Pathogenesis

Normallyafterameal,insulingetreleasedanditstimulates enzymesthatpromotesstorageandmetabolism. Insulinrequiredforeverycellexceptbrain,RBCandheart. Promotesglycogenesisviaglucose6phosphatase.Via formationofacetylcoaitstimulatessynthesisoffattyacids, aminoacids.ProvidesenergybyenteringTCA(electron transportchain).

ManagementofDKA&HHS
Dr.samarpandhem

Infastingstateinsulindecreasesandcatabolicpathwaysare stimulated. Ifinsulindeficiencypersistscounterregulatoryhormonesare pouredin,topromoteglycogenolysis(liverandmuscle), proteindegradation(deaminationandoxidation)and lipolysis(glycerolandFFA).Thelattertworesultsinmore ketoacidsformation. InDKAthereisnoinsulinwhereasinHHSthereisstillsome insulinthatcanreduce/stoptheketoacidsproduction.

DKA:Hyperglycemia,acidemiaandketosis. HHS:Hyperglycemia,dehydrationanddecrease consciousness(coma). Overlapcanoccur.DKAcanoccurintype2diabetes. 1/3rdHHSdonothaveapriorhistoryofdiabetes. Bothcanhavelactic,uraemic,ketoacidosisorother formofmetabolicacidosis. BothDKAandHHScanhappeninthesamepatient.

DKA
Etiology:skippinginsulindose,infection,MI,emotional stress,antipsycotics,pregnancyetc.MorecommonintypeI diabetics. Cl/f:abdominalpain,N&V,dehydration,fruity smell,kussmaulbreathing,coma(10%),pleuriticchestpain. developsovershortperiodoftime. Hyperglycemia,acidemiaandketosisintheappropriate clinicalsettingarecriteriaforthediagnosisofDKA. Ph<7.3,Hco3<15mmol/landbloodglucose>14mmol/l DKAcanhappeninnormoglycaemiaaswell.

Labdiagnosis
electrolytes: K+:high,lowornormal Na:loworhigh Mg+&Po4:highorlow highaniongap+metabolicalkalosis. Ketones:acetone,acetoacetateandbetahydroxybutyrate.Can measureinplasmaanddetectinurine.Nitroprussidetestdetects onlytheformertwo. BUN:raisedduetodehydrationanddegradationofaminoacids. Creatininemayraiseduetodehydrationbutsometimes acetoacetatecanerroneouslyincreaseit. Hbraised,leucocytosis,hypertriglyceridaemia,hyperuricaemia, increasedamylaseandlipasemaybenoted.

treatment
Focusesonfluids,electrolytesandinsulin. Fluid:around100ml/kgloss(510litres). 75%offluiddeficitshouldbereplacedwithin24hours. Firsthour2LN/S,nexthour1LN/Sthentherestcontinued givecolloidsifhypotensive. Electrolytes:K lossis35mmol/kg. replaceKifnormalorlowbeforestartinginsulin. correctNa totheglucoseandseewhetheritishigh orlowandchangethefluidaccordingly. Lowphosphate(<0.4mmol)needtobecorrected. CorrectMg.

Insulin:I/Vloadingdose0.10.15units/kgfollowedby0.1 units/kgperhour. repeathourlybloodglucose. Theaimshouldbe,nottodropglucose<12mmolinthefirst 24hoursandnottostopinsulin(needtorunatleast 0.5mmol/l).Changefluidscontainingdextroseifneeded. Duringcorrectionofacidosisifurineketonesorplasma ketonesaremeasuredwecannoticethattheyareincreasing (spurious)becauseofconversionofBetahydroxybutyrateto acetone&acetoacetate. Searchforthecauseandtreatthecause

Hco3:getscorrectedasDKAresolves. GiveNaHco3(100mmol)if lifethreatinghyperkalaemia,Ph<6.9,shock unresponsivetofluids. Cancausesodiumoverload,osmoticdiuresis, intracellularacidosis,CSFacidosis,,increasedco2production, hypokalemia,volumeoverload,alteredtissueoxygenation andreboundalkalosis. doesincreasetheproductionofketonesinspiteof glucoseandinsulinbeinggiven.

complications
Hypotensionandshock:usuallyfluiddepletion,consider acidosis,cardiacarrhythmias,MI,sepsis,bleedingandadrenal insufficiencyifpersistent. Thrombosis Cerebraledema:incidenceis0.51%.Morecommonin children.Subclinicalcerebraledemahappensin50%.Risk factorsaredegreeofhypocapnia,dehydration,failureof serumsodiumtoraiseandbicarbonateuse.Theaimisnotto reducebsl<15mmol/l. Renalfailure

HHS
Hyperglycemia,dehydrationandcoma. Relativeinsufficiencyofinsulin.hasgotjustenoughinsulin thatpreventsketonebodybutcannotprevent hyperglucagonaemia,glycogenolysisandgluconeogensis. Havelesslipolytichormones(GH&cortisol)solessFFAfound. Renalimpairment:isverycommonduetoosmoticfluid losses.ElderlypeopledonothaveenoughGFRsotheycannot excreteglucoseeffectivelyasaresulttheirserumglucose levelsincreasedramatically.Azotemiahappensduetofree waterloss. Cerebralimpairmentcommonduetoimpairedthirst mechanismsorinabilitytorespondtothirstduetospeechor motordeficits. Prodromeofprogressivepolyuria,polydipsiaandpolyphagia developsoverweeksbeforedevelopingfullblownHHS. Fevercommonbutneedtor/oinfectionasacause.Rapid respiration(mostlyduetolacticacidosis).

treatment
Etiology:type2diabetes,hyperalimentation,peritoneal dialysis,thiazides,antipsychotics,betablockers,phenytoin etc. Diagnosis:BSL>3035mmol/dl lessornoketones serumosmolality>350mosm/kg Ph>7.25,Hco3>15meq/l BUN:creat>30:1 Na+highorlow. Khighorlow.
Primarygoaloftreatmentistocorrectfluidandelectrolyte replacement Fluid:give100ml/Kginthefirst12hours.Give2litresofsalinein thefirsthour. Thereafteremphasisistoprovidefreewater. Canusecorrectedsodiumasaguidetoadministerwhatsolution touse. CorrectKbeforestartinginsulintherapy Insulin: usuallyverylowdosesarerequired.(1to5units/hour) patientsareverysensitivetoinsulinandrapiddiuresisof glucosehappensoncevolumeisexpanded. Donotallowglucosetodropprecipitously. AimBSL<15mmolforthefirst24 36hrstoprevent cerebraledema.

complications
Hypotension,thrombosis,cerebraledema

THEEND