A 61-year-old male is given acetazolamide to treat open-angle glaucoma. Upon diuresis, his urine is found to be highly alkaline. Which of the following accounts for the alkaline nature of this patient’s urine?

Inhibition of bicarbonate reabsorption in the proximal tubule

Inhibition of bicarbonate reabsorption in beta-intercalated cells

Inhibition of acid secretion in alpha-intercalated cells

Inhibition of chloride reabsorption in the distal convoluted tubule

Inhibition of chloride reabsorption in the thick ascending loop of Henle

An investigator is studying patients with acute decompensated congestive heart failure. He takes measurements of a hormone released from atrial myocytes, as well as serial measurements of left atrial and left ventricular pressures. The investigator observes a positive correlation between left atrial pressures and the serum level of this hormone. Which of the following is most likely the mechanism of action of this hormone?

Decreases sodium reabsorption at the collecting tubules

Increases potassium excretion at the collecting ducts

Constricts afferent renal arteriole

Decreases reabsorption of bicarbonate in the proximal convoluted tubules

Increases free water reabsorption from the distal tubules

A researcher is studying the effects of a new antihypertensive medication on urine osmolality. She first measures urine osmolality in different parts of the nephron of a healthy human control. The findings are shown below: Portion of nephron Urine osmolality (mOsmol/kg) Proximal convoluted tubule 300 Loop of Henle, descending limb 1200 Loop of Henle, ascending limb 200 Distal convoluted tubule 100 Collecting duct 600 Which of the following is the most likely explanation for the urine osmolality in the ascending limb of the loop of Henle?

Increased transcription of water channels

Increased bicarbonate reabsorption

On cardiology service rounds, your team sees a patient admitted with an acute congestive heart failure exacerbation. In congestive heart failure, decreased cardiac function leads to decreased renal perfusion, which eventually leads to excess volume retention. To test your knowledge of physiology, your attending asks you which segment of the nephron is responsible for the majority of water absorption. Which of the following is a correct pairing of the segment of the nephron that reabsorbs the majority of all filtered water with the means by which that segment absorbs water?

Proximal convoluted tubule via passive diffusion following ion reabsorption

Distal convoluted tubule via passive diffusion following ion reabsorption

Distal convoluted tubule via aquaporin channels

Thick ascending loop of Henle via passive diffusion following ion reabsorption

Collecting duct via aquaporin channels

A 55-year-old woman presents to the emergency room with severe abdominal pain for the past 24 hours. She has also noticed blood in her urine. She does not have any significant past medical history. Family history is significant for her mother having cholecystitis status post cholecystectomy at age 45. Her vital signs include: temperature 36.8°C (98.2°F), pulse 103/min, respiratory rate 15/min, blood pressure 105/85 mm Hg. Physical examination is significant for a woman continuously moving on the exam table in an attempt to get comfortable. Laboratory findings are significant for the following: Serum electrolytes Na 138 mEq/L N: 135–145 mEq/L K 4.0 mEq/L N: 3.5–5.0 mEq/L Cl 102 mEq/L N: 98–108 mEq/L CO2 27 mEq/L N: 22–32 mEq/L Ca 9.2 mEq/dL N: 8.4–10.2 mEq/dL PO4 3.5 mg/dL N: 3.0–4.5 mg/dL A 24-hour urine collection is performed and reveals a urinary calcium of 345 mg/day (ref: < 300 mg/day in men; < 250 mg/day in women). A non-contrast CT of the abdomen is performed and is shown in the exhibit. The patient’s symptoms pass within the next 12 hours with hydration and acetaminophen for pain management. She is prescribed a medication to prevent subsequent episodes. At which of the following parts of the nephron does this medication most likely work?

Descending limb of the loop of Henle

Thick ascending limb of the loop of Henle

A 57-year-old male is found to have an elevated prostate specific antigen (PSA) level on screening labwork. PSA may be elevated in prostate cancer, benign prostatic hypertrophy (BPH), or prostatitis. Which of the following best describes the physiologic function of PSA?

Regulation of transcription factors and phosphorylation of proteins

Response to peritoneal irritation

Distal tubule and collecting duct function for USMLE Step 1: High-Yield Physiology Lessons

Distal Convoluted Tubule - Thiazide's Territory

Renal Tubule: Solute and Water Reabsorption/Secretion

Early DCT is impermeable to water; continues to dilute tubular fluid by reabsorbing solutes.
Actively reabsorbs ~5% of filtered NaCl via the apical Na⁺-Cl⁻ Cotransporter (NCC).
- This transporter is the specific target inhibited by Thiazide diuretics (e.g., hydrochlorothiazide).
Site of Parathyroid Hormone (PTH) action to increase Ca²⁺ reabsorption:
- PTH upregulates the apical TRPV5 Ca²⁺ channel.
- Drives Ca²⁺ reabsorption via the basolateral Na⁺/Ca²⁺ exchanger.

⭐ Thiazide diuretics can lead to hypercalcemia by enhancing Ca²⁺ reabsorption in the DCT. This makes them useful for managing recurrent calcium kidney stones.

Principal Cells - The Water & Salt Boss

Location: Late distal convoluted tubule (DCT) & collecting ducts.
Primary Role: Fine-tuning of water & electrolyte balance under hormonal control.

Hormonal Regulation:

Aldosterone:
- Acts on basolateral mineralocorticoid receptors.
- Upregulates apical ENaC (↑ Na⁺ reabsorption) & ROMK channels (↑ K⁺ secretion).
- Also increases activity of basolateral Na⁺/K⁺-ATPase.
- Net Effect: ↑ Blood volume/pressure, ↓ plasma [K⁺] (hypokalemia).
ADH (Vasopressin):
- Binds to basolateral V2 receptors (Gs-coupled).
- Increases cAMP, leading to insertion of Aquaporin-2 (AQP2) channels on the apical membrane.
- Net Effect: ↑ Free water reabsorption, creating concentrated urine.

Principal cell: ENaC, ROMK, Na/K ATPase, Aldosterone, ADH

⭐ Amiloride and triamterene are K⁺-sparing diuretics that act by directly blocking the ENaC channel in principal cells.

Intercalated Cells - Acid-Base Crew

Function: Fine-tune acid-base balance in response to systemic pH.
Location: Collecting tubules.

Two main types:

α-intercalated cells (A for Acid-secreting):
- Active during acidosis.
- Apical: Secrete $H^+$ via $H^+$-ATPase.
- Basolateral: Reabsorb $HCO_3^-$.
- Also reabsorb $K^+$ via apical $H^+/K^+$-ATPase.
β-intercalated cells (B for Base-secreting):
- Active during alkalosis.
- Apical: Secrete $HCO_3^-$ via Pendrin exchanger.
- Basolateral: Reabsorb $H^+$.

Alpha and Beta Intercalated Cells in Distal Tubule

⭐ High-Yield: Aldosterone acts on α-intercalated cells to ↑ activity of the $H^+$-ATPase, promoting $H^+$ secretion and helping correct acidosis.

Hormonal Regulation - The Master Controllers

Aldosterone: Acts on principal cells → ↑Na⁺ reabsorption (ENaC) & ↑K⁺ secretion (ROMK). Also stimulates H⁺ secretion from α-intercalated cells, promoting acid excretion.
ADH (Vasopressin): Via V2 receptors, it inserts aquaporin-2 (AQP2) channels in principal cells → ↑H₂O reabsorption and concentrated urine.
ANP/BNP: Counteracts aldosterone. It inhibits Na⁺ reabsorption in the medullary collecting duct, promoting natriuresis and diuresis.

⭐ Aldosterone escape is a physiological response where high aldosterone levels are counteracted by increased ANP, preventing significant hypernatremia and edema despite continued sodium retention.

High‑Yield Points - ⚡ Biggest Takeaways

The Distal Convoluted Tubule (DCT) reabsorbs NaCl (blocked by thiazides) and is the major site of Ca²⁺ reabsorption, stimulated by PTH.

Principal cells in the collecting duct reabsorb Na⁺ and secrete K⁺, a process driven by aldosterone.

Intercalated cells fine-tune acid-base balance, with α-cells secreting H⁺ and β-cells secreting HCO₃⁻.

ADH regulates final urine concentration by increasing water permeability via aquaporin-2 channels.

K⁺-sparing diuretics work here by blocking aldosterone or ENaC channels.

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