Acid Base DisordersProf. Tahir Shafi

Why should we know about acid base disorders

What are acid base disordersHow to interpret acid base

disorderHow to establish the cause

Why to worry about acid base disordersAcid base homeostasis

fundamental for maintaining life Extreme acidemia or alkalemia

can◦alter tertiary protein structure

affecting enzyme activities ion transport

◦alter almost every metabolic pathway

Extreme acidemia can◦depress cardiac function, impair the

vascular response to catecholamines, and cause arteriolar vasodilation and venoconstriction, with resultant systemic hypotension and pulmonary edema.

Alkalemia can cause ◦cardiac arrhythmias, neuromuscular

irritability, and contribute to tissue hypoxemia.

◦fall in cerebral and myocardial blood flow

◦respiratory depression◦potassium abnormalities a common

accompaniment of acid-base disorders, also contribute to the morbidity.

Identification of mild to moderate disorders can give you important clue to the presence of unsuspected but may be otherwise important medical conditions

A patient has the following lab tests:ABG pH 7.4 PO2 100 mmHgPCO2 40 Bicarb 24 meq/lSodium 140 Potassium 4,2Chloride 80 Bicarb 24Creatinine 0.9 Glucose 110Which one of the following statements is correctA. He has normal acid base parametersB. He has metabolic acidosis and respiratory

alkalosisC. He has metabolic alkalosis and respiratory

acidosisD. He has metabolic acidosis and metabolic alkalosis

Regulation of acid base statusAcidity in the ECF measured by

[H]+ H+ = 38-42 nEq/L Average = 0.00004 mEq/L = 40

nEq/LpH - negative log of H+ in moles Maintenance of arterial pH within

normal range 7.38-7.42 with average pH 7.4

Henderson Hasselbach equation

pH = pk + logBaseAcid

6.1 + log HCO3

H2CO3

24apCO2

241.2

1.3=7.4

a =0.03 Log 20

Kassirer - Bleich Equation

H+ = 24 x pCO2

HCO3

pH and H+ are inversely relatedh H+ results in i pH - Acidemia i H+ and hpH – AlkalemiaNormal pH or H+ - Euphemia

Types of acid base disorders

H+ = 24 x pCO2

HCO3

RespiratoryAcidosis

Alkalosis

MetabolicAlkalosis

AcidosisStabilization of H+ for every primary disorder there must be physiological compensation by the opposite system

Compensations are predictable and can calculatedRespiratory compensation

Primary

pH Initial event

CompResp

Expected Cpmpensation

Met. Acidosis

i iHCO3 ipCO2 For 1 meq iHCO3, pCO2 i by 1-1.3 mmHgPCO2 = HCO3+ 15PCO2 = last 2 digits of pHpCO2 = (HCO3) x 1.5+8+2 Winter’s equation

Met. Alkalosis

h hHCO3 hpCO2 For 1 meq h HCO3,PCO2 h by 0.6 mmHgPCO2 =(HCO3 x 0.9) + 9PCO2 =(HCO3 x 0.7) + 20

H+ = 24 x pCO2

HCO3

Metabolic compensation

Primary pH Initial event

CompResp

Expected Cpmpensation

Ac. Resp. Acidosis i hpCO2 hHCO3 For every 10 mmHg h PCO2 ,HCO3 h

by 1

Ch. Resp. Acidosis

i hPCO2 hHCO3 For every 10 mmHg h PCO2, HCO3 h by 3.5

Acute Resp Alkalosis

h ipCO2 iHCO3 For every 10 mmHg i PCO2, HCO3 i by 2

Ch. Resp Alkalosis h ipCO2

iHCO3 For every 10 mmHg i PCO2, HCO3 i by 5

H+ = 24 x pCO2

HCO3

15

Rates of correctionBuffers function almost

instantaneouslyRespiratory mechanisms take

several minutes to hoursRenal mechanisms may take

several hours to days

Classification acid base disorders Simple

◦ Metabolic acidosis◦ Metabolic alkalosis◦ Respiratory acidosis◦ Respiratory alkalosis

Primary change in one component Secondary change in the other component within physiological

range Change in ph in the direction of primary change

Mixed◦ Double

Primary change with incomplete or over compensation with other component

◦ Triple◦ Quadruple

Normal acid base homeostasis

Metabolic acidosisExogenous

load HClOther acids

Types of metabolic acidosisAddition of acid other than HCl

◦Serum chloride normal, bicarbonate low

◦High anion metabolic acidosisAddition of HCl

◦Serum chloride high, bicarbonate low◦Normal anion or hyperchloremic

metabolic acidosis

Anion gap

Albumin is a major source of unmeasured anions!

Corrected AG = Observed AG + 2.5 x (4.5 – measured albumin)

If serum albumin is high, corrected anion gap will be lower

Metabolic AcidosisCauses of high Anion Gap metabolic acidosisK Diabetic KetoacidosisU UremiaS Salicylate intoxicationS Starvation ketosisM Methanol ingestionA Alcohol ketoacidosisU Unmeasured Osmoles, Ethylene Glycol, ParaldehydeL Lactic acidosis

MUDPILES Methanol, Uremia, DKA, Paraldehyde, INH/Iron toxicity, Lactic acidodis, Ethanol/Ethlene glycol, Salicylate toxicity

Metabolic AcidosisCauses of normal Anion Gap metabolic

acidosis

H HyperalimentationA AcetazolamideR Renal tubular acidosis D DiarrhoeaU Uretero sigmoidostomyP Pancreatic fistula

D – DiarrheaU – Ureteral diversionR – Renal tubular acidosisH – HyperalimentationA – AcetazolamideM - Miscellaneous (toluene,

amphotericin B

Hyperchloremic metabolic acidosis Normal or high ammonia

excretionDecreased ammonia excretion

Urine anion gap

Negative urine anion gap positive urine anion gap

Urine osmolal gapMeasured urine osmolality – calculated

urine osmolalityCalculated urine osmolality

= 2 (UNa + UK )+

< 150 mosm /l= impaired NH4 excretion>150 mosm/l = increased NH4 excretionUrine ammonia level = half urine osmolal gap

Urea6

Metabolic acidosis & osmolal gapEthyl Alcohol Acetaldehyde Acetic AcidMethyl Alcohol Formaldhyde Formic

AcidEthylene Alcohol Glycoaldehyde

Glycolic acid Glycooxalic acid Oxalic acid

OSMOLAL GAP = Measured osmolality- calculated osmolality

Normal = < 10-15 mOsmol/Kg of H2OCalculated serum osmolaliy = 2(Na) + + Urea

6BS18

Metabolic alkalosisAddition of base or loss of acid

from bodyHigh pH, high bicarbonate, high

pCO2

Metabolic alkalosisSaline responsive alkalosisLow urinary Cl- (<10 mmol/l)

Normal or low BP

vomitingPost diureticsAfter hypercapniaK+ depletionRefeeding alkalosis

Saline resistant alkalosis High Urinary Cl- (>10 mmol/l)

Normal BP High BP

Bartter’s syndrome Reno vascularDiuretics diseaseMg++ depletion Conn’s syndromeSevere K+ depletion Cushing’s syndrome

More then one problem?The “gap-gap” or “delta-delta” ratioIn the presence of a high AG

metabolic acidosis, ? another metabolic acid base disorder

Comparing the AG excess to the HCO3 deficit - D AG =D HCO3

D AG = (Observed AG – 12) D HCO3 = (Observed – Normal HCO3)

Mixed metabolic acid base disorders

D AGD HCO3 hh

CoexistentHypercholemic acidosis

delta/ delta <1

Coexistent Metabolic alkalosisdelta/delta > 1 hh

Mixed metabolic acid base disordersCorrected bicarbonate =

observed biacrbonate + > 24 meq/l g Metabolic Alkalosis< 24 meq/l g Metabolic Acidosis

D AG

Respiratory acid base disorders

H+ = 24 x pCO2

HCO3

Respiratory acidosis Respiratory alkalosisHypoventilation Hyperventilation

Primary eventChange in pCO2

Respiratory Alkalosis or AcidosisNeuro respiratory control

◦Central hypo or hyperventilation◦Intrinsic lung disease

A-a gradient (Alveolar arterial gradient)Alveolar O2 =(760 – 47) * 0.21* PCO2/0.8 =100Atmospheric pressure – water vapor pressure * FiO2* PaCO2

Arterial (a) =100 A-a gradient normal is < 10 in adults and < 20 in elderly

Respiratory AlkalosisLow pCO2, low bicarbonate, high pH

◦A–a difference >10 mm Hg (>20 mm Hg in elderly) - Hyperventilation with intrinsic lung disease, ventilation–perfusion mismatch, or both (e.g., pneumonia, pulmonary embolism)

◦A–a difference <10 mm Hg (<20 mm Hg in elderly) Hyperventilation without intrinsic lung disease (e.g., fever, pregnancy)

Respiratory AcidosisHigh pCO2, high bicarbonate, low

pH◦A–a difference >10 mm Hg (>20 mm

Hg in elderly) Hypoventilation with intrinsic lung disease, ventilation–perfusion mismatch, or both (e.g., pneumonia, pulmonary embolism)

◦A–a difference <10 mm Hg (<20 mm Hg in elderly) - Hypoventilation without intrinsic lung disease (CNS suppression)

Approach to Acid Base Disorders

HistoryPhysical examinationSerum electrolytes

◦Anion gap◦Delta/delta ratio

Arterial blood gasesUrinary electrolytes – Urinary

anion gap urine osmolal gapSerum osmolal gap

Acid Base AnalysisStep 1 : Look at pH. acidemic or

alkalemic?Step 2 : Look at pCO2

High – respiratory acidosisLow – respiratory alkalosis

Step 3: Look at HCO3 High – metabolic alkalosisLow – metabolic acidosis

Step 4: Determine primary event - direction of pH

Step 5: Is it simple or mixed disorder. compensatory response within physiological range ?

Golden rules: 1- Mixed problem present if only one component abnormal2- Normal pH – both components

abnormal3-Both components in same direction

Step 6 : Look at base excess if availableStep 7: If the respiratory disturbance is

present, is it acute or chronic?

Step 8 : Is there increased anion gap?

Step 9 : If anion gap increased, calculate corrected HCO3 or delta/delta

Step 10 : Calculate osmolal gap if ingestion of alcohols suspected

Step 11: Calculate urine anion gap or osmolol gap

Acid Base Disorders

pH 7.54PCO2 30 mmHgHCO3 25 meq/lNa+ 140 meq/lCl- 92 meq/lK+ 3.6 meq/l

Acid Base Disorders

pH 7.25pO2 70 mmHgPCO2 40 mmHgHCO3 17 meq/lNa+ 140 meq/lCl- 89 meq/lK+ 3.6 meq/l

A 55 years old man with renal failure presented with vomiting altered consciousness and fever

A. Respiratory acidosisB.Metabolic AcidosisC.Metabolic alkalosis

+ respiratory acidosis

D. Metabolic acidosis + Respiratory acidosisE. D + Metabolic alkalosis

Acid Base Disorders

pH 7.25pO2 70 mmHgPCO2 40 mmHgHCO3 17 meq/lNa+ 140 meq/lCl- 89 meq/lK+ 3.6 meq/lAG 140-(89+17) =34D AG = 34-10=24D HCO3 = 24-17=7 High A-a gradient

A ss years old man with renal failure presented with vomiting and pleuritic chest pain

Acid Base Disorders

pH 7.4PCO2 40 mmHgHCO3 24 meq/lNa+ 143 meq/lCl- 95 meq/lK+ 3.6 meq/lS. Albumin 1 gram/dl

16 years old boy , a case of FSGS on diuretics and Steroids presented with BP 70/40 mmHg

A. no acid base disorder

B. Respiratory acidosis

C. Metabolic alkalosis + resp acidosis

D. Metabolic acidosis +

resp alkalosisE, None of the above

Acid Base Disorders

pH 7.4PCO2 40 mmHgHCO3 24 meq/lNa+ 143 meq/lCl- 95 meq/lK+ 3.6 meq/lS. Albumin 1 gram/dl

16 years old boy , a case of FSGS on diuretics and Steroids presented with BP 70/40 mmHg

A. no acid base disorder

B. Respiratory acidosis

C. Metabolic alkalosis + resp acidosis

D. Metabolic acidosis +

resp alkalosisE, None of the above

AG =143-(95+24) = 24Corrected AG= 24+(4- Alb) * 2.5 = 31.5Delta AG = 21.5Delta bicarb = 0Mixed high anion gap metabolic acidosis + Alkalosis

Glucose 90 mg/dl

Urea 30 mg/dl

Serum Sodium 136 meq/l

Serum potassium 4 meq/l

Calc osm 291 mosm/l

Serum osm 311 mosm/l

Osmolar gap =20 delta OG=10

460 mg/l of ethanol or320 mg/l of methanol

Acid Base Disorders

HCO3 17 meq/lNa+ 140 meq/lCl- 89 meq/l

K+ 3.6 meq/l

Berend K et al. N Engl J Med 2014;371:1434-1445

If delta delta ratio=1 only high AG Met Acidosis

Berend K et al. N Engl J Med 2014;371:1434-1445

Base Excess = 0.9287 (HCO3 - 24.4 + 14.83

(pH - 7.4))

Predicted pH = 7.4 + pCO2 * 0.08

pH = Actual pH – predicted pHBase Excess = pH *10/0.15

For each 0.15 unit difference in pH Base excess or deficit will be =10

Approach to Acid Base DisordersTraditional or Boston approach Copen Hagen approach

◦Base excessStewart / Physiochemical approach

◦PCO2

◦Non-volatile weak ion acid buffer A Total Atotal = A- + AH (Albumin, Pi, SO4, Hb)

◦Strong ion difference (SID) (Na+K+Ca+Mg) – (Cl+Lac) = A- + HCO3 = 40-42

The physiologic or “Boston” method ◦ uses measurements of arterial pH, pCO2, and [HCO3−]

together with an analysis of the anion gap (AG) and a set of compensation rules.

2. The Base Excess (BE) or “Copenhagen” method uses◦ measurements of arterial pH and pCO2, and calculation

of the BE and the AG.3. The physicochemical or “Stewart” method uses

◦ Measurements of arterial pH and pCO2 together with the calculated apparent (SIDa) and effective (SIDe) “Strong Ion Difference,” the “Strong Ion Gap” (SIG = SIDa-SIDe), and the total concentration of plasma weak acids (Atot).