Acid-Base Balance Bruce M

Student version

Acid-Base Balance Bruce M. Koeppen, M.D., Ph.D. University of Connecticut Health Center

Introduction:

Analysis of acid-base disorders requires measurement of arterial blood gases, and in particular the Pco2 and - pH. In addition, it is often necessary to measure (or calculate) the [HCO3 ] of plasma, and what is termed the anion gap.

- Blood gases: Arterial blood gases allow analysis of the critical components of the CO2/HCO3 buffer system. + - CO2 + H2O ???H 2CO3 ? H + HCO3

It is from this relationship that the Henderson-Hasselbalch equation is derived:

[HCO − ] [HCO − ] pH = pK' + log 3 or pH = 6.1 + log 3 Pco 0.03Pco α 2 2

Where: pK’ is the apparent pK of the reaction of CO2 and H2O; and α is equivalent to a solubility constant for o CO2 on plasma. The values of 6.1 for the pK’ and 0.03 for α are specific for plasma at 37 C. The normal range for these parameters is as follows:

Pco2 = 33 - 44 mmHg (40 mmHg)* Po2 = 75 - 105 mmHg (100 mmHg) pH = 7.35 - 7.45 (7.40) - [HCO3 ] = 22 - 28 mEq/L (24 mEq/L)

* Normal value used for the problems in this conference.

Acid-base disorders resulting from a primary alteration in the Pco2 are termed respiratory disorders, while - those resulting from a primary alteration in the [HCO3 ] are termed metabolic disorders.

+ - Anion gap: When acid is added to the body fluids, the [H ] increases (pH decreases), and the [HCO3 ] decreases. In addition, the concentration of the anion, which is associated with the acid, will increase. This change in the [anion] provides a convenient way to analyze and help determine the cause of an acid-base disturbance by calculating what is termed the anion gap. The anion gap represents the difference between + - - the concentration of the major plasma cation (Na ) and the major plasma anions (Cl and HCO3 ), and - - reflects the concentration of anions other than Cl and HCO3 that must be present to balance the concentration of Na+.

+ - - Anion Gap = [Na ] - ([Cl ] + [HCO3 ])

Under normal conditions the anion gap is in the range of 8 - 16 mEq/L. An anion gap (i.e., a difference between the concentration of cations and anions) does not actually exist. All cations are balanced by anions. The gap simply reflects the parameters that are measured. In reality:

+ - - [Na ] + [unmeasured cations] = [Cl ] + [HCO3 ] + [unmeasured anions]

©Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center -1-

- - If the anion of the acid is Cl , the anion gap will be normal (i.e., the decrease in [HCO3 ] is matched by an increase in [Cl-]. The metabolic acidosis associated with diarrhea or renal tubular acidosis has a normal anion gap. In contrast, if the anion of the non-volatile acid is not Cl- (e.g., lactate, β- - hydroxybutyrate, etc.), the anion gap will increase (i.e., the decrease in [HCO3 ] is not matched by an increase in the [Cl-], but rather by an increase in the [unmeasured anion]). The anion gap is increased in the metabolic acidosis associated with renal failure, diabetes (ketoacidosis), lactic acidosis, or the ingestion of large quantities of aspirin. Thus, calculation of the anion gap is a useful way to identify the etiology of a metabolic acidosis.

Approach to analyzing acid-base disorders: The following simplified approach can be used to analyze clinical acid-base disturbances.

Ar teria l blood sam p le

pH < 7 .40 pH > 7 .40

Acid os is Alka l os is

- - [HCO3 ] < 24 m Eq / L Pco 2 > 40 m mHg [HCO3 ] > 24 m Eq/ L Pco 2 < 40 m m Hg

Meta bolic Res pira tory Met ab olic Res pirat ory Ac ido sis Ac idos is Al ka l os is Alka l os is

- - Pco 2 < 40 m m Hg [HCO3 ] > 24 m Eq/ L Pco 2 > 40 mm Hg [HCO3 ] < 24 mEq/ L

Resp ir at or y com pen sa tion Ren al com pen s ation Re spira tory com p en sat ion Ren al com p en sat ion - - 1.2 mm Hg ↓ Pco2 3.5 mEq/L ↑ [HCO3 ] 0.7 mm Hg ↑ Pco2 4 - 5 mEq/L ↓ [HCO3 ] - - per 1 mEq/L ↓ in [HCO3 ] per 10 mm Hg ↑ in Pco2 per 1 mEq/L ↑ in [HCO3 ] per 10 mmHg ↓ in Pco2

Recommended Reading: pp. 133 - 154. Koeppen and Stanton: Renal Physiology, 3rd ed., Mosby, 2001.

1. In order to stay in acid-base balance a 70 kg man must excrete 1mEq/kg/day of acid in the urine. If the urine contained no buffers, and if the minimum pH of urine is 4.0, how much acid could this man excrete if his urine output was 1 L/day? What impact would this have on his ability to maintain acid-base balance?

©Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center -2-

2. A 40 year old man has profuse diarrhea for 2 days. At the end of this time the following laboratory data are obtained (his body weight is 60 kg).

Serum [Na+] = 140 mEq/L (nl = 135 – 147 mEq/L) Serum [K+] = 3.0 mEq/L (nl = 3.5 – 5.0 mEq/L) Serum [Cl-] = 110 mEq/L (nl = 95 – 105 mEq/L)

- Serum [HCO3 ] = 15 mEq/L (nl = 22 – 28 mEq/L)

A. What will be the mechanisms by which his body will compensate for the decreased serum - [HCO3 ] in this man?

- - B. If the man’s serum [HCO3 ] was 24 mEq/L prior to the onset of his diarrhea, how much HCO3 - did he lose in his feces? (Hint: HCO3 is located in both the ECF and ICF, although the ICF concentration is less than that of the ECF concentration. To estimate the total amount of - - HCO3 in the body fluids assume that the volume of distribution of HCO3 is 50% of body weight or 30 L).

C. Estimate the ECF pH if respiratory compensation did not occur in this individual. (i.e., assume

that the Pco2 is fixed at its normal value of 40 mmHg).

D. Estimate the Pco2 and ECF pH after appropriate respiratory compensation.

3. Simple acid-base disorders can be diagnosed using the scheme outlined above (see page 2). What simple acid-base disorders are represented by the following arterial blood gas determinations (distinguish between acute and chronic respiratory acid-base disorders)?

- [HCO3 ] Pco2 pH mEq/L (mm Hg) Diagnosis Normal 7.40 24 40 A 7.23 10 25 ______B 7.46 30 44 ______

©Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center -3-

C 7.37 28 50 ______D 7.66 22 20 ______E 7.34 26 50 ______F 7.54 18 22 ______

4. An 18 year old man with insulin-dependent (Type I) diabetes mellitus is seen in the emergency department. He reports not taking his insulin during the previous 24 hours because he did not feel well and was not eating. He now has weakness, nausea, thirst, and frequent urination. His blood pressure is 100/60 mmHg supine and 80/50 erect. His pulse rate increases from 100/min. supine to 110/min. when erect. On physical examination he is found to have deep and rapid respiration (Kussmal respiration). At 1 AM the following laboratory data are obtained:

Plasma [Na+] = 130 mEq/L (nl = 135 - 147 mEq/L) Serum [Cl-] = 95 mEq/L (nl = 95 - 105 mEq/L) Plasma [K+] = 6.5 mEq/L (nl = 3.5 - 5.0 mEq/L

- Plasma [HCO3 ] = 7 mEq/L (nl = 22 - 28 mEq/L) Blood pH = 6.99 (nl = 7.35 - 7.45)

Arterial Pco2 = 18 mmHg (nl = 33 - 44 mm Hg) Plasma [glucose] = 600 mg/dL (nl = 70 - 110 mg/dL) Urine contains glucose and ketones (nl = absent)

The diagnosis of diabetic ketoacidosis is made, and the man is admitted to the hospital. Saline is administered intravenously, and insulin therapy begun. The results of therapy are illustrated below.

+ - Time Serum [K ] Plasma pH Serum [HCO3 ] Serum [glucose] (mEq/L) (mEq/L) (mg/dL) 1:00 AM 6.5 6.99 7 600 3:00 AM 4.5 7.10 12 400 4:00 AM 4.0 7.16 14 300 5:00 AM 3.5 7.20 16 250 7:00 AM 3.5 7.24 18 200

A. What type of acid-base disorder does this man have? What is the anion gap, and what is its significance?

B. What can you conclude about K+ balance in this man?

©Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center -4-

C. Explain why the serum [K+] fell during the first hour of treatment.

5. A previously healthy 28-year old is seen in the emergency room with right side flank pain. Shortly after arrival, he passes a small kidney stone. He denies any significant previous renal or gastrointestinal problems. There is a family history of kidney stones. The results of laboratory tests done in the emergency room include the following:

Plasma [Na+] = 137 mEq/L (nl = 135 - 147 mEq/L) Plasma [K+] = 3.1 mEq/L (nl = 3.5 - 5.0 mEq/L) Plasma [Cl-] = 111 mEq/L (nl = 95 - 105 mEq/L)

- Plasma [HCO3 ] = 13 mEq/L (nl = 22 - 28 mEq/L) Arterial pH = 7.28 (nl = 7.35 - 7.45)

Arterial Pco2 = 28 mm Hg (nl = 33 - 44 mm Hg Urine pH = 6.4

A. What is the acid base disorder, and what is its most likely cause?

- B. What is the mechanism for the decreased serum [HCO3 ] in this man?

6. A 50 year old man with a history of a duodenal ulcer is admitted to the hospital after several days of intermittent vomiting. His physical examination reveals signs of volume depletion (orthostatic changes in blood pressure, sunken eyes, flat neck veins, and poor skin turgor). Laboratory tests reveal:

Serum [Na+] = 140 mEq/L (nl = 135 - 147 mEq/L) Serum [K+] = 3.0 mEq/L (nl = 3.5 - 5.0 mEq/L) Serum [Cl-] = 98 mEq/L (nl = 95 - 105 mEq/L)

- Serum [HCO3 ] = 32 mEq/L (nl = 22 - 28 mEq/L) Arterial pH = 7.51 (nl = 7.35 - 7.45)

Arterial Pco2 = 41 mm Hg (nl = 33 - 44 mm Hg) Urine [Na+] = 5 mEq/L Urine [Cl-] = 5 mEq/L Urine [K+] = 40 mEq/L Urine pH = 5.5

A. What is the acid-base disorder?

B. How do you explain the urine electrolyte excretion pattern (why are the urine concentrations of Na+ and Cl- low, and why is the urine acidic)? What do these values tell you about the renal response to the metabolic alkalosis?

C. How do you explain this man’s hypokalemia?

D. How would you treat this man in order to correct his acid-base disorder?

7. A 12 year old girl presents to the emergency room with an acute asthmatic attack. Initial arterial blood gas values on room air are:

- Serum [HCO3 ] = 22 mEq/L (nl = 22 - 28 mEq/L) Arterial pH = 7.55 (nl = 7.35 - 7.45)

Arterial Pco2 = 28 mm Hg (nl = 33 - 44 mm Hg)

Arterial Po2 (room air) = 60 mm Hg (nl = 75 - 105 mm Hg)

A. What is the acid-base disorder when she presents to the emergency room?

Five hours later after receiving appropriate therapy (including 40% O2 by mask), she is tired and has quiet breath sounds on auscultation. Repeat arterial blood gases are obtained.

- Serum [HCO3 ] = 22.4 mEq/L (nl = 22 - 28 mEq/L) Arterial pH = 7.32 (nl = 7.35 - 7.45)

Arterial Pco2 = 45 mm Hg (nl = 33 - 44 mm Hg)

Arterial Po2 (room air) = 60 mm Hg (nl = 75 - 105 mm Hg)

B. What is the acid-base disorder after therapy, and how do you account for the change in the patient’s condition?

8. A 48 year old man is admitted to the hospital with renal failure secondary to diabetes mellitus. The following laboratory data is obtained.

Serum [Na+] = 135 mEq/L (nl = 135 - 147 mEq/L) Serum [K+] = 5.2 mEq/L (3.5 – 5.0 mEq/L) Serum [Cl-] = 100 mEq/L (nl = 95 - 105 mEq/L)

- Serum [HCO3 ] = 15 mEq/L (nl = 22 – 28 mEq/L) Serum [creatinine] = 8.2 mg/dL (nl = 0.6 – 1.2 mg/dL)

A. What is the acid-base disorder, and what is the anion gap?

- B. How much HCO3 would have to be administered to this man in order to normalize his serum - [HCO3 ] to 24 mEq/L (assume a body weight of 55 kg)? Once normalized, and assuming he - continues to have the same daily production of non-volatile acid, how much HCO3 would have to be administered on a daily basis to maintain a normal serum - [HCO3 ]?