The molecular biology of renal K+ channels is discussed in the medical textbook "Seldin and Giebisch's The Kidney: Physiology and Pathophysiology" by Wang W and Huang CL. After studying this chapter, the student should be able to answer the following questions:

1. Explain how HCO3- functions as a buffer and why it is important for the extracellular fluid.
2. Discuss how the metabolism of food produces acid and alkali and how the composition of the diet affects systemic acid-base balance.
3. Differentiate between volatile and nonvolatile acids and define net endogenous acid production (NEAP).
4. Explain the contributions of the kidneys and lungs to systemic acid-base balance and describe renal net acid excretion (RNAE).
5. Discuss the necessity of urinary buffers for the excretion of acid by the kidneys.
6. Describe the mechanisms of H+ transport in the different segments of the nephron and explain their regulation.
7. Explain how the various segments of the nephron contribute to the reabsorption of filtered HCO3-.
8. Discuss how the kidneys produce new HCO3-.
9. Describe how the kidneys produce ammonium and explain its role in renal acid excretion.
10. Identify the major mechanisms by which the body defends itself against changes in acid-base balance.
11. Compare and contrast simple metabolic and respiratory acid-base disorders and explain how they can be differentiated using arterial blood gas measurements.

The concentration of H+ in body fluids is significantly lower than that of other ions, such as Na+. This low concentration is commonly expressed as the negative logarithm, or pH. pH is crucial for the functioning of cellular, tissue, and organ processes. The body fluids have a pH range of 6.8 to 7.8, while the extracellular fluid (ECF) is normally maintained between 7.35 and 7.45. The intracellular fluid (ICF) has a slightly lower pH of 7.1 to 7.2, which is also tightly regulated.

The daily intake of acid and alkali through diet, as well as cellular metabolism, affects the pH of body fluids. To maintain acid-base balance and allow essential life processes to occur, the body requires appropriate mechanisms to handle this daily acid and alkali load. This chapter focuses on the maintenance of whole-body acid-base balance, with an emphasis on the role of the kidneys. The contributions of the lungs and liver are also discussed. Additionally, the impact of diet and cellular metabolism on acid-base balance is presented. Furthermore, disorders of acid-base balance are explored to illustrate the involved physiological processes. In this chapter, acid is defined as any substance that adds H+ to body fluids, while alkali is defined as a substance that removes H+ from body fluids.

Bicarbonate (HCO3-) plays a crucial role as a buffer in the ECF. With a normal plasma concentration of 23 to 25 mEq/L and a volume of 14 L for a 70-kg individual, the ECF can potentially buffer 350 mEq of H+. The HCO3- buffer system differs from other buffer systems in the body, such as phosphate, because it is regulated by both the lungs and kidneys. This regulation can be understood by considering the following reaction:

Equation 37.1
Wang W, Huang CL. The molecular biology of renal K+ channels. In: Alpern RJ, et al., eds. Seldin and Giebisch’s The Kidney: Physiology and Pathophysiology. 5th ed. Waltham, MA: Elsevier; 2013: 1601.
Upon completion of this chapter the student should be able to answer the following questions: 1.
How does HCO3 − operate as a buffer, and why is it an important buffer of the extracellular fluid?
2.
How does metabolism of food produce acid and alkali, and what effect does the composition of the diet have on systemic acid-base balance?
3.
What is the difference between volatile and nonvolatile acids, and what is net endogenous acid production (NEAP)?
4.
How do the kidneys and lungs contribute to systemic acid-base balance, and what is renal net acid excretion (RNAE)?
5.
Why are urinary buffers necessary for excretion of acid by the kidneys?
6.
What are the mechanisms for H+ transport in the various segments of the nephron, and how are these mechanisms regulated?
7.
How do the various segments of the nephron contribute to the process of reabsorbing the filtered HCO3 −?
8.
How do the kidneys produce new HCO3 −?
9.
How is ammonium produced by the kidneys, and how does its excretion contribute to renal acid excretion?
10.
What are the major mechanisms by which the body defends itself against changes in acid-base balance?
11.
What are the differences between simple metabolic and respiratory acid-base disorders, and how are they differentiated by arterial blood gas measurements?
he concentration of H+ in body fluids is low compared with that of other ions. For example, Na+ is present at a concentration some three million times greater than that of H+ ([Na+] = 140 mEq/L; [H+] = 40 nEq/L). Because of the low [H+] of the body fluids, it is commonly expressed as the negative logarithm, or pH.
Virtually all cellular, tissue, and organ processes are sensitive to pH. Indeed, life cannot exist outside of a range of extracellular fluid (ECF) pH from 6.8 to 7.8 (160–16 nEq/L of H+). Normally the pH of ECF is maintained between 7.35 and 7.45. As described in the pH of intracellular fluid (ICF) is slightly lower (7.1–7.2) but also tightly regulated.
Each day, acid and alkali are ingested in the diet. Also, cellular metabolism produces a number of substances that have an impact on the pH of body fluids. Without appropriate mechanisms to deal with this daily acid and alkali load and thereby maintain acid-base balance, many processes necessary for life could not occur. This chapter reviews the maintenance of whole-body acid-base balance. Although the emphasis is on the role of the kidneys in this process, the roles of the lungs and liver are also considered. In addition the impact of diet and cellular metabolism on acid-base balance is presented. Finally, disorders of acid-base balance are considered, primarily to illustrate the physiological processes involved. Throughout this chapter, acid is defined as any substance that adds H+ to body fluids, whereas alkali is defined as a substance that removes H+ from body fluids.
The HCO3 − Buffer System
Bicarbonate (HCO3 −) is an important buffer of the ECF. With a normal plasma [HCO3 −] of 23 to 25 mEq/L and a volume of 14 L (for a 70-kg individual) the ECF can potentially buffer 350 mEq of H+ . The HCO3 − buffer system differs from the other buffer systems of the body (e.g., phosphate) because it is regulated by both the lungs and kidneys. This is best appreciated by considering the following reaction:
Equation 37.1