Acid-Base Disorders Bradley J. Phillips, MD Burn-Trauma-ICU Adults & Pediatrics.

Acid-Base Disorders

Bradley J. Phillips, MDBradley J. Phillips, MD

Burn-Trauma-ICUBurn-Trauma-ICU

Adults & PediatricsAdults & Pediatrics

Definition

Normal pH = 7.35 - 7.45Normal pH = 7.35 - 7.45 AcidosisAcidosis

Primary respiratory = PPrimary respiratory = PCO2 CO2 > 44> 44

Primary metabolic = HCOPrimary metabolic = HCO33 < 22 < 22

Severe acidemia pH < 7.2Severe acidemia pH < 7.2 AlkalosisAlkalosis

Primary respiratory = PPrimary respiratory = PCO2CO2 < 36 < 36

Primary metabolic = HCOPrimary metabolic = HCO3 3 > 26> 26

Severe alkalosis pH > 7.6Severe alkalosis pH > 7.6

Acid-Base Homeostasis

Acid Metabolism (70 mmol/day)Acid Metabolism (70 mmol/day) sulphuric acid 25 mmol (aminoacid catabolism)sulphuric acid 25 mmol (aminoacid catabolism) organic acids 40 mmol (non-metabolized)organic acids 40 mmol (non-metabolized) phosphoric acid and othersphosphoric acid and others

Extracellular space contains 350 mmol HCOExtracellular space contains 350 mmol HCO33

Renal tubulesRenal tubules proximal reabsorbs 3800 mmol/d (85%)proximal reabsorbs 3800 mmol/d (85%) thick ascending limb reabsorbs 450 mmol (10%)thick ascending limb reabsorbs 450 mmol (10%) collecting duct generates new HCOcollecting duct generates new HCO3 3 (NH(NH44/PO/PO44))

Metabolic Disorders

CharacteristicsCharacteristics Change in HCOChange in HCO33

pH and pCOpH and pCO22 change change samesame direction direction

Respiratory Disorders

CharacteristicsCharacteristics Change in PCOChange in PCO22

pH and PCOpH and PCO2 2 change in change in differentdifferent directions directions

Acute and chronic Acute and chronic

Compensation

Correct pH to normalCorrect pH to normal NONO overcompensation overcompensation

exceptionexception: exogenous mechanism: exogenous mechanism Primary metabolic - respiratory change (PPrimary metabolic - respiratory change (PCO2CO2))

Primary respiratory - metabolic change (HCOPrimary respiratory - metabolic change (HCO33))

Physiologic Effects

AcidosisAcidosis Decreased myocardial contractilityDecreased myocardial contractility Decreased diaphragmatic contractilityDecreased diaphragmatic contractility Reduced threshold for ventricular fibrillationReduced threshold for ventricular fibrillation Complex and variable derangements in vascular smooth Complex and variable derangements in vascular smooth

muscle (sympathetic vs. catecholamines)muscle (sympathetic vs. catecholamines) Increased cerebral blood flowIncreased cerebral blood flow Variable effects upon serum electrolytesVariable effects upon serum electrolytes Alterations in drug mechanismsAlterations in drug mechanisms Shifts OShifts O22 dissociation curve to right dissociation curve to right

O2 Disassociation Curve

increase temperature2,3-DPGPCO2decrease in pH

decrease temperature2,3-DPGPCO2increase in pH

Physiologic Effects AlkalosisAlkalosis

Arrhythmogenic Arrhythmogenic Promotes coronary artery spasmPromotes coronary artery spasm Variable effect upon myocardial contractility Variable effect upon myocardial contractility

and vascular toneand vascular tone Lowers seizure thresholdLowers seizure threshold Transient reduction in cerebral blood flowTransient reduction in cerebral blood flow Lowers ionized calcium ( .03-.09 /0.1 pH)Lowers ionized calcium ( .03-.09 /0.1 pH) Suppresses respiratory functionSuppresses respiratory function Shift OShift O22 dissociation curve to left dissociation curve to left

Changes in Acid-Base DisordersDisorderDisorder PrimaryPrimary Comp.Comp. ExpectedExpected

AcidosisAcidosis

MetabolicMetabolic HCO HCO33 PCO PCO22 PCO PCO22 =1.5x HCO =1.5x HCO33(8 +/- 2)(8 +/- 2)

RespiratoryRespiratory

AcuteAcute PCO PCO22 HCO HCO33 pH=.008(PCO pH=.008(PCO22 -40) -40)

ChronicChronic pH=.003(PCO pH=.003(PCO22 -40) -40)

AlkalosisAlkalosis

MetabolicMetabolic HCO HCO33 PCO PCO22 PCO PCO22 =7x HCO =7x HCO33+(20+/-1.5) +(20+/-1.5)

RespiratoryRespiratory

AcuteAcute PCO PCO22 HCO HCO33 pH=.008(40- PCO pH=.008(40- PCO22))

ChronicChronic pH=.003(40- PCO pH=.003(40- PCO22))

Acid-Base Disturbances

Metabolic Acidosis

Net retention of HNet retention of H++

Physiological adaptationPhysiological adaptation buffering (bone/skeletal muscle)buffering (bone/skeletal muscle) increased ventilationincreased ventilation increased reabsorption/generation HCOincreased reabsorption/generation HCO33

Metabolic Acidosis

Obtain ABG Obtain ABG (rule out primary hyperventilation(rule out primary hyperventilation)) Determine Anion Gap (nl = 12)Determine Anion Gap (nl = 12)

differentiates between loss of HCO3 and differentiates between loss of HCO3 and accumulation of unmeasured acid anionsaccumulation of unmeasured acid anions

AG = serum Na - serum Cl - serum HCO3AG = serum Na - serum Cl - serum HCO3 AG affected byAG affected by hypoalbuminemiahypoalbuminemia

Metabolic Acidosis

Normal AG (Normal AG (ClCl--) ) (HHARDUP)(HHARDUP) HHypoaldosteronismypoaldosteronism HHyperosmolar nonketotic yperosmolar nonketotic

comacoma AAcetazolamidecetazolamide RRTATA DDiarrheaiarrhea UUtererosigmoidostomyileotererosigmoidostomyileo

stomystomy PPancreatic fistulaancreatic fistula

High AG High AG (MUD-PILES)(MUD-PILES) MMethanolethanol UUremiaremia DDKAKA PPoisonsoisons IIron, INHron, INH LLactic acidosisactic acidosis EEthanol, thanol, EEthylene glycolthylene glycol SSalicylate, alicylate, SStarvationtarvation

Organic Acids

Endogenous Endogenous KetoacidosisKetoacidosis

b-hydroxybutyrateb-hydroxybutyrate acetoacetateacetoacetate

Lactic acidosisLactic acidosis Severe renal Severe renal

insufficiencyinsufficiency phenolic aromatic acidsphenolic aromatic acids furanoic acidfuranoic acid dicarboxylic aciddicarboxylic acid

IngestedIngested salicylatesalicylate ethyleneglycol ethyleneglycol

metabolitesmetabolites glycolateglycolate glycoxalateglycoxalate oxalateoxalate

methanolmethanol formateformate

Hyperchloremic Acidosis

Net retention HCl or loss of HCONet retention HCl or loss of HCO3 3 in in

proportionate excess of chlorideproportionate excess of chloride normal quotient HCOnormal quotient HCO33/Cl > 0.25/Cl > 0.25

Loss of HCOLoss of HCO33 renal vs non-renalrenal vs non-renal

measurement of urine NHmeasurement of urine NH44++

NHNH44++ excretion < 1 mmol/kg (kidney primary) excretion < 1 mmol/kg (kidney primary)

Evaluation of Hyperchloremic Acidosis

Gluck SL. Lancet 352, Aug, 1998.

RTA

Gluck SL. Lancet 352, Aug, 1998.

Distal RTA (type 1) - impaired H+ secretion (urine pH > 5.5)

Proximal RTA (type 2) - impaired proximal HCO3 reabsorption

Defective ammoniagenesis (type4) - defective NH4+ production

Treatment: Metabolic Acidosis

Correct Underlying Disorder!!!!!

? Sodium Bicarbonate adminstration?

HCO3 required = .4 x wt (kg) x (25 - measured HCO3)

Risk of Sodium Bicarbonate Hypernatremia/hyperosmolality (1000 Hypernatremia/hyperosmolality (1000

mmol/L)mmol/L) Extracellular-fluid overloadExtracellular-fluid overload ““overshoot” alkalosisovershoot” alkalosis Worsening acidosisWorsening acidosis

buffering protons by bicarbonate = CObuffering protons by bicarbonate = CO22

raises the partial pressure of CO2 in fluidsraises the partial pressure of CO2 in fluids paradoxical worsening intra/extracellular acidosisparadoxical worsening intra/extracellular acidosis

limited ventilatory reserve, advance circulatory limited ventilatory reserve, advance circulatory failure or undergoing CPRfailure or undergoing CPR

Alternative Alkalinizing Agents

CarbicarbCarbicarb Equal sodium bicarbonate and sodium carbonateEqual sodium bicarbonate and sodium carbonate Carbonate stronger base, preference for buffering Carbonate stronger base, preference for buffering

hydrogen ionshydrogen ions Generates bicarbonate rather than CO2 and even Generates bicarbonate rather than CO2 and even

consumes CO2 when reacting with carbonic acidconsumes CO2 when reacting with carbonic acid Results: increases blood and intracellular pH with little Results: increases blood and intracellular pH with little

increase in CO2increase in CO2 Risks: Hypervolemia and hypertonicityRisks: Hypervolemia and hypertonicity

Alternative Alkalinizing Agents

THAMTHAM 0.3 Nitromethamine0.3 Nitromethamine Sodium free, buffers metabolic and respiratory acidsSodium free, buffers metabolic and respiratory acids Limits CO2 generation Limits CO2 generation Increases extra- and intracellular pHIncreases extra- and intracellular pH Not documents more efficacious than bicarbonateNot documents more efficacious than bicarbonate Side effects: hyperkalemia, hypoglycemia, ventilatory Side effects: hyperkalemia, hypoglycemia, ventilatory

depression, hepatic necrosis in neonatesdepression, hepatic necrosis in neonates

Metabolic Alkalosis

increase in alkali increase in alkali addition to ECFaddition to ECF gastric lossesgastric losses oral or parenteral sourcesoral or parenteral sourcesmineralocorticoidmineralocorticoid

stimulate H secretionstimulate H secretion

increased Na deliveryincreased Na delivery increased Na absorptionincreased Na absorption ““contraction alkalosis” contraction alkalosis”

impairment in renal impairment in renal HCOHCO33 excretion excretion K deficiencyK deficiency

stimulates HCOstimulates HCO33 exit exit

decreased Cl deliverydecreased Cl delivery impairs HCOimpairs HCO33 exit exit

raised CO2raised CO2 hormonal hormonal

angiotensin IIangiotensin II norepinephrinenorepinephrine

Metabolic alkalosis requires both to occur.

Metabolic Alkalosis

Chloride-responsive Chloride-responsive Urine (Cl) < 10-20Urine (Cl) < 10-20 Contraction alkalosisContraction alkalosis DiureticsDiuretics Villous adenomaVillous adenoma Gastric lossesGastric losses

Chloride-unresponsive Chloride-unresponsive Urine (Cl) > 10-20 Urine (Cl) > 10-20 DiureticsDiuretics VomitingVomiting AldosteronismAldosteronism Alkali intake (antacids)Alkali intake (antacids)

Treatment of Metabolic Alkalosis

Treat underlying disorder!!Treat underlying disorder!! Correct hypovolemia with NSCorrect hypovolemia with NS Correct hypokalemiaCorrect hypokalemia Acetazolamide Acetazolamide

inhibit carbonic anhydraseinhibit carbonic anhydrase decreased promixal tubular HCOdecreased promixal tubular HCO33 by 80% by 80%

IV dose 250 mg x1( pH corrects with 24 hrs)IV dose 250 mg x1( pH corrects with 24 hrs)

Treatment of Metabolic Alkalosis

If chloride deficitIf chloride deficit replace volumereplace volume deficit = .4 x wt (kg) x (100 - measured Cl)deficit = .4 x wt (kg) x (100 - measured Cl)

If chloride-unresponsiveIf chloride-unresponsive K replacement or mineralcorticoid antagonist (Aldactone)K replacement or mineralcorticoid antagonist (Aldactone)

If volume overload and unresponsive acetazolamideIf volume overload and unresponsive acetazolamide consider CAVH with Cl infusionconsider CAVH with Cl infusion

Prolonged gastric suctioningProlonged gastric suctioning Use histamine-2 antagonistUse histamine-2 antagonist

Respiratory Acid-Base Disorders

Blood pCOBlood pCO22 tightly regulated tightly regulated alternations alveolar ventilationalternations alveolar ventilation central control (chemoreceptors COcentral control (chemoreceptors CO22, pO, pO22, pH), pH)

Acidosis or alkalosisAcidosis or alkalosis primary increase/decrease in CO2 productionprimary increase/decrease in CO2 production may coexist with other acid-base disordersmay coexist with other acid-base disorders

Respiratory Acidosis

Inadequate ventilationInadequate ventilation AcuteAcute

pH changes .008 for every 1 mmHg changepH changes .008 for every 1 mmHg change

ChronicChronic pH changes .003 for every 1 mmHg changepH changes .003 for every 1 mmHg change


Airway obstructionAirway obstruction Status asthmaticus, severe asthma, COPDStatus asthmaticus, severe asthma, COPD Severe alveolar defects (edema, pneumonia, Severe alveolar defects (edema, pneumonia,

ARDS)ARDS) CNS depression (drugs, brainstem damage)CNS depression (drugs, brainstem damage) Neuromuscular impairmentNeuromuscular impairment Ventilatory restriction (PTX, flail chest, burns)Ventilatory restriction (PTX, flail chest, burns)


Increase in pCO2 Increase in pCO2 increase in HCOincrease in HCO33

intracellular bufferingintracellular buffering cellular loss of HCOcellular loss of HCO33 to ECF to ECF

adaptive renal HCOadaptive renal HCO33 reabsorption (late) reabsorption (late)

Clinical manifestationsClinical manifestations

anxiety

SOB

delirium

encephalopathy

myoclonus

seizures


TreatmentTreatment Supplemental oxygenSupplemental oxygen Aggressive pulmonary toiletAggressive pulmonary toilet Treatment of pneumoniaTreatment of pneumonia BronchodilatorsBronchodilators Removal of obstructionRemoval of obstruction Mechanical ventilationMechanical ventilation

Respiratory Alkalosis

HyperventilationHyperventilation AcuteAcute

pH changes .008 for every 1 mmHg changepH changes .008 for every 1 mmHg change

ChronicChronic pH changes .017 for every 1 mmHg changepH changes .017 for every 1 mmHg change


Metabolic Metabolic encephalopathyencephalopathy

Hepatic failureHepatic failure AnxietyAnxiety Early sepsisEarly sepsis Pulmonary embolismPulmonary embolism HypoxiaHypoxia

CHFCHF Severe head injury Severe head injury CVACVA Mechanical Mechanical

overventilationoverventilation Salicylate overdoseSalicylate overdose PregnancyPregnancy


Decrease in pCODecrease in pCO22 decrease in decrease in HCOHCO33 cellular uptake HCO3cellular uptake HCO3

Induces cellular uptake of K and phosphateInduces cellular uptake of K and phosphate Increases binding of ionized Ca to albuminIncreases binding of ionized Ca to albumin ManifestationsManifestations

arrhythmiasarrhythmias facial/peripherial paraesthesiasfacial/peripherial paraesthesias muscle crampsmuscle cramps syncopesyncope seizuresseizures


TreatmentTreatment Calm patientCalm patient Carbon dioxide rebreathingCarbon dioxide rebreathing Treat underlying disorderTreat underlying disorder Administer sedativeAdminister sedative Mechanical ventilationMechanical ventilation

Case Study #1

87 m found unresponsive in hospital bed87 m found unresponsive in hospital bed

Hospital HistoryHospital History POD 1 bladder cystoscopy-TURPPOD 1 bladder cystoscopy-TURP Overnight hydrated D5 1/2 NS at 75 cc/hrOvernight hydrated D5 1/2 NS at 75 cc/hr PMH: HTN, kidney stones, prostate CA, CADPMH: HTN, kidney stones, prostate CA, CAD

Case Study #1

Transferred to ICUTransferred to ICU Vitals Vitals

Temp 37.2Temp 37.2 BP 80/42BP 80/42 P 116, RR 24, P 116, RR 24, O2 sat 84%O2 sat 84%

PEPE Lungs cracklesLungs crackles Responsive to pain only, otherwise non-focalResponsive to pain only, otherwise non-focal

Case Study #1

WBCWBC HctHct PLTPLT NANA KK ClCl CO2CO2 BUNBUN CrCr GlucoseGlucose AlbAlb CaCa MgMg OsmOsm

Case Study #1


POD13.6517.781

1173.78616242.11052.26.40.7288

Admission9.9528.51831373.310528231.4250

Case Study #1


Admission9.9528.51831373.310528231.4250

POD13.6517.781

1173.78616242.11052.26.40.7288

PT/PTT

ABG

CXR

EKG

CPK

Anything else ?

Case Study #1


Admission9.9528.51831373.310528231.4250

POD13.6517.781

1173.78616242.11052.26.40.7288

PT 1.3 / PTT 44

ABG 7.26/83/29

CXR: pulm edema

EKG: NS ST-T changes

CPK: wnl

Anything else… ?

Case Study #1


Admission9.9528.51831373.310528231.4250

POD13.6517.781

1173.78616242.11052.26.40.7288

PT 1.3/PTT 44

ABG 7.26/83/29

CXR: pulm edema

EKG: NS ST-T changes

CPK: wnl

Anion gap…

S Osmolarity…

NA - CO2 - Cl = 15

2 Na + Glu/18 + BUN/2.8 = 248

Case Study #1 ICU Day 1ICU Day 1

IntubatedIntubated VasopressorsVasopressors PA catheterPA catheter

CI 2.1 L/min/m2CI 2.1 L/min/m2 Wedge 18 mmHgWedge 18 mmHg CVP 16CVP 16 SVR 2100SVR 2100

CT brain negativeCT brain negative EEG metabolic encephalopathyEEG metabolic encephalopathy

Diagnosis: Glycine Toxicity

TURP/continuous bladder irrigationTURP/continuous bladder irrigation Solution 1.5% glycineSolution 1.5% glycine

hypotonic (200 mOsm/L)hypotonic (200 mOsm/L) Usually continuous aspirated during procedureUsually continuous aspirated during procedure

absorption through venules in bladder wallabsorption through venules in bladder wall absorption through ruptured prostate capsuleabsorption through ruptured prostate capsule

Remains extracellularRemains extracellular osmotically activeosmotically active dilutional hyponatremia/elevated osmolal gapdilutional hyponatremia/elevated osmolal gap


Metabolic fateMetabolic fate transported intracellulartransported intracellular breakdown breakdown

creatinine, COcreatinine, CO22, H, H22O, NHO, NH44, glucose, glucose hippurate, glyoxylate, formate, oxalatehippurate, glyoxylate, formate, oxalate

Constellation of labsConstellation of labs hyponatremia and elevated osmolal gaphyponatremia and elevated osmolal gap increased serum NHincreased serum NH4 4 (metabolism to ammonia)(metabolism to ammonia)

hypocalcemia (binding oxalates)hypocalcemia (binding oxalates) anemia and thrombocytopenia (hemolysis/dilution)anemia and thrombocytopenia (hemolysis/dilution)


Clinical presentationClinical presentation nausea and emesisnausea and emesis hypotensionhypotension mental status changesmental status changes thrombocytopeniathrombocytopenia SOB (edema, worse with CHF)SOB (edema, worse with CHF)

TherapyTherapy Fluid and electrolyte managementFluid and electrolyte management


OutcomeOutcome sepsis could not be ruled outsepsis could not be ruled out started on antibioticsstarted on antibiotics dialysis could not be performed due to pt’s dialysis could not be performed due to pt’s

wisheswishes cystogram negative for perforationcystogram negative for perforation blood cx: e coliblood cx: e coli developed ARDS, ATN, SB ischemiadeveloped ARDS, ATN, SB ischemia POD 13 deathPOD 13 death

Acid-Base Disorders Bradley J. Phillips, MD Burn-Trauma-ICU Adults & Pediatrics.

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