Acid Base Equilibrium, Clinical Concepts and Acid Base Disorders

Acid Base Equilibrium, Clinical Concepts and Acid Base DisordersDr Sajith DamodaranUniversity College of Medical Sciences & GTB Hospital, DelhiHomeostasisThe Interstitial Fluid is the environment of the cells, and life depends on the constancy of this internal sea.Homeostatic Mechanisms : Maintain within a narrow range. Tonicity VolumeSpecific ion concentrationDefence of Tonicity (280-295mOsm/L)Vasopressin secretion Thirst Mechanism

Increased Osmolality of ECF

Thirst IncreasedVasopressin SecretionIncreased Water IntakeWater RetentionDilution of ECFInhibitoryHomeostasisDefence of Volume:ECF Na+ - Most importantRenin-Angiotensin-Aldosterone SystemVasopressin Secretion: Volume stimuli override osmotic regulationANP & BNP

Angiotensinogen Renin Angiotensin I ACEAngiotensin II

AldosteroneVasopressin

AdrenalCortexBrainKidneyNa RetentionWater RetentionBlood VesselVasoconstrictionThirstHomeostasisDefence of Specific Ionic Concentration:GlucoseNa+ & K+ Ca++ - Mainly by Parathyroid & CalcitoninMg++ - Incompletely understood mechanisms

Also dependent on H+ ion

pH is maintained within a narrow range.

Acid Base EquilibriumWhat is Acid Base Equilibrium About??Buffers?Fixed Cation?Base Excess/ Deficit?Anion Gap?Acid Base EquilibriumAcid Base Equilibrium is all about Maintenance of H+ ion concentration of the ECF.Source of H+ ion in Body:

CO2 from metabolismH+ load from AA metabolismStrenuous Exercise Lactic AcidDiabetic KAIngestion of NH4Cl, CaCl2Failure of Kidneys to Excrete PO4--, SO4--H+ ion12500 mEq/d50 - 100 mEq/dSome Basic ChemistryDefinitions:Arrhenius:Acid: H+ Donor in SolutionBase: OH- donor in Solution

Browsted and Lowry:Acid: Proton DonorBase: Proton AcceptorH20 can be both

Some Basic ChemistrySimple Rule of Thumb:Acid Higher conc. Of H+ ionBase Lower conc. Of H+ ionStrong Acid/Base Dissociates completely and irreversiblyWeak Acid/Base Dissociates partially and reversibly

Strong Electrolyte: Dissociates completely in solution at physiological pHEg: NaCl, KCl

Weak Electrolyte: Dissociates incompletely in solution at physiological pHEg: CO2 HCO3- System, ProteinsSome Basic ChemistrypH (Puissant of Hydrogen):Negative logarithm of H+ ion concentration to the base of 10

Why pH?Normal H+ ion conc: 0.00004meq/L or 40nEq/L or 4x10-9 mol/LpH converts to decimal numbers & takes away negative sign.Normal pH: 7.35-7.45Normal H+ Conc: 0.00002mEq/L 0.0001 mEq/L

Some Basic ChemistryPitfalls: Non-linear Negative Logarithmic scalepH Decreases as [H+] increases.Each unit change in pH from 7 represents 10 fold change in H+ ion conc.Eg: At pH 4, there are 10 times as much H+ than at pH 5, & 100 times as at pH 6Same numeric change in different portions of the pH scale implies vastly different nanomolar change in H+ ionsEg: pH 56 => 100 times greater change in ionic conc than when pH 7 8Body H+ ion conc is not as tightly controlled as the other ion, though the pH scale implies so.

Some Basic ChemistryWater (H2O)Water dissociates, but to a very low extent.H2O H+ + OH-But, a glass of water has a billion times more H2O than H+ & OH-At equilibrium:[H+] [OH-] = Kw[H2O]{Kw(Dissociation constant of water) changes with temperature}Or, [H+] [OH-] = KwpH of Water:Since at neutral pH, [H+] = [OH-][H+] = ROOT (Kw)Acidic solution, [H+] > ROOT (Kw), Basic sol, [H+] < ROOT(Kw)pH changes with temperature

Acid Base Equilibrium:Solutions:When substances are added to water, 3 simple rules have to be satisfied at all time:Electrical NeutralityMass conservationDissociation EquilibriumECF is a complex solution with strong ions, weak ions and CO2 dissolved in water.Acid Base Equilibrium:CO2 in Water:Can Dissolve in waterCan form - Carbonic Acid - Bicarbonate ion - Carbonate ion

CO2(gas) CO2(dissolved) Rate of Forward Reaction = Kf * PCO2 Rate of Reverse reaction = Kr *[CO2(dissolved) ] => [CO2(dissolved)] = Kf /Kr *PCO2

Kf /Kr = SCO2 (Solubility of CO2 ) = 0.03mEq/L/mm Hg at 370 C

}All these reactions have equilibrium Constants and can be solved at equilibrium.Acid Base Equilibrium:CO2 + H2O H2CO3 =>[CO2][H2O] = K*[H2CO3] => [H2CO3] = K*PCO2 H2CO3 H+ + HCO3- Henderson Equation: [H+ ] = K1 [H2CO3]/[HCO3- ]Modified Henderson Equation: [H+ ][HCO3- ] = K2 [CO2][H2O] [H+ ][HCO3- ] = K3 [CO2] [H+] = K*PaCO2/[HCO3-]

Acid Base Equilibrium:The Henderson-Hasselbalch Equation:CO2 + H2O H+ + HCO3- => [H+] = Ka * [CO2]/[HCO3-]Rearranging: =>1/[H+] = 1/Ka*[HCO3-]/[CO2]Taking Logarithm on both sides & Rearranging:=> pH= pKa + log10[HCO3-]/0.03*PCO2 Significance: Includes components of both Met & Resp Acid base disordersValue of any one variable can be determined if other two known. Mostly HCO3- is calculatedpH determined by ratio of [HCO3-]/PCO2 . Maintained at 20. Increase=> alkalosis, Decrease => AcidosisClinical Concepts: The Stewart ApproachDissociation equations can be solved mathematically. When the equations are solved-Independent Variables: SID, [Atot] & PaCO2 Constants : Dissociation constantsDependent Variables: [H+], [OH-], [HCO3-], [CO32-], [A+], [HA], [H2CO3], [CO2 dissolved]

Clinical Concepts: The Stewart ApproachDissociation equations can be solved mathematically. When the equations are solved-Independent Variables: SID, [Atot] & PaCO2 Constants : Dissociation constantsDependent Variables: [H+], [OH-], [HCO3-], [CO32-], [A+], [HA], [H2CO3], [CO2 dissolved]

Dependent Variables can only be changed by changing the independent variables!!!Clinical Concepts: The Stewart ApproachSID: Strong Ion Difference ([Na+] + [K+] + [Ca++] + [Mg++]) [Cl-]+ [other Strong Anions]Normal: 40-44mEq/L with normal protein levelsChange from normal is equivalent to SBEDehydration: Increases SID ==> AlkalosisDilution, Organic Acids, Hyperchloremia : Decreases SID ==> Acidosis

[Atot]: Total Amount of Weak Acid in SolutionAlbumin is the most important weak electrolyte in plasma.Other weak acids are Inorganic Phosphates, Plasma proteins. Hypoproteinemia: AlkalosisRenal Failure: Accumulation of Phosphate: AcidosisClinical Concepts:Base Excess: Amount of Acid or Alkali required to return plasma in vitro to normal pH under standard conditions.Standard BE: BE calculated for Anaemic Blood (Hb = 5Gm%).Since Hb effectively buffers plasma & ECF to a large extent.Quantity of Acid or Alkali required to return plasma in-vivo to a normal pH under standard conditionsAnion Gap:AG = [Na+] + [K+] - {[HCO3-] + [Cl-]}Normal Value: 8-12mEq/L, Unmeasured Anion: Albumin, Phosphate, sulphate, organic anionsAG decreases by 2.5mEq/L for every 1mEq/L decrease in Plasma albuminAG>16 ==> Ketones, lactate, salicylate, antifreeze, methanolCauses of Low AGIncreased unmeasured cations Ca, MgAddition of abnormal cations LiDecreased AlbAltered charge in Alb d/t acidosisHpyervisocity, severe hyperlipidemia underestimation of Na & Cl in lab.

In a mixed disorder like Malk f/b M Acidosis, the HCO3- & pH would be normal, but AG will be raised.19Clinical Concepts:Acid Base Equilibrium:Elimination of AcidRecovery/Regeneration of Base

Mechanisms that keep pH stableBufferingCompensationCorrectionComponents of Acid Base Equlibrium:Elemination of AcidRecovery/Regeneration of Base

Mechanisms that keep pH stableBuffering: Chemical buffers in body to immediately minimise the change in pHCompensation: Attempt to restore [HCO3- ]/PaCO2 ratio to normal by alteration of non deranged valueCorrection: Rearranging homeostasis by correcting primary metabolic derangement

20Clinical Concepts:Buffers:Definition: A substance that can bind or release H+ ions in solution, thus keeping the pH of the solution relatively constant despite addition of large amounts of acid or base.For Buffer HA,HA H+ + A-pH = pKa + log [A-]/[HA]When [A-] = [HA], pH= pK, buffering capacity is maximum.Ideal body buffer has pKa between 6.8 and 7.2Clinical Concepts:Most buffers are weak acids (Hbuffer) & their Na Salts (Nabuffer)Strong Acids Buffered by NaBufferHCl + NaBuffer H+ + Cl- +Na+ + Buffer Hbuffer + NaClStrong Bases buffered by HbufferNaOH + H Buffer Na+ + OH- + H+ + Buffer NaBuffer + H2O

Buffer Effectiveness Depends on:QuanitityH2CO3 /HCO3- - Most important Extracellular BufferProtein Buffers Most improtant Intracellular BufferpKa Buffering capacity maximum when pH=pKa Function well within 1 pH unit. (Eg: HCO3- - 5.1-7.1)

Hbuffer is a weak acid. So less H+ is realsed in solution as compared to HCl which is a strong acidIf no buffer were there, OH from NaOH would combine with H+ n reduce its concentration thus raising pH. But NaBuffer is a weak base, n less OH is released in solutiong. 22Clinical Concepts:Buffers in ECF:Carbonate-Bicarbonate Buffer53%Plasma (35%)Erythrocyte(18%)Hemoglobin35%Plasma Proteins7%Organic & Inorganic Phosphates5%

Buffers in ICF:Intracellular ProteinsH2PO4-HPO4- system

Intracellular buffers are responsible for ~85% buffering in Met. Acidosis and ~35% in met alk and almost complete buffering in respiratory acidosis and alkalosis

Clinical Concepts:Bicarbonate Buffer:HCl + NaHCO3- NaCl + H2CO3NaCl + H2O + CO2 useful only for metabolic acidHb System: Both Respiratory & Metabolic Acid in ECFForms Carbamino compounds with CO2 Buffers H+ directlyCO2 + H2O H2CO3 + KHb HHb + KHCO3HCO3- diffuses out & Cl- diffuses into cells Chloride shiftpKa 6.8CO2 combines with terminal AA of Hb to form Carbamino compounds. 15-25% of total co2 transport in bld.Co2 in RBC forms cabonic acid by CA n breaks down to H+ & OH-. The H+ is buffered by HHb. CO3- diffuses out and cl- comes in. Thus most of the change happens in plasma.Imidazole groups of Histidine residues in Hb act as buffer. 38 His residues in Hb.24Clinical Concepts:Protein Buffer:Predominant Intracellular Buffer Large total concentrationpK = 7.4AA have Acidic & Basic Free radicles.COOH + OH- COO- + H2O.NH3OH + H+ NH3 + H2OPhosphate Buffer:pK = 6.8Predominantly IntracellularAlso in renal tubular HCl + Na2HPO4 NaH2PO4 + NaClNaOH + NaH2PO4 Na2HPO4 + H2O

Clinical Concepts:Compensation:Pulmonary CompensationH+ + HCO3- H2CO3 CO2 + H2O H+ acts on medullary centres. Increased PaCO2 stimulates ventiallationMetabolic Acidosis Increased VentillationMetabolic Alkalosis Depression of VentillationBut, limited because Hypoxic stimulus can override HypercapniaClinical Concepts:Renal Compensatoin:

Mechanisms:Reabsorption of filtered HCO3- (4000-5000 mEq/d)Generation of fresh bicarbonateFormation of titrable acid (1mEq/Kg/d)Excretion of NH4+ in urine PERITUBULAR BLOODRENAL TUBULAR CELLGLOMULAR FILTRATEHCO3- + H+

CO2

HCO3- + H+

HCO3- + H+

HCO3- Na+ HPO42- Na+ NH3 Na+H2CO3CO2 + H2 OH2OH2PO4-H2PO4- NH4+ NH4+1. NaHCO32. NaHCO33. NaHCO3MAJOR RENAL MECHANISMS RESPONSIBLE FOR H+ EXCRETION/HCO3- RETENTIONCO2 can be obtained from blood or the tubular fluidGlutamineCO2CAClinical concepts: CompensationPrediction of Compensatory Responses on Simple Acid Base DisordersDisorderPrediction of CompensationMetabolic AcidosisPaCO2 = (1.5 x HCO3- ) + 8OrPaCO2 will 1.25mm Hg per mmol/L in [HCO3- ]OrPaCO2 = [HCO3- ] + 15Metabolic AlkalosisPaCO2 will 0.75 mm Hg per mmol/L in [HCO3- ]OrPaCO2 will 6mm Hg per 10 mmol/l in [HCO3- ]OrPaCO2 = [HCO3- ] + 15Respiratory Alkalosis Acute[HCO3- ] will 2mmol/L per 10 mmHg in PaCO2 Chronic[HCO3- ] will 4mmol/L per 10 mmHg in PaCO2 Respiratory Acidosis Acute[HCO3- ] will 1mmol/L per 10 mmHg in PaCO2 Chronic[HCO3- ] will 4mmol/L per 10 mmHg in PaCO2 DisorderPrediction of CompensationMetabolic AcidosisPaCO2 = (1.5 x HCO3- ) + 8OrPaCO2 will 1.25mm Hg (1.0-1.5) per mmol/L in [HCO3- ]OrPaCO2 = [HCO3- ] + 15Metabolic AlkalosisPaCO2 will 0.75 (0.25-1.0) mm Hg per mmol/L in [HCO3- ]OrPaCO2 will 6mm Hg per 10 mmol/l in [HCO3- ]OrPaCO2 = [HCO3- ] + 15, Max 55mmHgRespiratory Alkalosis Acute[HCO3- ] will 2mmol/L per 10 mmHg in PaCO2 Chronic[HCO3- ] will 4mmol/L per 10 mmHg in PaCO2 Respiratory Acidosis Acute[HCO3- ] will 1mmol/L per 10 mmHg in PaCO2 Chronic[HCO3- ] will 4mmol/L per 10 mmHg in PaCO2 Acid-Base Nomogram:

Clinical concepts:Effect of Temp:pH rises 0.015/0C drop in temp

Effect of PaCO2 on pH:pH changes by 0.08/10mm Hg change in PaCO2

Effect of change of [HCO3-] on pH:pH changes by 0.1/ 6 mEq change in [HCO3-]This is because CO2 is more soluble as blood cools and thus PCO2 drops.(4.5%/degree)Hb accepts more H+ when cooled.31Clinical Concepts:Effect of Electrolytes in Buffering:Potassium Ion: IntracellularHypokalemia - K+ Moves out H+ moves in - K+ & HCO3- reabsorption, H+ ExcretionSodium IonHyponatremia -- Na+ & HCO3- reabsorption & H+ excretionExtra HCO3- in Blood Extracellular Metabolic Alkalosis & Intracellular Metabolic Acidosis

32Clinical Concepts:Role of Bones:Exchange of Extracellular H+ for Na+ & Ca++ Acid load Demineralise BonesAlkaline load Deposition of CO32- in Bones

Time Course of Buffering:Plasma HCO3- ----> ImmediateInterstitial HCO3- -----> 15-20 MinIntracellular Proteins & Bones ----> 2-4 HoursAcid Base DisordersAcidosis/Alkalosis:Any process that tends to increase/decrease pHMetabolic: Primarily affects BicarbonateRespiratory: Primarily affects PaCO2

Acidemia/Alkalemia:Net effect of all primary and compensatory changes on arterial blood pH.Acid Base DisordersThe primary disorders:Metabolic AcidosisMetabolic AlkalosisRespiratory AcidosisAcuteChronicRespiratory AlkalosisAcuteChronic

DisorderPrimary ChangeCompensatory ChangeMetabolic AcidosisHCO3_PaCO2Metabolic AlkalosisHCO3_PaCO2Respiratory AcidosisPaCO2HCO3_Respiratory AlkalosisPaCO2HCO3_Acidosis:Clinical EffectsCVS:Combination of Effects of Direct depression and Catecholamine stimulationHeart Rate: Initial Increase then DecreaseRhythm: Increased Atrial & Ventricular DysrrhythmiasDue to Changes in S K+ Lower threshold for VFContractility: Increased contractility. Depression if pH Resp AcidosisCompensation expected:HCO3- = 24 + (64-40) x 0.1 = 24+2.4 = 26.4 or 24 + (64-40) x 0.4 = 24 + 9.6 = 33.6Diagnosis: Chronic Respiratory AcidosisMetabolic Acidosis: Causes:Increased Anion GapIncreased Production of Endogenous AcidKetoacidosis- DM, StarvationLactic AcidosisMixed- NKHC, AlcoholicAbnormal AA Met.CRF

Ingestion of ToxinsSalicylateMethanolEthylene GlycolParaldehyde, Toluene, SulphurRhabdomyolysisAny Acidosis that cant be explained by Respiratory component is due to Metabolic Acids.Primary Mechanisms:Consumption of HCO3- by non-volatile acidRenal wasting of HCO3-Rapid Dilution of ECF with Bicarb. Free fluid

46Metabolic Acidosis: Causes ContdNormal AG(Hyperchloremic)GI Loss of HCO3-DiarrheaFistula- Pancreatic, Biliary, Small IntestinalUreterosigmoidostomyObstructed Bowel LoopCholestrylamine, CaCl2, MgSO4

Renal Loss of BicarbRTACA InhibitorsHypoaldosteronismDilutional- Bicarb free fluidTPNIncreased Intake of Cl containing Acids NH4Cl, Lysine hydrochloride, Arginine HydrochlorideMetabolic Acidosis: pH 7.36PaCO2 26HCO3- - 13BE - -11pH Acidic but normalPaCO2 Decreased => Not RespiratoryHCO3- - Decreased => Metabolic AcidosisCompensation expected: 40 - (24-13)x1.25 =40-13.75 = 26.25Diagnosis: compensated Metabolic AcidosisTreatment:Alkali Therapy:Indications Normal AG (Hyperchloremic Acidosis)Slightly elevated AG (Mixed Hyperchloremic & AG Acidosis) AG due to Non Metabolisable Anion (Renal Failure)Goal: To slowly increase plasma HCO3- to 20-22 mmol/LAG Acidosis due to Accumulation of Organic metabolizable anion, if pH< 7.2Goal: pH to 7.15, Plasma HCO3- ~10mmol/LEither orally (NaHCO3 / Shohls solution) or IV (NaHCO3)Carbicarb, THAMAcute Respiratory AcidosisChronic Respiratory AcidosisCorrection of the causeRestoration of Adequate vent Mechanical ventillationDifficult to CorrectMeasure to Improve lung functionDepends on severity and rate of onset.Acute:Reversal of underlying causeRestoration of adequate ventillation Mechanical ventillationChronic:Difficult to correct.Measures to improve lung functionCarbicarb: This compound has an equimolar concentration of NaHCO3-and sodium carbonate. Because carbonate is a stronger base, it buffers H+in preference to HCO3-, resulting in the generation of HCO3-rather than CO2. This drug is not available in the United States.THAM is a sodium-free alkalizing solution containing 0.3N tromethamine. It buffers acids and limits the generation of CO2and has been used in some clinical situations to treat severe metabolic acidosis. Major adverse effects include hyperkalemia and hypoglycemia, and the drug should not be used in patients with oliguria or poor renal function. This drug is not used widely in the United States.

49Treatment:Problems with Bicarbonate TherapyCardiac Arrest: Both MA & RA50mL NaHCO3 Releases 200 mL CO2 Bicarb corrects MA but worsens RAIntracellular AcidosisCOP increase maybe due to increased intravascular volCSF AcidosisIncreased Plasma Osmolarity (3 mmol/50mL)Extracellular alkalosis - ODC to Left - Decreased Tissue OxygenationRebound AlkalosisDecreased Ca++ ---> Myocardial depressionAcidosis: Anaesthetic Considerations:Potentiation of depressant effects of sedatives and anaesthetic agentsExaggerated circulatory depressant effects more pronounced with agents that rapidly decrease symp toneIncreased opioid penetration into brainbasic drugs increased non ionised formIncreased arrhytmogenicity of halothaneRespiratory Acidosis augments NDMR delayed reversalSuccinyl Choline increases Serum K+ furtherAlkalosis:Physiologic Effects:Left shift of ODCHypokalemiaLow ionised Ca++Decreased CBFDepressed VentilatoinRespiratory AlkalosisBronchoconstrictionDecreased PVR

EffectDirectIndirectClinicalCerebral BF-0-Heart rate000Cardiac inotropy000Systemic Art tone+0+Syst venous tone000PA tone0--Airway tone+-+Uterine BF-0-Renal BF000Ionised Ca++ -0-Serum Potassium-0-52Respiratory Alkalosis: Primary Decrease in PaCO2Causes:Central StimulationPain AnxietyIschemiaTumorInfectionFeverDrugs: Salicylates, Progesterone, Doxapram

Peripheral StimulationHypoxemiaHigh AltitudePulmonary Disease: CHF, NCPE, PE, AsthmaSevere AnemiaUnknown Sepsis, Metabolic EncephIatrogenic: Ventilator InducedUsually d/t alveolar hyperventilation.53Respiratory Alkalosis:pH 7.5PaCO2 35HCO3- - 22

pH AlkalemiaPaCO2 Decrease => Respiratory AlkalosisExpected Compensation: 24-(40-35)x0.2 = 23 or24-(40-35)x0.4 = 22Diagnosis: Chronic Respiratory AlakalosisRespiratory Alkalosis:Treatment:Treatment of Underlying causeVentilator adjustmentsReassurance, Rebreathing from paper bagMetabolic alkalosis: Causes:ECF Contraction, Normotension,K+ Deficiency & 20 HyperreninemicHyperaldosteronismGastrointestinalVomitingNG suctionVillous AdenomaRenalDiureticsMg++ DeficiencyChronic HypokalemiaHypercalcemia/Hyperpara.Post Hypercapnic StateBarters syndromeSweat Cystic Fibrosis

Primary decrease in Bicarb56Metabolic alkalosis:Causes:ECF Expansion, Hypertension, K+ Deficiency & Mineralocorticoid ExcessHigh ReninRenal Artery StenosisAccelerated HTNLow ReninPrimary AldosteronismAdrenal Enzyme defectsCushings SyndromeOtherLiquorice

Exogenous HCO- Loads:Massive Blood TransfusionAcetate containing colloidsAlkali therapy + Renal FailureMilk-Alkali SyndromeMetabolic Alaklosis:pH 7.58PaCO2 48HCO3- - 44BE - +19pH AlkalemiaPaCO2 Increased => Not RespiratoryHCO3- - Increased => Metabolic AcidosisExpected Compensatoin: 40+(44-24)x0.8 = 56Diagnosis: Partially compensated Metabolic AlkalosisMetabolic Alkalosis:Treatment:Correction of underlying stimulus for HCO3- generation:Correction of cause of 10 HyperaldosteronismReduction of Gastric secretions: H2 Blockers, PPIReduction of Renal loss of H+ : Discontinue DiureticsRemove factors that sustain HCO3- ReabsorptionECF contraction NaCl administrationK+ deficiency KCl administrationAcetazolamideBut can cause K+ lossDilute HCl (0.1N HCl)Oral NH4Cl

Alkalosis:Anaesthetic considerations:Increased protein binding of opioids prolonged respiratory depressionDecreased cerebral blood flow Cerebral IschemiaAtrial and Ventricular dysrhythmias with hypokalemiaPotentiation of NDMR due to hypokalemiaAcid Base Disorders:PO2 90.6PCO2 53.8pH 7.484K+ - 3.7Na+ - 151HCO3- (A) 37.7HCO3- (S) 34.3BE 13.9SBE 14.1SO2 97.3pH AlkalemiaPCO2 Increased => Metabolic AlkalosisExpected Compensation: PaCO2 = 40+(13.7x0.75) = 50.2Body never overcompensatesDiagnosis:Metabolic Alkalosis + Respiratory AcidosisSummary:Acid Base Homeostasis is all about maintenance of normal H+ concentration.Changes in acid base status of ECF have profound and often unpredicatble clinical and laboratory effects, more so during anaesthesia.pH scale is a negative logarithmic scale with its inherent counterintutive results.The three independent variables which affect acid base status are SID, [Atot] & PaCO2. SBE as a measure for Metabolic acid base disturbance is most accurate and clinically validated.Anion gap must always be calculated, and effect of Plasma Albumin considered to decipher more accurately the complex acid-base disorders in critically ill patients.Bicarbonate therapy must be used with caution in view of its various deleterious effects.References:Millers Anesthesia, 7th EditionWylie And Churchill Davidsons A Practice of Anaesthsia, 7th EditionMorgan Michael & Clinical Application of Blood Gases, Shapiro, 5th Edition Harrisons Principles of Internal Medicine, 16th EditionGanongs Review of Medical Physiology, 20th EditionAcid-Base tutorial. Prof. Alan W Grogono, MD, FRCA www.acid-base.comA Basic Approach to body pH www.anaesthetist.com/icu/elec/ionz/Findex.htm#Stewart.htm

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