Complications of diabetes mellitus.ppt

complicationsofdiabetesmellitus ancabac rea alexandruschiopu complicationsofdiabetesmellitus acutecomplications ketoacidosisthehyperglycemichyperosmolarnonketoticsyndromehypoglycemiachroniccomplications disordersofthemicrocirculationneuropathiesnephropathiesretinopathiesmacrovascularcomplicationsfootulcers diabeticketoacidosis dka itoccurswhenketoneproductionbytheliverexceedscellularuseandrenalexcretion mostcommonlyoccursinapersonwithtype1diabetes inwhomthelackofinsulinleadstomobilizationoffattyacidsfromadiposetissuebecauseoftheunsuppressedadiposecelllipaseactivitythatbreaksdowntriglyceridesintofattyacidsandglycerol theincreaseinfattyacidlevelsleadstoketoneproductionbytheliver stressincreasesthereleaseofgluconeogenichormonesandpredisposesthepersontothedevelopmentofketoacidosis dkaoftenisprecededbyphysicaloremotionalstress suchasinfection pregnancy orextremeanxiety inclinicalpractice ketoacidosisalsooccurswiththeomissionorinadequateuseofinsulin diabeticketoacidosis dka thethreemajormetabolicderangementsindkaare hyperglycemiaketosismetabolicacidosisthedefinitivediagnosisconsistsofhyperglycemia bloodglucoselevels 250mg dl lowbicarbonate 15meq l andlowph 7 3 withketonemia positiveat1 2dilution andmoderateketonuria hyperglycemialeadstoosmoticdiuresis dehydration andacriticallossofelectrolytes hyperosmolalityofextracellularfluidsfromhyperglycemialeadstoashiftofwaterandpotassiumfromtheintracellulartotheextracellularcompartment extracellularsodiumconcentrationfrequentlyislowornormaldespiteentericwaterlossesbecauseoftheintracellular extracellularfluidshift thisdilutionaleffectisreferredtoaspseudohyponatremia serumpotassiumlevelsmaybenormalorelevated despitetotalpotassiumdepletionresultingfromprotractedpolyuriaandvomiting metabolicacidosisiscausedbytheexcessketoacidsthatrequirebufferingbybicarbonateions thisleadstoamarkeddecreaseinserumbicarbonatelevels manifestations thepersontypicallyhasahistoryof1or2daysofpolyuria polydipsia nausea vomiting andmarkedfatigue witheventualstuporthatcanprogresstocoma abdominalpainandtendernessmaybepresentwithoutabdominaldisease thebreathhasacharacteristicsmellbecauseofthepresenceofthevolatileketoacids hypotensionmaybepresentbecauseofadecreaseinbloodvolume anumberofthesignsandsymptomsthatoccurindkaarerelatedtocompensatorymechanisms theheartrateincreasesasthebodycompensatesforadecreaseinbloodvolumetherateanddepthofrespirationincrease i e kussmaul srespiration asthebodyattemptstopreventfurtherdecreasesinph treatment thegoalsintreatingdkaare toimprovecirculatoryvolumeandtissueperfusiontodecreaseserumglucosetocorrecttheacidosisandelectrolyteimbalancestheseobjectivesusuallyareaccomplishedthroughtheadministrationofinsulinandintravenousfluidandelectrolytereplacementsolutions identificationandtreatmentoftheunderlyingcause thehyperglycemichyperosmolarnonketotic hhnk syndrome thehyperglycemichyperosmolarnonketoticsyndromeischaracterizedbyhyperglycemia bloodglucose 600mg dl hyperosmolarity plasmaosmolarity 310mosm l anddehydration theabsenceofketoacidosis anddepressionofthesensorium itmayoccurinvariousconditionsincluding type2diabetesacutepancreatitissevereinfectionmyocardialinfarctiontreatmentwithoralorparenteralnutritionsolutionsitisseenmostfrequentlyinpeoplewithtype2diabetes twofactorsappeartocontributetothehyperglycemiathatprecipitatesthecondition anincreasedresistancetotheeffectsofinsulinanexcessivecarbohydrateintake thehyperglycemichyperosmolarnonketotic hhnk syndrome inhyperosmolarstates theincreasedserumosmolarityhastheeffectofpullingwateroutofbodycells includingbraincells theconditionmaybecomplicatedbythromboemboliceventsarisingbecauseofthehighserumosmolality themostprominentmanifestationsaredehydration neurologicsignsandsymptoms grandmalseizureshemiparesisaphasiamusclefasciculationshyperthermiavisualfieldlossnystagmusvisualhallucinationsexcessivethirsttheonsetofhhnksyndromeoftenisinsidious andbecauseitoccursmostfrequentlyinolderpeople itmaybemistakenforastroke treatment judiciousmedicalobservationandcarebecausewatermovesbackintobraincellsduringtreatment posingathreatofcerebraledema extensivepotassiumlossesthatalsohaveoccurredduringthediureticphaseofthedisorderrequirecorrection hypoglycemia hypoglycemiaoccursfromarelativeexcessofinsulininthebloodandischaracterizedbybelow normalbloodglucoselevels itoccursmostcommonlyinpeopletreatedwithinsulininjections butprolongedhypoglycemiaalsocanresultfromsomeoralhypoglycemicagents i e betacellstimulators manyfactorsprecipitateaninsulinreactioninapersonwithtype1diabetes including errorininsulindosefailuretoeatincreasedexercisedecreasedinsulinneedafterremovalofastresssituationmedicationchangesandachangeininsulinsitealcoholdecreaseslivergluconeogenesis andpeoplewithdiabetesneedtobecautionedaboutitspotentialforcausinghypoglycemia hypoglycemia becausethebrainreliesonbloodglucoseasitsmainenergysource hypoglycemiaproducesbehaviorsrelatedtoalteredcerebralfunction headachedifficultyinproblemsolvingdisturbedoralteredbehaviorcomaseizuresattheonsetofthehypoglycemicepisode activationoftheparasympatheticnervoussystemoftencauseshunger theinitialparasympatheticresponseisfollowedbyactivationofthesympatheticnervoussystem thiscausesanxiety tachycardia sweating andconstrictionoftheskinvessels i e theskiniscoolandclammy treatment themosteffectivetreatmentofaninsulinreactionistheimmediateingestionofaconcentratedcarbohydratesource suchassugar honey candy ororangejuice alternativemethodsforincreasingbloodglucosemayberequiredwhenthepersonhavingthereactionisunconsciousorunabletoswallow glucagonmaybegivenintramuscularlyorsubcutaneously insituationsofsevereorlife threateninghypoglycemia itmaybenecessarytoadministerglucoseintravenously thesomogyieffect thesomogyieffectdescribesacycleofinsulin inducedposthypoglycemicepisodes inpeoplewithdiabetes insulin inducedhypoglycemiaproducesacompensatoryincreaseinbloodlevelsofcatecholamines glucagon cortisol andgrowthhormone thesecounterregulatoryhormonescausebloodglucosetobecomeelevatedandproducesomedegreeofinsulinresistance thecyclebeginswhentheincreaseinbloodglucoseandinsulinresistanceistreatedwithlargerinsulindoses thehypoglycemicepisodeoftenoccursduringthenightoratatimewhenitisnotrecognized renderingthediagnosisofthephenomenonmoredifficult measurestopreventthisphenomenaincludearedistributionofdietarycarbohydratesandanalterationininsulindoseortimeofadministration thedawnphenomenon thedawnphenomenonischaracterizedbyincreasedlevelsoffastingbloodglucoseorinsulinrequirements orboth between5and9amwithoutprecedinghypoglycemia ithasbeensuggestedthatachangeinthenormalcircadianrhythmforglucosetolerance whichusuallyishigherduringthelaterpartofthemorning isalteredinpeoplewithdiabetes growthhormonehasbeensuggestedasapossiblefactor whenthedawnphenomenonoccursalone itmayproduceonlymildhyperglycemia butwhenitiscombinedwiththesomogyieffect itmayproduceprofoundhyperglycemia chroniccomplications thesedisordersoccurintheinsulin independenttissuesofthebodytissuesthatdonotrequireinsulinforglucoseentryintothecell thisprobablymeansthatintracellularglucoseconcentrationsinmanyofthesetissuesapproachorequalthoseintheblood chroniccomplicationscanbereducedbyintensivediabetictreatment peripheralneuropathies twotypesofpathologicchangeshavebeenobservedinconnectionwithdiabeticperipheralneuropathies thefirstisathickeningofthewallsofthenutrientvesselsthatsupplythenerve leadingtotheassumptionthatvesselischemiaplaysamajorroleinthedevelopmentoftheseneuralchanges thesecondfindingisasegmentaldemyelinizationprocessthataffectstheschwanncell thisdemyelinizationprocessisaccompaniedbyaslowingofnerveconduction theclinicalmanifestationsofthediabeticperipheralneuropathiesvarywiththelocationofthelesion classificationofdiabeticperipheralneuropathies somatic polyneuropathies bilateralsensory paresthesias includingnumbnessandtinglingimpairedpain temperature lighttouch two pointdiscrimination andvibratorysensationdecreasedankleandknee jerkreflexesmononeuropathiesinvolvementofamixednervetrunkthatincludeslossofsensation pain andmotorweakness amyotrophyassociatedwithmuscleweakness wasting andseverepainofmusclesinthepelvicgirdleandthigh autonomic impairedvasomotorfunctionposturalhypotensionimpairedgastrointestinalfunctiongastricatonydiarrhea oftenpostprandialandnocturnalimpairedgenitourinaryfunctionparalyticbladderincompletevoidingimpotenceretrogradeejaculationcranialnerveinvolvementextraocularnerveparalysisimpairedpupillaryresponsesimpairedspecialsenses diabeticnephropathy diabeticnephropathyistheleadingcauseofend stagerenaldisease accountingfor40 ofnewcases thetermdiabeticnephropathyisusedtodescribethecombinationoflesionsthatoftenoccurconcurrentlyinthediabetickidney themostcommonkidneylesionsinpeoplewithdiabetesarethosethataffecttheglomeruli variousglomerularchangesmayoccur includingcapillarybasementmembranethickening diffuseglomerularsclerosis andnodularglomerulosclerosis amongthesuggestedriskfactorsfordiabeticnephropathyare geneticandfamilialpredispositionelevatedbloodpressurepoorglycemiccontrolsmokinghyperlipidemiamicroalbuminuria pathogenesis threemajorhistologicchangesoccurintheglomeruliofpersonswithdiabeticnephropathy first mesangialexpansionisdirectlyinducedbyhyperglycemia perhapsviaincreasedmatrixproductionorglycosylationofmatrixproteins second gbmthickeningoccurs third glomerularsclerosisiscausedbyintraglomerularhypertension inducedbyrenalvasodilatationorfromischemicinjuryinducedbyhyalinenarrowingofthevesselssupplyingtheglomeruli theexactcauseofdiabeticnephropathyisunknown butvariouspostulatedmechanismsare hyperglycemia causinghyperfiltrationandrenalinjury advancedglycosylationproductsactivationofcytokines pathogenesis hyperglycemiaincreasestheexpressionoftransforminggrowthfactor beta tgf beta intheglomeruliandofmatrixproteinsspecificallystimulatedbythiscytokine tgf betamaycontributetothecellularhypertrophyandenhancedcollagensynthesisobservedinpersonswithdiabeticnephropathy inadditiontotherenalhemodynamicalterations patientswithovertdiabeticnephropathy dipstick positiveproteinuriaanddecreasinggfr generallydevelopsystemichypertension hypertensionisanadversefactorinallprogressiverenaldiseasesandseemsespeciallysoindiabeticnephropathy thedeleteriouseffectsofhypertensionarelikelydirectedatthevasculatureandmicrovasculature familialorperhapsevengeneticfactorsalsoplayarole certainethnicgroups particularlyafricanamericans personsofhispanicorigin andamericanindians maybeparticularlydisposedtorenaldiseaseasacomplicationofdiabetes pathogenesis retinopathies althoughpeoplewithdiabetesareatincreasedriskforthedevelopmentofcataractsandglaucoma retinopathyisthemostcommonpatternofeyedisease diabeticretinopathyischaracterizedbyabnormalretinalvascularpermeability microaneurysmformation neovascularizationandassociatedhemorrhage scarring andretinaldetachment amongthesuggestedriskfactorsassociatedwithdiabeticretinopathyarepoorglycemiccontrol elevatedbloodpressure andhyperlipidemia becauseoftheriskofretinopathy itisimportantthatpeoplewithdiabeteshaveregulardilatedeyeexaminations somepeopledevelopaconditioncalledmacularedema itoccurswhenthedamagedbloodvesselsleakfluidandlipidsontothemacula thepartoftheretinathatletsusseedetail thefluidmakesthemaculaswell whichblursvision pathogenesis diabeticretinopathyistheresultofmicrovascularretinalchanges hyperglycemia inducedthickeningofthebasementmembraneleadtoincompetenceofthevascularwalls thesedamageschangetheformationoftheblood retinalbarrierandalsomaketheretinalbloodvesselsbecomemorepermeable thelackofoxygenintheretinacausesfragile new bloodvesselstogrowalongtheretinaandintheclear gel likevitreoushumourthatfillstheinsideoftheeye withouttimelytreatment thesenewbloodvesselscanbleed cloudvision anddestroytheretina fibrovascularproliferationcanalsocausetractionalretinaldetachment thenewbloodvesselscanalsogrowintotheangleoftheanteriorchamberoftheeyeandcauseneovascularglaucoma pathogenesis diabeticretinalvascularleakage capillarynonperfusion andendothelialcelldamagearetemporaryandspatiallyassociatedwithretinalleukocytestasisinearlyexperimentaldiabetes retinalleukostasisincreaseswithindaysofdevelopingdiabetesandcorrelateswiththeincreasedexpressionofretinalintercellularadhesionmolecule 1 icam 1 severalinteractingandmutuallyperpetuatingbiochemicalpathwaysorsystems suchasthepolyolpathway nonenzymaticglycation oxidativestress proteinkinaseandtherenin angiotensinsystem maybeactivatedasaresultofsustainedhyperglycemiaindiabetes theseabnormallyactivatedpathwaysmayinturninfluenceseveralvasoactivefactorsandcytokines suchasvascularendothelialgrowthfactor interleukin 6 whichareimportantinmediatingthefunctionalandstructuralchangesofdiabeticretinopathy macrovascularcomplications diabetesmellitusisamajorriskfactorforcoronaryarterydisease cerebrovasculardisease andperipheralvasculardisease multipleriskfactorsforvasculardisease includingobesity hypertension hyperglycemia hyperlipidemia alteredplateletfunction andelevatedfibrinogenlevels frequentlyarefoundinpeoplewithdiabetes inpeoplewithtype2diabetes macrovasculardiseasemaybepresentatthetimeofdiagnosis intype1diabetes theattainedageandthedurationofdiabetesappeartocorrelatewiththedegreeofmacrovasculardisease diabeticfootulcers footproblemsarecommonamongpeoplewithdiabetesandmaybecomesevereenoughtocauseulcerationandinfection eventuallyresultinginamputation approximatel