Acid-Base Disorders

1. Acid-Base Disorders Stephen W. Smith, M.D. Department of Emergency Medicine Hennepin County Medical Center

2. Objectives Make a lifesaving diagnosis Prevent cardiac arrest from acidosis or alkalosis Evaluate any acid base disorder systematically

3. 18 y.o. WF presents in DKA ABG: pH 6.97 pCO2 27 Bicarbonate 6 If Pure metabolic acidosis, then pCO2=(1.5)(6) + 8= 17 Metabolic acidosis with respiratory acidosis: Fatigue from Compensation, hypokalemia, hypophosphatemia She is at risk for tiring out and becoming extremely acidotic. No panel available to check AG, probably Lactate; probably inc. AG Pt. is acidemic HCO3 is very low. Without pCO2 change, the pt�s pH would be very low. Is pCO2 adequate for the HCO3? Yes. No panel available to check AG, probably Lactate; probably inc. AG Pt. is acidemic HCO3 is very low. Without pCO2 change, the pt�s pH would be very low. Is pCO2 adequate for the HCO3? Yes.

4. Ratio of HCO3 to pCO2 determines pHdoubling or halving changes pH by 0.3

5. Metabolic Acidosis--Bad Impaired cardiac contractility Decreased threshold for v fib Decreased Hepatic and Renal perfusion Increased Pulm Vasc resistance Inability to respond to catecholamines Vascular collapse The causes of metabolic acidosis can be divided into two main groups: (1) those associated with increased production of organic acids (increased anion gap metabolic acidosis), and (2) those associated with a loss of bicarbonate or addition of chloride (normal anion gap metabolic acidosis). The causes of metabolic acidosis can be divided into two main groups: (1) those associated with increased production of organic acids (increased anion gap metabolic acidosis), and (2) those associated with a loss of bicarbonate or addition of chloride (normal anion gap metabolic acidosis).

6. Limit Bicarbonate TherapyDo not give unless HCO3 very low (< 6 mEq/L) Intracellular acidosis CO2 + H2O H2CO3 H+ + HCO3- Increases pCO2 and need for ventilation Carbicarb (NaBicarb + NaCarbonate) Tris buffer (THAM) Hypernatremia & Fluid overload Normal Saline: 150 mEq/l of Na Bicarb: 1000mEq/l; 1 amp is 50 cc�s = 50 mEq of Na As much Na as 1/3 liter normal saline Hypokalemia Shift of Oxyhemoglobin dissociation curve Initially injected into 3 liter plasma volume (not 5 liter blood volume because does not enter red cells) In vitro: small and transient (Goldsmith DJ et al, Clin Sci 93:593, Dec 97) Unpublished functional MRI studies show this is limited http://www3.interscience.wiley.com/journal/112150996/abstract � shows benefit of carbicarb over HCO3 Am J Physiol Heart Circ Physiol 256: H1316-H1321, 1989; 0363-6135/89 $5.00This Article Full Text (PDF) Buy or Rent Article for $0.99 (NEW!) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shapiro, J. I. Articles by Chan, L. Search for Related Content PubMed PubMed Citation Articles by Shapiro, J. I. Articles by Chan, L. AJP - Heart and Circulatory Physiology, Vol 256, Issue 5 1316-H1321, Copyright � 1989 by American Physiological Society ARTICLES Brain pH responses to sodium bicarbonate and Carbicarb during systemic acidosis J. I. Shapiro, M. Whalen, R. Kucera, N. Kindig, G. Filley and L. Chan Department of Medicine, University of Colorado Health Sciences Center, Denver 80262. Rats subjected to ammonium chloride-induced metabolic acidosis or respiratory acidosis caused by hypercapnia were given alkalinization therapy with either sodium bicarbonate or Carbicarb. Ammonium chloride induced dose-dependent systemic acidosis but did not affect intracellular brain pH. Hypercapnia caused dose-dependent systemic acidosis as well as decreases in intracellular brain pH. Sodium bicarbonate treatment resulted in systemic alkalinization and increases in arterial PCO2 in both acidosis models, but it caused intracellular brain acidification in rats with ammonium chloride acidosis. Carbicarb therapy resulted in systemic alkalinization without major changes in arterial PCO2 and intracellular brain alkalinization in both acidosis models. These data demonstrate that bicarbonate therapy of systemic acidosis may be associated with "paradoxical" intracellular brain acidosis, whereas Carbicarb causes both systemic and intracellular alkalinization under conditions of fixed ventilation.  Initially injected into 3 liter plasma volume (not 5 liter blood volume because does not enter red cells) In vitro: small and transient (Goldsmith DJ et al, Clin Sci 93:593, Dec 97) Unpublished functional MRI studies show this is limited http://www3.interscience.wiley.com/journal/112150996/abstract � shows benefit of carbicarb over HCO3 Am J Physiol Heart Circ Physiol 256: H1316-H1321, 1989; 0363-6135/89 $5.00This Article Full Text (PDF) Buy or Rent Article for $0.99 (NEW!) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shapiro, J. I. Articles by Chan, L. Search for Related Content PubMed PubMed Citation Articles by Shapiro, J. I. Articles by Chan, L. AJP - Heart and Circulatory Physiology, Vol 256, Issue 5 1316-H1321, Copyright � 1989 by American Physiological Society ARTICLES Brain pH responses to sodium bicarbonate and Carbicarb during systemic acidosis J. I. Shapiro, M. Whalen, R. Kucera, N. Kindig, G. Filley and L. Chan Department of Medicine, University of Colorado Health Sciences Center, Denver 80262. Rats subjected to ammonium chloride-induced metabolic acidosis or respiratory acidosis caused by hypercapnia were given alkalinization therapy with either sodium bicarbonate or Carbicarb. Ammonium chloride induced dose-dependent systemic acidosis but did not affect intracellular brain pH. Hypercapnia caused dose-dependent systemic acidosis as well as decreases in intracellular brain pH. Sodium bicarbonate treatment resulted in systemic alkalinization and increases in arterial PCO2 in both acidosis models, but it caused intracellular brain acidification in rats with ammonium chloride acidosis. Carbicarb therapy resulted in systemic alkalinization without major changes in arterial PCO2 and intracellular brain alkalinization in both acidosis models. These data demonstrate that bicarbonate therapy of systemic acidosis may be associated with "paradoxical" intracellular brain acidosis, whereas Carbicarb causes both systemic and intracellular alkalinization under conditions of fixed ventilation.

7. When to give bicarb Do NOT base it on pH Base it on HCO3 level < 6 For low pH If bicarb < 6 give bicarb 2 amps Recheck ABG If pCO2 > 1.5 (HCO3) + 8 then ventilate better Severe respiratory acidosis, pH < 7.00 (pCO2 > 100)

8. Severe Asthma Beta agonists don�t work at low pH Bicarb may be beneficial

9. Lactic Acidosis Type A: Tissue Hypoxia Toxins: Iron, Isoniazid, CN, metHgb, CO, HS Shock States Profound Anemia Massive catecholamines Hypoxia Anaerobic exertion seizures, sprinting Beriberi TPN and alcoholics Type B: Normal tissue O2 paucity of NAD+ excess of NADH (Alcoholic Ketoacidosis) Diabetes Mellitus Liver Failure Renal Failure Carcinoma Hypoglycemia EtOH ingestion Many others Pyruvate (ox) Lactate (red) NAD NADH The causes of lactic acidosis have been divided into those due to inadequate tissue oxygenation (type A) and those due to other factors, such as diabetes mellitus, hypercarbia, tumors, etc. (type B) The presence of acidosis with an increased anion gap in a patient in severe shock most often is due to lactic acidosis. In type A lactic acidosis, there is poor tissue oxygenation and perfusion. In type B, however, there is no evidence of decreased tissue perfusion, and the mechanism of the acidosis is unknown. Reeker W, Schneider G, Felgenhauer N, Tempel G, Kochs E: Metformin-induced lactic acidosis. =45 mmol/L Dtsch Med Wochenschr 125: 249�251, 2000 The causes of lactic acidosis have been divided into those due to inadequate tissue oxygenation (type A) and those due to other factors, such as diabetes mellitus, hypercarbia, tumors, etc. (type B) The presence of acidosis with an increased anion gap in a patient in severe shock most often is due to lactic acidosis. In type A lactic acidosis, there is poor tissue oxygenation and perfusion. In type B, however, there is no evidence of decreased tissue perfusion, and the mechanism of the acidosis is unknown. Reeker W, Schneider G, Felgenhauer N, Tempel G, Kochs E: Metformin-induced lactic acidosis. =45 mmol/L Dtsch Med Wochenschr 125: 249�251, 2000

10. Ketoacidosis Respirations Patients without medical complaints, e.g., medication refill UA in ill patients Weakness, dizziness, nausea, vomiting, abdominal pain, malaise, altered mental status, infectious symptoms Sensitivity 99% Specificity 69% PPV 35% NPV 100% Annals of Emergency Medicine 34(3):342-346, September 1999 Ketoacidosis can be caused by either an increase in the free fatty acid load to the liver or an increased conversion of free fatty acids to keto acids. Increased conversion of fatty acids to keto acids may occur in diabetic ketoacidosis, in alcoholism, and, to a lesser degree, in prolonged starvation or a high-fat diet. The most common keto acid formed is b-hydroxybutyrate, followed by acetoacetate and hydroxybutyric acid. The nitroprusside test is commonly used to document the presence of ketones in serum and urine. This test is positive with increased levels of acetoacetate or acetone, but not with b-hydroxybutyric acid. The more acidotic the patient is, the more b-hydroxybutyric acid is formed from acetoacetate. Therefore, the test may reveal little or none of the ketoacidosis present in a severely acidotic patient. One should not assume that ketones are absent or only minimally present if the nitroprusside test is negative or only weakly positive in patients with severe acidosis. Annals of Emergency Medicine 34(3):342-346, September 1999 Ketoacidosis can be caused by either an increase in the free fatty acid load to the liver or an increased conversion of free fatty acids to keto acids. Increased conversion of fatty acids to keto acids may occur in diabetic ketoacidosis, in alcoholism, and, to a lesser degree, in prolonged starvation or a high-fat diet. The most common keto acid formed is b-hydroxybutyrate, followed by acetoacetate and hydroxybutyric acid. The nitroprusside test is commonly used to document the presence of ketones in serum and urine. This test is positive with increased levels of acetoacetate or acetone, but not with b-hydroxybutyric acid. The more acidotic the patient is, the more b-hydroxybutyric acid is formed from acetoacetate. Therefore, the test may reveal little or none of the ketoacidosis present in a severely acidotic patient. One should not assume that ketones are absent or only minimally present if the nitroprusside test is negative or only weakly positive in patients with severe acidosis.

11. Toxins: increased AG acidosis Cyanide Salicylate Methanol Ethylene glycol Paraldehyde Iron Isoniazid All lead to the formation of acid metabolites and/or organic acids which result in an increase in the anion gap. Toxic Ingestions Intoxications with cyanide, salicylate, methanol, ethylene glycol, paraldehyde, toluene, sulfur, and formaldehyde lead to the formation of acid metabolites and/or organic acids that result in an increase in the anion gap. Some of these poisonings can be suspected clinically because of the presence of an increased osmolal gap If the patient has a high anion gap metabolic acidosis without chronic renal failure, shock, or diabetic ketoacidosis, intoxication with methanol or ethylene glycol should be the first consideration, especially if the osmolal gap is increased. Toxic Ingestions Intoxications with cyanide, salicylate, methanol, ethylene glycol, paraldehyde, toluene, sulfur, and formaldehyde lead to the formation of acid metabolites and/or organic acids that result in an increase in the anion gap. Some of these poisonings can be suspected clinically because of the presence of an increased osmolal gap If the patient has a high anion gap metabolic acidosis without chronic renal failure, shock, or diabetic ketoacidosis, intoxication with methanol or ethylene glycol should be the first consideration, especially if the osmolal gap is increased.

12. Toxic Alcohols cause increased AG after metabolism only Methanol�����.�.Formic acid Ethylene glycol����Glycolic acid Lactic acid Methanol The high anion gap is caused mainly by formic acid, a metabolite of methanol. Ethylene Glycol The toxic effects of ethylene glycol poisoning are produced by metabolites of ethylene glycol, including glycoaldehydes, glycolic acid, glyoxylic acid, and oxalate. Glycolic acid and lactic acid are responsible for the high anion gap. Oxalate is the primary factor in renal toxicity. Salicylates Salicylates directly stimulate the respiratory center, causing respiratory alkalosis. Later an increased metabolic rate with the production of more carbon dioxide may result in respiratory acidosis. Eventually the direct toxic effect on carbohydrate metabolism produces the classic high anion gap metabolic acidosis. Paraldehyde The elevated anion gap is caused by acetic acid and chloracetic acid. Diagnosis is made by detection of paraldehyde in the serum and acetaldehyde in the urine and blood. When a nitroprusside reaction test is used, paralydehyde may cause a false-positive reaction for ketones, called �pseudoketosis.�Methanol The high anion gap is caused mainly by formic acid, a metabolite of methanol. Ethylene Glycol The toxic effects of ethylene glycol poisoning are produced by metabolites of ethylene glycol, including glycoaldehydes, glycolic acid, glyoxylic acid, and oxalate. Glycolic acid and lactic acid are responsible for the high anion gap. Oxalate is the primary factor in renal toxicity. Salicylates Salicylates directly stimulate the respiratory center, causing respiratory alkalosis. Later an increased metabolic rate with the production of more carbon dioxide may result in respiratory acidosis. Eventually the direct toxic effect on carbohydrate metabolism produces the classic high anion gap metabolic acidosis. Paraldehyde The elevated anion gap is caused by acetic acid and chloracetic acid. Diagnosis is made by detection of paraldehyde in the serum and acetaldehyde in the urine and blood. When a nitroprusside reaction test is used, paralydehyde may cause a false-positive reaction for ketones, called �pseudoketosis.�

13. Acidemia and Alkalemia (pH) vs. acidosis and alkalosis (metabolic disorders) pH < 7.36 is acidemia pH > 7.44 is alkalemia Mixed disorders 7.40/25/pO2/15 Metabolic acidosis + resp alkalosis 7.40/40/pO2/24, with Cl 90 and AG 27 Metabolic acidosis + metabolic alk

14. Arterial: HCO3 , pCO2, and anion gap. (pH) pCO2 and HCO3 are what determine Rx Assess pCO2 by Winter�s formula Assess HCO3 of at least 6 mmol/L Electrolytes for AG beware i-STAT (Cl is most aberrant) etCO2 � do not use

15. Metabolic acidosis: ABG? VBG? Et CO2? Normal ABG: 7.40/40/pO2/24 Normal VBG: 7.33/47/pO2/24.16

16. VBG (and CO2) vs. ABG in DKA very few ill patients (mean HCO3 = 13) Annals EM 31(4):459, April 1998 very few ill patients (mean HCO3 = 13) Annals EM 31(4):459, April 1998

17. Carbon Dioxide Content (BMP) Total of all carbon dioxide present in the blood Normally 24 to 31 mEq/L Includes: Carbonic Acid (H2CO3) Pure dissolved CO2 Bicarbonate Carbamino Compounds BMP: CO2 = 4, HCO3 = 2-3 Carbon dioxide content refers to the total of all carbon dioxide present in the blood . Normally 24 to 31 mEq/L. In the plasma, CO2 content includes carbonic acid, bicarbonate, and carbamino compounds. The amount of carbonic acid present (averaging about 1.05 to 1.35 mEq/L) can be estimated by multiplying the PCO2 by 0.03. The arterial bicarbonate concentration normally is 24 mEq/L. The concentration of the carbamino compounds, which consist of various forms of CO2 combined with amino groups on proteins, averages about 0.5 to 1.0 mEq/L, depending on total CO2 and protein concentrations.Carbon dioxide content refers to the total of all carbon dioxide present in the blood . Normally 24 to 31 mEq/L. In the plasma, CO2 content includes carbonic acid, bicarbonate, and carbamino compounds. The amount of carbonic acid present (averaging about 1.05 to 1.35 mEq/L) can be estimated by multiplying the PCO2 by 0.03. The arterial bicarbonate concentration normally is 24 mEq/L. The concentration of the carbamino compounds, which consist of various forms of CO2 combined with amino groups on proteins, averages about 0.5 to 1.0 mEq/L, depending on total CO2 and protein concentrations.

18. Potassium Acute Acidosis: 0.1 change in pH change 0.5 change in serum K+ 7.10 K 4.5 to 6.0 Prolonged acidosis: Renal K+ wasting Alkalemia: Renal K+ wasting Patients with severe acidosis tend to have high serum potassium levels, and patients with severe alkalosis tend to have low serum potassium levels. In general, a rise or fall of 0.10 in pH is associated with a corresponding fall or rise of about 0.5 (0.3 to 0.8) mEq/L in serum potassium. The potassium level in serum is slightly higher than that in plasma because the clotting process releases some potassium.Patients with severe acidosis tend to have high serum potassium levels, and patients with severe alkalosis tend to have low serum potassium levels. In general, a rise or fall of 0.10 in pH is associated with a corresponding fall or rise of about 0.5 (0.3 to 0.8) mEq/L in serum potassium. The potassium level in serum is slightly higher than that in plasma because the clotting process releases some potassium.

19. Chloride Low chloride = metabolic alkalosis Na to Cl ratio should be 1.25-1.40 Examples 140, 105 normal 155, 105 (100-110) abnormal. Ratio 1.50 Low chloride can also be compensation for chronic respiratory acidosis Even if pH is normal or low, low chloride means alkalosis Plasma chloride and bicarbonate concentrations tend to move in opposite directions. Thus, patients who have a metabolic alkalosis (and high plasma bicarbonate levels) tend to have low plasma chloride levels, whereas those with metabolic acidosis (and low plasma bicarbonate levels) tend to have normal or elevated chloride levels. However, if there are increased amounts of unmeasured anions, such as lactate, present (causing an increased anion gap), bicarbonate may be very low and chloride may be normal or even low. Effect of PCO2 and HCO3- on pH A 1.0-mmHg rise in the PCO2 produces a decrease of about 0.01 in pH, while a 1.0 mEq/L decrease in bicarbonate produces a pH decrease of about 0.02 Plasma chloride and bicarbonate concentrations tend to move in opposite directions. Thus, patients who have a metabolic alkalosis (and high plasma bicarbonate levels) tend to have low plasma chloride levels, whereas those with metabolic acidosis (and low plasma bicarbonate levels) tend to have normal or elevated chloride levels. However, if there are increased amounts of unmeasured anions, such as lactate, present (causing an increased anion gap), bicarbonate may be very low and chloride may be normal or even low. Effect of PCO2 and HCO3- on pH A 1.0-mmHg rise in the PCO2 produces a decrease of about 0.01 in pH, while a 1.0 mEq/L decrease in bicarbonate produces a pH decrease of about 0.02

20. DKA, glucose = 900 Na = 120, Cl = 90 Normal ratio (1.33) Na = 120, Cl = 80 High ratio (1.50), alkalosis

21. Anion Gap Electroneutrality Na+, Cl-, and CO2 are measured ions Na + UC = Cl + CO2 + UA UA � UC = Na � (Cl + CO2) UA = Sum of unmeasured anions UC = Sum of unmeasured cations The concept of an anion gap in blood was described in 1939 by Gamble. It was felt that the law of electroneutrality required that the number of positive charges contributed by serum cations should equal the number of negative charges contributed by serum anions. Sodium (Na), chloride (Cl), and bicarbonate (HCO3) are considered the measured ions. Potassium is ignored because its value changes so little. Thus, the concept of electroneutrality can be expressed by the simple equation: Na + UC = Cl + HCO3 + UA where UC (unmeasured cations) indicates the sum of the charges of the cations other than sodium and UA (unmeasured anions) equals the sum of the charges of all of the anions other than chloride and bicarbonate.The concept of an anion gap in blood was described in 1939 by Gamble. It was felt that the law of electroneutrality required that the number of positive charges contributed by serum cations should equal the number of negative charges contributed by serum anions. Sodium (Na), chloride (Cl), and bicarbonate (HCO3) are considered the measured ions. Potassium is ignored because its value changes so little. Thus, the concept of electroneutrality can be expressed by the simple equation: Na + UC = Cl + HCO3 + UA where UC (unmeasured cations) indicates the sum of the charges of the cations other than sodium and UA (unmeasured anions) equals the sum of the charges of all of the anions other than chloride and bicarbonate.

22. Anion Gap, normal 8-15, > 18 = acidosis Increased: Decrease in UC or Increased UA Unmeasured Cations: total 11 mEq/L Potassium 4 Calcium 5 Magnesium 2 Unmeasured Anions: total 23 mEq/L Sulfates 1 Phosphates 2 Albumin 16 Lactic acid 1 Org. acids 3 The �unmeasured cations� usually total about 11 mEq/L and include potassium (4 mEq/L), calcium (5 mEq/L), and magnesium (2 mEq/L). The �unmeasured� serum anions include sulfates (1 mEq/L), phosphates (2 mEq/L), proteins (16 mEq/L), lactic acid (1 mEq/L), and other organic acids (3 mEq/L). Ordinarily, the sodium concentration is about 140 mEq/L, and the sum of the CO2 content and chloride anions is about 128 mEq/L. Thus, the difference (or anion gap) between the sodium concentration and the sum of these two anions averages about 12 mEq/L. In patients with excessive acid production, the anion gap tends to be increased. On the other hand, in patients with metabolic acidosis due to loss of bicarbonate, the anion gap usually stays relatively normal.The �unmeasured cations� usually total about 11 mEq/L and include potassium (4 mEq/L), calcium (5 mEq/L), and magnesium (2 mEq/L). The �unmeasured� serum anions include sulfates (1 mEq/L), phosphates (2 mEq/L), proteins (16 mEq/L), lactic acid (1 mEq/L), and other organic acids (3 mEq/L). Ordinarily, the sodium concentration is about 140 mEq/L, and the sum of the CO2 content and chloride anions is about 128 mEq/L. Thus, the difference (or anion gap) between the sodium concentration and the sum of these two anions averages about 12 mEq/L. In patients with excessive acid production, the anion gap tends to be increased. On the other hand, in patients with metabolic acidosis due to loss of bicarbonate, the anion gap usually stays relatively normal.

23. Increased AG Metabolic Acidosis: MUDPILES Methanol Uremia/Renal Failure DKA (AKA, SKA) INH, Iron--lactate Paraldehyde Lactic Acidosis Has many etiologies Cyanide, CO, Toluene, HS Poor perfusion Ethylene glycol Salicylates Methyl salicylate (Oil of wintergreen) Mg salicylate (Doan�s pills) Levraut J. et al. Reliability of anion gap as an indicator of blood lactate in critically ill patients. Intensive Care Medicine 23(417); 1997 Abstract�� Objective: To evaluate the sensitivity, specificity, and predictive values of an elevated anion gap as an indicator of hyperlactatemia and to assess the contribution of blood lactate to the serum anion gap in critically ill patients. Design: Prospective study. Setting: General intensive care unit of a university hospital. Patients: 498 patients, none with ketonuria, severe renal failure or aspirin, glycol, or methanol intoxication. Measurements and results: The anion gap was calculated as [Na+] - [Cl-] - [TCO2]. Hyperlactatemia was defined as a blood lactate concentration above 2.5 mmol/l. The mean blood lactate concentration was 3.7 � 3.2 mmol/l and the mean serum anion gap was 14.3 � 4.2 mEq/l. The sensitivity of an elevated anion gap to reveal hyperlactatemia was only 44 % [95 % confidence interval (CI) 38 to 50], whereas specificity was 91 % (CI 87 to 94) and the positive predictive value was 86 % (CI 79 to 90). As expected, the poor sensitivity of the anion gap increased with the lactate threshold value, whereas the specificity decreased [for a blood lactate cut-off of 5 mmol/l: sensitivity = 67 % (CI 58 to 75) and specificity = 83 % (CI 79 to 87)]. The correlation between the serum anion gap and blood lactate was broad (r 2 = 0.41, p < 0.001) and the slope of this relationship (0.48 � 0.026) was less than 1 (p < 0.001). The serum chloride concentration in patients with a normal anion gap (99.1 � 6.9 mmol/l) was comparable to that in patients with an elevated anion gap (98.8 � 7.1 mmol/l). Conclusions: An elevated anion gap is not a sensitive indicator of moderate hyperlactatemia, but it is quite specific, provided the other main causes of the elevated anion gap have been eliminated. Changes in blood lactate only account for about half of the changes in anion gap, and serum chloride does not seem to be an important factor in the determination of the serum anion gap.Levraut J. et al. Reliability of anion gap as an indicator of blood lactate in critically ill patients. Intensive Care Medicine 23(417); 1997 Abstract�� Objective: To evaluate the sensitivity, specificity, and predictive values of an elevated anion gap as an indicator of hyperlactatemia and to assess the contribution of blood lactate to the serum anion gap in critically ill patients. Design: Prospective study. Setting: General intensive care unit of a university hospital. Patients: 498 patients, none with ketonuria, severe renal failure or aspirin, glycol, or methanol intoxication. Measurements and results: The anion gap was calculated as [Na+] - [Cl-] - [TCO2]. Hyperlactatemia was defined as a blood lactate concentration above 2.5 mmol/l. The mean blood lactate concentration was 3.7 � 3.2 mmol/l and the mean serum anion gap was 14.3 � 4.2 mEq/l. The sensitivity of an elevated anion gap to reveal hyperlactatemia was only 44 % [95 % confidence interval (CI) 38 to 50], whereas specificity was 91 % (CI 87 to 94) and the positive predictive value was 86 % (CI 79 to 90). As expected, the poor sensitivity of the anion gap increased with the lactate threshold value, whereas the specificity decreased [for a blood lactate cut-off of 5 mmol/l: sensitivity = 67 % (CI 58 to 75) and specificity = 83 % (CI 79 to 87)]. The correlation between the serum anion gap and blood lactate was broad (r 2 = 0.41, p < 0.001) and the slope of this relationship (0.48 � 0.026) was less than 1 (p < 0.001). The serum chloride concentration in patients with a normal anion gap (99.1 � 6.9 mmol/l) was comparable to that in patients with an elevated anion gap (98.8 � 7.1 mmol/l). Conclusions: An elevated anion gap is not a sensitive indicator of moderate hyperlactatemia, but it is quite specific, provided the other main causes of the elevated anion gap have been eliminated. Changes in blood lactate only account for about half of the changes in anion gap, and serum chloride does not seem to be an important factor in the determination of the serum anion gap.

24. Anorexic 17 yo, dehydrated Na = 140 Cl = 105 CO2 = 22 AG = 13 Lactate = 7 Albumin = 1.9

25. Decreased or Negative Anion GapClin J Am Soc Nephrol 2: 162-174, 2007 Low albumin Unmeasured negative charges 1 g drop in albumin 2-2.5 mEq/liter drop in AG Bromism, multiple myeloma Other etiologies of low AG: Low K, Mg, Ca, increased globulins (Mult. Myeloma), Li, Br (bromism), I intoxication Negative AG more unmeasured cations than unmeasured anions Bromide, Iodide, Multiple Myeloma Other etiologies of low AG: Low K, Mg, Ca, increased globulins (Mult. Myeloma), Li, Br (bromism), I intoxication Negative AG more unmeasured cations than unmeasured anions Bromide, Iodide, Multiple Myeloma

26. 42 yo alcoholic Na = 140 Cl = 88 CO2 = 18 AG = 34 Delta CO2 = 25-18 = 7 Delta AG = 34 � 12 = 22 Anion gap M. acidosis + metabolic alkalosis

27. Delta Anion Gap vs. Delta HCO3 Simple AG Metabolic Acidosis decrease in plasma bicarbonate = increase in AG Anion Gap = 1 HCO3 > 1 is superimposed alkalosis 0 is non-anion gap acidosis 0-1 is both AG and non-AG acidosis In uncomplicated increased anion gap metabolic acidosis, the decrease (change) in plasma bicarbonate should be roughly equal to the increase (change) in the anion gap (that is, dAG/dHCO3 = 1.0). Whenever the anion gap changes much more or less than the bicarbonate, one should be suspicious of a coexisting or a mixed acid-base disorder. Ratios between 0.3 and 0.7 usually, but not always, indicate a mixed acid-base disorder or a preexisting low anion gap. Thus, the dAG/dHCO3 ratio is helpful in the diagnosis of mixed acid-base disorder because this ratio is usually close to 1.0 in typical organic acidoses. Values greater than 1.2 or less than 0.8 suggest the presence of a mixed acid-base disorder or an independent factor affecting the anion gap.In uncomplicated increased anion gap metabolic acidosis, the decrease (change) in plasma bicarbonate should be roughly equal to the increase (change) in the anion gap (that is, dAG/dHCO3 = 1.0). Whenever the anion gap changes much more or less than the bicarbonate, one should be suspicious of a coexisting or a mixed acid-base disorder. Ratios between 0.3 and 0.7 usually, but not always, indicate a mixed acid-base disorder or a preexisting low anion gap. Thus, the dAG/dHCO3 ratio is helpful in the diagnosis of mixed acid-base disorder because this ratio is usually close to 1.0 in typical organic acidoses. Values greater than 1.2 or less than 0.8 suggest the presence of a mixed acid-base disorder or an independent factor affecting the anion gap.

28. Severe diarrhea, cachectic, Kussmauling 7.10/18/pO2/7 Na = 155 Cl = 133 CO2 = 9 AG = 13 Don�t need ABG on everyone with diarrhea Lactate = 6

29. Metabolic Acidosis: Normal AGLoss of HCO3Failure to excrete [H+]Administration of [H+] Loss of HCO3 Severe diarrhea Ureteroileostomy Acetazolamide Failure to excrete [H+] Renal Tubular Acidosis Types 1-4 Toluene Administration of [H+] Ammonium chloride Normal Anion Gap (Hyperchloremic) Metabolic Acidosis The most frequent causes of bicarbonate loss resulting in normal anion gap (hyperchloremic) metabolic acidosis include severe diarrhea, pancreatic fistulas, RTA, adrenal insufficiency, and therapy with carbonic anhydrase inhibitors, ammonium chloride, arginine hydro-chloride, or amino acid hydrochlorides (as in TPN). There are three main types of RTA: RTA I, RTA II, and RTA IV. RTA I involves failure of the distal renal tubules to excrete acid properly and RTA-II involves bicarbonate wasting in the proximal renal tubules. Both RTA I and RTA II tend to cause a normal anion gap metabolic acidosis with hypokalemia. RTA IV usually causes hyperkalemia. Normal Anion Gap (Hyperchloremic) Metabolic Acidosis The most frequent causes of bicarbonate loss resulting in normal anion gap (hyperchloremic) metabolic acidosis include severe diarrhea, pancreatic fistulas, RTA, adrenal insufficiency, and therapy with carbonic anhydrase inhibitors, ammonium chloride, arginine hydro-chloride, or amino acid hydrochlorides (as in TPN). There are three main types of RTA: RTA I, RTA II, and RTA IV. RTA I involves failure of the distal renal tubules to excrete acid properly and RTA-II involves bicarbonate wasting in the proximal renal tubules. Both RTA I and RTA II tend to cause a normal anion gap metabolic acidosis with hypokalemia. RTA IV usually causes hyperkalemia.

30. Compensation Compensation is rarely complete Returns pH toward normal Compensation is not a secondary acidosis or alkalosis High altitude, pregnancy: nearly full compensation, but it takes time Acetazolamide hastens compensation Any abnormality that disturbs the normal ratio between arterial bicarbonate and carbonic acid tends to immediately stimulate a compensatory metabolic or respiratory response�to try to bring the ratio back to 7.35 if the primary problem is an acidosis or to 7.45 if the problem is an alkalosis. If we know what normal compensation is, then we can determine if the compensation we see in a particular patient is appropriate, or if there is a second or third disorder. Failure of compensatory mechanisms, or a combination of primary processes driving the pH in the same direction so that it rapidly falls and stays below 7.10 or rises above 7.60, is frequently lethal. Inability to compensate for an acid-base abnormality usually means a severe disturbance of ventilatory, renal, or general cellular function. Any abnormality that disturbs the normal ratio between arterial bicarbonate and carbonic acid tends to immediately stimulate a compensatory metabolic or respiratory response�to try to bring the ratio back to 7.35 if the primary problem is an acidosis or to 7.45 if the problem is an alkalosis. If we know what normal compensation is, then we can determine if the compensation we see in a particular patient is appropriate, or if there is a second or third disorder. Failure of compensatory mechanisms, or a combination of primary processes driving the pH in the same direction so that it rapidly falls and stays below 7.10 or rises above 7.60, is frequently lethal. Inability to compensate for an acid-base abnormality usually means a severe disturbance of ventilatory, renal, or general cellular function.

31. Respiratory Compensation Occurs Rapidly Metabolic Acidosis: Hyperventilation �Kussmaul Respirations� Deep > rapid (high tidal volume) Metabolic Alkalosis: Calculation not as accurate Hypoventilation Restricted by hypoxemia PCO2 seldom > 50-55 Commonly, compensation for a Pure metabolic Alkalosis: pCO2= 0.9 x HCO3 + 9 (not 15) pCO2 cannot go below 10 experimentally Resp. Compensation never raises the pH above 7.35 Commonly, compensation for a Pure metabolic Alkalosis: pCO2= 0.9 x HCO3 + 9 (not 15) pCO2 cannot go below 10 experimentally Resp. Compensation never raises the pH above 7.35

32. Metabolic Compensationrenal, slow, days Chronic Hypercapnia: HCO3 incr. 3.5 mmol/L for each 10 mmHg increase in PaCO2 > 40 Chronic Hypocapnia: HCO3 decreases 5 mmol/L for every 10 mmHg decrease in PaCO2 < 40 During acute and chronic hypocapnia and hypercapnia, the changes in HCO3 are almost linear over the range of PaCO2 (20 to 100 mmHg) encountered in altered pathologic states. Thus, you can predict to some degree what the HCO3 �should be� for any PaCO2. This observation leads to certain rules of thumb to characterize various acid-base abnormalities: During acute hypercapnia, HCO3 increases 1 mmol/L for each 10-mmHg increase in PaCO2 above 40 mmHg. During chronic hypercapnia, HCO3 increases 4 mmol/L for each 10-mmHg increase in PaCO2 above 40 mmHg. During acute hypocapnia, HCO3 decreases 2 mmol/L for every 10-mmHg decrease in PaCO2 below 40 mmHg. During chronic hypocapnia, HCO3 decreases at least 5 mmol/L for every 10-mmHg decrease in PaCO2 below 40 mmHg.During acute and chronic hypocapnia and hypercapnia, the changes in HCO3 are almost linear over the range of PaCO2 (20 to 100 mmHg) encountered in altered pathologic states. Thus, you can predict to some degree what the HCO3 �should be� for any PaCO2. This observation leads to certain rules of thumb to characterize various acid-base abnormalities: During acute hypercapnia, HCO3 increases 1 mmol/L for each 10-mmHg increase in PaCO2 above 40 mmHg. During chronic hypercapnia, HCO3 increases 4 mmol/L for each 10-mmHg increase in PaCO2 above 40 mmHg. During acute hypocapnia, HCO3 decreases 2 mmol/L for every 10-mmHg decrease in PaCO2 below 40 mmHg. During chronic hypocapnia, HCO3 decreases at least 5 mmol/L for every 10-mmHg decrease in PaCO2 below 40 mmHg.

33. Acute respiratory acidosis or alkalosis When pH is between 7.30-7.50: pH change of .08 per 10 mmHg pCO2 change 7.32/50/pO2/25, 7.26/60/pO2/26 7.48/30/pO2/22, 7.60/20/pO2/21 Kassirer-Bleich equationKassirer-Bleich equation

34. What�s this? 7.55/25/pO2/22

35. Respiratory Alkalosis: Etiology Salicylates Increased ICP Liver Failure Hypoxia CHF Pericardial effusion Pulmonary Embolus Hyperthyroidism Pregnancy Sympathomimetics Amphetamines Cocaine PCP Hyperventilation Shock Sepsis CNS disease In stressful situations such as shock, sepsis, or trauma, there is a tendency to hyperventilate and develop respiratory alkalosis with a PCO2 of 25 to 35 mmHg or less. If hypoxia or metabolic acidosis develops, the tendency to hyperventilation is increased even further. Severe respiratory alkalosis tends to perpetuate itself. If the arterial PCO2 falls, cerebral vasoconstriction occurs. In fact, each 1.0-mmHg drop in the arterial PCO2 reduces cerebral blood flow by about 2 to 4 percent. Thus, a severe respiratory alkalosis, especially if the PCO2 is less than 20 mmHg, can reduce cerebral blood flow enough to cause cerebral metabolic acidosis. This cerebral metabolic acidosis will then cause the respiratory center to increase ventilation even more, producing a progressively more severe respiratory alkalosis. The initial response to hypocapnia is a shift of hydrogen chloride and lactate ions out of the cell. In severe respiratory alkalosis, lactic acid levels may increase by 2.0 to 3.0 mmol/L. This buffering is rapid and may be complete within 15 min of the initiation of the hypocapnia. The renal compensation will also begin to take effect within 2 to 4 h after the onset of hypocapnia.In stressful situations such as shock, sepsis, or trauma, there is a tendency to hyperventilate and develop respiratory alkalosis with a PCO2 of 25 to 35 mmHg or less. If hypoxia or metabolic acidosis develops, the tendency to hyperventilation is increased even further. Severe respiratory alkalosis tends to perpetuate itself. If the arterial PCO2 falls, cerebral vasoconstriction occurs. In fact, each 1.0-mmHg drop in the arterial PCO2 reduces cerebral blood flow by about 2 to 4 percent. Thus, a severe respiratory alkalosis, especially if the PCO2 is less than 20 mmHg, can reduce cerebral blood flow enough to cause cerebral metabolic acidosis. This cerebral metabolic acidosis will then cause the respiratory center to increase ventilation even more, producing a progressively more severe respiratory alkalosis. The initial response to hypocapnia is a shift of hydrogen chloride and lactate ions out of the cell. In severe respiratory alkalosis, lactic acid levels may increase by 2.0 to 3.0 mmol/L. This buffering is rapid and may be complete within 15 min of the initiation of the hypocapnia. The renal compensation will also begin to take effect within 2 to 4 h after the onset of hypocapnia.

36. 25 y.o. IVDU s/p heroin OD pH 7.10 pCO2 87 Bicarbonate 26

37. Respiratory Acidosis: Etiology Inadequate minute ventilation Head, Chest, Spinal Cord trauma Sedative-Hypnotics Neuropathy/Myopathy Pulmonary Disorder Airway Obstruction Sleep Apnea Increased dead space ventilation COPD Increased carbohydrate metabolism TPN A PCO2 elevated above 45 mmHg is usually due to inadequate minute ventilation and/or increased dead space. In general, a rise in the PCO2 stimulates the respiratory center to increase respiratory rate and minute ventilation. With a sudden severe decrease in minute ventilation, the PCO2 rises rapidly and the pH may fall abruptly because bicarbonate compensation by the kidney is very slow. In completely apneic patients, the arterial PCO2 rises by about 2.0 to 3.0 mmHg/min. A high bicarbonate level in an ambulatory patient should make one suspicious of a chronic respiratory acidosis. Coma can occur at a PCO2 exceeding 65 to 70 mmHg; however, if the respiratory acidosis develops very slowly, coma may not develop until the PCO2 exceeds 100 to 110 mmHg. Respiratory acidosis, by definition, is present when the arterial PCO2 exceeds 45 mmHg and the pH is 7.39 or less. If the pH is less than 7.30, the respiratory acidosis is usually acute or there is a superimposed metabolic acidosis. If the carbon dioxide content of an electrolyte study is high, one should suspect a chronic respiratory acidosis or a metabolic alkalosis. A PCO2 elevated above 45 mmHg is usually due to inadequate minute ventilation and/or increased dead space. In general, a rise in the PCO2 stimulates the respiratory center to increase respiratory rate and minute ventilation. With a sudden severe decrease in minute ventilation, the PCO2 rises rapidly and the pH may fall abruptly because bicarbonate compensation by the kidney is very slow. In completely apneic patients, the arterial PCO2 rises by about 2.0 to 3.0 mmHg/min. A high bicarbonate level in an ambulatory patient should make one suspicious of a chronic respiratory acidosis. Coma can occur at a PCO2 exceeding 65 to 70 mmHg; however, if the respiratory acidosis develops very slowly, coma may not develop until the PCO2 exceeds 100 to 110 mmHg. Respiratory acidosis, by definition, is present when the arterial PCO2 exceeds 45 mmHg and the pH is 7.39 or less. If the pH is less than 7.30, the respiratory acidosis is usually acute or there is a superimposed metabolic acidosis. If the carbon dioxide content of an electrolyte study is high, one should suspect a chronic respiratory acidosis or a metabolic alkalosis.

38. 3 important equations Chronic respiratory acidosis: steady-state pCO2 is increased by 10 for every 3.5 increase in HCO3 Acute metabolic acidosis: pCO2 = 1.5 x HCO3 + 8 (+/- 2) Acute metabolic alkalosis: pCO2 = 0.9 x HCO3 + 15

39. 3 examples pH 6.80 pCO2 27 Bicarbonate 4 pCO2 = 1.5 x HCO3 + 8 (+/- 2) = 14 7.58/50/pO2/45 pCO2 = 0.9 x HCO3 + 15 7.23/85/pO2/35

40. 65 y.o. Veteran with COPD exacerbation 7.23/85/pO2/35 Pure chronic resp acidosis (baseline)? Chronic resp acidosis Superimposed acute resp acidosis (bad)? Chronic resp acidosis Superimposed acute resp alk (appropriate)? Case 1: delta PCO2= 20 Expected compensation is 2(4)=8 Thus 24+8= 32 Case 2: No compensation. delta pCO2=23 Gross calculation= 2(.08)=.16 7.4-0.16= 7.24 HCO3 Compensation should be 2(1 HCO3)=2 24+2=26 is expected HCO3Case 1: delta PCO2= 20 Expected compensation is 2(4)=8 Thus 24+8= 32 Case 2: No compensation. delta pCO2=23 Gross calculation= 2(.08)=.16 7.4-0.16= 7.24 HCO3 Compensation should be 2(1 HCO3)=2 24+2=26 is expected HCO3

41. Chronic Respiratory Acidosis + ? 7.23/85/pO2/35 For every 10 mmHg elevation of chronic pCO2 bicarb is 3.5 above normal Working backwards: 35-24=11. 11/3.5 = 3. 3 x 10 =30. 40 + 30 = 70 Baseline 7.32/70/pO2/35 Pt. has acute resp acidosis Case 1: delta PCO2= 20 Expected compensation is 2(4)=8 Thus 24+8= 32 Case 2: No compensation. delta pCO2=23 Gross calculation= 2(.08)=.16 7.4-0.16= 7.24 HCO3 Compensation should be 2(1 HCO3)=2 24+2=26 is expected HCO3Case 1: delta PCO2= 20 Expected compensation is 2(4)=8 Thus 24+8= 32 Case 2: No compensation. delta pCO2=23 Gross calculation= 2(.08)=.16 7.4-0.16= 7.24 HCO3 Compensation should be 2(1 HCO3)=2 24+2=26 is expected HCO3

42. 43 yo female Brought by friends from convention. Had been staggering, speaking incoherently, swearing, yelling. In APS, pt. was confused, agitated, speaking jibberish. Brought to ED. Friends left. 110/70 128 r 22 t 98 uncooperative, pretending to smoke cigarette o/w exam negative except for dry MM Valium, Benadryl, Droperidol given 125/65/64/142 AG = 23 7.67/35/78/40 2.1/37/3.9 U/A, Etoh, U tox all neg. lactate 1.5 resp. alk. + met. alk. + (because of large AG) met. acidosis

43. 43 yo female to MICU Cardiac arrest. Monitor shows torsade de pointes CPR Spontaneously back to NSR Intubated. Now ventilated, unconscious Pt. goes back into torsade. What immediate effective treatment was done?

45. Metabolic AlkalosisLow Chloride: Na/Cl ratio is > 1.4 (or delta AG high) Hypochloremia, �Chloride responsive� (treatment?) Chloride and potassium loss (not H+ loss): Vomiting, NG suction Diuretics Volume contraction including edematous states, esp. liver failure Alkali ingestion Anion gap increases usually not more than 5 mEq/l Post hypocapnia: (i.e. the metabolic compensation for resp. acidosis lingers after the resp. acidosis is resolved)Post hypocapnia: (i.e. the metabolic compensation for resp. acidosis lingers after the resp. acidosis is resolved)

46. Beware Severe Alkalemia General and Cerebral vasoconstrictor Shift of oxyhemoglobin dissociation Hypokalemia Increased SVR and decreased CO Decreased Contractility Cardiac arrhythmias refractory Seizures

47. Severe Alkalosis/alkalemia Be sure oxygenation OK Avoid respiratory stimulation Intubation and controlled hypoventilation Monitor K, Mg, PO4 Acetazolamide, 500 mg IV HCl infusion 0.1M solution (100 mmol/L, 0.2 mmol/kg/hour) Central line Total dose = ? HCO3 x kg x 0.5 (in mmoles)

48. 58 year old man with weeks of vomiting Chronic abdominal pain Ill appearing Anion gap= 145- (86 + 45)= 14 The patient is severely alkalemic (pH= 7.58) HCO3 is very high. Without compensation, 7.7 region (death) Respiratory compensation? Usually mild as in this case (pCO2= 49)Anion gap= 145- (86 + 45)= 14 The patient is severely alkalemic (pH= 7.58) HCO3 is very high. Without compensation, 7.7 region (death) Respiratory compensation? Usually mild as in this case (pCO2= 49)

49. 58 yo m with severe vomiting SEVERE metabolic alkalosis. Respiratory compensation keeps him alive If pCO2 = 40, pH = 7.73 If pCO2 = 30, pH = 7.86 Triggers for increased ventilation: pain, anxiety, hypoxia could lead to lethal alkalemia. HCl, or 500 mg IV diamox, or both Oxygen and sedation to control ventilation

50. Mixed disorders, summary

51. Mixed Disorders, summary pH > 7.44, pCO2 < 36 Resp alkalosis pH < 7.36, pCO2 > 44 Resp acidosis pH < 7.36, pCO2 < 36 Metabolic acidosis with compensation pH > 7.44, pCO2 > 44 Metabolic alkalosis with compensation pH < 7.36, pCO2 >>44, (HCO3 > 28) Chronic resp acidosis pH > 7.44, pCO2 << 36, (HCO3 < 22) Chronic resp alkalosis

52. Mixed Acid-Base Disorders: Is the degree of respiratory compensation for a metabolic acidosis too much or too little?

53. Mixed Acid-Base Disorders: High AG = metabolic acidosis Is the magnitude of the increase in AG equal to the magnitude of the decrease in serum bicarb? AG Change >> Bicarb Change (chloride is relatively low) Superimposed Met. Alkalosis

54. Mixed Alkalosis and Triple Disorder

55. Mixed Acid-Base: Example 1 27 y.o man with polyuria and polydipsia for one week, and intractable vomiting for 4 days. Today he is critically ill with a temp. of 104 F. 20(1.5) +8=38 expected PCO2: Thus, pCO2 is too low given the HCO320(1.5) +8=38 expected PCO2: Thus, pCO2 is too low given the HCO3

56. Mixed Acid-Base: Example 2 25 y.o. admitted with severe DKA. Initial ABG: 6.9 / 10 / pO2 / 2.4 The patient was initially severely acidemic and maximally compensated, and near death for that matter Now, the delta AG is 8, and the bicarb is improved to 10, which gives a delta bicarb of 14. The delta AG is less than the delta bicarb because of the increase in chloride that is now possible with rehydration and adequate perfusion of the kidney.The patient was initially severely acidemic and maximally compensated, and near death for that matter Now, the delta AG is 8, and the bicarb is improved to 10, which gives a delta bicarb of 14. The delta AG is less than the delta bicarb because of the increase in chloride that is now possible with rehydration and adequate perfusion of the kidney.

57. Mixed Acid-Base: Example 2 25 y.o. with severe DKA. Initial ABG: 6.9 / 10 / pO2 / 2.4 AG = 36 After 6 hours of resus with NS and bicarb: The patient was initially severely acidemic and maximally compensated, and near death for that matter Now, the delta AG is 8, and the bicarb is improved to 10, which gives a delta bicarb of 14. The delta AG is less than the delta bicarb because of the increase in chloride that is now possible with rehydration and adequate perfusion of the kidney.The patient was initially severely acidemic and maximally compensated, and near death for that matter Now, the delta AG is 8, and the bicarb is improved to 10, which gives a delta bicarb of 14. The delta AG is less than the delta bicarb because of the increase in chloride that is now possible with rehydration and adequate perfusion of the kidney.

58. Mixed Acid-Base: Example 3 72 y.o. man with a h/o PUD has been vomiting for 2 weeks. Vitals on presentation: P 140, BP 60/P

59. Quiz Case #1 An 80 year old man has been confused and c/o SOB for one week. He also has tinnitus. Family denies medications. The patient is alkalemic The pCO2 is quite low Bicarb looks low. Gap=around 20 Diagnosis?The patient is alkalemic The pCO2 is quite low Bicarb looks low. Gap=around 20 Diagnosis?

60. Quiz Case #1 Anion Gap= 143-(108+13)= 22, ? AG = 10 ? Bicarb= 25-13= 12 pCO2= 1.5 (12) + 8 = 26 (compared/w 15) Patient is Alkalemic (pH= 7.53) indicating a Superimposed Respiratory Alkalosis Gap is 20 Delta AG=8 Delta Bicarb=12 (A little NON AG acidosis) ---------------------- Looking at the numbers, you know the patient has a increase AG metabolic acidosis. The gap is high and the bicarb is low. Is the degree of respiratory compensation appropriate for this bicarb? No, the PCO2 should have been 26, but was 15. Since the body can�t �overcompensate� there is another disorder going on. A Concomitant resp. alkalosis. from salicilism.Gap is 20 Delta AG=8 Delta Bicarb=12 (A little NON AG acidosis) ---------------------- Looking at the numbers, you know the patient has a increase AG metabolic acidosis. The gap is high and the bicarb is low. Is the degree of respiratory compensation appropriate for this bicarb? No, the PCO2 should have been 26, but was 15. Since the body can�t �overcompensate� there is another disorder going on. A Concomitant resp. alkalosis. from salicilism.

61. Quiz Case # 2 23 year old AIDS patient c/o weakness and prolonged severe diarrhea. He appears markedly dehydrated. Diarrhea should make one think bicarb losses. The bicarb is 10. K+ is usually normally lost as well, and the pt. is hypokalemic. The pt�s sodium, BUN, and Cr are elevated, which is often the case with dehydration. The chloride is also very high here. The patient�s gas suggests acidemia. The pCO2 is also low. Let�s go over the numbers.Diarrhea should make one think bicarb losses. The bicarb is 10. K+ is usually normally lost as well, and the pt. is hypokalemic. The pt�s sodium, BUN, and Cr are elevated, which is often the case with dehydration. The chloride is also very high here. The patient�s gas suggests acidemia. The pCO2 is also low. Let�s go over the numbers.

62. Quiz Case # 2 Anion Gap= 147-(129 + 12) = 6 (low) The patient is Acidemic (pH 7.27) Respiratory compensation normal? 1.5 (HCO3) + 8 plus or minus 2 1.5 (11) + 8= 24.5 (compare with 25) The gap is 10 which is normal Thus, the bicarb is low, but there has been a stoichiometric chloride elevation, thus making the gap normal because chloride is measured. The patient is acidemic. Compensation? Pure, well compensated hyperchloremic metabolic acidosis.The gap is 10 which is normal Thus, the bicarb is low, but there has been a stoichiometric chloride elevation, thus making the gap normal because chloride is measured. The patient is acidemic. Compensation? Pure, well compensated hyperchloremic metabolic acidosis.

63. Quiz Case #3 45 y.o. alcoholic man has been vomiting for 3 days. Vitals: BP 100/70, P 110. Intern administered Valium 30 mg for tremulousness. Gas suggests acidemia, with a normal pCO2. The acidemia has to be metabolic. Bicarb is 19, and serum ketones return as positive. Again, the K+ is low despite the presence of acidemia. The patient�s corrected K+ would be around 2.5, and will fall in this direction with resuscitation. Gas suggests acidemia, with a normal pCO2. The acidemia has to be metabolic. Bicarb is 19, and serum ketones return as positive. Again, the K+ is low despite the presence of acidemia. The patient�s corrected K+ would be around 2.5, and will fall in this direction with resuscitation.

64. Quiz Case #3 Anion Gap= 145- (96 + 19)= 30 ? Bicarb= 24-19= 5 ? AG= 30-12= 18 Change in AG >> Change in Bicarb Superimposed Metabolic Alkalosis Respiratory compensation? 1.5 x (19) + 8= 36 (compared with pCO2=40) This patient should have easily been able to compensate for this degree of acidosis.This patient should have easily been able to compensate for this degree of acidosis.

65. Quiz Case #3 Anion Gap Metabolic Acidosis (AKA) Metabolic Alkalosis (Persistent Vomiting) Mild Respiratory Acidosis (Oversedation)

66. Summary of important points Acidosis/Alkalosis are metabolic states ? acidemia/alkalemia Doubling or halving the HCO3:pCO2 ratio changes pH by 0.3 Bicarbonate therapy based on bicarb = 6, not pH If bicarb >/= 6 and approp pCO2, then pH > 7.10 Very low pH with bicarb > 6 needs Rx with ventilation Know the anion gap and MUDPILES Anion Gap = 18 is metabolic acidosis no matter what the pH, pCO2, or bicarb. Normal Na/Cl ratio is 1.33 (140/105) Low Cl (Na/Cl ratio > 1.4, e.g. 140/99) is metabolic alkalosis (or chronic compensation for respiratory acidosis) Winter�s formula: pCO2 should be = 1.5 x HCO3 + 8 Compensation is rarely complete Metabolic Alkalosis is dangerous Resp Alkalosis is a sign of serious illness (not just �hyperventilating�)

67. The End

68. Base Deficit volume of distribution, extracellular fluid= 0.3 L/kg = (0.3L/kg) (kg) [(24 � HCO3) mEq/L2 E.g.: 70 kg person with bicarb of 3 0.3L/kg x 70kg x 21 mEq/L/L = 441 mEq 441mEq � 50 mEq/ml/ampule = 9 Amps of bicarb Suppose you want to get the bicarb back to 6 0.3 x 70 x (6-3) = 63 63 mEq � 50 mEq/ml/ampule = 1.25 Amps of bicarb