90 percent of filtered HCO 3 –

1. 90 percent of filtered HCO3–

2. Ammoniogenesis actively synthesize HCO3– in addition to secreting H+. H+ DistalPretubular Cell NH4+ NH3 H+ HCO3- 1mMol/Kg/day GLUTAMINE NH3 Tubular Lumen Pretubular Capillary HPO42– (pK 6.8) excretion in the urine is anothermechanism for H+ elimination H+ is trapped in the urine as the acid H2PO4– K+ GFR Increase Decrease

3. HEPATIC HCO3– “PRODUCTION” AND CONSUMPTION • The liver is the principal organ that clears lacticacid produced by differenttissues of the body • Each mole of lactic acid is accompanied by a mole of H+ . • Lactic acid taken up can be metabolized by two pathways; either oxidation to CO2, or gluconeogenesis to form glucose and glycogen. • Removal of free H+ during lactate metabolism in effect increases the available HCO3– pool by diminishing its consumption. • Decreased ECF pH stimulates hepatic lactate uptake unless the liver itself is ischemic or hypoxic. • Countering H+consumption during lactate metabolism is HCO3–consumption during synthesis of urea from protein and amino acid catabolism. Urea synthesis, which occurs only in the liver, can be written empirically as • Each mole of urea synthesis consumes two moles of HCO3– . Urea produced by the liver is excreted in the urine. A normal daily excretionof 30g urea in the urine translates to the equivalent of 1,000 mmol of HCO3–

4. ANALYTIC TOOLS USED IN ACID-BASE CHEMISTRY • The clinical significance of acid-base perturbations is determined by the underlying cause rather than the serum concentration of hydrogen and hydroxyl ions. • The accuracy of acid-base measurements, however, is not determined by the blood gas value alone, which measures volatile acid and pH. • Rather, measurement of each of the strong and weak ions that influence water dissociation, although cumbersome, is essential.

5. Carbon Dioxide-Bicarbonate (Boston) Approach Many physicians have incorrectly assigned the increase in HCO3- as compensation for raised PCO2 . It is not. The increased HCO3 - concentration reflects increased total CO2 in the body. Alterations in HCO3 - reflect its role as a buffer, CO2 by-product, and weak acid. First, the approach is not as simple as it seems, requiring the clinician to refer to confusing maps or to learn formulas and perform mental arithmetic. Second, the system neither explains nor accounts for many of the complex acid-base abnormalities

6. Base Deficit or Excess (Copenhagen) Approach • Whole blood buffer base (BB) • The sum of the bicarbonate and the nonvolatile buffer ions (essentially the serum albumin, phosphate, and hemoglobin) • Normally, BB = [Na+ ] + [K+ ] − [Cl− ]. • The major drawback of the use of buffer base measurements is the potential for changes in buffering capacity associated with alterations in hemoglobin concentration.

7. Base Deficit or Excess (Copenhagen) Approach • In 1958, Siggard-Anderson and colleagues developed a simpler measure of metabolic acid-base activity, the BDE (base deficit or excess). • They defined the BDE as the amount of strong acid or base required to return pH to 7.4, assuming a PCO2 of 40 mm Hg and temperature of 38°C. • in the 1960s : (nomograms)standardized base excess (SBE) • SBE = 0.9287 × [ HCO3− − 24.4 + (pH − 7.4)]

10. Base Deficit or Excess (Copenhagen) Approach • These measures may miss the presence of an acid-base disturbance entirely; for example a hypoalbuminemic (metabolic alkalosis), critically ill patient with a lactic acidosis may have a normal range pH, bicarbonate, and BE. This may lead to inappropriate therapy.

11. Anion Gap Approach • The first and most widely used tool for investigating metabolic acidosis is the anion gap (AG), developed by Emmit and Narins in 1975 • This is based on the law of electrical neutrality • Na++ K+-(Cl−+ HCO3−) = -10 to -12 mEq/L ??? • If the gap "widens" to, for example, -16 mEq/L, the acidosis is caused by UMAs (lactate or ketones).

13. Anion Gap Approach • what is or is not a normal gap? • Most critically ill patients are hypoalbuminemic, and many are also hypophosphatemic . • Corrected anion gap:Anion gap corrected (for albumin) = calculated anion gap + 2.5 × (normal albumin [g/dL] − observed albumin [g/dL]) • The second weakness with this approach is the use of bicarbonate in the equation. • An alteration in [HCO3- ] concentration can occur for reasons independent of metabolic disturbance, such as hyperventilation. • The base deficit (BD) and AG frequently underestimate the extent of the metabolic disturbance

14. Stewart-Fencl Approach A more accurate reflection of true acid-base status SID= [(Na+ + Mg2+ + Ca2+ + K+ ) − (Cl− + A− )] = 40 to 44mEq/L [Cl− ]corrected = [Cl− ]observed × ([Na+ ]normal/[Na+ ]observed) SIDa SIDe Strong Cations Strong Anions The normal SIG as 8 ± 2 mEq/L. SIDa = ( [Na+ ] + [K+ ] + [Mg2+ ] + [Ca2+ ] ) − [Cl− ] • SIDe = [HCO3− ] + (charge on albumin) +(charge on inorganic phosphate [Pi]) (in mmol/L)

15. Stewart-Fencl Approach • BDE = Standard BDE • CBE = Calculated BDE • BEG = BDE − CBE • BEfw = Changes in free water = 0.3 × (Na − 140) • BECl = Changes in chloride = 102 − (Cl − 140/Na) • BEalb = Changes in albumin = 3.4 × (4.5 − albumin) • CBE = BEfw + BECl +BEalb

16. Stewart-Fencl Approach [Cl− ] corrected = [Cl− ] observed × ([Na+ ] normal / [Na+ ] observed) • Hyperchloremic acidemia:[Cl− ]corrected >112 mEq/L. • Hypochloremic alkalemia:[Cl− ]corrected <100 mEq/L. • Dilutional acidemia: serum sodium< 136 mEq/L • Contraction alkalemia : serum sodium > 148 mEq/L • Hyperphosphatemic acidemia : [Pi]>2.0 mmol/L • Hypoalbuminemic alkalosis : [alb] < 3.5 g/dL

17. pH = 7.33 PCO2 = 30 mm Hg BE = -10 HCO3 = 15 , AG = 13 Na = 117 K = 3.9 Ca = 3.0 Mg = 1.4 Cl = 92 Pi = 0.6 mmol/Lalbumin = 6.0 g/L pH = 7.33 PCO2 = 30 mm Hg HCO3 = 15 AG = 13 AGcorrected = 23 BE = -10 SID = 18 Clcorrected = 112 and UMAcorrected = 18. • Non-AG metabolic acidosis • bicarbonate wasting, such as renal tubular acidosis or gastrointestinal losses • The degree of respiratory alkalosis is appropriate for the degree of acidosis (ΔBD = ΔPCO2 ) • SID is reduced to 18 mEq/L : free water excess, UMAs, and surprisingly, hyperchloremia • the alkalizing force at play: hypoalbuminemia? • The corrected AG mirrors the change in SID, but this is grossly underestimated by the BD ( 0.6g/dL )

18. Na = 117 K = 3.9 Ca = 3.0 Mg = 1.4 Cl = 92 Pi = 0.6 mmol/Lalbumin = 6.0 g/L pH = 7.33 PCO2 = 30 mm Hg HCO3 = 15 AG = 13 AGcorrected = 23 BE = -10 SID = 18 Clcorrected = 112 and UMAcorrected = 18. • This patient has a dilutional acidosis, a hyperchloremic acidosis, and a lactic acidosis!

19. ACID-BASE PROBLEMS IN DIFFERENT CLINICAL SETTINGS Step 1. Look at the pH. • 7.35 to 7.5 = normal or compensated acidosis • >7.5 = alkalosis • <7.35 = acidosis

20. ACID-BASE PROBLEMS IN DIFFERENT CLINICAL SETTINGS • Step 2. Look for respiratory component (volatile acid = CO2 ). • PCO2 = 35 to 45 (normal range) • PCO2 < 35 mm Hg = respiratory alkalosis or compensation for metabolic acidosis (if so, BD > -5). • PCO2 >45 = respiratory acidosis acute if pH < 7.35; chronic if pH in normal range and BE > 5

21. ACID-BASE PROBLEMS IN DIFFERENT CLINICAL SETTINGS • Step 3. Look for a metabolic component (i.e., buffer base use). • BD is the amount of strong cation required to bring pH back to 7.4, with PCO2 corrected at 40 mm Hg. • BEis the amount of strong anion required to bring pH back to 7.4, with PCO2 corrected at 40 mm Hg. • BE -5 to +5 = normal range • BE >5 = alkalosis • BD > -5 = metabolic acidosis

22. 1 Acidosis, CO2 < 35 mm Hg, ± BD > -5 = • acute metabolic acidosis 2 Normal-range pH, CO2 < 35, BD > -5 = • acute metabolic acidosis plus compensation 3 Acidosis, PCO2 > 45, normal-range BDE = • acute respiratory acidosis 4 Normal-range pH, PCO2 > 45, BE > +5 = • prolonged respiratory acidosis 5 Alkalosis, PCO2 > 45, BE > +5 = • metabolic alkalosis 6 Alkalosis, PCO2 < 35, normal-range BDE = • acute respiratory alkalosis 7 If the acid-base picture does not conform to any of these options, a mixed pattern exists.

23. Acid-Base Disturbances in Emergency Settings • The common disturbances are: acute respiratory acidosis acute respiratory alkalosis acute metabolic acidosis • Acute metabolic alkalosis is unusual.

24. Acute respiratory acidosis • Hypoventilation :loss of respiratory drive neuromuscular disorders chest wall disorders rapid, shallow breathing, which increases the fraction of dead-space ventilation. Acute respiratory alkalosis • Hyperventilation anxiety, central respiratory stimulation (salicylate poisoning)excessive artificial ventilation • Acute respiratory alkalosis usually accompanies acute metabolic acidosis • Reduction in PCO2 from baseline (usually 40 mm Hg)is equal to the magnitude of the BD.

26. BEfw = Changes in free water = 0.3 × (Na − 140) + 2.4 = 0.3 × ( 148 – 140 ) • BEalb = Changes in albumin = 3.4 × (4.5 − albumin) +8.5 = 3.4 × ( 4.5 – 2 ) • BECl = Changes in chloride = 102 − (Cl − 140/Na) -17 = 102 – ( 120 – 140/148 )

27. Stewart-Fencl Approach • BEfw = Changes in free water = 0.3 × (Na − 140) + 2.4 = 0.3 × ( 148 – 140 ) • BECl = Changes in chloride = 102 − (Cl − 140/Na) -17 = 102 – ( 120 – 140/148 ) • BEalb = Changes in albumin = 3.4 × (4.5 − albumin) +8.5 = 3.4 × ( 4.5 – 2 ) • CBE = BEfw + BECl +BEalb-6.1 = 2.4 + ( - 17 ) + 8.5 • BEG = BDE − CBE-5 = -11 – ( -6 )