Acid Base Balance PSN LHR

Acid Base BalanceAcid Base BalanceBasic Concepts, Problem SolvingBasic Concepts, Problem Solving

Dr. Aizaz Mand AhmadDr. Aizaz Mand AhmadProfessor of Nephrology,Professor of Nephrology,

National Institute of Kidney DiseasesNational Institute of Kidney DiseasesFederal Shaikh Zayed Postgraduate Medical Institute, Federal Shaikh Zayed Postgraduate Medical Institute,

Lahore.Lahore.

Acid Base BalanceAcid Base Balance

pH = A measure of acidity = -log[HpH = A measure of acidity = -log[H++]] pH & pK notations: pH= pK+log [Base]pH & pK notations: pH= pK+log [Base] H.H.EquationH.H.Equation

[Acid][Acid]

pH= pK+log [HCOpH= pK+log [HCO33]]

[PCO [PCO22x0.03]x0.03]

pK= 6.10pK= 6.10 pH= 6.10+log [24] pH= 6.10+log [24]

40x0.0340x0.03

pH= 6.10+log [24]pH= 6.10+log [24]

1.21.2

pH= 6.10+1.3=7.4pH= 6.10+1.3=7.4


[H[H++] = K [Acid]] = K [Acid] Henderson's EquationHenderson's Equation [Base][Base]

[H[H++] = 24 x PCO] = 24 x PCO22

HCOHCO33

[H[H++] = ] = 24 x 40 = 4024 x 40 = 40 24 24

at pH 7.4 [Hat pH 7.4 [H++] = 40] = 407.37.3 40 x 1.25 = 40 x 1.25 = 5050 7.27.2 40x1.25x1.25 = 40x1.25x1.25 = 62.562.57.5 7.5 40 x 0.8 = 40 x 0.8 = 3232 7.67.6 40 x 0.8 x 0.8 = 40 x 0.8 x 0.8 = 25.625.6

Relationship of HRelationship of H++ and pH and pH


Buffer SolutionBuffer Solution Is one which when added by acid or base minimizes the Is one which when added by acid or base minimizes the

change in pH. It consists of a weak acid & the conjugate base change in pH. It consists of a weak acid & the conjugate base of that acidof that acidStrong acid + buffer salt Neutral salt + weak acidStrong acid + buffer salt Neutral salt + weak acid

Acids produced in the bodyAcids produced in the bodyNon volatile / fixed acids = 50-70 mmolNon volatile / fixed acids = 50-70 mmolVolatile acids = 13,000-20,000 mmol of COVolatile acids = 13,000-20,000 mmol of CO22

Acid Base BalanceAcid Base BalanceRegulatory MechanismsRegulatory Mechanisms

AA. Chemical Buffer System . Chemical Buffer System 11stst line of defense - (slow) line of defense - (slow)

BB. Respiratory Component. Respiratory Component22ndnd line of defense - (fast) line of defense - (fast)

CC. Renal Mechanisms . Renal Mechanisms 33rdrd line of defense - (more slow)line of defense - (more slow)


AA. . Chemical BuffersChemical BuffersI. Extracellular I. Extracellular – HCOHCO--

33/H/H22COCO33 – phosphate phosphate – Plasma proteinsPlasma proteins

II. Intracellular II. Intracellular – Hemoglobin Hemoglobin – Tissue proteins Tissue proteins – Bone appatiteBone appatite– Organo phosph Organo phosph

complexes complexes

Acid Base BalanceAcid Base Balance HH+++Cl+Cl--+Na+Na+++HCO+HCO3 3 NaCl+H NaCl+H22COCO33 If 12 mmol of HCl are added to ECF, will be buffered by HCO-If 12 mmol of HCl are added to ECF, will be buffered by HCO-33

by 12 mmol/lby 12 mmol/l 12H12H+++12Cl+12Cl--+24Na+24Na+++24HCO+24HCO33 12 Na 12 Na+++12Cl-+12Na+12Cl-+12Na+++12 HCO+12 HCO--

33 +12H +12H22COCO33 12CO 12CO22+12H+12H22OO

BB. . Respiratory ComponentRespiratory Component If 12 COIf 12 CO22 not eliminated by ventilatory system not eliminated by ventilatory system

pH = 6.1 + log 12/1.2+12pH = 6.1 + log 12/1.2+12pH = 6.1 + log 12/ 13.2pH = 6.1 + log 12/ 13.2pH = 6.06pH = 6.06

If 12 CO2 are eliminated by lungsIf 12 CO2 are eliminated by lungspH = 6.1 + log 12/0.03x40=12/1.2pH = 6.1 + log 12/0.03x40=12/1.2pH = 6.1 + log 10pH = 6.1 + log 10pH = 7.10 Actually alveolar ventilation is increasedpH = 7.10 Actually alveolar ventilation is increasedpH = 6.1 + log 12/0.03x23pH = 6.1 + log 12/0.03x23pH = 6.1 + log 12/0.69pH = 6.1 + log 12/0.69pH = 7.34pH = 7.34


C. C. Renal Mechanisms (24-48 hrs)Renal Mechanisms (24-48 hrs) HH++ excretion excretion HCOHCO--

33 stores replenished stores replenished

2H2H+++SO+SO44----+24Na+24Na+++24HCO+24HCO3 3

-- 2Na 2Na+++SO+SO44

----+22Na+22Na+++22HCO+22HCO--33+2H+2H22COCO33

2CO2CO22+2H+2H22OO

Reclamation of BicarbonateReclamation of Bicarbonate

LUMENLUMEN

NaNa++

HCOHCO33--

HCOHCO33--+H+H++

HH22COCO33--

COCO22

HH22OO

CELLCELL PERITUBULARPERITUBULARFLUIDFLUID

C.AC.A

NaNa++

NaNa++ + +HCOHCO33--

HH++ HOH HOH

HCOHCO--33

++

COCO22

C.AC.AOHOH--

++

Regeneration of BicarbonateRegeneration of Bicarbonate

LUMENLUMEN

2 Na2 Na+ + HPOHPO44----

NaNa++HPOHPO4 4 ++HH++

NaNa++HH22 POPO44


NaNa++

NaNa++ + + HCOHCO--33

(New Bicarbonate)(New Bicarbonate)

HH++ HOH HOH

HCOHCO--33

++

COCO22

C.AC.AOHOH--

Titratable Titratable acidityacidity

NHNH44 Excretion Excretion

LUMENLUMEN

2Na2Na+ + SOSO44----

SOSO44----

2H2H++

2NH2NH33

2NH2NH44+SO+SO44----


2Na2Na++

2Na2Na++ + + 2HCO2HCO33--

(New Bicarbonate)(New Bicarbonate)

2H2H++ 2HOH 2HOH

2HCO2HCO33--

++

2CO2CO22

C.AC.A2OH2OH++

GlutamineGlutamine

2NH2NH33

NAE = T. Acidity + NHNAE = T. Acidity + NH44 excretion – HCO excretion – HCO--33 excretion excretion

Buffering of Volatile AcidsBuffering of Volatile Acids

TissueTissue Plasma Plasma RBCRBC

Dissolved Dissolved COCO22 ++ HH22OO

HH22COCO33

HH++ + HCO + HCO33--

HH++ buffered by buffered by Pr, HPOPr, HPO44

HCOHCO--33

ClCl--

OO22

COCO22

OO22

COCO22

++OHOH--

C.AC.A HOH HOHHCOHCO33

HH++

HbNH2+HbNH2+COCO22 Hb-NH-COO+H Hb-NH-COO+H+++ + (Carbamino Hb)(Carbamino Hb)

HbOHbO22 Hbn+ Hbn+ H H - - ++ HHb HHb

ClCl--

Acid Base DisordersAcid Base Disorders

pHpH HH++ 1 100 Event Event

CompensationCompensation

Metabolic acidosisMetabolic acidosis lowlow highhigh low HCOlow HCO33 low PCO low PCO22

Metabolic alkalosisMetabolic alkalosis highhigh lowlow high HCOhigh HCO33 high PCO high PCO22

Respiratory acidosisRespiratory acidosis lowlow highhigh high PCOhigh PCO22 high HCO high HCO33

Respiratory alkalosisRespiratory alkalosis highhigh lowlow low PCOlow PCO22 low HCO low HCO33

– EuphemiaEuphemia Normal pHNormal pH

– AcidemiaAcidemia Decreased pHDecreased pH

– AlkalemiaAlkalemia Increased pHIncreased pH

Metabolic AcidosisMetabolic Acidosis

Exogenous, Increased acid burden Exogenous, Increased acid burden Endogenous as in Lactate or ketoacidsEndogenous as in Lactate or ketoacids

Decreased acid excretion as in RTA 1Decreased acid excretion as in RTA 1 Loss of extra-cellular buffer (HCOLoss of extra-cellular buffer (HCO33) as in RTA 2 ) as in RTA 2 Lower GI lossLower GI loss

High AnionHigh Anion GapGap Metabolic Acidosis Metabolic AcidosisNormal Anion GapNormal Anion Gap or Hyperchloremic Metabolic Acidosis or Hyperchloremic Metabolic Acidosis

Metabolic AcidosisMetabolic AcidosisCauses of high Anion Gap metabolic acidosisCauses of high Anion Gap metabolic acidosis

KK Diabetic KetoacidosisDiabetic KetoacidosisUU UremiaUremiaSS Salicylate intoxicationSalicylate intoxicationSS Starvation ketosisStarvation ketosisMM Methanol ingestionMethanol ingestionAA Alcohol ketoacidosisAlcohol ketoacidosisUU Unmeasured Osmoles, Ethylene Glycol, ParaldehydeUnmeasured Osmoles, Ethylene Glycol, ParaldehydeLL Lactic acidosisLactic acidosis

MUDPILESMUDPILES MMethanol, ethanol, UUremia, remia, DDKA, KA, PParaldehyde, araldehyde, IINH/Iron NH/Iron toxicity, toxicity, LLactic acidodis, actic acidodis, EEthanol/Ethlene glycol, thanol/Ethlene glycol, SSalicylate toxicityalicylate toxicity


Causes of normal Anion Gap metabolic acidosisCauses of normal Anion Gap metabolic acidosis

HH HyperalimentationHyperalimentationAA AcetazolamideAcetazolamideRR Renal tubular acidosisRenal tubular acidosisDD DiarrhoeaDiarrhoeaUU Uretero sigmoidostomyUretero sigmoidostomyPP Pancreatic fistulaPancreatic fistula

Formulae To RememberFormulae To Remember

Metabolic AcidosisMetabolic AcidosisFor each 1mEq decrease in HCOFor each 1mEq decrease in HCO33, pCO, pCO22 decreases by 1.2 decreases by 1.2 or pCOor pCO22 = 1.5 (measured HCO = 1.5 (measured HCO33) + 8 ) + 8 ++ 2 2

Metabolic AlkalosisMetabolic AlkalosisFor each 1 mEq. Increase in HCOFor each 1 mEq. Increase in HCO33, pCO, pCO22 increases by 0.6 – 0.7 increases by 0.6 – 0.7 or pCO2 = 0.9 (measured HCOor pCO2 = 0.9 (measured HCO33 ) + 15 ) + 15 ++ 2 2


Respiratory AcidosisRespiratory AcidosisAcute:Acute: For each 10 mmHg increase in pCO For each 10 mmHg increase in pCO22, HCO, HCO33 increases by 1mEq / L and pH decreases by 0.08increases by 1mEq / L and pH decreases by 0.08Chronic:Chronic: For each 10 mmHg increase in pCO For each 10 mmHg increase in pCO22, HCO, HCO33

increases by 3.5 mEq / L and pH decreases by 0.03 increases by 3.5 mEq / L and pH decreases by 0.03 Respiratory AlkalosisRespiratory Alkalosis

Acute:Acute: For each 10 change in pCO For each 10 change in pCO22, HCO, HCO33 decreases by 2 & decreases by 2 & pH increases by 0.08pH increases by 0.08Chronic:Chronic: For each 10 change in PCO2, HCO For each 10 change in PCO2, HCO33 decreases by 5 decreases by 5 & pH increases by 0.03& pH increases by 0.03


pH will rise or fall by 0.1 ifpH will rise or fall by 0.1 if– [HCO3] changes by 6 mmol/l[HCO3] changes by 6 mmol/l– pCO2 changes by 1.58 kPA (1 kPA=7.6 mmHg)pCO2 changes by 1.58 kPA (1 kPA=7.6 mmHg)

Anion GapAnion Gap Law of electro neutrality:Law of electro neutrality:

– Blood plasma contains an = number of + Blood plasma contains an = number of + and – charges.and – charges.

The major cation is NaThe major cation is Na++..Minor cations are KMinor cations are K++, Ca, Ca++++ , Mg , Mg++++. .

The major anions are HC0The major anions are HC033-- & Cl & Cl--

(Routinely measured.)(Routinely measured.)– Minor anions include albumin, phosphate, Minor anions include albumin, phosphate,

sulfate (called unmeasured anions).sulfate (called unmeasured anions).– Organic acid anions include lactate and Organic acid anions include lactate and

acetoacetate,.acetoacetate,.

Anion Gap:Anion Gap:[Na][Na]+ + – [ Cl– [ Cl-- + HCO + HCO33--]]

This gap is due to unmeasured This gap is due to unmeasured anionsanionsNormal AG= 10-14(Average 10)Normal AG= 10-14(Average 10)

Unmeasured anions

Anion GapAnion Gap In metabolic acidosis, the In metabolic acidosis, the

strong acid releases strong acid releases protons that are buffered protons that are buffered primarily by [HC0primarily by [HC0--

33].].– This causes plasma HC0This causes plasma HC033

-- to to decrease, shrinking the HC0decrease, shrinking the HC033

-- on the ionogram.on the ionogram.

Anions that remain from Anions that remain from the strong acid, are added the strong acid, are added to the plasma.to the plasma.

– If HCl is added, the ClIf HCl is added, the Cl-- rises. rises. decreasing the HC0decreasing the HC033

--

If lactic acid is added, the If lactic acid is added, the lactate rises. Increasing the lactate rises. Increasing the total unmeasured anionstotal unmeasured anions

For High Anion Gap acidosisFor High Anion Gap acidosis, you wouldn't , you wouldn't use use

HCOHCO33 therapy until pH < 7.2 or 7.1 therapy until pH < 7.2 or 7.1

For Non-Anion Gap acidosisFor Non-Anion Gap acidosis, the primary , the primary problem is insufficient HCOproblem is insufficient HCO33, not over , not over

production of acid, so you would use HCOproduction of acid, so you would use HCO33

therapy to correct serum HCOtherapy to correct serum HCO33 to about 20. to about 20.

Metabolic AcidosisMetabolic AcidosisKey difference in treatment of High A-GAP and Key difference in treatment of High A-GAP and

Non-AGAP acidosisNon-AGAP acidosis

Metabolic AcidosisMetabolic AcidosisRenal FailureRenal Failure-- At GFR 40 – 50ml/min total NHAt GFR 40 – 50ml/min total NH44 excretion begins to fall excretion begins to fall-- Inability to excrete all the daily HInability to excrete all the daily H+ + loadload-- Decreased titratable acidity Decreased titratable acidity - Reduced HCOReduced HCO33 reabsorption reabsorptionDiabetic KetoacidosisDiabetic Ketoacidosis

Lack of insulin under utilization of glucose Lack of insulin under utilization of glucose FFA ketones are produced as alternate source of energyFFA ketones are produced as alternate source of energy

Aceto-acetic acid, B-OH butyric acid, AcetoneAceto-acetic acid, B-OH butyric acid, AcetoneSalicylate OverdoseSalicylate Overdose-- Acetylsalicylic acid Salicylic AcidAcetylsalicylic acid Salicylic Acid-- Respiratory alkalosis, Metabolic AcidosisRespiratory alkalosis, Metabolic Acidosis


Ethyl Alcohol Acetaldehyde Ethyl Alcohol Acetaldehyde Acetic AcidAcetic Acid

Methyl Alcohol Formaldhyde Methyl Alcohol Formaldhyde Formic AcidFormic Acid

Ethylene Alcohol Glycoaldehyde Glycolic acidEthylene Alcohol Glycoaldehyde Glycolic acidGlycooxalic acid Glycooxalic acid Oxalic acidOxalic acid

OSMOLAL GAP OSMOLAL GAP = Measured osmolality- calculated = Measured osmolality- calculated osmolality osmolality

Normal = < 10-15 mOsmol/Kg of H2ONormal = < 10-15 mOsmol/Kg of H2O

Metabolic Pathways of Four AlcoholsMetabolic Pathways of Four Alcohols


LACTIC ACIDOSISLACTIC ACIDOSIS Type AType A

– Cardiogenic shockCardiogenic shock– Hypovolemic shockHypovolemic shock– Septic shock Septic shock – Hypoxemia Hypoxemia

Type BType B– Ethanol, Methanol, Ethylene GlycolEthanol, Methanol, Ethylene Glycol– Biguanides, Biguanides, – SalicylatesSalicylates– Hereditary defectsHereditary defects

Normal lactate = 0.5 – 1.5mEq/l

Lactic Acidosis = 4 to 5 mEq/l


Renal Tubular Acidosis Renal Tubular Acidosis Hyperchloremia, Normal anion gapHyperchloremia, Normal anion gap– Type -1 (Classic-Distal RTA)Type -1 (Classic-Distal RTA)– Type -2 (Proximal RTA)Type -2 (Proximal RTA)– Type -4 (Hyperkalemic distal RTA)Type -4 (Hyperkalemic distal RTA)

APPROACH TO HYPERCHLOREMIC ACIDOSIS WITH APPROACH TO HYPERCHLOREMIC ACIDOSIS WITH HYPERKALEMIAHYPERKALEMIA

URINE pH during acidosisURINE pH during acidosis

< 5.5< 5.5 > 5.5> 5.5

PLASMA ALDOSTERONEPLASMA ALDOSTERONE HYPERKALEMIC DISTAL RTAHYPERKALEMIC DISTAL RTAlook for specific causelook for specific cause

LOWLOW NORMAL OR HIGH NORMAL OR HIGH

PLASMA CORTISOLPLASMA CORTISOL ALDOSTERONE RESISTANCEALDOSTERONE RESISTANCE

NORMALNORMAL LOW LOW

SELECTIVE ALDOSTERONE SELECTIVE ALDOSTERONE ADRENAL INSUFFICIENCYADRENAL INSUFFICIENCYDEFICIENCYDEFICIENCY

Metabolic AlkalosisMetabolic Alkalosis

Increased bicarbonate, decreased proton & chloride Increased bicarbonate, decreased proton & chloride concentration in ECF and alkalemiaconcentration in ECF and alkalemia

Loss of acid or addition of alkaliLoss of acid or addition of alkali Saline responsive (urinary Chloride <10 mmol/l)Saline responsive (urinary Chloride <10 mmol/l) Saline unresponsive(urinary Chloride >10 mmol/l)Saline unresponsive(urinary Chloride >10 mmol/l)

Symptoms & signsSymptoms & signs– Stupor, coma,Tissue hypoxia, Hypocalcemic symptoms, Stupor, coma,Tissue hypoxia, Hypocalcemic symptoms,

hypokalemia, Hypophosphatemia, hypomagnesemiahypokalemia, Hypophosphatemia, hypomagnesemia

Causes of Metabolic AlkalosisCauses of Metabolic Alkalosis Chloride Responsive Metabolic AlkalosisChloride Responsive Metabolic Alkalosis

– Vomiting, Villous adenoma,Vomiting, Villous adenoma,– Diuretic therapy, post hypercapnia stateDiuretic therapy, post hypercapnia state

Chloride Resistant Metabolic AlkalosisChloride Resistant Metabolic Alkalosis– Primary hyperaldosteronismPrimary hyperaldosteronism– Mineralocorticoid excess Mineralocorticoid excess

Glycyrrhizic acid, Cushing’s syndrome.Glycyrrhizic acid, Cushing’s syndrome. ACTH excess, High renin activity, K depletion Barter syndACTH excess, High renin activity, K depletion Barter synd. .

Milk-Alkali syndromeMilk-Alkali syndrome Acute alkali loadAcute alkali load

Metabolic AlkalosisMetabolic AlkalosisPathophysiologyPathophysiology

Chloride depletionChloride depletion

GFRGFR Stimulation of Renin Stimulation of Renin Proximal HCOProximal HCO33

Angiotensin System Angiotensin System reabsorptionreabsorption

Potassium depletionPotassium depletion Distal HCO Distal HCO33 reabsorptionreabsorption

Consequences of Losses of Gastric Secretion & Consequences of Losses of Gastric Secretion & Postulated FactorsPostulated Factors

Metabolic AlkalosisMetabolic Alkalosis

Saline responsive alkalosisSaline responsive alkalosis

Low urinary ClLow urinary Cl-- (<20 mmol/l) (<20 mmol/l)

Normal or low BPNormal or low BP

Gastric alkalosisGastric alkalosisDiureticsDiureticsAfter hypercapniaAfter hypercapniaKK++ depletion depletionRecovery phase of metabolic Recovery phase of metabolic acidosisacidosisRefeeding alkalosisRefeeding alkalosis

Saline resistant alkalosisSaline resistant alkalosis High Urinary ClHigh Urinary Cl-- (>30 mmol/l) (>30 mmol/l)

Normal BPNormal BP High BP High BP

Bartter’s syndrome Reno vascularBartter’s syndrome Reno vascularDiureticsDiuretics disease diseaseMgMg++++ depletion depletion Conn’s syndrome Conn’s syndromeSevere KSevere K++ depletion Cushing’s syndrome depletion Cushing’s syndrome

Causes of Respiratory AcidosisCauses of Respiratory Acidosis A. Decreased alveolar ventilation & COA. Decreased alveolar ventilation & CO22 removal removal

– Obstruction, prim. depression of respiratory center, Obstruction, prim. depression of respiratory center, mechanical or structural defect, mechanical or mechanical or structural defect, mechanical or neuromuscular defect, decreased stimulation of neuromuscular defect, decreased stimulation of respiratory center.respiratory center.

B. Decreased capillary exchange of COB. Decreased capillary exchange of CO22

cardiac arrest, circulatory shock, severe pulmonary cardiac arrest, circulatory shock, severe pulmonary edemaedema

Primary increase in pCOPrimary increase in pCO22 & decrease in pH & decrease in pHKidneys increase acid excretion which generates HCOKidneys increase acid excretion which generates HCO33..

Causes of Respiratory AlkalosisCauses of Respiratory Alkalosis

A. Increased CNS drive for respirationA. Increased CNS drive for respiration– Anxiety, CNS infection infarction or trauma, drugs, fever or sepsis, Anxiety, CNS infection infarction or trauma, drugs, fever or sepsis,

pregnancy & progesterone, liver diseasepregnancy & progesterone, liver disease B. Increased stimulation of chemo receptorsB. Increased stimulation of chemo receptors

– Anemia, carbon monoxide toxicity, pulmonary edema, pneumonia, Anemia, carbon monoxide toxicity, pulmonary edema, pneumonia, pulmonary emboli, decreased inspired Opulmonary emboli, decreased inspired O22 tension tension

C. Increased mechanical ventilationC. Increased mechanical ventilation– IatrogenicIatrogenic

Primary decrease in pCOPrimary decrease in pCO2 2 & high pH & low HCO& high pH & low HCO33

SymptomsSymptomsPeri-oral & extremity paraesthesiasPeri-oral & extremity paraesthesias


Types of disordersTypes of disorders Simple disordersSimple disorders Mixed disorders Mixed disorders

– (Double, Triple, Quadruple)(Double, Triple, Quadruple)

Anion GapAnion Gap : Na : Na++ – (Cl – (Cl- - + HCO+ HCO--33))

Normal : 12 (Range 10-14) Normal : 12 (Range 10-14) This gap is due to unmeasured anionsThis gap is due to unmeasured anions

Corrected HCOCorrected HCO33 = Measured HCO = Measured HCO33-- + (anion gap-12) + (anion gap-12)

Approach to Acid Base DisordersApproach to Acid Base Disorders

HistoryHistory ExaminationExamination Lab Data Lab Data

– Non electrolyte data: Urea, Creatinine, GlucoseNon electrolyte data: Urea, Creatinine, Glucose– Electrolytes data: NaElectrolytes data: Na++, K, K++, Cl, Cl--, HCO, HCO--

33

ABGsABGs Anion GapAnion Gap Osmolal GapOsmolal Gap

Clinical States & Acid Base DisorderClinical States & Acid Base Disorder

Clinical stateClinical state Acid-base disorderAcid-base disorder Pulmonary embolus Pulmonary embolus Respiratory alkalosis Respiratory alkalosis Hypotension Hypotension Metabolic acidosis Metabolic acidosis Vomiting Vomiting Metabolic alkalosis Metabolic alkalosis Severe diarrhea Severe diarrhea Metabolic acidosisMetabolic acidosis Cirrhosis Cirrhosis Respiratory alkalosis Respiratory alkalosis Renal failure Renal failure Metabolic acidosis Metabolic acidosis Sepsis Sepsis Respiratory alkalosis, Respiratory alkalosis,

metabolic acidosis metabolic acidosis Pregnancy Pregnancy Respiratory alkalosis Respiratory alkalosis

Urinary Anion GapUrinary Anion Gapu Urinary Anion Gap (NaUrinary Anion Gap (Na++ + K + K++ ) - Cl ) - Cl-- is an index of renal is an index of renal

ammonia secretion.ammonia secretion.u It is It is negativenegative in lower GI HCO3 loss but in lower GI HCO3 loss but positivepositive in RTA in RTA u The urine anion gap is most sensitive for distal RTA The urine anion gap is most sensitive for distal RTA u Proximal RTA's may have a preserved urine anion gap. Proximal RTA's may have a preserved urine anion gap. u Distal RTA--urine pH >5.5 on a FRESH urine sample even Distal RTA--urine pH >5.5 on a FRESH urine sample even

with severe acidosis with severe acidosis u Proximal RTA--urine acidification intact. Proximal RTA--urine acidification intact. u Can distinguish between them by Fractional Excretion of Can distinguish between them by Fractional Excretion of

bicarbonate WHEN SERUM BICARBONATE CORRECTED bicarbonate WHEN SERUM BICARBONATE CORRECTED (Proximal RTA >15%, Distal RTA <5%). (Proximal RTA >15%, Distal RTA <5%).

u Exceptions DKA, Volume depletionExceptions DKA, Volume depletion

Delta / Delta RatioDelta / Delta Ratio The Delta AG /Delta HCO3 ratio in an uncomplicated high The Delta AG /Delta HCO3 ratio in an uncomplicated high

AG metabolic acidosis should be between 1 and 2. AG metabolic acidosis should be between 1 and 2. A lower value (in which the AG is less than expected from A lower value (in which the AG is less than expected from

the HCO3) reflects either the HCO3) reflects either – urinary ketone losses (as in DKA), urinary ketone losses (as in DKA), – some cases of chronic renal failure (in which tubular damage some cases of chronic renal failure (in which tubular damage

allows filtered anions to be excreted but limits the degree of allows filtered anions to be excreted but limits the degree of hydrogen secretion) hydrogen secretion)

– combined high and normal AG acidosis, as might occur if diarrhea combined high and normal AG acidosis, as might occur if diarrhea were superimposed upon chronic renal failure . were superimposed upon chronic renal failure .

On the other hand, a Delta / Delta ratio above 2 indicates On the other hand, a Delta / Delta ratio above 2 indicates the plasma HCO3 is higher than expected from the rise in the plasma HCO3 is higher than expected from the rise in the AG; this usually reflects a concurrent metabolic the AG; this usually reflects a concurrent metabolic alkalosis, as with vomiting. alkalosis, as with vomiting.


ACID BASE ANALYSISACID BASE ANALYSISStep 1Step 1 : : Is the patient acidemic or alkalemic?Is the patient acidemic or alkalemic?Step 2Step 2 : : Is the overriding disturbance respiratory or Is the overriding disturbance respiratory or

metabolic?metabolic?Step 3Step 3 : : If the respiratory disturbance is present, is it If the respiratory disturbance is present, is it

acute or chronic?acute or chronic?Step 4Step 4 : : If metabolic acidosis is present, is there If metabolic acidosis is present, is there

increased anion gap?increased anion gap?Step 5Step 5 : : If metabolic disturbance is present, is the If metabolic disturbance is present, is the

respiratory system compensating adequately?respiratory system compensating adequately?Step 6Step 6 : : Are other metabolic disturbances present?Are other metabolic disturbances present?

Acid Base DisordersAcid Base DisordersEXAMPLESEXAMPLES

Case ICase I pHpH 7.217.21PCOPCO22 2525

HCOHCO33 1010

NaNa++ 130130ClCl-- 8080KK++ 5.15.1AGAG 4040Delta AGDelta AG 2828


Case IICase IIpHpH 7.317.31PCOPCO22 1010

HCOHCO33 55



Case IIICase IIIpHpH 7.077.07PCOPCO22 2828

HCOHCO33 88



Case IV Case IV pHpH 7.457.45PCOPCO22 7575

HCOHCO33 5050


Case 1Case 1

25 years old man with H/O recurrent renal stones has 25 years old man with H/O recurrent renal stones has following serum electrolyte datafollowing serum electrolyte data

SodiumSodium 137137PotassiumPotassium 3.53.5ChlorideChloride 112112BicarbonateBicarbonate 1717BUN BUN 1414Creatinine Creatinine 1.21.2AlbuminAlbumin 4.04.0

Case 1 ABGsCase 1 ABGs

– pHpH 7.31, 7.31, – pCOpCO22 30, 30, – HCOHCO33 1515

– Urine pH was 6.3.Urine pH was 6.3.– DIAGNOSIS ?DIAGNOSIS ?

Hyperparathyroidism?Hyperparathyroidism? Distal RTA ?Distal RTA ? Medullary Sponge Kidney ? Medullary Sponge Kidney ?

Case -1Case -1 History:History: A 49 yrs old woman was admitted with c/o anorexia, A 49 yrs old woman was admitted with c/o anorexia,

nausea,vomiting, shortness of breath, cough & ankle edema. She has nausea,vomiting, shortness of breath, cough & ankle edema. She has been taking furosemide 120 mg & digoxin 0.25 mg daily for heart failure.been taking furosemide 120 mg & digoxin 0.25 mg daily for heart failure.

Examination:Examination: P 130, BP 104/74, T 37 P 130, BP 104/74, T 3700C, RR 16. Her lips were cyanosed C, RR 16. Her lips were cyanosed and JVP raised. Pitting edema up to thighs. Heart enlarged with a gallop and JVP raised. Pitting edema up to thighs. Heart enlarged with a gallop rhythm at the apex, rales in both lungs. Abdomen distended with rhythm at the apex, rales in both lungs. Abdomen distended with ascites. Liver enlarged by 10 cm below the RCMascites. Liver enlarged by 10 cm below the RCM

Labs:Labs: Hb. 15 G/dl, Hct 51%, WBC 9100/cmm, Urine Sp.Gr.1010, pH 7, Hb. 15 G/dl, Hct 51%, WBC 9100/cmm, Urine Sp.Gr.1010, pH 7, Protein- negative, Sediment- nil. BUN 53 mg/dl, serum Cr.1.1mg/dl Protein- negative, Sediment- nil. BUN 53 mg/dl, serum Cr.1.1mg/dl Blood glucose 130 mg/dl. S.NaBlood glucose 130 mg/dl. S.Na++ 135, S.K 135, S.K++ 3.2, S. Cl 3.2, S. Cl-- 85 mEq/l. 85 mEq/l.

ABG = pH 7.49, pOABG = pH 7.49, pO22 50, pCO 50, pCO22 60 mmHg, HCO 60 mmHg, HCO33 38mmol/l 38mmol/l

Case 1 - QuestionsCase 1 - Questions

11. This woman shows. This woman shows A. Metabolic alkalosisA. Metabolic alkalosis B. Compensated respiratory acidosisB. Compensated respiratory acidosis C. Met. Alkalosis & Respiratory Acidosis C. Met. Alkalosis & Respiratory Acidosis

D. Lactic acidosisD. Lactic acidosis

Case - 2Case - 2

History:History: A 61 yrs old woman gave a h/o Right nephrectomy 16 yrs ago A 61 yrs old woman gave a h/o Right nephrectomy 16 yrs ago

with Left ureteric implantation to sigmoid colon. Subsequent to this with Left ureteric implantation to sigmoid colon. Subsequent to this

she had elevated BP and elevated serum chloride. She had a previous she had elevated BP and elevated serum chloride. She had a previous

h/o Ca cervix with bladder involvement treated by cystectomy, h/o Ca cervix with bladder involvement treated by cystectomy,

hysterectomy & pelvic irradiationhysterectomy & pelvic irradiation

Examination:Examination: P 84/min, BP 150/100 mmHg, RR 20/min, T 37C No P 84/min, BP 150/100 mmHg, RR 20/min, T 37C No

obvious distress but breathing was somewhat laboured. obvious distress but breathing was somewhat laboured.

Labs:Labs: Hb 14g/dl, Hct 41%, WBC 6400 DLC normal.BUN 50mgdl, Hb 14g/dl, Hct 41%, WBC 6400 DLC normal.BUN 50mgdl,

S.Creatinine 2.4mg/dl, S. Calcium 9.5mg/dl, Phosphorus 6.2 mg/dl, S.Creatinine 2.4mg/dl, S. Calcium 9.5mg/dl, Phosphorus 6.2 mg/dl,

NaNa++ 143, K 143, K++ 3.8, Cl 3.8, Cl-- 120mEq/l, S. uric acid 5 mg/dl, pH 7.30, CO 120mEq/l, S. uric acid 5 mg/dl, pH 7.30, CO2 2 11.511.5


1. 1. Uretero sigmoidostomy tends to produceUretero sigmoidostomy tends to produce A. HypokalemiaA. Hypokalemia B. Low serum bicarbonateB. Low serum bicarbonate C. Hyperchloremic acidosisC. Hyperchloremic acidosis D. All of theseD. All of these

2. 2. Cause of high serum chloride isCause of high serum chloride is A. Breakdown of excreted urea in the gut with subsequent A. Breakdown of excreted urea in the gut with subsequent

NHNH33 absorption & concomitant anion absorption absorption & concomitant anion absorption B. Selective Cl absorption from renal tubule because of B. Selective Cl absorption from renal tubule because of

acidosisacidosis C. Excessive NaCl absorption from the gutC. Excessive NaCl absorption from the gut D. None of the aboveD. None of the above


3.Which of the following are useful 3.Which of the following are useful in this conditionin this condition

A. Large fluid intakeA. Large fluid intake B. Maintenance antibioticsB. Maintenance antibiotics C. Sod. bicarbonate orallyC. Sod. bicarbonate orally D. Potassium & sodium citrateD. Potassium & sodium citrate

Mixed acid base disordersMixed acid base disorders

pHpH pCOpCO22 HCOHCO33 NaNa++ KK+ + ClCl AG D. AG AG D. AG ConditionCondition

7.107.10 5050 1515 140140 5.0 102 23 115.0 102 23 11 Renal F + Resp FRenal F + Resp F

6.996.99 3434 88 141141 6.0 105 286.0 105 28 16 16 CPRCPR

7.697.69 3030 3535 134134 4.0 844.0 84 15 15 3 3 Hepatic F + NG aspHepatic F + NG asp

7.607.60 4040 3838 131131 3.6 773.6 77 16 16 4 4 CHF + DiureticsCHF + Diuretics

7.447.44 5555 3636 135135 3.8 843.8 84 15 15 3 3 COPD + DiureticsCOPD + Diuretics

Mixed acid base disordersMixed acid base disorders

pHpH pCOpCO22 HCOHCO33 NaNa++ KK+ + ClCl AG D. AG Condition AG D. AG Condition

7.457.45 4848 3232 133133 4.2 854.2 85 16 4 16 4 ARDS + Acetate TPN ARDS + Acetate TPN

7.447.44 1212 88 136136 5.5 106 22 10 Renal F + G - Sepsis5.5 106 22 10 Renal F + G - Sepsis

7.407.40 1515 99 138138 4.1 110 19 7 Salicylate Toxicity4.1 110 19 7 Salicylate Toxicity

7.437.43 3939 2525 132132 3.7 84 23 11 Alcohol L Dis + Diure3.7 84 23 11 Alcohol L Dis + Diure

7.377.37 3535 2020 138138 4.0 934.0 93 25 13 DKA + HCO3 therapy 25 13 DKA + HCO3 therapy

7.547.54 4141 3434 140140 3.8 933.8 93 13 1 13 1 COPD + Mech . Vent COPD + Mech . Vent

Mixed Acid Base DisordersMixed Acid Base DisorderspHpH pCOpCO22 HCOHCO33 NaNa++ KK++ ClCl--

7.687.68 2828 3232 137137 3.53.5 91917.387.38 5757 3333 134134 4.74.7 77777.437.43 2525 1616 135135 3.23.2 97977.127.12 1616 55 137137 3.63.6 1141147.227.22 8080 3232 141141 4.34.3 99997.547.54 1212 1010 132132 3.23.2 1071077.097.09 6565 1919 136136 3.33.3 1051057.187.18 4444 1616 133133 5.75.7 1001007.367.36 3131 1717 132132 4.04.0 89897.407.40 4040 2424 143143 5.55.5 9595

Formulas for calculating laboratory values in Formulas for calculating laboratory values in acid-base disordersacid-base disorders

Equation 1.Equation 1. – Modified Henderson-Hasselbalch equation, to check validity of laboratory Modified Henderson-Hasselbalch equation, to check validity of laboratory

measurements obtainedmeasurements obtained H+ = 24 x PaCO H+ = 24 x PaCO22 ÷ HCO ÷ HCO33- = 40 nEq/L - = 40 nEq/L

Equation 2.Equation 2. – Law of electrical neutrality (ie, number of cations in serum must equal number of Law of electrical neutrality (ie, number of cations in serum must equal number of

anions)anions) Cl Cl-- + HCO + HCO33- + unmeasured anions = Na- + unmeasured anions = Na++ + unmeasured cations + unmeasured cations

Equation 3.Equation 3. – Anion gap: difference between unmeasured anions and unmeasured cations Anion gap: difference between unmeasured anions and unmeasured cations

(normal = 10 ± 4 mEq/L)(normal = 10 ± 4 mEq/L) Anion gap = Na Anion gap = Na++ - Cl - Cl-- - HCO - HCO33

Equation 4.Equation 4. – Delta anion gap: elevation of anion gap relative to decrease in HCODelta anion gap: elevation of anion gap relative to decrease in HCO33- (normal = 1 - (normal = 1

to 1.6)to 1.6) Delta anion gap = (anion gap - 10) ÷ (24 - HCO Delta anion gap = (anion gap - 10) ÷ (24 - HCO33-) -)

Formulas for calculating laboratory values in Formulas for calculating laboratory values in acid-base disordersacid-base disorders

Equation 5.Equation 5. – Osmole gap: difference between measured serum osmolarity and Osmole gap: difference between measured serum osmolarity and

calculated osmolarity (normal = 10 to 20 mOsm/L)calculated osmolarity (normal = 10 to 20 mOsm/L) Osmole gap = measured serum osm - calculated osm Osmole gap = measured serum osm - calculated osm

Equation 6.Equation 6. – Calculated osmolarityCalculated osmolarity

Calculated osm (mOsm/L) = (2 x Na Calculated osm (mOsm/L) = (2 x Na++) + (glucose ÷ 18) + (blood ) + (glucose ÷ 18) + (blood urea nitrogen ÷ 2.8) = 275 to 290 mOsm/L urea nitrogen ÷ 2.8) = 275 to 290 mOsm/L

Equation 7.Equation 7. – Law of electrical neutrality for urine anion gap (ie, number of anions Law of electrical neutrality for urine anion gap (ie, number of anions

in urine must equal number of cations)in urine must equal number of cations) Unmeasured anions + Cl Unmeasured anions + Cl-- = unmeasured cations + Na = unmeasured cations + Na++ + K + K++

Equation 8.Equation 8. – Urine anion gap: unmeasured anions - unmeasured cations (normal Urine anion gap: unmeasured anions - unmeasured cations (normal

= -20 to 0 mEq/L)= -20 to 0 mEq/L) Urine anion gap = Na Urine anion gap = Na++ + K + K++ - Cl - Cl--

Base Excess-Example 1 Base Excess-Example 1 pH = 7.2, PCOpH = 7.2, PCO22 = 60 mmHg, SBE = 0 mEq/L = 60 mmHg, SBE = 0 mEq/L

Overall change is acid. Overall change is acid. Respiratory change is also acid - therefore Respiratory change is also acid - therefore

contributing to the acidosis. contributing to the acidosis. SBE is normal - no metabolic compensation. SBE is normal - no metabolic compensation.

Therefore, pure respiratory acidosis. Therefore, pure respiratory acidosis. Typical of acute respiratory depression. Typical of acute respiratory depression.

Magnitude: marked respiratory acidosis Magnitude: marked respiratory acidosis

Base Excess Example 2 Base Excess Example 2 pH = 7.35, PCOpH = 7.35, PCO22 = 60 mmHg, SBE = 7 mEq/L = 60 mmHg, SBE = 7 mEq/L

Overall change is slightly acid. Overall change is slightly acid. Respiratory change is also acid - therefore contributing to the Respiratory change is also acid - therefore contributing to the acidosis. acidosis.

Metabolic change is alkaline - therefore compensatory. Metabolic change is alkaline - therefore compensatory. The respiratory acidosis is 20 mmHg on the acid side of normal (40). The respiratory acidosis is 20 mmHg on the acid side of normal (40).

To completely balance plus 20 would require 20 * 3 / 5 = 12 mEq/L To completely balance plus 20 would require 20 * 3 / 5 = 12 mEq/L SBE SBE

The actual SBE is 7 eEq/L, which is roughly half way between 0 and The actual SBE is 7 eEq/L, which is roughly half way between 0 and 12, i.e., a typical metabolic compensation. The range is about 6mEq/L 12, i.e., a typical metabolic compensation. The range is about 6mEq/L wide - in this example between about 3 and 9 mEq/L. wide - in this example between about 3 and 9 mEq/L.

Magnitude: marked respiratory acidosis with moderate metabolic Magnitude: marked respiratory acidosis with moderate metabolic compensation compensation

Base Excess Example 3Base Excess Example 3pH = 7.15, PCOpH = 7.15, PCO22 = 60 mmHg, SBE = -6 mEq/L = 60 mmHg, SBE = -6 mEq/L

Overall change is acid. Overall change is acid. Respiratory change is acid - therefore Respiratory change is acid - therefore

contributing to the acidosis. contributing to the acidosis. Metabolic change is Metabolic change is alsoalso acid - therefore acid - therefore

combined acidosis. combined acidosis. The components are pulling in same direction - The components are pulling in same direction -

neither can be compensating for the other neither can be compensating for the other Magnitude: marked respiratory acidosis and mild Magnitude: marked respiratory acidosis and mild

metabolic acidosis metabolic acidosis

Base Excess Example 4 Base Excess Example 4 pH = 7.30, PCOpH = 7.30, PCO22 = 30 mmHg, SBE = -10 mEq/L = 30 mmHg, SBE = -10 mEq/L Overall change is acid. Overall change is acid. Respiratory change is alkaline - therefore Respiratory change is alkaline - therefore NOTNOT contributing to the acidosis. contributing to the acidosis. Metabolic change Metabolic change isis acid - therefore responsible for the acidosis. acid - therefore responsible for the acidosis. The components are pulling in opposite directions. SBE is the acid component The components are pulling in opposite directions. SBE is the acid component

so it is primarily a metabolic problem with some respiratory compensation so it is primarily a metabolic problem with some respiratory compensation The metabolic acidosis is 10 mEq/L on the acid side of normal (0). To The metabolic acidosis is 10 mEq/L on the acid side of normal (0). To

completely balance 10 would require 10 * 5 / 3 = 17 mmHg respiratory completely balance 10 would require 10 * 5 / 3 = 17 mmHg respiratory alkalosis (= 23 mmHg) alkalosis (= 23 mmHg)

The actual PCOThe actual PCO22 is 30 eEq/L which is roughly half way between 23 and 40, i.e., is 30 eEq/L which is roughly half way between 23 and 40, i.e., a typical respiratory compensation. The range is about 10 mmHg wide - in this a typical respiratory compensation. The range is about 10 mmHg wide - in this example between about 27 and 37 mmHg. example between about 27 and 37 mmHg.

Magnitude: marked metabolic acidosis with mild respiratory compensation. Magnitude: marked metabolic acidosis with mild respiratory compensation.

Acid Base Balance PSN LHR

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