Acid Base Disorders Prof. Tahir Shafi

Why should we know about acid base disorders What are acid base disorders How to interpret acid base disorder How to establish the cause

Why to worry about acid base disorders Acid 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 mmHg PCO2 40 Bicarb 24 meq/l Sodium 140 Potassium 4,2 Chloride 80 Bicarb 24 Creatinine 0.9 Glucose 110 Which one of the following statements is correct He has normal acid base parameters He has metabolic acidosis and respiratory alkalosis He has metabolic alkalosis and respiratory acidosis He has metabolic acidosis and metabolic alkalosis

Regulation of acid base status Acidity in the ECF measured by [H]+ H+ = 38-42 nEq/L Average = 0.00004 mEq/L = 40 nEq/L pH - 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 + log Base Acid HCO3 H2CO3 24 apCO2 24 1.2 6.1 + log 1.3 =7.4 a =0.03 Log 20

Kassirer - Bleich Equation H+ = 24 x pCO2 HCO3

pH and H+ are inversely related h H+ results in i pH - Acidemia i H+ and hpH – Alkalemia Normal pH or H+ - Euphemia

Types of acid base disorders Acidosis Alkalosis Respiratory pCO2 HCO3 H+ = 24 x Alkalosis Acidosis Metabolic Stabilization of H+ for every primary disorder there must be physiological compensation by the opposite system

Compensations are predictable and can calculated Respiratory compensation H+ = 24 x pCO2 HCO3 Primary pH Initial event Comp Resp Expected Cpmpensation Met. Acidosis i iHCO3 ipCO2 For 1 meq iHCO3, pCO2 i by 1-1.3 mmHg PCO2 = HCO3+ 15 PCO2 = last 2 digits of pH pCO2 = (HCO3) x 1.5+8+2 Winter’s equation Met. Alkalosis h hHCO3 hpCO2 For 1 meq h HCO3,PCO2 h by 0.6 mmHg PCO2 =(HCO3 x 0.9) + 9 PCO2 =(HCO3 x 0.7) + 20

Metabolic compensation H+ = 24 x pCO2 HCO3 Primary pH Initial event Comp Resp Expected Cpmpensation Ac. Resp. Acidosis i hpCO2 hHCO3 For every 10 mmHg h PCO2 ,HCO3 h by 1 Ch. Resp. Acidosis hPCO2 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 For every 10 mmHg i PCO2, HCO3 i by 5

Rates of correction Buffers function almost instantaneously Respiratory mechanisms take several minutes to hours Renal 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 acidosis Exogenous load HCl Other acids

Types of metabolic acidosis Addition of acid other than HCl Serum chloride normal, bicarbonate low High anion metabolic acidosis Addition 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 Acidosis K Diabetic Ketoacidosis Causes of high Anion Gap metabolic acidosis K Diabetic Ketoacidosis U Uremia S Salicylate intoxication S Starvation ketosis M Methanol ingestion A Alcohol ketoacidosis U Unmeasured Osmoles, Ethylene Glycol, Paraldehyde L Lactic acidosis MUDPILES Methanol, Uremia, DKA, Paraldehyde, INH/Iron toxicity, Lactic acidodis, Ethanol/Ethlene glycol, Salicylate toxicity

Metabolic Acidosis Causes of normal Anion Gap metabolic acidosis H Hyperalimentation A Acetazolamide R Renal tubular acidosis D Diarrhoea U Uretero sigmoidostomy P Pancreatic fistula

D – Diarrhea U – Ureteral diversion R – Renal tubular acidosis H – Hyperalimentation A – Acetazolamide M - Miscellaneous (toluene, amphotericin B

Hyperchloremic metabolic acidosis Normal or high ammonia excretion Decreased ammonia excretion

Urine anion gap Negative urine anion gap positive urine anion gap

Urine osmolal gap Measured urine osmolality – calculated urine osmolality Calculated urine osmolality = 2 (UNa + UK )+ < 150 mosm /l= impaired NH4 excretion >150 mosm/l = increased NH4 excretion Urine ammonia level = half urine osmolal gap Urea 6

Metabolic acidosis & osmolal gap Ethyl Alcohol Acetaldehyde Acetic Acid Methyl Alcohol Formaldhyde Formic Acid Ethylene Alcohol Glycoaldehyde Glycolic acid Glycooxalic acid Oxalic acid OSMOLAL GAP = Measured osmolality- calculated osmolality Normal = < 10-15 mOsmol/Kg of H2O Urea 6 BS 18 Calculated serum osmolaliy = 2(Na) + +

Metabolic alkalosis Addition of base or loss of acid from body High pH, high bicarbonate, high pCO2

Metabolic alkalosis Saline responsive alkalosis Low urinary Cl- (<10 mmol/l) Normal or low BP vomiting Post diuretics After hypercapnia K+ depletion Refeeding alkalosis Saline resistant alkalosis High Urinary Cl- (>10 mmol/l) Normal BP High BP Bartter’s syndrome Reno vascular Diuretics disease Mg++ depletion Conn’s syndrome Severe K+ depletion Cushing’s syndrome

More then one problem? The “gap-gap” or “delta-delta” ratio In 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 Coexistent Metabolic alkalosis delta/delta > 1 hh D AG D HCO3 hh Coexistent Hypercholemic acidosis delta/ delta <1

Mixed metabolic acid base disorders Corrected bicarbonate = observed biacrbonate + > 24 meq/l g Metabolic Alkalosis < 24 meq/l g Metabolic Acidosis D AG

Respiratory acid base disorders Respiratory acidosis Respiratory alkalosis Hypoventilation Hyperventilation Primary event Change in pCO2 H+ = 24 x pCO2 HCO3

Respiratory Alkalosis or Acidosis Neuro respiratory control Central hypo or hyperventilation Intrinsic lung disease A-a gradient (Alveolar arterial gradient) Alveolar O2 =(760 – 47) * 0.21* PCO2/0.8 =100 Atmospheric pressure – water vapor pressure * FiO2* PaCO2 Arterial (a) =100 A-a gradient normal is < 10 in adults and < 20 in elderly

Respiratory Alkalosis Low 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 Acidosis High 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

Urinary electrolytes – Urinary anion gap urine osmolal gap History Physical examination Serum electrolytes Anion gap Delta/delta ratio Arterial blood gases Urinary electrolytes – Urinary anion gap urine osmolal gap Serum osmolal gap

Acid Base Analysis Step 1 : Look at pH. acidemic or alkalemic? Step 2 : Look at pCO2 High – respiratory acidosis Low – respiratory alkalosis Step 3: Look at HCO3 High – metabolic alkalosis Low – metabolic acidosis Step 4: Determine primary event - direction of pH

Step 5: Is it simple or mixed disorder. compensatory response within Step 5: Is it simple or mixed disorder. compensatory response within physiological range ? Golden rules: 1- Mixed problem present if only one component abnormal 2- Normal pH – both components abnormal 3-Both components in same direction Step 6 : Look at base excess if available Step 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 7.54 PCO2 30 mmHg HCO3 25 meq/l Na+ 140 meq/l Cl- 92 meq/l K+ 3.6 meq/l

Acid Base Disorders pH 7.25 pO2 70 mmHg PCO2 40 mmHg HCO3 17 meq/l A 55 years old man with renal failure presented with vomiting altered consciousness and fever pH 7.25 pO2 70 mmHg PCO2 40 mmHg HCO3 17 meq/l Na+ 140 meq/l Cl- 89 meq/l K+ 3.6 meq/l A. Respiratory acidosis Metabolic Acidosis Metabolic alkalosis + respiratory acidosis D. Metabolic acidosis + Respiratory acidosis E. D + Metabolic alkalosis

Acid Base Disorders pH 7.25 pO2 70 mmHg PCO2 40 mmHg HCO3 17 meq/l A ss years old man with renal failure presented with vomiting and pleuritic chest pain pH 7.25 pO2 70 mmHg PCO2 40 mmHg HCO3 17 meq/l Na+ 140 meq/l Cl- 89 meq/l K+ 3.6 meq/l AG 140-(89+17) =34 D AG = 34-10=24 HCO3 = 24-17=7 High A-a gradient

Acid Base Disorders 16 years old boy , a case of FSGS on diuretics and Steroids presented with BP 70/40 mmHg pH 7.4 PCO2 40 mmHg HCO3 24 meq/l Na+ 143 meq/l Cl- 95 meq/l K+ 3.6 meq/l S. Albumin 1 gram/dl no acid base disorder Respiratory acidosis Metabolic alkalosis + resp acidosis Metabolic acidosis + resp alkalosis E, None of the above

Acid Base Disorders 16 years old boy , a case of FSGS on diuretics and Steroids presented with BP 70/40 mmHg pH 7.4 PCO2 40 mmHg HCO3 24 meq/l Na+ 143 meq/l Cl- 95 meq/l K+ 3.6 meq/l S. Albumin 1 gram/dl no acid base disorder Respiratory acidosis Metabolic alkalosis + resp acidosis Metabolic acidosis + resp alkalosis E, None of the above AG =143-(95+24) = 24 Corrected AG= 24+(4- Alb) * 2.5 = 31.5 Delta AG = 21.5 Delta bicarb = 0 Mixed 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 or 320 mg/l of methanol

Acid Base Disorders HCO3 17 meq/l Na+ 140 meq/l Cl- 89 meq/l K+ 3.6 meq/l

Figure 1 Assessment of Acidosis Figure 1 Assessment of Acidosis. Reference values for the alveolar–arterial (A–a) oxygen tension difference are less than 10 mm Hg in young persons and less than 20 mm Hg in the elderly. ΔAG denotes delta anion gap, PaCO2 partial pressure of arterial carbon dioxide (mm Hg), PaO2 partial pressure of arterial oxygen (mm Hg), and RTA renal tubular acidosis. To convert the values for PaCO2, PaO2, and the alveolar–arterial difference to kilopascals, multiply by 0.1333. If delta delta ratio =1 only high AG Met Acidosis Berend K et al. N Engl J Med 2014;371:1434-1445

Figure 2 Assessment of Alkalosis Figure 2 Assessment of Alkalosis. Reference values for the alveolar–arterial (A–a) oxygen tension difference are less than 10 mm Hg in young persons and less than 20 mm Hg in the elderly. PaCO2 denotes partial pressure of arterial carbon dioxide (mm Hg), and PaO2 partial pressure of arterial oxygen (mm Hg). To convert the values for PaCO2, PaO2, and the alveolar–arterial difference to kilopascals, multiply by 0.1333. 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 pH Base Excess = pH *10/0.15 For each 0.15 unit difference in pH Base excess or deficit will be =10

Approach to Acid Base Disorders Traditional or Boston approach Copen Hagen approach Base excess Stewart / 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).