acid base disorder

ACID BASE ACID BASE DISORDERDISORDER

Ubaidur RahamanUbaidur Rahaman

Senior Resident, Senior Resident, CCM, SGPGIMSCCM, SGPGIMS

Lucknow, IndiaLucknow, India

Life is struggle, not against sin, not against money power…. but against

Hydrogen ion.- H .L. MENCKEN

loss of “bicarbonate of soda”loss of “bicarbonate of soda” as fundamental disturbance in patient dying of choleraas fundamental disturbance in patient dying of cholera

““Acid” delivers H+ and “base” delivers OH- into the solutionAcid” delivers H+ and “base” delivers OH- into the solution

strong acid or base- dissociates completely at physiological pHstrong acid or base- dissociates completely at physiological pH

strong ionstrong ion

do not bind easily, exist in free form.do not bind easily, exist in free form.

eg. Na, K, Ca, Mg, Cl,SO4-, Latate, ketoacidseg. Na, K, Ca, Mg, Cl,SO4-, Latate, ketoacids

strong cations- Arrhenius base; strong anions- Arrhenius acidstrong cations- Arrhenius base; strong anions- Arrhenius acid

1831: O’ Shaughnessy1831: O’ Shaughnessy

1903:1903: ArrheniusArrhenius

coined “ acid base balance”coined “ acid base balance”

carbonic acid equilibrium- CO2 + H2O ↔ H2CO3 ↔ Hcarbonic acid equilibrium- CO2 + H2O ↔ H2CO3 ↔ H++ + HCO3 + HCO3--

pH scale: pH = -log [H+ ] pH scale: pH = -log [H+ ]

expressed Henderson equation asexpressed Henderson equation as pH = 6.1 + log [ {HCO3- } / PCO2 ˣ 0.03 ] pH = 6.1 + log [ {HCO3- } / PCO2 ˣ 0.03 ]

Hendersen Hasselbalch equationHendersen Hasselbalch equation

1909 – Henderson 1909 – Henderson

1912 – Sorenson 1912 – Sorenson

1916 – Hasselbalch1916 – Hasselbalch

Acid base physiology in bodyAcid base physiology in body

Solution- H2O ; 60% of body weightSolution- H2O ; 60% of body weightH2OH2O↔ H↔ H++ + OH + OH--

All HAll H+ + are derived from water dissociation are derived from water dissociation

In pure water, at 25ºC [H+] and [OH-] = 1ˣ10-7 mmol/L and pH= 7

temperature ↑- pH ↓ temperature ↓- pH ↑

pH : ICF= 6.8-7.0, ECF= 7.4

ICF- relatively impermeable to ionic material,

pH remains constant despite dramatic change in ECF pH

ECF- pH affected due to fluid, electrolytes and CO2

Effect of changes in these factors

H2O↔ H+ + OH-

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-

Factors determining [H+] of ECF

1. Strong ions Na, K, Ca, Mg,

Cl, SO4, Lactate, Keto ions

2. Weak acids- Albumin, Pi

3. CO2

These factors must obey three distinct lawsThese factors must obey three distinct laws

1. Electrical neutralitysum of all cations = sum of all anions

2. Mass conservation substances remain constant unless added, removed, generated or destroyed

3. Dissociation equillibriumof all incompletely dissociated substances must be satisfied,

according to law of mass action

Therefore Therefore

[Na + K + Ca+ Mg] – [ Cl+ SO4+ Lactate + Keto ions] – [ HCO3+ Albumin + Pi] = 0

SID = HCO3+ Atot

∆ SID / Atot ∆ [H+]

↑ SID or ↓Atot ↓[H+] – alkalosis

↓ SID or ↑Atot ↑[H+]-- acidosis

↓albumin and ↓Pi may mask the effect of increased acid

Major sources of acids in bodyMajor sources of acids in body

Volatile acid-CO2 •result of oxidative metabolism

• 12,500 meq of HH++ / day • excreted through lungs

• buffered by Hb

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-CO2

dHb-histidine residue

Cl

Haldane effect

Chloride shiftCO2 also buffered directly by Hb and plasma proteins

Also carried in dissolved form

Major sources of acids in bodyMajor sources of acids in body

Metabolic acids•20-80 meq of HH++ /day

• buffered by HCO3 and weak acids( albumin and Pi)

• excreted through kidney

What neutralizes these AcidsWhat neutralizes these Acids

solution of two or more chemicals that minimizes changes in pH solution of two or more chemicals that minimizes changes in pH in response to addition of acid or basein response to addition of acid or base

BufferBuffer

most buffers are weak acidsmost buffers are weak acids HCO3- , Hb, Albumin, PiHCO3- , Hb, Albumin, Pi

ACID BASE ANALYSIS

Historical overview of acid- base analysisHistorical overview of acid- base analysis

Acid base analysis

Bicarbonate centered approach

Stewart strong ion equation

Constable simplifiedStrong ion equation

Hendersen- Hasselbalchequation

Singer- HastingsBuffer base

Strong ion approach

HCO3/ PaCO2equation

Base excess equation

Boston approachCopenhegen approach

Acid-base analysis: a critique of the Stewart and bicarbonate-centered approachesIra Kurtz, Jeffrey Kraut, Vahram Ornekian and Minhtri K. NguyenAm J Physiol Renal Physiol 294:F1009-F1031, 2008

Is it feasible to measure every possible fixed acid?No.

BUT indirectly can estimate the total amount of excess fixed acid

1.

Fixed acids in ECF- buffered predominantly by bicarbonate

• One bicarbonate molecule will react with one H+ molecule produced by one molecule of fixed acid

• HCO3 will decrease by one molecule for every molecule of fixed acid present.

Number of fixed acid = ∆ [HCO3] from baseline

PCO2/ HCO3 APPROACH ( BOSTON APPROACH)Schwartz and colleague, Tufts University, Boston, USA

Normogram was developed using retrospective data from large population of patients

ACID- BASE NORMOGRAM USING BOSTON APPROACHACID- BASE NORMOGRAM USING BOSTON APPROACH

Metabolic

Acidosis- ∆PaCO2= 1.5 ˣ ∆ HCO3 + 8 ± 2Alkalosis- ∆PaCO2= 0.7 ˣ ∆ HCO3 + 21 ± 2

Respiratory acidosis

Acute - ∆HCO3= 1 ˣ (∆ PaCO2/10) Chronic - ∆HCO3= 4 ˣ (∆ PaCO2/10)

Respiratory alkalosis

Acute - ∆HCO3= 2 ˣ (∆ PaCO2/10) Chronic- ∆HCO3= 4 ˣ (∆ PaCO2/10)

ACID- BASE calculation USING BOSTON APPROACHACID- BASE calculation USING BOSTON APPROACH

DOES ∆HCO3 truly QUNTIFIES METABOLIC COMPONENT?

Is PaCO2 and HCO3 are independent of one another?

NO

PCO2 also will change the bicarbonate

+

Buffering in whole blood by HCO3 ≠ buffering In the ECF ( Blood is a better buffer then the whole ECF because of its content of the buffer Hb.)

In ECF apart from HCO3, other non volatile buffer- albumin, Pi are also present

Boston approach assesses compensation as another primary disorder

Quantification of metabolic componentQuantification of metabolic component independent of acute change in PCO2 independent of acute change in PCO2

BUFFER BASE (BB) BUFFER BASE (BB)

1948 – Singer and Hastings1948 – Singer and Hastings

BB = fixed cations – fixed anions= Na + K - Cl

BB = [HCO3- ] + [ A- ] [ A- ] = non bicarbonate buffer anions= Hb, Albumin, Pi

Fixed ions= strong ions

Acute change in PCO2 ↔ equal and opposite change in [HCO3-] and [ A-] Acute change in PCO2 ↔ equal and opposite change in [HCO3-] and [ A-] BB remains unaffected BB remains unaffected

BufferBuffer solution of two or more chemicals that minimizes changes in pH in response to solution of two or more chemicals that minimizes changes in pH in response to

addition of acid or base.addition of acid or base. most buffers are weak acids –HCO3- , Hb, Albumin, Pimost buffers are weak acids –HCO3- , Hb, Albumin, Pi

Quantification of metabolic componentQuantification of metabolic component independent of acute change in PCO2 independent of acute change in PCO2

Standardized base excess ( SBE) – serum base excess to negate dynamic Standardized base excess ( SBE) – serum base excess to negate dynamic effect of RBC in acid- base and electrolyte exchange.effect of RBC in acid- base and electrolyte exchange.

base deficit/ excess(BDE)base deficit/ excess(BDE)1948 – Sigaard- Anderson1948 – Sigaard- Anderson

amount of strong acid or base that must be added to whole blood in vitro to

restore the pH to 7.4 while the PCO2 is kept at 40 mmHg at 38C

Blood-gas machines calculate SBE as:Blood-gas machines calculate SBE as:

SBE = 0.9287 * (HCO3- - 24.4 + (14.83 * (pH – 7.4)SBE = 0.9287 * (HCO3- - 24.4 + (14.83 * (pH – 7.4)

based on data derived retrospectively from large population of patients normogrambased on data derived retrospectively from large population of patients normogramwas developedwas developed

Acid- base Normogram and calculation based on BDE approachAcid- base Normogram and calculation based on BDE approach ( Copenhegen approach) ( Copenhegen approach)

Metabolicacidosis - ∆PaCO2= ∆ SBE

alkalosis- ∆PaCO2= 0.6* ∆ SBE

RespiratoryAcute acidosis/ alkalosis -∆ SBE= 0

chronic acidosis- ∆ SBE= 0.4* ∆PaCO2

OK, We can detect quantitatively the metabolic acid- base disorder, OK, We can detect quantitatively the metabolic acid- base disorder, but but

can we detect the cause?can we detect the cause?

Metabolic acidosishyperchloremic vs unmeasured anions( lactic/ ketoacids)

Metabolic alkalosis hypochloremic vs hypoalbuminemic

Hypoalbuminemic critically ill patient with lactic acidosis may have a normal pH, HCO3 and BE

We can miss the presence of acid- base disorder

Leading to

Inappropriate and inadequate therapy

ANION GAP(AG)ANION GAP(AG)Emmett and NarinsEmmett and Narins

Based on law of electroneutralityBased on law of electroneutrality

AG= [Na + K ] – [Cl+ HCO3]= A + UMA

MeasuredCations

[Na][K]

Measuredanions

[Cl][HCO3]

A-

UMA-

A- = weak acids= Albumin, Pi

UMA= unmeasured anions= unmeasured strong anions= lactate, keto ions

Normal AG= 12 ± 4= A-

UMA= 0

}

Lactic/ keto acidosis= UMAAG> 16

But But if [A-] are reduced

(hypoalbuminemia, hypophosphatemia)AG may be normal in lactic/ketoacidosis

CORRECTED ANION GAPCORRECTED ANION GAPFIGGE AND COLLEAGUEFIGGE AND COLLEAGUE

Calculated AG+ 2.5 ( 4.5 - s. albumin)

BUT

we are still using HCO3 in the equationwhich may be affected independent to metabolic disturbance

What is the answer?What is the answer?

BDE and AG approach may underestimate extent of metabolic disturbance

STRONG ION APPROACHSTRONG ION APPROACH1878- Stewart1878- Stewart

Based on law of electroneutrality, mass conservation and dissociation equillibrium

SID = [Na + K +Ca + Mg ] – [Cl + UMA]= BB = HCO3 + ATOT

Strong cations

[Na][K]

[Ca][Mg]

HCO3

Strong anions

[Cl][SO4][UMA]

ATOT

ATOT = weak acids= Albumin, Pi


Normal SID= 40-44 meq/L= HCO3 + ATOT

UMA= 0

}

STRONG ION GAPSTRONG ION GAP

SIDa = [Na + K +Ca + Mg ] – [Cl ]

Strong cations

[Na][K]

[Ca][Mg]

HCO3

[UMA]

Strong anions

[Cl][SO4]

ATOT

ATOT = weak acids= Albumin, Pi


SID Gap = SIDe – SIDaNormal SID Gap = 0

} SIDe = HCO3 + ATOT}If SID Gap < 0 – UMA

SID Gap = UMA

EFFECT OF CHANGE IN STRONG IONEFFECT OF CHANGE IN STRONG ION

Metabolic Acidosis

↓ SID• water excess - dilutional

•↓ Na• ↑ Cl, Lactate, keto ions,

↑ATOT

• ↑ Pi, Albumin

Metabolic Alkalosis

↑ SID• water deficit - contraction

•↑ Na• ↓ Cl, Lactate, keto ions,

↓ ATOT

• ↓ Pi, Albumin

BASE DEFICIT/ EXCESS (BDE) GAPGilfix and colleague

Recalculation of BDE using Strong ion, free water and albumin

BDE Gap = BDEmeas – BDE calc

Normal BDE gap = 0

If gap + = UMA

BDEBDENaClNaCl = [Na + Cl] – 38 = [Na + Cl] – 38

BDEBDEAlbAlb = 2.5 [ 4.2 – s. Alb] = 2.5 [ 4.2 – s. Alb]

BDEcalc = BDEBDEcalc = BDENaCl NaCl + + BDEBDEAlbAlb

Na- 117, Na- 117, K-3.9K-3.9Ca-3,Ca-3,Mg- 1.4 Mg- 1.4 Cl- 92Cl- 92Pi- 0.6 mmol/dlPi- 0.6 mmol/dlAlbumin- 0.6Albumin- 0.6 g/dl g/dl

pH- 7.33pH- 7.33

PaCO2-30 PaCO2-30

HCO3- 15 HCO3- 15

SBE: -10SBE: -10

AG=10, corrAG=19.5∆PaCO2= ∆BE= no respiratory component

Impression: high AG metabolic acidosis

with respiratory compensation

Is this that simple as it appears?

Consider following patient:

ACIDOSIS 1. Excess free water- dilutional2. Hyperchloremia3. UMA- lactate/ fixed renal

acid/ ketoacids

ALKALOSIS:• Hypoalbuminemia• hypophosphatemia

BDENacl= (117-92) – 38 = -13BDE alb = 2.5 ( 4.2- 0.6) = 9.5BDEcalc = (-13) + (9.5) = - 3.5

BDE gap = (-10) –( - 3.5) = - 6.5 = UMA

Let’s re-evaluate it with BDE gap approach:

ph and BDE does not mirror this severity of metabolic disturbance.Owing to alkalinizing force – hypoalbuminemia, and hypophosphatemia

Knowing this will definitely improve our management strategy

For

ces

at p

lay

Na-144Na-144K- 4K- 4Cl- 110Cl- 110pH- 7.28pH- 7.28Pco2- 24Pco2- 24HCO3- 8HCO3- 8BE -16BE -16Lactate- 11Lactate- 11

Urea- 10Urea- 10Creatinine- 2Creatinine- 2Albumin- 4Albumin- 4 Impression:

high AG metabolic acidosis- lactic acidosiswith respiratory compensation

The patient is aggressively volume resuscitated and brought to the operating room.The patient is aggressively volume resuscitated and brought to the operating room.A blood gas and serum chemistry are taken on the patient, A blood gas and serum chemistry are taken on the patient,

now mechanically ventilated in the intensive care unitnow mechanically ventilated in the intensive care unit

A 45-year-old man RTA, is bleeding, pulse is weak, Blood pressure is 90/50 mm Hg, A 45-year-old man RTA, is bleeding, pulse is weak, Blood pressure is 90/50 mm Hg, heart rate is 120 beats/min, respiratory rate is 36/min, and temperature is 35°C.heart rate is 120 beats/min, respiratory rate is 36/min, and temperature is 35°C.Blood chemistry and ABG is following:Blood chemistry and ABG is following:

BDENacl= (144-110) – 38 = -4 BDE alb = 2.5 ( 4.2- 4.0) = 0.5 BDEcalc = (-4) + (0.5) = - 3.5

BDE gap = (-16) –( - 3.5) = -12.5 = UMA= lactate ∆PaCO2= ∆BE= no respiratory component

After 12 hours, blood chemistry and gas is following:After 12 hours, blood chemistry and gas is following:

Impression hyperchloremic metabolic acidosis

+ lactic acidosis

Na-148,Na-148,K- 3K- 3Cl- 120Cl- 120lactate 5lactate 5pH 7.33pH 7.33Pco2 35Pco2 35HCO3- 18HCO3- 18BE -11BE -11

urea 10urea 10creatinine 2creatinine 2albumin 2albumin 2

Is the patient still under-resuscitated?Is the patient still under-resuscitated?Let’s re-evaluate ABG using BDE approachLet’s re-evaluate ABG using BDE approach

Patient is adequately resuscitated but with NS– leading to hyperchloremia

BDENacl= (148-120) – 38 = -10 BDE alb = 2.5 ( 4.2- 2.0) = 5.0

BDEcalc = (-10) + (5) = - 5

BDE gap = (-11) –( - 5) = - 6= UMA= latate ∆PaCO2 <∆BE= mild respiratory acidosis

Evaluation by different Evaluation by different methodsmethods

Na-156Na-156K- 3.98K- 3.98Cl- 121Cl- 121pH- 7.22pH- 7.22Pco2- 33Pco2- 33HCO3- 13.5HCO3- 13.5BD-10.1BD-10.1Lactate- 3.2Lactate- 3.2

BUN- 8BUN- 8Creatinine- 1.87Creatinine- 1.87Albumin- 3.1Albumin- 3.1Pi- 6.5Pi- 6.5

Impression:1. high anionic gap metabolic acidosis- UMA

2. Coexisting metabolic alkalosis

28 year female, case of Acute liver failure unknown etiology, in septic shock,28 year female, case of Acute liver failure unknown etiology, in septic shock, acute lung injury and acute kidney injury- non oliguric.acute lung injury and acute kidney injury- non oliguric.

AG = 156 – (121 + 13.5 ) = 21.5

Corrected AG= 21.5 + 2.5 (4.2 – 3.0) = 21.5 + 3 = 24.5

Delta Gap = 24.5 – 12/ 24 – 13.5 = 12.5/ 10.5 = 1.19

continued….

Na-156Na-156K- 3.98K- 3.98Cl- 121Cl- 121pH- 7.22pH- 7.22Pco2- 33Pco2- 33HCO3- 13.5HCO3- 13.5BD-10.1BD-10.1Lactate- 3.2Lactate- 3.2

BUN- 8BUN- 8Creatinine- 1.87Creatinine- 1.87Albumin- 3.1Albumin- 3.1Pi- 6.5Pi- 6.5

Impression:1. Metabolic acidosis- mineral related- precaution regarding fluid selection

2. Metabolic acidosis- UMA related- optimize perfusion and watch for renal function

3. Metabolic alkalosis- albumin related- not to be treated

BDENacl= (156-121) – 38 = -3 BDE alb = 2.5 ( 4.2- 3.1) = 3 BDEcalc = (-3) + (3) = 0

BDE gap = (-10.1) –( 0) = -10.1 = UMA

UMA= lactate+ renal acids

Re evaluation using SID- BDE approach

Na-143Na-143K- 4.4K- 4.4Cl- 103Cl- 103pH- 7.36pH- 7.36Pco2- 46Pco2- 46HCO3- 26HCO3- 26BE – 0.5BE – 0.5

BUN- 37BUN- 37Creatinine- 1.18Creatinine- 1.18Albumin- 3.0Albumin- 3.0


32 years male, severe acute pancreatitis- biliary- CTSI-10, septic shock, DIC32 years male, severe acute pancreatitis- biliary- CTSI-10, septic shock, DIC

AG = 143– (103 + 26.8 ) = 13.8

Corrected AG= 13.8 + 2.5 (4.2 – 3.0) = 13.8 + 3 = 16.8

continued….

Na-143Na-143K- 4.4K- 4.4Cl- 103Cl- 103pH- 7.36pH- 7.36Pco2- 46Pco2- 46HCO3- 26HCO3- 26BE – 0.5BE – 0.5Lactate- 4Lactate- 4


Impression:1. metabolic acidosis – UMA: has to be treated

2. Metabolic alkalosis- mineral related: precaution regarding fluid

3. Metabolic alkalosis- albumin related: not to be treated

Re evaluating using SID- BDE approachRe evaluating using SID- BDE approach

BDENacl= (143-103) – 38 = +2 BDE alb = 2.5 ( 4.2- 3.0) = 3 BDEcalc = (+2) + (3) = +5

BDE gap = (0.5) –( +5) = - 4.5 = UMA





42 years female, severe acute pancreatitis- biliary- post necresectomy, PCD in situ42 years female, severe acute pancreatitis- biliary- post necresectomy, PCD in situ

AG = 152– (109 + 28 ) = 15

Corrected AG= 15 + 2.5 (4.2 – 3.0) = 15 + 3 = 18

continued….


Impression:1. metabolic acidosis – UMA: has to be treated

2. Metabolic alkalosis- mineral related: precaution regarding fluid

3. Metabolic alkalosis- albumin related: not to be treated

Re evaluating using SID- BDE approachRe evaluating using SID- BDE approach

BDENacl= (152-109) – 38 = +5 BDE alb = 2.5 ( 4.2- 3.0) = 3 BDEcalc = (+5) + (3) = +8

BDE gap = (+3.4) –( +8) = - 4.6 = UMA



PRACTICAL APPROACH

Primary acid basedisorder

RespiratoryMetabolic

AcidosisAlkalosisAcidosis Alkalosis

Primary Metabolicacidosis

co existing another metabolic disorderMetabolic acidosis due to loss of HCO3

Metabolic akalosis

Loss of HCO3Renal or GI origin

Unmeasured anionsLactic acid, keto acids,

Methanol, ethanol, ethylene glycol, salicylates

Small/ large bowel secretion

bile lossFistula/ PCD

diarrhoea

Renal lossEarly renal insuficiencyRenal tubular disorders

acetazolamide

metabolic acidosis

Normal anionic GapHigh anionic Gap

HCO3 loss

co existing NAG Met Acid

Unmeasured anions

Urine loss

Calculate anion gap

Calculate delta gap

co existingMet Alk

Calculate UrineAnion gap

GI loss

ANION GAP(AG)ANION GAP(AG)

AG= [Na + K ] – [Cl+ HCO3]=

A + UMA

A- = weak acids= Albumin, Pi


Normal AG= 12 ± 4= A-

UMA= 0

Lactic/ keto acidosis= UMAAG> 16

Delta Gap or Gap Gap

AG excess/ HCO3 deficit =

(Measured AG – 12) / (24 – measured HCO3)

If there is no HCO3 loss or Cl loss

deficit in HCO3 = excess of AG

Delta Gap or Gap Gap

If there is HCO3 lossDeficit in HCO3 > excess in AG

ratio of AG excess / deficit in HCO3 = 1

ratio of AG excess / deficit in HCO3 < 1

If there is Cl lossDeficit in HCO3 < excess in AG

ratio of AG excess / deficit in HCO3 > 1

coexistant NAG Met acid

coexistant Met Alk

URINE ANION GAPURINE ANION GAP(UAG)(UAG)

(urine [Na] + urine [K] ) – ( urine [Cl] ) normal UAG = 0

renal HCO3 loss

Non renal cause of HCO3 lossUAG becomes negative

( -20 to -50 meq/L)

UAG remains

positive or slightly negative

Primary Metabolicalkalosis

Loss of Chloride

DiureticHypokalemia

Volume depletion

Mineralocorticoid excesshypokalemia

GIurine

Loss of gastric secretions

ThankYouThankYou

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