Acid & Base

John R. Foringer, M.D.

Division of Renal Diseases and Hypertension
Section of Critical Care Nephrology
john.r.foringer@uth.tmc.edu
(713) 500-6868
 152 104 30
3.6 15 1.0 ABG: 7.42/24/115

Why do we call Normal Saline normal?

What is the Na concentration of ½ NS with 2 Amps of NaHCO3?

Simple Acid-Base Disturbances

pH = pK’ + log10 [HCO3]

(0.0301)(paCO2)

pH = 6. 1 + log ( metabolic component)

(respiratory
component)

_
HCO3 & CO2 = pH

_
CO2 & HCO3 = pH
 Understanding Normal Acid-Base Handling

 Metabolic processes in the body lead to the production of acid

 The catabolism of glucose and fatty acids produces CO 2 and H2O,

effectively carbonic acid.

 About 1 mEq/Kg body weight of H+ is produced a day in the body.

 Respiratory elimination of CO2 and cellular buffers handle this acid load.

 Renal excretion of acid must be maintained.

 Understanding Normal Acid-Base Handling

 The Kidney
• Reabsorbs 4500 mEq of HCO3 per day
• Generates new HCO3 to replenish buffer stores
• The Proximal tubule does most of the work
 Luminal membrane carbonic anhydrase

This is stimulated
by an  PCO2
 Understanding Normal Acid-Base Handling

 The Kidney
• The Distal tubule reclaims the remainder of the HCO3
 Uses cytoplasmic carbonic anhydrase
 Also eliminates H+ = to the nonvolatile acid production

Stimulated by aldosterone
and  PCO2

The Kidney will excrete NH4 to eliminate the H+

 Normal renal processes of acid handling

Proximal tubule Distal Nephron / Collecting Duct

HCO3 - H+ + HCO3- CO2 + H2O

HCO3-
HCO3- H+ secretion and HCO3-
regeneration
H+

Urine
 To Blood Kidney
Bicarbonate CO2 + H2O
reabsorption HCO3
HCO3- HCO3- + H+ H+ CO2

Titratable acid CO2 + H2O

formation
HPO42-
HCO3 -
HCO3- + H+ H+ H2PO4-

Ammonium Glutamine
excretion
HCO3- HCO3- NH4+ NH4+
 Understanding Normal Acid-Base Handling

 Other organs involved in acid-base regulation

• The Gut
 Stomach adds H+ to the gut lumen
 Below the pylorus - HCO3 is added to the gut

Proton-secreting cell Bicarbonate-secreting cell

Gut Lumen
H+ HCO3

CO2 +H2O  HCO3 + H+ CO2 +H2O  HCO3 + H+

HCO3 H+
Blood
 Understanding Normal Acid-Base Handling

 Other organs involved in acid-base regulation

• The Liver
 Detoxification of NH4+
• Hepatic synthesis of urea then urinary secretion (consumes
HCO3-).

• Hepatic synthesis of glutamine from NH4+ then conversion of

glutamine in the kidney to NH4+ (renal ammoniagenesis) and
secretion in the urine (no HCO3- consumption).
Simple Acid-Base Disorders

 Metabolic Acidosis

 Metabolic Alkalosis

 Respiratory Acidosis

 Respiratory Alkalosis
 Mixed Acid-Base Disturbances

• Definition
– Combination of two or more of the 4
simple disturbances (primary)
• Examples
– Mixed respiratory-metabolic disorders
– Mixed metabolic disorders
 Compensatory Responses in Simple
Acid-Base Disorders

Disorder Primary Secondary Response

Abnormality
Respiratory
Acidosis Hypoventilation HCO3- - generation
(cellular buffering &
renal)
Alkalosis Hyperventilation HCO3- - consumption
(cellular buffering &
renal)
Metabolic
Acidosis Loss of HCO3- or Increase in ventilation
gain of H+ (plus chemical buffering)
Alkalosis Gain of HCO3- or Decrease in ventilation
loss of H+ (plus chemical buffering)
 What is the Base Excess?
• Proposed as an indicator of acid-base status that was
not influenced by PaCO2
• It is the sum of the concentration of buffer anions
– HCO3 and hemoglobin
• Problem is this only works in vitro
• In vivo as the PCO2 rises the Δ HCO3 is attenuated by
flux into the interstitial fluid compartment

• Now to overcome this: Standard Base Excess

– SBE = 0.93 ([HCO3] -24.4) + 13.79 (pH -7.4)
– Estimates the amount of base needed to restore the
metabolic acid-base status to normal in the entire
extracellular fluid compartment
 A New Trend in Trauma Surgery

In 3,102 trauma patients. Serum HCO3 measurement shows a strong linear correlation
and similar predictive ability compared with the arterial BD. Serum HCO3 may be safely
and accurately substituted for arterial BD measurement in critically injured patients.

FitzSullivan et al., Am J of Surg. Volume 190, Issue 6, Pages 827-994 (December 2005)
Metabolic Acidosis
Why Acidosis is Bad
Changes in Cardiac Output with Declining pH

Kraut et al., AJKD, 38 Pages 703-727 (October 2001)

 Evaluating a Low HCO3

• No acid/base disorder can be diagnosed without an ABG

• With every Chem 7 there is an anion gap and a calculated osm

Anion Gap = Na - (HCO3 + Cl)

Serum Osm = 2(Na) + BUN + Glc

2.8 18
Assessment of a Low Serum HCO3
Classification of Metabolic Acidosis
 Lactic Acid
• Type I – proportional increase in lactate and pyruvate
• Type II – Lactate higher than pyruvate
• Type A – tissue hypoxia
• Type B – arises from malignancy, liver disease, inborn errors of
metabolism, or ingestion of toxins
 Treatment of Metabolic (Lactic) Acidosis

• Treatment with NaHCO3

– An estimate of replacement
• Dose of bicarbonate = (0.5 X BW) X (desired HCO3 – current HCO3)
• Goal of replacement is a pH above 7.2
 Treatment of Lactic Acidosis
• Should we treat lactic acid with HCO3 ?
– ↑PFK activity (rate limiting enzyme of glycolysis)
– Acidosis ↓and alkalosis ↑ lactate production
– ↑ CO2 production
– Impairs cardiac performance
– Large fluid load

 What about Dialysis?

 Add HCO3
 Remove lactic acid (MW 90.08 vs β2-microglobulin 11,815)
 Treatment of Lactic Acidosis with HCO3

Kraut et al., AJKD, 38 Pages

703-727 (October 2001)
 Treatment of Ketoacidosis with HCO3

Kraut et al., AJKD, 38 Pages 703-

727 (October 2001)
 Treatment of Lactic Acidosis

• Dichloroacetate
– Promotes oxidation of lactate (pyruvate dehydrogenase) →→ acetyl-coenzyme A
+ carbon dioxide
– 252 patients with lactic acidosis, placebo-controlled, randomized trial of
intravenous sodium dichloroacetate
– Only 12 percent of the dichloroacetate-treated patients and 17 percent of

the placebo patients survived to be discharged

– Statistically significant but clinically unimportant changes in arterial-
blood lactate concentrations and pH and fails to alter either
hemodynamics or survival

Stacpoole P., et al. N Engl J Med 1992; 327:1564-1569, Nov 26, 1992.
 Treatment of Lactic Acidosis

• THAM (0.3 N tromethamine) Tris-Hydroxymethyl Aminomethane

– Sodium-free solution
– Buffers both metabolic acids (THAM + H+ →→ THAM+)
and respiratory acids (THAM + H2CO3 →→ THAM+ + HCO3-)
[proton and CO2 scavenger]
– Limits carbon dioxide generation and increases both extracellular
and intracellular pH
– Serious side effects
• including hyperkalemia, hypoglycemia, ventilatory depression, local
injury in cases of extravasation, and hepatic necrosis in neonates
• Renal excretion
 Treatment of Lactic Acidosis
• Carbicarb
– Equimolar concentrations of sodium bicarbonate and sodium
carbonate
– Carbonate is a stronger base (CO32- + H+ →→ HCO3-)
– Carbonate ion can react with carbonic acid, thereby
consuming carbon dioxide
• (CO32- + H2CO3 →→ 2HCO3-).
– Increased blood and intracellular pH with little or no rise in
the arterial or venous partial pressure of carbon dioxide
– Risks of hypervolemia and hypertonicity

Bersin RM. Circulation 1988;77:227-233.

Kucera RR. Crit Care Med 1989;17:1320-1323.
 NaCl vs. NaHCO3 vs. Carbicarb vs. THAM

Arterial ([H+]a) and mixed venous ([H+]v) hydrogen ion concentrations at baseline (B), during ventricular fibrillation (VF), and during cardiopulmonary
resuscitation (CPR). Open circles, sodium chloride (NaCl) controls; solid circles, bicarbonate; solid squares, Carbicarb; open squares, THAM. [up arrow]
Indicates the timing of buffer dose administration.

Bar-Joseph, et al., Crit Care Med, Volume 26(8), August 1998, pp 1397-1408.
 NaCl vs. NaHCO3 vs. Carbicarb vs. THAM

Arterial lactate, and arterial bicarbonate (HCO3) concentrations during control measurements (C), during ventricular fibrillation (VF), and during
cardiopulmonary resuscitation (CPR). Mean +/- SEM values. Open circles, sodium chloride (NaCl) controls; solid circles, bicarbonate; solid
squares, Carbicarb; open squares, THAM. [up arrow]Indicates the timing of buffer dose administration

Bar-Joseph, et al., Crit Care Med, Volume 26(8), August 1998, pp 1397-1408.
 THAM in Acute Lung Injury

KALLET et al., Am. J. Respir. Crit. Care Med., Volume 161, Number 4, April 2000, 1149-1153.
 THAM in Acute Lung Injury

KALLET et al., Am. J. Respir. Crit. Care Med., Volume 161, Number 4, April 2000, 1149-1153.
 Tromethamine Buffer Modifies the Depressant Effect of Permissive
Hypercapnia on Myocardial Contractility in Patients with Acute
Respiratory Distress Syndrome
• Several studies have indicated that at the same extracellular pH, hypercapnic acidosis
induces more myocardial depression and decrease in intramyocardial pH than
metabolic acidosis.

• Hypercapnia causes rapid diffusion of CO2 into myocytes, and the resultant
intracellular acidosis impairs myocardial contractility.

•This explains why attempts to correct respiratory acidosis with CO2-generating

buffers such as sodium bicarbonate may simply worsen intramyocardial acidosis.

• Only 12 patients

THOMAS WEBER, Et al.

Department of Anesthesiology and General Intensive Care, University of Vienna, Austria; and Department of
Anesthesiology, Division of Critical Care, College of Physicians and Surgeons of Columbia University, New York, New York
Am. J. Respir. Crit. Care Med., Volume 162, Number 4, October 2000, 1361-1365
 Evaluating a low serum HCO3

Non-elevated Anion Gap acidosis:

 Hyperchloremia

 Failure of the kidney to conserve bicarbonate or to secrete H

Renal tubular acidosis

 Gastro-intestinal loss of HCO3

 Disorders Responsible for
Hyperchloremic Acidosis
(Normal
(Normal Anion
Anion Gap)
Gap)

 Gastrointestinal Bicarbonate Loss

 Diarrhea
 Renal Acidification Defects
 Proximal, classical distal RTA, and hyperkalemic distal
RTA
 Early chronic renal failure
 Ingestion or administration of acid, hyperalimentation
 Drugs
 Evaluating a Low Serum HCO3

 Diarrhea
 Below the pylorus - HCO3 is added to the gut with a
gain of H+ to the blood

Proton-secreting cell Bicarbonate-secreting cell

Gut Lumen
H+ HCO3

CO2 +H2O  HCO3 + H+ CO2 +H2O  HCO3 + H+

HCO3 H+
To Blood
 Evaluating a Low Serum HCO3

 Renal Tubular Acidosis

 Impaired ammonium excretion can be demonstrated by the urine

net negative charge (anion gap):

urine Na + + urine K+ + urine NH4+ = urine Cl-

UNa +
+ UK+ - UCl- = -UNH4+

 Normally: UNa +
+ UK+ - UCl- = -UNH4+ = < -20 in the face of acidemia

 In RTA’s ammonium excretion is impaired, therefore

In RTA’s: UNa + + UK+ - UCl- = -UNH4+ = 0

( range +20 to –80)
 Normal physiology of acid excretion:
Proximal tubule

• Responsible for reabsorption of the HCO3

filtered at the glomerulus; bulk reabsorption
Blood Tubular fluid
HCO3-
H 2O Carbonic anhydrase

Na+ H+ + OH- Na+ CO2 + OH-

Carbonic
H+ H+ H2O
HCO3- anhydrase

H2CO3
 Proximal Renal Tubular Acidosis

Proximal tubule Distal Nephron / Collecting Duct

HCO3 - H+ + HCO3- CO2 + H2O

HCO3-
HCO3-
Impaired (diminished) H+ secretion and HCO3-
HCO3- absorption
regeneration
H+
HCO3-
 Distal RTA’s

 Impaired (diminished) H+ secretion by the distal

nephron (CCT) will result in either:

• Classic Distal RTA:

Direct impairment of H+ ion secretion or from H+ backleak

• Hyporeninemic Hypoaldosteronemic RTA (Type IV RTA):

Inadequate aldosterone effect
 Distal RTA
Proximal tubule Distal Nephron / Collecting Duct
H+ secretion and HCO3- regeneration

HCO3- HCO3- + H+ CO2 + H2O

HCO3-
HCO3-
A. Impaired (diminished) H+
secretion hence diminished HCO3-
H+ regeneration

B. Back-leak can also

diminish H+ secretion
 NH4 in urine - AMPHOTERICIN
Metabolic Alkalosis
 Evaluating an elevated Serum HCO3-

 Metabolic alkalosis

 Respiratory acidosis

Therefore, diagnosis requires a concomitant arterial pH.

 Evaluating an Elevated Serum HCO3-

 Causes of Metabolic Alkalosis

• Effective ECV Contraction resulting in secondary
Hyperreninemic Hyperaldosteronism

• Hypermineralocorticoidism resulting in ECV

expansion and Hypertension.

• Exogenous Alkali Loads

 Evaluating an Elevated Serum HCO 3-

Proximal tubule Distal Nephron / Collecting Duct

Low GFR
Impaired
HCO3 - H+ + HCO3- CO2 + H2O
filtration

HCO3-
Increased -
HCO3-
absorption
H+
HCO3-
Evaluating an Elevated Serum HCO3
Evaluating an Elevated Serum HCO3
Evaluating an Elevated Serum HCO3
 Treatment of Metabolic Alkalosis

 Low Urine [Cl-] (< 20 mEq/L)

• 0.9% NaCl
• Potassium Chloride

 High Urine [Cl-] (>25 mEq/L)

• Cause specific (surgery, angioplasty,
specific drug therapy)
Respiratory Acid-Base Disorders
 Respiratory Acid-Base Disorders
 Alkalosis
– Central nervous system lesions, pregnancy,
endotoxemia, salicylates, hepatic failure,
hypoxemia, anxiety, pain

Compensation:
Respiratory alkalosis: Acute resp alkalosis
HCO3  2 mEq/L per 10 mmHg  PCO2
Chronic resp acidosis
HCO3  5 mEq/L per 10 mmHg PCO2
 Respiratory Acid-Base Disorders
 Respiratory Acidosis
• Central - drugs (anesthetics, morphine, sedatives), stroke, infection
• Airway - obstruction, asthma
• Parenchyma - emphysema, pneumoconiosis, bronchitis, adult respiratory
distress syndrome
• Neuromuscular - poliomyelitis, kyphoscoliosis, myasthenia, muscular
dystrophies
• Miscellaneous - obesity, hypoventilation

Compensation:
Respiratory acidosis: Acute respiratory acidosis
HCO3  1 mEq/L per 10 mmHg  PCO2
Chronic respiratory acidosis
HCO3  4 mEq/L per 10 mmHg  PCO2
 Normal Lab Values

Sodium (Na) 140 mEq/L

Potassium (K) 4.0 mEq/L
Chloride (Cl) 100 mEq/L
Bicarbonate (HCO3) 24 mEq/L

Blood Gas: pH 7.44

PaCO2 40 mmHg

Normal Anion Gap: 12

 35-year-old man admitted to the hospital with pneumonia and the following
lab values:

ARTERIAL BLOOD GASES SERUM ELECTROLYTES

pH 7.52 Na + 145 mEq/L
PaCO2 30 mm Hg K+ 2.9 mEq/L
PaO2 62 mm Hg Cl- 98 mEq/L
HCO3- 22 mEq/L

Does the patient have an Alkalosis or Acidosis? Alkalemia, pH is 

Respiratory: the PaCO2

Is it respiratory or metabolic? is low as is the HCO3

Is the disorder compensated or not?

The answer:
 35-year-old man admitted to the hospital with pneumonia and the following
lab values:

ARTERIAL BLOOD GASES SERUM ELECTROLYTES

pH 7.52 Na + 145 mEq/L
PaCO2 30 mm Hg K+ 2.9 mEq/L
PaO2 62 mm Hg Cl- 98 mEq/L
HCO3- 22 mEq/L

Does the patient have an Alkalosis or Acidosis? Alkalemia, pH is 

Respiratory: the PaCO2

Is it respiratory or metabolic? is low as is the HCO3

Yes, the predicted HCO3 is

Is the disorder compensated or not?
22 mEq/L
How do we know what the HCO3 should be?
Remember, the HCO3 will  2 mEq/L for every 10 mmHg
the PaCO2  as acute compensation.

The answer: Compensated Respiratory Alkalosis

 The following values are found in a 65-year-old patient who has had poor oral
intake for the last week.

ARTERIAL BLOOD GASES Serum Electrolytes

pH 7.51 Na + 155 mEq/L
PaCO2 53 mm Hg K+ 5.5 mEq/L
Cl- 90 mEq/L
HCO3- 40 mEq/L

Does the patient have an Alkalosis or Acidosis? Alkalemia, the pH is 

Metabolic: the HCO3 is 

Is it respiratory or metabolic? and the PaCO2 is 

Is the disorder compensated or not? Yes, the PaCO2

should be 55 mmHg
How do we now what the PaCO2 should be?
The predicted PaCO2 should be the HCO3 plus 15.
In this example the HCO3 is 40 thus the PaCO2 should be near 55.

The answer: Compensated Metabolic Alkalosis

 68-year-old man with emphysema

Arterial blood gas Serum Electrolytes

pH 7.34 Na+ 138
PaCO2 70 mm Hg K+ 4.7
Cl- 91
HCO3- 36

Does the patient have an acidosis or alkalosis? Acidemia

Is it metabolic or respiratory? Respiratory

Is the respiratory acidosis compensated for? Yes, the HCO3 should be 36 mEq/L

Remember the HCO3 will  4 mEq/L for every 10 mm Hg  the

PaCO2 in chronic respiratory acidosis.
In this case the PaCO2 by 30 mmHg thus the HCO3  by 12 mEq/L
In acute respiratory acidosis the HCO3 will 1 mEq/L.

The answer: Compensated Respiratory Acidosis

 What is (are) the acid-base disorder(s) evident in the following values, from a 27-year-old woman with acute renal
failure?

Arterial Blood Gas Serum Electrolytes

pH 7.32 Na+ 144 mEq/L
PaCO2 23 mm Hg K+ 4 mEq/L
Cl - 108 mEq/L
HCO3- 10 mEq/L

Does the patient have an acidosis or alkalosis? Acidemia

Is it metabolic or respiratory? Metabolic

Now that we have determined a metabolic High Anion Gap at 26

acidosis, is the anion gap normal or elevated?
Remember the anion gap = Na - (HCO3 + Cl) and normal is 12

Now that we have determined a high anion The drop in HCO3

gap what made the anion gap go up?

So does the drop in HCO3 equal

Yes, the  HCO3 (14) = the  Anion gap (14)
the increase in the anion gap?

Is the respiratory compensation adequate? Yes, the PaCO2 should be 23 mmHg

Use Winter’s Formula to predict the PaCO 2 with a metabolic acidosis: 1.5 (HCO 3) + 8 (2)

The answer: Compensated High Anion Gap Metabolic Acidosis

 55-year-old-man seen for newly diagnosed renal failure

Arterial blood gas Serum chemistries

pH 7.38 Na+ 140 Cr 1.9
PaCO2 30 K+ 3.2 HGB 8.0
Cl- 115
HCO3- 14

Does the patient have an acidosis or alkalosis? Acidemia

Is it metabolic or respiratory? Metabolic

Now that we determined a metabolic acidosis The anion gap

what do we check next? The anion gap = 11
Remember the anion gap = Na - (HCO3 + Cl) and normal is 12

Thus this is a normal anion gap acidosis or a hyperchloremic

acidosis, notice the Chloride is 115 mEq/L.

Is the metabolic acidosis compensated? Yes, the PaCO2 should be 29

Remember Winter’s Formula, 1.5 (HCO3) +8 (2)

The answer: Compensated Hyperchloremic Metabolic Acidosis

 27-year-old woman with acute renal failure

Arterial blood gas Serum electrolytes

pH 7.12 Na+ 140
PaCO2 13 mm Hg K+ 4.0
Cl- 115
HCO3- 5

Does the patient have an acidosis or alkalosis? Acidemia

Is it metabolic or respiratory? Metabolic

So, what is the anion gap? Anion gap = 20

Is the  anion gap = to the  HCO3? NO,  anion gap = 8

 HCO3 = 19

Thus the  HCO3 > the  anion gap, this means the HCO3 went down more than the
anion gap went up.
Something made the HCO3 drop further, the two disorders that decrease the HCO3
even further are:
Hyperchloremic metabolic acidosis or compensation for a respiratory alkalosis.

Is the respiratory compensation adequate? Yes, the predicted PaCO2 = 15 mmHg

The Answer: Compensated High Anion Gap Metabolic Acidosis with a

Hyperchloremic Metabolic Acidosis
 19yo college student was found by roommate on floor.
Diaphoretic and comatose.
BP 150/80, P 155/min and regular, RR 40/min

152 104 30
3.6 15 1.0 ABG: 7.42/24/115

Does the patient have an acidosis or alkalosis? Don’t know the pH is normal

So, where do we start? A good place to start is the anion gap

The anion gap = 33
Thus there is at least a high anion gap metabolic acidosis

So, now what? Check the  HCO3 and  anion gap

The  HCO3 = 24 - 15 = 9
The  anion gap = 33 - 12 = 21
Thus they are not equal

The anion gap went up more than the HCO3 went down.
So, what does this mean?
Thus there is something keeping the HCO3 up.
 19yo college student was found by roommate on floor.
Diaphoretic and comatose.
BP 150/80, P 155/min and regular, RR 40/min

152 104 30
3.6 15 1.0 ABG: 7.42/24/115

This suggest there is either a

So, we determined the  anion gap >  HCO3 Metabolic alkalosis or a
Respiratory acidosis with
compensation, both will cause
the HCO3 to be high

So, check Winter’s formula to The predicted PaCO2 is 30

determine the respiratory This is higher than the measured PaCO2,
compensation. [1.5 (HCO3) + 8] thus the patient has a respiratory alkalosis

The answer: High anion gap met acidosis with met alkalosis with resp alkalosis