5. Buffers

8. HA [H+].[A-]

14. Kidneys

18. H2 po41-[H+] [ H po42- ]

23. Case Study • A 4-year-old girl was admitted to the emergency room because of poor intake, vomiting, fever and abdominal pain over the last 3 days. • Mother denied any history of drug ingestion. • Past medical history is significant for recurrent urinary tract infections. • The BP was 90/57 mmHg, PR 90/min, and respirations 32/min

24. Case Study (cont’d) • Laboratory data on admission revealed a serum Na+ of 135 mEq/, K + 6.2 mEq/L, Cl- 117 mEq/L, HCO3- 10 mEq/L, BUN 23 mg/dL, creatinine 0.4mg/dL,glucose 100 mg/dL, calcium 9.2 mg/dL, phosphorous 4.0 mg/dL, uric acid 4.8 mg/dL. • Arterial blood pH was 7.10, and pCO2 28 mmHg.

25. Case Study (cont’d) • Urinalysis showed a pH of 6.5, negative for blood or protein. • The urine sediment was normal. • Urine Cl- was 52, Na+ 68, and K+ 25.

26. Quiz • What acid-base is present? • What is the most likely diagnosis? • What investigation would establish the diagnosis?

27. Step 1 What is the primary acid-base disturbance? • Metabolic acidosis is the primary acid-base disorder: - Low blood pH (7.10) • - Low HCO3- level (10 mEq/L)

28. Step 2 Is the metabolic acidosis associated with a normal or an increased anion gap?AG = Na+ - (Cl- + HCO3-)

29. Patient has a normal AG acidosis • Serum AG = (135) - [(117+16)] • = (135) - (133) • = 12 mEq/L • The fall in serum HCO3- level in this patient is matched by an equal rise in the serum Cl- concentration, thus the patient has normal anion gap acidosis

30. Causes of normal AG acidosis • GI bicarbonate loss • Use of carbonic anhydrase • Hyperalimentation • Ureteral diversions • NH4Cl infusions • Renal tubular acidosis (RTA)

31. Step 3 Is the respiratory compensation adequate? • pCO2 = 1.2 HCO3- • pCO2 = 1.2 (25-10) or 18 mmHg • Expected pCO2 = (40-18) = 22 mmHg • Patient’s pCO2 = 28 mmHg • Patient’s pCO2 > the expected pCO2 Respiratory Acidosis

32. Our patient has a mixed acid-base disorder • Normal AG metabolic acidosis plusRespiratory acidosis

33. The urine AG • Urine AG = (UC +) - (UA-) • Urine Cl- > Urine (Na+ + K+)

34. The usefulness of the urine AG in the evaluation of distal RTA • A negative urine AG suggests the presence of a normal distal urinary acidification • A positive urine AG (Na+ + K +) > Cl- suggests the presence of impaired distal urinary acidification

35. Urine AG as an index of NH4- excretion • NH4+ is an unmeasured cation and its excretion at the distal tubule is usually accompanied by Cl- excretion (NH4Cl) • The urinary AG should become progressively negative as the rate of NH4Cl excretion increases • Under normal condition the urine AG is negative

36. Classification of RTA • Classic distal RTA (RTA-1) • Proximal RTA (RTA-2) • Hyperkalemic distal RTA (RTA-IV)

37. Quiz What is the most likely diagnosis? • The most likely diagnosis is RTA-IV • 1. Normal AG acidosis • 2. Hyperkalemia • 3. Urine pH >5.5 • 4. Positive urine AG

38. Quiz What is the most likely cause of RTA-IV? • A. Acute non-obstructive pyelonephritis • B. Acute pyelonephritis with VUR • C. Addison disease • D. Non-obstructive pyelonephritis B. Pyelonephritis with VUR

39. Quiz What investigations you order to confirm this diagnosis? • A. Renal sonogram • B. Urine β2 microglobulin • C. DMSA scan • D. VCUG • E. DTPA scan A. Renal sonogram

40. Our patient has a positive urine AG Urine (Na+ + UK+) > Urine Cl- • Urine AG = [(Na+ + K+ )] - (Cl-) • = [(68 + 25)] -(52) • = (93) - (52) • = 41 mEq/L • The positive urine AG is consistent with the impaired distal urinary acidification

41. Differential diagnosis of impaired distal renal acidification • Classic distal RTA (RTA-I) • Hyperkalemic distal RTA (RTA-IV)

42. RTA-1 Urine pH >5.5 Severe hypokalemia Low urine citrate exc Nephrocalcinosis Urolithiasis RTA-IV Urine pH varies hyperkalemia Normal urine citrate Decreased renin and aldosterone secretion Characteristics of RTA

43. Causes of classic distal RTA (RTA-I) • Idiopathic • Familial • Hypercalciuria • Amphotricin B • Chronic active hepatitis • Medullary sponge kidney

44. Causes of hyperkalemicdistal RTA (RTA-IV) • Urinary tract obstruction • Vesicoureteral reflux • Interstitial nephritis • Systemic lupus erythematosis • Diabetes mellitus • Primary hypoaldosteronism

45. Case Study • A 12-year-old girl was admitted to the emergency department in a semi-comatose condition. Blood pressure was 110/65 mmHg; pulse 87/min; and respiratory rate 22/min. The remainder of the PE was normal. • Laboratory data on admission revealed serum Na+ of 135 mEq/, K + 2.1 mEq/L, Cl- 117 mEq/L, HCO3- 10 mEq/L, BUN 13 mg/dL, creatinine 0.4 mg/dL, and glucose 90 mg/dL.

46. Case study (cont’d) • Arterial blood pH was 7.10, and PCO2 33 mmHg. Urinalysis showed a pH of 7.0. The urine sediment was normal • The patient was intubated and potassium was given intravenously.

47. Quiz • What acid-base disorder is present? • What is the most likely diagnosis? • What investigation would establish the diagnosis?

48. Step 1: Review ABG data What is the primary acid-base disturbance? • Blood pH =7.10 • HCO3- = 10 mEq/L • PCO2 = 33 mmHg The findings of low HCO3- and low pH suggest a primary metabolic acidosis

49. Step 3: Review serum electrolytes? Is the metabolic acidosis associated with a normal or an increased anion gap? • Serum AG = (135) - [(117+16)] • patient has normal AG acidosis • = (135) - (133) Normal AG =12 mEq/L

50. Step 2: Assess respiratory compensation Is the respiratory compensation adequate? • Patient’s PCO2 = 33 mmHg ∆PCO2 = 1.2 ∆HCO3- • ∆PCO2 = 1.2 (25-10) or 18 mmHg • Expected PCO2 = (40-18) = 22 mmHg Patient’s PCO2> the expected pCO2