1. THE UNIVERSITY OF OKLAHOMA, TULSA Acid-Base Disorders Charles J. Foulks, MD, FACP Professor of Medicine School of Community Medicine

2. THE UNIVERSITY OF OKLAHOMA, TULSA [H + ] Metabolism Origin of H + : fats, CHO –15-20 mol of CO 2 per day produced Volatile acid –Protein: S, N, P containing amino acids Fixed acid Must buffer and then excrete H + Fixed acid buffered by HCO 3, proteins, bone

3. THE UNIVERSITY OF OKLAHOMA, TULSA [H + ] Metabolism CO 2 buffered by RBCs: –C0 2 enters RBCs the with CA C0 2 + H2O H + +HCO 3 - HCO 3 - actively transported into plasma H + retained in RBCs Lungs: HCO 3 - reenters RBCs, equation reversed and CO 2 excreted

4. THE UNIVERSITY OF OKLAHOMA, TULSA [H + ] Metabolism Meat diet: 1-2 mEq H+ per gram protein intake –Sulfuric acid: cysteine, methionine –HCl: lysine, arginine, histidine –HCO 3 - : aspartate, glutamate, and citrate from vegetable sources Actually H+ consumed in metabolism and HCO 3 - left behind –Net effect: 50-100 mMol net H+ added

5. THE UNIVERSITY OF OKLAHOMA, TULSA Summary Statement Acid-base physiology describes (1) how the lungs regulate arterial pCO 2 in the face of variable CO 2 production and (2) how the kidneys regulate arterial HCO 3 by reabsorbing filtered bicarbonate and replacing bicarbonate lost in buffering acids The goal is to maintain a pCO 2 of 40 mm Hg and a bicarbonate of 24 mEq/L (mmol/L). This results in a pH of 7.4.

6. THE UNIVERSITY OF OKLAHOMA, TULSA Language of Acid-Base Disorders Acidemia, alkalemia Acidosis, alkalosis Respiratory (CO 2 ) Metabolic (HCO 3 - ) Normal pH= 7.40, nl pCO 2 = 40, nl HCO 3 = 24

7. THE UNIVERSITY OF OKLAHOMA, TULSA Acid-Base Rules The pH is governed by the ratio of pCO 2 /HCO 3 - (IGNORE THE UNITS) When working an acid-base problem, ALWAYS put the ratio pCO 2 /HCO 3 - down on paper first [H+] = 24 (pCO2/HCO - 3 ) (24 is a fudge factor for the units) pH is expressed as [H + ] nanoEq/mL (nEq/mL)

8. THE UNIVERSITY OF OKLAHOMA, TULSA Acid-Base Rules The body always wishes to maintain a pH of 7.40. Therefore, any primary perturbation in this ratio means that the body will act to restore that ratio. It’s like dancing: if your partner goes one way, you should too.

9. THE UNIVERSITY OF OKLAHOMA, TULSA Acid-Base Rules PrimaryCompensation  pCO 2  HCO 3 -  pCO 2  HCO 3 -  HCO 3 -  pCO 2  HCO 3 -  pCO 2 [H + ] = 24 (pCO 2 /HCO 3 - )

10. THE UNIVERSITY OF OKLAHOMA, TULSA Acid-Base Rules The compensating partner has five choices: 1.Change in the proper direction, but too far. 2.Change in the proper direction, but just right. 3.Change in the proper direction but not far enough. 4.Not change at all. 5.Change in the wrong direction.

11. THE UNIVERSITY OF OKLAHOMA, TULSA Acid-Base Rules Always look at the pH first –If it is < 7.40 then you have an acidotic process Only 2 ways: –  pCO 2 or  HCO 3 - (Could have both) If the pCO 2 > 40, then respiratory acidosis –Compensation would be HCO 3 > 24 –Special case: if pCO 2 > than it should be but is < 40 If the HCO 3  < 24, metabolic acidosis –Compensation would be pCO 2 < 40 If both: two primary disorders

12. THE UNIVERSITY OF OKLAHOMA, TULSA Acid-Base Rules If pH > 7.40, then you have an alkalotic process –Only 2 ways: –  pCO 2 or  HCO 3 (Could have both) –If pCO 2 < 40, then respiratory alkalosis Compensation would be HCO 3 < 24 –If HCO 3 > 24, then metabolic alkalosis Compensation would be pCO 2 > 40 –If both, then two primary disorders

13. THE UNIVERSITY OF OKLAHOMA, TULSA Acid-Base Rules Compensation 1.Change too far: a second primary disorder. 2.Change just right, compensation. 3.Change too little, a second primary disorder. 4.Not change at all, a second primary disorder. 5.Change in the wrong direction, a second primary disorder.

14. THE UNIVERSITY OF OKLAHOMA, TULSA Metabolic Acidosis 1.Primary fall in HCO 3 - because of addition of H + -R - or HCl If H + -R - added, then leaves tracks in the anion gap. AG= [Na + ] –([Cl - + HCO 3 - ]); normal is 10- 15 (14+2) 2.If H + -R - was added, the HCO 3 - falls by the amount of R - added. 3.The R - group is the unmeasured anion. What used to be Na-HCO 3 is now Na-R and HCO 3 -. 4.Compensation means pCO 2 will fall.

15. THE UNIVERSITY OF OKLAHOMA, TULSA Metabolic Acidosis Types of H + -R - –lactic acid –paraldehyde –oxalic acid –ethylene glycol –salicylates –ketones (diabetic, starvation, alcoholic) –formic acid (methanol) –uremic

16. THE UNIVERSITY OF OKLAHOMA, TULSA Metabolic Acidosis Non-anion gap (hyperchloremic) (Addition of HCl) NaHCO 3 + HCl  HCO 3 - + NaCl Renal in origin: Renal Tubular Acidosis Proximal: defect in reclamation of HCO 3 -, normal acidification Distal: defect in acidification, normal HCO 3 - reclamation Both associated with hypokalemia Type IV: defect in acidification, hyperkalemic

17. THE UNIVERSITY OF OKLAHOMA, TULSA Metabolic Acidosis Winter’s formula ONLY IN METABOLIC ACIDOSIS Predicts the compensation of pCO 2 pCO 2exp = [ [HCO 3 - ] x 1.5] + 8  2 Example: if the HCO 3 - is 12 pCO 2exp = [12 x 1.5] + 8  2 = 26  2

18. THE UNIVERSITY OF OKLAHOMA, TULSA Metabolic Acidosis Using this example, if the HCO 3 - is 12, it is a simple disorder if the pCO 2 is 24- 28 If the pCO 2 < 24, then it is too far: therefore, a primary respiratory alkalosis If the pCO 2 > 28, not far enough, therefore, a primary respiratory acidosis

19. THE UNIVERSITY OF OKLAHOMA, TULSA Metabolic Acidosis: Problems 40 yo man admitted with RR of 30, Na 142, K 3.6, Cl 100, HCO 3 12, pH 7.28, pCO 2 26 Step 1. pH is acid, bicarbonate is low: metabolic acidosis. What is the AG? AG is 30, short differential Step 2. Is there compensation? pCO 2exp = [12 x 1.5] + 8  2 = 26  2 Yes, this is a simple disorder. Step 3. Causes?

20. THE UNIVERSITY OF OKLAHOMA, TULSA Metabolic Acidosis: Problems Using the case in slide 20, change the pCO 2 to 18. HCO 3 - = 12. Step 1 is the same. Metabolic acidosis Step 2 reveals that the pCO 2 is too low (Should be 26  2), therefore there is a primary respiratory alkalosis. Step 3. Causes of met acid the same, why is there a primary respiratory alkalosis?

21. THE UNIVERSITY OF OKLAHOMA, TULSA Metabolic Alkalosis Bicarbonate is filtered and reabsorbed proximally and is generated distally. Met alkalosis requires 2 events: –Generation of bicarbonate –Maintenance of hyperbicarbonatemia

22. THE UNIVERSITY OF OKLAHOMA, TULSA Metabolic Alkalosis Generation events: –Loss of HCl in vomiting –Volume depletion –Excess of aldosterone (mineralocorticoid) –Post-hypercapnic –Diuretics

23. THE UNIVERSITY OF OKLAHOMA, TULSA Metabolic Alkalosis Maintenance events: Something must raise the proximal tubule’s ability to increase reabsorption of the increased filtered bicarbonate load. Think of a dam. Normal top of dam is 24 mEq/L Maintenance events: –hypokalemia –excess aldosterone –volume depletion (hypoperfusion) –hypercapnia

24. THE UNIVERSITY OF OKLAHOMA, TULSA Compensation for Metabolic Alkalosis No good rule for estimating the pCO 2exp. In general, the pCO 2 will not be above 50-55 torr unless oxygen is given. If supplemental oxygen is given then the pCO 2 may be > 60. Highest I’ve seen is 98 torr.

25. THE UNIVERSITY OF OKLAHOMA, TULSA Metabolic Alkalosis Treatment: Must identify the generation event and the maintenance event. Must treat both of them. Remember that metabolic alkalosis is usually associated with –hypokalemia –hypochloremia

26. THE UNIVERSITY OF OKLAHOMA, TULSA Metabolic Alkalosis: Problems 40 yo man admitted with Na 140, K 3.0, Cl 86, bicarbonate 40, pH 7.52, pCO 2 51. Step 1. pH > 7.40, therefore an alkalosis present; bicarbonate > 24 therefore, metabolic alkalosis. Step 2. Did the pCO 2 rise? Yes, under 55 and therefore probably compensation. What is the AG? AG = 14, no metabolic acidosis. Step 3. Causes of generation and maintenance.

27. THE UNIVERSITY OF OKLAHOMA, TULSA Respiratory Disorders Acute disorders cause a larger change in the pH than chronic disorders. Renal compensation may take 3 days to complete. Acute: for every pCO 2 change of 10 the pH will change 0.08 pH units. Chronic: for a pCO 2 change of 10 the pH will change 0.04 pH units.

28. THE UNIVERSITY OF OKLAHOMA, TULSA Respiratory Disorders Assume the patient has a pCO 2 of 50, what should the pH be? Acute: pCO 2 change is 50-40 = 10. pH should be 7.32. (7.40-0.08). Chronic: pCO 2 change is 50-40 = 10. pH should be 7.36 (7.40-0.04). Therefore, if the pH is between 7.32 and 7.36, you have a simple respiratory acidosis. What if pH < 7.32? pCO 2 = 50 –Metabolic acidosis as well. What if > 7.36? pCO 2 = 50 –Metabolic alkalosis as well.

29. THE UNIVERSITY OF OKLAHOMA, TULSA Respiratory Disorders Assume the patient has a pCO 2 of 30, what should the pH be? Acute: pCO 2 change is 40-30 = 10. pH should be 7.48. Chronic: pCO 2 change is 40-30 = 10. pH should be 7.44. Therefore, if the pH is between 7.48 and 7.44, you have a simple respiratory alkalosis. If pH > 7.48, then a metabolic alkalosis also. If pH < 7.44, then a metabolic acidosis also.

30. THE UNIVERSITY OF OKLAHOMA, TULSA Respiratory Alkalosis Voluntary hyperventilation Hypoxemia (includes altitude) Liver failure Anxiety hyperventilation syndrome Any acute pulmonary problem, e.g., acute pulmonary embolism, pneumonia, mild asthma attack, mild pulmonary edema, any infectious or catabolic illness. ASA

31. THE UNIVERSITY OF OKLAHOMA, TULSA Respiratory Acidosis Central nervous system depression, e.g., drug overdose, anesthesia Chest bellows weakness or dysfunction, e.g., myasthenia gravis, polio, massive obesity, diaphragm paralysis, flail chest, paralyzing agents, low energy (glucose, phosphate), low potassium Disease of lungs and/or upper airway, e.g., severe asthma attack, chronic obstructive pulmonary disease, severe pneumonia, severe pulmonary edema, upper airway obstruction

32. THE UNIVERSITY OF OKLAHOMA, TULSA ABG Interpretation Strategy for Interpretation Write this ratio down: pCO 2 /HCO 3 –Look at pH first, determine if it is acidotic or alkalotic –Look at the ratio and see which condition for the disorder was met. –Next, did the partner go in the right direction? If not then a second primary disorder is present –If so then: too far, not far enough or just right? If just right, then compensation; if not then another primary disorder

33. THE UNIVERSITY OF OKLAHOMA, TULSA Case 1 An asymptomatic patient is found to have the following laboratory values: Na+138 mEq/L K+3.9 mEq/L Cl-112 mEq/L HCO3-14 mEq/L Most likely culprit? RTA

34. THE UNIVERSITY OF OKLAHOMA, TULSA Case 2 A 64-year-old disoriented woman is brought to the emergency room. No history is obtainable. She is tachypneic (respiratory rate is 35/min) and confused, but physical examination is otherwise not remarkable. Laboratory studies include: Na+144 mEq/LArterial bloodpH 7.24 K+4.4 mEq/LHCO3- 9 Cl-107 mEq/L pCO 2 22 mm Hg 1.What is her acid-base abnormality? 2.What are the possible causes?

35. THE UNIVERSITY OF OKLAHOMA, TULSA Case 2 She has normal serum creatinine concentration and plasma ketone level with is undetectable. Possible diagnoses? Salicylate overdose

36. THE UNIVERSITY OF OKLAHOMA, TULSA Another subtle clue: Na+ 144, Cl - 107 Na + up by 3%; Cl - up by 7% Na + and Cl - should always follow each other by the same percentage –Effect of water distribution If they go in different directions or don’t move the same percentage then there is another acid-base disorder. –Much easier than the delta/delta Chronic respiratory alkalosis before the intoxication.

37. THE UNIVERSITY OF OKLAHOMA, TULSA Case 4 A 50-year-old man is more successful as a lawyer than as a husband. His recent divorce and the financial settlement have pushed his cigarette and Cutty Sark consumption to unreasonable levels, and flared his long-standing peptic ulcer disease. “Doc, I’ve about had it. I’ve been vomiting for four days.” You admit him to the hospital. His BP is 110/70, falling to 70/60 when he sits up. Resting pulse rate is 98/min. Skin turgor is poor, and he has obviously lost weight.

38. THE UNIVERSITY OF OKLAHOMA, TULSA Case 4 His Hct is 46%, BUN 28 mg/dL, serum creatinine 1.4 mg/dL. Urinalysis shows S.G. 1.028, no protein, and an normal sediment. Other laboratory studies include: Na+135 mEq/LArterial pH7.58 K+ 2.6 mEq/LpCO 2 42 torr Cl- 83 mEq/L HCO 3 - 42 mEq/L What is the acid-base disorder? –Primary metabolic alkalosis –Primary respiratory alkalosis Use common sense

39. THE UNIVERSITY OF OKLAHOMA, TULSA Case 5 Following a debridement for necrotizing fasciitis, a 58-year-old woman develops severe diarrhea caused by pseudomembranous colitis. The volume of diarrheal fluid is approximately 1/2 liter/hour. Except for a history of moderately severe chronic bronchitis and exertional breathlessness, her past history is unremarkable. Results of the initial laboratory tests are: Na+138 mEq/LArterial pH6.97 K+ 2.8 mEq/L[H+]107 nEq/L Cl-115 mEq/LpCO 2 40 mm Hg HCO 3 - 9 mEq/L What is the acid-base disorder? Primary hyperchloremiac metabolic acidosis AND Primary respiratory acidosis

40. THE UNIVERSITY OF OKLAHOMA, TULSA Case 6 A 44 year old moderately dehydrated man was admitted with a two day history of acute severe diarrhea. Electrolyte results: Na+ 134, K+ 2.9, Cl- 108, HCO3- 16, BUN 31, Cr 1.5. ABG: pH 7.31 pCO2 33 mmHg HCO3 16 pO2 93 mmHg Diagnosis? –Metabolic acidosis, non-AG Note the divergence of the Na and Cl –Compensation? Yes

41. THE UNIVERSITY OF OKLAHOMA, TULSA Case 7 A 22 year old female with type I DM, presents to the emergency department with a 1 day history of nausea, vomiting, polyuria, polydypsia and vague abdominal pain. P.E. noted for deep sighing breathing, orthostatic hypotension, and dry mucous membranes. Labs: Na 132, K 6.0, Cl 93, HCO3- 11 glucose 720, BUN 38, Cr 2.6. UA: pH 5, SG 1.010, ketones negative, glucose positive. Plasma ketones trace. ABG: pH 7.27 HCO3- 10 PCO2 23 What is the acid base disorder? –Primary AG metabolic acidosis, compensated. Where are the ketones? BOHB

42. THE UNIVERSITY OF OKLAHOMA, TULSA Case 8 A previously well 55 year old woman is admitted with a complaint of severe vomiting for 5 days. Physical examination reveals postural hypotension, tachycardia, and diminished skin turgor. The laboratory finding include the following: Electroyes: Na 140, K 3.4, Cl 77 HCO3- 9, Cr 2.1 ABG: pH 7.23, PCO2 22mmHg Disorder? –Primary AG metabolic acidosis with compensation Na+ unchanged but Cl- down 23% Metabolic alkalosis present as well.

43. THE UNIVERSITY OF OKLAHOMA, TULSA Case 9 A 70 year old man with history of CHF presents with increased shortness of breath and leg swelling. ABG: pH 7.24, PCO2 60 mmHg, PO2 52 HCO3- 27 What is the acid base disorder? –Primary respiratory acidosis –Acute or chronic? pH range: 0.04x2=0.08 chronic: pH 7.32 pH range: 0.08x2=0.16 acute: pH 7.24 Acute

44. THE UNIVERSITY OF OKLAHOMA, TULSA Pearls Always write down the ratio Partners should move in the same direction. Go too far, just right, not enough, not change, wrong way Na + and Cl - should move the same direction by the same percentage. If they don’t another disorder present. Winter’s formula for met acidosis only pH changes based on pCO 2 changes No good rules for metabolic alkalosis Always calculate the AG

45. THE UNIVERSITY OF OKLAHOMA, TULSA Pearls Maximum pCO 2 for compensation without oxygen is 50-55 torr. Triple disorders are possible: –Met. Acidosis, met. Alkalosis, and a respiratory disorder. Must look at AG and do Na and Cl move the same.