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

In a healthy patient with no renal abnormalities, several mechanisms are responsible for moving various filtered substances into and out of the tubules. Para-aminohippurate (PAH) is frequently used to estimate renal blood flow when maintained at low plasma concentrations. The following table illustrates the effect of changing plasma PAH concentrations on PAH excretion: Plasma PAH concentration (mg/dL) | Urinary PAH concentration (mg/dL) 0 | 0 10 | 60 20 | 120 30 | 150 40 | 180 Which of the following mechanisms best explains the decreased rate of increase in PAH excretion observed when plasma PAH concentration exceeds 20 mg/dL?

Saturation of PAH transport carriers

Decreased glomerular filtration of PAH

Increased rate of PAH reabsorption

Increased flow rate of tubular contents

Increased diffusion rate of PAH

A 72-year-old man being treated for benign prostatic hyperplasia (BPH) is admitted to the emergency department for 1 week of dysuria, nocturia, urge incontinence, and difficulty initiating micturition. His medical history is relevant for hypertension, active tobacco use, chronic obstructive pulmonary disease, and BPH with multiple urinary tract infections. Upon admission, he is found with a heart rate of 130/min, respiratory rate of 19/min, body temperature of 39.0°C (102.2°F), and blood pressure of 80/50 mm Hg. Additional findings during the physical examination include decreased breath sounds, wheezes, crackles at the lung bases, and intense right flank pain. A complete blood count shows leukocytosis and neutrophilia with a left shift. A sample for arterial blood gas analysis (ABG) was taken, which is shown below. Laboratory test Serum Na+ 140 mEq/L Serum Cl- 102 mEq/L Serum K+ 4.8 mEq/L Serum creatinine (SCr) 2.3 mg/dL Arterial blood gas pH 7.12 Po2 82 mm Hg Pco2 60 mm Hg SO2% 92% HCO3- 12.0 mEq/L Which of the following best explains the patient’s condition?

Metabolic acidosis complicated by respiratory acidosis

Metabolic acidosis complicated by respiratory alkalosis

Non-anion gap metabolic acidosis

Respiratory alkalosis complicated by metabolic acidosis

Respiratory acidosis complicated by metabolic alkalosis

A 70-year-old woman is brought to the emergency department due to worsening lethargy. She lives with her husband who says she has had severe diarrhea for the past few days. Examination shows a blood pressure of 85/60 mm Hg, pulse of 100/min, and temperature of 37.8°C (100.0°F). The patient is stuporous, while her skin appears dry and lacks turgor. Laboratory tests reveal: Serum electrolytes Sodium 144 mEq/L Potassium 3.5 mEq/L Chloride 115 mEq/L Bicarbonate 19 mEq/L Serum pH 7.3 PaO2 80 mm Hg Pco2 38 mm Hg This patient has which of the following acid-base disturbances?

Non-anion gap metabolic acidosis with respiratory compensation

Anion gap metabolic acidosis with respiratory compensation

Non-anion gap metabolic acidosis

A person is exercising strenuously on a treadmill for 1 hour. An arterial blood gas measurement is then taken. Which of the following are the most likely values?

pH 7.57 PaO2 100, PCO2 23, HCO3 21

pH 7.56, PaO2 100, PCO2 44, HCO3 38

pH 7.32, PaO2 42, PCO2 50, HCO3 27

pH 7.38, PaO2 100, PCO2 69 HCO3 42

pH 7.36, PaO2 100, PCO2 40, HCO3 23

Titratable acid excretion - Free USMLE Review

Titratable Acid - The Phosphate Shuttle

Primary urinary buffer system for excreting non-volatile acids (e.g., from diet).
Mechanism involves trapping secreted $H^+$ in the tubular fluid by a filtered buffer, primarily phosphate.
For every $H^+$ secreted and buffered, a new $HCO_3^-$ is generated and returned to the blood, replenishing the body's buffer stores.

The phosphate buffer system's pKa is ~6.8, making it highly effective in the physiological pH range of urine.

⭐ High-Yield: Titratable acid excretion accounts for eliminating ~30-40 mEq/day of fixed acid. The amount is limited by the quantity of phosphate filtered by the glomerulus.

Regulation & Quantification - Acid Accounting

Titratable Acid (TA) is a measure of protons ($H^+$) excreted in the urine bound to buffers, primarily phosphate ($HPO_4^{2-}$).

Quantification: Measured by titrating urine with a strong base (e.g., NaOH) back to the normal blood pH of 7.4.
Net Acid Excretion (NAE): Represents the total renal contribution to acid-base balance.
- $NAE = (\text{Titratable Acid}) + (NH_4^+) - (\text{Urinary } HCO_3^-)$
Phosphate Buffer System: The main urinary buffer system ($H_2PO_4^- / HPO_4^{2-}$) has a pKa of ~6.8, making it highly effective at physiological urine pH.
Limitation: TA formation is limited by the quantity of buffers (especially phosphate) filtered by the glomerulus.

Renal Phosphate Buffer System and Titratable Acid Excretion

⭐ In chronic acidosis, renal ammoniagenesis is the primary, adaptive response for acid excretion, increasing dramatically while titratable acidity remains relatively fixed.

Clinical Context - Acidosis in Action

Metabolic acidosis (e.g., DKA, lactic acidosis) triggers a crucial renal compensatory response to excrete the excess H⁺ load and restore pH.

Cellular Action: Type A intercalated cells in the collecting ducts ↑ H⁺ secretion into the tubular fluid via apical H⁺-ATPase pumps.
Urinary Buffering: Secreted H⁺ immediately binds to filtered buffers to prevent a precipitous drop in urine pH.
- Phosphate: The primary titratable acid buffer.
- $H^+ + HPO_4^{2-} \rightarrow H_2PO_4^-$
- This traps H⁺, allowing for its excretion as titratable acid.

Renal H+ excretion, NH4+ excretion, and HCO3- reclamation

⭐ While titratable acid excretion helps, the ammonia buffer system ($NH_3/NH_4^+$) is quantitatively the most important mechanism for excreting large acid loads, especially in chronic acidosis, due to its ability to be significantly upregulated.

High‑Yield Points - ⚡ Biggest Takeaways

Titratable acid is H⁺ excreted by urinary buffers, mainly the phosphate buffer system (HPO₄²⁻ → H₂PO₄⁻).

This is key for excreting fixed, non-volatile acids from protein metabolism.

Occurs in α-intercalated cells of the distal tubule and collecting ducts.

Accounts for ~1/3 of net acid excretion; ammonium (NH₄⁺) handles the majority.

Its capacity is limited by the filtered phosphate load, unlike the highly adaptable ammonia system.

Excretion increases in acidosis but is not significantly upregulated in chronic acidosis.