Acid-Base Problem Solving

CASE 1:FEVER AND SEVERE DIARRHEA IN A MAN WITH CROHN DISEASE A 34-year-old man has had Crohn disease for 12years. He presented initially with ileitis and has had 3surgeries for obstructive complications. Ileum resectionhas resulted in bile salt and fat malabsorption. Recently,the Crohn disease has spread to the large bowel. For thelast 2 years, he has also had seronegative spondyloarthropathy-another complication of Crohn disease.His current medications include sulfasalazine, oralprednisone, azathioprine, cholestyramine (for bile saltmalabsorption), and NSAIDs.He now presents with a temperature of 38.5C(101.5F), a heart rate of 104 beats per minute (with regularrhythm), a respiration rate of 22 breaths per minute, andblood pressure of 100/60 mm Hg. Pulse oximetry suggestsnormal oxygen saturation. The chest radiograph findingsare consistent with bacterial pneumonia. Because the patientis immunosuppressed, cefuroxime and erythromycinare started. A nasogastric tube on low intermittent suctionis placed to compensate for vomiting and ileus.Three days after admission, the patient's temperaturedecreases and severe diarrhea develops; blood culture resultsare positive for penicillin-resistant Streptococcus pneumoniae.Erythromycin is discontinued. Results of a stoolexamination, which are available 24 hours later, are positivefor Clostridium difficile.Because of continued tachycardia and tachypnea, anarterial blood gas analysis and an electrolyte panel areordered. Blood gas analysis reveals the following values:

• p^H: 7.33.
• PCO₂: 20 mm Hg.
• Bicarbonate (calculated): 12 mEq/L.Electrolyte levels are as follows:
• Sodium: 138 mEq/L.
• Potassium: 2.9 mEq/L.
• Chloride: 122 mEq/L.
• Bicarbonate (measured): 14 mEq/L.

The albumin level is 2.5 g/dL.Application of the 5 rules (

Table 1

) reveals thefollowing:

1.

Acidemia is present because the systemic p

^H

is lessthan 7.40 (7.33).

2.

The acidemia represents a metabolic process becausethe bicarbonate level is less than 25 mEq/L. If this were aprimary respiratory process, the PCO

₂

would have beenelevated (greater than 44 mm Hg), not decreased as it ishere (20 mm Hg).

3.

The anion gap is normal {(138 -[122 + 14]) + 2.5 (toadjust for the 1-g drop in albumin) = 4.5}.

4.

The bicarbonate level decreased from 25 mEq/L to 12mEq/L (a total decrease of 13). To compensate, the PCO2should have decreased by 1.3 X 13, or 17. A PCO

₂

that is17 less than normal (40 mm Hg) would be 23 mm Hg.The fact that the PCO

₂

here is more than 2 mm Hg lowerthan this value (20 mm Hg) indicates that the patient alsohas a respiratory alkalosis.

5.

The bicarbonate level is 11 mEq/L lower than normal,but the chloride level (122 mEq/L) is approximately22 mEq/L higher than normal (100 mEq/L). This ishigher than the "one-to-one" rule would have predictedand thus indicates that this patient also has a metabolicalkalosis.The patient has a triple acid-base disturbance:non-anion gap metabolic acidemia (from diarrhea), respiratoryalkalosis (from tachypnea), and metabolic alkalosis(from vomiting and nasogastric tube suction).Remember that non-anion gap metabolic acidosisis a result of either gut loss of bicarbonate from diarrheaor renal loss of bicarbonate from renal tubular acidosis.Measurement of electrolytes in a random urine sampleconfirms the suspicion that diarrhea secondary to the patient'sC

difficile

colitis is responsible for the acidosis.Electrolyte concentrations are:

• Sodium: 9 mEq/L.
• Potassium: 15 mEq/L.
• Chloride: 60 mEq/L.

Always measure urinary electrolytes to determinecharge neutrality-there should never be "sparks" in theurine! This patient's urine has 24 positive charges (sodium+ potassium) and 60 negative charges (chloride). Becauseof his systemic acidemia (p

^H

, 7.33), the kidney is excretingexcess acid as ammonium chloride (NH

₄

Cl), a titratableacid. This excretion is consistent with normal aniongap metabolic acidosis that results from the gut loss of bicarbonatewith an appropriate renal response (titratableacid excretion in the urine greater than 20 mEq/L).

Outcome of this case

. Oral vancomycin andcholestyramine were prescribed. The volume of stool improvedover the next 5 days. Venous blood gases were analyzedto avoid further arterial punctures (

Box

). The bicarbonateconcentration increased from 12 to 22 mEq/L,and the p

^H

increased from 7.33 to 7.42. As the patient's pneumonia subsided, the PCO

₂

returned to normal. Thealkalosis gradually resolved once the nasogastric tube wasremoved, intravenous 0.9% saline was discontinued, andvomiting ceased.

CASE 2:

VOMITING, TACHYCARDIA, ANDHYPERGLYCEMIA IN A WOMAN WITHTYPE 1 DIABETES

A 26-year-old woman with type 1 diabetes presentswith tachycardia, fever, vomiting, and hyperglycemia.Three weeks earlier she contracted a viral illness for whichshe took aspirin 4 or 5 times a day. In the last week shehas had abdominal discomfort associated with nausea andvomiting, which have precluded any oral intake and ledher to stop taking insulin.Her diabetic control has been variable; 2 months earlierher hemoglobin A

_1c

was 7.8%. She has had 2 episodesof ketoacidosis in the preceding year, both secondary tourinary tract infections.The patient is oriented but anxious and diaphoretic.Temperature is 37.7C (99.9F); supine heart rate, 122beats per minute with regular rhythm; upright heart rate,136 beats per minute with regular rhythm; respirationrate, 14 breaths per minute; blood pressure, 100/60 mmHg supine and 94/60 mm Hg upright. Pulse oximetrysuggests normal oxygen saturation. Heart examination revealsa soft flow murmur at the cardiac apex. There is diffuseabdominal tenderness without guarding, rebound, orrigidity. Stool is guaiac-positive. The patient has mild backgroundretinopathy. An arterial blood gas analysis revealsthe following values:

• p^H: 7.40.
• PCO₂: 36 mm Hg.
• Bicarbonate (calculated): 25 mEq/L.Electrolyte concentrations are as follows:
• Sodium: 140 mEq/L.
• Potassium: 4.2 mEq/L.
• Chloride: 95 mEq/L.
• Bicarbonate (measured): 25 mEq/L.

The albumin level is normal.Because this patient's p

^H

is in the normal range,it almost seems as if the 5 rules are not necessary. Nothingcould be further from the truth. When a primaryprocess is compensated for by a secondary acid or basedisturbance, the change in pH caused by the primaryprocess is mitigated but not completely normalized. However,when 2 primary processes compete, they can "meetin the middle," so to speak, and the normal pH can bedeceiving. That is why, especially in sick patients, rule 3,

"Always calculate the anion gap,"

is essential to clinicalsuccess.Even though rules 1 and 2 are moot here, the aniongap is elevated at 20 (140 -[25 + 95]). This is diagnosticof an anion gap metabolic acidosis. Since the p

^H

is normaldespite an elevated anion gap, there must be an equal,competing alkalotic process. What is the process? Becausethe PCO

₂

is near normal (36 mm Hg), it does notappear to be a respiratory process.Application of rule 5 (the "one-to-one" rule) can behelpful here. The anion gap has increased by 10 from anormal of 10; it is now 20. The one-to-one rule stipulatesthat the bicarbonate level must, therefore, have decreased10 mEq/L. This would have resulted in a bicarbonatelevel of 15 mEq/L-if the starting point had been a normallevel of 25 mEq/L. Since this has not occurred-thebicarbonate level here is 25 mEq/L-then the startingpoint had to have been 35 mEq/L. This elevation in the starting bicarbonate level indicates an occult metabolicalkalosis.

Hospital course

. The patient's diagnosis was diabetescomplicated by simultaneous anion gap metabolicacidosis and metabolic alkalosis. Her osmol gap was lessthan 10. Her glucose level was 343 mg/dL. Although theurinary chloride level was greater than 20 mEq/L, it was presumed that she had a contraction alkalosis from vomitingand that the elevated urinary chloride level was theresult of a glucose diuresis. Volume resuscitation (0.9%saline at 250 mL/h) and an insulin drip were initiated.The composition of the anion gap was interesting. Itincluded ketones from diabetic ketoacidosis and organicacid metabolites that had resulted from elevated salicylatelevels. Endoscopy revealed gastritis, and tests for

Helicobacterpylori

were positive.During the first 24 hours of treatment, aspirin wasdiscontinued and the patient received insulin and intravenousfluid; the anion gap decreased to normal. Later, a10-day triple-drug regimen was initiated to treat the

Hpylori

infection; results of a subsequent urea breath testwere negative. Diabetic control improved, and no otherbacterial infection was detected.

CASE 3:

WOMAN WITH HYPERTENSION AND HYPOKALEMIA

A 42-year-old woman presents with difficult-to-controlhypertension and hypokalemia. She has beenhypertensive for 10 years; however, during the past yearher blood pressure has ranged between 160/104 and180/112 mm Hg, despite the initiation of 3-drug therapy(hydrochlorothiazide, enalapril, and nifedipine), withwhich she has been compliant. Results of a physical examinationare otherwise normal. Initial laboratory resultsare as follows:

• Sodium: 146 mEq/L.
• Potassium: 2.8 mEq/L.
• Bicarbonate (measured): 38 mEq/L.
• Blood urea nitrogen: 9 mg/dL.
• Creatinine: 0.9 mg/dL.
• Venous p^H: 7.50.

The combination of venous pH and electrolyte levelsseen here suggests metabolic alkalemia and hypokalemiain a hypertensive patient. Since the patient is ambulatory,it is not critical to check the PCO

₂

for respiratory compensation.It is possible to proceed directly to the algorithmfor determining the cause of metabolic alkalosis(see

Algorithm III

on page 387).The first step is to measure urinary electrolytes todetermine whether the chloride level is elevated. The resultsare as follows:

• Sodium: 25 mEq/L.
• Potassium: 30 mEq/L.
• Chloride: 40 mEq/L.

The urinary p

^H

is 7.5.The patient has a high urinary chloride alkalosis.(The slight disparity in charges-55 positive, 40 negative-can be accounted for by a bicarbonate diuresis.) This finding, in the context of her elevated blood pressure,narrows the differential diagnosis.Measurement of renin and aldosterone levels can furthernarrow the differential in patients such as this woman,who have hypertension and a high urinary chloride metabolicalkalosis (

Table 2

). This patient's plasma renin levelis 0.2 ng/mL/h; her plasma aldosterone level is 40 ng/dL.The aldosterone-to-renin ratio is 80:1. In the setting ofhypokalemia, metabolic alkalosis, high urinary chlorideexcretion, and hypertension, a ratio greater than 20:1strongly suggests primary aldosterone hypersecretion.A subspecialist is consulted. Following the discoveryof aldosterone excess, it is necessary to confirm that thehypersecretion is autonomous and to determine whetherit is caused by hyperplasia or an adenoma in the adrenalglands.Autonomy was documented first by showing thatthe renin level did not increase when the patient wasgiven furosemide or assumed an upright posture (ingestionof a diuretic and standing up normally increaserenin values). Moreover, volume administration (2 L ofnormal saline over a 4-hour period) did not lower aldosteronelevels (saline administration reduces aldosteronelevels in patients with secondary hyperaldosteronism,which is caused by decreased volume or an elevatedrenin level).To determine whether the hyperaldosteronism wasthe result of hyperplasia or an adrenal adenoma, the aldosteronelevel was measured with the patient in an uprightposition (serum, 36 ng/dL; her urinary level was 40 μg/24hours). Upright posture does not produce any change inadenomatous secretion but is associated with an increasein aldosterone levels in patients with adrenal gland hyperplasia.The patient's 18-hydroxycorticosterone level wasalso measured (100 ng/dL, in a blood sample); increasedlevels are associated with an adenoma.

Outcome of this case

. This patient had an adenoma,which was resected. Following resection, her bloodpressure decreased to 140/90 mm Hg, her potassiumlevel normalized, and the metabolic alkalemia resolved.