CPPDKA05.ppt - CLINICAL PATHOPHYSIOLOGY CASE 4

CLINICAL CLINICAL PATHOPHYSIOLOGYPATHOPHYSIOLOGY

CASE 4CASE 4

Janet Lin, MD, MPHJanet Lin, MD, MPH

Assistant ProfessorAssistant Professor

Department of Emergency Department of Emergency MedicineMedicine

Emergency Department Emergency Department PresentationPresentation

• 22 y.o. female22 y.o. female

• VomitingVomiting– Multiple episodesMultiple episodes– 2 days duration2 days duration

• Lethargic, but Lethargic, but arousablearousable

• Abdominal painAbdominal pain– GeneralizedGeneralized

HISTORY OF PRESENT HISTORY OF PRESENT ILLNESSILLNESS

• No feverNo fever

• No chillsNo chills

• No prior similar episodesNo prior similar episodes

• OtherOther

PAST MEDICAL HISTORYPAST MEDICAL HISTORY

• NoneNone

• No medicationsNo medications

VITAL SIGNSVITAL SIGNS

• Pulse 120Pulse 120

• Respirations 36Respirations 36

• Blood pressure Blood pressure 100/60100/60

• Temperature 98Temperature 9800FF

• Oxygen saturation Oxygen saturation 100%100%

• Pain: nonePain: none

PHYSICAL EXAMINATIONPHYSICAL EXAMINATION

• Skin: pale & drySkin: pale & dry

• Mucous Mucous membranes: dry & membranes: dry & crackedcracked

• Heart: normal with Heart: normal with tachycardiatachycardia

• Lungs: clear with Lungs: clear with tachypneatachypnea

PHYSICAL EXAMINATIONPHYSICAL EXAMINATION

• Abdomen: soft, Abdomen: soft, minimally tenderminimally tender

• Neuro: no focal Neuro: no focal findingsfindings

• No evidence of No evidence of traumatrauma

Conclusions?

DIFFERENTIAL DIAGNOSISDIFFERENTIAL DIAGNOSIS

• 1.1.

• 2.2.

• 3.3.

• 4.4.

• 5.5.

• 6.6.

DIAGNOSTIC TESTSDIAGNOSTIC TESTS

• Blood testsBlood tests

• Urine testsUrine tests

• Radiology testsRadiology tests

• Special testsSpecial tests

Why is each test ordered?

BEDSIDE GLUCOSE TESTINGBEDSIDE GLUCOSE TESTING

• Glucose oxidase Glucose oxidase reagent stripreagent strip

• Light meter Light meter increases increases sensitivitysensitivity

• Sensitive to light, Sensitive to light, heat, moistureheat, moisture

• More accurate in More accurate in the low rangethe low range

Accucheck: 180-240 mg/dL

DIAGNOSTIC TESTSDIAGNOSTIC TESTSElectrocardiogram (ECG)Electrocardiogram (ECG)

• Normal sinus Normal sinus rhythm rhythm

• Normal T-wavesNormal T-waves

• No ST changesNo ST changes

Look for evidence of hyperkalemia!

BEDSIDE DIAGNOSTIC BEDSIDE DIAGNOSTIC TESTSTESTS• Urine glucose and Urine glucose and

acetoneacetone– ClinitestClinitest– AcetestAcetest– Chemstrips bGChemstrips bG

Glucose: 4+

Ketones: 2+

DIAGNOSTIC TESTSDIAGNOSTIC TESTS

• Blood testsBlood tests– Serum ElectrolytesSerum Electrolytes

NaNa ClCl BUNBUNGluGlu

KK COCO22 CrCr

130130 100100 3030540540

4.04.0 1212 1.81.8

CORRECTION FOR SERUM CORRECTION FOR SERUM SODIUMSODIUM

• The sodium level is reduced by 1.6 The sodium level is reduced by 1.6 mEq/L for every 100 mg/dL the mEq/L for every 100 mg/dL the glucose level is over 100 mg/dLglucose level is over 100 mg/dL

• 540 mg/dL – 100 mg/dL = 440 mg/dL540 mg/dL – 100 mg/dL = 440 mg/dL

• 1.6 X 4.4 = 7.041.6 X 4.4 = 7.04

• Corrected Sodium = 130 +7 = 137 Corrected Sodium = 130 +7 = 137 mEq/LmEq/L

Estimation of Serum Potassium Estimation of Serum Potassium if pH were Normalif pH were Normal

• Serum potassium will fall by 0.6 Serum potassium will fall by 0.6 mEq/L for each 0.1 increase in pHmEq/L for each 0.1 increase in pH

• pH 7.4 – 7.2 = 0.2pH 7.4 – 7.2 = 0.2

• 0.2 x 0.6 mEq/L = 1.2 mEq/L0.2 x 0.6 mEq/L = 1.2 mEq/L

• 4.0 mEq/L – 1.2 mEq/L = 2.8 mEq/L4.0 mEq/L – 1.2 mEq/L = 2.8 mEq/L– The expected serum potassium level The expected serum potassium level

when pH is corrected will be when pH is corrected will be dangerously lowdangerously low

DIAGNOSTIC TESTSDIAGNOSTIC TESTS

• Arterial blood gases:Arterial blood gases:– pH: 7.20pH: 7.20

– POPO22: 105 mmHg: 105 mmHg

– PCOPCO2 2 : 20 mmHg: 20 mmHg

– HCOHCO33--: 12 mEq/L: 12 mEq/L

Metabolic Acidosis with Respiratory Compensation

DIAGNOSTIC TESTSDIAGNOSTIC TESTS

• Serum acetone: + @ 1:8 dilutionSerum acetone: + @ 1:8 dilution

SERUM OSMOLALITYSERUM OSMOLALITY

• Correlates to mental statusCorrelates to mental status

• Measured by freezing point Measured by freezing point depressiondepression

• Calculated from clinical chemistriesCalculated from clinical chemistries– OSM = 2(Na) + Glu/18 + BUN/3OSM = 2(Na) + Glu/18 + BUN/3– OSM = 2(130) + 540/18 + 30/3OSM = 2(130) + 540/18 + 30/3– OSM = 300 mOSM/LOSM = 300 mOSM/L– Normal OSM = 285 – 295 mOSM/LNormal OSM = 285 – 295 mOSM/L

DIABETES MELLITUSDIABETES MELLITUS

• First described in Egypt 3000 years First described in Egypt 3000 years agoago

• Estimated true prevalence: 18.2 Estimated true prevalence: 18.2 million Americansmillion Americans

• Annual cost: $132 billionAnnual cost: $132 billion

• Initial presentation is diabetic Initial presentation is diabetic ketoacidosis (DKA) in 10% of casesketoacidosis (DKA) in 10% of cases

DIABETIC KETOACIDOSIS (DKA)DIABETIC KETOACIDOSIS (DKA)

• State of State of endocrinologic endocrinologic imbalanceimbalance– Insulin deficiencyInsulin deficiency– Counter-regulatory Counter-regulatory

hormone excesshormone excess

DIABETIC KETOACIDOSIS (DKA)DIABETIC KETOACIDOSIS (DKA)Biochemical CharacteristicsBiochemical Characteristics

• HyperglycemiaHyperglycemia– Blood sugar > 300 Blood sugar > 300

mg/dLmg/dL

• KetonemiaKetonemia– Serum ketones positive Serum ketones positive

at at >> 1:2 dilution 1:2 dilution (sodium nitroprusside (sodium nitroprusside test)test)

• AcidosisAcidosis– pH < 7.30pH < 7.30

– HCOHCO33-- < 15 mEq/L < 15 mEq/L

Hyperglycemia

AcidosisKetonemia

DKA

Factors Predisposing to the Factors Predisposing to the Development of DKADevelopment of DKA• Lack of adequate knowledge of the Lack of adequate knowledge of the

disease (2/3)disease (2/3)• Psychological problemsPsychological problems• Financial difficultiesFinancial difficulties• Intercurrent illness (> 80%)Intercurrent illness (> 80%)

– Infection (30-40%)Infection (30-40%)– VomitingVomiting– Myocardial infarctionMyocardial infarction– CVACVA– PregnancyPregnancy– Other stressorsOther stressors

PATHOPHYSIOLOGY OF DKAPATHOPHYSIOLOGY OF DKA

DKA

COUNTER-REGULATORY HORMONE EXCESS

INSULIN DEFICIENCY

INSULIN DEFICIENCYINSULIN DEFICIENCY

• Relative or Relative or absoluteabsolute

• Prevents glucose Prevents glucose from entering cellsfrom entering cells

• Intracellular Intracellular “starvation”“starvation”

COUNTER-REGULATORY COUNTER-REGULATORY HORMONES HORMONES

• Stress and intracellular starvation Stress and intracellular starvation cause release of:cause release of:– CatecholaminesCatecholamines– GlucagonGlucagon– CortisolCortisol– Growth hormoneGrowth hormone

COUNTER-REGULATORY COUNTER-REGULATORY HORMONE EFFECTSHORMONE EFFECTS

• GluconeogenesisGluconeogenesis•Breakdown of proteins and conversion of Breakdown of proteins and conversion of

amino acids into glucoseamino acids into glucose

• GlycogenolysisGlycogenolysis•Breakdown of liver glycogen into glucoseBreakdown of liver glycogen into glucose

• LipolysisLipolysis•Breakdown of adipose tissue into non-Breakdown of adipose tissue into non-

esterified fatty acids (NEFA)esterified fatty acids (NEFA)

PATHOPHYSIOLOGY OF DKAPATHOPHYSIOLOGY OF DKA

• Hyperglycemia Hyperglycemia results from:results from:– Blockage of Blockage of

intracellular glucose intracellular glucose transporttransport

– Counter-regulatory Counter-regulatory hormone effectshormone effects

Insulin Deficiency

Hyperglycemia

CRH Excess

Effects of Hyperglycemia in Effects of Hyperglycemia in DKADKA

HYPERGLYCEMIA

HYPEROSMOLARITY GLUCOSURIA

Mental StatusChanges

Effects of Hyperglycemia in Effects of Hyperglycemia in DKADKA

GLUCOSURIA

OSMOTIC DIURESIS

DEHYDRATION

Effects of Hyperglycemia in Effects of Hyperglycemia in DKADKA

KETOACIDS

HYDROGEN IONS

ACIDOSISACIDOSIS

PATHOPHYSIOLOGY OF DKAPATHOPHYSIOLOGY OF DKA

ELECTROLYTE IMBALANCE

ACIDOSIS DEHYDRATION

DIAPHORESIS TACHYPNEA

PATHOPHYSIOLOGY OF DKAPATHOPHYSIOLOGY OF DKA

DEHYDRATION

SHOCK

INCREASEDACIDOSIS

DECREASED GFR

ACUTE TUBULAR NECROSIS

INCREASED HYPERGLYCEMIA

CLINICAL PRESENTATIONCLINICAL PRESENTATIONEarly SymptomsEarly Symptoms

• Due to hyperglycemiaDue to hyperglycemia– PolyuriaPolyuria– PolydipsiaPolydipsia– PolyphagiaPolyphagia– Visual disturbancesVisual disturbances

• Due to muscle breakdown and dehydrationDue to muscle breakdown and dehydration– Weight lossWeight loss– WeaknessWeakness

CLINICAL PRESENTATIONCLINICAL PRESENTATIONLater SymptomsLater Symptoms

• Due to ketonemiaDue to ketonemia– AnorexiaAnorexia– NauseaNausea– VomitingVomiting– Fruity acetone breathFruity acetone breath

• Due to acidosisDue to acidosis– Abdominal painAbdominal pain– Kussmaul respirations (deep, regular, Kussmaul respirations (deep, regular,

sighing)sighing)

CLINICAL PRESENTATIONCLINICAL PRESENTATIONLater SymptomsLater Symptoms

• Due to hyperosmolarityDue to hyperosmolarity– Altered level of consciousnessAltered level of consciousness

•Alert patients have OSM < 330 mOSM/kgAlert patients have OSM < 330 mOSM/kg

•20% of patients are alert20% of patients are alert

•10% of patients are comatose10% of patients are comatose

CLINICAL PRESENTATIONCLINICAL PRESENTATIONLater SymptomsLater Symptoms

• Due to Due to hypokalemiahypokalemia– Gastric stasis and Gastric stasis and

ileusileus– Muscle crampsMuscle cramps– Cardiac Cardiac

dysrhythmiasdysrhythmias

CLINICAL PRESENTATIONCLINICAL PRESENTATIONDKA PearlsDKA Pearls

• Vague symptomsVague symptoms

• Hyperpyrexia rareHyperpyrexia rare

• Severe in cases in Severe in cases in those who cannot those who cannot communicatecommunicate

• Signs & Symptoms ≠ Signs & Symptoms ≠ Biochemical Biochemical AbnormalityAbnormality

• Dehydrated patient Dehydrated patient who is still voiding = who is still voiding = DKADKA

DIABETIC KETOACIDOSIS DIABETIC KETOACIDOSIS Differential DiagnosisDifferential Diagnosis

• HypoglycemiaHypoglycemia

• MeningitisMeningitis

• Acute abdomenAcute abdomen

• GastroenteritisGastroenteritis

• Respiratory Respiratory infectioninfection

• Toxic ingestionToxic ingestion

• CVACVA

• Brainstem Brainstem hemorrhagehemorrhage

• UremiaUremia

• Alcoholic Alcoholic ketoacidosisketoacidosis

• Starvation ketosisStarvation ketosis

DKA MANAGEMENTDKA MANAGEMENT

• INTRAVENOUS FLUID INTRAVENOUS FLUID ADMINISTRATIONADMINISTRATION

• INSULIN THERAPY INSULIN THERAPY

• ELECTROLYTESELECTROLYTES

• MONITOR USING A FLOW SHEETMONITOR USING A FLOW SHEET

• (BICARBONATE THERAPY)(BICARBONATE THERAPY)

DKA MANAGEMENTDKA MANAGEMENT

• INTRAVENOUS FLUID ADMINISTRATIONINTRAVENOUS FLUID ADMINISTRATION– Lowers blood glucose by as much as 18%Lowers blood glucose by as much as 18%– Normalizes pHNormalizes pH– Normal saline, 1 L over 30 minNormal saline, 1 L over 30 min– Then, Normal saline, 1 L over 1-2 hThen, Normal saline, 1 L over 1-2 h– Then, 0.5 NS @ 300-500 mL/h, guided by Then, 0.5 NS @ 300-500 mL/h, guided by

urine outputurine output

DKA MANAGEMENTDKA MANAGEMENTElectrolytesElectrolytes

• PotassiumPotassium– Level will fall precipitously with Level will fall precipitously with

treatmenttreatment– Hold only if peaked T-waves on ECGHold only if peaked T-waves on ECG– 20-40 mEq in the first liter of fluid20-40 mEq in the first liter of fluid

•½ as chloride½ as chloride

•½ as phosphate½ as phosphate

– Monitor hourlyMonitor hourly

DKA MANAGEMENTDKA MANAGEMENTFlow SheetFlow Sheet

• Hourly Hourly ObservationsObservations– ElectrolytesElectrolytes– GlucoseGlucose– OsmolalityOsmolality– Blood gasesBlood gases– OutputOutput– Vital signsVital signs– Mental statusMental status

DKA MANAGEMENTDKA MANAGEMENTInsulin TherapyInsulin Therapy

• Route of Route of AdministrationAdministration– IM: delayed absorptionIM: delayed absorption– SQSQ

• High doses High doses

• Rapid fluctuationsRapid fluctuations

– IV continuous infusionIV continuous infusion• Low doseLow dose

• Linear declineLinear decline

• Less hypoglycemiaLess hypoglycemia

• Less hypokalemiaLess hypokalemia

• Adjustments easyAdjustments easy

DKA MANAGEMENTDKA MANAGEMENTInsulin TherapyInsulin Therapy

• IV continuous IV continuous infusioninfusion

• 0.1 unit/kg/h0.1 unit/kg/h• Loading dose of 0.1 Loading dose of 0.1

unit/kg used by someunit/kg used by some• For BS>1000; 0.05 For BS>1000; 0.05

units/kg/hunits/kg/h• When BS reaches 300, When BS reaches 300,

reduce to 0.05 reduce to 0.05 units/kg/h & add units/kg/h & add glucose to the fluidglucose to the fluid

• Continue until acidosis Continue until acidosis corrected, BS controlled corrected, BS controlled & ketonemia resolved.& ketonemia resolved.

DKA MANAGEMENTDKA MANAGEMENTBicarbonate TherapyBicarbonate Therapy

• ComplicationsComplications– Shift of oxyhemoglobin dissociation Shift of oxyhemoglobin dissociation

curve to the leftcurve to the left– Hypokalemia & hypomagnesemiaHypokalemia & hypomagnesemia– Overcorrection alkalosisOvercorrection alkalosis– Paradoxical CSF acidosisParadoxical CSF acidosis– Cerebral edemaCerebral edema

• Evidence for effectiveness: lackingEvidence for effectiveness: lacking

DKA MANAGEMENTDKA MANAGEMENTBicarbonate TherapyBicarbonate Therapy

• Consider only if pH < 7.0Consider only if pH < 7.0

• If used, DO NOT PUSH!If used, DO NOT PUSH!– Administer as 1-2 mEq/kg over 2 hAdminister as 1-2 mEq/kg over 2 h

DKA DISPOSITIONDKA DISPOSITION

• ICUICU– Age < 2 years or > 60 yearsAge < 2 years or > 60 years– pH < 7.0pH < 7.0– Serious concurrent illnessSerious concurrent illness– (Blood sugar > 1000)(Blood sugar > 1000)

• Outpatient ManagementOutpatient Management– AlertAlert– No persistent vomitingNo persistent vomiting– Mild acidosis, ketonemia & dehydrationMild acidosis, ketonemia & dehydration

DKA SUMMARYDKA SUMMARY

• DKA may be the presenting complaint DKA may be the presenting complaint in new diabetics, up to 10% of the timein new diabetics, up to 10% of the time

• DKA is a state of endocrinological DKA is a state of endocrinological imbalance involving insulin AND imbalance involving insulin AND counter-regulatory hormonescounter-regulatory hormones

• DKA is characterized by the presence of DKA is characterized by the presence of hyperglycemia, acidosis and ketonemia.hyperglycemia, acidosis and ketonemia.

DKA SUMMARYDKA SUMMARY

• Laboratory evaluation of the DKA patient is Laboratory evaluation of the DKA patient is complex and must be repeated on an complex and must be repeated on an hourly basis until the patient is stablehourly basis until the patient is stable

• The most important components of the The most important components of the management of the DKA patient are fluid management of the DKA patient are fluid and electrolyte management. and electrolyte management.

• Insulin is an essential but secondary Insulin is an essential but secondary component of management. component of management.

• Bicarbonate therapy is rarely indicated. Bicarbonate therapy is rarely indicated.