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Solute and Water Transport Along the Nephron: Tubular Function
Learning Objectives
Upon completion of this chapter, the student should be able to answer the following questions :
- 1
What three processes are involved in the production of urine?
- 2
What is the composition of “normal” urine?
- 3
What transport mechanisms are responsible for NaCl reabsorption by the nephron? Where are they located along the nephron?
- 4
How is water reabsorption “coupled” to NaCl reabsorption in the proximal tubule?
- 5
Why are solutes but not water reabsorbed by the thick ascending limb of Henle’s loop?
- 6
What transport mechanisms are involved in secretion of organic anions and cations? What is the physiological relevance of these transport processes?
- 7
What is glomerulotubular balance, and what is its physiological importance?
- 8
What are the major hormones that regulate NaCl and water reabsorption by the kidneys? What is the nephron site of action of each hormone?
- 9
What is the aldosterone paradox?
The formation of urine involves three basic processes: (1) ultrafiltration of plasma by the glomerulus, (2) reabsorption of water and solutes from the ultrafiltrate, and (3) secretion of selected solutes into tubular fluid. Although an average of 115 to 180 L/day in women and 130 to 200 L/day in men of essentially protein-free fluid is filtered by the human glomeruli each day, a
a Normal glomerular filtration rate (GFR) averages 115 to 180 L/day in women and 130 to 200 L/day in men. Thus the volume of the ultrafiltrate represents a volume that is approximately 10 times that of the extracellular fluid volume (ECFV). For simplicity, we assume throughout the remainder of this section that GFR is 180 L/day.
less than 1% of the filtered water and sodium chloride (NaCl) and variable amounts of other solutes are typically excreted in urine ( Table 34.1 ). By the processes of reabsorption and secretion, the renal tubules determine the volume and composition of urine ( Table 34.2 ), which in turn allows the kidneys to precisely control the volume, osmolality, composition, and pH of the extracellular and intracellular fluid compartments. Transport proteins in cell membranes of the nephron mediate reabsorption and secretion of solutes and water in the kidneys. Approximately 5% to 10% of all human genes code for transport proteins, and genetic and acquired defects in transport proteins are the cause of many kidney diseases ( Table 34.3 ). In addition, numerous transport proteins are important drug targets. This chapter discusses NaCl and water reabsorption, transport of organic anions and cations, the transport proteins involved in solute and water transport, and some of the factors and hormones that regulate NaCl transport. Details on acid-base transport and on K + , Ca ++ , and inorganic phosphate (P i ) transport and their regulation are provided in Chapters 35 through 37 .
TABLE 34.1
Filtration, Excretion, and Reabsorption of Water, Electrolytes, and Solutes by the Kidneys
| Substance | Measure | Filtered a | Excreted | Reabsorbed | % Filtered Load Reabsorbed |
|---|---|---|---|---|---|
| Water | L/day | 180 | 1.5 | 178.5 | 99.2 |
| Na + | mEq/day | 25,200 | 150 | 25,050 | 99.4 |
| K + | mEq/day | 720 | 100 | 620 | 86.1 |
| Ca ++ | mEq/day | 540 | 10 | 530 | 98.2 |
| HCO 3 − | mEq/day | 4320 | 2 | 4318 | 99.9+ |
| Cl − | mEq/day | 18,000 | 150 | 17,850 | 99.2 |
| Glucose | mmol/day | 800 | 0 | 800 | 100.0 |
| Urea | g/day | 56 | 28 | 28 | 50.0 |
a The filtered amount of any substance is calculated by multiplying the concentration of that substance in the ultrafiltrate by the glomerular filtration rate (GFR); for example, the filtered amount of Na + is calculated as [Na + ]ultrafiltrate (140 mEq/L) × GFR (180 L/day) = 25,200 mEq/day.
TABLE 34.2
Composition of Urine
| Substance | Concentration |
|---|---|
| Na + | 50–130 mEq/L |
| K + | 20–70 mEq/L |
| Ammonium (NH 4 + ) | 30–50 mEq/L |
| Ca ++ | 5–12 mEq/L |
| Mg ++ | 2–18 mEq/L |
| Cl − | 50–130 mEq/L |
| Inorganic phosphate (Pi) | 20–40 mEq/L |
| Urea | 200–400 mmol/L |
| Creatinine | 6–20 mmol/L |
| pH | 5.0–7.0 |
| Osmolality | 500–800 mOsm/kg H 2 O |
| Glucose | 0 |
| Amino acids | 0 |
| Protein | 0 |
| Blood | 0 |
| Ketones | 0 |
| Leukocytes | 0 |
| Bilirubin | 0 |
The composition and volume of urine can vary widely in the healthy state. These values represent average ranges. Normal water excretion typically ranges between 0.5 and 1.5 L/day.
Data from Valtin HV. Renal Physiology. 2nd ed. Boston: Little, Brown; 1983.
TABLE 34.3
Selected Monogenic Renal Diseases Involving Transport Proteins
| Diseases | Mode of Inheritance | Gene | Transport Protein | Nephron Segment | Phenotype |
|---|---|---|---|---|---|
| Cystinuria type I | AR | SLC3A1, SLC7A9 | Amino acid symporters | Proximal tubule | Increased excretion of basic amino acids, nephrolithiasis (kidney stones) |
| Proximal renal tubular acidosis (RTA) | AR | SLC4A4 | Na + /HCO 3 − symporter | Proximal tubule | Hyperchloremic metabolic acidosis |
| X-linked nephrolithiasis (Dent’s disease) | XLR | CLCN, OCRL1 | Chloride channel | Distal tubule | Hypercalciuria, nephrolithiasis |
| Bartter syndrome | AR-type I | SLC12A1 | Na + /K + /2Cl − symporter | TAL | Hypokalemia, metabolic alkalosis, hyperaldosteronism |
| AR-type II | KCNJ1 | ROMK potassium channel | TAL | Hypokalemia, metabolic alkalosis, hyperaldosteronism | |
| AR-type III | CLCNKB | Chloride channel (basolateral membrane) | TAL | Hypokalemia, metabolic alkalosis, hyperaldosteronism | |
| AR-type IV | BSND, CLCNKA CLCNKB | Subunit of chloride channel, chloride channels | TAL | Hypokalemia, metabolic alkalosis, hyperaldosteronism | |
| Hypomagnesemia-hypercalciuria syndrome | AR | CLDN16 | Claudin-16, also known as paracellin 1 | TAL | Hypomagnesemia-hypercalciuria, nephrolithiasis |
| Gitelman syndrome | AR | SLC12A3 | Thiazide-sensitive Na + /Cl − symporter | Distal tubule | Hypomagnesemia, hypokalemic metabolic alkalosis, hypocalciuria, hypotension |
| Pseudohypoaldosteronism type I | AR | SCNN1A, SCNN1B, and SCNN1G | α, β, and γ subunits of ENaC | Collecting duct | Increased excretion of Na + , hyperkalemia, hypotension |
| Pseudohypoaldosteronism type II | AD | MLR | Mineralocorticoid receptor | Collecting duct | Increased excretion of Na + hyperkalemia, hypotension |
| Liddle syndrome | AD | SCNN1B, SCNN1G | β and γ subunits of ENaC | Collecting duct | Decreased excretion of Na + , hypertension |
| Nephrogenic diabetes insipidus (NDI) type II | AR/AD | AQP2 | Aquaporin 2 water channel | Collecting duct | Polyuria, polydipsia, plasma hyperosmolality |
| Distal renal tubular acidosis | AD/AR | SLC4A1 | Cl − /HCO 3 − antiporter | Collecting duct | Metabolic acidosis, hypokalemia, hypercalciuria, nephrolithiasis |
| Distal renal tubular acidosis | AR | ATP6N1B | Subunit of H + - ATPase | Collecting duct | Metabolic acidosis, hypokalemia, hypercalciuria, nephrolithiasis |
There are over 300 different solute transporter genes that form the so-called SLC (solute carrier) family of genes.
AD , Autosomal dominant; AR , autosomal recessive; ENaC , epithelial Na + channel; TAL , thick ascending limb of Henle’s loop; XLR , X-linked recessive.
Modified from Nachman RH, Glassock RJ. NephSAP . 2010;9(3).
Solute and Water Reabsorption Along the Nephron
The general principles of solute and water transport across epithelial cells were discussed in Chapter 2 .
Quantitatively, reabsorption of NaCl and water represent the major function of nephrons. Approximately 25,000 mEq/day of Na + and 179 L/day of water are reabsorbed by the renal tubules (see Table 34.1 ). In addition, renal transport of many other important solutes is linked either directly or indirectly to reabsorption of Na + . In the following sections, the NaCl and water transport processes of each nephron segment and their regulation by hormones and other factors are presented.
Proximal Tubule
The proximal tubule reabsorbs approximately 67% of water, Na + , Cl − , K + , and most other solutes filtered by the glomerulus. In addition the proximal tubule reabsorbs virtually all the glucose, proteins and amino acids filtered by the glomerulus, as well as most of the HCO 3 − . The key element in proximal tubule reabsorption is Na + ,K + -ATPase in the basolateral membrane. Reabsorption of every substance, including water, is linked in some manner to the operation of Na + ,K + -ATPase.
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