METABOLIC ACIDOSIS

Objectives

Review physiology of acid-base balance Determine gap versus non-anion gap metabolic

acidosis Overview of RTAs Practice with clinical vignettes

Normal Physiology

Daily production of acid (H+) mostly from diet

Balanced by renal excretion of acids and/or reclamation of base (HCO3

-)

Metabolic Acidosis Disorder

1) Overproduction of acids = ↑H+

2) Increased extra-renal loss of base = ↓ HCO3-

3) Decrease in renal acid secretion = ↑H+

4) Poor renal absorption of base = ↓ HCO3-

Expected Compensation

Acid/Base Formulas

Winter’s Formula (CO2) = 1.5 [HCO3-] + 8 ± 2

Anion Gap = Na+ – Cl- + HCO3-

Correct for hypoalbuminemia Increase AG by 2.5 for every 1 decrease in albumin

Unmeasured Anions = Lactate, Phosphate, Sulfate ∆ Anion gap / ∆ [HCO3

-]

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

Non-anion Gap Metabolic Acidosis

“HARD UP” Hyperalimentation Acetazolamide Renal tubular acidosis (RTA) Diarrhea Ureteral diversion Pancreatic fistula

Low Anion Gap (<3)

Increase in unmeasured cations

Hyper-Ca Hyper-Mg Hyper-K Lithium intoxication Paraproteinemia

Decrease in unmeasured anions

Hypoalbuminemia Dilution

Urine Anion Gap

UAG= (UNa + UK + UNH4) – (UCl - UHCO3)

POSITIVE if renal disease NEGATIVE if normal or GI bicarbonate losses

Proximal (type 2) RTA

Impaired proximal tubule HCO3- reabsorption

In steady state distal nephron can accommodate and acidify urine pH < 5.5

Hypokalemia Increased NaHCO3 to the distal tubules Increased aldosterone activity reabsorbing Na+ and

secreting K+

Distal (type 1) RTA

Impaired distal secretion of H+

Causes impairment in regeneration of HCO3-

Unable to acidify urine pH < 5.5 Associated with hypo-K Associated with nephrocalcinosis and

nephrolithiasis Increase in urinary luminal Ca2+ from bone mineral

dissolution for buffering systems High urine pH decreases solubility of Ca2+ phosphate

complexes

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

RTA Review

Proximal (type 2) Poor HCO3 reclamation Normal / hypo-K Urine pH < 5.5 (variable) HCO3 14-20

Distal (type 1) Reduced H+ secretion Normal / hypo-K Urine pH > 5.5 (constant) HCO3 <10 mEq/L Nephrocalcinosis

Hyperkalemic (type 4) Aldosterone deficiency Reduced H+ secretion Hyperkalemia Urine pH < 5.3 HCO3 >15

RTA of Renal Failure Decreased renal mass Hyperkalemia Urine pH < 5.5 Abnormal renal function

Approach to Acid/Base Disorders

1. Acidemia or Alkalemia2. ∆ PCO2 and serum HCO3 from normal (-osis)3. Calculate anion gap4. PCO2 and HCO3 compensation

– Winter’s: Expected pCO2 = 1.5 [HCO3-] + 8 +/- 2

– Delta-Delta = Measured AG – 12 / 24 – [HCO3-]

– Metabolic Alkalosis: Expected pCO2 = 0.7 [HCO3-] +

20 mmHg (range +/- 5) 5. Differential Diagnosis6. Treat underlying condition unless pH within

critical range

Delta-Delta

ABG Warm-Up

pH / PaCO2 / HCO3

7.28 / 50 / 23

7.10 / 38 / 14

7.48 / 55 / 34

→ Respiratory Acidosis

→ Metabolic Acidosis

→ Metabolic Alkalosis + Respiratory compensation

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

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

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?

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

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, UNa=32, UK=21, UCl=80 ABG – 7.27 / 30 / 90

Non-anion gap Metabolic acidosis

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

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 NH4

+ production and excretion

Sources of Cl- responsive alkalosis

Vomiting and NG suction Diarrhea

Congenital Chloride Diarrhea Villous Adenoma

Diuretics Loop diuretics Metolazone Thiazides

Post-hypercapneic state

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

Exogenous Alkali

Persistent metabolic alkalosis when the body is deficient in K+ or Cl- stores

Hypercalcemia Milk alkali syndrome (Ca2+ containing antacids) Alkali administration Massive pRBC transfusion >10U (Citrate) Refeeding syndrome

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

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)