1. METABOLIC ACIDOSIS

2. Objectives  Review physiology of acid-base balance  Determine gap versus non-anion gap metabolic acidosis  Overview of RTAs  Practice with clinical vignettes

3. Normal Physiology  Daily production of acid (H + ) mostly from diet  Balanced by renal excretion of acids and/or reclamation of base (HCO 3 - )

4. Metabolic Acidosis Disorder 1) Overproduction of acids = ↑H + 2) Increased extra-renal loss of base = ↓ HCO 3 - 3) Decrease in renal acid secretion = ↑H + 4) Poor renal absorption of base = ↓ HCO 3 -

5. Expected Compensation

7. Acid/Base Formulas  Winter’s Formula (CO2) = 1.5 [HCO 3 - ] + 8 ± 2  Anion Gap = Na + – Cl - + HCO 3 -  Correct for hypoalbuminemia  Increase AG by 2.5 for every 1 decrease in albumin  Unmeasured Anions = Lactate, Phosphate, Sulfate  ∆ Anion gap / ∆ [HCO 3 - ]

8. Elevated Anion Gap (>12)  “MUDPILES”  Methanol  Uremia  Diabetic ketoacidosis / Starvation ketoacidosis  Paraldehyde  Isoniazid / Iron  Lactic acidosis  Ethanol / Ethylene glycol  Salicylates  CO, cyanide, hydrogen sulfide, sulfur, theophylline, toluene

9. Non-anion Gap Metabolic Acidosis  “HARD UP”  Hyperalimentation  Acetazolamide  Renal tubular acidosis (RTA)  Diarrhea  Ureteral diversion  Pancreatic fistula

10. Low Anion Gap (<3) Increase in unmeasured cations  Hyper-Ca  Hyper-Mg  Hyper-K  Lithium intoxication  Paraproteinemia Decrease in unmeasured anions  Hypoalbuminemia  Dilution

11. Urine Anion Gap  UAG= (U Na + U K + U NH4 ) – (U Cl - U HCO3 )  POSITIVE if renal disease  NEGATIVE if normal or GI bicarbonate losses

12. Proximal (type 2) RTA  Impaired proximal tubule HCO 3 - reabsorption  In steady state distal nephron can accommodate and acidify urine pH < 5.5  Hypokalemia  Increased NaHCO 3 to the distal tubules  Increased aldosterone activity reabsorbing Na+ and secreting K+

13. Distal (type 1) RTA  Impaired distal secretion of H +  Causes impairment in regeneration of HCO 3 -  Unable to acidify urine pH < 5.5  Associated with hypo-K  Associated with nephrocalcinosis and nephrolithiasis  Increase in urinary luminal Ca 2+ from bone mineral dissolution for buffering systems  High urine pH decreases solubility of Ca 2+ phosphate complexes

14. Hyperkalemic (type 4) RTA  Decreased H + and K + secretion  Urine pH < 5.5  Etiology due to mild/moderate CKD, DM, autoimmune disorders  Deficiency of circulating aldosterone  Impairment of distal luminal electronegativity in the cortical collecting duct

15. RTA Review  Proximal (type 2)  Poor HCO 3 reclamation  Normal / hypo-K  Urine pH < 5.5 (variable)  HCO 3 14-20  Distal (type 1)  Reduced H + secretion  Normal / hypo-K  Urine pH > 5.5 (constant)  HCO 3 <10 mEq/L  Nephrocalcinosis  Hyperkalemic (type 4)  Aldosterone deficiency  Reduced H + secretion  Hyperkalemia  Urine pH < 5.3  HCO 3 >15  RTA of Renal Failure  Decreased renal mass  Hyperkalemia  Urine pH < 5.5  Abnormal renal function

16. Approach to Acid/Base Disorders 1. Acidemia or Alkalemia 2. ∆ PCO 2 and serum HCO 3 from normal (-osis) 3. Calculate anion gap 4. PCO 2 and HCO 3 compensation – Winter’s: Expected pCO2 = 1.5 [HCO 3 - ] + 8 +/- 2 – Delta-Delta = Measured AG – 12 / 24 – [HCO 3 - ] – Metabolic Alkalosis: Expected pCO2 = 0.7 [HCO 3 - ] + 20 mmHg (range +/- 5) 5. Differential Diagnosis 6. Treat underlying condition unless pH within critical range

17. Delta-Delta

18. ABG Warm-Up  pH / PaCO 2 / HCO 3  7.28 / 50 / 23  7.10 / 38 / 14  7.48 / 55 / 34 → Respiratory Acidosis → Metabolic Acidosis → Metabolic Alkalosis + Respiratory compensation

19. Case #1  60 y/o woman with HTN, admitted after 7 days of severe vomiting.  Appears ill, hypotensive with tachycardia  (+) Rebound tenderness w/ no bowel sounds  BMP – 140/3.2/80/11/90/3<90  ABG – 7.29 / 24  AG Metabolic acidosis + Metabolic alkalosis

20. Case #2  64 y/o man admitted to ICU for PNA and septic shock.  4 days of SOB and fever  Afebrile, BP 85/50, HR 110, RR 22  (+) Crackles and heart murmur, pedal edema  BMP – 135/4.8/103/10/22/1.4<115, Albumin=3.8  ABG – 6.94 / 48 / 51  AG Metabolic acidosis + Respiratory acidosis

21. Case #3  15 y/o male with no reported PMH  Complains of light sensitivity  Short stature based on growth chart, bowed-legs  Initial labs: 145/3.9/108/14/12/0.8<99 UA with pH=5.3  What next?

22. Case #4  44 y/o female with cirrhosis, HD#2 for fever and abdominal pain  Meds: Spironolactone, Lasix, Lactulose  Tm=100.8, BP 74/55, HR 72  Appears cachetic  Abdomen distended, (+) TTP, 1+ BLE edema  BMP – 128/5.1/104/12/20/1.3<84, Albumin=1.4  ABG – 7.25 / 28 / 78  AG Metabolic acidosis

23. Case #5  66 y/o man with type II DM, HTN  8 days of diarrhea, abdominal pain, decreased PO  Grandson w/ similar symptoms 1 week ago  Meds: Enalapril, Atenolol, HCTZ, Metformin  Normal vitals, (+) FOBT  BMP – 136/3.9/114/13/21/1.2<128, Albumin=4  Urine pH=6, U Na =32, U K =21, U Cl =80  ABG – 7.27 / 30 / 90  Non-anion gap Metabolic acidosis

24. Metabolic Alkalosis  Metabolic Alkalosis Initiation:  Net loss of H +  Net addition of HCO3 - (alkali ingestion)  External loss of fluid containing Cl - (contraction alkalosis)  Maintenance mechanisms:  Cl - depletion  K + depletion  Hypercapnea  Rarely; primary disorders of specific ion channels in the Loop of Henle, distal tubule or collecting ducts

25. Chloride Depletion  Selective Cl - (eg nasogastric suction) produces a major increase in serum bicarbonate  Low urine chloride  K + depletion sustains the metabolic alkalosis  Increases H + secretion via H + / K + ATPase  Increase NH 4 + production and excretion

26. Sources of Cl - responsive alkalosis  Vomiting and NG suction  Diarrhea  Congenital Chloride Diarrhea  Villous Adenoma  Diuretics  Loop diuretics  Metolazone  Thiazides  Post-hypercapneic state

27. Chloride-resistant Metabolic Alkalosis  Mineralocorticoid excess  1 ° hyperaldosternism  Adenoma  Cushing’s syndrome  ACTH tumor  Renin tumor  Androgenetic syndrome  Fludrocortisone treatment  Apparent excess of mineralocorticoid  Licorice or Altoids (Glycyrrhizic acid)  Liddle’s syndrome  11B-Hydroxysteroid dehydrogenase deficiency  High-dose Glucocorticoids Normotensive  Severe K + deficiency  Bartter’s and Gitelman’s

28. Exogenous Alkali  Persistent metabolic alkalosis when the body is deficient in K + or Cl - stores  Hypercalcemia  Milk alkali syndrome (Ca 2+ containing antacids)  Alkali administration  Massive pRBC transfusion >10U (Citrate)  Refeeding syndrome

29. Management of Metabolic Alkalosis  Treat underlying condition  If severe pH > 7.60 treat with hemodialysis  Chloride Responsive  Normal Saline or ½ Normal Saline  Rate 50-100 cc/hr over maintenance rate  Replete K +  PPIs minimize gastric losses  If diuretic induced can use K + sparing diuretics to limit alkalosis

30. Management of Metabolic Alkalosis  Chloride Resistant:  In a patient in an edematous state Acetazolamide  Mineralocorticoid excess; restoration of normal mineralocorticoid activity Surgical Removal K + sparing diuretics + K + supplements  Bartter’s and Gitelman’s syndrome K + sparing diuretics + K + supplements NSAIDs (Bartter’s)