Medical Physiology, 3rd Edition

Acid-Base Transport by Different Segments of the Nephron

Most nephron segments secrete H⁺ to varying degrees.

The nephron reclaims virtually all the filtered in the proximal tubule (~80%), thick ascending limb (~10%), and distal nephron (~10%)

The kidney reabsorbs the largest fraction of filtered (~80%) along the proximal tubule (Fig. 39-3A). By the end of the proximal tubule, luminal pH falls to ~6.8, which represents only a modest transepithelial H⁺ gradient compared with the plasma pH of 7.4. Thus, the proximal tubule is a high-capacity, low-gradient system for H⁺ secretion. The thick ascending limb of the loop of Henle (TAL) reabsorbs an additional 10% of filtered , so that by the time the tubule fluid reaches the distal convoluted tubule (DCT), the kidney has reclaimed ~90% of the filtered . The rest of the distal nephron—from the DCT to the inner medullary collecting duct (IMCD)—reabsorbs almost all the remaining ~10% of the filtered . Although the latter portion of the nephron reabsorbs only a small fraction of the filtered , it can lower luminal pH to ~4.4. Thus, the collecting tubules and ducts are a low-capacity, high-gradient system for H⁺ transport.

FIGURE 39-3 Acid-base handling along the nephron. In A, the numbered yellow boxes indicate the fraction of the filtered load reabsorbed by various nephron segments. The green boxes indicate the fraction of the filtered load that remains in the lumen at various sites. In B, the red boxes indicate the moieties of acid secretion associated with either the formation of titratable acid (TA) or the secretion of . The yellow boxes indicate the formation of new or reabsorption by the TAL. The values in the boxes are approximations.

The amount of lost in the urine depends on urine pH. If the [CO₂] in the urine were the same as that in the blood, and if urine pH were 5.4, the [] in the urine would be 0.24 mM, which is 1% of the 24 mM in blood (see p. 630). For a urine production of 1.5 L/day, the kidneys would excrete 0.36 mmol/day of . For a filtered load of 4320 mmol/day, this loss represents a fractional excretion of ~0.01%. In other words, the kidneys reclaim ~99.99% of the filtered . Similarly, at a nearly maximally acidic urine pH of 4.4, urine [] would be only 0.024 mM. Therefore, the kidneys would excrete only 36 µmol/day of filtered and would reabsorb ~99.999%.

The nephron generates new , mostly in the proximal tubule

The kidney generates new in two ways (see Fig. 39-3B). It titrates filtered buffers such as to produce “titratable acid,” and it titrates secreted NH₃ to . In healthy people, excretion is the more important of the two and contributes ~60% of net acid excretion or new .

Formation of Titratable Acid

The extent to which a particular buffer contributes to titratable acid (see Fig. 39-2B) depends on the amount of buffer in the lumen and luminal pH. The titratable acid due to phosphate is already substantial at the end of the proximal tubule (Table 39-4), even though the proximal tubule reabsorbs ~80% of the filtered phosphate. The reason is that the luminal pH equals the pK of the buffer at the end of the proximal tubule. The titratable acid due to phosphate rises only slightly along the classical distal tubule (i.e., DCT, connecting tubule [CNT], and initial collecting tubule [ICT]), because acid secretion slightly exceeds phosphate reabsorption. The titratable acid due to phosphate rises further as luminal pH falls to 4.4 along the collecting ducts in the absence of significant phosphate reabsorption.

TABLE 39-4

Titratable Acidity of Creatinine and Phosphate Along the Nephron*

^*Note that other buffers in the urine contribute to the total titratable acid, which increases with the excreted amount of each buffer and with decreases in urine pH. In this example, we assume a plasma [phosphate] of 1.3 mM, a plasma [creatinine] of 0.09 mM, and a GFR of 180 L/day.

^†We assume that the proximal tubule secretes an amount of creatinine that is equivalent to 20% of the filtered load.

P_i, inorganic phosphate; PT, proximal tubule.

Although the late proximal tubule secretes creatinine, the titratable acid due to creatinine (see Table 39-4) is minuscule at the end of the proximal tubule, because luminal pH is so much higher than creatinine's pK. However, the titratable acidity due to creatinine increases substantially along the collecting ducts as luminal pH plummets. The urine contains the protonated form of other small organic acids (e.g., uric, lactic, pyruvic, and citric acids) that also contribute to titratable acid.

Excretion

Of the new that the nephron generates, ~60% (~40 mmol/day) is the product of net excretion (see Fig. 39-3B), which is the result of five processes: (1) the proximal tubule actually secretes slightly more than ~40 mmol/day of , (2) the TAL reabsorbs some and deposits it in the interstitium, (3) some of this interstitial recycles back to the proximal tubule and thin descending limb (tDLH), (4) some of the interstitial enters the lumen of the collecting duct, and finally, (5) some of the interstitial enters the vasa recta and leaves the kidney. As we shall see on p. 831, the liver uses some of this to generate urea, a process that consumes . Thus, the net amount of new attributable to excretion is (1) − (2) + (3) + (4) − (5).