acid-base disorders sharon anderson, m.d. division of nephrology and hypertension may 2003

Acid-Base Disorders

Sharon Anderson, M.D.

Division of Nephrology and Hypertension

May 2003

General Acid-Base Relationships

Henderson-Hasselbach equation:

pH = pK + log HCO3

_ /pCO2

H+ = 24 x pCO2/HCO3

_

0.1pH unit = 10 nm/L H+

Approach to Acid-Base Disorders

1. Consider the clinical setting! 2. Is the patient acidemic or alkalemic? 3. Is the primary process metabolic or

respiratory? 4. If metabolic acidosis, gap or non-gap? 5. Is compensation appropriate? 6. Is more than one disorder present?

Simple Acid-Base Disorders

Primary Compensatory

Disorder pH H+ Disorder Response

Metabolic acidosis HCO3

_ pCO2

Metabolic alkalosis HCO3

_ pCO2

Respiratory acidosis pCO2 HCO3

_

Respiratory alkalosis pCO2 HCO3

_

Metabolic Acidosis

Etiology: Inability of the kidney to excrete the dietary H+ load, or increase in the generation of H+ (due to addition of H+ or loss of HCO3

-)

Metabolic Acidosis: Elevated Anion Gap

AG = Na+ - (Cl- + HCO3-) = 12 ± 2

[Note: Diagnostic utility is best when AG > 25]

Causes: Ketoacidosis

Lactic acidosis

Intoxications

Renal failure

Rhabdomyolysis

Anion Gap in Hypoalbuminemia

The true anion gap is underestimated in hypoalbuminemia (= fall in unmeasured anions); AG must be adjusted

Formulas for adjusted AG:– For every 1.0 fall in albumin, increase AG by 2.5– Consider the patient’s “normal” AG to be (2 x alb) +

(0.5 x phosphate)– Adjusted AG = Observed AG + (2.5 x [normal alb -

adjusted alb]

Ketosis

Diabetes

Starvation

Alcoholic

Isopropyl alcohol*

* Ketosis with normal AG and HCO3

_

Ketosis: Points to Remember

-- Normal AG and HCO3_ = isopropyl alcohol

-- Beta-hydroxbutyrate not seen by ketotest

-- Acetoacetate spuriously Cr

-- False positive ketotest:

paraldehyde, disulfiram, captopril

Lactic Acidosis

Type A: Hypoxic

Lactate:pyruvate > 10:1

Type B: Glycolytic

Lactate:pyruvate = 10:1

Intoxications Causing High AG Acidosis

Aspirin - [high salicylate level; also primary respiratory alkalosis]

Methanol - [optic papillitis] Ethylene Glycol - [calcium oxalate crystals] Paraldehyde

Use of venous vs. arterial pH

As compared with arterial blood gasses:

pH 0.03-0.04

pCO2 7-8 mmHg

HCO3 2 mEq/L

The Delta/Delta: AG/ HC03

Rationale:

For each unit INCREASE in AG (above normal), HC03 should DECREASE one unit (below normal)

“Normal” values: AG = 12, HC03 = 24

Use of the Delta/Delta: Examples

AG HCO3 Diagnosis

18 ( 6) 18 ( 6) Appropriate; pure AG acidosis

18 ( 6) 22 ( 2) HCO3 has less than

predicted, so HCO3 is too high;

mixed AG acidosis AND met alk

18 ( 6) 12 ( 12) HCO3 has more than

predicted, so HCO3 is too low;

mixed AG AND non-AG acidosis

Causes of Low Anion Gap

Etiology: Fall in unmeasured anions

or rise in unmeasured cations

Hyperkalemia Lithium intoxication

Hypercalcemia Multiple myeloma

Hypermagnesemia

Artefactual: hypernatremia, bromide, hyperlipidemia

Osmolar Gap

Measured serum osmolality >

calculated serum osmolality by > 10 mOsm

Calc Sosm = (2 x Na) + BUN/2.8 + Glu/18

Causes of High Osmolar Gap

Isotonic hyponatremia

Hyperlipidemia

Hyperproteinemia

Mannitol

Glycine infusion

Chronic renal failure

Ingestions

Ethanol, isopropyl alcohol, ethylene glycol, mannitol

Contrast Media

Relationship between AG and Osmolar Gap

AG Osm gap Comments

Ethylene glycol + + * Double gap

Methanol + + * Double gap

Renal failure + + * Double gap

Isopropyl alcohol - +

Ethanol - +

Lipids, proteins - +

Causes of Normal AG (Hyperchloremic) Metabolic Acidosis

High K+ Low K+

Adrenal insufficiency Diarrhea

Interstitial nephritis RTA

NH4Cl, Arg HCl Ureteral diversion

Use of the Urine Anion Gap (UAG) in Normal AG AcidosisBatlle et al. NEJM 318:594, 1988

Urine AG = (Na + K) - Cl

Negative UAG = Normal, or GI loss of HCO3

Positive UAG = altered distal renal acidification

Caveats: Less accurate in patients with volume depletion (low urinary Na); and in patients with increased excretion of unmeasured anions (e.g. ketoacidosis), where there is increased excretion of Na and K to maintain electroneutrality)

Use of the Urinary AG in Normal Gap AcidosisBatlle et al. NEJM 318:594, 1988

Plasma K UAG U pH Diagnosis

Normal - < 5.5 Normal

Normal-low - > 5.5 GI HCO3 loss

High + < 5.5 Aldo deficiency

High + > 5.5 Distal RTA

Normal-low + > 5.5 Proximal RTA

Use of the Urine Osmolal Gap

When UAG is positive, and it is unclear if increased cation excretion is responsible, urine NH4 concentration

can be estimated from urine osmolal gap Calc Uosm = (2 x [Na+K]) + urea nitrogen/2.8 + glu/18 The gap between the calculated and measured Uosm =

mostly ammonium In patients with metabolic acidosis, urine ammonium

should be > 20 mEq/L. Lower value = impaired acidification

Renal Tubular Acidosis

Type 1 (distal) Type 2 (proximal) Type 4

Defect distal acid. prox HCO3 reab aldo

HCO3 May be < 10 12-20 > 17

Urine pH > 5.3 Variable < 5.3

Plasma K Usually low Usually low High

Response Good Poor Fair

to HCO3 Rx

Calculation of Bicarbonate Deficit

Bicarb deficit = HCO3- space x HCO3

- deficit/liter

HCO3- space = 0.4 x lean body wt (kg)

HCO3- deficit/liter = [desired HCO3

-] - [measured HCO3-]

Osmolar GapAnionGap GI Fluid Loss?

UremiaLactateKetoacidsSalicylate

EthyleneglycolMethanol

Normal IncreasedDiarrheaIleostomyEnteric fistula

Urine pH

Distal RTA (Type 1)Serum K

Proximal RTA (Type 2)

Type 4RTA

High Normal

NoYes

> 5.5< 5.5

HighLow

Approach to Metabolic Acidosis

Metabolic Alkalosis

Etiology: Requires both generation of metabolic alkalosis (loss of H+ through GI tract or kidneys) and maintenance of alkalosis (impairment in renal HCO3 excretion)

Causes of metabolic alkalosis

Loss of hydrogen

Retention of bicarbonate

Contraction alkalosis Maintenance factors: Decrease in GFR, increase in HCO3

reabsorption

Use of Spot Urine Cl and K

Urine Chloride Very Low(< 10 mEq/L)

Vomiting, NG suctionPostdiuretic, posthypercapneicVillous adenoma, congenitalchloridorrhea, post- alkali

> 20 mEq/L

Urine Potassium

> 30 mEq/L

Diuretic phase of diuretic Rx, Bartter’s, Gitelman’s, primary aldo, Cushings, Liddle’s, secondary aldosteronism

Low (< 20 mEq/L)

Laxative abuseOther profound K depletion

Treatment of Metabolic Alkalosis

1. Remove offending culprits.

2. Chloride (saline) responsive alkalosis: Replete volume with NaCl.

3. Chloride non-responsive (saline resistant) alkalosis:

Acetazolamide (CA inhibitor)

Hydrochloric acid infusion

Correct hypokalemia if present

Calculation of Bicarbonate Excess

Bicarb excess = HCO3- space x HCO3

- excess/liter

HCO3- space = 0.5 x lean body wt (kg)

HCO3- excess/liter = [measured HCO3

-] - [desired HCO3-]

Respiratory Acidosis

Causes of Respiratory Acidosis

Inhibition of medullary respiratory center

Disorders of respiratory muscles and chest wall

Upper airway obstruction

Disorders affecting gas exchange across pulmonary capillaries

Mechanical ventilation

Respiratory Alkalosis

Causes of Respiratory Alkalosis

Hypoxemia

Pulmonary disease

Stimulation of medullary respiratory center

Mechanical ventilation

Mixed Acid-Base Disorders: Clues

-- Degree of compensation for primary

disorder is inappropriate

-- Delta AG/delta HCO3

_ = too high or too low

-- Clinical history

Problem 1

A 30-yo man with DM presents with a week of polyuria, polydipsia, fever to 102, nausea, and abdominal pain. He is orthostatic on admission.

130 I 94 I 75 I 906 pH 7.14

6.1 I 6 I 2.3 pCO2 18

pO2 102

Problem 1, cont.

1. Anticipate the disorder

DKA (with anion gap acidosis)

2. Acidemic or alkalemic? 3. Metabolic or respiratory?

pH = acidemic; must be metabolic (low HCO3, low pCO2)

4. If metabolic acidosis: gap or non-gap?

AG = 30; + anion gap metabolic acidosis

5. Is compensation appropriate?

pCO2 should = last 2 digits of pH [18] or (1.5 x HCO3) + 8 [17]

6. Mixed disorder?

AG = 30 (18); HCO3 = 618); thus simple AG met acidosis

130 I 94 I 75 I 906 7.14/18/102

6.1 I 6 I 2.3

Problem 2

A 30-yo man with DM presents with a week of polyuria, polydipsia, fever to 102, and vomiting for four days.

135 I 89 I 50 I 1181 pH 7.26

6.1 I 10 I 2.3 pCO2 23

pO2 88

Problem 2, cont.1. Anticipate the disorder

DKA (AG acidosis); met alk from vomiting

2. Acidemic or alkalemic? 3. Metabolic or respiratory?

pH = acidemic; must be metabolic (low HCO3, low pCO2)

4. If metabolic acidosis: gap or non-gap?

AG = 36; + anion gap metabolic acidosis

5. Is compensation appropriate?

pCO2 should = last 2 digits of pH [26] or (1.5 x HCO3) + 8 [23]

6. Mixed disorder?

AG = 36 (24); HCO3 = 1014); HCO3 is too high; mixed AG metabolic acidosis and

metabolic alkalosis

135 I 89 I 50 I 1181 7.26/23/88

6.1 I 10 I 2.3

Problem 3

A 30-yo man with DM presents with a week of polyuria, polydipsia, fever to 102, and diarrhea.

138 I 111I 49 I 650 pH 7.26

5.5 I 8I 1.4 pCO2 23

pO2 88

Problem 3, cont.1. Anticipate the disorder

DKA (AG acidosis); nongap met acidosis from diarrhea

2. Acidemic or alkalemic? 3. Metabolic or respiratory?

pH = acidemic; must be metabolic (low HCO3, low pCO2)

4. If metabolic acidosis: gap or non-gap?

AG = 19; + anion gap metabolic acidosis

5. Is compensation appropriate?

pCO2 should = last 2 digits of pH [26] or (1.5 x HCO3) + 8 [23]

6. Mixed disorder?

AG = 19 (7); HCO3 = 816); HCO3 is too low; mixed AG metabolic acidosis and

metabolic acidosis (nongap)

138 I 111 I 49 I 650 7.26/23/88

5.51 I 8 I 1.4

Problem 4

A 30-yo man with DM presents with a week of polyuria, polydipsia, fever, cough, and prurulent sputum.

140 I 104 I 75 I 1008 pH 6.95

7.0 I 7 I 2.6 pCO2 33

pO2 60

Problem 4, cont.

1. Anticipate the disorder

DKA (AG acidosis); resp alk or resp acidosis from hypoxemia/pneumonia

2. Acidemic or alkalemic? 3. Metabolic or respiratory?

pH = acidemic; must be metabolic (low HCO3, low pCO2)

4. If metabolic acidosis: gap or non-gap?

AG = 29; + anion gap metabolic acidosis

140 I 104 I 75 I 1008 6.95/33/60

7.0 I 7 I 2.6

Problem 4, cont.

5. Is compensation appropriate?

pCO2 should = last 2 digits of pH [95!!] or (1.5 x

HCO3) + 8 [18]; pCO2 is too high so he has a

superimposed respiratory acidosis

6. Mixed disorder?

AG = 29 (17); HCO3 = 717); so metabolic acidosis is pure AG acidosis. Thus, mixed AG metabolic acidosis and respiratory acidosis

140 I 104 I 75 I 1008 6.95/33/60

7.0 I 7 I 2.6

Problem 5

A 31-yo woman who is 33 weeks pregnant presents with a 2-day history of vomiting.

140 I 104 I 8 I 85 pH 7.64

3.0 I 26 I 0.6 pCO2 25

pO2 93

Problem 5, cont.

1. Anticipate the disorder

Pregnancy: resp alk Vomiting: met alk

2. Acidemic or alkalemic?

pH = alkalemic

3. Metabolic or respiratory?

If resp, HCO3 should be low; if metabolic, then pCO2 should be

high; must have both

4. If metabolic acidosis: gap or non-gap?

N/A; no acidosis; no AG

140 I 104 I 8 I 85 7.64/25/93

3.0 I 26 I 0.6

Problem 5, cont.

5. Is compensation appropriate?

NO (by eyeball, for reasons listed above)

6. Mixed disorder?

Yes, mixed metabolic and respiratory alkalosis. No acidosis component.

140 I 104 I 8 I 85 7.64/25/93

3.0 I 26 I 0.6

Problem 6

A 60-yo man has crushing chest pain, SOB and diaphoresis. He has HTN, for which he takes HCTZ. Exam shows BP 88/60, bilateral crackles, S3. EKG shows ischemia; CXR = pulmonary edema.

140 I 94 I 45 I 300 pH 7.14

5.9 I 20 I 1.9 pCO2 60

pO2 52

Problem 6, cont.1. Anticipate the disorder

Pulm edema -> resp alk or resp acidosis; shock -> metabolic acidosis; HCTZ -> metabolic alkalosis

2. Acidemic or alkalemic?

pH = acidemic

3. Metabolic or respiratory?

If resp, HCO3 should be > 24 in compensation; if metabolic, then pCO2

should < 40; must have both respiratory and metabolic acidoses

4. If metabolic acidosis: gap or non-gap?

AG = 26; + anion gap metabolic acidosis

140 I 94 I 45 I 300 7.14/60/52

5.9 I 20 I 1.9

Problem 6, cont.

5. Is compensation appropriate?

NO (by eyeball, for reasons listed above)

6. Mixed disorder? Anything else?

AG = 26 (14); HCO3 = 20); so HCO3 is

too high; must have a superimposed metabolic alkalosis.

Thus, triple disorder: respiratory acidosis, anion gap metabolic acidosis, and metabolic alkalosis

140 I 94 I 45 I 300 7.14/60/52

5.9 I 20 I 1.9

Problem 7

A 55-yo woman with a history of a CVA presents to clinic complaining of shortness of breath.

140 I 100 I 30 I 115 pH 7.36

3.9 I 30 I 1.5 pCO2 38

pO2 91

Problem 7, cont.

1. Anticipate the disorder

Resp alk due to CNS disorder or acute pulmonary process

2. Acidemic or alkalemic?

pH = acidemic

3. Metabolic or respiratory? 4. If metabolic acidosis: AG?

HCO3 is high (not metabolic acidosis); pCO2 is < 40 (not

respiratory acidosis); AG is normal (10), so what’s going on??

140 I 100 I 30 I 115 7.36/38/91

3.9 I 30 I 1.5

Problem 7, cont.

LAB ERROR!

By Henderson-Hasselbach

H+ = 24 x pCO2/HCO3 = 24 x (38/30) = 30

pH should be 7.50

140 I 100 I 30 I 115 7.36/38/91

3.9 I 30 I 1.5

Problem 8

You are in the ER, and are aware that the lab has been having intermittent problems with the chemistry autoanalyzer. A 30-yo diabetic man, well known to you from previous visits, comes in with severe nausea and vomiting. His blood alcohol level is very high. The ER attending advises you to check his labs and send him home if they are OK.

140 I 84I 28 I 160 pH 7.40

3.0 I 24I 1.3 pCO2 40

pO2 88

Problem 8, cont.

1. Anticipate the disorder

Vomiting -> met alk; if unconscious, resp acidosis

2. Acidemic or alkalemic? 3. Metabolic or respiratory?

pH, pCO2 and HC03 are all normal --> no apparent

disorder

4. Lab error? Check H-H equations.

H+ = 24 x (pCO2/HCO3) = 24 x (40/24) = 40, so pH = 7.40

5. Do you send him home?

140 I 84 I 28 I 160 7.40/40/88

3.0 I 24 I 1.3

Problem 8, cont.

5. Do you send him home?

AG = 32; + anion gap acidosis

AG = 32 (20); HCO3 = 240); so HCO3 is too high;

must have a superimposed metabolic alkalosis.

Thus, mixed AG acidosis and metabolic alkalosis

140 I 84 I 28 I 160 7.40/40/88

3.0 I 24 I 1.3

Problem 9

A 58-yo man with cirrhosis and Type 2 DM presents with fever, abdominal pain, SOB, and vomiting.

159 I 112 I 55 I 160 pH 7.31

3.3 I 12 I 2.8 pCO2 19

pO2 77

Problem 9, cont.

1. Anticipate the disorder

Renal dis --> acidosis; dead gut --> lactic acidosis; vomiting --> met alk; pain --> resp alk; liver disease --> resp alk

2. Acidemic or alkalemic? 3. Metabolic or respiratory?

pH = acidemic; must be metabolic (low HCO3, low pCO2)

4. If metabolic acidosis: gap or non-gap?

AG = 35; + anion gap metabolic acidosis

159 I 112 I 55 I 160 7.31/19/77

3.3 I 12 I 2.8

Problem 9, cont.

5. Is compensation appropriate?

pCO2 should = last 2 digits of pH [31; not] or (1.5 x

HCO3) + 8 [26]; pCO2 is too low so he has a

superimposed respiratory alkalosis

6. Mixed disorder?

AG = 35 (23); HCO3 = 1212); so HCO3 is too high,

so there must be a metabolic alkalosis.

Thus, triple disorder: AG metabolic acidosis, respiratory alkalosis, and metabolic alkalosis

159 I 112 I 55 I 160 7.31/19/77

3.3 I 12 I 2.8

Problem 10

A 70-yo man presents with vomiting and abdominal pain, for which he has been taking Rolaids. He is hypotensive and has a tender abdomen.

140 I 69 I 40 I 118 pH 7.74

3.4 I 40 I 1.5 pCO2 30

pO2 105

Problem 10, cont.

1. Anticipate the disorder

Dead gut --> lactic acidosis; vomiting or Rolaids --> met alk; pain --> resp alk

2. Acidemic or alkalemic? 3. Metabolic or respiratory?

pH = alkalemic; must be both metabolic (high HCO3) and

respiratory (low pCO2)

4. If metabolic acidosis: gap or non-gap?

AG = 31; + anion gap metabolic acidosis

140 I 69 I 40 I 118 7.74/30/105

3.4 I 40 I 1.5

Problem 10, cont.

5. Is compensation appropriate?

Cannot compute, too many disorders

6. Mixed disorder?

AG = 31 (19); HCO3 = 40, not down; so HCO3 is

too high, so there must be a metabolic alkalosis.

Thus, triple disorder: AG metabolic acidosis, respiratory alkalosis, and metabolic alkalosis

140 I 69 I 40 I 118 7.74/30/105

3.4 I 40 I 1.5