A 36-year-old woman is admitted for dizziness, weakness, poor appetite, fatigue, and salt-craving for 4 weeks. She has history of asthma, and not on any medications. She has a family history of type 1 diabetes and hypothyroidism. On admission, her blood pressure (BP) is 100/60 mmHg with a pulse rate of 100 (sitting), and 80/48 mmHg with a pulse rate of 120 beats/min (standing). Her temperature is 99.6 °F. Laboratory values are as follows:
Based on the above history and laboratory values, which one of the following fluids is APPROPRIATE in addition to pertinent hormone administration?

The orthostatic BP and pulse changes suggest volume depletion. Hyponatremia, hyperkalemia, elevated BUN and creatinine, hypoglycemia, and high urinary Na ⁺ excretion suggest adrenal insufficiency (Addison’s disease), which is due to glucocorticoid and mineralocorticoid deficiency. Her signs and symptoms are related to volume depletion and electrolyte abnormalities. Hypotension is related to loss of both Na ⁺ and water caused by deficiency of the above hormones.

In addition to administration of hydrocortisone and fludrocortisones , the patient needs normal saline administration to improve total body volume (D is correct). Both volume repletion and hormone treatment improve BP and electrolytes.

D5W may improve hyperkalemia and glucose, but not adequate to improve volume (A is incorrect). 5 % albumin may expand volume, but is not indicated in this patient (B is incorrect). Ringer’s lactate may exacerbate hyperkalemia and hypercalcemia (about 10 % of patients with Addison’s disease have hypercalcemia) with little effect on hyponatremia. Thus, C is incorrect. Half-normal saline is not adequate to replete the entire fluid in this patient (E is incorrect).

It is always important to know how much infused crystalloid or colloid will remain in the intravascular compartment to improve volume status and hemodynamic status. Which one of the following fluids contributes MOST to the intravascular compartment?

In order to answer the question, it is important to remember the percentage of total body water and its distribution in various fluid compartments. In a 70 kg man with lean body mass, the total body water accounts for 60 % of body weight (42 L), and two-thirds of this water (i.e., 28 L) is in the intracellular fluid (ICF) and one-third (i.e., 14 L) is in the extracellular fluid (ECF) compartment (Fig. 1.1 ). Of these 14 L of ECF water, 3.5 L (25 %) is present in the intravascular and 11.5 L (75 %) in the interstitial compartments. Accordingly, if 1 L of D5W is infused, approximately 664 mL will move into the ICF and 336 mL will remain in the ECF compartment. Of these 336 mL, only 84 mL (25 %) will remain in the intravascular compartment (Fig. 1.2 ).

The retention of hypotonic solutions such as 0.45 % NaCl (half-normal) is different. 0.45 % NaCl is considered to be a 50:50 mixture of normal saline and free water. If 1 L of 0.45 % NaCl is infused, the free water (500 mL) is distributed between ICF (333 mL) and ECF (167 mL) compartments. Of 167 mL, only 42 mL (25 %) will remain in the intravascular compartment. Considering the other 500 mL, which behaves like 0.9 % saline, 375 mL (75 %) will move into the interstitial space, and 125 mL stays in the intravascular compartment (Fig. 1.3 ). Thus, the total volume remaining intravascularly after 1 L of infusion would be only 167 mL (42 + 125 = 167 mL).

On the other hand, more fluid is retained in the intravascular space with isotonic fluids. If 1 L of normal saline is infused, all of the fluid will remain in the intravascular compartment, and then approximately 750 mL will move into the interstitial compartment, leaving 250 mL in the intravascular compartment (Fig. 1.4 ). The movement of saline into the interstitial compartment occurs approximately 30 min after infusion. During this period of intravascular stay of saline, volume status and BP improve. Urine output may or may not improve until additional volume is infused. Similar volume changes occur with Ringer’s lactate. Thus, E is correct.

Infusion of colloids results in even much more retention of fluids in the intravascular compartment. If 1 L of 5 % albumin is infused, 900 mL will stay in the intravascular compartment and 100 mL in the interstitial compartment. Albumin stays in the intravascular compartment for >16 h.

Approximate distribution of various crystalloids and colloids (albumin) in body compartments in the absence of shock or sepsis is summarized in the following table (Table 1.1 ).

A 24-year-old woman is admitted for fever with chills and weakness. She is found to be hypotensive and tachycardic. Blood cultures are positive for Staphylococcus aureus, and the diagnosis of septic shock is made. There is no peripheral edema. Based on the sensitivity , the patient is started on vancomycin. Pertinent labs:

Which one of the following fluids is APPROPRIATE for initial resuscitation?

Relative intravascular volume depletion is usual in septic shock. This patient has evidence of intravascular volume depletion. Therefore, the choice of fluid is normal saline (C is correct). Rapid infusion of at least 1 L of saline is needed within an hour and then at least 150–200 mL/h until BP, tissue perfusion, and oxygen delivery are acceptable. Note that the patients with septic shock can develop pulmonary edema at pulmonary capillary wedge pressures <18 mmHg. Raising Hb >10 g/dL is not beneficial; therefore, transfusion of pRBCs is not required (A is incorrect). However, the patient needs transfusion of pRBCs once her Hb drops below 7 g/dL.

Ringer’s lactate may be considered in the absence of lactic acidosis and hyperkalemia . Because of low Cl ⁻ , the patient is less prone to develop acute kidney injury, as compared with normal saline. However, Ringer’s lactate and half-normal saline may not be appropriate (B and D are incorrect).

Albumin may help restore BP and tissue perfusion, if BP does not improve with substantial amount of normal saline and the patient has trace edema. However, peripheral edema may be present in patients with septic shock without adequate volume replacement because of extravasation of fluid into the interstitium due to increased vascular permeability. Vasopressors, in addition to albumin, may be required to improve BP, tissue perfusion, and gas exchange. However, albumin is not the initial choice of fluid resuscitation. Thus, E is incorrect.

A 30-year-old man is admitted to the trauma service with multiple abdominal wounds that required splenectomy and repair of several organs. He has multiple surgical drainages. His blood pressure is 120/80 mmHg with a pulse rate of 80. His labs:

Which one of the following fluids contributes MOST to the intravascular compartment?

This patient has multiple electrolyte problems because of nonrenal losses. Therefore, the appropriate fluid for initial therapy is Ringer’s lactate, which contains Na ⁺ , Cl ⁻ , K ⁺ , Ca ²⁺ , and lactate. This fluid should be continued until all electrolyte abnormalities are corrected (D is correct).

D5W is not an appropriate fluid for this patient, as he has hypokalemia, and dextrose would further lower serum [K ⁺ ]. This may cause weakness and arrhythmia. Also, normal saline alone is not appropriate because it may lower [K ⁺ ] even further by urinary excretion. Although normal saline with K ⁺ administration would minimize loss of K ⁺ , it may not improve other electrolyte abnormalities.

A 72-year-old man with history of hypertension , type 2 diabetes, coronary artery disease with stent placement, and CHF is admitted for dyspnea at rest. He noticed swelling of his legs for 4 weeks despite salt restriction and diuretics. His LV ejection fraction (EF) is 40 %. Medications include humalog (75/25) 20 units QD, furosemide 40 mg BID, metolazone 2.5 mg QD, spironolactone 12.5 mg QD, carvedilol 12.5 mg BID, ramipril 10 mg QD, atorvastatin 40 mg QD, clopidogrel 75 mg QD, and aspirin 81 mg QD. BP 100/60 mmHg, pulse 102 beats/min, marked JVD, crackles, an S₃, positive hepatojugular reflex, and pitting edema up to knees. Labs: Na⁺ 134 mEq/L, K⁺ 3.8 mEq/L, Cl⁻ 90 mEq/L, HCO₃ ⁻ 28 mEq/L, BUN 46 mg/dL, creatinine 1.8 mg/dL, eGFR <60 mL/min, and glucose 100 mg/dL. HgbA1c 7 %. Urinalysis is significant for 2+ proteinuria. EKG shows tachycardia. He weighs 98 kg. Based on the above history and lab values, which one of the following is the MOST appropriate initial management in this patient?

The patient needs symptomatic relief immediately from volume overload. Continuous IV furosemide (5 mg/h) is probably better than IV bolus because of established safety profile, greater urine output, and less renal impairment. If diuresis is poor on furosemide, nesiritide should be tried until urine output is improved. The recommended dose of nesiritide is 2 μg/kg bolus followed by 0.01 μg/kg/min. Nesiritide causes vasodilation in the venous and arterial, including coronary vasculature. It also decreases venous and ventricular pressures with slight increase in cardiac output. As a result, dyspnea may improve. With the use of nesiritide, the requirement for furosemide decreases. If urine output is not adequate, nitroglycerine at 20 μg/min should be considered. Since nitroglycerine causes hypotension, monitoring of BP is extremely important, and the drug should be discontinued once systolic BP is <90 mmHg. Increasing metolazone dose is inappropriate.

The patient improved symptomatically over a 48 h period; however, his urine output and edema did not improve substantially. His weight decreased from 98 to 96 kg. Repeat labs show creatinine of 2.1 mg/dL. His BP is maintained at 100/56 mmHg. What would be the next appropriate step?

Adrenergic agonists such as dobutamine should be considered in view of low EF. Dobutamine improves cardiac output by decreasing afterload and increasing inotropy. Renal perfusion also improves at doses of 1–2 μg/kg/min (C is correct). Other treatment options do not improve the patient’s clinical status, and may be harmful.

Despite dobutamine , the urine output did not improve significantly in 24 h. Milrinone, which is a phosphodiesterase inhibitor was started with a bolus dose of 25 μg/kg followed by 0.1 μg/kg/min to improve inotropy. BP, urine output, and edema did not improve. BP is 90/70 mmHg. Serum chemistry shows creatinine level of 3.2 mg/dL. Which one of the following treatment strategies is APPROPRIATE to improve his condition?

The patient developed type 2 cardiorenal syndrome . Diuretics, nesiritide, and nitroglycerine should be discontinued. Of all the available options, CVVHDF is the suitable option because it can improve both fluid status and creatinine (C). PD is a slow process, and HD may not be helpful in view of low BP. Tolvaptan may not work that well in this patient with low EF and decreased urine output. Aquapheresis is indicated in patients with CHF, but it increases creatinine even further. Thus, starting the patient on CVVHDF is a better option than other interventions.

A 50-year-old woman with alcohol abuse presents to the Emergency Department for the first time with dyspnea, worsening abdominal distention, and swollen legs for the last 4 weeks. Past medical history includes 1 pint of alcohol a day for 20 years. She is not on any medications. She eats regular diet. BP is 124/68 mmHg with pulse rate of 80 beats/min. She has crackles, an S₃, tense ascites, and pitting edema up to the knees. Pertinent labs: serum [Na⁺] 128 mEq/L; [K⁺] 3.6 mEq/L; creatinine 0.8 mg/dL. Chest X-ray shows pulmonary congestion. Which one of the following choices regarding her management is CORRECT?

Since her major problem is Na ⁺ and water retention , restriction of both will help lose weight. Since the patient has crackles with pulmonary congestion, she would benefit from IV infusion of a loop diuretic such as furosemide (40 mg BID; some prefer to give 80 mg). Thus, C is correct. Once patient is stable, spironolactone at 100 mg should be started initially with up-titration every 2–3 days by 100 mg up to 400 mg/day. If, urine output is not adequate, furosemide up to 160 mg (80 mg BID) should be tried. Bed rest is advisable to improve cardiac output and GFR. Her ascites and CHF should improve. If her ascites does not improve despite the above treatment modality, large volume paracentesis with 5 % albumin (8 g/L) replacement is recommended. Daily weight, BP, and intake/output (I/O) should be recorded. Other options are not appropriate.

With the above management , she lost 14 kg in 7 days. Her serum [Na⁺] is 134 mEq/L, and creatinine remains at 0.8 mg/dL. She received education about restricted Na⁺ diet and abstinence from alcohol, and discharged on spironolactone 400 mg QD and furosemide 80 mg BID. She is given clinic appointment in 2 weeks. In the clinic, she was found to have severe volume depletion, and weight loss of another 4 kg. Her ascites did not increase during this 2-weeks period. What would you do next?

She should be hospitalized for volume replacement and stabilization. Diuretics should be stopped, and 5 % albumin should be given (100 g/day). A liter of normal saline can be considered with 50 g of 5 % albumin the next day. Daily weight with BP and I/Os should be followed. On discharge, furosemide dose should be decreased to 40 mg BID with reducing dose of spironolactone, as indicated. Follow-up in 1–2 weeks is needed. Choices A to D are inappropriate.

A 46-year-old man is referred to you by a primary care physician for evaluation of proteinuria and leg edema for 3 months. The patient is healthy otherwise. He is not on any medications; however, he has a long history of smoking. The patient noticed edema of lower extremities 2 months ago. He has mild shortness of breath on walking. BP is 132/80 mmHg with a pulse rate of 74 beats/min. Physical examination is normal other than pitting edema in lower extremities. Serum chemistry and complete blood count are normal (creatinine 0.8 mg/dL). Serum albumin is 3.2 g/dL. Urinalysis reveals 4+ proteinuria and fatty casts. Urine protein to creatinine ratio is 7.2, and 24 h protein is 7.1 g. His urinary Na⁺ is 142 mEq/L. He weighs 94 kg. The patient agrees to renal biopsy, which shows membranous nephropathy . Workup for secondary causes of membranous nephropathy is negative. He has no insurance. Which one of the following choices regarding the initial management of his edema is CORRECT?

Restriction of Na ⁺ (88 mEq) in the diet is the first step in the management. Furosemide 40 mg QD and lisinopril (an ACE-I) 20 mg QD should be started to improve edema and proteinuria . Limiting water at this time is not appropriate. The patient’s weight, edema, BP, proteinuria, creatinine, K ⁺ , and urinary Na ⁺ for compliance of diet should be followed frequently. Adding amiloride seems to lower proteinuria, if no or partial response to lisinopril is observed.

A 48-year-old woman with small cell lung cancer is brought to the emergency department with altered mental status of 4 days duration and questionable seizure disorder. Her husband says that the patient is sipping water frequently because of dry mouth. Her BP is 130/80 mmHg with pulse of 74 beats/min. Following 2 L of 0.45 % saline in 24 h, the following lab data are obtained:
Regarding electrolyte-free water clearance ( ), which one of the following is CORRECT?

The concept of is used to calculate the kidneys’ ability to conserve or excrete the daily intake of fluids to maintain normal serum [Na ⁺ ]. Whenever water balance is disturbed, either hypo- or hypernatremia develops. In such a situation, calculation of is helpful in evaluating serum [Na ⁺ ] by using the following formula:
where V is urine volume/24 h, U _Na , U _K , and P _Na are urine Na ⁺ , K ⁺ , and plasma Na ⁺ concentrations in mEq/L. Substituting the data from the patient, we obtain
Whenever the value is negative, the kidney is adding water to the body, resulting in hyponatremia. On the other hand, when the is positive, the kidney is removing water from the body with the resultant hypernatremia. The patient received hypotonic solution with further reduction in serum [Na ⁺ ]. Thus, option B is correct.

A 72-year-old woman, who lives alone, was admitted for weakness, inability to walk, and forgetfulness over a 2-week period of time. She cooks her own meals. She is slightly lethargic. Physical examination shows BP 124/74 mmHg; pulse 78/min and no orthostatic hypotension. Lung and heart examination is normal. Labs are:

Which one of the following is the MOST likely cause for her hyponatremia ?

The patient does not have pseudohyponatremia, as serum glucose and total protein are normal. Also, she does not have hypertonic hyponatremia because her serum glucose is normal and she has no osmolal gap, suggestive of the presence of either mannitol or glycerol (A and B are incorrect).

Based on physical examination, the patient has euvolemic hyponatremia. Generally, the typical American diet generates a minimum of 600 mOsm per day (assuming 60 g protein intake). All of these mOsm are excreted either in 12 L of urine, if urine osmolality is 50 mOsm/kg H ₂ O or 0.5 L of urine if urine osmolality is 1200 mOsm/kg H ₂ O (Total mOsm/Urine osmolality or 600/50 = 12 L or 600/1200 = 0.5 L). Thus, a normal individual with intact diluting and concentrating ability can excrete urine from 0.5 to 12 L without any change in water balance (or plasma osmolality).

The patient has urine osmolality of 110 mOsm/kg H ₂ O; therefore, she can excrete all her mOsm in 2.2 L of urine (110/50 = 2.2 L). However, her total mOsm were only 110, suggesting poor solute intake. If this patient drinks >2.7 L (2.2 + 0.5 L insensible loss) of fluids daily and her solute excretion is only 110 mOsm, she will be in a positive water balance with subsequent development of hyponatremia.

Lack of solute intake impairs the kidney’s ability to dilute the urine to <100 mOsm/kg H ₂ O, as reduced solute excretion limits water excretion. Her hyponatremia will improve with diet that contains at least 60 g protein, salt (100 mEq Na ⁺ ), and 40–60 mEq K ⁺ . Thus, the patient carries the diagnosis of hyponatremia due to tea and toast (C is correct).

She does not have either HCTZ-induced hyponatremia or SIADH, as other labs such as uric acid (usually low in both conditions) is normal for her age (D and E are incorrect).

A 44-year-old menstruating woman had abdominal surgery lasting for 4 h. Perioperatively, she received normal saline to maintain BP and urine output. Postoperatively, she received 0.45 % saline at 120 mL/h, and morphine for pain. Her urine output was 110 mL/h. 24 h later, she was awake and complained of nausea and headache. The following labs were available at the time of consultation :
Which one of the following regarding the amount of water deficit is CORRECT?

The following two formulas can be used to calculate water excess :

Thus, choice D is correct.

A 27-year-old man with resection of pineal gland tumor developed persistent hyponatremia . He complains of weakness and mild dizziness. Physical examination reveals a BP of 114/70 mmHg and a pulse rate of 100 beats/min (supine), 100/60 mmHg and a pulse rate of 120 beats/min (standing), respiratory rate of 16/min, and a temperature of 99.1 °F. Cardiac exam is normal. Lungs are clear to auscultation. There is no peripheral edema. He receives 2.5 L of normal saline daily.

Lab studies:
Which one of the following is the MOST likely cause of this patient’s hyponatremia?

Pseudohyponatremia is related to extremely high levels of proteins and triglycerides. Although triglycerides were not measured, his total protein concentration was normal. Therefore, this patient does not have pseudohyponatremia.

Vomiting is a consideration; however, serum [Cl ⁻ ] and urinary [K ⁺ ] are not consistent with vomiting. In general, patients with late vomiting conserve Na ⁺ , and excrete low Na ⁺ because of volume depletion. Also, K ⁺ excretion is enhanced in both early and late vomiting. Therefore, option B is incorrect.

Adrenal insufficiency is also a consideration in view of normal to low BP and increased pulse rate as well as increased urinary Na ⁺ excretion. However, normal Cl ⁻ , HCO ₃ ⁻ and glucose levels exclude the diagnosis of adrenal insufficiency.

Hypotonic hyponatremia , low serum uric acid level, relatively normal BP, high urine Na ⁺ and osmolality suggest the diagnosis of SIADH. However, high pulse rate and slightly elevated HCO ₃ ⁻ and BUN levels are unusual in patients with SIADH. Patients with SIADH are euvolemic and lower their serum Na ⁺ levels with normal saline. The clinical presentation of this patient is suggestive of volume depletion, rather than euvolemia. Therefore, SIADH is unlikely in this patient.

Cerebral salt wasting (CSW) is the most likely cause of this patient’s hyponatremia. Hypovolemia and serum as well as urine studies are consistent with CSW . Thus, option D is correct.

A 42-year-old man was admitted for subarchnoid hemorrhage . Following clipping of the aneurysm, he develops hyponatremia (Na⁺ dropped from 136 to 124 mEq/L). A tentative diagnosis of cerebral salt wasting (CSW) was made. Which one of the following distinguishes CSW from SIADH?

CSW occurs in patients with subarachnoid hemorrhage and other CNS disorders. It is characterized by low blood and plasma volumes and negative salt balance. CSW and SIADH are characterized by hypotonic hyponatremia, ability to excrete Na ⁺ , low serum uric acid level because of increased secretion, resulting in high FE _{uric acid} and normal serum K ⁺ levels. However, FE _{uric acid} returns to baseline once the cause of SIADH is corrected but it will remain high in patients with CSW. Also remains high in CSW and is normal in SIADH.

Which one of the following choices regarding treatment of hyponatremia is CORRECT in the above patient?

Patients with CSW are hypovolemic with low BP and orthostatic changes because they lose salt in the urine. Therefore, the treatment to improve serum [Na ⁺ ] is volume expansion with NaCl and fludrocortisone. Thus, choice D is correct. Other treatment modalities do not improve serum [Na ⁺ ] in patients with CSW. Choices A, B, C, and E are beneficial in patients with SIADH.

A 20-year-old woman collapses at a wild party several hours after taking ecstasy. Which one of the following electrolyte abnormalities is MOST likely to be found in this subject?

Ecstasy is a popular name for a ring-substituted form of methamphetamine. It gained the popularity of a “club drug” among adolescents, young adults and subjects attending “rave” parties. Among other side effects, such as rhabdomyolysis, arrhythmias, and renal failure, ecstasy causes symptomatic hyponatremia and sudden death. Ecstasy induces vasopressin secretion and retention of water in the stomach and intestine by decreasing GI motility. Hyponatremia develops as a result of water reabsorption from the GI tract and excessive oral intake in the presence of high vasopressin levels. Thus, option D is correct. Other options have very little role in the development of hyponatremia in the presence of ecstasy.

A marathon runner was disoriented and delirious post-race, and was found to have a serum [Na⁺] 128 mEq/L. His weight was slightly higher than pre-race weight. Which one of the following is the MOST appropriate fluid administration?

The recommended initial fluid management in symptomatic exercise-induced, euvolemic hyponatremic patient is 3 % saline in small volume boluses. Hypotonic fluids such as 0.45 % saline or isotonic D5W should be avoided because of further decrease in serum [Na ⁺ ]. Normal saline (0.9 %) is the fluid of choice to replace volume, although a study reported good results with isotonic saline in athletes. Isotonic saline may not be a suitable solution to correct hyponatremia in patients with elevated or inappropriate high levels of vasopressin. Although both 3 and 7.5 % saline are hypertonic, 3 % saline is usually the preferred fluid for symptomatic hyponatremic patients. Thus, answer C is correct.

A 60-year-old woman with history of lung cancer is admitted for weakness and lethargy for 4 weeks. Her serum [Na⁺] is 120 mEq/L. She weighs 60 kg. Her serum osmolality is 250 mOsm/kg H₂O with urine osmolality of 616 mOsm/kg H₂O. The diagnosis of SIADH is made. What would be her serum [Na], if she receives 1 L of isotonic saline?

The selection of fluids in the treatment of SIADH depends on a clear-cut understanding of the fluid, serum, and urine osmolalities. In addition, the physician should evaluate the total body water ( TBW ) content as well as the total body Na ⁺ (TB _Na ) content. I would like to use TB _Na content rather than total plasma osmolality because both calculations would yield similar results. A systematic approach would yield the correct answer.

First, calculate TBW and TB_Na of the patient as follows:

Second, calculate the amount of urine volume that is required to excrete the osmoles of a given fluid to be administered to the patient. This can be calculated by dividing urine osmolality into fluid osmolality.

In the above patient, the new serum [Na ⁺ ] can be obtained as follows:

The patient received 1 L of 0.9 % saline; however, the patient excreted all the osmoles in 0.5 L of urine. Therefore, the patient retained 0.5 L of free water, which causes the TBW to increase from 30 to 30.5 L. Assuming the TB _Na remains at 3600 mEq, the new serum [Na ⁺ ] would be:
Thus, in a patient with the diagnosis of SIADH , administration of 0.9 % NaCl would result in lower rather than increase in serum [Na ⁺ ]. Thus, option C is correct.

An 80-year old woman was admitted for nausea, headache, and psychosis for 2 days: Past medical history includes hypertension, and her physician increased hydrochlorothiazide (HCTZ), from 12.5 to 25 mg daily. The patient was drinking water more than usual. Her BP was 120/70 mmHg and pulse rate of 80 beats/min. There were no orthostatic BP and pulse changes. Serum chemistry : Na⁺ 112 mEq/L, K⁺ 3.2 mEq/L, Cl⁻ 90 mEq/L, and glucose 90 mg/dL. The urine osmolality is 220 mOsm/kg H₂O. She weighs 70 kg. Which one of the following statements regarding her hyponatremia is CORRECT?

Hyponatremia is a well-documented complication of diuretic use. About 73 % of cases of hyponatremia were related to thiazide diuretic use. 20 % of cases were attributed to a combination of thiazides and K ⁺ -sparing diuretics, and 8 % were related to furosemide use. Thus, HCTZ rather than furosemide is the most common cause of hyponatremia because thiazides impair maximum urinary dilution but not concentrating ability. Urine osmolality is usually >100 mOsm/kg H ₂ O among thiazide users. The expected urine osmolality for this degree of hyponatremia (118 mEq/L) with normal diluting capacity should be about 50 mOsm/kg H ₂ O. However, this patient is unable to lower urine osmolality <100 mOsm/kg H ₂ O because of the effect of HCTZ on renal water handling. HCTZ decreases free H ₂ O clearance (i.e., more water reabsorption) and causes inability to lower urine osmolality to <100 mOsm/kg H ₂ O.

Furosemide impairs concentrating ability of the kidney, and free water clearance is increased rather than decreased. Therefore, furosemide alone does not cause hyponatremia, but a combination of HCTZ and furosemide can result in hyponatremia. However, some patients may develop hyponatremia with orthostatic BP and pulse changes with chronic use of furosemide due to total body Na ⁺ and water loss. Thus, the answers A, B, D, and E are incorrect.

Which one of the following strategies regarding treatment of hyponatremia is CORRECT?

This patient has acute symptomatic hyponatremia, which requires immediate treatment . Although controversial, treatment should be prompt in view of preventing progression of cerebral edema and hypoxia, which far exceed the risk of osmotic demyelination. Initially, serum [Na ⁺ ] should be corrected by 2 mEq/L per hour from 112 to 118 mEq/L in 3–4 h until symptoms resolve. Then, correction should not exceed 18 mEQ in 48 h to 130 mEq/L with 3 % or normal saline (D is correct). Administration of hypertonic saline should be adjusted to achieve the target serum [Na ⁺ ] by frequent determinations of serum [Na ⁺ ] and urine Na ⁺ and K ⁺ levels.

Restriction of fluids and discontinuation of HCTZ are not appropriate for acute symptomatic hyponatremia, although adequate after relief of symptoms. Administration of normal saline is inadequate and inappropriate to this patient. Also, rapid connection of serum [Na ⁺ ] to 130 mEq/L in 6 h may be a risk for osmotic demyelination . Thus, answers A, B, C, and E are incorrect.

It should be noted that a patient with hyponatremia and hypokalemia who is admitted for weakness can be successfully treated with KCl.

Which one of the following possible mechanism regarding thiazide-induced hyponatremia is FALSE?

Thiazides cause not only mild asymptomatic but also severe symptomatic hyponatremia, as shown in the above case. The disorder is also life-threatening in some susceptible patients. Although the mechanisms for thiazide-induced hyponatremia are not fully understood, several possible explanations have been suggested. These include: (1) volume contraction; (2) early diuretic-induced inactivation of TGF system; (3) decreased GFR due to above two mechanisms; (4) stimulated release of vasopressin and increased H ₂ O reabsorption; (5) relative decrease in vasodilatory PG synthesis in elderly subjects with unopposed vasopressin action; and (6) decrease in urinary dilution.

In addition, diuretic-induced hypokalemia may further exacerbate hyponatremia by transcellular cation exchange (due to osmolality changes), in which K ⁺ moves out of the cell to improve hypokalemia and Na ⁺ moves into the cell to maintain electroneutrality. Therefore, options A to D are correct.

Loss of Na ⁺ and H ₂ O occurs soon after HCTZ use; however, chronically H ₂ O loss is less than Na ⁺ loss (E is false).

A 49-year-old male was brought to the Emergency Department for evaluation of nausea, fatigue, and weakness for 24 h. His wife says that he had been having binge drinking without any food intake. He is not taking any medications. On physical examination, he was euvolemic. His weight is 70 kg. BP is 100/60 mmHg with a pulse rate of 82 beats/min. Serum [Na⁺] is 120 mEq/L; [K⁺] 3.8 mEq/L; BUN 8 mg/dL; creatinine 0.6 mg/dL; and osmolality 230 mOsm/kg H₂O. Urine studies are: Osmolality 75 mOsm/kg H₂O; Na⁺ 10 mEq/L; and K⁺ 20 mEq/L. The diagnosis of beer potomania was made. Assuming no urine output in 2–3 h, which one of the following is the MOST appropriate therapy for this patient?

Treatment of acute symptomatic hyponatremia due to binge drinking is a therapeutic challenge to physicians because of waning and waxing symptoms. A review of the literature on hyponatremia due to beer ingestion shows administration of 0.9 % NaCl, 0.45 % NaCl with KCl supplementation, and 3 % NaCl and fluid restriction to no treatment. Thus, treatment of hyponatremia depends on the severity and duration of onset of symptoms.

This patient has mild to moderate symptoms of hyponatremia. The appropriate treatment appears 0.9 % saline rather than 3 % saline (B is correct). Rapid correction of serum Na ⁺ from 120 to 126 mEq/L by 3 % saline is not necessary in this patient. Furthermore, rapid correction of serum Na ⁺ to >130 mEq/L in an alcoholic may precipitate osmotic demyelination syndrome. Therefore, either infusion of 0.9 % saline (1 L in 24 h) or fluid restriction to increase serum Na ⁺ by <10 mEq/L in 24 h or <18 mEq/L in 48 h is advisable.

D5W is not the solution of initial choice in this patient because it is converted into free H ₂ O and may lower serum [Na ⁺ ] even further. D5W can be started if caloric intake is needed after serum [Na ⁺ ] reaches approximately 128 mEq/L. Also, fluid restriction with supplementation of NaCl tablets is not the appropriate choice.

A 28-year-old woman was admitted for nausea, vomiting, blurred vision, and questionable seizures. She was electively intubated for air-way protection . Further history was obtained from the mother, who stated that the patient had nonbloody diarrhea for 2 days and drank several liters of water. The patient is a strict vegan, and in good health, and does not take any medications. Physical examination revealed a thin female with a BP of 116/72 mmHg with a pulse of 98 beats/min. Lung and heart examination were normal. There was no peripheral edema. Her weight was 64 kg. Six weeks ago she delivered a healthy baby and her serum [Na⁺] was 140 mEq/L. The laboratory results showed:

Assuming her total output (diarrheal fluid, urine output, and insensible loss) is 2 L/day, how much water she may have consumed that lowered her serum [Na ⁺ ] from 140 to 114 mEq/L?

First, calculate her total body water (TBW) and total body Na ⁺ prior to admission, and then calculate water excess .
Second, add total output for 2 days (4 L) to water excess of 7.3 L. Therefore, the patient may have consumed approximately 11 L of water. Thus, answer C is correct.

In the Emergency Department, she received 100 mL of 3 % NaCl, and her urine output was noted to be 200 mL/h. Repeat serum [Na⁺] in 4 h was 119 mEq/L. She was extubated. The patient did not receive any IV fluids or other interventions for the next 20 h. The urine output increased to 300 mL/h. After 24 h, her serum [Na⁺] was 141 mEq/L. Which one of the following is the MOST appropriate next step in the management of her hyponatremia?

Although serum [Na ⁺ ] can be corrected rapidly in polydipsic patients, the increase of 27 mEq in 24 h is too rapid because of increased urine output. Serum [Na ⁺ ] may further increase, if urine output does not decrease. Therefore, the appropriate management at this time is to prevent further increase in serum [Na ⁺ ], and demyelination, and these changes can be reversed by readministration of DDAVP and hypotonic fluids. Studies in animals and humans suggest that this type of management is appropriate to prevent further increase in serum [Na ⁺ ]. DDAVP 1–2 μg IV should be started with free water boluses or D5W. Thus, option E is correct. Infusion of hypotonic solutions alone is not sufficient to reverse demyelination.

A 32-year-old woman with AIDS was referred to the renal clinic for evaluation of persistent hyponatremia. There was no history of recent infections, but admits to daily intake of beer and at times depression. The patient is thin but not cachectic. BP is 120/80 mmHg with a pulse of 78 beats/min. There are no orthostatic changes. Examination of lung and heart are normal. No peripheral edema is appreciated. Serum and urine chemistries :

Which one of the following treatments is INAPPROPRIATE in this patient?

The answer: is D

Except for SSRI, other treatment modalities have been tried to improve chronic asymptomatic hyponatremia in patients with ectopic production or stimulation of ADH. SSRIs such as sertraline, paroxetine, and duloxetine inhibit the reuptake of serotonin, thus causing hyponatremia. SSRIs induce SIDAH by several mechanisms that include: (1) stimulation of ADH secretion; (2) augmentation of ADH action in the renal medulla; (3) resetting the osmostat that lowers the threshold for ADH secretion; and (4) interaction of SSRIs with other medications via p450 enzymes, resulting in enhanced action of ADH. Thus, D is correct. Dilantin inhibits ADH secretion, so that it will improve hyponatremia.

A 65-year-old man with small cell cancer of left lung is found to have hyponatremia due to SIADH . He is seen by a nephrologist, who started him on a fluid restriction of 1 L/day. Patient refused to take demeclocycline because of his alcohol use and urea for gastrointestinal upset. For a while, his serum [Na⁺] was maintained between 130 and 135 mEq/L. The patient was given a follow-up visit in 3 months, at which time he presented with weakness, fatigue, and the inability to concentrate during conversation. He also complained that he had a sense of falling. He checked his BP which was 140/78 mmHg. He admitted to drinking >1 L of fluids/day because of increased thirst. His serum [Na⁺] is 124 mEq/L, and euvolemic. Other laboratory results are consistent with SIADH. What is the appropriate step in the management of his hyponatremia?

The patient is symptomatic from his chronic hyponatremia. Impairment in cognitive function and falls with fractures are not uncommon in patients with chronic hyponatremia . The patient should be admitted to the hospital for two reasons: (1) to improve symptoms with an increase in serum [Na ⁺ ] to 128–130 mEq/L in a 24 h period, and (2) consideration for an oral vaptan, as the patient is noncompliant to fluid restriction. Tolvaptan is the oral form that is available as 15, 30, and 60 mg tablets.

Tolvaptan should be started in a hospital setting for monitoring of serum [Na ⁺ ] during the dosage-titration phase. The drug is started at 15 mg once daily and titrated up to 60 mg daily without fluid restriction. Once this patient’s symptoms improve, he can be discharged 2–3 days on a fixed dose of tolvaptan.

Tolvaptan is indicated in patients with euvolemic and hypervolemic hyponatremic patients. It should not be used in patients with hypovolemic hyponatremia. Clinical studies have shown beneficial effects of tolvaptan.

The SALT trials , which included patients with SIADH, CHF, and cirrhosis, showed that tolvaptan increased serum [Na ⁺ ] by 4.5 mEq/L on day 4, and 7.4 mEq/L over a 30-day period compared with fluid restriction alone. The patients were also followed up for a mean of 701 days. Mean serum [Na ⁺ ] increased from 131 to >135 mEq/L.

This patient will benefit from tolvaptan use to increase his serum [Na ⁺ ] and prevent falls and fractures. Thus, C is correct. Other options do not help long-term hyponatremia.

A 3-month-old infant is admitted for irritability. Physical examination is unremarkable other than a BP of 128/92 mmHg. Serum [Na] is 123 mEq/L, creatinine <0.3 mg/dL; BUN 5 mg/dL, vasopressin <1 pg/mL (normal 1–13.3), urine osmolality 284, and urine Na⁺ 35; other chemistries are normal. Which one of the following is the MOST likely diagnosis in this infant?

NSIADH is similar to SIADH, but rare. It was first described in 2005 in infants with hyponatremia and high urine osmolality. Unlike SIADH, patients with NSIADH have undetectable or extremely low ADH levels. NSIADH is a gain-of-function mutation in vasopressin V2 receptor (B is correct). Treatment is fluid restriction, urea, and vaptans. NSIADH was also described in patients older than 10 years of age. Other options are incorrect because these conditions are associated with high ADH levels. It should be noted that in drug-induced hyponatremia, the ADH levels may be normal or high.

Which one of the following is the LEAST likely cause of nonhypotonic hyponatremia?

In a case report, topical application of granulated sugar to an infected wound resulted in hypertonic hyponatremia. Unlike oral sucrose, directly absorbed sucrose from a wound into circulation does not metabolize into glucose and fructose. This results in hypertonic hyponatremia . Elevated proteins as in multiple myeloma, a different form of cholesterol found in lipoprotein X (2) or triglycerides cause isotonic hyponatremia. Lipoprotein X has been described in patients with cholestatic liver disease such as primary biliary cirrhosis. Patients with severe triglyceridemia will have a lactescent serum. However, methanol causes osmolal gap but not nonhypotonic hyponatremia.

A 50-year-old hypertensive man is admitted for headache and altered mental status. A CT scan of the head shows subarachnoid hemorrhage . He is receiving hyperalimentation, and his urine output is 4 L/day. Also, the nurse notices diarrhea of 1-day duration. His serum Na⁺ is 149 mEq/L, K⁺ 3.3 mEq/L, HCO₃ ⁻ 26 mEq/L, BUN 44 mg/dL, creatinine 1.6 mg/dL, and glucose 200 mg/dL. His urine Na⁺ is 70 mEq/L, and urine osmolality 380 mOsm/kg H₂O. His volume status is adequate. Which one of the following is the MOST likely cause of his hypernatremia?

Patients with either nephrogenic diabetes insipidus or partial central diabetes insipidus have mostly water diuresis rather than high solute diuresis. The osmolal excretion is normal in diabetes insipidus. Patients with diabetes insipidus have low urine osmolality despite a high serum osmolality or hypernatremia. The patient is excreting a total of 1520 mOsm/day (380 × 4 = 1520). Therefore, the patient has solute diuresis. Thus, options A and B are unlikely in this patient. Option C is also unlikely because the urinary Na ⁺ level is 70 mEq/L, which is high in conditions such as diarrhea. In a patient with diarrhea, the kidney conserves rather than excreting Na ⁺ . Option E is also unlikely because the patient does not have any volume expansion due to hypertonic saline infusion, and the patient should have a sodium diuresis. The patient has osmotic diuresis, which is the cause of his hypernatremia (D is correct). In general, the urine osmolality in osmotic diuresis is relatively higher than serum osmolality. The following flow diagram (Fig. 1.5 ) shows the differential diagnosis of polyuria.

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