NH 4 + NH 3 H + HCO 3 - 1mMol/Kg/day GLUTAMINE NH 3 H+H+ Distal Pretubular Cell K + GFR Ammoniogenesis actively synthesize HCO 3 – in addition to secreting H +. HPO 4 2– (pK 6.8) excretion in the urine is another mechanism for H + elimination H + is trapped in the urine as the acid H2PO 4 –
HEPATIC HCO 3 – “PRODUCTION” AND CONSUMPTION principal 1.The liver is the principal organ that clears lactic acid produced by different tissues of the body 2.Each mole of lactic acid is accompanied by a mole of H +. oxidationgluconeogenesis 3.Lactic acid taken up can be metabolized by two pathways; either oxidation to CO 2, or gluconeogenesis to form glucose and glycogen. 4.Removal of free H + during lactate metabolism in effect increases the available HCO 3 – pool by diminishing its consumption. stimulates 5.Decreased ECF pH stimulates hepatic lactate uptake unless the liver itself is ischemic or hypoxic. synthesis of urea 6.Countering H + consumption during lactate metabolism is HCO 3 – consumption during synthesis of urea from protein and amino acid catabolism. Urea synthesis, which occurs only in the liver, can be written empirically as 7.Eachtwo 30g urea1,000 mmol of HCO 3 – 7.Each mole of urea synthesis consumes two moles of HCO 3 –. 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 HCO 3 –
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.
Carbon Dioxide-Bicarbonate (Boston) Approach 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 Many physicians have incorrectly assigned the increase in HCO 3 - as compensation for raised PCO 2. It is not. The increased HCO 3 - concentration reflects increased total CO 2 in the body. Alterations in HCO 3 - reflect its role as a buffer, CO 2 by-product, and weak acid.
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.
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 PCO 2 of 40 mm Hg and temperature of 38°C. in the 1960s : (nomograms ) standardized base excess (SBE) SBE = 0.9287 × [ HCO 3 − − 24.4 + (pH − 7.4)]
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.
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 − + HCO 3 − ) = -10 to -12 mEq/L ??? If the gap "widens" to, for example, -16 mEq/L, the acidosis is caused by UMAs (lactate or ketones).
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 [HCO 3 - ] 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 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 [HCO 3 - ] 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 Anion Gap Approach
A more accurate reflection of true acid-base status SID= [(Na + + Mg 2+ + Ca 2+ + K + ) − (Cl − + A − )] = 40 to 44mEq/L [Cl− ]corrected = [Cl− ]observed × ([Na+ ]normal/[Na+ ]observed) Stewart-Fencl Approach SIDe SIDa Strong Cations Strong Anions SIDa = ( [Na + ] + [K + ] + [Mg 2+ ] + [Ca 2+ ] ) − [Cl − ] SIDe = [HCO 3 − ] + (charge on albumin) + (charge on inorganic phosphate [Pi]) (in mmol/L) The normal SIG as 8 ± 2 mEq/L.
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 Stewart-Fencl Approach
Na = 117 K = 3.9 Ca = 3.0 Mg = 1.4 Cl = 92 Pi = 0.6 mmol/L albumin = 6.0 g/L pH = 7.33 P CO 2 = 30 mm Hg HCO 3 = 15 AG = 13 AG corrected = 23 BE = -10 SID = 18 Cl corrected = 112 and UMA corrected = 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 ) pH = 7.33 P CO 2 = 30 mm Hg BE = -10 HCO 3 = 15, AG = 13
Na = 117 K = 3.9 Ca = 3.0 Mg = 1.4 Cl = 92 Pi = 0.6 mmol/L albumin = 6.0 g/L pH = 7.33 P CO 2 = 30 mm Hg HCO 3 = 15 AG = 13 AG corrected = 23 BE = -10 SID = 18 Cl corrected = 112 and UMA corrected = 18. This patient has a dilutional acidosis, a hyperchloremic acidosis, and a lactic acidosis!
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
ACID-BASE PROBLEMS IN DIFFERENT CLINICAL SETTINGS Step 2. Look for respiratory component (volatile acid = CO2 ). PCO2 = 35 to 45 (normal range) PCO2 -5). PCO2 >45 = respiratory acidosis acute if pH 5
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. BE is 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 ACID-BASE PROBLEMS IN DIFFERENT CLINICAL SETTINGS
1 Acidosis, CO 2 -5 = acute metabolic acidosisacute metabolic acidosis 2 Normal-range pH, CO 2 -5 = acute metabolic acidosis plus compensationacute metabolic acidosis plus compensation 3 Acidosis, PCO 2 > 45, normal-range BDE = acute respiratory acidosisacute respiratory acidosis 4 Normal-range pH, PCO 2 > 45, BE > +5 = prolonged respiratory acidosisprolonged respiratory acidosis 5 Alkalosis, PCO 2 > 45, BE > +5 = metabolic alkalosismetabolic alkalosis 6 Alkalosis, PCO 2 < 35, normal-range BDE = acute respiratory alkalosisacute respiratory alkalosis 7 If the acid-base picture does not conform to any of these options, a mixed pattern exists.
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.