The Urinary System : Functional Anatomy and Urine Formation by the Kidneys

Excretion of Metabolic Waste Products, Foreign Chemicals, Drugs, and Hormone Metabolites

The kidneys are the primary means for eliminating most of the waste products of metabolism that are no longer needed by the body. These products include urea (from the metabolism of amino acids), creatinine (from muscle creatine), uric acid (from nucleic acids), end products of hemoglobin breakdown (e.g., bilirubin), and metabolites of various hormones . These waste products must be eliminated from the body as rapidly as they are produced. The kidneys also eliminate most toxins and other foreign substances that are produced by the body or ingested, such as pesticides, drugs, and food additives.

Regulation of Water and Electrolyte Balances

For maintenance of homeostasis, excretion of water and electrolytes must match intake precisely. If intake exceeds excretion, the amount of that substance in the body will increase. If intake is less than excretion, the amount of that substance in the body will decrease. Although temporary (or cyclic) imbalances of water and electrolytes may occur in various physiological and pathophysiological conditions associated with altered intake or renal excretion, the maintenance of life depends on restoration of water and electrolyte balance.

Intake of water and many electrolytes is usually governed by a person’s eating and drinking habits, requiring the kidneys to adjust their excretion rates to match the intakes of various substances. Figure 26-1 shows the response of the kidneys to a sudden 10-fold increase in sodium intake from a low level of 30 mEq/day to a high level of 300 mEq/day. Within 2 to 3 days after raising the sodium intake, renal excretion also increases to about 300 mEq/day so that the balance between intake and output is rapidly re-established. However, during the 2 to 3 days of renal adaptation to the high sodium intake, there is a modest accumulation of sodium that raises extracellular fluid volume slightly and triggers hormonal changes and other compensatory responses that signal the kidneys to increase their sodium excretion.

The capability of the kidneys to alter sodium excretion in response to changes in sodium intake is tremendous. Experimental studies have shown that in many people, sodium intake can be increased to 1500 mEq/day (more than 10 times normal) or decreased to 10 mEq/day (<0.1 of normal), with relatively small changes in extracellular fluid volume or plasma sodium concentration. This phenomenon is also true for water and for most other electrolytes, such as chloride, potassium, calcium, hydrogen, magnesium, and phosphate ions. In the next few chapters, we discuss the specific mechanisms that permit the kidneys to perform these amazing feats of homeostasis.

Regulation of Arterial Pressure

As discussed in Chapter 19 , the kidneys play a dominant role in long-term regulation of arterial pressure by excreting variable amounts of sodium and water. The kidneys also contribute to short-term arterial pressure regulation by secreting hormones and vasoactive factors or substances (e.g., renin ) that lead to the formation of vasoactive products (e.g., angiotensin II).

Regulation of Acid–Base Balance

The kidneys contribute to acid–base regulation, along with the lungs and body fluid buffers, by excreting acids and by regulating the body fluid buffer stores. The kidneys are the only means of eliminating certain types of acids from the body, such as sulfuric acid and phosphoric acid, which are generated by the metabolism of proteins.

Regulation of Erythrocyte Production

The kidneys secrete erythropoietin , which stimulates production of red blood cells by hematopoietic stem cells in the bone marrow, as discussed in Chapter 33 . One important stimulus for erythropoietin secretion by the kidneys is hypoxia . The kidneys normally account for almost all the erythropoietin secreted into the circulation. In people with severe kidney disease or who have had their kidneys removed and have been placed on hemodialysis, severe anemia develops as a result of decreased erythropoietin production.

Regulation of 1,25-Dihydroxyvitamin D ₃ Production

The kidneys produce 1,25-dihydroxyvitamin D ₃ ( calcitriol ), the active form of vitamin D, by hydroxylating this vitamin at the “number 1” position. Calcitriol is essential for normal calcium deposition in bone and calcium reabsorption by the gastrointestinal tract. As discussed in Chapter 80 , calcitriol plays an important role in calcium and phosphate regulation.

Glucose Synthesis

The kidneys synthesize glucose from amino acids and other precursors during prolonged fasting, a process referred to as gluconeogenesis . The kidneys’ capacity to add glucose to the blood during prolonged periods of fasting rivals that of the liver.

With chronic kidney disease or acute failure of the kidneys, these homeostatic functions are disrupted, and severe abnormalities of body fluid volumes and composition rapidly occur. With complete renal failure, enough potassium, acids, fluid, and other substances accumulate in the body to cause death within a few days unless clinical interventions such as hemodialysis are initiated to restore, at least partially, the body fluid and electrolyte balances.