocervicalFascia
MCCismulOplechildbirth
PaOentwillc/ourinaryleakageand/orincomplete Treatment:
emptyingofthebladder
MILD=notreatmentnecessary/Kegels
MILD(grade1):MildherniaOonintovagina(usuallyno
symptoms) MOD=Pessary(holdseverythinginplace)
MOD(grade2):Bladdersinksintovaginalopening SEVERE=SurgicalcorrecOon
SEVERE(grade3):Bladderbulgesoutofvaginal
opening
INCONTINENCE
Urge:feelingasthoughtheyalwayshaveto
urinate
Stress:weakpelvicoormusclescause
leakagewithincreasedabdominalpressure
Overow:duetoanatomicalobstrucOon
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URGEINCONTINENCE URGEINCONTINENCE,Cont.
Detrusermuscleac'vityisincreased Treatment:
LeadstospasOcityofthebladder(UMN InchildrenImipramine
lesion) InadultsOxybutynin
BladdercapacityislowbecauseofrepeOOve
bladderemptying(lowresidualvolume) ForbothputthemonaurinaOonschedule
Normalsphincterpressur toensurenoaccidents
KEYTODx:alwaysfeelasthoughtheyhaveto
gotothebathroom
STRESSINCONTINENCE
Causedbyweakpelvicoormuscles
Anyincreaseinabdominalpressureleadstoasudden
lossofurine
Detrusermuscleandbladdercapacityremainsnormal
Sphincterpressureisdecreased
MCCisobesity(toomuchestrogen=toomuchmuscle
relaxaOon)
Treatment:Weightloss+Kegelexercises(1stline)
Pseudoephedrineas2ndlinetosOmulatesphincter
constricOon
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OVERFLOWINCONTINENCE
Causedbyananatomicalobstruc'on
Bladderscapacityisincreased/detruser
acOvitydecreased/sphincterpressure
increased
PaOentc/oaweakurinarystream,dribbling
aTerurinaOon,urgency/frequency
MCCsOVERFLOWINCONTINENCE CYSTITIS(UTI)
Newborns:posteriorurethralvalves MCinsexuallyacOvefemales,elderly,andthose
withcathetersintheurethra
Children:strictures MCCisE.Coli(nitriteposiOve),S.SaprophyOcus
(catheters)
Adultmen:BPH
NitritenegaOvending=Enterococcus
Adultwomen:uterineprolapseandcystocele
Si/Sx:Dysuria,urgency,lowerabdominalpain
Treatment:surgicalcorrecOon/removalofthecauseof Treatment:TMPSMX(Bactrim),forrefractory
obstrucOon
casesuseuoroquinolone(ex.Ciprooaxiacin)
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ThePenisDevelofUrethra
Dorsal=topofpenis
Ventral=bogomofpenis
THEPENIS
Theurethradevelopmentbeginsdorsallyand
movesventrally
EarlyterminaOonoffusionleadsto
hypospadias(ventralside)
HYPOSPADIAS HYPOSPADIAS
IstheMCcongenitalGUabnormality
IsanconnecOonbetweenthebaseofthe
penisandtheurethra
MCproblemisthepredisposiOontoUTIs
Mgmt:thisrequiressurgicalcorrecOon
immediately(d/thighriskofUTIs)
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COMMONPENILEINFLAMMATORY
URETHRITIS
PROBLEMS
Balan''s:inammaOonoftheforeskinand WhenapaOentc/odysuria,theresan
headofthepenis(d/tS.Aureus) infecOonintheurethra
MCCisChlamydiatrachomaOs(90%areAsx)
Phimosis:scarringoftheforeskin,adheresto 2ndMCCisN.Gonorrhea(90%men
symptomaOc,50%femalesaresymptomaOc)
theheadofthepenis
**Chlamydiadoesntalwayscoinfectwith
Paraphimosis:scarringoftheforeskin, gonorrhea,butndinggonorrheausuallyhas
adherestothebaseofthepenis coinfecOonwithchlamydia
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StagingCancer
Stage1:Notvisible,only1stlayerofcellsis
involved
CANCER Stage2:Wecannotseeitbutcanfeelit,1stand
2ndlayerofcellsinvolved
Stage3:Localstructuresinvaded
Stage4:Metastasis
Anosymptomspresent
Bsymptomsarepresent
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WhattodowithaMASS?? NEOPLASIA
Ovarianorbreastmassremoveitrst BENIGN MALIGNANT
Anywhereelsetestitrst,removeif Wellcircumscribed Notcircumscribed
Freelymobile IsadherenttosurroundingJssue
malignant Encapsulated Notencapsulated
Doesntgrowoutsideofcapsule Outgrowsitscapsule
Doesntoutgrowitsbloodsupply Outgrowsitsbloodsupply
Doesnotmetastasize Willmetastasize
Followsnormalphysiologyrules Doesntfollownormalphysiology
rules
MALIGNANTNEOPLASIA CHEMOTHERAPYANDRADIATION
Need2thingstoensuretheirsuccess Targetrapidlydividingcells
Angiogenin:requiredtohelpcancerproduce Chemotherapytokillcancercells
itsownbloodvessels(reqlotsofATP) Radia7ontoinducenewmutaRonsandcease
Endosta7n:isanRangiogenic,preventsnew celldivision
formsofcancerfromtakingoveritsblood
supply
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METASTASIS
Occurswhencanceroutgrowsitslocalblood
supply
BBPAL
BBrain HOWTONAMEATUMOR
BBone
PPericardium
AAdrenals
LLiver
Stepstonamingeverytumor Stepstonamingeverytumor
2namestoeverytumor Sometumors/cancerdontfollowtherules
Re7noblastoma
1stname:ComesfromtheMCRssuetypeinthe
area(Gland=Adeno,Bone=Osteo,Skin= Nephroblastoma
Fibroma,etc) Mesothelioma
Hepatoma
2ndname:ComesfromtheRssuefromwhichit
originates Seminoma
Iforiginatesfromepithelium=Carcinoma Teratoma
IforiginatesfromconnecRveRssue=Sarcoma Lymphoma
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InteresRngtumortypes
Hamartomas:arefocalmalformaRonsthat
resembleneoplasms,howevertheyarebenign
(MCseenintheLungs,Heart,and
Hypothalamus) HIGHYIELDCANCERS
Choristomas:thisisanormalgrowthofsome (fromheadtotoe)
Rssuetype,butiffoundinanabnormal
locaRon(Ex.Endometriosisendometrial
Rssuefoundoutsideoftheuterus)
BRAINCANCER
MCIntracranial(2ndMCprimaryCNS
neoplasm)Meningioma
MCPrimarybraintumorAstrocytoma
THEBRAIN
MCCofbraintumorMetastasis
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Meningioma
The2ndMCprimaryneoplasmoftheCNS
Arisesfromthearachnoidcellsofthe
arachnoidvilli
Symptomsproducedb/citdisplacesbrain
Rssue
Psammomabodiespresent
Usuallysmallandbenign(sxd/tsize)
Astrocytoma
IstheMCprimarybraintumor GLIOMA:MCseenontheopRcnerve(OpRc
Originatefromtheastrocytes NerveGlioma)
Causesmonocularblindness
Therearespecictypesofastrocytomas: OLIGODENDROGLIOMA:Ifperipheralwecall
Glioma,Oligodendroglioma,Ependymoma itaSchwannoma,ifcentralwecallitan
Oligodendroglioma
EPENDYMOMA:arisefromependymalcells
(cellsliningtheventricles)
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GradingASTROCYTOMAS ClassifyingASTROCYTOMAS
Grade1Slowgrowing,LTsurvival NarrowZoneofInltraJon:hasaclearoutline
onimaging
Grade2RelaRvelyslowgrowing,oaengo
frombenigntomalignant
Includesthefollowing:
Grade3AnaplasRc,associatedwith Pilocy7castrocytoma(slowgrowing,grade1)
neurologicalsymptoms(seizure,HA,AMS)
Subependymalgiantcellastrocytoma(slow
Grade4GBM,mostmalignantand growing,grade1)
aggressive PleomorphicXanthroastrocytoma(slowgrowing,
grade1)
ClassifyingASTROCYTOMAS GLIOBLASTOMAMULTIFORME
DiuseZoneofInltraJon:haveunclear TheMCprimarymalignantbraintumor
marginsonimaging Isagrade4astrocytoma
Growsandspreadsaggressively
Includethefollowing:
Lowgradeastrocytoma(relaRvelyslowgrowing, Caucasian/asianmales>50,hxoflowgrade
maychangefrombenigntomalignant,grade2) astrocytoma(increaserisk)
Anaplas7castrocytoma(grade3,causeof Dx:Tissuesample
neurologicalproblemsseizure,AMS,HA) MustbesurgicallyremovedradiaRonasan
GlioblastomaMul7forme(grade4,most adjunctisnecessaryb/cofitsdiuseinvasion
malignant/aggressivebraintumor) (doublessurvivalrate)
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NEUROFIBROMATOSIS:
CafauLaitspots(hyperpigmentedmacules)
NEUROCUTANEOUSSYNDROMES Neuromasandbromas
(aquickreview) Type1Chrom17
Type2Chrom22
STURGEWEBERSYNDROME: TUBEROUSSCLEROSIS:
Portwinestainon(V1) AshandLeafspotswhichare
AngiomasofthebrainandreRna hypopigmentedmaccules
Tubors(Primarybraintumors)
Renalcellcarcinoma
Rhabdomyomas/Rhabdomyosarcomaofthe
heart
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SEIZURES
Theyarespontaneousanduncontrolled
Letssidetrackforamoment. depolariza7onofthebrain
Recurrent/idiopathicseizuresareknownas
SEIZURES Epilepsy
Ifacauseisknown,wecannotcallitepilepsy
SEIZUREGeneralizedvs.Focal WorkUpforSEIZURES
Generalized:therewillbeaLOC 1st:Give02(remember#1causeofseizureis
Thewholebraindepolarizessotheycannotspeak,
think,reason,ordoanythingelserequiringhigher ischemia)
mentalfuncRon 2nd:RuleoutamasslesionwithCTorMRI
Focal/Par7al:theymaintainconsciousness 3rd:R/Oinfec7onofbrainwithLP(remember
Onlypartofthebrainisdepolarizing(therestisfully the2ndMCCofseizureisinfecRon)
funcRonal)
4th:GetCBCandchemistrypanel(3rdMCCis
ToddsParalysis:postictalfaRguecausedbya anelectrolyteproblem)
completelackofATP
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GENERALIZEDSEIZURES
Tonicclonicseizure TonicClonicseizuretheMCgeneralized
Febrileseizure seizure
Myotonicseizure PaRentsRensandjerksthebodyaround
Atonicseizure ThisistheGrandMalseizure
BenignRolandicseizure 1stlinetx:Valproate.2ndlinetx:Phenytoinor
LennoxGasteauseizure Carbamazepine
StatusEpilep7cus
Absenceseizures
Febrileseizures:notdangerous,6criteriafordiagnosis Myotonicseizure:thisisabenigncondiRon
Criteria: wherebythepaRentexperiencesacutefullbody
1. Feveratanynumber(speedyonsetiskeytodx) muscularcontracRons
2. Generalizedseizure SomeRmesreferredtobypaRentsasjumps
3. LasRng<20minutes MCinvolvesthearms,neck,andshoudlers
4. Noneuralproblemsbefore/aaerseizure 1stlinetx:ValproicAcid
5. EEGisnormal
6. Ageof6mn6yr Atonicseizure:completelossofmuscletone
PaRentsfalltotheground
Tx:Acetaminophentolowerfever,reassurance
Fromthefrontallobe(corRcospinaltract)
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BenignRolandicseizure:aseizurethatoccursMC StatusEpilep7cus:seizurelasRng>20minutes
duringthenight Isamedicalemergency
PaRentgetsonesidedparasthesias,inabilitytospeak, 1stlinedrugisLorazepamorDiazepam(forimmediate
drooling control)
CanbeparRalaswell,theydonotremember FollowwithPhenytoinloadingforcontrol
LennoxGasteauseizure:daily,frequentseizuresof Absenceseizures:MCseizureinchildren
dierenttypes Theygetstaringspells
Usuallyaccompaniedbydevelopmentaldelays+ Istheonlyseizurewithoutapostictalphase
behavioralproblems CanrecreatebyhavingthepaRenthypervenRlate
MCseenin2nd6thyearoflife 1stlinetx:Ethosuxamide
FOCALSEIZURES
Canstartfromanywhere Jacksonianseizure:
Candeterminewhereitstartedfromthendings IniRatesintheprimarymotorcortex
MCCare:Mass,Stroke,orInfecRon Symptomsbegintomarchfromonemuscleto
another
EEGisdiagnos7c:Demonstratesa3spike
parerneverysecond
TemporalLobeseizureakapsychomotor
Marching/Jacksonianseizurestartsinthemotor seizure
cortexandmarchesthroughallofthemuscles
HallucinaRonsstartrightbeforetheseizurestarts
Temporallobeseizureisfocal 1stlinetx:Carbamazepine
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THEPITUITARY
Mosttumorsofthepituitaryarenonfunc7onal
GalactorrheaandamenorrheaaretheMC
ndings
THEPITUITARY
TheMCpituitarytumoristhepituitaryadenoma
(isnonfunc7onal)
TheMCfunc7onaltumorofthepituitaryisthe
Prolac7noma
TheMCcancerofthepituitaryisthe
Adenocarcinoma(rare)
ChromophobesnonfuncRonal/non
staining
THEPINEALGLAND
AcidophilsproduceGHandProlacRn
BasophilsproduceACTH,TSH,FSH,andLH
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THEPINEALGLAND
MCtumorofpinealglandisthePineal
Adenoma(Pinealoma)
LeadtoplasyofCN6d/titslocaRon
TUMORSOFTHEPOSTERIORFOSSA
Mayleadtoprecociouspubertyinmalesb/f
9yrorfemalesb/f8yr
MCcancerofthePinealglandisthe
Adenocarcinoma
CLASSICFINDINGS Medulloblastoma
EarlymorningvomiRngisaclassicsignof Highlyaggressive/malignant
posteriorfossatumors MCoriginatefromthe4thventricle(b/t
brainstemandcerebellum)
CausedbyCTZsRmulaRon
Theyhaveuniquehistologybecausetheyare
Medulloblastoma unabletodierenRateintotheirdesRnedcell
Craniopharyngioma types
Perivascularpseudoroseèsare
verycharacterisRcof
medulloblastoma
12
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Craniopharyngioma
AbenigntumorthatdevelopsfromRathkes
pouch
IsMCseenin510yrolds
Causessxin3ways:ICP,Pituitary
dysfuncRon,CN2damage
THEANTERIORMEDIASTINUM
Letstalkaboutthe4Ts
TCELLLEUKEMIAS&LYMPHOMAS
TUMORS/CANCEROFTHEMEDIASTINUM THYMUS
THYROID/PARATHYROID
TERATOMA
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TCELLLEUKEMIAS HAIRYCELLLEUKEMIA
Hairycellleukemia Aka:HairyTcellLeukemia
Tcelllymphomas Oneoftheraretcellleukemias
75%isofBcellorigin,25%isofTcellorigin
Cellscontainuniquehairymembrane
projec7ons,ORfriedeggappearance
UniquediagnosRcsinvolveTRAPposi7velab
nding
MYCOSISFUNGOIDES
IstheMCformofpurelyTcellleukemia
Presentswitharashthatjustwontgoaway!
SkinbiopsydemonstratesmalignantTcellsthatcontain
dangerouslevelsofmucopolysaccharides
**pathtodiagnosisisthatsteroidsandan7fungalcreams
willnothelpatall**
OnCBC,thelymphocyteshavecharacterisRcindenta7ons
OnceitreachescirculaRonitisknownasSezary
Syndrome
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THETHYMUS
Associatedwithallautoimmunediseases
exceptforGraves(itisimmunopriviledged)
Thymusisdervivedfromthe3rdbranchial
pouch
MCtumorofthethymus:Thymoma
MCcancerofthethymus:Adenocarcinoma
(rare)
THYROID THYROID&PARATHYROID
Ruleofthumb. MCmassofthyroid:Thyroglossalductcyst(midline,
riseswithswallowing)
MCtumorofthyroid:Follicularadenoma
CYSTICNODULE+HOTNODULE=GoodPx MCcancerofthyroid:Papillarycarcinoma
Psammomabodiespresent
SOLIDNODULE+COLDNODULE=BadPx IflocalMETSthenprognosis
isgood(Papillaryhasagoodpx,
medullarydoesnot)
RiskfactorispervioushxofneckradiaRon
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CysRcNeckMasses SolidNeckMasses
ThyroglossalductcysttheMCcysRcneckmass Aremostworrisome
Diagnosis:1stU/SforvericaRon,thenFNA(will Ifitisacoldnodule,malignancyriskis20%
bebothdxandtxastheneedleisinsertedthe
uidescapesandcystcollapses) Ifcoldnodule+hxofpreviousradiaRonwedo
alobectomy
RAIU:todetectwhethernoduleishotorcold IfcoldnodulewithouthxofpreviousradiaRon
HotNoduleishyperacRve(good) wedoabiopsyifmalignanttolobectomy
ColdNodulenonfuncRonal(incrmalignancy IfnoduleisHOTtreatforhyperthryoidism
risk)
THRYOIDParafollicularCells PARATHYROIDS
Posterioraspectofthethyroid Locatedbehindthethyroidgland
MCtumor:Adenoma
MCtumor:ParathyroidAdenoma
MCcancer:Medullarycarcinomaofthyroid ParathyroidAdneomaistheMCCofisolated
(ismorecommonthanAdenomaonlyRme) hypercalcemiainAmerica
MCcancer:Adenocarcinoma(rare)
Parafolluclarcellssecretecalcitonin(oppose Dx:DoanU/S
PTH,inhibitosteoclastsfrombone **dontforgetthisisaMENsyndrome
reabsorpRon)
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THEMIDDLEMEDIASTINUM THEHEART
2veryimportantstructuresinthemiddle Thereare4importantlayerstotheheart,and
mediasRnum theycanalldevelopmasses
THEHEART Endocardium:innermostlayeroftheheart
THELUNGS Myocardium:middlelayer
Epicardium:outerlayer(raretogettumorsor
cancershere)
Pericardium:encasestheheart
ENDOCARDIUM: MYOCARDIUM:
MCtumor:Myxoma(MCseeninLAiswhy Isathickmuscularlayer
wecallitanatrialmyxoma) MCtumor:Rhabdomyoma
MCinmiddleagedfemalewhopassesoutfor MCcancer:Rhabdomyosarcoma(MCseenin
afewseconds,thenrecovers youngchildren<5yr)
WillhearaplopwhenauscultaRngtheheart
MCcancer:Angiosarcoma(rare)
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THELUNGS
PERICARDIUM: MCmassinchildren:Hamartoma(abdgrowthof
normalRssue)
MCmassinadults:Granular(MCCbyfungus)
MCtumor:Fibroma MCtumor:Adenoma
MCcancer:Metastasis
MCcancer:Metastasis
MCPrimarycancer:Bronchogenic
Adenocarcinoma
MCIntrathoraciccancer:Squamouscell
carcinoma(linkedtosmoking)
CentrallyLocated
Squamouscellcarcinoma:
Linkedtosmoking
ProducesPTH(highserumCa2+,lowserumPO4)
Smallcellcarcinoma:
Linkedtosmoking
ProducesACTH(Cushings),ADH,PTH,andTSH
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PeripherallyLocated PNEUMOCONIOSES
BronchogenicAdenocarcinoma: ANTHRACOSIS:doesntcausecancer,Black
Lung,d/tLTcoalmining
BronchoalveolarAdenocarcinoma: ASBESTOSIS:malignantmesothelioma
Onlylungcancernotlinkedtosmoking SILICOSIS:d/texposuretosilicadust(sand
Isrelatedtopneumoconioses blasRng,mining)
BERYYLIOSIS:exposuretouorescentlight
bulbs
BISSINOSIS:exposuretocoron
LUNGCANCERMgmt ThePleuralCavity
1ststepalways:Lookatoldradiographyif MCtumor:Mesothelioma
available(lookingforchanges) MCcancer:Mesothelioma
Theseareferruginousbodies(ie.Asbestos
berscoatedwithiron)
Willseepsammomabodiesandpleural
thickening
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THENASOPHARYNX
MCmass:Polyp
THENASOPHARYNX MCtumor:Fibroma
MCcancer:Nasopharyngealcarcinoma
THEORALCAVITY
MCtumor:Fibroma
MCcancer:Squamouscellcarcinoma
THEORALCAVITY
MClocaJons:1stLips,2ndTipoftongue,3rd
Floorofthemouth
Anyonewhochewstobaccohasgreatestriskof
canceronthelower/innerlip,thenRpofthe
tongue
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THEESOPHAGUS
MCtumor:Leiomyoma
THEESOPHAGUS MCcancer:Squamouscellcarcinoma
MCcancerinlower1/3:Adenocarcinoma
(Barrersesophagusgives10%risk)
THESTOMACH
MCtumor:Leiomyoma
MCcancer:Adenocarcinoma
THESTOMACH Stomachcancerhasthefollowingassd:
Virchowsnode
LiniRsplasRca
Signetringcells
Kruckenburgtumor
Severeweightloss
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RISKFACTORSFORUPPERGICANCER
MCCissmoking
2ndMCCisexcessivealcoholintake
3rdMCCisnitrites(smokedmeats,smoked THESMALLINTESTINE
shreleasesfreeradicals)
4thMCCisJapaneseheritage(hotsaki)
**no7cetheyareallirritants**
THESMALLINTESTINE
MCtumor:Leiomyoma
MCcancer:Adenocarcinoma THEAPPENDIX
MCcancerintheIleum:Lymphoma(contains
anenormousamtoflymphoidRssuePeyers
patch,MALT,GALT)
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THEAPPENDIX
MCtumor:Leiomyoma
MCcancer:Carcinoid THECOLON
DoesNOTmetastasize
Carcinoidsyndrome(large5HTrelease)
ushing,diarrhea,andwheezing
THECOLON RISKFACTORSFORCOLONCANCER
MCtumor:Leiomyoma #1Lowberdiet
#2Highfatdiet
MCndings:
AppleCorelesion #3Polyps(Villoushashighestriskof
Pencilthinstool malignancy40%)
Melena(indicatesrightsidedbleed,upperGI
bleed)
#4UlceraJveColiJs(10%increasedriskwith
UC)
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POLYPS
THELIVER
MCmass:Cyst
MCtumor:AdenomaandAVMs
THELIVER MCcancer:Metastasis
MCPrimarycancer:Hepatocellular
Adenocarcinoma
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HepaRcAdenomas ArteriovenousMalformaRons
MCassociatedwithhighlevelsofestrogenor ConnecRonsbetweenthearteryandveinis
steroiduse anatomicallyincorrect
Mayrupturewithincreasedintraabdominal LeadstoadecreaseinAV02dierenceand
pressure(mayleadtodangeroushemorrhage) thusincreasedvenous02
MCseeninfemalesusingOCPs Greatestriskisthetendencytoruptureand
bleed
AMVsyndormesinclude:OslerWeberRendu
andVonHippelLindau
THEGALLBLADDER
MCtumor:Leiomyoma
THEGALLBLADDER MCcancer:Adenocarcinoma
Carrieswithitapoorpxbecauseithides
undertheliver(5%5yrprognsosi)
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THEBILIARYTRACT THEPANCREAS
MCmass:Choledochalcyst MCmass:Cyst
MCtumor:Cholangioma MCtumor:Adenoma
MCcancer:Cholangiosarcoma MCcancer:Adenocarcinoma
Riskofcancerincreaseswithchronicscarring
(PBC,Sclerosingcholangi:s)
THEPANCREASMCCofJaundice PANCREATICADENOMAS
Innewborns:Choledochalcyst Glucagonoma:glucose,lipids,ketones
Inchildren:PancreaRRs(d/ttrauma) Insulinoma:highinsulin&CpepRdelevels
Inadults:PancreaRts(d/talcohol,jaundice) Gastrinoma:gastrinlevelshighalltheRme,
ulcersthroughoutsmallbowelZollinger
Ellisonsyndrome
Somatosta7noma:causessevereconsRpaRon
VIPoma:secretorydiarrhea
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THEOVARY
MCmass:Follicularcyst
MCtumor:Serouscystadenoma
THEOVARY
MCcancer:Serouscystadenocarcinoma
Highlymalignant
OVARIANTUMORS OVARIANTUMORS
Fibroma:osmoRcallyacRve,associatedwith Choriocarcinoma:highhCGlevels
pleuraleusionsand/orascites SertoliLeydigcelltumor:testosterone
Meigssyndromeascitesandpleural leadstomasculinizaRon/virilizaRoninfemale
eusionduetotumor(resolveswithtumor Mucinouscystadenocarcinoma:very
removal) mucinous(pseudomyxomaperitoneii)ifit
Granulosacelltumor:highestrogen burtsintheabdominalcavityitcanleadto
(precociouspuberty) widespreadscarring,causingpseudomyxoma
Yolksactumor:highFPlevels (rapidlyfatal)
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Teratoma:strumaovariicontainall3
embryoniclayers(endo,meso,ecto)
Majorityofteratomasgotheectodermalpath
(skin,bone,hair)
THEUTERUS
**ovariantumorsliketobecomeendoderm
(MCthyroidRssue)lookforGraveswithout
aneckmass,shehasstrumaovarii(starton
betablockers)
THEUTERUS
MCmass:Poly
MCtumor:Leiomyoma(akabroids)
THECERVIX
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THECERVIX
MCmass:Warts(HPV,SyphiliRcwarts)
MCtumor:Fibromas
THEVAGINA
MCcancer:Squamouscellcarcinoma
THEVAGINA
MCmass:Warts,Bartholincyst
MCtumor:Fibroma
THEKIDNEY
MCcancer:Inupper:Squamouscell
carcinomaofthecervix(containsthemucosa),
lower:containsthemuscletumor:
Rhabdomyoma,Cancer:Rhabdomyosarcoma
(sarcomabotyroides)
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THEKIDNEY
MCmass:Cyst
MCtumor:Adenoma
THEADRENALS
MCcancer:ChildrenWilmstumor
(nephroblastoma),AdultsRenalcell
carcinoma
THEADRENALS
MCmass:Cyst
MCtumor:Adenoma
THEBLADDER
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THEBLADDER
MCmass:DiverRculum
MCtumor:Leiomyoma
THEPROSTATE
MCcancer:TransiRonalcelladenocarcinoma
THEPROSTATE
MCtumor:BPH
THETESTICLES
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THETESTICLES
MCmass:
InnewbornsHydrocele(willtransilluminate)
Inchildren/adultsHematoma THESKIN
InolderadultsVaricocele(MCcomplicaRon
issterility)
MCtumor:Adenoma
MCcancer:1styroflife:Yolksaccancer
Inteens/adulthood:Seminoma
THESKIN
MCmass:Acrochordon(skintag),and
Hemangioma
MCtumor:Fibroma
MCcancer:Basalcellcarcinoma
MCmalignancy:Squamouscellcarcinoma
Mostmalignantskincancer:Malignant
melanoma
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THEBONES
THEBONEEpiphysis THEBONEMetaphysis
MadeofcarRlage MadeofOsteocytes
MCtumor:Chondroma MCtumor:Osteoma
MCcancer:Chondrosarcoma MCcancer:Metastasis
MCprimarycancer:Osteosarcoma
NOTE:thisareaismadeofcarRlage,sothisis
notabonecancer,thusitisnotthesiteof
boneMETS
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METAPHYSEALOSTEOSARCOMA
Seenmainlyinadults
Codmanstriangle:occurswhenthecancer
breakspastthemetaphysealcapsule
Starburstpaèrn:developsatthecortexin
responsetocancergrowingpastCodmans
triangle
NOTE:RegardlessofwhichismenRoned,itis
osteosarcoma
THEBONEDiaphysis EwingsSarcoma
MadeofOsteocytes Aprimarybonecancerinchildren
MCtumor:Osteoma Atthediaphysis
MCcancer:Metastasis OnionSkinningofthebone
MCprimarycancer: d/texpansionandscarring
InchildrenEwingssarcoma(11;22 overandover(equivalentto
translocaRon) hyalinizaRoninavessel)
InadultsPlasmocytomaorMulRple TranslocaRon11;22
Myeloma
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MulRpleMyeloma
Plasmacytoma:singlelesion
Mul7pleMyeloma:mulRpleosteolyRclesion
IgG:theMCheavychain(monoclonalspike THEBREAST
90%oftheanRbodiesareIgG)
Kappa:theMClightchain(90%ofAbshave
kappachaininthem)BenceJonesproteins
Leadstohypercalcemia
RouleauformaRon(stackedRBCsbecauseanIgG
cameandstuckthemalltogether)
THEBREAST THEBREASTOtherHYbreastcancers
MCmass:Cyst IntraductalPapilloma:bleedingofthenipple
MCtumor: (onlybenignbreasttumorpresw/bleeding)
If<25yrFibroadenoma(estrogenphases
withoutovulaRonsRmulatesductalgrowth) LobularAdenocarcinoma:unilateral,cells
If>25yrFibrocysRcdisease(estrogen/ linedupinsingleleonhistology
progesterone)
MCcancer:IntraductalAdenocarcinoma Comedocarcinoma:focalareasofnecrosis
(lookslikeareasofacnewithnecrosis)
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BREASTCANCERSCREENING
InammatoryAdenocarcinoma:lyphaRc Baselinebreastexam:atage35
inltraRon,Peaudorangeisthemost Ages4050:annualbreastexambyphysician,
malignantbreastcancer(rapidlyspreads)
monthlySBE
Ages5079:annualmammogram
CystosarcomaPhylloides:rapidlygrowing
massthatstopsgrowingabruptlyNOT Age79andup:noindicaRonforbreastexam
associatedwithmenstrualcycle
RequireslargeareaofresecRon(cystosarcoma
phylloides)
CYSTICvs.FIRMBREASTMASS,Mgmt. FINALBREASTMgmt.
Iflumpfoundtobebenign:nofurthertxnecessary
Iflumpfoundtobemalignant:modiedmastectomy
(takesbreastRssue,leavesnipple,leavespecmajor/
minor,leavesribs,insertimplantiftheywant)
Doanodaldissec7on
Checkforestrogen/progesteronereceptorposi7vity
(wemaybeabletouseSERMs)
Tx:
Tamoxifen/Raloxifeneforestrogen+cases
ChemotherapyforpremenopausalpaRents
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SERMs(Tamoxifen/Raloxifene) CANCERANTIGENS
MOA:Agonismandantagonismattheestrogen PSAProstate DESMINSkeletalmuscle
receptors CEAcolon,liver origin
Tamoxifen:Antagonistatbreast,agonistatboneand AFPyolksaccancers VIMENTINConnecRveRssue
uterus(watchuterinecancer)
S100melanoma Ca125Ovarian
Raloxifene:Antagonistatbreastanduterus,agonistat
bone(isideal) hCGchoriocarcinoma Ca19PancreaRc
RbreRnoblastoma/Ewings BCL2FollicularLymphoma&
**allSERMsdecreaseriskofestrogenreceptor+breast RETMEN2,MEN3 Burkirs(lessspecBurkirs)
cancermostSERMsimproveosteoporosis CMYCBurkirsLymphoma
LMYCSmallcelllungcancer
A/Es:everythingassociatedwithexcessestrogen
NMYCNeuroblastoma
CANCERMARKERS
T(9;22):Philchrom(CML) BRCA:BreastCA
T(8;14):Burkirslymphoma p53:Assdwith60%of
T(14;18):Follicular cancers
lymphoma
T(11;22):Ewings
osteosarcoma
T(15;17):AMLor
PromyeloblasRcleukemia
ERB:BreastCA
HER2NEU:BreastCA
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GRAMPOSITIVEBACTERIA
MICROBIOLOGY
GRAMPOSITIVEBACTERIA
TRANSPEPTIDATIONSTEP
PEPTIDOGLYCANWALL
Gram+vebacteriahaveathickpepRdoglycan ThisstepisthehookingtogetherofNAMand
wall(atleast40layersthick) NAGusingaDalaDala
3componentsrequiredtobuildthe Disruptedwithpenicillinsandcephalosporins
pepRdoglycanwall(NAcetylmuramicacid,N PCNandCephalosporinsmimicDalaDala
Acetylglucosamine,andDalaDala)
DalaDalawillhooktheNACandNAG
together(transpepRdaRonstep)
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GRAMPOSITIVETECHOICACID GRAMNEGATIVEBACTERIA
Providesrigidity
ArractsposiRvelychargedions
GramposiRvecelllysisreleasestechoicacid
whichcancausefeverandvasodilaRon
Rarelywilltechoicacidleadtosymptomsof
shock
GRAMNEGATIVEINFECTIONS ENDOTOXINS
Theendotoxin(Lipopolysaccharide)is Corean7genmostimmunogenicpartofthe
responsibleforcausingillness bacterium(dierentineverybacteria)
KillingagramnegaRvecellwillcausethe Oan7gensimilarineachbacteriafamily
contentstoleakoutofthecell Lipopolysaccharidearachedtoouter
membrane,responsibleforproblems
PaRentwillgetworseforashortperiodof
associatedwithgramnegaRveinfecRons
RmeaaeradministraRonofanRbioRcs
Tolllikereceptor4andCD14triggerthe
macrophagesandendotheliumtosecrete
inammatorycytokinesandnitricoxide
39
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NONMEMBRANEDAMAGING
EXOTOXINS
EXTRACELLULARLYACTINGTOXINS
Thesearesynthesizedbybacterialcellsand Hyaluronidase
thenreleasedtohelpthemthrive Coagulase
Extracellularlyac7ng(nonmembrane Fibrinolysin
damagingandmembranedamaging) Lipase
Intracellularlyac7ng
IgAprotease
Collagenase
MEMBRANEDAMAGING
INTRACELLULARACTINGEXOTOXINS
EXTRACELLULARLYACTINGTOXINS
Hemolysins ADPRibosylTransferases(diphtheria,
Leukocidins pseudomonas,cholera,E.Coli,bordetella
pertussi)
Phospholipase
MOA:inacRvaRonofboundproteins
lecithinase
NonRibosyla7ngToxins(Shiga,Anthrax,
Tetanus,Botulinum,Pyocyanin,Adenylate
cyclase,NADglycohydrolase)
MOA:dierspertoxin
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GRAMPOSITIVEEXOTOXINS GRAMNEGATIVEEXOTOXINS
StaphAureus E.Coli
StrepPyogenes BordetellaPertussis
BacillusAnthracis VibrioCholera
CornybacteriumDiphtheria
ClostridiumTetani
ClostridiumBotulinum
ClostridiumPerfringens
OSMOTICvs.SECRETORYDIARRHEA PHASESOFBACTERIALGROWTH
Osmo7cdiarrheasarecausedbyan
indigesRblesolutethatowsthroughthe
lumenoftheGIandosmoRcallydrawswater
Secretorydiarrheasaretoxinmediatedand
leadtotheacRvesecreRonofwaterintothe
GIlumen
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THEGRAMSTAIN STEPSTOGRAMSTAINING
HelpstodierenRatebetweengram+and Step1:AddiRonofcrystalviolent(tobind
grambacteria exposedpepRdoglycan)
Gram+vestainsblue/purple(isstainingofthe
pepRdoglycan) Step2:AddiRonofIodine
Gramvestainspink
Step3:Washtheslidewithalcohol
Step4:AddiRonofSarin
UNIQUECULTUREREQUIREMENTS
MacConkeysAgar:E.Coli,Enterobacter,
Klebsiella(alllactosefermenters)
ChocolateAgar:H.Inuenza
BloodAgar(Loers):CornybacteriaDiptheria NORMALFLORAANDHIGHYIELD
LowensteinJensenAgar:MycobacteriumTB NUGGETS
CharcoalYeast:LegionellaPnemophilia
SabouraudsAgar:FungalinfecRons
ThayerMarJn:Gonorrhea
BordetGengou(potato):BordetellaPertussis
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NORMALFLORA NORMALFLORA
ProtecRon SKINStaphEpidermidis
ChangeswithexposuretoabnormaliRes NOSEStaphAureus
Changeswithage VAGINALactobacilli,GroupBStrep
Immunosuppressionresultsinfungaltakeover OROPHARYNXStrepViridans
(Candida) GINGIVAAcRnomyces
COMMONLYENCOUNTEREDSKIN
VIRULENCEFACTORSOFBACTERIA
INFECTIONS
TechoicAcidGram+veBacteria CelluliRs:
EndotoxinsGramveBacteria MasRRs:
CapsulesactsasprotecRonforthebacteria,largest PeriorbitalCelluliRs
capsulebelongstoNeisseria OrbitalCelluliRs
An7phagocy7csurfacesMprotein(S.Pyogenes), BalanRRs:
ProteinA(S.Aureus) Carbuncle:
Sporesdormantbacteriathatreleasetoxinifexposed Furuncle:
toheat FolliculiRs:
NeurotoxinsClostridium BlephariRs:
CordFactorpreventsbacteriafrombeing FasciiRs:
phaocytosed(M.Tuberculosis) PanniculiRs
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UREASEPOSITIVEBUGS CURVEDRODS
Proteus Vibrio
Pseudomonas Campylobacter
Ureoplasma Listeria
Nocardia H.Pylori
Cryptococcus
H.Pylori
StaphSaprophyRcus
Brucellosis
AGRAMPOSITIVEFLOWCHART
GRAMPOSITIVEANDGRAM
NEGATIVEBACTERIA
44
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GRAM+COCCIINCLUSTERS
StaphAureus
StaphEpidermidis
STAPHYLOCOCCUS StaphSaprophyRcus
GRAM+COCCIINCLUSTERS STAPHAUREUS
StaphAureus Hasayellowpigment,iscoagulasePosiJve,FermentsMannitol, Containscertainenzymesthathelpitthrive
andcontainsaBetaLactamase
(catalase,betalactamase,coagulase,and
streptokinase)
Staph Hasawhitepigment,iscoagulasenegaRve,issensiRveto Isyellow/goldincolor
Epidermidis Novobiocin,andisseenininfecRontodevicessuchas:centrallines, ContainstoxinsthatproducesomedramaRc
prostheRcdevices,andshunts.
consequences(Scaldedskinsyndrome,toxic
shocksyndrome,enterotoxin)
Staph Hasnopigment,isNovobiocinresistant,andisassociatedwithUTIs
SaprophyJcus innewlysexuallyacRvefemales(usuallytheyareteenagers) Involvedinalargenumberofillnesses
PseudomonaspiggybacksonStaphAureus,so
alwaysassociatethemtogether
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ENZYMESUSEDBYSTAPHAUREUS
Catalase:usedtobreakdownperoxide
Betalactamase:helpsprotectthemfrom
anRbioRcswithbetalactamrings
Coagulase:eatsthroughclots
Staphylokinase:eatsthroughclots
STAPHAUREUSTOXINS
StaphScaldedSkinSyndrome
Redrashalloverthebody
Palmsandsolesareaected
CausesexfoliaRonoftheskin(Nikolskyssign)
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STAPHAUREUSTOXINS STAPHENTEROTOXIN
ToxicShockSyndrome Causesfoodpoisoning
SevereN/V/D
Highfever Severeabdominalcramping
Hypotension WorkswithinjustafewhoursofingesRon
Rashonpalmsandsoles
STAPHEPIDERMIDIS STAPHSAPROPHYTICUS
Catalase+,Coagulaseve Catalase+,Coagulaseve
Hasawhitepigmenttoit Nopigmenttothisbacteria
Normalskinora Residesinthebladderandurinarytract
InfecRonsareusuallyhospitalacquired Isthe2ndMCCofUTIaaerE.Coli
ItgrowsonplasRcdevicesplacedinthebody
(catheters,prostheRcs,lines,shunts,etc)
Removetheinfecteddevice,treatwith
Vancomycin
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STREPTOCOCCUS
Gram+cocciinchains
Dividedbygroupsanddegreesofhemolysis
STREPTOCOCCUS Alphahemolysis(green):StrepPneumonia,
Viridansgroup(GroupD)
Betahemolysis(clear):GroupAandGroupB
Gammahemolysis(red):Enterococcus
ALPHAHEMOLYSIS BETAHEMOLYSIS
Causedbyhydrogenperoxideproducedbythe Isacompletehemolysiscausedbystreptolysin
bacteria Hemolyzedareaappearslightyellowand
transparent
Createsdarkgreencolonies StreptolysinOis02sensiRveandsecretedby
Greenhemolysis(akaincompleteorparRal mostgroupAstrepstrains
hemolysis) StreptolysinSis02stableandisproducedby
mostGroupAstrepstrains
StrepPneumonia GroupAStrep(Pyogenes)isbetahemolyRc
StrepViridans(GroupDstrep) GroupBStrep(AgalacRae)isweaklybeta
hemolyRc.
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GAMMAHEMOLYSIS STREPPNEUMONIA
Gammehemolysismeansnohemolysis Isagram+diplocccus
IncludesEnterococcusspecies(E.Faecalis) Displaysalphahemolysis(green)
Therearearound90strainsofS.Pneumonia,
however23strainsareresponsibleformostof
thediseases
Vaccineshouldbegiventothose>65yr,
children<2yr,andthosewithsicklecell
disease
STREPPNEUMONIA UPPERvs.LOWERRESPIRATORYINFECTION
Isfoundintheupperrespiratorytract UpperrespiratoryinfecRonsgoalongwith
IstheMCCofmeningiRsinadultsandchildren nasaldischarge,earpain,sorethroat
Sinusi7s(acute) LowerrespiratoryinfecRonsshouldbe
O77smedia consideredwhencough,sputum,andsystemic
symptomsareseen
Osteomyeli7s
MustdoaCXRtodierenRatebetweena
Pneumonia(communityacquired,orwithin pneumoniaandothereRologies
rst72hrofhospitalizaRon)
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STREPVIRIDANS(GroupD) SUBACUTEBACTERIALENDOCARDITIS
AlphahemolyRc CausedbyS.Viridans
Candevelopaaerdentalsurgeryifnot
IncludesS.Viridans,S.Sanguinis,S.Salivarius) prophylaxedappropriately(Amoxicillin)
S.Viridansisthe#1causeofsubacute OslerNodes(painfulnodesinngers)
bacterialendocardi7s(previousdamagewill RothSpots(reRnalhemorrhages,palespotson
predispose) fundoscopy)
SplinterHemorrhages(embolitothenailbeds,is
StrepMutansisthecauseofdentalcaviRes nonspecic)
JanewayLesions(nontendernodulesonpalms
orsoles)
GROUPASTREP(Pyogenes) RHEUMATICFEVER
IsbetahemolyRc(producesaclearzoneonagar) Aninammatorydiseasethatdevelops23wk
IstheMCCofStrepThroat aaerastreppyogenesinfecRon
CancauselocalizedskininfecRonslikeImpeRgo, Mayinvolvetheheart,joints,brain,orskin
erysipelas,andcelluliRs
CanleadtonecroRzingfasciiRs
MajorJonescriteria(2fordiagnosis)
CanleadtoScarletFever MinorJonescriteria(2minor+1major)
Mayleadtoautoimmunemediated TreatwithanRinammatoryforthe
complicaRonssuchasRheumaRcFeverand/or symptomsaswellasanRbioRcstogetridof
AcutepostinfecRousglomerulonephriRs theStrepinfecRon
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GROUPBSTREP(AgalacRae) ENTEROCOCCUS
IsbetahemolyRc E.Faecalis(9095%),E.Faecium(510%)
ArefacultaRveanaerobes
IstheMCCofneonatalsepsis
ProducelacRcacid
WetestforGBSbeforegivingbirthwitha Aregram+cocciinpairs
vaginalandanalswab,prophylaxifnecessary FoundintheintesRnes
withIVpenicillin Causesnitritenega7veUTIs
InfecRonsseenMCinimmunocompromised
paRents
TreatmentisVancomycin(duetobeinghighly
resistanttoPCNandCephalosporins)
MENINGITIS
Inababy02monthsofage,GroupBStrepis
theMCC(2ndisE.Coli,3rdisListeria)
2months10yrtheMCCisS.Pneumonia(2nd
MCCisNeisseriaMeningiRs)
1021yrtheMCCisNeisseriaMeningiRs,the
2ndMCCisS.Pneumonia
>21yrofagetheMCCisS.Pneumonia
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CSFFINDINGSINMENINGITIS GRAMPOSITIVERODS
Listeria
Bacillus(sporeformer)
Cornybacterium
Clostridium(sporeformer)
LISTERIA BACILLUSCEREUS
Theonlygram+withanendotoxin Isasporeformingbacteria
IsacurvedrodthatdemonstratesatumblingmoRlity Foundinsoilandfood
Growthoccursintracellularly
2toxinsleadtoeithervomiRngordiarrhea
ListeriaMonocytogenescancausemonocytosis
(whatelsecausesmonocytosis??) Eme7cToxin:fromreheatedfriedrice,onsetis
CanhurttheplacentaandleadtoaborRon from30minutes6hrcausesvomiRngand
Thrivesinanironrichenvironmentthusisoaenseen someRmesdiarrhea
inpaRentswithhemochromatosis DiarrheaToxin:frommeatsandsauces,
Listeriameningi7sseeninpaRentswithcancerand increasescAMPandcausesawaterydiarrhea
inrenaltransplantpaRents within18hrs
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BACILLUSANTHRACIS CORNYBACTERIUM
Toxinwith3factors(lethal,edema,and CornybacteriumDiphtheria
protecRve) ContainsatoxinthatADPribosylatesEF2
Cutaneousanthraxleadstomalignant Bacterialookslikechineselerers
pustulesthatcauseskinnecrosis(notdeadly) Isanintracellularpathogen
PulmonaryanthraxcausesWoolSorters
Cancauseheartblock(whatelsecauses
Disease,leadingtomediasRnalhemorrhagic
heartblock??)
lymphadeniRs(isdeadly)
CancausetheformaRonofa
pseudomembrane
CLOSTRIDIUM CLOSTRIDIUMDIFFICILE
C.Dicile CausesagastroenteriRsassociatedwith
C.Perfringens anRbioRcuse(theydestroyE.Coli)
C.Tetani WhileassociatedwithClindamycin,itcan
C.Botulism occurasaresultofallbacteria
PseudomembranousColi7s:greymembrane
andyellowplaquesinthecolon
VancomycinisthemosteecRvedrug,
Metronidazoleistreatmentofchoice
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CLOSTRIDIUMPERFRINGENS CLOSTRIDIUMTETANI
Gasgangrene(MCindiabeRcs) Associatedwithdirtywounds
FoodpoisoningcausinggastroenteriRs Thetoxininhibitsthereleaseofglycineinthe
(enterotoxin) spinalcord,leadstointensecontracRonsof
thewholebody
Tetanustoxoidvaccineshouldbegiveninfully
vaccinatedpeoplewithaseverelydirtywound
ifitsbeen>5yrsincelastbooster
TETANUSVACCINATIONS CLOSTRIDIUMBOTULISM
ToxininhibitsthepresynapRcreleaseof
acetylcholine
Leadstoaccidparalysis
Respiratoryfailurecausedbyfailureofthe
diaphragm(musclefailure)
Childrencommonlyaectedbyhoneyand
molasses(avoidhoneyin1styearoflife)
Adultsgetitfromacannedfooditem
containingspores
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ACNE ACNE
Causedbythegram+,anaerobicbacteria Treatmentinvolves:
PropionobacteriumAcne Benzoylperoxide(exposesto02)
Whiteheads:akaWhiteComedomes,areclear AnRbioRcs(killsbacteria)
vesicles ReRnoicacid(speedsupskincellproliferaRon)
Blackheads:akaBlackComedomes,sebum
oxidizesandturnsblack
NEISSERIA
Gramvediplocci
DierenRatebetweenMeningiRdisand
Gonorrheabyaddingmaltose
HasanIgAprotease
Isencapsulatedwiththelargestcapsule
Releasesanendotoxinduringthelogphase
(onlyonethatdoesthis)
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NEISSERIAMENINGITIDIS WATERHOUSEFRIDERICHSENSYNDROME
Fermentsmaltoseandglucose Widespreadmeningococcemialeadsto
IstheMCCofmeningiRsinpaRentswhoare hemorrhageintooneorbothadrenals.
1021yrofage
Hypotension
Isamajorcauseofmorbidityandmortality
duringchildhood Shock
SpreadviarespiratorysecreRonsandsaliva DIC(lookforDdimerandbrinsplitproducts)
Endotoxinislipooligosaccharide Widespreadpurpura
CancauseWaterhouseFriderichsenSyndrome DevelopmentofadrenocorRcalinsuciency
(hemorrhagicadrenaliRs)
NEISSERIAGONORRHEA
Fermentsglucose,wontfermentmaltose
Itspiliallowittoadherewelltotheurinary
tract
Isthe#1causeofpurulentSTDs
Isthe#2causeofSTDs(chlamydiais#1)
CancauseFitzHughCurRssyndrome
CancausegonococcalarthriRs
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BORDETELLAPERTUSSIS PASTEURELLAMULTOCIDA
CausesWhoopingCough(3stages) CelluliRsassociatedwithdogorcatbite
VaccinaRonisimportant TreatwithAmoxicillin
ExotoxinADPribosylatestheGisubunitofthe
Gprotein
HighcAMPlevelsincreasemucusinthelungs
Cancauseextremelymphocytosis
MCCofdeathisduetosuoca7on
Treatwitherythromycin
BRUCELLA BARTONELLAHENSELAE
Brucellosis Isresponsibleforcatscratchdisease
Causesafeverthatuctuates57Rmesper Carriedbyfelines
day(undulaRng) Isoneof3bugsthatstainswithsilverstain
SeenMCinthosewhohandleanddeliver Treatmentonlyrequiredinseverecases(LN
animalsasitisfoundintheanimalplacenta enlargement,tenderLNs,etc)Azithromycin
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FRANCISELLATULARENSIS HAEMOPHILUS
TransmiredbyrabbitsmostoftheRme Gramve,pleomorphicrods
Mayalsobetransmiredbydeerandother Partofnormaloraofposteriorpharynx
rodents 80%ofhaemophilusarenotencapsulated
LeadstoTularemia (noninvasiverespiratorydiseases)
TreatwithStreptomycinorTetracycline 20%areencapsulated(cancausesystemic
illnesses)
SystemicformisH.InuenzatypeB
H.INFLUENZA H.INFLUENZATYPEB
Isthe2ndMCCofthefollowingproblems. IstheMCCofepiglom7s
SinusiRs EpigloRsisamedicalemergency
ORRsmedia PaRentisdrooling,in3pointposiRon(leaning
BronchiRs forward),fever,stridor
Pneumonia Immediateintuba7onisnecessary
PreventablewithHiBvaccine
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H.AEGYPTIUS H.DUCREYI
IsacommoncauseofmildconjuncRviRs IstheMCCofchancroid
Iscommonlyconfusedwithpinkeye IsseenalongwithunilateralpaininLNs
TreatwithCeariaxone
Sincewerediscussingpainful
genitallesions
Letstakealookattherestof
them!
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PAINFULGENITALLESIONS
Chancroid(H.Ducreyi)
Herpes(HSV1and2)
LymphogranulomaVenereum(Chlamydia
TrachomaRs)
GranulomaInguinale(Calymmatobacterium
Donovini)
NONPAINFULGENITALLESIONS SYPHILIS
Syphilis(TreponemaPallidum) PrimarySyphilis:chancreappearsatsiteof
GenitalWarts(HPV) contactwithinapproximately21days
MolluscumContagiosum(Molluscum Isasingle,rm,painlessnodule
ContagiosumVirus) Willpersistfor36weeksifnotreatment
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SYPHILIS SYPHILIS
SecondarySyphilis:at410weeksaaer LatentSyphilis:serologicproofwithoutsigns
primaryinfecRon orsymptomsofinfecRon
ManydierentformsofmanifestaRon
Candeveloprash(pustularormaculopapular),
ontrunk(aswellasonpalmsandsoles)
Developmentofcondylomalatummayoccur
Systemicsymptomsarecommon(fever,
malaise,etc)
SYPHILIS SYPHILIS
Ter7arySyphilis:315yearsaaeriniRal DiagnosiswithVDRLorRPR
infecRon BestdiagnosRcstepisFTAAbs
Lateneurosyphilis(5%)
Cardiovascularsyphilis(10%) TreatmentforearlyinfecRonissingledoseIM
Gummatoussyphilis(15%) PenicillinG
TreatmentforlateinfecRonisIVPenicillinG
for10days
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GRAMNEGATIVELACTOSEFERMENTERS
Klebsiella(Fastfermenter)
E.Coli(Fastfermenter)
Enterobacter(Fastfermenter)
Citrobacter(Slowfermenter)
Serra7a(Slowfermenter)
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KLEBSIELLA
Klebsiellaisthe3rdMCCofUTIs
GRAMNEGATIVERODSTHATARE KlebsiellapneumoniaisseenMCinthe
homelessandalcoholics
FASTLACTOSEFERMENTERS
Isanencapulatedbacterium
Currantjellysputum
E.COLI E.COLI
Responsibleformakingup95%ofthenormal TestforsteatorrheawithSudanBlackstain
oraoftheintesRnes Calciumoxalatestonesisaresultoflossof
EnterotoxigenicE.Coli(ETEC) calciumbindingproteins
EnteropathogenicE.Coli(EPEC)
EnteroinvasiveE.Coli(EIEC)
EnterohemorrhagicE.Coli(EHEC)
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E.COLI ENTEROBACTER
Responsibleforproducingmostofthebodys 2mainenterobacterspeciesweneedtoknoware
CloacaeandAerogenes
vitaminK(clongfactors2,7,9,10)
E.Cloacae:isagramnegaRve,rodshaped
AlsoinvolvedinbioRn,folicacid,and bacteriumthatcancauseUTIsandrespiratory
pantothenicacidproducRon tractinfecRons
TreatwithGentamycin
HelpsinabsorbingvitaminB12
E.Aerogenes:causesnosocomialinfecRonsin
thosewhoareimmunocompromised
Mayoccurduetovenouscathetersandaaer
surgicalprocedures
SERRATIAMARSCESENS
MCassociatedwithnosocomialinfecRons
suchasUTIs,pneumonia,andwound
GRAMNEGATIVERODSTHATARE
infecRons
SLOWLACTOSEFERMENTERS SerraRagrowsbestinmoistenvironments(the
bathroomespecially)
ContainsRfactorsthatgiveitintrinsic
resistancetomanyanRbioRcs
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GRAMNEGATIVENONFERMENTERSOF
CITROBACTER LACTOSE
Anencapsulatedorganism Pseudomonas(Oxidase+)
SeenMCinrst2monthsoflife,presenRngas Shigella(Oxidase)
mulRplecerebralabscesses Salmonella(Oxidase)
Hasabilitytoproducecitricacid Proteus(Oxidase)
PSEUDOMONAS PSEUDOMONASCOMMONQUESTIONS
CloselyrelatedtoStaph.Aureus(theyusethesame IstheMCCofdeathinburnpaRentin2ndweek
enzymes) WhirlpoolFolliculi7s:duetoanimproperlychlorinated
Veryprevalentinthehospital(commoncauseof whirlpool(causesoozingfromhairfollicles)
nosocomialinfecRons)2ndMCCofdeathinhospitals
LikesdiabeRcs,neutropenics,cysRcbrosis,andburn TennisShoeFolliculi7s:fromrubberonsolesofshoes
paRents Malignanto77sexterna:fromthemastoidprocess
Hasayellowpigmentandagreenpigment Recurrentpulmonaryinfec7onsinCFpaRents
Hasaclassicfruitysmelltoit EcthymaGangrenosum:cutaneousinfecRonin
LovesplasRc(catheters,endotrachealtubes),as immunocompromised/criRcallyillpaRents
opposedtoS.EpidermiswhichlikesplasRcdevices
deepertothesin
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EcthymaGangrenosum SHIGELLA
Veryvirulentbacteriaresponsiblefor
gastroenteriRs
Outbreakscommontodaycarecenters
Shigatoxin(exotoxin)cancauseseizures
IntheUS:ShigellaSonneiicauses
gastroenteriRs
OutsidetheUS:ShigellaDysentery
SALMONELLA SALMONELLATYPHI
Anencapsulatedbacterium Causestyphoidfever
MCCofosteomyeliRsinsicklecellpaRents Foundincontaminatedwater
EaRngrawchickenorraweggscancause
gastroenteriRs(requiresingesRonoflarge
CancauseaclassictriadofIntes7nalburning,
amountofbacteria) Fever,rosespots
Causesaselflimiteddiarrheathatispurulentand Cancauseheartblock
bloody
S.Enteri7disistheMCstrainfoundinUS
S.DysenteryistheMCstrainfoundoutsideofUS
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BIOTINDEFICIENCY PROTEUS
Eggwhitesyndrome ProteusspeciesarenormalintesRnalora
AvidinbindstobioRnirriversibly P.MirabiliscausesmostproteusinfecRons
Cookingeggsdegradesavidin Isoneoftheureaseposi7vebugs
IncreasedurinepHischaracterisRcnding
Ureasehydrolyzesureatoammonia
PROTEUS STRUVITECALCULI
FormaRonofstruvitestonesleadtostaghorn
calculi
UseMacConkeysagartodiagnose(cant
fermentlactose)
TreatwithQuinolones
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Vibrio
GRAMNEGATIVESTHATDONTMEET CampylobacterJejuni
THEPREVIOUSCRITERIA Yersinia
VIBRIO CAMPYLOBACTERJEJUNI
VibrioCholera Isacurvedrod
Isfoundinpoultry(undercookedorill
VibrioParahemoly7cus preparedmeatsareacommonculprit)
IstheMCCofgastroenteri7scausedbyfood
VibrioVulnicus poisoning
Usuallyselflimited,ifdiarrheaisbloodyor
theresahighfever,giveErythromycin
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YERSINIA
YersiniaPes7s:foundindirtinthe
SouthwesternporRonoftheUS,carriedby
prairiedogs
ATYPICALBACTERIA
IsresponsibleforthePneumonicPlague,the
BubonicPlague,andtheSepRcemicPlague Chlamydia
SRlloccurstoday Mycoplasma
IsgramnegaRverodwithbipolarstaining Legionella
(lookslikeasafetypin) Ureaplasma
CHLAMYDIA CHLAMYDIA
ChlamydiaTrachoma7s: ChlamydiaPneumonia:
MCCofneonatalblindness(trachoma) TheMCCofatypicalpneumoniainnewborns
MCCofectopicpregnancy(scarsfallopian (upto2months)
tubes,leadstoinferRlity) AectstheintersRRum(intersRRal
MCCofasymptomaRcSTD pneumonia)
MCCofLymphogranulomaVenereum Staccatocough
SymptomsoutofproporRontondings
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MYCOPLASMA LEGIONELLA
Hasnocellwall LegionellaPneumonia:
Hasnoepitheliallining IstheMCCofatypicalpneumoniainpeople>
40yr
MycoplasmaPneumonia:theMCCofatypical SilverstainposiRve
pneumoniain1030yrolds(walking Foundinstandingwater,inheaters,andinair
pneumonia) condiRoningsystems
IntersRRalpneumoniawithsymptomsoutof Oaenfoundinhotelsandmotels
proporRontophysicalndings
LEGIONELLAPNEUMOPHILIA UREAPLASMAUROLYTICUM
GranulomatousinammaRon Nocellwallandnoepitheliallining(similarto
Cancauseheartblock Mycoplasma)
IsaureaseposiRvebug
Pon7acFever:causesfeverandnonspecic CancausevaginiRsonoccasion(sexualabuse)
symptoms
Legionnairesdiseases:causesfullblown
pneumonia
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FUNGI&PARASITES
ANTIFUNGALMOAs ANTIFUNGALMEDICATIONS
POLYENES:bindsergosterol,formstransmembrane
channel,ionsleakoutAmphoBandNystaRn
AZOLES:inhibitenzymeLanosterol14alphaDemethylase,
blockingconversionoflanosterolintoergosterol
ALLYLAMINES:inhibitSqualeneEpoxidase,thusinhibiRng
synthesisofergosterolthisisTerbinane
FLUCYTOSINE:inhibitsDNAreplicaRonofthefungus,
preventsproteinsynthesisoffungus(isapyrimidine
analogue)
GRISEOFULVIN:interfereswithmicrotubulesfuncRon
(inhibitsmitosis)
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COMMONLYUSDANTIFUNGAL
POLYENES
MEDICATIONS
Nysta7n:fororalcandida(thrush),usedasa AmphotericinB:givenIVforsystemicfungal
swishandswallowtreatment
infecRons
Miconazole:usedtopicallyforringworm,jock
itch,oralthrush Willcausehyperkalemiabecauseitdrillsholes
Tolnaoate:thisisTinacRn,forathletesfoot incellsaswell
Terbinane:usedfornailbedfungalinfecRons Nysta7n:oralswishandswallowforthrush
Flucytosine:inhibitsmitosis(pyrimadine
analogue)
AmphotericinB:drillsholesincellmembrane,
usedIVforsystemicinfecRons
Thrush ERGOSTEROLSYNTHESISINHIBITORS
Ketoconazole:inhibitsP450,blocks5alpha
reductase(ismosteecRveanRfungal)
Fluconazole:hasstrongCNSpenetraRon(best
ofthemall)
Itraconazole
Miconazole:forringworm,jockitch
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MICROTUBULEINHIBITOR PURINEINHIBITOR
Griseofulvin Flucytosine:worksinthefollowingtwo
EecRveagainstallRneainfecRons ways.
InducesP450(decreaseseecRvenessof 1stInterfereswithRNAbiosynthesis
medicaRonsusingthissystem) 2ndInhibitsfungalDNAsynthesis
PIEDRA
AninfecRonofthehairshaa
BlackandWhite
SUPERFICIALFUNGALINFECTIONS BlackPiedraiscausedbyPiedraiaHortae
(looksblackonthehair)
WhitePiedraiscausedbyseveralspeciesof
trichospora(lookswhiteonthehair)
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4MAINCLASSESOFCUTANEOUS
FUNGALINFECTIONS
Trichophyton:causeofathletesfoot,
ringworm,jockitch,aswellasskin/scalp,
beard,andnailinfecRons
Microsporum:causesRneacapiRs,Rnea
corporus,ringworm,andmanyother
dermatophytoses
Epidermophyton:supercialandcutaneous
fungalinfecRons
Dermatophyton:supercialfungalinfecRons
TINEA
T.Capi7s(scalp)
T.Corporis(body)
T.Versicolor(backd/tM.Furfur)
T.Manis(betweenthengers)
T.Cruris(jockitch)
T.Pedis(betweenthetoesathletesfoot)
T.Unguium(undernailbeds)
T.Nigra(brownspotsonkeraRnizedlayerofskin
d/tCladosporiumWerneckii)
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DEEPFUNGALINFECTIONS
Onychomycosis:fungalinfecRonofmulRple
nailbeds
IstheMCnailproblem
Occursmoreoaeninthetoenails,butoccurs
inboth
MCCisthedermatophyteTrichophyton
Rubrum
CANDIDAALBICANS SYSTEMICMYCOSES
Canbebothsystemicorsupercial Coccidioidomycosis
Isabuddingyeastwithpseudohyphae Histoplasmosis
Causesthrushinimmunocompromised Blastomycosis
paRents Paracoccidioidomycosis
CausesvaginiRs
TreatasupercialcandidalinfecRonwith
nystaRn,andasystemicwithAmphoB(both
arePolyenes)
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COCCIDIOIDOMYCOSIS HISTOPLASMOSIS
AkaValleyFever RespiratorydiseasefoundinMississippiandOhio
IsendemictoSouthwesternUSandNorthwest RiverValley(Midwest)
Mexico CausedbyHistoplasmaCapsulatum(foundin
Isasphericalyeast birdandbatdroppings,aswellaspoultryhouses
Presentseitherasamilddiseasewithulike andcaves)
symptoms,orasseverediseasepresentswith Primarilyaectslungsbutcanspreadelsewhere
pneumonia,lungnodules,anddisseminaRon
Milddiseaserequiresnotreatment SeencommonlyinAIDSpaRents
SeverediseaserequiresAmphoBand Fatalifleauntreated
Fluconazole Treatment:AmphoBfollowedbyItraconazole
BLASTOMYCOSIS PARACOCCIDIOIDOMYCOSIS
FoundintheNortheastUSA IsseeninRuralLaRnAmerica
Foundinpigeonsandisassociatedwithroren Hasashipwheelappearance
wood Aectsthemucusmembranesofthemouth
Isabroadbuddingyeast (lips,buccalmucosa)
CancausepulmonaryinfecRonssuchaslobar
Ifonlyinthelungsthereoaenisntany
pneumonia
symptoms.Butifitspreadsthenmany
Treatment:mosteecRveisAmphoB+
possibleproblems
ucytosine(althoughSulfadrugsareeecRve
andcheaper)
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OPPORTUNISTICFUNGALINFECTIONS CANDIDAALBICANS
CandidaAlbicans Isadiploidfungus
AspergillusFumigatus CausesopportunisRcinfecRonsin
CryptococcusNeoformans immunocompromised
MucorandRhozopusspecies Thrush
Vaginalcandidiasis(vulvovaginiRs)
Disseminatedcandidiasis
Chronicmucocutaneouscandidiasis
3CAUSESOFVAGINITIS
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ASPERGILLUS
Septatehyphaethatbranchat45,hasrare
fruiRngbodies
A.Flavus:producesAatoxinfoundinnuts
A.Fumigatus:causesproblemsbelow
Causesallergicbronchopulmonaryaspergillosis
Causesalungcavityaspergilloma[fungusball]
Cancauseinvasiveaspergillomain
immunocompromisedindividuals
CRYPTOCOCCUSNEOFORMANS
Anencapsulatedyeast(stainwithIndiaInk)
Rarelycausesproblemsinhealthypeople
LeadstoCryptococcalMeningiRsinAIDS
paRents
Treat:2wkIVAmphoB+Fluconazole,
followedby10wkFluconazoleunRlCD4count
>100
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MUCORANDRHIZOPUS PNEUMOCYSTISCARINII
MucormycosisisatermtodescribeinfecRon IsayeastthatcausesPCPpneumoniainAIDS
withMucorandRhizopus paRents
SeenindiabeRcs SeenonceCD4countdrop<200
Aectsthemucusmembranesinthenose ProphylaxonceCD4hits200withTMPSMX
mostcommonly(canaectanything) (Bactrim)
PrompttreatmentwithAmphoBfor46wks
SPOROTHRIXSCHENCKII
Isadimorphicfungus
MCseeninpeoplewithRosegardens,asthe
funguslivesonthethornsandgetsintroduced
whentheygetpricked
CauseslesionsthatfollowtheLNdrainage
pathwayknownasascendinglymphangiRs
TreatwithItraconazole
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TREMATODES(LiverFlukes)
Includes:
Schistosomiasis
PARASITES
Cutaneouslarvemigrans
ClonorchisSinensis
ParagonimusWestermani
SCHISTOSOMIASIS CUTANEALARVAMIGRANS
Snailsarethehost IstheMCacquireddermatosisfromtropical
Caughtbywalkingbarefootthroughaswamp andsubtropicalregions(especiallySouthern
LivercancercausedbyS.Mansoni UnitedStates)
Lookslikeastringundertheskin,isextremely
SCCofthebladdercausebyS.Hematobium
itchy
Cancausebrosis,granulomaformaRon,and
inammaRonofthespleenandliver Treatment:Thiabendazole
Treatment:Praziquantel
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CUTANEALARVAMIGRANS CHLONORCHISSINENSIS
AcquiredbyeaRngundercookedsh
SeenMCinasianpopulaRonsduetocultural
reasons
CausesinammaRonofthebiliarytract(will
seeincreasedalkalinephosphatase)
Treatment:Praziquantel
PARAGONIMUSWESTERMANI TAPEWORMS
AcquiredbyeaRngundercookedcrabmeat
LeadstoinammaRonandbacterialinfecRon Includes:
ofthelungs TaeniaSolium
Treatment:Praziquantel EchinococcusGranulosus
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TAENIASOLIUM T.SOLIUM,NEUROCYSTICERCOSIS
AcquiredbyeaRngundercookedpork
Cangrowupto50mormoreinlength
DisseminaRonleadstocysRcercosis,whichcanhavea
widerangeofeects
NeurocysRcercosisoccurswhenitreachesthebrain
(Seizure,brainlesions,blindness,tumorlikegrowths)
Treatment:DOCforuncomplicatedcaseis
Praziquantel,forcysRcercosis/neurocysRcercosisuse
Albendazole+Steroids(decreasesinammaRon)
ECHINOCOCCUS HOOKWORMS
Isfoundindogfeces
Causesasolitarycysttoformintheliver Includes:
(hydaRdcyst) AncylostomaDuodenale
ReleaseofanRgensfromthiscystcanleadto NecatarAmercanus
anaphylaxis
Treatment:Albendazole
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ANCYLOSTOMADUODENALE AncylostomaDuodenale
Isahookwormthathooksintothesmall
intesRne
GetsinbypenetraRngtheskinofthefeet
Mildsymptomsmayincludeirondeciency
anemiaandabdominalpains
Severesymptomscanbeproteindeciency
andheartfailure(rare)
Treatment:AlbendazoleorMebendazole
(alternaRvetxisPyrantelPamoate)
NECATARAMERICANUS PINWORMS
CloselyrelatedtoAncylostomaDuodenale EnterobiusVermicularisistheonlypinworm
Samesymptomsandsametreatment CausessevereperinanalpruriRs(dueto
deposiRonofeggsaroundtheanus)
scotchtapetestisclassicclueforthis
infecRon
Treatment:MebendazoleorPyrantel
Pamoate
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ROUNDWORMS ASCARISLUMBRICOIDES
Isagiantroundworm,eggsareevenvisiblein
Includes: feces
AscarisLumbricoides(Giant) IsthelargestandMCwormthatinfectshumans
StrongyloidesStercoralis
TrichinellaSpiralis Canreachupto35cminlength
LoaLoa Transmiredfecalorally(poorsanitaRonincreases
DracunculusMedinensis riskofinfecRon)
ToxocaraCanis Diagnosis:eggsarevisualizedinfeces(theyare
OnchocercaVolvulus large)
WuchereriaBancroai Treatment:Mebendazole
STRONGYLOIDESSTERCORALIS TRICHINELLASPIRALIS
Areconsideredtobeathreadworm MCcomesfromundercookedpork
Theyarefoundinsoilandenterthroughtheskinofthe Thereare2phasestohowitworks
feet Phase1(Enteral)aectstheintesRnaltract
TheyliveinthemucosaltunnelsofthesmallintesRne (diarrhea,nausea,dyspepsia)
andinfecRonisusuallyasymptomaRc Phase2(Parenteral)aectseverythingelse
GIsymptomsincludeabdominalpain+diarrhea (travelsthroughvasculatureandRssues),leadsto
PulmonarysymptomsincludeLoerssyndrome inammaRon,pain,weakness.
DermatologicalsymptomsincludeurRcarialrashon Telltalesignisperiorbitaledema(d/tvasculiRs)
hips/waist/burocks CNStrichinosiscanbefatal
Treatment:IvermecRnorAlbendazole/Thiabendazole Treatment:Thiabendazole
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LOALOA LoaLoaTheAfricanEyeWorm
Istransmiredbydeery(inUSA)
IsendemictoWesternAfrican(Esp.Congoand
Sudanrainforests)
CausesinammaRonoftheskin
CanseeitcrawlingacrosstheconjuncRva
Treatment:Diethylcarbamazine
DRACUNCULUSMEDINENSIS RemovalofDracunculusMedinensis
IsknownastheGuineaWorm
Causedbydrinkingwaterthatisinfestedwith
crustaceanswhoareinfected
Femalewormmigrates(usuallytofeet)and
burrowsundertheskin,causingpainand
severeburningsensaRon
Treatment:Niridazole(hasstrongCNSside
eectstohumans)oritisslowlypulledout
withasRck.
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TOXOCARA ONCHOCERCAVOLVULUS
T.Canis:fromdoglarva Transmiredbythefemaleblacky
T.CaJ:fromcatlarva Isthe2ndMCCofinfecRousblindnessinthe
TheseareusuallyasymptomaRcinadults,but world(RiverBlindness)
mayleadtogranulomasinthereRnaandin BlindnessiscausedbyitssymbioRc
theviscera relaRonshipwithWolbachiaPiperRs,which
Treatment:Diethylcarbamazine causessevereinammaRonandthus
blindness
Treatment:IvermecRn
ElephanRasiscausedbyWuchereria
WUCHERERIABANCROFTI
Bancroai
Spreadviathefemalemosquito
LeadstoblockageofthelymphaRcsandthus
elephanRasis
Treatment:Bestsingledrugis
Diethylcarbamazine,butmulRdrugtherapyof
IvermecRn+Deithylcarbamazineor
AlbendazoleismoreeecRveoverall
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ProtozoaintheBRAIN
TOXOPLASMOSIS
PROTOZOA
Fromcatfeces(caughtbyhandlinglirer)
Mustavoidwhenpregnant
Leadstoaringenhancedlesionoftheparietal
lobe
Treatment:Pyrimethamine+Sulfadiazine
ProtozoaintheBRAIN ProtozoaintheBRAIN
NAEGLERIAFOWLERI TRYPANOSOMA
T.GambienseorT.Rhodesience(MCC)
Caughtbyswimminginfreshwaterlakes
TransmiredbytheTseTsey
throughthecribriformplate(musthave
2stages:1stHemolyRcphase(HA,fever,joint
trauma)
pain,pruriRs),2ndNeurologicalphase
Causesarapidlyfatalfulminant (confusion,ataxia,sleepcycledisturbances)
meningoencephaliRs(deadwithin23days) Treatment:1ststage:IVEornithine,2ndstage:IV
Melarsoprol
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ProtozoaintheCORNEA ProtozoaintheHEART
Acanthamoeba:eatsthroughthecornea TrypanosomaCruzii:akaChagasDisease
whenleavingcontactsinfortoolongcan CaughtfromtheReduuvidbugfoundinSouth
causebothkeraRRsandencephaliRs. America
Aectsthegangliaandcausesachalasia
Erlichiosis:passedfromthesalivaofadog
throughthesideoftheeyecausingHA,
muscleaches,faRgue.
Treatment:Doxycycline
ProtozoaintheLUNGS ProtozoaintheGI
Pneumocys7sCarinii(PCP): GiardiaLamblia:causesGiardiasis(bloaRng
AectsAIDSpaRentwhenCD4countdrops andfoulsmellingdiarrhea
below200 Transmiredthroughcystsinthewater(classic
CanvisualizewithSilverStain drinkingfromastreaminfecRon)
AectsType1pneumocytes LeadstoinammaRonandatrophyofthevilli
Treat/prophylaxwithTMPSMX whichleadstodecreasedabsorpRonand
diarrhea
Treatment:Metronidazole
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ProtozoaintheGI ProtozoaintheGU
EntamoebaHistoly7ca: TrichomonasVaginalis:
CausesmulRpleliverabscesses
IsoneoftheMCCofvaginiRs(aaercandida
Treatment:Metronidazole
andGardnerella)
Cryptosporidium: Treatment:Metronidazole
IstheMCCoflifethreateningdiarrheainAIDS
paRents
IsacommoncauseofselflimiRngdiarrheain
healthyindividuals
Treatment:SymptomaRcmanagementonly
ProtozoaintheSKIN
LeischmaniasisLeischmaniaDonovani LeischmaniaDonovani:
LeischmaniaRhodiensis Aectstheskinoftheface/nostrils
Eatsawayattheface
Leischmaniasis:
CausedbytheSandy LeischmaniaRhodiensis:
Causesarash/sorethateventuallyerupts Progressiontotheorgans
Whenorgansareinvolved,wecallitKalaAzar
Treatmentforall:SRbogluconate
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ProtozoaintheLYMPHATICS ProtozoaintheBLOOD
Babesiosis:
WucheriaBancrooi: TransmiredfromtheIxodesRck(sameonecausingLymedisease)
CauseslymphaRcobstrucRon Isseenontheeastcoast(LongIsland,ocoastofMassachusers)
ItreproducesinsideRBCs,buddingin4direcRons(createsthelook
LeadstoelephanRRs ofamaltesecrossintheRBC)
CasesareusuallyeitherAsxorpresentwithmildfever,anemia,and
Treatment:Bestsingledrugis suddendeath
Severecasesaresimilartomalaria(highfever,shakingchills,
Diethylcarbamazine,butmulRdrugtherapyof hemolyRcanemia)
IvermecRn+Deithylcarbamazineor Treatment:Mildcasesareselflimited,severecasesuse2drug
regimenofAzithromycin+Atovaquone
AlbendazoleismoreeecRveoverall Lifethreateningcaseswarrantexchangetransfusion
ProtozoaintheBLOOD PLASMODIUMMALARIA
Plasmodium: TheMCstrainofplasmodiumaroundthe
Dierentspeciesofplasmodiumareresponsible world
formalaria AlsoknownasQuartanMalaria
Transmiredbythefemaleanophelesmosquito Causesafeverat3dayintervals
P.Malaria MildestformofPlasmodiuminfecRon,which
P.Falciparum canlastalifeRmeifleauntreated
P.Vivax Treatment:Chloroquine
P.Ovale
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PLASMODIUMVIVAX&OVALE PLASMODIUMFALCIPARUM
P.OvalegoestomatureRBCs IsthedeadliestformofPlasmodium
Isresponsibleforalmostallcasesofmalaria
P.VivaxgoestoimmatureRBCs
CauseshemolysisofRBCs(Hbincreases,
(reRculocytes) Haptoglobindecreases)
Theybothaecttheliver Causesadarkeningoftheurinecalledblack
waterfever
P.Vivaxisachronicformofmalaria
Seizures,confusion,kidneyfailure,and
Feverspikesevery2daysinboth respiratoryfailurearepossible
Treatment:treatbothwithChloroquine Feverspikesevery2days
Treatment:Quinine
TIPSFORPREVENTINGMALARIA PROPHYLACTICREGIMENS
ABCDsofmalariaprevenRonareimportant
andcansignicantlylowerrisk.
AAwareness
BBiteprevenRon
CChemoprophylaxis
DDiagnosisandtreatment
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MALARIATREATMENTS
TreatmentforP.Falciparum:Quinine
TreatmentforP.Malaria,Ovale,andVivax:
Chloroquine
Forchloroquineresistantstrainsof
PlasmodiumuseeitherMeoquineor
Primaquine
RICKETTSIASPECIES
THEREMAININGTOPICS. Ricke`siaricke`sia:causesRMSF(rash
starRngonhands,wrist,forearms,ankles,
Rickersia feetandmovingcentrally)
IsaRckbornedisease
Spirochetes
SeenMCinmid/southAtlanRcstates
Mycobacterium
TreatwithDoxycyclineorChlormaphenicol
(forallrickersialinfecRons)
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RICKETTSIASPECIES SPIROCHETES
Ricke`siaTyphi:aeabornediseasethat Leptospira(Leptospirosis)
causesendemictyphus BorreliaBurgdorferi(LymeDisease)
Ricke`siaProwazekii:alouseborndisease BorreliaRecurren7s(RelapsingFever)
thatcausesendemictyphus TreponemaPallidum(Syphilis)
Ricke`siaTsutsugamushi:achiggerborne
TreponemaPertenua(Yaws)
diseasethatcausesscrubtyphus
SepulinaPilosicoli(IntesRnalSpirochetosis)
Ricke`siaAkari:amiteborndiseasethat
causesrickersialpox
SPIROCHETES SPIROCHETES
Leptospira:causesLeptospirosis BorreliaBurgdorferi:causesLymeDisease
Transmiredthroughraturine TransmiredbyIxodesRck
Seenmainlyinsewageworkers Threestagestotheprogressionofthedisease
Seeninproductsthatsitinwarehousesasrats 1ststage:Bullseyerash(pathognomonic),
urinateonthem(popularquesRonissoda usuallyresolveswithin1month
cans) 2ndstage:Flulikesymptoms
Isabiphasicdisease(beginswithulike 3rdstage:ArthriRs
symptoms,Asxperiod,thenmeningiRs,liver Treatment:Doxycycline(pregnantptrequires
failure,andrenalfailure) ceariaxone)
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SPIROCHETES SPIROCHETES
BorreliaRecurren7s:causesRelapsingFever TreponemaPallidum:causessyphilis
Transmiredviathehumanbodylouse
Hastheabilitytoaltersurfaceproteins,which
isresponsibleforcausingrecurringfever
Treatment:Doxycycline
SPIROCHETES MYCOBACTERIUM
TreponemaPertenue:causesacondiRon Notatruebacterium
knownasYaws(seenonlyintropics) CellwallcontainspepRdoglycans,membrane
Causedbyskintoskincontact containsMycolicAcid(itsuniquefeature)
Has3phasessimilartosyphilis,butlesionsare Clinicaltreatmentisbasedondestroyingthe
notgenital mycolicacid(achievedwithIsoniazid)
TerRarystageismarkedbyseverebone,joint, M.Avium
andsoaRssuedestrucion M.Leprae
M.Tuberculosis
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ISONIAZID MYCOBACTERIUMLEPRAE
WorkswellagainstMycobacteriumbecauseit CausesLeprosy(akaHansensdisease)
inhibitsthesynthesisofmycolicacid Hypopigmentedpatchesorredpatcheswith
MustsupplementwithB6toprevent lossofsensaRon
neuropathies Peripheralnervethickening
Sideeectsinclude:MyosiRs,hepaRRs, Acidfastbacillionmicrobiology
hepaRcnecrosis,neuropathies,oxidaRonof Treatment:Dapsone+Clofazimine+Rifampin
RBCs,andinhibiRonofP450 (for6mnth2yr)
MYCOBACTERIUMAVIUM TUBERCULOSISPrimaryInfecRon
SeenwhenCD4countsdropbelow50inAIDS PrimaryTBisasymptomaRc
paRents GhonfocusandGhoncomplexformaRon
SymptomsaresimilartoTB,inaddiRontoGI Chordfactor(virulence)
symptomsthatmaybepresent(pain,
diarrhea)
ProphylaxiswithAzithromycin
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TBPPDTest WhenthePPDisposiRve
ThesizeofinduraRoniswhatmakesaPPD Ifposi7vewithnosymptomsdoanxray
testeitherposiRveornegaRve Ifposi7vewithsymptomsRIPEtreatament
5mmisposiRveinimmunocompromised isstarted
10mmisposiRveinhealthcareworkers,
peopleinconnedspaces,andincarcerated
individuals
15mmisposiRveineveryone
IMPAIRMENTOFCELLMEDIATED
IMMUNITY
Mycobacteriumremainsaliveinside
macrophages
Immunesystemcompromisecanallowthe
mycobacteriumtoexplodefromthisandinto
theairways
Thisisgoingtoleadtohemoptysisbecauseof
thevascularitysurroundingthefocus
Mycobacteriummovestoupperlobesand
createsacavitywebecomesymptomaRc
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SECONDARYTB SECONDARYTB
TBbreaksfreeoftheGhonfocus Whatyouwillsee
Hemoptysisistherstsignthatthishas Hemoptysis
occurred Fever
Movementtotheapexwhen02levelsare Nightsweats
highest(cavitaRonsbrocaseous) Weightloss
CavitaRonswillremainforlifeandarea
AaerreplicaRon,disseminaRoncanoccur
favoritespotforAspergillosis
DISSEMINATEDTB(Miliary) TBPROPHYLAXISANDTREATMENT
TBspreadsthroughouttheenRrebodyonceit ProphylaxisrequiresINH+B6for912months(upon
replicatesinthecavity posiRvePPD)
GI Newprophylaxis(largedoseINH1x/wk+RifapenRn),
LNs for3months
Bone RIPEfor4monthsforeveryonewhoisposiRveif
Skin improvement(ie.INHandRifampinsensiRve),2drug
regimenfor8moremonths
Pathognomonicndingisacoldabscessalongthe IfnotsensiRve,conRnue4drugregimenfor8more
psoasmuscle months
CNS AhistoryofhavingBCGvaccinedoesntexcuse
Kidneys prophylacRctreatmentforlatentinfecRon
Adrenals
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THETBDRUGS AndFinally
Rifampin:bacteriocidal,majorAEis
hepatotoxicity(dofrequentLFTs)
Isoniazid:bacteriocidalagainstreplicaRng TheToRCHInfec7ons
bacteria,majorAEisperipheralneuropathy(give Toxoplasmosis
B6)
Pyrazinamide:stronglybacteriocidalinacidic Syphilis(other)
environments,majorAEisarthralgia(not Rubella
dangerous,dontneedtostopdrug)
Ethambutol:bacteriostaRc,majorAEsinclude: Cytomegalovirus
opRcneuriRs,redgreencolorblindness, Herpes
hyperuricemia,andarthralgias.
TOXOPLASMOSIS SYPHILIS
CausesmulRpleringenhancedlesionsinthe Syphiliswillhurtthebonesinafetus
parietallobe
Flarenedforehead
Caughtbyhandlingcatlirerwhichisdirtywith
feces Saddlenose
HealthyindividualsareasymptomaRc Micrognathia
Immunesuppressionwillcausesymptoms(thisis Hutchinsonsteeth(sharpenedteeth)
whypregnancymakessomeonesymptomaRc)
Sabreshins
Treatment:avoidcatlirer,pyrimethamine/
sulfadiazinecombinaRon Snues(sniesinasyphiliRcchild)
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RUBELLA CYTOMEGALOVIRUS
Germanmeasles IstheMCCofcongenitalblindness(aracks
Blueberrymunrash reRna)
Cataracts GetcentralcalcicaRons(asopposedtotoxo
PDA whichisparietallobe)
Aracksthemidline(bladder,gait,etc)
Hearingloss
LinktoauRsm
HERPESVIRUS
InfecRonoccurswhenbabypassesthrough
vaginaduringacRveinfecRon
Outbreakwithin2weeksofbirthrequiresc
secRoninsteadofvaginaldelivery
Acyclovirgiveninlasttrimestercanhelpto
preventoutbreaks
CausestemporallobeencephaliRs
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VIRUSESTHEBIGPICTURE
VIROLOGY
ASYMPTOMATICPERIODOF
ANTIVIRALPHARMACOLOGY
INFECTION
Mainlyactontheinvasion,uncoaRng,and Knownastheviremic(prodromal)period
replicaRonphases IncludesInvasionandAdhesion
Preven7nginvasion:simplybywashinghands IsasymptomaRc
rouRnelythroughouttheday
Preven7nguncoa7ng:Amantadine,
Rimantadine[forinuenzaA]
Preven7ngreplica7on:Acyclovir,Valcyclovir,
etc
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THEECLIPSEPERIOD SYMPTOMATICPERIOD
IncludespenetraRon,uncoaRng,replicaRon, Theviremicperiod
andassembly Releaseofnewlyformedviruses(lysogeny)
ThereisfaRguebecauseweuseourownATP FaRgue,malaise,fever.Andallothersignsof
tocreatemorevirus infecRon
Wecannotvisualizethevirusintheblood(all
lockedupinthecells)
DNAVIRUSES
Allaredoublestranded[Exc:Parvovirusand
Hepadnavirus]
Allreplicateinthenucleus[Exc:Poxvirus]
Allassembleonthenuclearmembrane
Nakedviruses:Parvovirus,Adenovirus,and
Papovavirus
EnvelopedDNAviruses:Hepadna,
Herpesvirus,Poxvirus
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TRICKSTOHELPYOUDOWELLIN
RNAVIRUSES
VIROLOGY
AllRNAvirusesaresinglestranded[Exc: DNAorRNA?
Reoviruses] +vestrand.RNAisinthemRNAformget
AllRNAvirusesreplicateinthecytoplasm[Exc: intotranslaRonfasterinfecRonoccursfaster
RetrovirusandInuenza] vestrandRNAisnotyetinmRNAform
AllRNAvirusesassembleonthecell needsmoreRmetogettotranslaRon
membrane infecRonoccursmuchslower(13weeks)
AllRNAvirusesareenveloped[Exc:Coxsackie
virus]
VIRALGENETICS RECOMBINATION
Recombina7on:istheexchangeofgenes
between2chromosomes
Reassortment:istheexchangeofviral
segmentsresponsibleforH1N1pandemic
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REASSORTMENT VIRALGENETICS
Complementa7on:afuncRonalvirussupplies
afuncRonalproteinthatservesbothitanda
fellownonfuncRonalvirus
Phenotypicmixing:coaRngacertainvirus
withthesurfaceproteinsofanothervirus
THESEGMENTEDVIRUSES OBLIGATEAEROBES
Importantbecausereassortmentofthese Theyneed02inordertogrow
leadstopandemics(worldwide) Nocardia
ReassortmentcasesanRgenicshias Pseudomonas
Includes:Bunyavirus,Orthomyxovirus, Mycobacterium
Arenavirus,andReovirus Bacillus
NaggingPestsMustBreathe
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OBLIGATEANAEROBES OBLIGATEINTRACELLULARBUGS
Theseliveandgrowinan02depleted Thesebugscanonlyliveinsidethecells
environemnt Rickersia
Clostridium Chlamydia
Bacteroides
AcRnomyces StayInsideWhenItsReallyCold
FACULTATIVEINTRACELLULAR
HEPATITIS
ORGANISMS
Canlivebothinsideandoutsideofacell Hepa77sA
Salmonella HepaRRsAcausedbyPicornavirus(RNA)
Brucella Transmissionisfecaloral(badwater,food)
Mycobacterium IncubaRonof26weeks
Listeria Selflimited
Francisella
Hepa77sE
Legionella
CausedbyCalicivirus(RNA)
Yersinia CourseissimilartoHepaRRsA
Dangerousinpregnantwomen
SomeBugsMayLiveFacultaRveLY Causedbycontaminatedwater(Mostcommonly)
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DNAVIRUSLIST
HEPADNA
HERPESVIRUSES
ADENOVIRUS
DNAVIRUSES
PARVOVIRUS
PAPILLOMAVIRUS
POLYOMAVIRUS
POXVIRUS
HEPATITIS HEPATITIS
Hepa77sB Hepa77sC
CausedbyHepadnavirus(DNA) CausedbyFlavivirus(RNA)
IncubaRonperiodof26months IncubaRonperiodof2030yr
#1causeoftransmissionisthroughuseof #1causeisbloodtransfusion,#2issexual
usedneedles(#2issexualtransmission,#3is 6080%ofcasesbecomechronic
verRcaltransmission) Signicantlyincreasescancerrisk
10%ofcasesbecomechronic Highriskofcirrhosis
Cancerriskisincreased
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HEPATITIS THEHEPATITISMOLECULE
Hepa77sD
CausedbyDeltavirus
CoinfecRonwithhepaRRsBbecauseitneeds
thehepBenvelope
HEPATITIS
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HERPESVIRUS TESTINGFORHERPESVIRUSES
HSV1&2 TzanckTest:usedforHSV1&2,aswellasVZV
VZV Swabsanopenvesicle
EBV FordetecRonofmulRnucleatedgiantcells
CMV
HHV6(Roseola)
HHV8(KaposisSarcoma)
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DIAGNOSINGEBV ADENOVIRUS
PE:pharyngiRs,fever,severefaRgue, PharyngoconjuncRvalFever
splenomegaly,lymphadenopathy EpidemicconjuncRviRs
Peripheralsmear:giantsinglenucleatedRBC ConjuncRviRs
Monospottest:canbeusedtodetectthe2 Acuterespiratorydisease
anRbodiesfoundinEBVinfecRon AcutehemorrhagiccysRRs
GastroenteriRs
**Mostimportant**
Avoidcontactsports
PARVOVIRUS PAPILLOMAVIRUS
ParvoB19(5thdisease) HPV(Warts,CIN,andCervicalcancer)
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POLYOMAVIRUS POXVIRUS
JCVirus(PML) Smallpox
MolluscumContagiosum
RNAVIRUSLIST
PICORNA
CALICIVIRUS
REOVIRUS
TOGAVIRUS
RETROVIRUS
ORTHOMYXOVIRUS
PARAMYXOVIRUS
RHAMDOVIRUS
FILOVIRUS
CORONAVIRUS
ARENAVIRUS
BUNYAVIRUS
DELTAVIRUS
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PICORNAVIRUS HERPANGINACoxsackieA
Polio
Echovirus
Rhinovirus
Coxsackievirus
HepaRRsAvirus
HF&MDISEASECoxsackieA CALICIVIRUS
HepaRRsE
Norwalkvirus
110
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REOVIRUS FLAVIVIRUS
Reovirus(ColoradoTickFever) HepaRRsC
Rotavirus Yellowfever
Denguefever
St.LouisEncephaliRs
WestNileVirus
TOGAVIRUS RETROVIRUS
Rubella(Germanmeasles) HTLV(Tcellleukemia)
EasternEquineEncephaliRs HIV/AIDS
WesternEquineEncephaliRs
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ORTHOMYXOVIRUS PARAMYXOVIRUS
Inuenza Parainuenza(Croup)
RSV
Measles
Mumps
CROUPSteepleSign
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RHABDOVIRUS FILOVIRUS
Rabies Ebolavirus
Marburgvirus
CORONAVIRUS ARENAVIRUS
Coronavirus(commoncoldsummer) LymphocyRcchoriomeningiRs(LCV)
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BUNYAVIRUS DELTAVIRUS
CaliforniaencephaliRs HepaRRsD
Sandy/RiavalleyFever
Hantavirus
CrimeanCongohemorrhagicfever
IMMUNOLOGY
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ANTIGENS ANTIGENS
Anythingthatelicitsaresponsefromyour Canbedividedinto2dierenttypes.
immunesystem HaptensandImmunogens
MCtheyareproteins Thebiggestfactordeterminingwhetherornot
2ndMCtheyarecarbohydrates somethingelicitsanimmuneresponse
(immunogenicity)isvaribility
HAPTENS IMMUNOGEN
Dontsetotheimmunesystem Willsetotheimmunesystem
Theyaretoosmall Isbigenoughtoelicitaresponse
Canwemakeahaptenmoreimmunogenic?
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THECARRIEREFFECT
WecantakeahaptenandsRckitontothe
surfaceofanimmunogentoelicitaresponse
toboth
Aslongastheyarebothdigestedbya
macrophagewecangetanimmunogenic
responsetothehapten
ACTIVEIMMUNITY FUNCTIONOFINTERLEUKIN1
Weeithergetinfectedorgetthevaccines RecruitsThelpercells
VaccinaRonspresentuswiththedisease SRmulatesfever
haptensowedonthavetoexperiencean
illness Producesnonspecicsymptomsinresponse
Wetakeahaptenandaàchittothe toanillness
immunogen,thiswaywegetprotecRonwithout
gengsick
Ourmacrophagesengulf,process,andwegetan
IgGagainstthehapten(eventhoughweve
neverhadtheinfecRon)
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DECREASINGTHEIMMUNOGENS
FEVER
IMMUNOGENICITY
IL1hasbeenreleased Therearethingswedoonadailybasisthat
WatchtheHRwhenafeverispresent areaimedatdecreasingthechanceswegetan
Feverparernscangiveyouadiagnosis immuneresponsetosomething
DonttouchafeverunRlitreaches101.5 Wewashourhands/bodies
WeuseanRsepRcs/disinfectants
WeusesterilizaRontechniques
THETWOARMSOFTHEIMMUNE HUMORALANDCELLMEDIATED
SYSTEM SYSTEMS
HumoralPatrolstheblood
IfyouwanttoknowwhoissRmulaRngthe
humoralimmunesystem,simplytakeablood
culture
DeciencyofBcellsorneutrophilswillkillyou
viatheblood
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HUMORALANDCELLMEDIATED
SYSTEMS
CellMediatedPatrolstheRssues
TondoutwhatissRmulaRngthecell
mediatedimmunesystemtakeaRssuesample
DefectoftheTcellsormacrophageswillkill
youthroughtheRssues
LEUKOCYTES
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WBCVALUES VIRUSESTHATCANCAUSELEUKOPENIA
Leukopenia(lowWBC)is<4,000
Normalvalueis4,00012,000 ParvovirusB19
Leukocytosis(highWBC)is>12,000 HepaRRsEandC
Leukemia? AnyviruscansuppressyourWBCs
DRUGSCAUSINGLEUKOPENIA STEPSTOINCREASINGLEUKOCYTECOUNT
VinblasJne(BMSuppression)
AZT(BMSuppression) DemarginaRon
Chloramphenicol(BMSuppression) PavemenRng
Benzene(BMSuppression) MarginaRon
Carbamazepine(Agranulocytosis) Diapedesis
Ticlopidine(Agranulocytosis) MigraRon
Clozapine(Agranulocytosis)
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MCCOFLEUKOCYTOSIS LEFTSHIFT
StressDemarginaRon Movementfrommaturestatetostateof
InfecRons immaturity
Leukemia Releaseofcellsfromthebonemarrowbefore
Lymphoma theyarefullymatured(tocompensate)
MyelodysplasRcsyndromes
LeukemoidreacRons
LEUKOCYTOSIS
WBCs PMNs BANDS BLASTS
Stress Increased Increased

DemarginaRon
InfecRon Increased Increased
LEUKEMIAS
Leukemia Increased >5%
Leukemoid Increased <5%

ReacRon
Lymphoma
Myelodysplasia
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LEUKEMIAS
AML
ALL
CML
CLL
AMLvs.ALL AMLvs.ALL
AML:AuerRodsarepathognomonicforAML An7metabolitessuchasmethotrexatework
Myeloblastswillstain+vewithSudanBlack wellforALL
(Lymphoblastswillnot) Prednisoneisanexcellentadjunctbecauseit
killsTcells
ALL:LymphoblastswillbePAS+,asweas PrognosisforALLisbestifpaRentisbetween
posiRvestainingforterminaldeoxythymidine 110yrofage
ALLhastheCALLA,whichisananRgenof AMLcarriesaworseprognosis
ALLtellsusthatitwillrespondtochemo
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CMLvs.CLL CMLvs.CLL
CML:MaturemyelocyRccellswillleavetheBM CLL:Youwillseethisprimarilyinthose>50yr
andbecomecancerousintheperiphery ofage
Neutrophilsproliferateandbecomenumerous
Diuselymphadenopathyisalwaysseen
Monocoytesproliferateandbecomenumerous
MacrophagesenterRssuesandproliferate(as
Hasthebestprognosis
theirownuniqueRssuespecicmacrophage) Wedonttreatunlessthewhitecellcountis
PMNs,Monocytes,andMacrophagesarevery signicantlyelevatedusingalkylaRngagents
highinCML(onlyleukemiawithhighlevelsof
thesecells)
HAIRYCELLLEUKEMIA
IsararesubtypeofCLL
AccumulaRonofabnormalBcells
Thepathognomonicndingishairy
projecRonsofthecells
ConrmatorydiagnosisiswithTRAP
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ALL015yr
AML1530yr
CML3050yr
CLL>50yr LYMPHOMAS
LYMPHOMA HODGKINSLYMPHOMA
2040yr
Highlytreatable
ReedSternbergcellsarepathognomonic
SwollenLNisthecommonpresentaRon
Which3LNsaremostworrisome??
Thereare4typesofHodgkinslymphoma
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4TYPESOFHODGKINSLYMPHOMA 4TYPESOFHODGKINSLYMPHOMA
NODULARSCLEROSING LYMPHOCYTEPREDOMINANT
Morecommoninwomen Therearemanylymphocytes
Hastheleast#ofRScells CarriesthebestprognosisofallHodgkinssub
Carriesanintermediateprognosis(compared types
withalltypesofHodgkinslymphoma) Rare
Common
4TYPESOFHODGKINSLYMPHOMA 4TYPESOFHODGKINSLYMPHOMA
LYMPHOCYTEDEPLETED MIXEDCELLULARITY
Hastheleast#oflymphocytesascompared ManyRScellsmixedwithmanyinammatory
cells(lymphocytes,hisRocytes,eosinophils)
withothertypesofHodgkinslymphoma
AssociatedwithEBV
HastheworstprognosisofallHodgkins
Intermediateprognosis
sybtypes
Common
Rare
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NONHODGKINSLYMPHOMA FOLLICULARLYMPHOMA
SeenMCinpaRentswhoare t(14;18)
immunocompromised Givesanoverexpressionofthebcl2gene
Canpresentwitheitherabdominalmassor AveragesurvivalfromRmeofdiagnosisis10yr
jawmass
Follicularlymphoma(MCtype)
Burkirslymphoma
BURKITTSLYMPHOMA STAGINGLYMPHOMA
t(8;14) Stage1:1groupofLNsisinvolved
Involvesthecmycgene Stage2:2groupsofLNsonthesamesideof
associatedwithEBV thediaphragmareinvolved
Thereare3commonvariaRonsofBurkirs Stage3:2ormoregroupsofLNsonboth
Histologyshowstheclassicstarrysky sidesofthediaphragminvolved
appearance Stage4:metastasisthroughoutthebody
Endemicvariant,sporadicvariant,and
immunodeciencyassociatedvariant
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LYMPHOMATREATMENT BONEMARROWSPECIFICSYNDROMES
Severaldierenttreatmentregimensexist Polycythemiarubravera
MOPP(Mechlorethamine,Oncovin, EssenRalthrombocytopenia
Procarbazine,Prednisone) AplasRcanemia
CHOP(Cyclophosphamide,Hydroxyurea, Myelobrosis
Oncovin,Procarbazine)
ABVD(Adriamycine,Bleomycin,VincrisRne,
Dacarbazine)
POLYCYTHEMIARUBRAVERA ESSENTIALTHROMBOCYTHEMIA
Allofyourcelllinesareincreased Youseeanincreaseinallcelllines
RBCsareincreasedthemost Plateletsareincreasedthemost(>600,000for
Hematocrit>60%isseen(bestdxcriterium) diagnosistobemade)
PrimaryPRVduetobonemarrow ThispaRentmustbeonanRplatelettherapy
SecondaryPRVduetoincreasedproducRonof toreducethrombosisrisks(aspirin,
clopidogrel,Rclpidine,dipyridamole)
erythropoieRn(naturallyorarRcally)
Phlebotomyismainstayofmanagement Hydroxyureatolowerplateletcount
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APLASTICANEMIA MYELOFIBROSIS
Allcelllinesaredepleted DestrucRonandsubsequentscarringofthe
MCCisviralordrugrelated bonemarrow
ALLcanbeanunderlyingcauseof
CheckreRculocytecounttoidenRfywhether
myelobrosis
BMisthecause
Expecttoseeteardropcellsaswellasalow
RemovalofcausaRveagentiscuraRve reRculocytecount
Stemcellreplacementistheonlycure
Bloodtransfusiononaregularbasiswillbe
required
LYMPHOCYTEDEVELOPMENT
UnderstandingwhereeachstepoftheBcell
andTcelldevelopmentoccurcanhelpdeal
LYMPHOCYTES withquesRons
Understandingdrugsandvirusesthatcan
MONOCYTES interferewithbonemarrowwillhelpyou
understandwhatcausessuppression
GRANULOCYTES UnderstandingwheretheyeachdierenRate
canhelpyougureoutatonofinformaRon
thatisntgiveninthevignere
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BIGPICTUREROLEOFBCELLS
Componentofhumoralimmunesystem
MakeanRbodiesagainstanRgens
PerformtheroleofanRgenpresenRngcell
DevelopintomemoryBcellsaaerananRgen
interacRon
BLYMPHOCYTEINTRODUCTION BLYMPHOCYTEINTRODUCTION
Developinthebonemarrow Haveclonality(dividesmanyRmesupon
ImmatureBcellhassurfaceCD9andCD10,as encounteringasingleanRgen)
wellasIgM IncreasesanityforfutureanRgen
Theymatureinthespleen(leavewithIgDon encounters
surface)CD19,CD20,IgM,IgD Ampliestheimmuneresponseinsubsequent
TheydierenRateinthegerminalcentersof encounters(improvedimmuneresponse
lymphoidRssue specicity)
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TLYMPHOCYTEINTRODUCTION TCELLSATTHETHYMUS
AsTcellsdeveloptheyhaveaCD3 TcellentersundierenRated
UponleavingtheBMtheyallhaveCD4and Undergonega7veselecRonrst,then
CD8ontheirsurface undergoposi7veselecRon(clonaldeleRon)
MaturaRoninthethymus(atrophiesduring 1stroundofclonaldele7on(negaRve
selecRon)selecRonforCD8rst,thenCD4
adolescence)
2ndroundofclonaldele7on(posiRve
AsingleTcellcontrolsmanyBcells selecRon)selecRonforanity
(remember98%Bcells,2%Tcells)
Thymusinvolutesandisreplacedwithfary
Rssueinadulthoodandduringpregnancy
1STROUNDOFCLONALDELETION 2ndROUNDOFCLONALDELETION
(NegaRveSelecRon) (PosiRveSelecRon)
CD8swhogetthroughareeithercytotoxicor The2ndroundwillhelpuschoosebasedon
Tsuppressors theproperanityofeachcelltype(posiRve
CD8respondstoMHC1complex(monitors selecRon)
self) CD4cellsarenonself,sowewanttochoose
Tsuppressors:jobistosuppressaninfecRon thosewiththestrongestanity
fromspreading CD8cellsareself,sowewanttochoose
Tcytotoxic:jobistokillaninfectedcell thosewiththeweakestanity
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NATURALKILLERCELLS(NK) NKCELLKILLING
OnceCD4andCD8havematured(butbefore PerforaRon
leavingthymus),NKcellsareputoutand Programmingacelltoapoptose
entercirculaRonwithTcells
GuideBcellstocoatwithanRgen
DoNOTgothroughclonaldeleRon
NKcellshaveCD16andCD56surfacemarkers
NKcellswillrespondtoMHC1an7gens Levamisole:enhancestheNKcellskilling
Workvia:perforaRon,programmingcellfor abiliRes(promisinganRcancerdrug)
apoptosis,tellingBcelltocoatwithan
anRbodysomacrophageseatit
CD8CELLSREVIEW THELPERCELLS
ArerstonesthroughclonaldeleRon Twotypes
ExpressMHC1complex Th1respondtocellmediated(nonbacterial)
RespondtoMCH1anRgens(self) Th2respondtohumoral(bacterial)
Tc(Cytotoxic)destroyaninfectedcell
Th(Helpers)preventthespreadofaninfecRon Thcellsareresponsibleformakingallofthe
interleukins(exceptIL1)
ProduceinterferongammaandTNFgamma
ControlBcellsandmacrophages
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TCELLSFormaRonofaGranuloma
AgranulomaisformedwhenTcellssurround
aninfecRonTcellsthensecrete2things:
TumorNecrosisFactorGamma(TNF)
Interferon
THEINTERLEUKINS THEPRIMARYIMMUNERESPONSE
IL1: 1stRmeyoucomeincontactwithananRgen
IL2: IgM:arrivesin3days,peaks2weeks,lasts2
IL3: months
IL4: IgG:arrivesin2weeks,peaks2months,lasts
IL5: 1year
IL6: HowcanweapplythistovaccinaRons??
IL10
IL12:
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THEMEMORYRESPONSE
Developsaround12months
Fullydevelopedby15months
OnlyinvolvesIgG
IgG:arrivesin3days,peaksat5years,lasts
for10years
HowcanweapplythistovaccinaRons??
ANTIBODYSTRUCTUREAND
FUNCTION
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ROLEOFIMMUNOGLOBULIND ROLEOFIMMUNOGLOBULINE
IgD IgE
Isasurfacemarkeronly Isamonomer(1FAB,1Fc)
Doesntxcomplement
AcRveinbindingbothallergensandparasites
HyperIgE=Jobssyndrome
ROLEOFIMMUNOGLOBULINA ROLEOFIMMUNOGLOBULINM
FoundmainlyinmucosaandsecreRons Amonomerasasurfacemarker
IsadimerinmucosaandsecreRons(2Fabs,2
Fcs) Apentamerwheninthebloodstream(5Fab,
Isamonomerintheblood 5Fc)
IgAisfoundinbreastmilk Fixescomplementat2places(C1andC3)
IgAdeciencyseeninmanydiseases Waldenstromsmacroglobulinemia
Hasasecretoryproteinthatprotectsitfrom
degredaRonbyharshenvironments(stomach) WiscoÀldridgedisease
Heavychaindisease(IgAmulRplemyelomaof
bowelwall)
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ROLEOFIMMUNOGLOBULING THECOMPLEMENTSYSTEM
Thereare4subtypesofIgG Helpskillencapsulatedorganismsbyaracking
thesurfaceofaforeigncell
IgG1:FcporRongivesittheabilitytocrossthe
Encapsulatedorganismsare??
placenta(givingimmunitytothefetus)
RecurringNeisseriainfecRons(MACdefect)
IgG2:istheMCsubclassdeciency C5a:ifnotbrokendownbyesteraseleadsto
IgG3:deciencyrelatedtochroniclung localizedangioedema(MCeyelidsand/orlips)
infecRons Classicalpathway(triggeredbyC1complex)
IgG4:doesntxcomplement Alterna7vepathway(triggeredbyspontaneous
C3hydrolysis)
FORMATIONOFMAC 4TYPESOFHYPERSENSITIVITY
TYPE1:Immediate,involvesmastcellsand
eosinophils,nocomplementinvolved,involves
IgE
Anaphylaxisisclassicexample
TYPE2:Cytotoxic,isanarackonself,dueto
complementarackaaeriniRalRssue
destrucRon
Autoimmunediseasesaretype2
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4TYPESOFHYPERSENSITIVITY IMMUNOLOGYANDTHERHESUSFACTOR
TYPE3:Immunecomplexdeposi7on Canbe++,+,
AccidentalarackontheRssues WeworrywhenmotherisRhandthefatheris
Rh+
Complementisusedinexcesssolevelswillbe
low 1stchildisnotatrisk
Allsubsequentchildrenareatrisk
Thereare6nephroRcsyndromeswithlow
complement,aswellasSLEandRA Aaer1stchildgiveRhogamwithin72hr
DuringsubsequentpregnanciesRhogamat28
TYPE4:Cellmediated(Tcellsandmacrophages) wkandagainaoerdelivery
ClassicexampleiscontactdermaRRs KleinhauerBetketesttoadjustRhogamdosages
UNDERSTANDINGBLOODTYPING TYPEANDCROSS
ABOtesRngislookingforaparRcularanRgenon CROSSMATCH:testswhetheryouhavepreformed
thesurface anRbodiestoadonorslymphocytesoaRng
AnRgensaresugars aroundinyourserum
PresenceofaparRcularanRgenmeansyouhave Usingradiolabelledcomplementwecandetect
anRbodiestotheotherotherbloodtype whethertheanRbodiesarachtoadonors
BloodtypeOhasnoan7gens(universaldonor, anRgens
canonlyreceivetypeOblood)
Ifradiolabelledcomplementdisappearsitmeans
BloodtypeABhasnoan7bodies(wontreject arachmentoccurred,therearepreformed
anybloodtype,isuniversalrecipient,canonly
donatetoanotherABtype) anRbodies,andthisdonorsRssuewillnotwork
forus
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TYPEANDCROSS TYPEANDCROSS
MIXEDLYMPHOCYTEREACTION: HLATYPING:looksforsimilariResintheMHC
InvolvesmixingapaRentslymphocyteswith Gooddonorshaveatleast60%matching
irradiateddonorlymphocytes Parentsaretheworst(never>50%)
Weaddradiolabelledthymidine Siblingsusuallybest
ReplicaRon=radioacRvity=rejecRon
IfwegetlirletonoradioacRvitywehavea
match(lowestnumberoutofalldonorswillbe
thebestmatch)
TYPESOFREJECTION
Hyperacute:within12hoursoftransplant
Notreatment,simplyremovetheorgan
Acute:Tcellsandmacrophagesonbiopsy
Istreatablewithprednisoneandcyclosporine
(addiRondosagesabovetheiniRaldosages)
Chronic:Fibrosis/calcicaRonsonbiopsy
Removaloforganrequired
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TYPESOFREJECTION MONOCYTES
Graovs.Host:MCaaerBMtransplant AremacrophagesthataresRllincirculaRon
TransplantedorgansareexposedtoradiaRon EnterRssue,changethename
priortotranplant,thusGvs.Hisrare TransformaRonismediatedbyinterferon
Alwaysthinkbonemarrowinagraavs.host TheycontainonlyNADPHoxidase
rejecRon
MCsignisapainfulrashontheskin
PROBLEMSWITHTHEMONOCYTES
Monocytosis(<15%)
Extrememonocytosis(>15%)STELS
Mononucleosis
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MONONUCLEOSIS
UsuallycausedbyEBV
Looksjustlikestrepthroat(dierenRate
baseduponpopulaRonandonset)
CBCshowsTcellsandmacrophages
EBVisheterophilean7bodyposi7ve
MajorcomplicaRonisrupturedspleen(barr
fromcontactsportsunRlresolved)
THEGRANULOCYTES NEUTROPHILS
Neutrophils(60%) Themostabundantgranulocyte
Eosinophils(2%) Bandsareimmatureneutrophilswith
Basophils(<1%) maximumgermghRngcapabiliRes
Theyaretheimmunesystems1stlineof
defense
Theyshowupat24hr,peakat3days
IL10suppressescellmediatedarm
IL12enhancesthecellmediatedarm
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KILLINGORGANISMSUSINGTHE
NEUTROPHILS RESPIRATORYBURST
10%arecirculaRng,90%aremarginated CanoccurinPMNs,monocytes,and
PMNsaretherstlineofdefenseandcreate macrophages
Peroxide(H202) UsesoxygentocreateareacRveoxygen
species,whichthencreatesperoxideand
Catalaseconvertsperoxideinto2H20s(to subsequentlyHypochlorite
protectourownproteinsfromdegredaRon) FailuretodothisresultsinChronic
WhichbacteriaarecatalaseposiRve? GranulomatousDisease
HowdowedealwithcatalaseposiRve Occursmostcommonlyaround7dayspost
bacteria? infecRon
CHRONICGRANULOMATOUSDISEASE
DeciencyofNADPHOxidase
Phagocytosisofbacteriathatnevergets
destroyed
AccumulaRonofgranulomasthroughoutmany
organs
Anywhereamacrophagecantravelwecan
developgranulomas
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NEUTROPENIA EOSINOPHILS
TheMCCwillbeavirusordrugs HelpghtinfecRons
Wehavetocalculatetheabsoluteneutrophil Helpghtparasites
countbeforedeterminingourneutrophilsin InvolvedinallergicreacRonsandasthma
circulaRon: EosinophiliaisseeninNAACP
AbsolutePMNCount=
(%PMNs+%Bands)WBC
EOSINOPHILICGRANULEPROTEINS THEPRIMARYRESPONSE
UponsRmulaRontheeosinophilreleases ThisisanasymptomaRcresponsetothe1st
granulescontaining4typesofproteins encounterofanallergen
MajorBasicProtein(MBP) AllergenispresentedtoTlymphocytes
EosinophilicPeroxidase(EPO) TcellsbindtoBcells(viaCD40ligand)
EosinophilicCa7onicProtein(ECP) TcellsmakeIL4
EosinophilDerivedNeurotoxin(EDN) BcellsmakeIgE
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THESECONDARYRESPONSE MASTCELLS
Thisresponseproducesphysicalsymptoms Immediatelyreleasehistamine
IgEisawaiRngtheverysameanRgenthatit ReleaseSRSAwithin48hoursofsRmulaRon
prepareditselfforduringtheprimary ReleasetheEosinophilicchemotacRcforfor
response anaphylaxisakaECFA
IgEsRmulatesmastcelldegranulaRon
MastcelldegranulaRonproducessymptoms
HISTAMINE 1STGENERATIONANTIHISTAMINES
Isresponsibleforalloftheacutesymptoms Workbycompe77velyblockingtheH1
experiencedduringanallergicreacRon receptors
Redness ArelipophilicandcancrosstheBBB
PruriRs StronganRcholinergicproperRes(1st
Flushing generaRon)
Warmingoftheskin Lastsfor46hr
Wheezing
Swelling
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ANTIHISTAMINES ANTIHISTAMINES
1stGeneraJon:HighlySeda7ve 1stGeneraJon:ModeratelySeda7ve
Diphenhydramine(Benadryl) Pyrilamine
Dimenhydrinate(Dramamine,Gravol)
Hydroxyzine 1stGeneraJon:LowSedaJon
Promethazine(alphablockade,orthohypo) Meclizine(An:vert)
**HydroxyzineandPromethazineareanR Cyclizine
emeRcs
2NDGENERATIONANTIHISTAMINES FASTACTINGDECONGESTANTS
MuchlesssedaRon(decreasedlipophilicity) WorkfastbysRmulaRngthealpha1receptors
LongerlasRng andvasoconstricRng
LessanRcholinergiceects Phenylephrinethemainingredientinmost
CommonOTCmedsforseasonalallergices OTCnasalsprays
PseudoephedrineisfoundinmanyOTCcold
Ce7rizine(Zyrtec)
medicines
Loratadine(ClariRn)
Fexofenadine(Allegra)
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SLOWREACTINGSUBSTANCEOF EOSINOPHILCHEMOTACTICFACTOROF
ANAPHYLAXIS(SRSA) ANAPHYLAXIS(ECFA)
Ahighlypotentbronchoconstrictor Arractseosinophils
Producesthelatersymptomsexperienced Thischemicaliswhatleadstoeosinophilia
duringallergies(48hr) duringallergicreacRons
Ifsomeonediesduringanasthmaarack,this
isthelikelycause
TYPE1HYPERSENSITIVITIES TYPE4HYPERSENSITIVITIES
Arehistaminemediated(mastcellandIgE) AredelayedreacRonsthatarecellmediated
Allgettreatedwithsteroids Atopicderma77s
ErythemiaMul7forme Contactderma77s
Ur7caria Eczema
ToxicEpidermalNecrolysis(TEN)
StevenJohnsonSyndrome
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ASTHMA BASOPHILS
Intrinsicasthma(bornwithit,coldairsetsit Areprecursorstomastcells
o) Weusecromolynornedocromyltoprevent
Extrinsicasthma(duetoenvironmental theirdegranulaRon
factors)
Environmentalfactorsincludedustmites,
smoking,exposuretoothernoxioussRmuli
Treatment/Management??
ASTHMAMANAGEMENTMainArack ASTHMAMANAGEMENTController
Relief MedicaRons
STEROIDS MASTCELL LONGACTING LEUKOTRIENE
ALBUTEROL IPRATROPIUM STABILIZERS BETA RECEPTOR
AGONISTS ANTAGONISTS
USE: MedicaJons
Mechanismof
MECHANISM AcRon
OFACTION:
MainUses
OTHERNOTES:
AdverseEects
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TCELLIMMUNODEFICIENCIES
DiGeorgeSyndrome
Chronicmucocutaneouscandidiasis
Steroiduse
IMMUNODEFICIENCIES Cyclosprine
SCID
Hairycellleukemia
Tcelllymphomas
WiskorAldridgeSyndrome
HIV
DiGEORGESYNDROME CHRONICMUCOCUTANEOUSCANDIDIASIS
Tcelldefectiscausedbyamissing3rd PaRentsdisplaycandidalinfecRonsonthe
pharyngealpouch skin,mucusmembranes,andngernails
Inferiorparathyroidsmissing(hypocalcemia) DuetoadefectofTcells
PTHiselevated FlareupswarrantanRfungaltreatmentfor
Chromosome22associated(CATCH22) 12weeks
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ANTIFUNGALTHERAPY ANTIFUNGALTHERAPY
POLYENES:bindsergosterol,formstransmembranechannel,ions
leakout
AmphoB+FlucytosineSystemicFungal
InfecRons
AZOLES:inhibitenzymeLanosterol14alphaDemethylase, VaginalcandidaMiconazole(Monistat)
blockingconversionoflanosterolintoergosterol
OralcandidaNysta7n
ALLYLAMINES:inhibitSqualeneEpoxidase,thusinhibiRng Fluconazole3xperweekpreventsrecurring
synthesisofergosterol fungalinfecRonsinimmunocompromised
FLUCYTOSINE:inhibitsDNAreplicaRonofthefungus,prevents
Fluconazole1dosetreatmentforcandidiasis
proteinsynthesisoffungus(isapyrimidineanalogue) (Diucan)
Ketoconazoleblocks5alphareductase(can
GRISEOFULVIN:interfereswithmicrotubulesfuncRon(inhibits causegynocomasRa)
mitosis)
STEROIDS MAINSTEROIDSUSEDINMEDICINE
KillTcellssoaTcellcannotprocessan Prednisone:mainoralformused
anRgen Hydrocor7sone:maintopicalandinjectable
formsused
Importanttounderstandtheoverall Methylprednisone:mainIVformused
physiologicaleectsaswellasthemainanR Flu7casoneandMometasone:nasalallergies
inammatoryacRons Fludrocor7sone:usedinadrenalinsuciency
AdministraRonof>5mgofprednisoneperday Megesterol:usedtoincreaseappeRteincancer
paRents
willshutdowntheHPAaxiswithin1week
Dexamethasone:usedinDexamethasone
suppressiontest(Cushingstest)
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CYCLOSPORINE SCID
BlocksTcellfuncRon CausedbyadeciencyofAdenosine
UsedintransplantpaRentstoprolongthe Deaminase
transplantedorganslongeRvity DisruptsDNAsynthesis
Inhibitscalcineurin(requiredtomakeILs) Rapidlydividingcellsaredisrupted
TandBcellsgetdisruptedbecausebotharms
Sideeectsinclude: oftheimmunesystemareinterrupted
RecurringinfecRonsofBOTHbacterialand
nonbacterialnature
HAIRYCELLLEUKEMIA TCELLLYMPHOMAS
IsmorefrequentlyaTcellleukemia CutaneousTcelllymphomas(Mycosis
HairyprojecRonsfromcellsmembrane fungoides,Sezarysyndrome)
TRAPposiRve ExtranodalTcelllymphoma
MediasRnalmetastasiscommonlyoccurs Anaplas7clargecelllymphoma
Angioimmunoblas7cTcelllymphoma
147
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WISCOTTALDRIDGESYNDROME BCELLDEFICIENCIES
Anxlinkedrecessivediseaseseeninfair Brutonsagammaglobulinemia
Commonvariableimmunedeciency
skinnedpeople Leukemias
TcellinteracRonswiththeBcellsisaected Plasmocytoma
MulRplemyeloma
(hurRngbotharmsoftheimmunesystem) Heavychaindisease
WillseenormalIgAandIgE,lowlevelsofthe SelecRveIgAdeciency
others SelecRveIgG2deciency
JobsSyndrome
TIEsyndrome:Thrombocytopenia, SCID
Infec7ons,Eczema WiscorAldridgesyndrome
BRUTONSAGAMMAGLOBULINEMIA COMMONVARIABLEIMMUNEDEFICIENCY
Anxlinkedrecessivedisorder ThispresentsjustlikeBrutons,butusually
MutaRoninBrutonstyrosinekinaseleadsto aaerthe1styearoflife
defectinBcelldevelopment(trappedinpro Isadiagnosisofexclusion
Bstage)
PaRentwontproduceadequate
Presentsinearlychildhoodwithrecurring
infecRonsintherespiratorytract immunoglobulinswhenexposedtopathogens
BloodworkshowsnoBcells Recurrentbacterialinfec7onsasBcellsare
primarilyaected
TreatmentinvolvesIVIGinfusions12xper
month
148
9/17/11
LEUKEMIAS PLASMACYTOMA
ForeveryTcellintheperipherythereare98 Isasinglelesion,malignantplasmacelltumor
Bcells(mostleukemiasarethusBcell) ineitherthesoaRssuesorthebone
Bcellsarestuckinanimmaturestate(blasts) Intheboneitoaenbecomesmalignant
melanoma(overadecade)
SoaRssueformsareusuallyresectableand
curable
MULTIPLEMYELOMA HEAVYCHAINDISEASE
AslowgrowingcancerwithmulRplelesionsof Excessiveheavychainsaresecreted,theyare
thebones(spineandribsMCaected) truncatedandnonfuncRonal
Alkalinephosphataserises
TheMCheavychaindiseaseistheIgAtype
IgGisMCspike
BenceJonesproteins(kappalightchains)
ThisaectstheGIandcausesmalabsorpRon
SeenMCaaer50yrofage Biopsyisrequiredfordiagnosis
RBCsstackedinrouleauformaRon
CRAB(calciumincreased,renalfailure,anemia,
bonepain)
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SELECTIVEIgADEFICIENCY SELECTIVEIgG2DEFICIENCY
IgApatrolsthemucosaandthesecreRons, ThisgoeshandinhandwiththeIgAdeciency
thuswellseemanymucosalinfecRons IgGisourmainopsin(idenResacelltobe
MostoftheRmeitgoeshandinhandwith digestedbyamacrophage)
selecRveIgG2deciency DeciencywillleadtorecurrentinfecRons
Anaphylaxisfollowingatransfusionisatell withencapsulatedorganisms(whatarethey?)
talesignofIgAdeciency
JOBSSYNDROME SCID
CausedbyabnormalPMNchemotaxis Remember:recurringbacterialandnon
MCseethisinaredhairedfemale(paleskin bacterialinfecRons
alsocommonlyseen) Adenosinedeaminasedeciency
Coarsefacies TandBcellsarebothaected
Staphabscesses
Primaryteethareusuallyretained
IgEiselevated
Dermatologicalproblems(eczema)
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WISCOTTALDRIDGE PMNANDMACROPHAGEDEFECTS
Myeloperoxidasedeciency
NADPHOxidasedeciency(CGD)
AbsoluteNeutropenia
ChediakHigashisyndrome
HIV
Retrovirus(RNADNARNAprotein)
SubSaharaAfricaisthemostaectedplace
HAARTtherapyhassignicantlyreducedthe
deathratesduetoHIV
HIV BiggestRFisafemaleinarelaRonshipwitha
bisexualman
HIVexposedtomucosaincreasesriskofinfecRon
(vagina,anus)
WhereyouhavemoreCD4receptorsyoucanget
HIV
151
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WHEREARETHEMOSTCD4
THEHIVSTRUCTURE
RECEPTORS?
Cervix
Bloodvessels
Macrophages
Thcells
CNS
TesRcles
CANCER KAPOSISSARCOMA
CervicalcanceriscommoninHIV Oaenthe1stcancerseeninAIDSpaRents
KaposissarcomaiscommoninHIV Producesnodulesthatarered/purple/brown
TesRcularlymphomasarecommoninHIV Involveanyofthese:Skin,Mouth,GItract,
Respiratorytract
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HIVIMMUNITY
CCR5GeneMuta7onwillinhibitarachment
ofHIVin80%ofcases
CCR5mutaRonhomozygous=paRentis
immune
CCR5mutaRonheterozygous=paRent
developsAIDSatamuchslowerpace
CCR5mutaRonblocksGP120binding
HIVSCREENING HIVTREATMENT
ELIZAisthersttestwerunwhenHIVis HAARTtreatmentisiniRatedwhentheCD4
suspected(highlysensiRve) countdropsbelow500,ORifthereisahigh
viralload
ConrmaRonismadewithWesternBlot
(highlyspecic) WeuseacombinaRon,usuallyconsisRngof2
reversetranscriptaseinhibitorsand1
proteaseinhibitor(usually)
Proteaseinhibitors
Reversetranscrip7oninhibitors(Nucleosides
andNonnucleosides)
153
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PROTEASEINHIBITORS REVERSETRANSCRIPTASEINHIBITORS
Inhibitvirusassemblyblockingtheprotease InhibitreversetranscriptaseoftheHIVvirus
enzyme PreventtheincorporaRonoftheviralgenome
Saquinavir intothehostsDNA
Indinavir(AE:thrombocytopenia,kidneystones) Nucleosideinhibitors(NRTI):Zidovudine
Nelnavir (AZT),Didanosine(ddI),Zalcitabine(ddC),
Stavudine(d4T),Lamivudine(3TC),and
Ritonavir Abacavir
AEs:allcauseN/V,hyperglycemia,lipid Nonnucleosideinhibitors(NNRTI):
abnormaliRes Nevirapine,Delavirdine,Efavirenz
WHENTOBEGINPROPHYLAXIS THESULFADRUGSPCPPROPHYLAXIS
BeginsPCPprophylaxiswhenCD4<200 13%ofpeopleareallergictosulfadrugs
TMPSMXforPCPprophylaxis Upto60%ofHIVpaRentsexperienceallergic
reacRonstosulfas
BeginMycobacteriumAviumComplex
prophylaxiswhenCD4<50100 TheMCreacRontosulfadrugsisarash
AzithromycinforMACprophylaxix AnaphylaxisisthemostworrisomeiniRal
reacRon
BeginToxoplasmosisprophylaxiswhenCD4<100 MegaloblasRcanemiawithoutneurological
TMPSMXdoublestrengthoncedaily ndingsiscommon(givefolinicacid
supplement)
154
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SULFAANTIBIOTICS(TMPSMX) MACPROPHYLAXIS
WhenCD4countisbetween50100
Azithromycinisthe1stlinedrugforMAC
prophylaxis
MustruleoutanacRveMACinfecRonbefore
starRngprophylaxis
Macrolildes(azithromycin)workbyinhibiRng
proteinsynthesisbyblockingtranslocaRon(at
50sribosome)
GIdiscomfortistheMCsideeect
TOXOPLASMOSISPROPHYLAXIS
ToxoplasmosisinfecRoninAIDSiscausedbya
latenttoxoinfecRon
StartprophylaxiswithTMPSMXwhenCD4<
100
TMPSMXmustbeuseddoublestrength
155

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