Metabolic Acidosis

Residents’ Conference

11/1/01

Romulo E. Colindres, MD

Primary Acid-Base Disorders

Disorder pH HCO3- pCO2

Metabolic Acidosis

Metabolic Alkalosis

Respiratory Acidosis

Respiratory Alkalosis

Compensatory Responses toPrimary Acid-Base Disorders

Disorder Primary Change Compensatory ResponseMetabolic acidosis Fall in plasma bicarbonate For every 1 mEq/L decrease in

bicarbonate, the pCO2 falls by 1.2 mmHg

Metabolic alkalosis Rise in plasma bicarbonate For every 1 mEq/L rise in bicarbonate, the pCO2 rises 0.6-0.7 mmHg

Respiratory acidosis Rise in pCO2 Acute: For every 10 mmHg rise in pCO2, the bicarbonate rises 1 mEq/LChronic: For every 10 mmHg rise in pCO2, the bicarbonate rises 3.5 mEq/L

Respiratoryalkalosis

Fall in pCO2 Acute: For every 10 mmHg fall in pCO2, the bicarbonate falls 2 mEq/LChronic: For every 10 mmHg fall in pCO2, the bicarbonate falls 4 mEq/L

SERUM ANION GAP

[Na + K] + Unmeasured Cations =

[Cl + HCO3] + Unmeasured Anions

[Na + K] - [Cl + HCO3] =

Unmeasured Anions (UC) - Unmeasured Cations (UC) . CAN OMIT K.

[Na] - [Cl + HCO3) = UA-UC; Normal Value: 10+/- 2mEq/L. Increase in anion gap usually indicates an increase in unmeasured anions: albumin, PO4, SO4, anions of organic acids.

Anion Gap

Na+140

HCO3-

24

Cl-104

Proteins 16Organic Acids 5 PO4 SO4 3

K 5Ca 5Mg 2

Cations Anions

Na+140

HCO3-

24

Cl-104

AG 12

AG = Na+ - (Cl+HCO3)

CAUSES OF METABOLIC ACIDOSIS

1 Excessive Acid Production

• Endogenous

• Exogenous

2 Bicarbonate Wasting

• Diarrhea

• Renal (Type 2 RTA)

3 Decreased Excretion of Acid (Impaired NH4+ excretion)

• Renal Failure

• Impaired Distal Acidification (RTA 1)

• Hypoaldosteronism (RTA 4)

4 Combination of Above

METABOLIC ACIDOSIS: INDICIS OF SEVERITY

• pH <7.2

• [HCO3] < 10mEq/L

• Massive continuous production of acid

• Poor respiratory compensation ( pCO2 fall less than 1.25 mm Hg for each mEq/L fall in HCO3 concentration)

Acid Production

• Carbohydrates/Fats 15,000 mmol/d CO2 (Volatile acid)

CO2 + H20 H2CO3 H+ + HCO3-

Lungs

• Proteins 50-100 mEq/d H2SO4 (Fixed Acid)

– H+ + HCO3- H2CO3

– H+ + Intracellular Base- HBase

– H+ excretion in the kidney

Limits rise in [H+]

RENAL EXCRETION OF ACID

• The kidneys must excrete 50 to 100 mEq of acid to regenerate the bicarbonate used to buffer the fixed acid generated from metabolism each day

• The daily acid load cannot be excreted unless all of the filtered HCO3 is reabsorbed

• Excretion of an acid urine is a necessary but not sufficient condition to excrete the daily acid load: free H+ concentration in the urine is very low (<0.05mEq/L) in a maximally acid urine

• Acid excretion comes from H+ secretion and binding to NH4+ and phosphate

Proximal Tubule: Bicarbonate Reabsorption

3Na+

2K+

Peritubularcapillary

Tubular lumen

ATPaseH+

OH- + CO2

H2O

HCO3-

CA

Na+

Na+

H+ HCO3- +

H2CO3

CO2 + H2O

CANa+

HCO3-

Proximal Tubule: Titratable Acid

3Na+

2K+

Peritubularcapillary

Tubular lumen

ATPaseH+

OH- + CO2

H2O

HCO3-

CA

Na+

Na+

H+

Na+

HCO3-

HPO42- +

H2PO4-

Collecting Duct -Intercalated Cell: Titratable Acid

Peritubularcapillary

Tubular lumen

ATPase H+

OH- + CO2

H2O

HCO3-

CACl-

HPO42- + H+

H2PO4-

HCO3-

Cortical Collecting Duct-Ammonium “Trapping”

3Na+

2K+

Peritubularcapillary

Tubular lumen

ATPase

ATPase

H+

NH3

+NH3

NH4+

H+

OH- + CO2

H2O

HCO3-

CACl-

3Na+

2K+

Peritubularcapillary

Tubular lumen

NH4+

Na+

NH4+

Glutamine

Glutamate-

Glutaminase

Na+

NH4+

2Cl-NH4

+

NH3

ATPaseH+

NH3

+

NH4+

Ammonia Synthesis and Transport

ATPase

Renal Acid-Base Regulation

• 4000 mEq HCO3- filtered in proximal tubule must

be reabsorbed - no net acid excretion• Minimal urine pH is 4.5 only 40-80 mol per

day can be excreted as free H+; Excretion of the daily acid load as free H+ would require 2000 liters of urine output/day– H+ is excreted in the form of urinary buffers,

H2PO4- and NH4

+

METABOLIC ACIDOSIS WITH INCREASED ANION

GAPNaHCO3 + Lactic acid--->Na Lactate +

CO3H2----> [Na] - [Cl +HCO3 + Lactate]

• Usually caused by increased production of endogenous or exogenous organic acid

• Salt (anion) may be quickly metabolized or excreted yielding a hyperchloremic acidosis

Gap Metabolic Acidosis Due to Presence of Ketoacids

Na+140

Cl-105

HCO3 10

Ketoacid 13

Pr, OA, P,S12 Anion Gap = 25pH = 7.25

HCO3 = 10pCO2 = 25AG = 25

Differential Diagnosis of AG Metabolic Acidosis

Methanol poisoningUremia (advanced, SO4, PO4)Diabetic ketoacidosis -Other ketoses

EtOH Starvation

Paraldehyde (rare)Ischemia-LactateEthylene glycolSalicylate toxicity

DIFFERENTIAL DX OF ANION & OSMOLAR GAP ACIDOSES

Anion Gap >16Alcoholic KetoacidosisDiabetic KetoacidosisLactic AcidosisSalicilate ToxicityMethanol/Ethylene Glycol

Osmolar Gap >25 mOsm/KgMethanol IntoxicationEthylene Glycol

Osmolar Gap < 25 mOsm/Kg Alcoholic Ketoacidosis Diabetic Ketoacidosis Lactic Acidosis Salicylate Toxicity Methanol/Ethylene Glycol in Late Phase

KETOACIDOSIS EVOLVES FROM HIGH AG NL. AG ACIDOSIS

LIVER

H+ Ket +Na HCO3

Na Ket

URINE

BLOOD

MUSCLE

Na Ket Reabsorption Maintains High AG

Na Ket

+ H2O Excretion

Na Ket NaHCO3 Na + H2O W/out Cl AG, Cl

S HCO3,but not to nl S AG to nl

GFR

INSU

LIN

HYPERCHLOREMIC METABOLIC ACIDOSIS

HCL + NaHCO3---> NaCl and H2CO3--->

CO2 +H2O Therefore: anion gap unchanged since [Na] - (increased [Cl] + decreased [HCO3]).

• Loss of HCO3 in stool• Loss of HCO3 in urine (RTA 2)• Decreased excretion of NH4 (RTA 1 and 4 and

renal failure)• Increased production of acid but prompt excretion

of anion (treatment of DKA, toluene)

Normal Anion Gap Metabolic Acidosis in a Patient with Diarrhea

Na+140

HCO3 15

Cl-113

AG 12

pH = 7.32HCO3- = 15pCO2 = 30AG = 12

URINE ANION GAP:AN INDIRECT MEASUREMENT OF NH4+

EXCRETION IN HYPERCHLOREMIC METABOLIC ACIDOSIS

Urine Anion Gap: [Na] + [K] - [Cl]

Since: [Na] + [K] + Unmeasured (U) Cations =

[Cl] + Unmeasured (U) Anions

Therefore, [Na] + [K] - [Cl]= U Anions- U Cations

U Anions = Sulfates, Phosphates, etc.

U Cation = Mainly NH4+

Normal Value: 0

Hyperchloremic Metabolic Acidosis: -20 to -50 = Appropriately Increased NH4+ Excretion

Practical Approach (Hyperchloremic metabolic acidosis)

Urine Anion Gap

Negative PositiveType 2 RTA

Diarrhea

DKA/Toluene

HCl (Hyperalimentation) Urine pH and Plasma K

Urine pH < 5.5, K Urine pH > 5.5, K nl/low Urine pH > 5.5, K

Type 4 RTA Type 1 (secretory defect Type 1 (voltage)

Early CRF or back-leak)

METABOLIC ACIDOSIS:BICARBONATE

THERAPY• Avoid if metabolic acidosis is transient and

moderate and renal function is adequate, particularly with increased anion gap acidosis, since anions of organic acids can regenerate HCO3

• Only a small inmediate increase (2-3 mEq/L) in plasma [HCO3] is necessary to get patient out of danger if there is normal respiratory compensation

Relationship Between pH and [HCO3-]

25

20

15

10

5

7.10 7.20 7.30 7.40

pH

[HC

O3- ]

meq

/L

Small changes in [HCO3-] cause large changes in pH

Therapy in Patients with Severe Acidosis

• Initial goal is to raise the pH to ~7.20

– decreased risk of arrhythmias

– improved cardiac contractility and responsiveness to catecholamines

• Further correction is generally not necessary acutely

– may cause volume overload

– may reduce O2 delivery to the tissues

– may result in hypercarbia

METABOLIC ACIDOSIS:BICARBONATE

THERAPY• Rapid I.V. administration of HCO3 is

important only in patients with severe metabolic acidosis

• Serial Measurements of [HCO3]

• Give oral HCO3 if possible

• Assume volume of distribution of HCO3 to be 50% of lean body weight

METABOLIC ACIDOSIS: BICARBONATE THERAPY

• Chronic renal failure: HCO3, not citrate to avoid Aluminum absorption. Give a large dose for several days to achieve a [HCO3] of approx.20mEq/L. Maintenance dose of about 40 mEq/day

• Chronic RTA 1: 1-2 mEq/Kg/day of Na-K citrate after increasing [HCO3] to desired level

• RTA 2: 10-15 mEq/Kg/day• RTA 4: Correct hyperkalemia

Normal [H+]

40 nanoequivalents per liter

One-millionth the concentration of sodium, potassium and chloride

Modified Henderson-Hasselbach Equation

[H+] = 24pCO2

[HCO3-]

Bicarb-CO2 System in Response to H+ Load

30 mEq H+ ECF

24 mEq/L HCO3

-

ECF22 mEq/L

HCO3-

30 mmol CO2 = 2 mmol/L CO2

Dissolved CO2 1.2 mmol/L + 2 mmol/L = 3.2 mmol/L pCO2 107 mmHg

[H+] = 2410722 = 116 nEq/L pH = 6.94

[H+] = 24 3722

= 39 nEq/L pH = 7.396

No change in VE

.

VE

.

Change in Tubular Fluid pH

pH pH0.2

0

0.4

0.8

1.2

0.20

0.4

0.8

1.2

1.6

2.0

2.4

0 20 40 60 80 100

Proximal Tubule, % Distalconvolution,

%0 100

Ureteralurine

Gottschalk CW, Lassiter WE, Mylle M, Am J Physiol, 198:581, 1960.

Decreased Efficacy of Respiratory Compensation with Worsening Acidosis

Condition HCO3- pCO2 H+ pH

Normal 24 40 40 7.40

Moderately 15 30 50 7.30

Severe

Life Threatening 5 20 100 7.00