Functions of the Kidney

The kidneys are involved in the following processes:
* Excretion of unwanted substances, such as cellular metabolic waste, excess salts, and toxins. One product of amino acid metabolism is nitrogen-containing waste material, a chief form of which is urea. After synthesis in the liver, urea is transported in the blood to the kidneys for elimination. The kidneys have a specialized mechanism for the elimination of urea and other nitrogenous wastes.
* Maintenance of water balance. Although the amount of water gained and lost in a day can vary tremendously, the kidneys can adapt to these variations, so that the volume of body water remains remarkably stable from day to day.
* Regulation of the acid-base balance of body fluids. Acids are constantly being produced by cellular metabolism. Certain foods can yield acids or bases, and people may also ingest antacids, such as bicarbonate. However, if the body is to function normally, the pH of body fluids must remain in the range of 7.35 to 7.45.
* Regulation of blood pressure. The kidneys depend on blood pressure to filter the blood. If blood pressure falls too low for effective filtration, the cells of the JG apparatus release renin. This enzyme activates angiotensin, a blood protein that causes blood vessels to constrict, thus raising blood pressure. Angiotensin also stimulates the adrenal cortex to produce the hormone aldosterone, which promotes retention of sodium and water, also raising blood pressure.
* Regulation of red blood cell production. When the kidneys do not get enough oxygen, they produce the hormone erythropoietin (EPO), which stimulates the red cell production in the bone marrow. EPO made by genetic engineering is now available to treat severe anemia, such as occurs in the end stage of kidney failure.

Formation of Urine

The following explanation of urine formation describes a complex process, involving many back-andforth exchanges between the bloodstream and the kidney tubules. As fluid filtered from the blood travels slowly through the twists and turns of the nephron, there is ample time for exchanges to take place. These processes together allow the kidney to “fine tune” body fluids as they adjust the composition of the urine.

Glomerular Filtration The process of urine formation begins with the glomerulus in the glomerular capsule. The walls of the glomerular capillaries are sievelike and permit the free flow of water and soluble materials through them. Like other capillary walls, however, they are impermeable to blood cells and large protein molecules, and these components remain in the blood (Fig. 18-7). Because the diameter of the afferent arteriole is slightly larger than that of the efferent arteriole (see Fig. 18-7), blood can enter the glomerulus more easily than it can leave. Thus, blood pressure in the glomerulus is about three to four times higher than it is in other capillaries.

Figure 18-7 Filtration process in the formation of urine. Blood pressure inside the glomerulus forces water and dissolved substances into the glomerular (Bowman) capsule. Blood cells and proteins remain behind in the blood. The smaller diameter of the efferent arteriole as compared with that of the afferent arteriole maintains the hydrostatic (fluid) pressure.

To understand this effect, think of placing your thumb over the end of a garden hose as water comes through. As you make the diameter of the opening smaller, water is forced out under higher pressure. As a result of increased fluid (hydrostatic) pressure in the glomerulus, materials are constantly being pushed out of the blood and into the nephron’s glomerular capsule. Movement of water and dissolved materials through a membrane under pressure is called filtration. This movement of materials under pressure from the blood into the capsule is therefore known as glomerular filtration. The fluid that enters the glomerular capsule, called the glomerular filtrate, begins its journey along the tubular system of the nephron. In addition to water and the normal soluble substances in the blood, other substances, such as vitamins and drugs, also may be filtered and become part of the glomerular filtrate.

Tubular Reabsorption The kidneys form about 160 to 180 liters of filtrate day. However, only 1 to 1.5 liters of urine are eliminated daily. Clearly, most of the water that enters the nephron is not excreted with the urine, but rather, is returned to the circulation. In addition to water, many other substances the body needs, such as nutrients and ions, pass into the nephron as part of the filtrate, and these also must be returned. Therefore, the process of filtration that occurs in the glomerular capsule is followed by a process of tubular reabsorption. As the filtrate travels through the nephron’s tubular system, water and other needed substances leave the tubule and enter the surrounding tissue fluid, or interstitial fluid (IF). They move by several processes:
* Diffusion. The movement of substances from an area of higher concentration to an area of lower concentration (following the concentration gradient).
* Osmosis. Diffusion of water through a semipermeable membrane.
* Active transport. Movement of materials through the plasma membrane against the concentration gradient using energy and transporters.
The substances that leave the nephron and enter the interstitial fluid then enter the peritubular capillaries and return to the circulation. In contrast, most of the urea and other nitrogenous waste materials are kept within the tubule to be eliminated with the urine.

Tubular Secretion Before the filtrate leaves the body as urine, the kidney makes final adjustments in composition by the process of tubular

secretion. In this process, some substances are actively moved from the blood into the nephron. Potassium ions are moved into the urine by this process. Importantly, the kidneys regulate the acid-base (pH) balance of body fluids by the active secretion of hydrogen ions. Some drugs, such as penicillin, also are actively secreted into the nephron for elimination.

Concentration of the Urine The amount of water that is eliminated with the urine is regulated by a complex mechanism within the nephron that is influenced by antidiuretic hormone (ADH), a hormone released from the posterior pituitary gland. The process is called the countercurrent mechanism because it involves fluid traveling in opposite directions within the ascending and descending limbs of Henle’s loop. The countercurrent mechanism is illustrated in Figure 18-8. Its essentials are as follows: As the filtrate passes through Henle’s loop, electrolytes, especially sodium, are actively pumped out by the nephron’s cells, resulting in an increased concentration of the interstitial fluid. Because the ascending limb of Henle’s loop is not very permeable to water, the filtrate at this point becomes increasingly dilute (see Fig. 18-8). As the filtrate then passes through the more permeable DCT and collecting duct, the concentrated fluids around the nephron draw water out to be returned to the blood. (Remember, according to the laws of osmosis, water follows salt.) In this manner, the urine becomes more concentrated as it leaves the nephron and its volume is reduced.
The hormone ADH makes the walls of the DCT and collecting tubule more permeable to water, so that more water will be reabsorbed and less will be excreted with the urine. The release of ADH from the posterior pituitary is regulated by a feedback system. As the blood becomes more concentrated, the hypothalamus triggers more ADH release from the posterior pituitary; as the blood becomes more dilute, less ADH is released. In the disease diabetes insipidus, there is inadequate secretion of ADH from the hypothalamus, which results in the elimination of large amounts of dilute urine accompanied by excessive thirst.

Summary of Urine Formation
The processes involved in urine formation are summarized below and illustrated in Figure 18-9.
1. Glomerular filtration allows all diffusible materials to pass from the blood into the nephron.
2. Tubular reabsorption moves useful substances back into the blood while keeping waste products in the nephron to be eliminated in the urine.
3. Tubular secretion moves additional substances from the blood into the nephron for elimination. Movement of hydrogen ions is one means by which the pH of body fluids is balanced.
4. The countercurrent mechanism concentrates the urine and reduces the volume excreted. The pituitary hormone ADH allows more water to be reabsorbed from the nephron.

Figure 18-8 Countercurrent mechanism for concentration of urine. Concentration is regulated by means of intricate exchanges of water and electrolytes, mainly sodium, in the loop of Henle, distal convoluted tubule, and collecting duct. The intensity of color shows changing concentrations of the interstitial fluid and filtrate.

Figure 18-9 Summary of urine formation in a nephron.