All questions
Question 1
A 65-year-old man with a 40-pack-year smoking history and recently diagnosed small cell lung cancer presents to the emergency department with increasing confusion and lethargy over the past 3 days. He has no history of head trauma or neurologic disease. His temperature is 37.1°C (98.8°F), blood pressure is 130/80 mm Hg, pulse is 88/min, and respirations are 16/min. Physical examination reveals a lethargic man who is oriented only to person. He has no focal neurologic deficits. Laboratory studies show a serum sodium of 118 mEq/L, serum osmolality of 245 mOsm/kg, and urine osmolality of 450 mOsm/kg.
Which of the following is the most likely mechanism underlying this patient's hyponatremia?
- Decreased aldosterone secretion leading to renal sodium wasting
- Ectopic ADH secretion leading to excessive free water retention (correct answer)
- Impaired glomerular filtration leading to volume overload
- Primary polydipsia overwhelming renal excretory capacity
Explanation: This patient presents with euvolemic hyponatremia, characterized by low serum sodium and osmolality in the setting of inappropriately concentrated urine (urine osmolality > 100 mOsm/kg). This clinical picture, especially in a patient with small cell lung cancer, is classic for the Syndrome of Inappropriate Antidiuretic Hormone (SIADH). Small cell lung cancer can ectopically produce ADH, which acts on the collecting ducts to increase aquaporin channels, leading to excessive free water reabsorption and dilutional hyponatremia.
Question 2
A 19-year-old woman with type 1 diabetes mellitus is brought to the emergency department by her roommate due to altered mental status. For the past two days, she has had nausea, vomiting, and abdominal pain. She has not taken her insulin. On examination, she is breathing rapidly and deeply. Her breath has a fruity odor. An arterial blood gas analysis shows: pH 7.15, PaCO2 20 mm Hg, and HCO3- 8 mEq/L.
In response to this patient's acid-base disturbance, which of the following represents the primary renal compensatory mechanism?
- Decreased reabsorption of filtered bicarbonate in the proximal tubule
- Increased secretion of H+ and generation of new bicarbonate (correct answer)
- Secretion of bicarbonate into the tubular lumen by intercalated cells
- Decreased activity of the Na+/K+-ATPase in the basolateral membrane
Explanation: The patient is in diabetic ketoacidosis, which causes a high anion gap metabolic acidosis. The primary renal compensation for metabolic acidosis is to increase the excretion of acid and conserve bicarbonate. This is achieved by increasing the secretion of H+ ions into the tubular fluid by the α-intercalated cells of the collecting duct and the proximal tubule cells. For each H+ secreted, a new bicarbonate ion is generated and returned to the blood, helping to correct the acidosis.
Question 3
A 22-year-old woman with a history of an eating disorder is evaluated for persistent muscle weakness and cramping. She admits to self-induced vomiting several times daily for the past month. Her blood pressure is 95/60 mm Hg and pulse is 105/min. Laboratory studies show: pH 7.52, PaCO2 48 mm Hg, HCO3- 35 mEq/L, serum K+ 2.8 mEq/L. A urine sample reveals a pH of 5.5.
Which of the following best explains the finding of an acidic urine in this patient with metabolic alkalosis?
- Increased filtered load of bicarbonate overwhelming reabsorptive capacity
- Volume contraction stimulating aldosterone and H+ secretion (correct answer)
- Primary defect in the chloride-bicarbonate exchanger in the collecting duct
- Respiratory compensation for the primary metabolic disturbance
Explanation: This patient has metabolic alkalosis from vomiting (loss of HCl). The associated volume depletion activates the renin-angiotensin-aldosterone system. Aldosterone increases sodium reabsorption in the collecting duct at the expense of potassium and H+ secretion. The hypokalemia also contributes by promoting H+ secretion in exchange for K+ reabsorption via the H+/K+-ATPase in intercalated cells. This results in excretion of an acidic urine despite systemic alkalosis, a phenomenon known as 'paradoxical aciduria.'
Question 4
A 62-year-old woman with congestive heart failure is treated with furosemide. During a follow-up visit, she complains of significant muscle weakness and fatigue. An ECG shows U waves and flattened T waves. Laboratory results confirm a serum potassium of 2.7 mEq/L.
Furosemide causes potassium wasting primarily by inhibiting which of the following transporters in the renal tubules?
- Na+/K+-ATPase on the basolateral membrane of the proximal tubule
- Na+/Cl- cotransporter in the distal convoluted tubule
- Na+/K+/2Cl- cotransporter in the thick ascending limb of the loop of Henle (correct answer)
- Epithelial sodium channel (ENaC) in the collecting duct
Explanation: Furosemide is a loop diuretic that acts by inhibiting the Na+/K+/2Cl- (NKCC2) cotransporter in the apical membrane of cells in the thick ascending limb of the loop of Henle. This inhibition reduces the reabsorption of these ions, leading to significant natriuresis and diuresis. The blockade also disrupts the generation of the positive luminal potential, which normally drives paracellular reabsorption of cations like Ca2+ and Mg2+. The increased delivery of sodium to the distal nephron stimulates the renin-angiotensin-aldosterone system and enhances potassium secretion in the collecting ducts, leading to hypokalemia.
Question 5
A 35-year-old man who sustained a severe head injury in a motor vehicle accident is being monitored in the intensive care unit. Over the past 24 hours, his urine output has increased to 8 L. He is now confused and agitated. Laboratory studies show a serum sodium of 158 mEq/L and serum osmolality of 325 mOsm/kg. His urine osmolality is 150 mOsm/kg.
This patient's hypernatremia is a direct consequence of impaired reabsorption of which of the following substances in the collecting ducts?
- Sodium
- Urea
- Potassium
- Water (correct answer)
Explanation: The clinical presentation of polyuria, hypernatremia, high serum osmolality, and inappropriately dilute urine is characteristic of diabetes insipidus (DI). In the context of head trauma, this is most likely central DI, caused by damage to the hypothalamus or posterior pituitary, leading to deficient ADH secretion. ADH normally promotes free water reabsorption in the collecting ducts by increasing the insertion of aquaporin-2 channels. Without ADH, the collecting ducts are impermeable to water, leading to the excretion of a large volume of dilute urine and a subsequent increase in serum sodium concentration due to pure water loss.
Question 6
A 10-year-old boy is diagnosed with Fanconi syndrome. He has polyuria, growth retardation, and rickets. Laboratory testing reveals a normal anion gap metabolic acidosis, hypophosphatemia, hypokalemia, and glucosuria with a normal serum glucose level.
The metabolic acidosis in this patient is primarily due to a defect in the reabsorption of which substance in the proximal tubule?
- Chloride
- Phosphate
- Bicarbonate (correct answer)
- Amino acids
Explanation: Fanconi syndrome is a generalized dysfunction of the proximal convoluted tubule. This leads to impaired reabsorption of numerous substances, including bicarbonate, glucose, amino acids, and phosphate. The inability to reabsorb the filtered load of bicarbonate results in significant bicarbonate wasting in the urine. This loss of base from the body is the primary cause of the normal anion gap metabolic acidosis seen in proximal (Type 2) RTA, which is a key feature of Fanconi syndrome.
Question 7
A 70-year-old man with poorly controlled type 2 diabetes and moderate chronic kidney disease (eGFR 40 mL/min) is noted to have a persistent serum potassium of 5.8 mEq/L on routine lab work. He is not taking any medications known to cause hyperkalemia. Further workup reveals a normal anion gap metabolic acidosis.
This combination of findings is most consistent with a disorder involving which of the following?
- Impaired function of the H+/K+-ATPase in intercalated cells
- Decreased synthesis or effect of aldosterone (correct answer)
- Overproduction of organic acids
- Defective reabsorption in the thick ascending limb
Explanation: This patient has Type 4 Renal Tubular Acidosis, which is characterized by hyperkalemia and a normal anion gap metabolic acidosis. This is the most common form of RTA and is often seen in patients with diabetes and chronic kidney disease. The underlying pathophysiology is either deficient aldosterone production (hyporeninemic hypoaldosteronism) or resistance to its effects in the collecting duct. Aldosterone is necessary for both potassium and hydrogen ion secretion. Its deficiency or resistance leads to retention of both K+ and H+, causing hyperkalemia and acidosis.
Question 8
A 48-year-old woman is found to have hypertension (165/105 mm Hg) during a routine physical examination. Laboratory studies reveal a serum potassium of 3.0 mEq/L and a bicarbonate level of 32 mEq/L. Her plasma renin activity is suppressed, and a 24-hour urine collection shows elevated aldosterone levels. An abdominal CT scan reveals a right-sided adrenal adenoma.
The electrolyte and acid-base abnormalities in this patient are caused by the direct action of aldosterone on which part of the nephron?
- Proximal convoluted tubule
- Thick ascending limb of the loop of Henle
- Distal convoluted tubule
- Principal and intercalated cells of the collecting duct (correct answer)
Explanation: This patient has primary hyperaldosteronism (Conn's syndrome). Aldosterone's primary site of action is the late distal tubule and the collecting duct. It acts on the principal cells to increase the expression of apical epithelial sodium channels (ENaC) and basolateral Na+/K+-ATPases, promoting sodium reabsorption and potassium secretion. It also acts on the α-intercalated cells to stimulate H+ secretion via the H+-ATPase. The combined effect of increased K+ and H+ secretion leads to the characteristic findings of hypokalemia and metabolic alkalosis.
Question 9
A 58-year-old man with severe congestive heart failure has a blood pressure of 90/60 mm Hg and signs of poor renal perfusion. His renin-angiotensin-aldosterone system is highly activated.
In addition to its vasoconstrictive effects, angiotensin II directly promotes sodium and water retention by stimulating which of the following transport processes in the proximal convoluted tubule?
- Na+/H+ exchange (correct answer)
- Na+/K+/2Cl- cotransport
- Na+/Cl- cotransport
- K+/Cl- cotransport
Explanation: Angiotensin II has multiple effects on the kidney to increase sodium and water retention. One of its key direct effects is on the proximal convoluted tubule, where it stimulates the activity of the Na+/H+ exchanger (NHE3) on the apical membrane. This increases sodium reabsorption from the tubular fluid into the cell. The associated H+ secretion also facilitates bicarbonate reabsorption via the action of carbonic anhydrase. This leads to increased reabsorption of sodium, bicarbonate, and osmotically obligated water, contributing to volume expansion.
Question 10
A 34-year-old man is brought to the emergency department after ingesting an entire bottle of aspirin in a suicide attempt. He is agitated, breathing rapidly, and complaining of ringing in his ears. Initial arterial blood gas results show: pH 7.42, PaCO2 20 mm Hg, HCO3- 12 mEq/L.
Which of the following best describes the acid-base disturbances present in this patient?
- Pure metabolic acidosis
- Pure respiratory alkalosis
- Metabolic acidosis and respiratory acidosis
- Metabolic acidosis and respiratory alkalosis (correct answer)
Explanation: Salicylate (aspirin) overdose classically causes a mixed acid-base disorder. Initially, salicylates directly stimulate the medullary respiratory center, causing hyperventilation and a primary respiratory alkalosis (low PaCO2). Subsequently, salicylates uncouple oxidative phosphorylation and inhibit enzymes in the Krebs cycle, leading to the accumulation of organic acids (ketoacids, lactate) and a primary anion gap metabolic acidosis (low HCO3-). The patient's labs show a low PaCO2 (respiratory alkalosis) and a low HCO3- (metabolic acidosis). The near-normal pH reflects the opposing effects of the two primary disorders.
Question 11
A 59-year-old man with cirrhosis due to chronic hepatitis C presents with worsening ascites and peripheral edema. He is started on spironolactone in addition to furosemide. The goal of adding spironolactone is to counteract the potassium-wasting effects of furosemide.
Spironolactone achieves its potassium-sparing effect by acting as an antagonist at which of the following receptors?
- Vasopressin V2 receptor
- Angiotensin II type 1 receptor
- Mineralocorticoid receptor (correct answer)
- Beta-1 adrenergic receptor
Explanation: Spironolactone is a potassium-sparing diuretic that functions as a competitive antagonist of the mineralocorticoid (aldosterone) receptor in the collecting duct. In patients with cirrhosis, secondary hyperaldosteronism contributes to sodium and water retention. By blocking the action of aldosterone, spironolactone prevents the transcription and insertion of epithelial sodium channels (ENaC) and Na+/K+-ATPases in principal cells. This reduces sodium reabsorption and, consequently, decreases the luminal negative potential that drives potassium secretion, thus 'sparing' potassium.
Question 12
A 24-year-old graduate student presents to the emergency department with lightheadedness, shortness of breath, and tingling around her mouth and in her fingertips. She is extremely anxious about an upcoming exam. Her respirations are 30/min and deep. An arterial blood gas analysis shows pH 7.55, PaCO2 25 mm Hg, and HCO3- 23 mEq/L.
The patient's neurologic symptoms are most directly related to a decrease in the serum concentration of which of the following?
- Total calcium
- Ionized calcium (correct answer)
- Serum potassium
- Serum magnesium
Explanation: The patient is hyperventilating due to anxiety, leading to respiratory alkalosis (low PaCO2, high pH). In a state of alkalemia, albumin and other plasma proteins become more negatively charged, which increases their binding of positively charged ions, particularly calcium. This leads to a decrease in the physiologically active, ionized form of calcium (Ca2+), even though the total serum calcium concentration remains unchanged. Hypocalcemia increases neuronal excitability, causing the characteristic perioral numbness, paresthesias, and potentially tetany (carpopedal spasm).
Question 13
A 66-year-old man with end-stage renal disease on hemodialysis presents with bone pain and a recent wrist fracture from a minor fall. Laboratory studies show: serum calcium 8.2 mg/dL, serum phosphate 6.5 mg/dL, and parathyroid hormone (PTH) 800 pg/mL (normal 10-65 pg/mL).
The elevated parathyroid hormone level in this patient is primarily a response to which of the following renal abnormalities?
- Decreased production of 1,25-dihydroxyvitamin D (correct answer)
- Increased renal tubular reabsorption of calcium
- Excessive urinary loss of phosphate
- Increased secretion of fibroblast growth factor 23 (FGF-23)
Explanation: This patient has secondary hyperparathyroidism due to chronic kidney disease (CKD). In CKD, two major factors stimulate PTH secretion. First, the failing kidneys are unable to excrete phosphate, leading to hyperphosphatemia. Second, and more importantly, the damaged renal parenchyma has reduced activity of 1-alpha-hydroxylase, the enzyme that converts 25-hydroxyvitamin D to its active form, 1,25-dihydroxyvitamin D (calcitriol). Low calcitriol levels lead to decreased intestinal calcium absorption, causing hypocalcemia. Both hypocalcemia and the lack of negative feedback from calcitriol on the parathyroid glands lead to a massive, sustained increase in PTH secretion.
Question 14
A 72-year-old man with type 2 diabetes mellitus, hypertension, and stage 3 chronic kidney disease is brought to the clinic for a routine follow-up. He was started on lisinopril 3 weeks ago for blood pressure control and proteinuria. He reports feeling more fatigued than usual. His blood pressure is 135/85 mm Hg. An ECG shows peaked T waves. Laboratory studies are significant for a serum potassium of 5.9 mEq/L.
The medication recently started is most likely causing this patient's hyperkalemia by which of the following mechanisms?
- Inhibition of the Na+/K+/2Cl- cotransporter in the thick ascending limb
- Direct blockade of the epithelial sodium channel (ENaC) in the collecting duct
- Reduced angiotensin II production leading to decreased aldosterone secretion (correct answer)
- Increased H+/K+-ATPase activity in the intercalated cells of the collecting duct
Explanation: Lisinopril is an ACE inhibitor, which blocks the conversion of angiotensin I to angiotensin II. Reduced angiotensin II levels lead to decreased secretion of aldosterone from the adrenal cortex. Aldosterone normally promotes potassium secretion in the distal nephron by upregulating the epithelial sodium channel (ENaC) and the renal outer medullary potassium channel (ROMK). Therefore, ACE inhibitor therapy can lead to hyperkalemia by reducing aldosterone-mediated potassium excretion.
Question 15
A 55-year-old man with a history of chronic alcohol use disorder is hospitalized for alcohol withdrawal. He develops seizures. Laboratory tests reveal a serum calcium of 6.9 mg/dL. An infusion of calcium gluconate produces only a transient increase in his serum calcium level. Further investigation reveals a serum magnesium level of 0.8 mg/dL.
The refractory hypocalcemia in this patient is best explained by the low magnesium level's effect on which of the following?
- Increasing urinary calcium excretion
- Decreasing intestinal calcium absorption
- Impairing parathyroid hormone secretion and action (correct answer)
- Enhancing calcitonin release from the thyroid gland
Explanation: Severe hypomagnesemia is a common cause of refractory hypocalcemia, particularly in patients with alcoholism. Magnesium is required for the normal functioning of the calcium-sensing receptor and for the secretion of parathyroid hormone (PTH). Severe hypomagnesemia impairs PTH release from the parathyroid glands. Furthermore, it causes end-organ resistance to the effects of PTH at the bone and kidney. This combination of decreased PTH secretion and peripheral PTH resistance leads to hypocalcemia that will not correct until the magnesium deficiency is addressed.
Question 16
A 68-year-old man with a long history of chronic obstructive pulmonary disease (COPD) is hospitalized for an acute exacerbation. He is increasingly somnolent. An arterial blood gas measurement on room air shows: pH 7.25, PaCO2 80 mm Hg, and HCO3- 28 mEq/L. His condition stabilizes over the next 48 hours.
If his PaCO2 remains elevated, which of the following changes in renal function is expected to occur over the next several days to compensate for this acid-base disorder?
- Decreased ammonia production by proximal tubule cells
- Increased renal bicarbonate reabsorption and generation (correct answer)
- Increased urinary phosphate excretion
- Decreased sodium reabsorption in the collecting duct
Explanation: The patient has acute respiratory acidosis due to CO2 retention from his COPD exacerbation. The appropriate physiological compensation is renal. Over several days, the kidneys will increase their net acid excretion. This involves two main processes: increased reclamation of all filtered bicarbonate and increased generation of new bicarbonate, primarily through enhanced ammonium (NH4+) synthesis and secretion by proximal tubule cells and increased H+ secretion. This leads to a rise in serum bicarbonate, which helps to normalize the pH.
Question 17
A healthy 25-year-old hiker becomes lost in the desert with a limited water supply. After 24 hours of significant dehydration, he is rescued.
Which of the following sets of physiological changes is most likely to be found in this individual upon rescue?
- Decreased plasma osmolality, decreased ADH, decreased urine osmolality
- Increased plasma osmolality, increased ADH, increased urine osmolality (correct answer)
- Increased plasma osmolality, decreased ADH, decreased urine osmolality
- Decreased plasma osmolality, increased ADH, increased urine osmolality
Explanation: Dehydration leads to a loss of free water, which concentrates the solutes in the blood, causing an increase in plasma osmolality. This change is sensed by osmoreceptors in the hypothalamus, which stimulates both the sensation of thirst and the release of antidiuretic hormone (ADH) from the posterior pituitary. ADH travels to the kidneys and acts on the collecting ducts, increasing their permeability to water. This allows for maximal water reabsorption from the filtrate, resulting in the production of a small volume of highly concentrated urine (high urine osmolality) to conserve body water.
Question 18
An 80-year-old woman with a history of hypertension and osteoporosis is started on hydrochlorothiazide. Two weeks later, routine laboratory tests are performed.
In addition to the intended effect on blood pressure, which of the following sets of electrolyte abnormalities is most likely to be seen in this patient?
- Hyperkalemia and hypocalcemia
- Hyperkalemia and hypercalcemia
- Hypokalemia and hypocalcemia
- Hypokalemia and hypercalcemia (correct answer)
Explanation: Hydrochlorothiazide is a thiazide diuretic that inhibits the Na+/Cl- cotransporter in the distal convoluted tubule. This leads to several characteristic electrolyte disturbances. The increased delivery of sodium to the collecting duct promotes potassium secretion, leading to hypokalemia. Uniquely among diuretics, thiazides increase calcium reabsorption in the distal tubule by enhancing the activity of the basolateral Na+/Ca2+ exchanger, which can lead to hypercalcemia. Other common side effects include hyponatremia and hyperuricemia.
Question 19
A medical student is studying renal physiology. She learns that under normal conditions, the vast majority of a key buffer is reabsorbed from the glomerular filtrate to maintain acid-base balance.
Which of the following nephron segments is responsible for reabsorbing approximately 85% of the filtered load of bicarbonate?
- Proximal convoluted tubule (correct answer)
- Thick ascending limb of the loop of Henle
- Distal convoluted tubule
- Cortical collecting duct
Explanation: The proximal convoluted tubule is the primary site for bicarbonate (HCO3-) reabsorption, reclaiming about 85% of the filtered load. This process is dependent on the enzyme carbonic anhydrase and the Na+/H+ exchanger on the apical membrane. H+ is secreted into the lumen, where it combines with filtered HCO3- to form H2CO3. Carbonic anhydrase on the brush border converts H2CO3 to CO2 and H2O, which diffuse into the cell. Inside the cell, cytoplasmic carbonic anhydrase reverses the reaction, and the regenerated HCO3- is transported across the basolateral membrane into the blood.
Question 20
A 45-year-old woman with Sjögren syndrome presents for evaluation of recurrent kidney stones, which analysis revealed to be composed of calcium phosphate. She also reports generalized weakness. Laboratory studies show a non-anion gap metabolic acidosis with a serum potassium of 3.1 mEq/L. A urine sample shows a pH of 6.8.
This patient's condition is most likely caused by a defect in which of the following renal processes?
- Proximal tubular bicarbonate reabsorption
- Distal tubular hydrogen ion secretion (correct answer)
- Aldosterone binding to its mineralocorticoid receptor
- Ammonia synthesis in the proximal convoluted tubule
Explanation: This patient presents with a classic triad for distal (Type 1) Renal Tubular Acidosis (RTA): non-anion gap metabolic acidosis, hypokalemia, and an inability to acidify the urine (urine pH > 5.5). The underlying defect is in the α-intercalated cells of the distal tubule and collecting duct, which are unable to secrete H+ into the lumen. This impairs acid excretion and bicarbonate generation, leading to systemic acidosis. Chronic acidosis leads to calcium release from bone and hypercalciuria, which, combined with the alkaline urine, promotes the formation of calcium phosphate stones.