Metabolic AcidosisMetabolic Acidosis

Alex Flaxman, MD, MSEAlex Flaxman, MD, MSE

PresentationPresentation

50 yo M, 4d h/o 50 yo M, 4d h/o vomitingvomiting & R inf chest/RUQ pn & R inf chest/RUQ pn

Wife adds 10-15 lb wt loss x4d and Wife adds 10-15 lb wt loss x4d and lethargiclethargic, , sleeping “23 hrs/day”sleeping “23 hrs/day”

Vomiting:Vomiting:– After eating, but also when doesn’t eat, NBNB. Has After eating, but also when doesn’t eat, NBNB. Has

been able to tolerate Gatorade, and has been able to tolerate Gatorade, and has increased his increased his intake of Gatorade.intake of Gatorade.

Pain:Pain:– R-sided, underneath ribs, occ rad to LR-sided, underneath ribs, occ rad to L

““Prior’s”Prior’s”

Pt in ED Pt in ED MICU 8/04 for same MICU 8/04 for same– S/p CTAP, UGI & LGI endoscopyS/p CTAP, UGI & LGI endoscopy– Investigated for Investigated for toxidrometoxidrome– Denies EtOH, home-made alcohol, antifreeze, Denies EtOH, home-made alcohol, antifreeze,

ethylene glycol, MeOH, pica, or other tox ethylene glycol, MeOH, pica, or other tox exposures. exposures. DOH visit to home.DOH visit to home.

EGD 6 wks agoEGD 6 wks ago for N/V, neg as per pt for N/V, neg as per pt

Travel 3 wks ago to Palm Beach, FLTravel 3 wks ago to Palm Beach, FL

ROSROS

General: -chills, +fatigueGeneral: -chills, +fatigue

CV:CV: CP CP

Resp:Resp: SOB, Cough SOB, Cough

GI:GI: N/V, abd pn, -diarrhea, -blood N/V, abd pn, -diarrhea, -blood

GU:GU: -freq/hematuria/urgency -freq/hematuria/urgency

All:All: NKDANKDAPMH:PMH:Depression x2yrs, hyperchol, discDepression x2yrs, hyperchol, disc

herniations Lherniations L33, L, L44, L, L55 s/p bk inj s/p bk inj

PSH:PSH: Laminectomy x2, UGI, LGI,Laminectomy x2, UGI, LGI,EGD 6 wks agoEGD 6 wks ago

Meds:Meds: Compazine x1d, Nexium, Zoloft,Compazine x1d, Nexium, Zoloft,Vicodin, SommaVicodin, Somma

PMD:PMD:@BI@BI

Tobacco:Tobacco: 1 ppd, h/o 2-3 ppd1 ppd, h/o 2-3 ppd

EtOH:EtOH: DeniesDenies

Drugs:Drugs: DeniesDenies

Vital SignsVital Signs

BP BP 161/103161/103

P P 129129

RR 2424

OO22 97%97%

TT 99.4 PR99.4 PR

PnPn 10/1010/10

ExamExam

General:General: WDWN, NAD, WDWN, NAD, tachypneictachypneicPul:Pul: CTABCTAB

CV:CV: Tachy, reg, STachy, reg, S11, S, S22, -m/r/g, -m/r/g

Abd:Abd: NABS, RUQ tend, epig tend, NABS, RUQ tend, epig tend, +masses-+masses-

liver edge ~ 9 cm inf to costal marginliver edge ~ 9 cm inf to costal marginRectal:Rectal: Guaiac neg w/ no stoolGuaiac neg w/ no stoolExt:Ext: -edema, hyperpig L foot cool-edema, hyperpig L foot cool

R R PT 2+PT 2+ DP +DopplerDP +DopplerLL PT +DopplerPT +Doppler DP +DopplerDP +Doppler

EKGEKGSR @ 124 w/ LAESR @ 124 w/ LAE

? Q II, aVF (new from 8/31/04)? Q II, aVF (new from 8/31/04)

? ST elev V2, V3? ST elev V2, V3

Sinus tach new from 8/21/04Sinus tach new from 8/21/04

CXRCXRNAD, -free airNAD, -free air

NG LavageNG Lavage

Yellow-green material, no bloodYellow-green material, no blood

What labs do you want?What labs do you want?

17.1

50.916.3 465

N 96L 3M 3

136 3112

6 1179

10.3

4.3

LabsLabs

13.6

31.51.2

Lipase 159Troponin 0.02

More LabsMore Labs

UACloudyProt 100WBC 0-5RBC 0-3Hyaline Casts 0-5

AST 74ALT 6Alk 163TB 3.6DB 0Alb 5.2TP 9.7

Lactate 2.2

Acetone neg

EtOH 0

Serum osmolarity 290

Now What?Now What?

ABGABG

136 112

6

RecallRecall

7.12 / 18 / 105 / RA / 8.37.12 / 18 / 105 / RA / 8.3

Rule 1: Acidosis or AlkalosisRule 1: Acidosis or Alkalosis

AcidosisAcidosis

7.12 / 18 / 105 / RA / 8.37.12 / 18 / 105 / RA / 8.3

Rule 2: Metabolic, Respiratory, BothRule 2: Metabolic, Respiratory, Both

MetabolicMetabolic

7.12 / 18 / 105 / RA / 8.37.12 / 18 / 105 / RA / 8.3

AG = ?AG = ?

Rule 3: Anion GapRule 3: Anion Gap

= Na – Cl – HCO= Na – Cl – HCO33

136 112

6

7.12 / 18 / 105 / RA / 8.37.12 / 18 / 105 / RA / 8.3

= 136 – 112 – 6= 136 – 112 – 6= 18= 18

So we have an…So we have an…

Anion Gap Metabolic AcidosisAnion Gap Metabolic Acidosis

Rule 4: Degree of CompensationRule 4: Degree of Compensation

For metabolic acidosis,For metabolic acidosis,

Expected PExpected PCOCO22 = 1.5(HCO3) + 8 = 1.5(HCO3) + 8 ± 2± 2

= 1.5(6) + 8 ± 2= 1.5(6) + 8 ± 2

= 9 + 8 ± 2= 9 + 8 ± 2

= 17 ± 2= 17 ± 2

= 15, 19= 15, 19

Actual Actual PPCOCO22 is 18 is 18 appropriate compensation appropriate compensation

7.12 / 18 / 105 / RA / 8.37.12 / 18 / 105 / RA / 8.3

Rule #5: Rule #5: δδ//δδ

Any takers?Any takers?

136 112

6

7.12 / 18 / 105 / RA / 8.37.12 / 18 / 105 / RA / 8.3

AG = 18 (nl 6.6-10.6)

HCO3 = 6 (nl 24)

Rule #5: Rule #5: δδ//δδ

AG should be 10 but is now 18, for a AG should be 10 but is now 18, for a difference of difference of 88

The AG went up by The AG went up by 88, so the , so the HCOHCO33 should should go down by go down by 88..

So HCOSo HCO33 should be 24 – should be 24 – 88 = 16 but is = 16 but is really 6.really 6.

The HCO3 is lower than predicted so there is also a concurrent non-AG metabolic acidosis.

Causes of AG Metabolic AcidosisCauses of AG Metabolic AcidosisMUD PILESMUD PILES

Methanol: wood Methanol: wood alcohol, grain alcohol alcohol, grain alcohol (moonshine), paint (moonshine), paint thinners, windshield thinners, windshield washer fluidwasher fluid

UremiaUremia

DKA, AKADKA, AKA

Paraldehyde, Paraldehyde, propylene glycolpropylene glycol

Ingestions (INH, iron, Ingestions (INH, iron, XTC, cocaine)XTC, cocaine)

Lactic AcidosisLactic Acidosis

EtOH, Ethylene glycolEtOH, Ethylene glycol

SalicylatesSalicylates

Other causesOther causes

““P” – PhenforminP” – PhenforminToluene poisoning (glue sniffing)Toluene poisoning (glue sniffing)Other organic acidsOther organic acids– Lactic acidLactic acid– AcetoneAcetone– Ketoacids: hydroxybutyrate / acetoacetateKetoacids: hydroxybutyrate / acetoacetate– Hippuric AcidHippuric Acid– 5-oxyproline5-oxyproline– SalicylatesSalicylates

Lactic AcidosisLactic Acidosis

Usually increase in the L isomerUsually increase in the L isomer– Type AType A

2° to hypoxia (hypoperfusion, sepsis)2° to hypoxia (hypoperfusion, sepsis)

– Type BType BNot d.t. hypoxia: seizures, liver failure, thiamine Not d.t. hypoxia: seizures, liver failure, thiamine deficiencydeficiency

D-Lactic AcidosisD-Lactic Acidosis- increase in the D - increase in the D isomerisomer

D-LactateD-Lactate

D-Lactate: External SourcesD-Lactate: External Sources

Ingestion of fermented fruits and Ingestion of fermented fruits and vegetables: pickles, yogurt, sauerkrautvegetables: pickles, yogurt, sauerkraut

LR and dialysate contain dl-lactate (50/50)LR and dialysate contain dl-lactate (50/50)

Propylene glycol ?metabolism?Propylene glycol ?metabolism?

D-Lactate: Internal SourcesD-Lactate: Internal Sources

In the gut, glucose is metabolized by flora In the gut, glucose is metabolized by flora to lactate:to lactate:

l-Lactatel-Lactate

d-Lactated-Lactate

Produced via the methyl-glyoxal pathway Produced via the methyl-glyoxal pathway (part of threonine catabolism)(part of threonine catabolism)(threonine is an essential amino acid)(threonine is an essential amino acid)

D-Lactate: Internal SourcesD-Lactate: Internal Sources

Pyruvate ↔ Pyruvate ↔ dl-Lactate via Lactate Dehydrogenasedl-Lactate via Lactate Dehydrogenase

BUTBUT

Pyruvate ↔ l-Lactate requires l-LDHPyruvate ↔ l-Lactate requires l-LDH

Pyruvate ↔ d-Lactate requires d-LDHPyruvate ↔ d-Lactate requires d-LDH

Mammals do not have d-LDHMammals do not have d-LDH

D-Lactate: Getting rid of itD-Lactate: Getting rid of it

Slowly metabolized? Not.Slowly metabolized? Not.

d-hydroxy-acid-dehydrogenased-hydroxy-acid-dehydrogenase– Mitochondrial enzymeMitochondrial enzyme– In many tissues (especially liver and kidney)In many tissues (especially liver and kidney)– Converts d-lactate (and other substrates) to Converts d-lactate (and other substrates) to

pyruvatepyruvate

But overall, d-lactate is metabolized more But overall, d-lactate is metabolized more slowly than l-lactateslowly than l-lactate

D-Lactic AcidosisD-Lactic Acidosis

An increase in D-Lactate (duh)An increase in D-Lactate (duh)

SymptomsSymptoms

AMSAMSSlurred speechSlurred speechConfusionConfusionInability to Inability to concentrateconcentrateSomnolenceSomnolenceHallucinationsHallucinationsClumsinessClumsiness

WeaknessWeaknessAtaxia / unsteady gaitAtaxia / unsteady gaitNystagmusNystagmusIrritableIrritableAbusive behaviorAbusive behaviorPtosisPtosisAsterixisAsterixis

TachypneaTachypnea

Risk FactorRisk Factor

Anything that results in increased delivery of Anything that results in increased delivery of undigested carbohydrates to the colonundigested carbohydrates to the colon

Risk FactorsRisk Factors

Short Bowel SyndromeShort Bowel Syndrome#1 Surgical resection#1 Surgical resection

#2 Intestinal bypass (bariatric surgery)#2 Intestinal bypass (bariatric surgery)– Feeding tube placementFeeding tube placement

Intestinal malabsorption?Intestinal malabsorption?– Chronic pancreatitisChronic pancreatitis

Risk Factors Not from the H&PRisk Factors Not from the H&P

Alteration of normal colon flora to a Alteration of normal colon flora to a predominance of Gm+ anaerobes predominance of Gm+ anaerobes (lactobacillus)(lactobacillus)

? Colonic stagnation? Colonic stagnation

Impaired metabolismImpaired metabolism

Precipitating FactorsPrecipitating Factors

Excessive oral food intakeExcessive oral food intake– Especially carbohydrates (like Especially carbohydrates (like GatoradeGatorade))

Change in enteral feeding formulaChange in enteral feeding formula

LabsLabs

Renal function normal or abnormalRenal function normal or abnormal

AG Metabolic acidosisAG Metabolic acidosis– Can have non-AG metabolic acidosisCan have non-AG metabolic acidosis

Elevated serum or urine D-lactateElevated serum or urine D-lactate– Serum level > 3 mmol/LSerum level > 3 mmol/L

Ancillary TestsAncillary Tests

LP: CSF D-lactate levels same as serumLP: CSF D-lactate levels same as serum

EEG: b/l diffuse, high-voltage slow waves EEG: b/l diffuse, high-voltage slow waves without focal abnormalitywithout focal abnormality

Stool culture: predominance of Gm+ Stool culture: predominance of Gm+ anaerobic organismsanaerobic organisms– LactobacillusLactobacillus– BifidobacteriumBifidobacterium– EubacteriumEubacterium

Immediate TreatmentImmediate Treatment

A-B-CA-B-C

NPONPO

IV dextrose (e.g. D5NS)IV dextrose (e.g. D5NS)

TreatmentTreatment

SupportiveSupportive

Adjust feeding tubeAdjust feeding tube

Adjust enteral feeding formulaAdjust enteral feeding formula

Change diet to starch instead of carbohydrates Change diet to starch instead of carbohydrates recurrent attacksrecurrent attacks

Surgical: reanastomosisSurgical: reanastomosis

Oral abx: neomycin, vanco, kanamycin, metroOral abx: neomycin, vanco, kanamycin, metro

Bicarb- unclearBicarb- unclear

TreatmentTreatment

Increase luminal pHIncrease luminal pH– CaCOCaCO33, MgCl, MgCl22– HCOHCO33

AbxAbx– Oral vanco, metro, or neomycinOral vanco, metro, or neomycin

Although can cause overgrowth of lactobacillusAlthough can cause overgrowth of lactobacillus

DialysisDialysis– Corrects acidosisCorrects acidosis– Clears d-LactateClears d-Lactate

Other Interesting PointsOther Interesting Points

d-Lactate levels correlate poorly with d-Lactate levels correlate poorly with symptomssymptoms

Normal humans infused with d-lactate do Normal humans infused with d-lactate do not develop symptomsnot develop symptoms

Other acidoses to the same pH do not Other acidoses to the same pH do not cause similar symptomscause similar symptoms

Final dorky Interesting PointFinal dorky Interesting Point

AG metabolic acidosis AG metabolic acidosis andand concurrent concurrent non-AG metabolic acidosisnon-AG metabolic acidosis

Why?Why?

136 112

6

7.12 / 18 / 105 / RA / 8.37.12 / 18 / 105 / RA / 8.3

Final dorky Interesting PointFinal dorky Interesting Point

In D-lactate acidosis the increase in the In D-lactate acidosis the increase in the AG tends to be less than the decrease in AG tends to be less than the decrease in the HCO3.the HCO3.

In L-lactic acidosis where the increase in In L-lactic acidosis where the increase in the AG tends to be greater than the the AG tends to be greater than the reduction in the bicarb.reduction in the bicarb.

Final dorky Interesting PointFinal dorky Interesting Point

1.1. Much lower renal threshold for d-lactate Much lower renal threshold for d-lactate than for l-lactatethan for l-lactate

2.2. Loss of the sodium salt of D-lactic acid in Loss of the sodium salt of D-lactic acid in the stool (the H+ is resorbed from the the stool (the H+ is resorbed from the lumen or reacts with secreted HCOlumen or reacts with secreted HCO33) but ) but

the organic ion does notthe organic ion does not

Take Home Points- GeneralTake Home Points- General

1.1. Consider ABG’s more oftenConsider ABG’s more often

2.2. Look for causes of metabolic acidosisLook for causes of metabolic acidosis

3.3. In unclear cases, or cases where MUD PILES In unclear cases, or cases where MUD PILES fails, send tests for organic acids (e.g. d-fails, send tests for organic acids (e.g. d-lactate and ß-hydroxybutyrate)lactate and ß-hydroxybutyrate)

4.4. Involve intensivist earlyInvolve intensivist early

Take Home Points- d-LactateTake Home Points- d-Lactate

1.1. For patients with short bowel (or other For patients with short bowel (or other malabsorption risks), consider D-lactic malabsorption risks), consider D-lactic acidosis.acidosis.

2.2. Also consider when AG acidosis and:Also consider when AG acidosis and:a)a) Nl “lactate” levels and no acetoneNl “lactate” levels and no acetone

b)b) Short bowel or other malabsorption syndromeShort bowel or other malabsorption syndrome

c)c) Preceded by food ingestion (and symptoms Preceded by food ingestion (and symptoms improve after discontinuation)improve after discontinuation)

d)d) Characteristic neurological findingsCharacteristic neurological findings