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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