1. Acid Base Physiology Overview Jeff Kaufhold, MD FACP 2010

2. Acid Base Physiology Where does Acid come from? Where does Acid come from? Physiologic control Physiologic control Regulation Regulation Rules of Thumb Rules of Thumb Cases Cases

3. Source of Acid Cellular Metabolism 32,000 mEq/day Cellular Metabolism 32,000 mEq/day Converted to CO2 and Water in the Cell Converted to CO2 and Water in the Cell Organic16,000 milliMole Organic16,000 milliMole Cleared by Lung Cleared by Lung Inorganic70 mEq Inorganic70 mEq Cleared by Kidneys Cleared by Kidneys

4. Physiologic Control Normal pH is 7.3-7.5 Normal pH is 7.3-7.5 Equivalent to only 40 Nanomole/liter of free H+ (0.0017 mEq) Equivalent to only 40 Nanomole/liter of free H+ (0.0017 mEq) Compared to 2000 mEq of sodium Compared to 2000 mEq of sodium Must be buffered and eliminated Must be buffered and eliminated

5. Buffer System Bicarbonate Bicarbonate Anion Gap is a measure of buffer capacity Anion Gap is a measure of buffer capacity Proteins (predominantly albumin) Proteins (predominantly albumin) RBC’s carry hemoglobin which can conveniently bind acid and carry away from tissue to lungs RBC’s carry hemoglobin which can conveniently bind acid and carry away from tissue to lungs

6. Excretion of Acid Lungblows off CO2 and traps H+ as H2O Lungblows off CO2 and traps H+ as H2O Kidney Kidney Lumenal carbonic anhydrase in proximal tubule to reclaim filtered bicarb Lumenal carbonic anhydrase in proximal tubule to reclaim filtered bicarb Basolateral Carbonic Anhydrase in Distal tubule to extract H+ from blood and excrete it Basolateral Carbonic Anhydrase in Distal tubule to extract H+ from blood and excrete it Ammoniagenesis in interstitium to buffer urine pH. Ammoniagenesis in interstitium to buffer urine pH. Disorders here lead to RTA Disorders here lead to RTA

7. Acid base Regulation Henderson hasselbach equation: Henderson hasselbach equation: pH = 6.1 + log (HCO3/0.3pCO2) pH = 6.1 + log (HCO3/0.3pCO2) Rearranged to Linear relationship: Rearranged to Linear relationship: H+ = 24 (pCO2/HCO3) H+ = 24 (pCO2/HCO3) Based on the reaction mediated by Carbonic Anhydrase: Based on the reaction mediated by Carbonic Anhydrase: Co2 + H2O H+ + HCO3 Co2 + H2O H+ + HCO3

8. Rules of Thumb metabolic acidosis metabolic acidosis pCO2 = 1.5 (HCO3) + 8 (+/- 2) pCO2 = 1.5 (HCO3) + 8 (+/- 2) metabolic alkalosis metabolic alkalosis pCO2 = 0.9 (HCO3) + 9 (+/- 2) pCO2 = 0.9 (HCO3) + 9 (+/- 2) pCO2 should be same as last two digits of pH (pCO2 = 40 when pH is 7.40) for simple metabolic disorder pCO2 should be same as last two digits of pH (pCO2 = 40 when pH is 7.40) for simple metabolic disorder

9. Rules of THumb respiratory acidosis respiratory acidosis acute HCO3 increases 1 mEq for each 10 mmHg pCO2 acute HCO3 increases 1 mEq for each 10 mmHg pCO2 chronic HCO3 up 3.5 mEq for each 10 mmHg pCO2 chronic HCO3 up 3.5 mEq for each 10 mmHg pCO2

10. Rules of Thumb respiratory alkalosis respiratory alkalosis acute HCO3 decreases 2 mEq/ each 10 mmHg pCO2 acute HCO3 decreases 2 mEq/ each 10 mmHg pCO2 chronic HCO3 down 5 mEq/ each 10 mmHg pCO2 chronic HCO3 down 5 mEq/ each 10 mmHg pCO2

11. HOW TO EVALUATE CLINICAL PROBLEMS IN ACID-BASE 1. calculate the anion gap and potential bicarb 1. calculate the anion gap and potential bicarb 2. is pH acidic or basic? 2. is pH acidic or basic? 3. is pCO2 alkalotic ( 40) 3. is pCO2 alkalotic ( 40) 4. is HCO3 calculated by ABG machine consistent with measured HCO3 on lytes? 4. is HCO3 calculated by ABG machine consistent with measured HCO3 on lytes? If not, samples are not simultaneous and conclusions may be invalid If not, samples are not simultaneous and conclusions may be invalid 5. Apply rules of thumb - if values are consistent, a simple disorder is present with appropriate compensation, if not, suspect a second disorder. 5. Apply rules of thumb - if values are consistent, a simple disorder is present with appropriate compensation, if not, suspect a second disorder.

12. Simple Acid Base Case 1 38 y.o. male with CKD due to chronic GN. 38 y.o. male with CKD due to chronic GN. Increased weakness and lethargy Increased weakness and lethargy BP 135/75, T 98 P 75 R 22 BP 135/75, T 98 P 75 R 22 No edema, no rales, no rub. No edema, no rales, no rub. Na 134Cl 100 BUN 159 Na 134Cl 100 BUN 159 K 5.6 CO2 14 creat 15 K 5.6 CO2 14 creat 15 pH 7.26/pCO2 27 pO2 85 pH 7.26/pCO2 27 pO2 85

13. Simple Case 1 Na 134Cl 100 BUN 159 Na 134Cl 100 BUN 159 K 5.6 CO2 14 creat 15 K 5.6 CO2 14 creat 15 pH 7.26/pCO2 27 pO2 85 pH 7.26/pCO2 27 pO2 85 Step 1 Anion Gap Step 1 Anion Gap Potential bicarb? Potential bicarb? Step 2 Acidemia or Alkalemia? Step 2 Acidemia or Alkalemia? Step 3 Which way is pCO2 going? Step 3 Which way is pCO2 going?

14. Simple Case 1 Na 134Cl 100 BUN 159 Na 134Cl 100 BUN 159 K 5.6 CO2 14 creat 15 K 5.6 CO2 14 creat 15 pH 7.26/pCO2 27 pO2 85 pH 7.26/pCO2 27 pO2 85 Step 3 Note: can only hyper or HypO- ventilate, can’t do both at same time! Step 3 Note: can only hyper or HypO- ventilate, can’t do both at same time! Step 4 make sure ABG and lytes are drawn at same time/bicarb is consistent Step 4 make sure ABG and lytes are drawn at same time/bicarb is consistent Step 5 apply rules of thumb. Step 5 apply rules of thumb.

15. Rules of Thumb metabolic acidosis metabolic acidosis pCO2 = 1.5 (HCO3) + 8 (+/- 2) pCO2 = 1.5 (HCO3) + 8 (+/- 2) metabolic alkalosis metabolic alkalosis pCO2 = 0.9 (HCO3) + 9 (+/- 2) pCO2 = 0.9 (HCO3) + 9 (+/- 2) pCO2 should be same as last two digits of pH (pCO2 = 40 when pH is 7.40) for simple metabolic disorder pCO2 should be same as last two digits of pH (pCO2 = 40 when pH is 7.40) for simple metabolic disorder

16. Rules of Thumb metabolic acidosis metabolic acidosis pCO2 = 1.5 (HCO3) + 8 (+/- 2) pCO2 = 1.5 (HCO3) + 8 (+/- 2) This case 27 = 1.5(14) +8 (+-2) This case 27 = 1.5(14) +8 (+-2) Therefore simple metabolic acidosis with respiratory compensation. Therefore simple metabolic acidosis with respiratory compensation.

17. Causes of Anion Gap Metabolic Acidosis Methanol Methanol Uremia Uremia Diabetic Ketoacidosis Diabetic Ketoacidosis Paraldehyde Paraldehyde Iron or Isoniazid Iron or Isoniazid Lactic acidosis Lactic acidosis Ethanol/ethylene Glycol Ethanol/ethylene Glycol Salicylates Salicylates

18. Causes of Non Gapped Metabolic Acidosis GI losses GI losses Diarrhea Diarrhea Pancreatic fistula Pancreatic fistula Renal Losses Renal Losses RTA RTA Acetazolamide/Diamox Acetazolamide/Diamox Addison’s disease Addison’s disease Iatrogenic infusions: Normal saline, TPN Iatrogenic infusions: Normal saline, TPN

19. Metabolic Alkalosis GI losses of HCl (N/V) or Ileostomy GI losses of HCl (N/V) or Ileostomy Renal disorders eg, Bartter syndrome, Renal disorders eg, Bartter syndrome,Bartter syndromeBartter syndrome Drug use Drug use Loop or thiazide diuretics Loop or thiazide diuretics Licorice Licorice Tobacco chewing Tobacco chewing Glucocorticoids Glucocorticoids Antacids (eg, magnesium hydroxide) Antacids (eg, magnesium hydroxide) Calcium carbonate Calcium carbonate Chronic Respiratory ACIDosis Chronic Respiratory ACIDosis COPD, Sleep apnea COPD, Sleep apnea

20. Simple Acid Base Case 2 40 y.o. female with status asthmaticus. 40 y.o. female with status asthmaticus. Temp 101, P 108, R 28, BP 138/85 Temp 101, P 108, R 28, BP 138/85 1 st gas drawn. Started treatment. 1 st gas drawn. Started treatment. 4 hours later is less alert, disoriented 4 hours later is less alert, disoriented 2 nd gas drawn. 2 nd gas drawn. Place on vent and resp tx/steroids Place on vent and resp tx/steroids 3 rd gas drawn 24 hours later. 3 rd gas drawn 24 hours later.

21. Simple Acid base case 2 Admit: Admit: Na K Cl CO2 pH pCO2 pO2 HCO Na K Cl CO2 pH pCO2 pO2 HCO 135 3.5 100 21 7.50 30 80 20 135 3.5 100 21 7.50 30 80 20 Step 1 Anion Gap Step 1 Anion Gap Potential bicarb? Potential bicarb? Step 2 Acidemia or Alkalemia? Step 2 Acidemia or Alkalemia? Step 3 Which way is pCO2 going? Step 3 Which way is pCO2 going?

22. Simple case 2 Na K Cl CO2 pH pCO2 pO2 HCO Na K Cl CO2 pH pCO2 pO2 HCO 135 3.5 100 21 7.50 30 80 20 135 3.5 100 21 7.50 30 80 20 respiratory alkalosis respiratory alkalosis acute HCO3 decreases 2 mEq/ each 10 mmHg pCO2 acute HCO3 decreases 2 mEq/ each 10 mmHg pCO2 chronic HCO3 down 5 mEq/ each 10 mmHg pCO2 chronic HCO3 down 5 mEq/ each 10 mmHg pCO2

23. Simple Acid base case 2 Deteriorated: Deteriorated: Na K Cl CO2 pH pCO2 pO2 HCO Na K Cl CO2 pH pCO2 pO2 HCO 137 4.2 97 26 7.25 60 48 25 137 4.2 97 26 7.25 60 48 25 Step 1 Anion Gap Step 1 Anion Gap Potential bicarb? Potential bicarb? Step 2 Acidemia or Alkalemia? Step 2 Acidemia or Alkalemia? Step 3 Which way is pCO2 going? Step 3 Which way is pCO2 going?

24. Simple case 2 Na K Cl CO2 pH pCO2 pO2 HCO Na K Cl CO2 pH pCO2 pO2 HCO 137 4.2 97 26 7.25 60 48 25 137 4.2 97 26 7.25 60 48 25 respiratory acidosis respiratory acidosis acute HCO3 increases 1 mEq for each 10 mmHg pCO2 acute HCO3 increases 1 mEq for each 10 mmHg pCO2 chronic HCO3 up 3.5 mEq for each 10 mmHg pCO2 chronic HCO3 up 3.5 mEq for each 10 mmHg pCO2

25. Simple Acid base case 2 24 hours later: 24 hours later: Na K Cl CO2 pH pCO2 pO2 HCO Na K Cl CO2 pH pCO2 pO2 HCO 138 4.0 95 31 7.45 43 140 30 138 4.0 95 31 7.45 43 140 30 Step 1 Anion Gap Step 1 Anion Gap Potential bicarb? Potential bicarb? Step 2 Acidemia or Alkalemia? Step 2 Acidemia or Alkalemia? Step 3 Which way is pCO2 going? Step 3 Which way is pCO2 going?

26. Simple case 2 Na K Cl CO2 pH pCO2 pO2 HCO Na K Cl CO2 pH pCO2 pO2 HCO 138 4.0 95 31 7.45 43 140 30 138 4.0 95 31 7.45 43 140 30 respiratory acidosis respiratory acidosis acute HCO3 increases 1 mEq for each 10 mmHg pCO2 acute HCO3 increases 1 mEq for each 10 mmHg pCO2 chronic HCO3 up 3.5 mEq for each 10 mmHg pCO2 chronic HCO3 up 3.5 mEq for each 10 mmHg pCO2 Kidneys reabsorb bicarb in response to increased pCO2, but it takes time. Kidneys reabsorb bicarb in response to increased pCO2, but it takes time.

27. Case 3 Mixed acid base disturbance 32 y.o. female with chronic pyelonephritis and CKD. Admitted with N/V and DOE. 32 y.o. female with chronic pyelonephritis and CKD. Admitted with N/V and DOE. Right pleural effusion, S3. Right pleural effusion, S3. 1 st set of labs obtained. 1 st set of labs obtained. Thoracentesis performed and within minutes dyspnea markedly increased. Pt intubated and 2 nd set of labs drawn. Thoracentesis performed and within minutes dyspnea markedly increased. Pt intubated and 2 nd set of labs drawn.

28. Mixed Acid base case 3 Admitted: Admitted: Na K Cl CO2 pH pCO2 pO2 HCO Na K Cl CO2 pH pCO2 pO2 HCO 130 5.0 94 15 7.32 32 48 16 130 5.0 94 15 7.32 32 48 16 Step 1 Anion Gap Step 1 Anion Gap Potential bicarb? Potential bicarb? Step 2 Acidemia or Alkalemia? Step 2 Acidemia or Alkalemia? Step 3 Which way is pCO2 going? Step 3 Which way is pCO2 going? Step 4 compare Step 4 compare Step 5 which rule of thumb to use? Step 5 which rule of thumb to use?

29. Rules of Thumb metabolic acidosis metabolic acidosis pCO2 = 1.5 (HCO3) + 8 (+/- 2) pCO2 = 1.5 (HCO3) + 8 (+/- 2) This case 32 = 1.5(15) +8 (+-2) This case 32 = 1.5(15) +8 (+-2) Therefore simple metabolic acidosis with respiratory compensation. Therefore simple metabolic acidosis with respiratory compensation.

30. Mixed Acid base case 3 After thoracentesis: After thoracentesis: Na K Cl CO2 pH pCO2 pO2 HCO Na K Cl CO2 pH pCO2 pO2 HCO 131 7.8 92 9 6.90 50 48 10 131 7.8 92 9 6.90 50 48 10 Step 1 Anion Gap Step 1 Anion Gap Potential bicarb? Potential bicarb? Step 2 Acidemia or Alkalemia? Step 2 Acidemia or Alkalemia? Step 3 Which way is pCO2 going? Step 3 Which way is pCO2 going? Step 4 compare Step 4 compare Step 5 None of the rules of thumb apply! Step 5 None of the rules of thumb apply!

31. Mixed acid base case 3 Bonus points: Bonus points: Why did the Anion Gap rise so quickly? Why did the Anion Gap rise so quickly? Why did the K concentration rise so quickly? Why did the K concentration rise so quickly?

32. Mixed Disturbance Case 4 44 y.o male with alcoholism and indiscriminate taste in the nature of the alcohol, admitted with intoxication and severe abdominal pain. 44 y.o male with alcoholism and indiscriminate taste in the nature of the alcohol, admitted with intoxication and severe abdominal pain. N/V, Dyspnea, Cough with rales in right base, abd diffuse tenderness, no rebound. N/V, Dyspnea, Cough with rales in right base, abd diffuse tenderness, no rebound. Diagnosed with pneumonia and pancreatitis. Diagnosed with pneumonia and pancreatitis.

33. Mixed case 4 Na K Cl CO2 pH pCO2 pO2 HCO Na K Cl CO2 pH pCO2 pO2 HCO 142 3.4 98 20 7.28 41 58 20 142 3.4 98 20 7.28 41 58 20 Step 1 Anion Gap Step 1 Anion Gap Potential bicarb? Potential bicarb? Step 2 Acidemia or Alkalemia? Step 2 Acidemia or Alkalemia? Step 3 Which way is pCO2 going? Step 3 Which way is pCO2 going? Step 4 compare Step 4 compare Step 5 which rule of thumb to use? Step 5 which rule of thumb to use?

34. Mixed case 4 Na K Cl CO2 pH pCO2 pO2 HCO Na K Cl CO2 pH pCO2 pO2 HCO 142 3.4 98 20 7.28 41 58 20 142 3.4 98 20 7.28 41 58 20 Step 1 Anion Gap24 Step 1 Anion Gap24 Potential bicarb?12 so actual bicarb = 32 Potential bicarb?12 so actual bicarb = 32 Step 2 Acidemia or Alkalemia? Step 2 Acidemia or Alkalemia? Step 3 Which way is pCO2 going? Step 3 Which way is pCO2 going? Not dropping as it should (pt can’t hyperventilate effectively due to pneumonia) Not dropping as it should (pt can’t hyperventilate effectively due to pneumonia)

35. Mixed Disturbances Usually due to: Usually due to: Nausea and vomiting causing GI induced alkalosis (NG suction does same thing) Nausea and vomiting causing GI induced alkalosis (NG suction does same thing) Respiratory compromise leads to insufficient respiratory compensation, and may lead to hypoxia and Lactic acidosis superimposed on underlying condition. Respiratory compromise leads to insufficient respiratory compensation, and may lead to hypoxia and Lactic acidosis superimposed on underlying condition. Key to recognizing these: Potential bicarb! Key to recognizing these: Potential bicarb!