1. Evaluation and Analysis of Acid-Base Disorders Ebadur Rahman FRCP (Edin),FASN, Specialty Certificate in Nephrology (UK) MRCP (UK), DIM (UK), DNeph (UK), MmedSciNephrology (UK). Consultant & clinical tutor Department of Nephrology Riyadh Armed Forces Hospital

2. Approximately 15,000 mmol of carbon dioxide (CO2) is produced each day, which combines with water to form carbonic acid (H2CO3). Metabolic reactions generate several thousand mmol per day of organic acids, such as lactic acid and citric acid. Approximately 50 to 100 meq of nonvolatile acid is produced each day from diet. Acid-base balance is maintained by – normal pulmonary excretion of carbon dioxide, – metabolic utilization of organic acids, – and renal excretion of nonvolatile acids

3. RENAL ROLE IN ACID-BASE BALANCE — Reclaiming filtered bicarbonate — – 85 to 90 % of the filtered load is reclaimed in proximal tubule. – 10 % is reclaimed in the distal nephron, primarily via hydrogen secretion by a proton pump (H-ATPase). – no bicarbonate in the final urine. Acid excretion — – The average daily acid load on a typical diet is approximately 1 meq/kg. – minimum urine pH in humans is 4.5 to 5.0.

6. The principal buffers in the urine ammonia (excreted as ammonium) and phosphate. Ammonium excretion requires the renal synthesis of ammonia and the secretion of hydrogen ions from the collecting tubular cells into the tubular lumen

7. Proximal (type 2) RTA – originates from a partial defect in proximal tubular bicarbonate reabsorption. Distal RTA is caused by – defects in distal hydrogen ion excretion

9. Acid-Base Analysis Blood gas (pH, CO 2 ) Serum chemistry (Na, Cl, HCO 3 ) History

10. CO 2 = Acid –  CO 2 =  pH (acidemia) –  CO 2 =  pH (alkalemia) HCO 3 = Base –  HCO 3 =  pH (alkalemia) –  HCO 3 =  pH (acidemia)

11. Acidemic vs. Alkalemic pH < 7.35 = Acidemic pH > 7.45 = Alkalemic

12. Reference ranges and points ParameterReference rangeReference point pH7.35-7.457.40 P CO 2 33-44 mm Hg40 mm Hg P O 2 75-105 mm Hg80mm Hg HCO 3 - 22-28 mEq/L24mEq/L Anion gap8-16 mEq/L12 mEq/L Osmolar gap<10 mOsm/L

13. Acid-Base Normals: pH= 7.40 (7.35 - 7.45) PCO 2 = 40 (35 - 45) HCO 3 = 24 (22 - 26)

14. ABG: 7.40 / 40 / 80 / 24 – pH – PaCO 2 – PaO 2 – HCO 3

15. Delta ratio Assessment <0.4Hyperchloraemic normal anion gap acidosis 0.4 – 0.8 Combined high AG and normal AG acidosis Note that the ratio is often <1 in acidosis associated with renal failure 1 - 2 Uncomplicated high-AG acidosis Lactic acidosis: average value 1.6 DKA more likely to have a ratio closer to 1 due to urine ketone loss (if patient not dehydrated) >2 Pre-existing increased [HCO 3 - ]: concurrent metabolic alkalosis pre-existing compensated respiratory acidosis ratio = Anion gap/[HCO 3 - ] = (AG – 12)/(24 - [HCO 3 - ])

16. Four Primary Disorders: PCO 2 < 35 = respiratory alkalosis PCO 2 > 45 = respiratory acidosis HCO 3 < 22 = metabolic acidosis HCO 3 > 26 = metabolic alkalosis – Can have mixed pictures with compensation – Can have up to 3 abnormality simultaneously (1 respiratory + 2 metabolic) – The direction of the pH will tell you which is primary!

17. Look at dirrection of arrows Metabolic all arrow same dirrection – Ph / HC03 / PC02= METABOLIC ACIDOSIS – Ph / HC03 / PC02= METABOLIC ALKALOSIS

18. Look at dirrection of arrows RESPIRATORY arrow dirrection oposite to PH – Ph / HC03 / PC02= RESPIRATORY ALKALOSIS – Ph / HC03 / PC02= RESPIRATORY ACIDOSIS

20. Compensation Primary DisturbancepHHCO 3 - P CO 2 Compensation Respiratory acidosis<7.35Compensatory increase Primary increaseAcute: 1-2 mEq/L increase in HCO 3 - for every 10 mm Hg increase in P CO 2 Chronic: 3-4 mEq/L increase in HCO 3 - for every 10 mm Hg increase in P CO 2 Respiratory alkalosis>7.45Compensatory decrease Primary decreaseAcute: 1-2 mEq/L decrease in HCO 3 - for every 10 mm Hg decrease in P CO 2 Chronic: 4-5 mEq/L decrease in HCO 3 - for every 10 mm Hg decrease in P CO 2 Metabolic acidosis<7.35Primary decreaseCompensatory decrease 1.2 mm Hg decrease in P CO 2 for every 1 mEq/L decrease in HCO 3 - Metabolic alkalosis>7.45Primary increaseCompensatory increase 0.6-0.75 mm Hg increase in P CO 2 for every 1 mEq/L increase in HCO 3 -, P CO 2 should not rise above 55 mm Hg in compensation

21. Simple Acid-Base Disorders

22. Acute Respiratory Alkalosis

23. Acute Respiratory Acidosis

24. Chronic Respiratory Acidosis with Metabolic Compensation

25. Metabolic Alkalosis with Respiratory Compensation

27. Example # 1: Blood gas: 7.50 / 29 / 23 Alkalemic – pH 7.50 – PaCO 2 29 – HCO 3 24

28. Acute respirstory alkalosis Low PCO 2 is the primary (respiratory alkalosis) No metabolic compensation = acute process Acute Respiratory Alkalosis Acute: 1-2 mEq/L decrease in HCO 3 - for every 10 mm Hg decrease in PCO 2

29. A 65-year-old man with a history of emphysema comes to the physician with a 3-hour history of shortness of breath. pH7.18 P CO 2 58 mm Hg P O 2 61 mm Hg HCO 3 - 25 mEq/L

30. R acid acute-History suggests hypoventilation, supported by increased P CO 2 and lower than anticipated P O 2. Acute: 1-2 mEq/L increase in HCO 3 - for every 10 mm Hg increase in P CO 2 Chronic: 3-4 mEq/L increase in HCO 3 - for every 10 mm Hg increase in P CO 2 Respiratory acidosis (acute) incomplete/no renal compensation.

31. Example # 2: Blood gas: 7.25 / pco2-60 /Hco3 -26

32. Elevated CO 2 is primary (respiratory acidosis) No metabolic compensation= acute process Acute Respiratory Acidosis

33. Example # 3: Blood gas: 7.34 / 60 / 31 Acidemic Elevated CO 2 is primary (respiratory acidosis) Metabolic compensation has occurred = chronic process Chronic Respiratory Acidosis with Metabolic Compensation* * true metabolic compensation takes 3 days (72hrs)

34. Example # 4: Blood gas: 7.50 / 48 / 36 Alkalemic Elevated HCO 3 is primary (metabolic alkalosis) Respiratory compensation has occurred = acute /chronic ? Metabolic Alkalosis with Respiratory Compensation*-incomplete *Respiratory compensation takes only minutes

35. Example # 5: Blood gas: 7.20 / 21 / 8 Acidemic Low HCO 3 Is primary (metabolic acidosis) Respiratory compensation is present Metabolic Acidosis with Respiratory Compensation

36. Anion Gap (AG): The calculated difference between the positively charged (cations) and negatively charged (anions) electrolytes in the body: AG= Na + - (Cl - + HCO 3 - ) Normal AG = 12 ± 2 (10 – 14)

37. Rule Calculate the anion gap. If the anion gap is  20, there is a primary metabolic acidosis regardless of pH or serum bicarbonate concentration Principle: The body does not generate a large anion gap to compensate for a primary disorder (anion gap must be primary)

38. High anion metabolic acidosis Renal failure DKA ETHANOL OR METHANOL POISONING

39. Rule Calculate the excess anion gap (total anion gap – normal anion gap) and add this value to the measured bicarbonate concentration: – if the sum is > than normal bicarbonate (> 30) there is an underlying metabolic alkalosis – if the sum is less than normal bicarbonate (< 23) there is an underlying nonanion gap metabolic acidosis 1.Excess AG = Total AG – Normal AG (12) 2.Excess AG + measured HCO 3 = > 30 or < 23?

40. Mixed Acid-Base Disorders

41. M acid high AG A 20-year-old man with a history of diabetes is brought to the emergency department with a 3-day history of feeling ill. He is non-adherent with his insulin. Urine ketones are 2+ and glucose is 4+. pH7.26Na + 136 mEq/L P O 2 110 mm HgK + 4.8 mEq/L P CO 2 19 mm HgCl - 101 mEq/L HCO 3 - 8 mEq/LCO 2, total10 mEq/L Glucose343 mg/dLUrea49 mg/dL Creatinine1 mg/dL.

42. History suggests diabetic ketoacidosis. AG = 136-101-8=27 mEq/L Metabolic acidosis with appropriate respiratory compensation

43. pH7.26Na + 136 mEq/L P O 2 110 mm HgK + 4.8 mEq/L P CO 2 19 mm HgCl - 101 mEq/L HCO 3 - 8 mEq/LGlucose343 mg/dL Urea49 mg/dL Creatinine1 mg/dL 1.2 mm Hg decrease in P CO 2 for every 1 mEq/L decrease in HCO 3 -. HCO 3 - decrease = 24-8 = 16 mEq/L P CO 2 decrease predicted = 1.2 x 16 = 19 mm Hg. subtract from 40 mm Hg (reference point) = 21 mm Hg

44. A 43-year-old man comes to the physician with a 3-day history of diarrhea. He has decreased skin turgor. pH7.31Na + 134 mEq/L P O 2 -- mm HgK + 2.9 mEq/L P CO 2 31 mm HgCl - 113 mEq/L HCO 3 - 16 mEq/LUrea74 mgl/dL Creatinine3.4 mmol/L History is limited. Metabolic acidosis with respiratory compensation.

45. Description pH7.31Na + 134 mEq/L P O 2 -- mm HgK + 2.9 mEq/L P CO 2 31 mm HgCl - 113 mEq/L HCO 3 - 16 mEq/LUrea74 mg/dL Creatinine3.4 mg/dL AG = 134-113-16=5 mEq/L 1.2 mm Hg decrease in P CO 2 for every 1 mEq/L decrease in HCO 3 -. HCO 3 - decrease = 24-16 = 8 mEq/L P CO 2 decrease predicted = 1.2 x 8 = 10 mm Hg. subtract from 40 mm Hg (reference point) = 30 mm Hg

46. Remember the Rules 1.Look at the Ph: 2.Calculate the anion gap: if AG  20 there is a primary metabolic acidosis (regardless of pH or HCO 3 ) 3.Calculate the excess anion gap, add it to HCO 3 : Excess AG = Total AG – Normal AG (12) Excess AG + HCO 3 = ? If sum > 30 there is an underlying metabolic alkalosis If sum < 23 there is an underlying nonanion gap metabolic acidosis

47. Example # 1 Blood gas: 7.50 / 20 / 15 Na= 140, Cl = 103 Alkalemic Low CO 2 is primary (respiratory alkalosis) Partial metabolic compensation for chronic condition? AG = 22 (primary metabolic acidosis) Excess AG (AG – 12) + HCO 3 = 25 (no other primary abnormalities) Respiratory Alkalosis and Metabolic Acidosis The patient ingested a large quantity of ASA and had both centrally mediated resp. alkalosis and anion gap met. Acidosis associated with salicylate overdose

48. Example # 2 Blood gas: 7.40 / 40 / 24 Na= 145, Cl= 100 pH normal AG = 21 (primary metabolic acidosis) Excess AG (AG – 12) + HCO 3 = 33 ( underlying metabolic alkalosis) Metabolic Acidosis and Metabolic Alkalosis This patient had chronic renal failure (met. acidosis) and began vomiting (met. alkalosis) as his uremia worsened. The acute alkalosis of vomiting offset the chronic acidosis of renal failure = normal pH

49. Example # 3 Blood gas 7.50 / 20 / 15 Na= 145, Cl = 100 Alkalemic Low CO 2 is primary (respiratory alkalosis) AG = 30 (primary metabolic acidosis) Excess AG (AG – 12) + HCO 3 = 33 (underlying metabolic alkalosis) Respiratory alkalosis, Metabolic Acidosis and Metabolic Alkalosis This patient had a history of vomiting (met. alkalosis), poor oral intake (met. acidosis) and tachypnea secondary to bacterial pneumonia (resp. alkalosis)

50. How Many Primary Abnormalities Can Exist in One Patient? Three primary abnormalities is the max because a person cannot simultaneously hyper and hypoventilate One patient can have both a metabolic acidosis and a metabolic alkalosis – usually one chronic and one acute

51. Example # 5 Blood gas: 7.15 / 15 / 5 Na= 140, Cl= 110 Acidemic Low HCO 3 - primary (metabolic acidosis) AG= 25 (metabolic acidosis is anion gap type) Excess AG + HCO 3 = 18 (underlying nonanion gap metabolic acidosis) Anion Gap and Nonanion gap Metabolic Acidosis Diabetic ketoacidosis was present (anion gap met. acidosis). Patient also had a hyperchloremic nonanion gap met. acidosis secondary to failure to regenerate bicarbonate from ketoacids lost in the urine.

52. 40 year male admitted to surgical unit due to infected diabetic foot.other co-morbidities hypertension and dyslipidemia were reasonabally controlled.He was febrile with temperature 38.5c and blood pressure 130/80.His laboratory investigations showed. WBC.12 Hb.9.6. Platelets.822 while renal profile showed. Serum Urea 8mmol/L Serum creatinine 76 umol/L, Serum Na 142 mmol/L serum K 6.5 mmol/L. ABGs.PH.7.4 Hco3 24, K 4.9 mmol/L.What is most likely diagnosis. A.Type IV Renal tubular acidosis B.Pseudohperkalemia C.Type II renal tubular acidosis D.Type I renal tubular acidosis E.Addison’s disease.

53. Answer:B Type IV renal tubular acidosis is common in diabetic patients with acidosis and hyperkalemia, While others two types I &II have hypokalemia and acidosis.Patient did not have acidosis or features of Addisons disease.Postassium in ABGs was within normal limits which suggested patient had pseudohyperkalemia secondary to thrombocytosis.

54. 20 years female known to have type 1 diabetes mellitus,she missed her insulin dose presented to emergency room complaining of recurrent vomiting,on examination she is tachypnic with repiratory rate of 22,blood pressure 100/60mmHg.Pulse 95/min and afebrile.Other systemic review unremarkable.Laboratory investigations showed.Urine ketone 3,+Glucose 2+.ABG’s.PH.7.2 HCO3 26 PCO2 30.Renal profile.urea 5mmol/L creatinin 65 umol/L Na.140mmol/L K 3.5mmol/L Cl.95,Random blood sugar 20 mmol/L.what is acid base abnormality in this patient. A.Metabolic acidosis B.Respirtaory acidosis C.Mixed metabolic and respiratory acidosis D.High anion gap metabolic acidosis,metablolic and respiratory alkalosis E.Normal anion gap metabolic acidosis, metabolic and respiratory alkalosis.

55. Answer: D.This young female developed High anion gap metabolic acidosis secondary to ketones in the blood, Repiratory alkalosis due to tachypnia secondary to anxiety and metabolic alkalosis due to recurrent vomiting.Her Calculated Anion gap is 140- (95+26)=19

56. 16 years female was referred for further investigations for short stature and stone disease.she was behind her milestones.Laboratory investigations showed.MSU, PH 7 otherwise bland sediment.Renal profile.Na 135mmol/L K 2.9 mmol/L Chloride 115 mmolL, Serum urea and Creatinine normal.Serum HCO3 10.what is the diagnosis. A.Type 1 renal tubular acidosis B.Type 2 renal tubular acidosis C.Type 4 renal tubulare acidosis D.High anion gap metabolic acidosis E.Metabolic alkalosis.

57. Answer: A.Anion gap for this patient is 10 while the patient having low bicarbonate suggesting metabolic acidosis.It is normal anion gap metabolic acidosis.As there is history of nephrolithiasis and patient is hypokalemia which favours the diagnosis of type 1 renal tubular acidosis.Urinary PH is 7 which is high and these patient can not acidify urine and maintain urinary PH always above 5.5 due to defect in the secretion of H ion in the distal convoluted tubules.

58. 60 years old male was treated ifosfamide based chemotherapy for soft tissue sarcoma.He was found persistant hypokalemia with low serum bicarbonate level on laboratory investigations.His current laboratory investigations are as following.Renal profile.Serum Urea 7 mmol/L, Serum creatinine 95 umol/L, Serum Na 140mmol/L and Serum K 3 mmol/L, Serum chloride 113mmol/L.ABG’s.PH.7.4,HCO3,18 and PCO2.47.What kind of acid base disorder happened. A..Metabolic alkalosis B..Type 1 renal tubular acidosis C..Type 2 renal tubular acidosis D..Type 4 renal tubular acidosis E..Respiratory acidosis.

59. Answer: C.Ifosfamide chemotherapy is effective in treating soft tissue cancer and it causes proximal renal tubular defect leading to proximal renal tubular acidosis with hyperchloremic,hypokalemic,normal anion gap metabolic acidosis.Here anion gap is 9.