Question 1#

A 33-year-old woman presents to the primary care physician for a month-long history of palpations and diarrhea. She has no known medical history. She denies taking any prescribed medication and has not traveled anywhere recently; however, she reports being exposed to “lots of sick people” as part of her job as a nurse. On physical examination, she appears anxious, but the rest of her examination results, including vital signs, are within normal limits. Her BMI is 21 kg/m2 . Laboratory studies are as follows:

• Sodium 139 mEq/L (mmol/L)
• Potassium 3.6 mEq/L (mmol/L)
• Chloride 117 mEq/L (mmol/L)
• Bicarbonate 16 mEq/L (mmol/L)
• Glucose 135 mg/dL
• BUN 12 mg/dL
• Creatinine 0.7 mg/dL
• Albumin 4.2 g/dL

Which of the following is the MOST likely cause for her laboratory abnormalities?

A. Laxative abuse

Correct Answer: A

This patient has a normal anion gap metabolic acidosis which can be seen in patients abusing laxatives. Stool contains a significant amount of bicarbonate along with potassium and sodium. With increased amounts of diarrhea, bicarbonate is lost, leading to a metabolic acidosis. Other causes of normal anion gap metabolic acidosis include renal causes, such as RTA, which emphasizes the importance of measurement of the urine anion gap (U_Na + U_K − U_Cl ). The urine anion will aid in estimating the kidneys’ ability to excrete acid. A positive urine anion gap is suggestive of renal causes of a normal anion gap metabolic acidosis, whereas a negative urine anion gap points toward a gastrointestinal source, such as diarrhea.

The first step with this kind of presentation is to determine the type of acid-base and electrolyte disturbance. Once it is determined that it is a normal anion gap metabolic acidosis, the second step is to differentiate between renal causes versus extrarenal causes by calculating the urine anion gap; a positive urine anion gap points toward renal causes whereas a negative urine anion gap is mostly of gastrointestinal etiology. 

Reference:

1. Goldstein MB, Bear R, Richardson RMA, Marsden PA, Marsden ML, Haleperin ML. The urine anion gap: a clinically useful index of ammonium excretion. Am J Med Sci. 1986;292(4):198-202. 

Question 2#

A 43-year-old man is brought by the police to the emergency department after being found unresponsive on the street. He appears unkempt and disheveled. On physical examination, his temperature is 36.0°C, blood pressure is 146/92 mm Hg, pulse rate is 84 beats/min, and respiratory rate is 10 breaths/min. He is not oriented to time and place. Laboratory data show the following:

• Sodium 144 mEq/L (mmol/L)
• Potassium 4.3 mEq/L (mmol/L)
• Chloride 108 mEq/L (mmol/L)
• Bicarbonate 8 mEq/L (mmol/L)
• Glucose 135 mg/dL
• BUN 18 mg/dL
• Creatinine 1.1 mg/dL
• Albumin 4.0 g/L
• Lactate 0.8 mmol/L
• TSH 3.60 mIU/L

An arterial blood gas is also obtained which shows:

• pH 7.28
• pCO₂ 18 mm Hg
• plasma osmolality 278 mOsm/kg H₂O

Which of the following is the MOST likely diagnosis in this patient?

A. Ethylene glycol poisoning

Correct Answer: A

The patient presents with an increased anion gap metabolic acidosis of 28—calculated anion gap = Na − (HCO₃ + Cl). In addition, his serum bicarbonate level is reduced to 8 mEq/L with a plasma osmolal gap of 12 mOsm/kg H₂O. Altogether, this points to ethylene intoxication. The osmolal gap is defined as the difference between the measured and the calculated plasma osmolality using the formula below:

Calculated plasma osmolality = (2 × plasma sodium) + glucose/18 + BUN/2.8

Ethylene glycol is commonly found in automotive coolants and cleaners, and ingestion of ethylene glycol will cause an increased anion gap metabolic acidosis with increased plasma osmolal gap of >10 mOsm/kg H₂O. Of note, methanol poisoning will also lead to similar findings. Isopropyl poisoning will also have an increased osmolal gap of >10 mOsm/L, but it does not usually cause an anion gap metabolic acidosis.

Reference:

1. Jacobsen D, Bredesen JE, Eide I, Østborg J. Anion and osmolal gaps in the diagnosis of methanol and ethylene glycol poisoning. J Intern Med. 1982;212(1):17-20.

Question 3#

An 87-year-old lady is being evaluated in the nursing home after being found to be more lethargic. She had been complaining of decreased appetite due to abdominal pain and ongoing diarrhea for the last 3 days. Her past medical history is significant for hypertension, type II diabetes mellitus, chronic back pain, and diverticulosis. Her medications include metformin, insulin, lisinopril, and naproxen. On physical examination, her:

• temperature is 37.8°C
• blood pressure is 118/82 mm Hg
• pulse rate is 104 beats/min
• respiratory rate is 10 breaths/min

Laboratories obtained show the following:

• Sodium 140 mEq/L (mmol/L)
• Potassium 3.4 mEq/L (mmol/L)
• Chloride 99 mEq/L (mmol/L)
• Bicarbonate 20 mEq/L (mmol/L)
• Glucose 243 mg/dL
• BUN 22 mg/dL
• Creatinine 1.6 mg/dL (baseline 1.1)
• Albumin 3.7 g/L
• Lactate 1.0 mmol/L

ABG:

• pH 7.52
• pCO₂ 20 mm Hg

Which of the following is the MOST likely diagnosis in this patient?

A. Metabolic acidosis with compensation

Correct Answer: E

The patient has a mixed acid-base disorder. Her pH is alkalotic. Upon closer look, it appears that she has a respiratory alkalosis (pCO₂ 20 mm Hg). To determine whether this is an acute or chronic respiratory alkalosis, the following formula can be used: 1-2-4-5 rule.

In acute respiratory alkalosis, for every decrease in PaCO₂ by 10, the HCO₃ − decreases by 2.

In chronic respiratory alkalosis, for every decrease in PaCO₂ by 10, the HCO₃ − decreases by 5.

Based on that, her expected HCO₃ − is approximately 14 mEq/L. However, in this case, it is 21 mEq/L which is higher than expected. This suggests that there is concurrent metabolic alkalosis present. This is also confirmed by calculating the Δ-Δ ratio—(calculated AG – expected AG)/24 – measured HCO₃ −—which aids in determining the presence of any other normal AG metabolic acidosis or if this is a pure high AG metabolic acidosis.

In this case, the Δ-Δ ratio is >1, indicating that there is in fact a metabolic alkalosis present. A Δ-Δ ratio < 1 suggests a normal AG metabolic acidosis.

Reference:

1. Berend K, De Vries APJ, Gans ROB. Physiological approach to assessment of acid–base disturbances. N Engl J Med. 2014;371:1434- 1445. 

Question 4#

A 32-year-old male is referred to the nephrologist for abnormal laboratory values. He was recently seen by his primary care physician for his annual physical examination. During his visit, he was told that his “urine was abnormal.” The patient does not have any known medical history except for a 26-year pack-year smoking history. He is normothermic with a blood pressure of 128/90 mm Hg, pulse rate of 58 beats/min, and respiratory rate of 12 breaths/min. The rest of his physical examination is unremarkable. His family history is only significant for arthritis and “thyroid disease.” Further laboratory studies obtained show the following: 

• Sodium 142 mEq/L (mmol/L)
• Potassium 3.3 mEq/L (mmol/L)
• Chloride 117 mEq/L (mmol/L)
• Bicarbonate 10 mEq/L (mmol/L)
• Glucose 243 mg/dL
• BUN 22 mg/dL
• Creatinine 1.3 mg/dL (baseline is 1.1)
• Albumin 4.2 g/L
• Urine pH 5.6
• Urine sodium 62 mEq/L
• Urine potassium 85mEq/L
• Urine chloride 126 mEq/L
• Urine calcium 378 mg/dL

What is the MOST likely diagnosis in this patient?

A. Gitelman syndrome

Correct Answer: B

This patient likely has RTA type 1. In patients with RTA type 1, there is impairment of acidification in the distal part of the nephrons. Because the kidney is unable to excrete hydrogen ions, this defect leads to the secretion of NH⁴⁺ . Patients with RTA type 1 usually have non–anion gap acidosis (which is also found in patients with RTA type 2 and 4). However, the main difference between the types of RTA is that type 1 will also have very low levels of HCO₃ − , high urine pH of >5.5 (as the kidney is unable to maximally acidify the urine), and positive urine anion gap. In this case, the patient’s urine anion gap is 19 based on the formula, Urine anion gap = U_Na + U_K − U_Cl . 

Main causes of RTA type I include autoimmune diseases, such as rheumatoid arthritis and Sjögren syndrome, obstructive nephropathy, and nephrotoxins, including toluene and amphotericin B. There is a hereditary cause for RTA type 1 which is usually diagnosed in infants or childhood. Though the clear mechanism of acquired RTA type I is unclear, it has been suggested that this due to defective H⁺ -K⁺ ATPase function at the apical surface of the α-type intercalated cells of the collecting duct.

In children, this can manifest with polyuria, stunted growth, recurrent nephrocalcinosis, and hypercalciuria. In adults, RTA type 1 will also lead to nephrocalcinosis. Treatment consists of managing the underlying disorders but can sometimes include usage of thiazide diuretics and/or NaHCO₃ and K⁺ supplementation. 

While all types of RTA lead to hyperchloremic non–anion gap metabolic acidosis, the main differences between types of RTA are laid out in the table below:

Reference:

1. Soriano JG. Renal tubular acidosis: the clinical entity. J Am Soc Nephrol. 2002;13:2160-2170.

Question 5#

A 64-year-old woman is being treated in the local intensive care unit (ICU) for septic shock due to Streptococcus pneumoniae. She weighs 120 kg. She is started on empiric antibiotics and resuscitated with 30 mL/kg of normal saline without significant improvement. She is therefore temporarily started on vasopressor support. She improves after 4 days and is weaned off all vasopressors. She extubated to noninvasive ventilation. However, her voice remains hoarse, and she fails her swallow evaluation. She remains on intravenous fluids for hydration for 3-day history of diarrhea.

Laboratory data obtained on admission:

What is the MOST likely cause for her laboratory abnormalities?

A. Contraction alkalosis

Correct Answer: C

Iatrogenic causes of non–anion gap metabolic acidosis are common in the setting of critical ill patients, who require aggressive fluid administration, particularly when chloride-rich solutions such as 0.9% saline are used. When large amounts of sodium chloride–containing solutions are administered, the chloride concentration in the serum will rise more than that of sodium as the serum chloride levels are normally lower than serum sodium. Therefore, the strong ion difference (SID) decreases and leads to a reduction of the positive plasma charge. To compensate for this, the chloride reacts with bicarbonate to produce protons and buffer the pH. This leads to depletion of bicarbonate stores and subsequently an acidosis. 

Reference:

1. Kraut J, Kurtz I. Treatment of acute non-anion gap metabolic acidosis. Clin Kidney J. 2015;8(1):93-99.